Changes In Oxygenation Research Articles

Changes of transcutaneous oxygen pressure in compressed areas of surgical patients: A prospective study of influencing factors

ObjectiveTo compare the transcutaneous oxygen pressure (tcpO2) measurement values and changes in compressed areas of surgical patients before and after surgery and to explore the related factors influencing the tcpO2 changes before and after surgery. MethodsResearchers selected 100 patients who underwent elective surgery in a tertiary comprehensive hospital from November 2021 to September 2022. A self-designed general information questionnaire was used to collect patient general information and disease-related data, including gender, age, smoking and drinking history, hypertension, diabetes, local skin temperature and humidity, related biochemical indicators, and activities of daily living score. Researchers used a transcutaneous oxygen pressure meter to measure and record the tcpO2 of the compressed areas (sacrococcygeal area, scapula area, and heel area) before and after surgery. ResultsAmong the 100 patients, 37.00 % (37/100) developed type I/II pressure ulcers after surgery, and 30 patients (81.08 %) showed regression within 2 h after surgery. There was no statistically significant difference in the preoperative tcpO2 measurement values of the scapula and heel areas between the group with and without pressure ulcers, but the preoperative tcpO2 measurement value of the sacrococcygeal area in the group without pressure ulcers was higher than that in the group with pressure ulcers (P < 0.01). The factors affecting the preoperative tcpO2 measurement value of the sacrococcygeal area were smoking and surgical type. After surgery, the tcpO2 measurement values of the three areas in the group with pressure ulcers were significantly lower than those in the group without pressure ulcers (P < 0.01). Comparing the tcpO2 values of different areas, it was found that the tcpO2 value was lowest in the sacrococcygeal area, followed by the heel area, and the tcpO2 value in the scapula area was highest both before and after surgery (P < 0.01). The main factors affecting the postoperative tcpO2 measurement value were diabetes, Glassgow score, surgical time, and intraoperative red blood cell transfusion. ConclusionThe measurement of tcpO2 is related to the incidence of surgically acquired pressure ulcers, and this technology may become an important tool for quantitative assessment of the risk of pressure ulcers.

Reconstructing hypoxia on the eastern Arabian sea continental shelf during the past ∼7400 years: A multi-proxy approach

Shallow-sea environmental variations in the eastern Arabian Sea (EAS) have been related to monsoon variability, poorly ventilated intermediate water, and primary productivity changes. To understand these conditions, benthic foraminiferal assemblages, oxygen isotope ratios, and total organic carbon content have been examined in sediment Core SK291/GC13 from the EAS. We aim to retrieve decadal to centennial time-scale changes in past oxygenation and paleoproductivity during the last 7400 calibrated years before the present (cal yr BP). Our proxy data suggest that the oxic benthic foraminifera species were dominant during ∼7400–6000 cal yr BP. The change from oxic to dysoxic occurred during ca. 6000–3500 cal yr BP, and transition from dysoxic to suboxic environmental conditions happened at ca. ∼3500 cal yr BP. These changes are contemporaneous with weakening of the Indian summer monsoon beginning at ∼5500 cal yr BP which culminated into a major arid phase so-called ca 4.2 ka event in the Indian subcontinent. The EAS experienced low productivity during the early phase of our studied interval (∼7400–6000 cal yr BP) and higher productivity in the middle Holocene (6000–3000 cal yr BP), as revealed by the total organic carbon and benthic assemblages. Furthermore, productivity increased in the warm period and decreased in the Little Ice Age on a decadal scale. The spectral analysis of total organic content and suboxic species indicates a 23-year Hale (solar) cycle during the last millennium, indicating a close relationship between solar activity and monsoon variability. The strengthening of the El Nino-Southern Oscillation perhaps amplified due to increased solar activity in the last millennium, which influenced the climate of the EAS. The study highlights paleo-oxygenation shifts based on benthic foraminiferal assemblages, which are crucial for understanding changes in the oxygen minimum zones (OMZs) and their potential impacts on marine ecosystems.

