Browsing by Subject "Oxygen"
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Item Bronchopulmonary Dysplasia: Executive Summary of a Workshop(Elsevier, 2018-06) Higgins, Rosemary D.; Jobe, Alan H.; Koso-Thomas, Marion; Bancalari, Eduardo; Viscardi, Rose M.; Hartert, Tina V.; Ryan, Rita M.; Kallapur, Suhas G.; Steinhorn, Robin H.; Konduri, Girija G.; Davis, Stephanie D.; Thebaud, Bernard; Clyman, Ronald I.; Collaco, Joseph M.; Martin, Camilia R.; Woods, Jason C.; Finer, Neil N.; Raju, Tonse N. K.; Pediatrics, School of MedicineComment in Bronchopulmonary Dysplasia: The Ongoing Search for One Definition to Rule Them All. [J Pediatr. 2018] Midlife crisis? In its 50th year, BPD redefines itself. [J Pediatr. 2018]Item Carbon and Phosphorus Cycling in Arabian Sea Sediments across the Oxygen Minimum Zone(Longdom Publishing, 2017-11-09) Filippelli, Gabriel M.; Cowie, Gregory L.; Earth and Environmental Sciences, School of ScienceSeveral studies have focused on carbon, oxygen, and phosphorus dynamics across the modern oxygen minimum zone (OMZ) to constrain how signals of modern systems get “locked in” upon burial. In this study, a sequential phosphorus fractionation technique was applied to surficial and sub-surface sediments from stations at depths spanning the OMZ on the Pakistan margin of the Arabian Sea in order to test the oxygen-carbon-phosphorus connection in modern marine sediments. Some early diagenetic loss of phosphorus compared to organic carbon was observed, but a significant portion of the released phosphorus was retained by uptake on oxyhydroxides and by the formation of an authigenic phosphorus-bearing phase. This process is unaffected by station location relative to the OMZ, and results in an effective organic carbon-to-reactive-phosphorus sediment ratio that is close to the average observed for open-ocean sediments, regardless of bottom water oxygen content.Item Early Brain and Abdominal Oxygenation in Extremely Low Birth Weight Infants(Springer Nature, 2022) Chock, Valerie Y.; Smith, Emily; Tan, Sylvia; Ball, M. Bethany; Das, Abhik; Hintz, Susan R.; Kirpalani, Haresh; Bell, Edward F.; Chalak, Lina F.; Cotten, C. Michael; Widness, John A.; Kennedy, Kathleen A.; Ohls, Robin K.; Seabrook, Ruth B.; Patel, Ravi M.; Laptook, Abbot R.; Mancini, Toni; Sokol, Gregory M.; Walsh, Michele C.; Yoder, Bradley A.; Poindexter, Brenda B.; Chawla, Sanjay; D’Angio, Carl T.; Higgins, Rosemary D.; Van Meurs, Krisa P.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network; Pediatrics, School of MedicineBackground: Extremely low birth weight (ELBW) infants are at risk for end-organ hypoxia and ischemia. Regional tissue oxygenation of the brain and gut as monitored with near-infrared spectroscopy (NIRS) may change with postnatal age, but normal ranges are not well defined. Methods: A prospective study of ELBW preterm infants utilized NIRS monitoring to assess changes in cerebral and mesenteric saturation (Csat and Msat) over the first week after birth. This secondary study of a multicenter trial comparing hemoglobin transfusion thresholds assessed cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE) and relationships with perinatal variables. Results: In 124 infants, both Csat and Msat declined over the first week, with a corresponding increase in oxygen extraction. With lower gestational age, lower birth weight, and 5-min Apgar score ≤5, there was a greater increase in oxygen extraction in the brain compared to the gut. Infants managed with a lower hemoglobin transfusion threshold receiving ≥2 transfusions in the first week had the lowest Csat and highest cFTOE (p < 0.001). Conclusion: Brain oxygen extraction preferentially increased in more immature and anemic preterm infants. NIRS monitoring may enhance understanding of cerebral and mesenteric oxygenation patterns and inform future protective strategies in the preterm ELBW population. Impact: Simultaneous monitoring of cerebral and mesenteric tissue saturation demonstrates the balance of oxygenation between preterm brain and gut and may inform protective strategies. Over the first week, oxygen saturation of the brain and gut declines as oxygen extraction increases. A low hemoglobin transfusion threshold is associated with lower cerebral saturation and higher cerebral oxygen extraction compared to a high hemoglobin transfusion threshold, although this did not translate into clinically relevant differences in the TOP trial primary outcome. Greater oxygen extraction by the brain compared to the gut occurs with lower gestational age, lower birth weight, and 5-min Apgar score ≤5.Item The effect of intraoral suction on oxygen-enriched surgical environments: a mechanism for reducing the risk of surgical fires(American Dental Society of Anethesiology, 2014) VanCleave, Andrea M.; Jones, James E.; McGlothlin, James D.; Saxen, Mark A.; Sanders, Brian J.; Vinson, LaQuia A.; Department of Pediatric Dentistry, IU School of DentistryIn this study, a mechanical model was applied in order to replicate potential surgical fire conditions in an oxygen-enriched environment with and without high-volume suction typical for dental surgical