pO2 Levels Research Articles

The difference between arterial pCO2 and etCO2 after cardiac arrest – Outcome predictor or marker of unfavorable resuscitation circumstances?

IntroductionIn former studies, the arterio-alveolar carbon dioxide gradient (ΔCO2) predicted in-hospital mortality after initially survived cardiac arrest. As early outcome predictors are urgently needed, we evaluated ΔCO2 as predictor for good neurological outcome in our cohort. MethodsWe retrospectively analyzed all patients ≥18 years of age after non-traumatic in- and out of hospital cardiac arrest in the year 2018 from our resuscitation database. Patients without advanced airway management, incomplete datasets or without return of spontaneous circulation were excluded. The first arterial pCO2 after admission and the etCO2 in mmHg at the time of blood sampling were recorded from patient's charts. We then calculated ΔCO2 (pCO2 – etCO2). For baseline analyses, ΔCO2 was dichotomized into a low and high group with separation at the median. Good neurological outcome on day 30, expressed as Cerebral Performance Category 1–2, defined our primary endpoint. Survival to 30 days was used as secondary endpoint. ResultsOut of 302 screened patients, 128 remained eligible for analyses. ΔCO2 was lower in 30-day survivors with good neurological outcome (12.2 mmHg vs. 18.8 mmHg, p = 0.009) and in 30-day survivors (12.5 mmHg vs. 20.0 mmHg, p = 0.001). In patients with high ΔCO2, a cardiac etiology of arrest was found less often. They had a higher body mass index, longer duration of resuscitation, higher amounts of epinephrine, lower pO2 levels but both higher pCO2 and blood lactate levels, resulting in lower blood pH and HCO3− levels at admission.In a crude binary logistic regression analysis, ΔCO2 was associated with 30-day neurological outcome (OR = 1.041 per mmHg of ΔCO2, 95% CI 1.008–1.074, p = 0.014). This association persisted after the adjustment for age, sex, witnessed arrest and shockable first rhythm. However, after addition of the duration of resuscitation or the cumulative epinephrine dosage to the model, ΔCO2 lost its association. ConclusionΔCO2 at admission after a successfully resuscitated cardiac arrest is associated with 30 days survival with good neurological outcome. However, a higher ΔCO2 may rather be a surrogate for unfavorable resuscitation circumstances than an independent outcome predictor.

Correlation Analysis of Early Renal Injury in Elderly Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

ObjectiveTo investigate the correlation between serum cystatin C (Cys-C) and beta-2 (β2) microglobulin (β2-MG) levels and renal injury in elderly patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with a view to detecting renal injury in its early stages.MethodsA total of 106 patients with AECOPD were enrolled and divided into three groups according to their oxygen partial pressure (PO2) levels: severe hypoxia group, moderate hypoxia group, and mild hypoxia group. Another 60 healthy subjects were selected as the control group. General clinical data were collected from all the study subjects, along with measurements of arterial blood gas, Cys-C, β2-MG, serum creatinine (Scr), urea nitrogen (BUN), partial pressure of carbon dioxide (PCO2), and high-sensitivity C-reactive protein (hs-CRP).ResultsThe levels of hs-CRP, Cys-C, β2-MG, Scr, and BUN were highest in the severe hypoxia group, followed by the moderate hypoxia group, then the mild hypoxia group, and lowest in the control group. The differences between the groups were statistically significant for these indicators (P < 0.05). Apart from in the cases of Scr and BUN, there were no statistically significant differences between the mild group and the control group (P > 0.05). The levels of Cys-C and β2-MG were positively correlated with the levels of hs-CRP, PCO2, Scr, and BUN and negatively correlated with PO2 levels. hs-CRP and PO2 were high-risk factors influencing Cys-C levels, and β2-MG was a risk factor influencing Cys-C levels. The level of PO2 was a high-risk factor influencing β2-MG levels, and PCO2 and Cys-C were risk factors influencing β2-MG levels.ConclusionRenal injury was found to be present in patients with AECOPD and worsened with increasing degrees of hypoxia. Hypoxia and inflammation might be risk factors for renal injury in patients with AECOPD, Cys-C and β2-MG could be sensitive indicators for the early detection of renal injury.