P.030 Remote ischemic conditioning in acute ischemic stroke and small vessel disease – a feasibility study

Background: We tested the hypothesis that delivering remote ischemic conditioning (RIC) with an adjunct tissue reflectance sensor (TRS) device may be feasible in patients with acute ischemic stroke (AIS) and cerebral small vessel disease (cSVD). Methods: AIS patients with neurological deficits within 7 days of symptom onset were screened for moderate to severe cSVD. Eligible patients were randomized 2:1 to receive intervention RIC or sham RIC (7 days). The primary outcome measure was intervention feasibility. It was assessed as an intervention-related comfort by a 5-point Likert scale during each session (1-very uncomfortable, 5-very comfortable). The secondary outcome measure was assessment of TRS derived dermal blood concentration and blood oxygenation changes during RIC. Results: Forty-seven (32 intervention, 15 sham) patients were enrolled at a median (IQR) 39.7 (25-64) hours after symptom onset, with mean±SD age of 75±12 years, 22 (46.8%) were females and median baseline NIHSS of 5(3-7). The Likert scale was 3.5 (3-4) in the intervention group and 4 (4-5) in the sham group. The TRS derived blood concentration and blood oxygenation changes were proportionate in the intervention arm and absent in the sham arm. Conclusions: RIC treatment with TRS is feasible in patients with AIS+cSVD. The efficacy of RIC needs further assessment.

Photoacoustic Imaging-Guided Self-Adaptive Hyperthermia Supramolecular Cascade Nano-Reactor for Diabetic Periodontal Bone Regeneration.

Commencing with the breakdown of the diabetic osteoimmune microenvironment, multiple pathogenic factors, including hyperglycemia, inflammation, hypoxia, and deleterious cytokines, are conjointly involved in the progression of diabetic periodontal bone regeneration. Based on the challenge of periodontal bone regeneration treatment and the absence of real-time feedback of blood oxygen fluctuation in diabetes mellitus, a novel self-adaptive hyperthermia supramolecular cascade nano-reactor ACFDG is constructed via one-step supramolecular self-assembly strategy to address multiple factors in diabetic periodontal bone regeneration. Hyperthermia supramolecular ACFDG possesses high photothermal conversion efficiency (32.1%), and it can effectively inhibit the vicious cycle of ROS-inflammatory cascade through catalytic cascade reactions, up-regulate the expression of heat shock proteins (HSPs) under near-infrared (NIR) irradiation, which promotes periodontal bone regeneration. Remarkably, ACFDG can provide real-time non-invasive diagnosis of blood oxygen changes during periodontal bone regeneration through photoacoustic (PA) imaging, thus can timely monitor periodontal hypoxia status. In conclusion, this multifunctional supramolecular nano-reactor combined with PA imaging for real-time efficacy monitoring provides important insights into the biological mechanisms of diabetic periodontal bone regeneration and potential clinical theranostics.

Development and Characterization of Hemoglobin Microbubbles for Acoustic Blood Oxygen Level Dependent Imaging.

Oxygen levels in tissues and organs are crucial for their normal functioning, and approaches to monitor them non-invasively have wide biological and clinical applications. In this study, we developed a method of acoustically detecting oxygenation using contrast-enhanced ultrasound (CEUS) imaging. Our approach involved the use of specially designed hemoglobin-based microbubbles (HbMBs) that reversibly bind to oxygen and alter the state-dependent acoustic response. We confirmed that the bioactivity of hemoglobin remained intact after the microbubble shell was formed, and we did not observe any significant loss of heme. We conducted passive cavitation detection (PCD) experiments to confirm whether the acoustic properties of HbMBs vary based on the level of oxygen present. The experiments involved driving the HbMBs with a 1.1 MHz focused ultrasound transducer. Through the PCD data collected, we observed significant differences in the subharmonic and harmonic responses of the HbMBs when exposed to an oxygen-rich environment versus an oxygen-depleted one. We used a programmable ultrasound system to capture high-frame rate B mode videos of HbMBs in both oxy and deoxy conditions at the same time in a two-chambered flow phantom and observed that the mean pixel intensity of deoxygenated HbMB was greater than in the oxygenated state using B-mode imaging. Finally, we demonstrated that HbMBs can circulate in vivo and are detectable by a clinical ultrasound scanner. To summarize, our results indicate that CEUS imaging with HbMB has the potential to detect changes in tissue oxygenation and could be a valuable tool for clinical purposes in monitoring regional blood oxygen levels.

Patent Ductus Arteriosus—To Close or Not to Close?

(N Engl J Med. 2024;390(4):370–371) Patent ductus arteriosus (PDA) is the most frequently encountered cardiac condition in neonates. The ductus arteriosus plays the crucial role of allowing blood to bypass the lungs in the fetal stage. At birth, with the initiation of lung function, changes in pressure and oxygen lead to the closure of the ductus arteriosus, redirecting blood flow through the newly operational pulmonary circulation. When a baby is born too early, birth is not enough to cause the duct to close, resulting in PDA.