applications. During 41 trials, 3 combustion events were measured: an audible pop, a visible flash of light, and full ignition. In at least 11 of 21 trials without suction, all 3 conditions were observed, sometimes with an extent of fire that required early termination of the experimental trial. By contrast, in 18 of 20 with-suction trials, ignition did not occur at all, and in the 2 cases where ignition did occur, the fire was qualitatively a much smaller, candle-like flame. Statistically comparing these 3 combustion events in the no-suction versus with-suction trials, ignition (P = .0005), audible pop (P = .0211), and flash (P = .0092) were all significantly more likely in the no-suction condition. These results suggest a possible significant and new element to be added to existing surgical fire safety protocols toward making surgical fires the "never-events" they should be.Item The EGLN-HIF O2-Sensing System: Multiple Inputs and Feedbacks(Cell Press, 2017-06-15) Ivan, Mircea; Kaelin, William G., Jr.; Medicine, School of MedicineItem Estimated Cost-effectiveness of Solar-Powered Oxygen Delivery for Pneumonia in Young Children in Low-Resource Settings(American Medical Association, 2021-06) Huang, Yiming; Mian, Qaasim; Conradi, Nicholas; Opoka, Robert O.; Conroy, Andrea L.; Namasopo, Sophie; Hawkes, Michael T.; Pediatrics, School of MedicineImportance: Pneumonia is the leading cause of childhood mortality worldwide. Severe pneumonia associated with hypoxemia requires oxygen therapy; however, access remains unreliable in low- and middle-income countries. Solar-powered oxygen delivery (solar-powered O2) has been shown to be a safe and effective technology for delivering medical oxygen. Examining the cost-effectiveness of this innovation is critical for guiding implementation in low-resource settings. Objective: To determine the cost-effectiveness of solar-powered O2 for treating children in low-resource settings with severe pneumonia who require oxygen therapy. Design, setting, and participants: An economic evaluation study of solar-powered O2 was conducted from January 12, 2020, to February 27, 2021, in compliance with the World Health Organization Choosing Interventions That Are Cost-Effective (WHO-CHOICE) guidelines. Using existing literature, plausible ranges for component costs of solar-powered O2 were determined in order to calculate the expected total cost of implementation. The costs of implementing solar-powered O2 at a single health facility in low- and middle-income countries was analyzed for pediatric patients younger than 5 years who required supplemental oxygen. Exposures: Treatment with solar-powered O2. Main outcomes and measures: The incremental cost-effectiveness ratio (ICER) of solar-powered O2 was calculated as the additional cost per disability-adjusted life-year (DALY) saved. Sensitivity of the ICER to uncertainties of input parameters was assessed through univariate and probabilistic sensitivity analyses. Results: The ICER of solar-powered O2 was estimated to be $20 (US dollars) per DALY saved (95% CI, $2.83-$206) relative to the null case (no oxygen). Costs of solar-powered O2 were alternatively quantified as $26 per patient treated and $542 per life saved. Univariate sensitivity analysis found that the ICER was most sensitive to the volume of pediatric pneumonia admissions and the case fatality rate. The ICER was insensitive to component costs of solar-powered O2 systems. In secondary analyses, solar-powered O2 was cost-effective relative to grid-powered concentrators (ICER $140 per DALY saved) and cost-saving relative to fuel generator-powered concentrators (cost saving of $7120). Conclusions and relevance: The results of this economic evaluation suggest that solar-powered O2 is a cost-effective solution for treating hypoxemia in young children in low- and middle-income countries, relative to no oxygen. Future implementation should prioritize sites with high rates of pediatric pneumonia admissions and mortality. This study provides economic support for expansion of solar-powered O2 and further assessment of its efficacy and mortality benefit.Item Existence, functional impairment, and lung repair potential of endothelial colony-forming cells in oxygen-induced arrested alveolar growth(Ovid Technologies Wolters Kluwer -American Heart Association, 2014-05-27) Alphonse, Rajesh S.; Vadivel, Arul; Fung, Moses; Shelley, William Chris; Critser, Paul John; Ionescu, Lavinia; O’Reilly, Megan; Ohls, Robin K.; McConaghy, Suzanne; Eaton, Farah; Zhong, Shumei; Yoder, Merv; Thébaud, Bernard; Department of Pediatrics, IU School of MedicineBACKGROUND: Bronchopulmonary dysplasia and emphysema are life-threatening diseases resulting from impaired alveolar development or alveolar destruction. Both conditions lack effective therapies. Angiogenic growth factors promote alveolar growth and contribute to alveolar maintenance. Endothelial colony-forming cells (ECFCs) represent a subset of circulating and resident endothelial cells capable of self-renewal and de novo vessel formation. We hypothesized that resident ECFCs exist in the developing lung, that they are impaired during arrested