Organic geochemistry evidence for wildfire and elevated pO2 at the Frasnian–Famennian boundary

The Devonian experienced radiations of plants and animals, as well as a major mass extinction event during the Frasnian–Famennian (FF) interval. Proposed triggers have been linked to volcanism, extraterrestrial impact, sea-level fluctuations, and climate cooling, etc. However, the nature of the wildfires and its role in the biotic evolution have been rarely investigated for the FF interval. Here, we report organic geochemistry proxies (e.g., polycyclic aromatic hydrocarbons, PAHs) in three sections from New York (USA) to further investigate the wildfire activity and its potential link with the environmental and biotic perturbations around the FF interval. The studied intervals are dominated by three-ring PAHs which display an increasing abundance stratigraphically towards the FF boundary (FFB). An increase of 6-ring over 3-ring PAHs across the FFB is also observed for the studied sections, indicating elevated burning temperature. Additionally, slightly increased plant wax abundance and average chain length values and relatively constant Pr/Ph ratios are observed. Collectively, these results propose an increased burning frequency over the FF interval caused by elevated pO2 level, rather than a change in aridity. Terrestrial input only slightly increased across the FFB, and there is limited evidence for ocean anoxia. This correlates with the hypothesis that pCO2 drawdown and climate cooling could have been a driving mechanism of the FF biocrisis.

Development of a novel method for measuring tissue oxygen pressure to improve the hypoxic condition in subcutaneous islet transplantation

Subcutaneous tissue is a promising site for islet transplantation, but poor engraftment, due to hypoxia and low vascularity, hinders its prevalence. However, oxygen partial pressure (pO2) of the subcutaneous space (SC) and other sites were reported to be equivalent in several previous reports. This contradiction may be based on accidental puncture to the indwelling micro-vessels in target tissues. We therefore developed a novel optical sensor system, instead of a conventional Clark-type needle probe, for measuring tissue pO2 and found that pO2 of the SC was extremely low in comparison to other sites. To verify the utility of this method, we transplanted syngeneic rat islets subcutaneously into diabetic recipients under several oxygenation conditions using an oxygen delivery device, then performed pO2 measurement, glucose tolerance, and immunohistochemistry. The optical sensor system was validated by correlating the pO2 values with the transplanted islet function. Interestingly, this novel technique revealed that islet viability estimated by ATP/DNA assay reduced to less than 75% by hypoxic condition at the SC, indicating that islet engraftment may substantially improve if the pO2 levels reach those of the renal subcapsular space. Further refinements for a hypoxic condition using the present technique may contribute to improving the efficiency of subcutaneous islet transplantation.

Imaging of the right ventricle in predicting the development of chronic thromboembolic pulmonary hypertension (CTEPH)

There is increasing evidence in the literature emphasizing the importance of right ventricular (RV) imaging in the prognosis of pulmonary hypertension. We aimed to investigate the predictive role of RV dysfunction parameters assessed by echocardiography (ECHO) and thorax computed tomography (CT) in developing CTEPH. We included prospectively patients diagnosed with pulmonary embolism (PE). All patients underwent ECHO and CT within 24 hours after admission. We repeated CT and ECHO after six months and one year to assess the incidence of CTEPH and the predictive role of RV dysfunction factors in the development of CTEPH. We included twenty-two patients (seven male) with a mean age of 53.9±17.9 years; CTEPH developed in two patients during the follow-up. Baseline PO2 levels were significantly lower in patients with CTEPH (61.5±11.4 vs 77.8±25.2, p&lt;0.05). The baseline RV diameter, RV EF, and systolic PAP levels evaluated by ECHO differed significantly in two patients who developed CTEPH. Two patients that developed CTEPH had the lowest RVS (-10.3% and -11.7%). This study claims that hypoxemia, decreased RV EF, RVS, increased systolic PAP values in ECHO, and increased RV/LV ratio evaluated in thorax CT indicate the severity of RV dysfunction in acute PE and may predict CTEPH development.

The effect of targeted hyperoxemia in a randomized controlled trial employing a long-term resuscitated, model of combined acute subdural hematoma and hemorrhagic shock in swine with coronary artery disease: An exploratory, hypothesis-generating study.

Controversial evidence is available regarding suitable targets for the arterial O2 tension (PaO2) after traumatic brain injury and/or hemorrhagic shock (HS). We previously demonstrated that hyperoxia during resuscitation from hemorrhagic shock attenuated cardiac injury and renal dysfunction in swine with coronary artery disease. Therefore, this study investigated the impact of targeted hyperoxemia in a long-term, resuscitated model of combined acute subdural hematoma (ASDH)-induced brain injury and HS. The prospective randomized, controlled, resuscitated animal investigation consisted of 15 adult pigs. Combined ASDH plus HS was induced by injection of 0.1 ml/kg autologous blood into the subdural space followed by controlled passive removal of blood. Two hours later, resuscitation was initiated comprising re-transfusion of shed blood, fluids, continuous i.v. noradrenaline, and either hyperoxemia (target PaO2 200 – 250 mmHg) or normoxemia (target PaO2 80 – 120 mmHg) during the first 24 h of the total of 54 h of intensive care. Systemic hemodynamics, intracranial and cerebral perfusion pressures, parameters of brain microdialysis and blood biomarkers of brain injury did not significantly differ between the two groups. According to the experimental protocol, PaO2 was significantly higher in the hyperoxemia group at the end of the intervention period, i.e., at 24 h of resuscitation, which coincided with a higher brain tissue PO2. The latter persisted until the end of observation period. While neurological function as assessed using the veterinary Modified Glasgow Coma Score progressively deteriorated in the control group, it remained unaffected in the hyperoxemia animals, however, without significant intergroup difference. Survival times did not significantly differ in the hyperoxemia and control groups either. Despite being associated with higher brain tissue PO2 levels, which were sustained beyond the intervention period, targeted hyperoxemia exerted neither significantly beneficial nor deleterious effects after combined ASDH and HS in swine with pre-existing coronary artery disease. The unavailability of a power calculation and, thus, the limited number of animals included, are the limitations of the study.