#1551 The presence of proteinuria is associated with impaired cerebral oxygenation during exercise in chronic kidney disease

Abstract Background and Aims Cognitive impairment and reduced exercise tolerance are common in patients with chronic kidney disease (CKD), in part due to reduced brain function. Cerebral perfusion and oxygenation are significant determinants of brain activation and have been shown to be significantly impaired in CKD. This analysis aims to examine the impact of proteinuria on cerebral oxygenation during a mild physical stress in patients with pre-dialysis CKD. Method 66 patients with CKD stage 2-4 were included in this post-hoc analysis; 24-h urine samples were used for evaluation of proteinuria. All participants underwent a 3-min intermittent handgrip exercise (HG) at 35% of their maximal voluntary contraction. Changes in cerebral oxygenation (oxyhemoglobin-O2Hb) and deoxyhemoglobin-HHb) and regional blood volume (total hemoglobin-tHb) were continuously recorded during HG-exercise by near-infrared spectroscopy (NIRS). Results No significant differences between the 2 groups were detected in age (proteinuric vs nonproteinuric: 68.4 ± 10.6 vs 67.2 ± 10.8; p = 0.676), eGFR (41.3 ± 18.9 vs 46.3 ± 14.8; p = 0.248) and BMI (28.4 ± 4.9 vs 28.1 ± 4.8; p = 0.803). The MMSE score (proteinuric vs nonproteinuric: 28.0 ± 1.6 vs 28.0 ± 1.7; p = 0.938) and MVC (22.3 ± 7.0 vs 23.9 ± 7.5; p = 0.416) were not significantly different between groups. The average response in cerebral oxygenation during exercise was lower in patients with proteinuric CKD (O2Hb: 1.02 ± 0.87 vs 1.61 ± 0.95; p = 0.018 and diffO2Hb 1.53 ± .97 vs 2.07 ± 1.25; p = 0.065). The average tHb response (index of regional-blood-volume) was also lower in patients with proteinuria (0.51 ± 1.08 vs 1.16 ± 0.92 p = 0.013); however, no differences in HHb (-0.50 ± 0.55 vs -0.45 ± 0.54; p = 0.717) –an index of oxygen extraction capacity- among groups were detected. In univariate linear analysis the level of proteinuria did not show significant correlations with NIRS parameters. Conclusion The presence and not the level of proteinuria is associated with impaired brain activation during a mild physical task in patients with predialysis CKD. Future studies evaluating the role of proteinuria in the decline of cerebral function and cognitive impairment are needed.

Phosphate-associated sulfate in Lingula shells represents a potential archive for seawater sulfate composition

The marine sulfur cycle is highly sensitive to redox environments at the Earth's surface. Fluctuations in atmospheric pO2 level or marine redox environments are commonly associated with changes in seawater sulfate concentration, sulfate sulfur (S) and oxygen (O) isotopes. Thus, the marine S cycle through the Earth's ancient past provides a first-order constraint on the redox evolution of the Earth's surface. Reconstructions of the marine S cycle have been approached through analyses of various sulfate-bearing geological materials, such as sedimentary barite, evaporitic sulfate (e.g., gypsum), carbonate associated sulfate (CAS), and phosphate-associated sulfate (PAS) in phosphatic ores. These geological materials have their own pros and cons. In this study, we focus on PAS in Lingula brachiopods, which possess phosphatic shells and have a long evolutionary history since Cambrian times. Biogenic phosphate typically has a higher sulfate concentration than carbonate and phosphate ores, and is less vulnerable to diagenetic alteration. Here, we analyzed modern Lingula shells from the South China Sea and fossil Lingula shells collected from the Late Devonian Xiejingsi Formation of South China. Living and fossil Lingula shells have similar P/S ratios (PO43−/SO42−) of ∼76, and S and O isotopes of PAS (δ34SPAS and δ18OPAS) in each group show limited variations. For living Lingula shells, the mean values of δ34SPAS and δ18OPAS are +15.0 ± 1.5‰ and + 9.8 ± 0.4‰, respectively, which are ∼6‰ lower and comparable to those of modern seawater sulfate compositions (δ34SSW and δ18OSW-SO4), probably due to vital effects. For fossil Lingula shells, δ18OPAS (14.1 ± 0.9‰) is identical to coeval evaporite. The range of δ34SPAS is encompassed by the values of both coeval evaporite and CAS, but the mean value of δ34SPAS (29.5 ± 0.9‰) is higher. Thus, fossil Lingula shells show a good potential for reconstructing δ34SSW and δ18OSW-SO4 values.

Determinants and Practice Variability of Oxygen Administration during Surgery in the United States: A Retrospective Cohort Study.