alveolar growth in experimental bronchopulmonary dysplasia, and that exogenous ECFCs restore disrupted alveolar growth. METHODS AND RESULTS: Human fetal and neonatal rat lungs contain ECFCs with robust proliferative potential, secondary colony formation on replating, and de novo blood vessel formation in vivo when transplanted into immunodeficient mice. In contrast, human fetal lung ECFCs exposed to hyperoxia in vitro and neonatal rat ECFCs isolated from hyperoxic alveolar growth-arrested rat lungs mimicking bronchopulmonary dysplasia proliferated less, showed decreased clonogenic capacity, and formed fewer capillary-like networks. Intrajugular administration of human cord blood-derived ECFCs after established arrested alveolar growth restored lung function, alveolar and lung vascular growth, and attenuated pulmonary hypertension. Lung ECFC colony- and capillary-like network-forming capabilities were also restored. Low ECFC engraftment and the protective effect of cell-free ECFC-derived conditioned media suggest a paracrine effect. Long-term (10 months) assessment of ECFC therapy showed no adverse effects with persistent improvement in lung structure, exercise capacity, and pulmonary hypertension. CONCLUSIONS: Impaired ECFC function may contribute to arrested alveolar growth. Cord blood-derived ECFC therapy may offer new therapeutic options for lung diseases characterized by alveolar damage.Item Hydrogen Sulfide as an Oxygen Sensor(Mary Ann Liebert, Inc., 2014-05-07) Olson, Kenneth R.; IU School of Medicine, South BendSignificance: Although oxygen (O2)-sensing cells and tissues have been known for decades, the identity of the O2-sensing mechanism has remained elusive. Evidence is accumulating that O2-dependent metabolism of hydrogen sulfide (H2S) is this enigmatic O2 sensor. Recent Advances: The elucidation of biochemical pathways involved in H2S synthesis and metabolism have shown that reciprocal H2S/O2 interactions have been inexorably linked throughout eukaryotic evolution; there are multiple foci by which O2 controls H2S inactivation, and the effects of H2S on downstream signaling events are consistent with those activated by hypoxia. H2S-mediated O2 sensing has been demonstrated in a variety of O2-sensing tissues in vertebrate cardiovascular and respiratory systems, including smooth muscle in systemic and respiratory blood vessels and airways, carotid body, adrenal medulla, and other peripheral as well as central chemoreceptors. Critical Issues: Information is now needed on the intracellular location and stoichometry of these signaling processes and how and which downstream effectors are activated by H2S and its metabolites. Future Directions: Development of specific inhibitors of H2S metabolism and effector activation as well as cellular organelle-targeted compounds that release H2S in a time- or environmentally controlled way will not only enhance our understanding of this signaling process but also provide direction for future therapeutic applications. Antioxid. Redox Signal. 22, 377–397. “Nothing in Biology Makes Sense Except in the Light of Evolution” —Theodosius Dobzhansky (29)Item MicroRNA-210 Regulates Mitochondrial Free Radical Response to Hypoxia and Krebs Cycle in Cancer Cells by Targeting Iron Sulfur Cluster Protein ISCU(Public Library of Science, 2010-04-26) Favaro, Elena; Ramachandran, Anassuya; McCormick, Robert; Gee, Harriet; Blancher, Christine; Crosby, Meredith; Devlin, Cecilia; Blick, Christopher; Buffa, Francesca; Li, Ji-Liang; Vojnovic, Borivoj; Neves, Ricardo Pires das; Glazer, Peter; Iborra, Francisco; Ivan, Mircea; Ragoussis, Jiannis; Harris, Adrian L.; Medicine, School of MedicineHypoxia in cancers results in the upregulation of hypoxia inducible factor 1 (HIF-1) and a microRNA, hsa-miR-210 (miR-210) which is associated with a poor prognosis. Methods and Findings In human cancer cell lines and tumours, we found that miR-210 targets the mitochondrial iron sulfur scaffold protein ISCU, required for assembly of iron-sulfur clusters, cofactors for key enzymes involved in the Krebs cycle, electron transport, and iron metabolism. Down regulation of ISCU was the major cause of induction of reactive oxygen species (ROS) in hypoxia. ISCU suppression reduced mitochondrial complex 1 activity and aconitase activity, caused a shift to glycolysis in normoxia and enhanced cell survival. Cancers with low ISCU had a worse prognosis. Conclusions Induction of these major hallmarks of cancer show that a single microRNA, miR-210, mediates a new mechanism of adaptation to hypoxia, by regulating mitochondrial function via iron-sulfur cluster metabolism and free radical generation.Item Novel early life risk factors for adult pulmonary hypertension(Sage, 2019) Goss, Kara N.; Austin, Eric D.; Battiola, Therese J.; Tepper, Robert S.; Lahm, Tim; Pediatrics, School of MedicineThe role of perinatal insults in the development of adult onset pulmonary hypertension (PH) is unclear. We surveyed patients with and without PH for a history of early life risk factors, and identified prematurity, oxygen use, and respiratory illness each as risk predictors for development of adult PH.