P-029: OCCLUSIONCHIP: A FUNCTIONAL MICROCAPILLARY OCCLUSION ASSAY COMPLEMENTARY TO EKTACYTOMETRY FOR ASSESSING RED CELL HEALTH IN SICKLE CELL DISEASE

Purpose: Red blood cell (RBC) deformability is a biomarker to assess the clinical status and response to therapy in sickle cell disease (SCD). RBC deformability has been measured by ektacytometry for decades, using shear or osmolar stress. However, ektacytometry averages the RBC population, and cannot report small fractions of abnormal RBCs. A single cell-based, functional RBC deformability measurement provides essential information on the presence of unmodified cell populations that can perpetuate disease complications after the implementation of drug or cell-based therapies. There are two goals in this study: to determine the reproducibility of values generated by the standardized OcclusionChip assay and commercially available Oxygen Gradient Ektacytometry (LORRCA); and to determine if the OcclusionChip assay could complement Ektacytometry for detection of abnormal RBCs in small fractions. Materials and methods: OcclusionChip microfluidic assay design includes a gradient of capillary network-inspired micropillar arrays embedded into the microfluidic channel forming microcapillaries from 20 μm down to 4 μm. This mimics the non-uniform, continuously changing capillaries in the capillary bed, retaining RBCs with significantly decreased deformability in the upstream array with coarser openings, and those with modestly decreased deformability in the downstream array with finer openings. Micropillar arrays were coupled with two 60-μm side passageways mimicking capillary bed arteriovenous anastomoses. This helps regulate blood flow; when an upstream portion of the array is obstructed, incoming RBCs can flow into the microfluidic anastomosis and re-enter the array downstream. To test the relative merits of the OcclusionChip and Ektacytometry, we measured the elongation index (EI by Oxygen Gradient Ektacytometry) and occlusion index (OI by OcclusionChip) of blood samples containing gradient concentrations of glutaraldehyde-stiffened RBCs. We also tested clinical blood samples obtained from subjects with SCD using oxygen gradient ektacytometry, which measures the EI at a range of pO2 level (159 mmHg to ~5 mmHg), and the hypoxic OcclusionChip assay, which measures OI at physiologic hypoxic pO2 level (45 mmHg). Results: We tested glutaraldehyde-stiffened RBCs for up to 1% volume fraction; ektacytometry detected no significant change in Elongation Index (EI), while the OcclusionChip showed significant differences in OI (Figure 1). OcclusionChip detected a significant increase in OI in RBCs from an individual with sickle cell trait (SCT) and from a subject with SCD who received allogeneic hematopoietic stem cell transplant (HSCT), as the sample was taken from normoxic (pO2:159 mmHg) to physiologic hypoxic (pO2:45 mmHg) conditions (Figure 2). Oxygen gradient ektacytometry detected no difference in EI for SCT or HSCT. Conclusion: The OcclusionChip assay is more sensitive to alterations in RBC deformability in SCD, particularly when %hemoglobin S (HbS) is small, thus able to complement Ektacytometry for a more accurate assessment of patient clinical status. These results suggest that the single cell-based OcclusionChip enables the detection of HbS-related RBC abnormalities in SCT and SCD, particularly when the HbS level is low. We conclude that the OcclusionChip is complementary to the population-based Ektacytometry assays and provides additional sensitivity and capacity to detect small but clinically significant populations of abnormal RBC.Figure 1. The OcclusionChip enables the detection of small-fraction glutaraldehyde-stiffened RBCs in mixtures with normal RBCs. (A) Elongation Index (EI) by ektacytometry. (B) Occlusion Index (OI) results on the same RBC mixtures.Figure 2. OcclusionChip enables detection of HbS-related RBC abnormalities under hypoxia in SCT and SCD. Shown are (A) Elongation Index (EI) results by oxygen gradient ektacytometry and (B) Occlusion Index (OI) results by the OcclusionChip. The authors do not declare any conflict of interest