The best approaches to supplemental oxygen administration during surgery remain unclear, which may contribute to variation in practice. This study aimed to assess determinants of oxygen administration and its variability during surgery. Using multivariable linear mixed-effects regression, the study measured the associations between intraoperative fraction of inspired oxygen and patient, procedure, medical center, anesthesiologist, and in-room anesthesia provider factors in surgical cases of 120 min or longer in adult patients who received general anesthesia with tracheal intubation and were admitted to the hospital after surgery between January 2016 and January 2019 at 42 medical centers across the United States participating in the Multicenter Perioperative Outcomes Group data registry. The sample included 367,841 cases (median [25th, 75th] age, 59 [47, 69] yr; 51.1% women; 26.1% treated with nitrous oxide) managed by 3,836 anesthesiologists and 15,381 in-room anesthesia providers. Median (25th, 75th) fraction of inspired oxygen was 0.55 (0.48, 0.61), with 6.9% of cases less than 0.40 and 8.7% greater than 0.90. Numerous patient and procedure factors were statistically associated with increased inspired oxygen, notably advanced American Society of Anesthesiologists classification, heart disease, emergency surgery, and cardiac surgery, but most factors had little clinical significance (less than 1% inspired oxygen change). Overall, patient factors only explained 3.5% (95% CI, 3.5 to 3.5%) of the variability in oxygen administration, and procedure factors 4.4% (95% CI, 4.2 to 4.6%). Anesthesiologist explained 7.7% (95% CI, 7.2 to 8.2%) of the variability in oxygen administration, in-room anesthesia provider 8.1% (95% CI, 7.8 to 8.4%), medical center 23.3% (95% CI, 22.4 to 24.2%), and 53.0% (95% CI, 52.4 to 53.6%) was unexplained. Among adults undergoing surgery with anesthesia and tracheal intubation, supplemental oxygen administration was variable and appeared arbitrary. Most patient and procedure factors had statistical but minor clinical associations with oxygen administration. Medical center and anesthesia provider explained significantly more variability in oxygen administration than patient or procedure factors.

Milrinone in persistent pulmonary hypertension of newborn: a scoping review.

Persistent pulmonary hypertension of the newborn (PPHN) is a common neonatal condition in newborns admitted to the neonatal intensive care units (NICUs). PPHN has still a high mortality and morbidity. Inhaled nitric oxide (iNO) is the first line vasodilator therapy for PPHN in high income countries. In low-to-middle income countries (LMICs), availability of iNO remains scarce and expensive. The purpose of this scoping review was to evaluate the current existing literature for milrinone therapy in PPHN and to identify the knowledge gaps in milrinone use in infants with PPHN. The available evidence for milrinone remains limited both as monotherapy and as an adjuvant to iNO. The studies were heterogeneous, conducted in different settings, with different populations and more importantly the endpoints of these trials were short-term outcomes such as changes in oxygenation and blood pressure. Large prospective studies investigating long-term outcomes, mortality, and the need for Extracorporeal membrane oxygenation (ECMO) are warranted. Randomized controlled trials with milrinone as monotherapy are needed in LMICs where iNO availability remains limited. IMPACT: Milrinone has a potential role in the management of PPHN both as an adjuvant to iNO as well as a monotherapy. This scoping review identified the problems existing in the published literature on milrinone and the barriers to generalization of these results. Multi-centre randomized controlled trials on milrinone, especially involving centers from low- and middle-income countries are needed, where it can be evaluated as first-line pulmonary vasodilator therapy.

Hepatic Oxygenation Changes and Symptomatic Intradialytic Hypotension.

Clinical studies on differences among changes in cerebral and hepatic oxygenation during hemodialysis (HD) in patients with and without intradialytic hypotension (IDH) are limited. We investigated changes in intradialytic cerebral and hepatic oxygenation before systolic blood pressure (SBP) reached the nadir during HD and compared these differences between patients with and without symptomatic IDH. We analyzed data from 109 patients with (n = 23) and without (n = 86) symptomatic IDH who were treated with HD. Cerebral and hepatic regional oxygen saturation (rSO2), as a marker of tissue oxygenation and circulation, was monitored during HD using an INVOS 5100c oxygen saturation monitor. Changes in cerebral or hepatic rSO2 when SBP reached the nadir during HD were compared between the groups of patients. The cerebral rSO2 before HD in patients with and without symptomatic IDH was 49.7 ± 11.2% and 51.3 ± 9.1% (p = 0.491). %Changes in cerebral rSO2 did not significantly differ between the two groups from 60 min before the SBP nadir during HD. Hepatic rSO2 before HD in patients with and without symptomatic IDH was 58.5 ± 15.4% and 57.8 ± 15.9% (p = 0.869). The %changes in hepatic rSO2 were significantly lower in patients with symptomatic IDH than in those without throughout the observational period (p &lt; 0.001). We calculated the area under the receiver operating characteristic curve (AUC) and estimated cutoff values for changes in hepatic rSO2 as a symptomatic IDH predictor. The predictive ability at 5 and 40 min before symptomatic IDH onset was excellent, with AUCs and cutoff values of 0.847 and 0.841, and -10.9% and -5.0%, respectively. Hepatic oxygenation significantly decreased more in patients with symptomatic IDH before its onset, than in those without symptomatic IDH, whereas changes in cerebral oxygenation did not differ. Evaluating changes in hepatic oxygenation during HD might help to predict symptomatic IDH.

Assessing changes in regional cerebral hemodynamics in adults with a high-density full-head coverage time-resolved near-infrared spectroscopy device.

Cerebral oximeters have the potential to detect abnormal cerebral blood oxygenation to allow for early intervention. However, current commercial systems have two major limitations: (1)spatial coverage of only the frontal region, assuming that surgery-related hemodynamic effects are global and (2)susceptibility to extracerebral signal contamination inherent to continuous-wave near-infrared spectroscopy (NIRS). This work aimed to assess the feasibility of a high-density, time-resolved (tr) NIRS device (Kernel Flow) to monitor regional oxygenation changes across the cerebral cortex during surgery. The Flow system was assessed using two protocols. First, digital carotid compression was applied to healthy volunteers to cause a rapid oxygenation decrease across the ipsilateral hemisphere without affecting the contralateral side. Next, the system was used on patients undergoing shoulder surgery to provide continuous monitoring of cerebral oxygenation. In both protocols, the improved depth sensitivity of trNIRS was investigated by applying moment analysis. A dynamic wavelet filtering approach was also developed to remove observed temperature-induced signal drifts. In the first protocol ( years; five females, five males), hair significantly impacted regional sensitivity; however, the enhanced depth sensitivity of trNIRS was able to separate brain and scalp responses in the frontal region. Regional sensitivity was improved in the clinical study given the age-related reduction in hair density of the patients ( years; 14 females, 13 males). In five patients who received phenylephrine to treat hypotension, different scalp and brain oxygenation responses were apparent, although no regional differences were observed. The Kernel Flow has promise as an intraoperative neuromonitoring device. Although regional sensitivity was affected by hair color and density, enhanced depth sensitivity of trNIRS was able to resolve differences in scalp and brain oxygenation responses in both protocols.

Interdependence of cellular and network properties in respiratory rhythm generation

How breathing is generated by the preBötzinger complex (preBötC) remains divided between two ideological frameworks, and a persistent sodium current (INaP) lies at the heart of this debate. Although INaP is widely expressed, the pacemaker hypothesis considers it essential because it endows a small subset of neurons with intrinsic bursting or "pacemaker" activity. In contrast, burstlet theory considers INaP dispensable because rhythm emerges from "preinspiratory" spiking activity driven by feed-forward network interactions. Using computational modeling, we find that small changes in spike shape can dissociate INaP from intrinsic bursting. Consistent with many experimental benchmarks, conditional effects on spike shape during simulated changes in oxygenation, development, extracellular potassium, and temperature alter the prevalence of intrinsic bursting and preinspiratory spiking without altering the role of INaP. Our results support a unifying hypothesis where INaP and excitatory network interactions, but not intrinsic bursting or preinspiratory spiking, are critical interdependent features of preBötC rhythmogenesis.

Phase 1 Study of MK-5475, an Inhaled Soluble Guanylate Cyclase Stimulator, in Participants with Pulmonary Hypertension Associated with Chronic Obstructive Pulmonary Disease.