Tumoral oxygenation and biodistribution of Lonidamine oxygen microbubbles following localized ultrasound-triggered delivery

Prior work has shown that microbubble-assisted delivery of oxygen improves tumor oxygenation and radiosensitivity, albeit over a limited duration. Lonidamine (LND) has been investigated because of its ability to stimulate glycolysis, lactate production, inhibit mitochondrial respiration, and inhibit oxygen consumption rates in tumors but suffers from poor bioavailability. The goal of this work was to characterize LND-loaded oxygen microbubbles and assess their ability to oxygenate a human head and neck squamous cell carcinoma (HNSCC) tumor model, while also assessing LND biodistribution. In tumors treated with surfactant-shelled microbubbles with oxygen core (SE61O2) and ultrasound, pO2 levels increased to a peak 19.5 ± 9.7 mmHg, 50 s after injection and returning to baseline after 120 s. In comparison, in tumors treated with SE61O2/LND and ultrasound, pO2 levels showed a peak increase of 29.0 ± 8.3 mmHg, which was achieved 70 s after injection returning to baseline after 300 s (p < 0.001). The co-delivery of O2andLNDvia SE61 also showed an improvement of LND biodistribution in both plasma and tumor tissues (p < 0.001). In summary, ultrasound-sensitive microbubbles loaded with O2 and LND provided prolonged oxygenation relative to oxygenated microbubbles alone, as well as provided an ability to locally deliver LND, making them more appropriate for clinical translation.

Widespread wildfires linked to early Albian Ocean Anoxic Event 1b: Evidence from the Fuxin lacustrine basin, NE China

Wildfires are an important source of disturbances in the Earth's system and are of great significance for understanding the interactions between environmental, atmospheric and vegetation changes over deep time. The early Cretaceous was a “high-fire” interval with frequent and widespread wildfires globally, but the timing and global significance of these wildfire events during this time remain uncertain. We undertook a multi-proxy study evaluating kerogen macerals, inertinite reflectance, and polycyclic aromatic hydrocarbons (PAHs) from mudstones to characterize wildfire activity in the Albian coal-forming Fuxin lacustrine Basin, and correlate these with (i) environmental and floral changes on land, and (ii) well-dated marine events including the early Albian Oceanic Anoxic Event 1b (OAE 1b), to consider their environmental and climatic significance. The presence of high inertinite contents demonstrate that multiple, widespread wildfire events occurred during the early Albian, which are correlated stratigraphically to the Kilian, Paquier and Leenhardt sub-events of the early Albian OAE 1b. Inertinite reflectance values ranging from 0.6% to 3.8%Ro show that wildfires in the early Albian were dominated by ground fires, with a smaller proportion of surface fires and almost no crown fires. Atmospheric oxygen concentration (pO2) levels, estimated from inertinite contents, attained ~25% during the early Albian, which exceeded the present atmospheric oxygen level of 21% and was able to support sustained combustion. Climatic conditions and frequent wildfire activity in the early Albian might have acted as an important control on vegetation distribution and diversification, which possibly further promoted the evolution of early angiosperms during the early Cretaceous. Wildfire activity resulted in the burning and destruction of both vegetation and soil structure, enhancing the post-fire erosion associated with intensified continental weathering under warmer and more humid conditions during the early Albian OAE 1b interval. These episodes of high wildfire activity correlate with high nutrients and organic matter levels in lakes and thereby contributed to eutrophication and anoxia in lacustrine and in contemporaneous oceanic systems.

Reduction of enteric methane production with palm oil: Responses in dry matter intake, rumen fermentation and apparent digestibility in sheep