This phase 1 study (NCT04370873) evaluated safety and pharmacokinetics/pharmacodynamics (PK/PD) of MK-5475 in participants with pulmonary hypertension associated with COPD (PH-COPD). Eligible participants were 40-80 years old with COPD (FEV1/FVC <0.7; FEV1 >30% predicted) and PH (mean pulmonary arterial pressure ≥25 mmHg). Participants were randomized 2:1 to MK-5475 or placebo via dry-powder inhaler once daily for 7 days in Part 1 (360 µg) or 28 days in Part 2 (380 µg). Safety was assessed by adverse events (AEs) and arterial blood oxygenation. Part-2 participants had pulmonary vascular resistance (PVR; primary PD endpoint) and pulmonary blood volume (PBV; secondary PD endpoint) measured at baseline and Day 28. A non-informative prior was used to calculate posterior probability (PP) that the between-group difference (MK-5475 - placebo) in mean percent reduction from baseline in PVR was less than -15%. Nine participants were randomized in Part 1, and 14 participants in Part 2. Median age of participants (86.4% male) was 68.5 years (41-77 years); 95.5% had moderate-to-severe COPD. Incidences of AEs were comparable between MK-5475 and placebo: overall (5/14 [36%] versus 5/8 [63%]), drug-related (1/14 [7%] versus 2/8 [25%]), and serious (1/14 [7%] versus 1/8 [13%]). MK-5475 caused no meaningful changes in arterial blood oxygenation or PBV. MK-5475 versus placebo led to numerical improvements from baseline in PVR (-21.2% [95% CI: -35.4, -7.0] versus -5.4% [95% CI: -83.7, 72.9]), with between-group difference in PVR less than -15% and calculated PP of 51%. The favorable safety profile and numerical reductions in PVR observed support further clinical development of inhaled MK-5475 for PH-COPD treatment.

THE PRESENCE OF PROTEINURIA IS ASSOCIATED WITH IMPAIRED CEREBRAL OXYGENATION DURING EXERCISE IN CHRONIC KIDNEY DISEASE

Objective: Cognitive impairment and reduced exercise tolerance are common in patients with chronic kidney disease (CKD), in part due to reduced brain function. Cerebral perfusion and oxygenation are significant determinants of brain activation and have been shown to be significantly impaired in CKD. This analysis aims to examine the impact of proteinuria on cerebral oxygenation during a mild physical stress in patients with pre-dialysis CKD. Design and method: 66 patients with CKD stage 2-4 were included in this post-hoc analysis; 24-h urine samples were used for evaluation of proteinuria. All participants underwent a 3-min intermittent handgrip exercise (HG) at 35% of their maximal voluntary contraction. Changes in cerebral oxygenation (oxyhemoglobin-O2Hb) and deoxyhemoglobin-HHb) and regional blood volume (total hemoglobin-tHb) were continuously recorded during HG-exercise by near-infrared spectroscopy (NIRS). Results: No significant differences between the 2 groups were detected in age (proteinuric vs nonproteinuric: 68.4±10.6 vs 67.2±10.8; p=0.676), eGFR (41.3±18.9 vs 46.3±14.8; p=0.248) and BMI (28.4±4.9 vs 28.1±4.8; p=0.803). The MMSE score (proteinuric vs nonproteinuric: 28.0±1.6 vs 28.0±1.7; p=0.938) and MVC (22.3±7.0 vs 23.9±7.5; p=0.416) were not significantly different between groups. The average response in cerebral oxygenation during exercise was lower in patients with proteinuric CKD (O2Hb: 1.02±0.87 vs 1.61±0.95; p=0.018 and diffO2Hb 1.53±.97 vs 2.07±1.25; p=0.065). The average tHb response (index of regional-blood-volume) was also lower in patients with proteinuria (0.51±1.08 vs 1.16±0.92 p=0.013); however, no differences in HHb (-0.50±0.55 vs -0.45±0.54; p=0.717) –an index of oxygen extraction capacity- among groups were detected. In univariate linear analysis the level of proteinuria did not show significant correlations with NIRS parameters. Conclusions: The presence and not the level of proteinuria is associated with impaired brain activation during a mild physical task in patients with predialysis CKD. Future studies evaluating the role of proteinuria in the decline of cerebral function and cognitive impairment are needed.

ULK1 Mediated Autophagy-Promoting Effects of Rutin-Loaded Chitosan Nanoparticles Contribute to the Activation of NF-κB Signaling Besides Inhibiting EMT in Hep3B Hepatoma Cells.

Liver cancer remains to be one of the leading causes of cancer worldwide. The treatment options face several challenges and nanomaterials have proven to improve the bioavailability of several drug candidates and their applications in nanomedicine. Specifically, chitosan nanoparticles (CNPs) are extremely biodegradable, pose enhanced biocompatibility and are considered safe for use in medicine. CNPs were synthesized by ionic gelation, loaded with rutin (rCNPs) and characterized by ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS) and transmission electron microscopy (TEM). The rCNPs were tested for their cytotoxic effects on human hepatoma Hep3B cells, and experiments were conducted to determine the mechanism of such effects. Further, the biocompatibility of the rCNPs was tested on L929 fibroblasts, and their hemocompatibility was determined. Initially, UV-vis and FTIR analyses indicated the possible loading of rutin on rCNPs. Further, the rutin load was quantitatively measured using Ultra-Performance Liquid Chromatography (UPLC) and the concentration was 88 µg/mL for 0.22 micron filtered rCNPs. The drug loading capacity (LC%) of the rCNPs was observed to be 13.29 ± 0.68%, and encapsulation efficiency (EE%) was 19.55 ± 1.01%. The drug release was pH-responsive as 88.58% of the drug was released after 24 hrs at the lysosomal pH 5.5, whereas 91.44% of the drug was released at physiological pH 7.4 after 102 hrs. The cytotoxic effects were prominent in 0.22 micron filtered samples of 5 mg/mL rutin precursor. The particle size for the rCNPs at this concentration was 144.1 nm and the polydispersity index (PDI) was 0.244, which is deemed to be ideal for tumor targeting. A zeta potential (ζ-potential) value of 16.4 mV indicated rCNPs with good stability. The IC50 value for the cytotoxic effects of rCNPs on human hepatoma Hep3B cells was 9.7 ± 0.19 μg/mL of rutin load. In addition, the increased production of reactive oxygen species (ROS) and changes in mitochondrial membrane potential (MMP) were observed. Gene expression studies indicated that the mechanism for cytotoxic effects of rCNPs on Hep3B cells was due to the activation of Unc-51-like autophagy-activating kinase (ULK1) mediated autophagy and nuclear factor kappa B (NF-κB) signaling besides inhibiting the epithelial-mesenchymal Transition (EMT). In addition, the rCNPs were less toxic on NCTC clone 929 (L929) fibroblasts in comparison to the Hep3B cells and possessed excellent hemocompatibility (less than 2% of hemolysis). The synthesized rCNPs were pH-responsive and possessed the physicochemical properties suitable for tumor targeting. The particles were effectively cytotoxic on Hep3B cells in comparison to normal cells and possessed excellent hemocompatibility. The very low hemolytic profile of rCNPs indicates that the drug could be administered intravenously for cancer therapy.

Multi-model comparison of trends and controls of near-bed oxygen concentration on the northwest European continental shelf under climate change

Abstract. We present an analysis of the evolution of near-bed oxygen in the next century in the northwest European continental shelf in a three-member ensemble of coupled physics–biogeochemistry models. The comparison between model results helps highlight the biogeochemical mechanisms responsible for the observed deoxygenation trends and their response to climate drivers. While all models predict a decrease in near-bed oxygen proportional to climate change intensity, the response is spatially heterogeneous, with hotspots of oxygen decline (up to −1 mg L−1) developing along the Norwegian trench in the members with the most intense change, as well as areas where compensating mechanisms mitigate change. We separate the components of oxygen change associated with the warming effect on oxygen solubility from those due to the effects of changes in transport and biological processes. We find that while warming is responsible for a mostly uniform decline throughout the shelf (−0.30 mg L−1 averaged across ensemble members), changes in transport and biological processes account for the detected heterogeneity. Hotspots of deoxygenation are associated with enhanced stratification that greatly reduces vertical transport. A major change in circulation in the North Sea is responsible for the onset of one such hotspot that develops along the Norwegian trench and adjacent areas in the members characterised by intense climate change. Conversely, relatively shallow and well-mixed coastal areas like the southern North Sea, Irish Sea and English Channel experience an increase in net primary production that partially mitigates oxygen decline in all members. This work represents the first multi-model comparison addressing deoxygenation in the northwest European shelf and contributes to characterising the possible trajectories of near-bed oxygen and the processes that drive deoxygenation in this region. As our downscaled members factor in riverine inputs and small- and medium-scale circulation, which are not usually well represented in earth system models, results are relevant for the understanding of deoxygenation in coastal and shelf systems.

A single exposure to 100% normo-baric oxygen therapy appears to improve sequence learning processes by increasing prefrontal cortex oxygen saturation