The aim of the trial was to assess the effect of palm oil (PO; Elaeis guineensis Jacq.) in a basal ration of low-quality Pennisetum purpureum grass on DMI, enteric CH4 emissions, rumen fermentation and apparent digestibility in hair sheep. Eight non-castrated male Pelibuey sheep with an average live weight (LW) of 28 ± 1.1 kg housed in metabolic crates inside respiration chambers, were used in a replicated 4 × 4 Latin square design. Each period lasted 18 days (13 days for adaptation to handling and rations, and 5 days for measurements of response variables). A control (CON) ration and three PO levels were evaluated: 20, 40 and 60 g/kg as a percentage of dry matter (DM) in the ration. The basal ration had a 70:30 forage:concentrate ratio (DM basis). Individual DMI was measured daily. Measurement of apparent digestibilities of nutrients was carried out by total collection of feces. Samples of rumen liquor were taken postprandial from sheep, subsequently, the molar proportion of VFA was determined. Enteric CH4 production (L/d) was measured using head boxes. Average intakes of DM per day (855 g/d), DM/kgW0.75 (64 g/d), organic matter (OM; 809 g/d) and crude protein (CP; 106 g/d) were not affected by treatment (P > 0.05). Neutral detergent fiber (NDF) and crude fat (CF) intake were reduced linearly (P < 0.05) as the percentage of PO in the ration was increased. Apparent digestibilities of DM, OM and NDF were not affected by the inclusion of PO (P > 0.05). Molar proportion of propionic acid in the rumen increased linearly as the level of PO inclusion in the ration was augmented (P < 0.05). The acetic:propionic acid ratio decreased linearly (P < 0.01) from 2.02 for the control ration to 1.66 for the ration with 60 g/kg PO. Enteric CH4 emissions decreased with increasing levels of PO in the ration (P < 0.01). Energy loss (MJ/d) as CH4 was reduced (P < 0.01), as well as methane energy loss as a proportion of gross energy intake (Ym; P < 0.01) and CH4 emission per year (EF; P < 0.01). Results demonstrate that PO is a promising by-product for mitigating CH4 emissions in hair sheep fed low-quality tropical grasses, with reductions of up to 14.1 %, without negative effects on DMI, nutrient intake and ration digestibility.

Constraining marine anoxia under the extremely oxygenated Permian atmosphere using uranium isotopes in calcitic brachiopods and marine carbonates

The redox chemistry change in ancient oceans has profoundly shaped the evolutionary trajectories of animals. Uranium isotopes (δ238U) in marine carbonate sediments have widely been used to place quantitative constraints on the oxygenation state of the oceans through geological history. However, syndepositional and post-depositional diagenesis impose a positive and variable δ238U offset in the carbonate sediments relative to contemporaneous seawater, leaving uncertainties on quantification of anoxic seafloor areas in the past. Studies from modern settings suggest that Low-Magnesium Calcite (LMC) in articulate brachiopod shells are diagenetic resistant materials that may faithfully record the δ238U value of ancient seawater. However, this notation has not yet been validated in geological records. Here, we test this hypothesis by analyzing paired brachiopod shells and the host carbonate rocks from several Permian stratigraphic successions in South China. Forty-nine articulate brachiopod fossil shells and twenty-six host carbonate rocks from the Early Permian to the Late Permian were investigated. We performed a rigorous screening to monitor the diagenetic process that might have influenced the δ238U of the shells using a scanning electronic microscope, cathodoluminescent microscopy, and major and trace elements. We estimate that 53% of the shells preserve the primary seawater δ238U signals. Using the screened δ238U values of shells and bulk carbonates, we suggest there were four episodes of expanding marine anoxia during the Permian that are temporally coincident with periods of volcanism. The first two oceanic anoxic events occurred at a time when atmospheric pO2 levels were predicted to be higher than today. The last two events are temporally coincident or immediately preceding the end-Guadalupian and the end-Permian mass extinctions, respectively, confirming previous suggestions that marine anoxia was a critical factor in driving marine animal extinctions.

Hypersalinity effects on O2 flux across the diffusive boundary layer of leaves in the tropical seagrass Thalassia testudinum

Hypersalinity is a major stressor to seagrasses, particularly in highly evaporative coastal estuaries and lagoons as well as those subjected to brine effluent from desalination systems, a condition likely to be heightened under a warming climate. While hypersalinity has been well established to cause physiological dysfunction, the effects on internal seagrass pO2 and O2 flux to the water column has not been explicitly studied. We examined the pO2 across the leaf diffusive boundary layer and estimated O2 flux rates from T. testudinum leaves at 35, 45, 55, and 65 salinity in the light and dark using O2 microsensors. Leaf segments were used to examine photophysiological responses and leaves of shoots in intact cores with multiple shoots to evaluate internal leaf pO2 flux that incorporates whole-plant sinks. Steady-state pO2 levels internally and at the leaf surface were also quantified at light saturation and in the dark. We found hypersalinity (45–65) primarily affected the O2 dynamics of T. testudinum leaves in the light based on leaf segments and whole plants. Net and gross photosynthetic rates of leaf segments were significantly lower at 55 and 65 salinities compared to controls (35), and net photosynthesis at 65 salinity was significantly lower than at 55 salinity. In contrast, the light required to compensate for leaf respiration (Icomp) was not affected by hypersalinity, and photosynthetic efficiency was only significant between 35 and 55 salinities above compensation irradiances (Φ(I comp – 200)), suggesting lesser effects of hypersalinity on photosynthesis at low irradiance below compensation (0–50 μmol photon m−2 s−1). We propose that hypersalinity, particularly ≥55 causes photosynthetic dysfunction limiting leaf O2 production, specifically Pmax at high irradiance. Further, our data indicate that with increasing hypersalinity more of the O2 produced by leaves in intact shoots is consumed by meristems and/or belowground tissues and the sediment. These O2 sinks are likely more significant than O2 lost to leaf respiration (RD) that was not shown to increase with salinity in experiments using leaves in isolation. Thus, hypersalinity not only affects the physiology, growth and reproduction of seagrasses, but also their O2 balance. For seagrass species growing at their upper salinity thresholds, a management strategy that lowers hypersalinity exposure would limit loss of seagrasses to O2 imbalance from hypersalinity effects on photosynthesis and ecosystem O2 demand.