Previously, we showed that a normo-baric 100 % oxygen treatment (NbOxTr) enhances motor learning processes, e.g., visuomotor adaptation (VMA) and sequence learning (SL). However, this work was limited to behavioral outcomes and did not identify the physiological mechanistic underpinnings of these improvements. Here, we expand on this research to investigate the effects of a NbOxTr on the oxygen tissue saturation index (TSI) level of the prefrontal cortex (PFC) when performing a SL task and whether potential SL improvements relate to increased TSI levels in the PFC. Twenty four right-handed young, healthy adults were randomly assigned to a NbOxTr group (normo-baric 100 % oxygen, n = 12) or a control group (normal air, n = 12). They received their respective treatments via a nasal cannula during the experiment. Oxygen TSI levels of the right and left PFC were measured via near-infrared spectroscopy (NIRS) throughout different SL task phases (Baseline, Training, Testing). The NbOxTr increased the TSI of the PFC in the Training phase (p < 0.01) and positively affected SL retention in the Testing phase (p < 0.05). We also found a positive correlation between TSI changes in the right PFC during the gas treatment phase (3.4 % increase) and response time (RT) improvements in the SL task training and retention phase (all p < 0.05). Our results suggest that a simple NbOxTr increases the oxygenated hemoglobin availability in the PFC, which appears to mediate the retention of acquired SL improvements in healthy young adults. Future studies should examine treatment-related oxygenation changes in other brain areas involved and their relation to enhanced learning processes. Whether this NbOxTr improves SL in neurologically impaired populations should also be examined.

Carboxyhemoglobin predicts oxygenator performance and imminent oxygenator change in extracorporeal membrane oxygenation

BackgroundThe continuous exposure of blood to a non-biological surface during extracorporeal membrane oxygenation (ECMO) may lead to progressive thrombus formation in the oxygenator, hemolysis and consequently impaired gas exchange. In most centers oxygenator performance is monitored only on a once daily basis. Carboxyhemoglobin (COHb) is generated upon red cell lysis and is routinely measured with any co-oximetry performed to surveille gas exchange and acid–base homeostasis every couple of hours. This retrospective cohort study aims to evaluate COHb in the arterial blood gas as a novel marker of oxygenator dysfunction and its predictive value for imminent oxygenator change.ResultsOut of the 484 screened patients on ECMO 89, cumulatively requiring 116 oxygenator changes within 1833 patient days, including 19,692 arterial COHb measurements were analyzed. Higher COHb levels were associated with lower post-oxygenator pO2 (estimate for log(COHb): − 2.176 [95% CI − 2.927, − 1.427], p < 0.0001) and with a shorter time to oxygenator change (estimate for log(COHb): − 67.895 [95% CI − 74.209, − 61.542] hours, p < 0.0001). COHb was predictive of oxygenator change within 6 h (estimate for log(COHb): 5.027 [95% CI 1.670, 15.126], p = 0.004).ConclusionCOHb correlates with oxygenator performance and can be predictive of imminent oxygenator change. Therefore, longitudinal measurements of COHb in clinical routine might be a cheap and more granular candidate for ECMO surveillance that should be further analyzed in a controlled prospective trial design.

Effects of Intrapulmonary Percussive Ventilation in Nonventilated Patients Who Are Critically Ill on Length of Stay, Oxygenation, and Pulmonary Complications: A Randomized Controlled Trial

IntroductionPulmonary complications such as chest infection and pulmonary atelectasis may lead to respiratory failure, prolonged intensive care unit (ICU) stay and poor outcomes. Routine application of respiratory physiotherapy interventions is not supported by the current body of evidence. Intrapulmonary percussive ventilation (IPV) is used to treat various clinical conditions; however, the evidence to support its effectiveness in ICU remains weak. This study aimed to evaluate the effectiveness of IPV in improving outcomes in patients admitted to intensive care. Research questionWhat is the effect of IPV on ICU length of stay, oxygenation and pulmonary complications in non-ventilated critically ill patients compared to commonly applied chest physiotherapy (CPT). DesignRandomised controlled trial MethodsOf 201 patients screened, 106 were recruited. Participants with a respiratory impairment were randomly allocated to either the IPV or the CPT group. Both groups received two treatment sessions daily. Data were analysed for 100 participants for ICU length of stay, changes in oxygenation, respiratory rate and radiological findings. ResultsThe median LOS in the IPV group was 3.5 days (1.9, 5.9); in the CPT group, the LOS was 5.2 days (3.4, 9.9). The mean difference in LOS was 1.56 days (CI = 1.2 to 2.1 P = 0.002). The between-group difference (IPV minus CPT) for pre- to post-intervention SpO2 was 0.94% (95% CI = 0.43 to 1.45, P < 0.001). The between-group difference (IPV minus CPT) in respiratory rate was 2.1 breaths/minute, (95% CI: 0.9 to 3.2, P < 0.001). No significant difference in radiological atelectasis score was observed (P = 0.65). ConclusionsThis study showed that the IPV intervention reduced ICU-LOS and respiratory rate, with a small improvement in oxygenation compared to CPT interventions in non-ventilated patients. The use of IPV intervention may improve outcomes in critically ill patients with impaired respiratory function.