Oxygen sensor of the heart.

How oxygen is sensed by the heart and what mechanisms mediate its sensing remain poorly understood. As recent reports show that low PO2 levels are detected by the cardiomyocytes in a few seconds, the rapid and short applications of low levels of oxygen (acute hypoxia), which avoid multiple effects of chronic hypoxia, may be used to probe the oxygen-sensing pathway of the heart. Here, we explored the oxygen-sensing pathway, focusing primarily on cellular surface membrane proteins that were first exposed to low PO2. Such studies suggest that acute hypoxia primarily targets the cardiac calcium channels, where either the channel itself or moieties closely associated with it, for instance heme-oxygenase-2 (HO-2) interacting through kinase phosphorylation, signal the α-subunit of the channel to the altered levels of PO2. Amino acids 1572-1651, the CaMKII phosphorylation sites (S1487 and S1545), CaM-binding sites (I1624 and Q1625), and Ser1928 of the carboxyl tail of the α-subunit appear to be critical residues that sense oxygen. Future studies on HO-2 knockout mice or CRISPR/Cas9 gene-edited human-induced pluripotent stem-cell-derived cardiomyocytes that reduce CaM-binding affinity are likely to provide deeper insights into the O2-sensing mechanisms.

Oxygen Monitoring in Model Solutions and In Vivo in Mice During Proton Irradiation at Conventional and FLASH Dose Rates.

FLASH is a high-dose-rate form of radiation therapy that has the reported ability, compared with conventional dose rates, to spare normal tissues while being equipotent in tumor control, thereby increasing the therapeutic ratio. The mechanism underlying this normal tissue sparing effect is currently unknown, however one possibility is radiochemical oxygen depletion (ROD) during dose delivery in tissue at FLASH dose rates. In order to investigate this possibility, we used the phosphorescence quenching method to measure oxygen partial pressure before, during and after proton radiation delivery in model solutions and in normal muscle and sarcoma tumors in mice, at both conventional (Conv) (∼0.5 Gy/s) and FLASH (∼100 Gy/s) dose rates. Radiation dosimetry was determined by Advanced Markus Chamber and EBT-XL film. For solutions contained in sealed glass vials, phosphorescent probe Oxyphor PtG4 (1 µM) was dissolved in a buffer (10 mM HEPES) containing glycerol (1 M), glucose (5 mM) and glutathione (5 mM), designed to mimic the reducing and free radical-scavenging nature of the intracellular environment. In vivo oxygen measurements were performed 24 h after injection of PtG4 into the interstitial space of either normal thigh muscle or subcutaneous sarcoma tumors in mice. The "g-value" for ROD is reported in mmHg/Gy, which represents a slight modification of the more standard chemical definition (µM/Gy). In solutions, proton irradiation at conventional dose rates resulted in a g-value for ROD of up to 0.55 mmHg/Gy, consistent with earlier studies using X or gamma rays. At FLASH dose rates, the g-value for ROD was ∼25% lower, 0.37 mmHg/Gy. pO2 levels were stable after each dose delivery. For normal muscle in vivo, oxygen depletion during irradiation was counterbalanced by resupply from the vasculature. This process was fast enough to maintain tissue pO2 virtually unchanged at Conv dose rates. However, during FLASH irradiation there was a stepwise decrease in pO2 (g-value ∼0.28 mmHg/Gy), followed by a rebound to the initial level after ∼8 s. The g-values were smaller and recovery times longer in tumor tissue when compared to muscle and may be related to the lower initial endogenous pO2 levels in the former. Considering that the FLASH effect is seen in vivo even at doses as low as 10 Gy, it is difficult to reconcile the amount of protection seen by oxygen depletion alone. However, the phosphorescence probe in our experiments was confined to the extracellular space, and it remains possible that intracellular oxygen depletion was greater than observed herein. In cell-mimicking solutions the oxygen depletion g-vales were indeed significantly higher than observed in vivo.

Distribution of Oxygen Partial Pressures in Native Capillary Fingertip Blood Samples From a Large Diabetes Patient Population.

A data set comprising 28 533 oxygen partial pressure (pO2) values gathered from nonarterialized fingertip capillary blood samples of a large diabetes population is reported. Data were gathered routinely as part of the ongoing clinical surveillance activities of a blood glucose monitoring (BGM) system manufacturer. Overall, a mean pO2 level of 75.3 mm Hg was recorded, with a standard deviation (SD) of 10.6 mm Hg and a range of 27.7 to 151.5 mm Hg. This data set, unique in terms of size, gathered more than 14 years at four separate clinical sites, provides a robust and comprehensive representation of an unmanipulated pO2 fingertip capillary sample distribution, which should be of interest for physiological reasons, but also from a medical device development perspective, in which the effect of pO2 on device performance may be an important design consideration.

TO STUDY PARAMETERS CO-RELATING OUTCOME OF NON-INVASIVE VENTILATION IN ACUTE RESPIRATORY FAILURE

Background: Respiratory failure is a condition in which the respiratory system fails in one or both of its gas-exchanging functions- oxygenation of pulmonary arterial blood and carbon dioxide elimination from mixed venous blood. NIV is used as a replacement for invasive ventilation in a few conditions, and its exibility also allows it to be a valuable component in patient management. Its use in acute respiratory failure is well accepted and widespread. AIM: This study was conducted to study various parameters such as baseline PCO2 levels, pH, PO2 levels, Heart rate, respiratory rate, and their correlation with the outcome of Non-invasive Ventilation. This is a prospective observational studyMethods: conducted on 100 patients admitted with either Type-I or Type -II respiratory failure. Results: Respiratory rate &lt;30, Heart rate &lt;130, PCO2 45-70 are associated with good outcomes of Non-invasive ventilation. Type of respiratory failure, sputum aerobic culture are not predictors of NIV outcomes. NIV in acute respiratory failure, irrespective of the type of respiratoryConclusion: failure helps in improving gas exchange, reduces intubation and length of hospital stay hence, its use as the rst modality of treatment in patients without overt contraindications is recommended. Overall, NIV is safe and effective in patients with acute respiratory failure as there are no major complications associated with its use.

Applying Dialysis Bags to Grow Microalgae and Measure Grazing Rates by Secondary Producers

Traditional methods using sealed bottles to determine the grazing rates by secondary producers neglect chemical changes induced by biological activities during the incubation, giving rise to instable levels of nutrients, pH, pCO2, pO2 and other chemicals along with changing microalgal cell concentrations and grazers’ metabolism. Here, we used dialysis bags, which allows exchanges of nutrients and gases, to grow microalgae and to determine grazing rates of secondary producers. The specific growth rate of diatom within the dialysis bags increased with increasing water velocities, indicating its suitability to grow microalgae under dynamic water conditions. Then, we compared the grazing rates by the heterotrophic dinoflagellate Noctiluca scintillans measured with the traditional method using polycarbonate (PC) bottles and the approach with the dialysis bags, and found that these two methods gave rise to comparable grazing rates. Nevertheless, the concentrations of inorganic nitrogen and phosphate in the closed PC bottles were about 89–94% lower than those in the dialysis bags due to the microalga’s assimilation. Subsequently, we applied it to determine the grazing rates by a copepod and an oyster (in the presence of other grazers). Consistent results were obtained using the dialysis bags to determine grazing rates by copepods. During the mesocosm (3000 L) experiment in the presence of primary and secondary producers, the grazing rates by the oyster Crassostrea angulata were determined based on the difference of phytoplankton biomass within and outside of the dialysis bags that held all organisms in the mesocosm except the oyster. Since the dialysis bags are permeable to gases, the grazing rates by the oyster under 410 (AC) and 1,000 (HC) μatm CO2 were successfully measured, with a promising result that HC significantly increased the oyster’s grazing. We concluded that using dialysis bags to grow microalgae and to determine grazing rates is a reliable approach, especially under different levels of CO2 and O2.

Study of Utility of Basic Arterial Blood Gas Parameters and Lactate as Prognostic Markers in Patients With Severe Dengue

BackgroundThe importance of prognostication in critical care cannot be over-emphasized, especially in the context of diseases like dengue, as their presentation may vary from mild fever to critical life-threatening illness. With the help of prognostic markers, it is possible to identify patients at higher risk and thus improve their outcome with timely intervention. Basic arterial blood gas (ABG) parameters, i.e., potential of hydrogen (pH), partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2) and bicarbonate are useful parameters, especially in critical care medicine as they are known to vary with the severity of illness. Hyperlactatemia is often referred to as a “powerful predictor of mortality”. Basic ABG parameters and lactate have been used as an essential prognostic modality in critically ill patients for decades; however, the evidence remains limited for their role as prognostic markers in patients with severe dengue.MethodWe carried out an observational retrospective cohort study comprising 163 patients with severe dengue, admitted between July 2021 and November 2021 at Medical Intensive Care Unit (MICU) of Shri Ram Murti Smarak Institute of Medical Sciences (SRMS IMS), Bareilly, Uttar Pradesh, India. Basic ABG parameters and lactate levels at the time of admission to MICU were compared between survivor and non-survivor groups of patients with severe dengue in order to evaluate their prognostic utility as predictors of mortality.ResultspH (p<0.0001), PO2 (p=0.01) and bicarbonate (<0.0001) levels were significantly lower, while PCO2 (p=0.002) and lactate (p<0.0001) levels were significantly higher in non-survivor group as compared to survivor group. Lactate was found to be the best prognostic marker with Area Under the Curve (AUC) of 88.7% on Receiver Operating Characteristics (ROC) analysis.ConclusionBasic arterial blood gas parameters and lactate can be used as feasible prognostic markers in patients with severe dengue.

Straw returning mediates soil microbial biomass carbon and phosphorus turnover to enhance soil phosphorus availability in a rice-oilseed rape rotation with different soil phosphorus levels

The alleviation of phosphorus (P) limitation by increasing carbon (C) input is an effective strategy for improving crop production and P uptake efficiency. However, the effects of straw returning on soil microbial biomass P (MBP) turnover and P fractions in paddy-upland rotation remain poorly understood. Soil MBP turnover involves the mineralization and immobilization of organic P (Po), potentially altering P fractions and reducing the risk of P loss. The effects of straw returning on soil MBP turnover, P fractions and crop P utilization during the rice-oilseed rape rotation were evaluated in two field experiments with different soil Po levels. The treatments included no P fertilizer (-P), P fertilizer (+P) and P fertilizer plus straw returning (+P + S). The crop P uptake and cumulative P utilization efficiency were increased by straw returning. Straw addition promoted microbial biomass, decreased the MBC:MBP ratio in Po-high soil, increased the MBC:MBP ratio in Po-low soil, and increased the MBP turnover rates and fluxes in both soils. According to structural equation modeling (SEM), soil MBC and MBP had significant effects on crop P uptake directly or via P fractions. In Po-high soil, straw addition increased inorganic P (Pi) (NaHCO3 and NaOH) and decreased Po content by increasing the MBP turnover, while the Po-low soil mainly increased Po content. Among multiple observed variables, MBP was the most important driving factor controlling P uptake in Po-high soil, while MBC and NaOH-Pi were the best driving factors in Po-low soil. Additionally, the soil MBC, MBP and MBC:MBP ratios were higher in the oilseed rape season than in the rice season. Consequently, straw returning improves soil P availability by increasing MBP turnover, which is beneficial for improving P utilization.

Effect of Mild Acidosis on CA2+ Signaling in Rat Carotid Body Chemoreceptor Cells: Role of CAV, ASIC, and Task

Carotid body (CB) glomus cells serve as peripheral chemoreceptors that detect changes in arterial O2 pressure (pO2) and pH, and adjust the level of ventilation to help maintain a normal level of blood pO2 and pH. Severe levels of hypoxia and acidosis are well known to cause sustained rise in cytosolic Ca2+ concentration ([Ca2+]c) in CB glomus cells. We showed recently that isolated gloms cells exhibit spontaneous [Ca2+]c oscillations and that mild levels of hypoxia increase the frequency and amplitude of Ca2+oscillations to augment the secretory response. To understand how mild levels of acidosis regulate Ca2+signaling in glomus cells, we studied the effects of small changes in extracellular pH (pHo) on the kinetics of Ca2+oscillations and the roles of Cav, ASIC and TASK. A decrease in pHo from 7.4 to 7.3 (mild acidosis) and 7.2 (moderate acidosis) produced significant increases in the frequency and amplitude of Ca2+ oscillations without affecting the resting basal [Ca2+]c. These effects on Ca2+ oscillations were not blocked by 0.1 mM amiloride (an ASIC inhibitor) that blocked Na‐H exchange in glomus cells. Mild acidosis was associated with a small but significant inhibition of TASK current and cell depolarization. The increase in Ca2+oscillations produced by mild acidosis was strongly inhibited by nifedipine (1 µM; L‐type Cav inhibitor), as well as by TTA‐P2 (20 µM; T‐type Cav inhibitor). Mild acidosis (0.1 pH unit decrease) and mild hypoxia (~5% O2) produced similar levels of change in the kinetics of Ca2+oscillations and produced an additive effect on Ca2+oscillations. Our study shows that mild to moderate levels of acidosis inhibit TASK to increase Ca2+ influx via both L‐ and T‐type Cav, resulting in increased frequency and amplitude of Ca2+ oscillations. Our study also indicate that ASICs are not involved in the stimulatory effects of mild acidosis on Ca2+oscillations.