24 research outputs found

    How Supraphysiological Oxygen Levels in Standard Cell Culture Affect Oxygen-Consuming Reactions.

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    Most mammalian tissue cells experience oxygen partial pressures in vivo equivalent to 1-6% O2 (i.e., physioxia). In standard cell culture, however, headspace O2 levels are usually not actively regulated and under these conditions are ~18%. This drives hyperoxia in cell culture media that can affect a wide variety of cellular activities and may compromise the ability of in vitro models to reproduce in vivo biology. Here, we review and discuss some specific O2-consuming organelles and enzymes, including mitochondria, NADPH oxidases, the transplasma membrane redox system, nitric oxide synthases, xanthine oxidase, and monoamine oxidase with respect to their sensitivities to O2 levels. Many of these produce reactive oxygen and/or nitrogen species (ROS/RNS) as either primary end products or byproducts and are acutely sensitive to O2 levels in the range from 1% to 18%. Interestingly, many of them are also transcriptional targets of hypoxia-inducible factors (HIFs) and chronic cell growth at physioxia versus 18% O2 may alter their expression. Aquaporins, which facilitate hydrogen peroxide diffusion into and out of cells, are also regulated by HIFs, indicating that O2 levels may affect intercellular communication via hydrogen peroxide. The O2 sensitivities of these important activities emphasize the importance of maintaining physioxia in culture.Peer Reviewe

    Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

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    Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

    Synthesis and electrochemical characterisation of poly(tempoacrylate)

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    A new polymer containing TEMPO radical groups has been characterised by ESR and cyclic voltammetry; electrodes modified with this polymer display high electroactivity for amine oxidation.</p

    Synthesis and electrochemical characterisation of poly(tempoacrylate)

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    A new polymer containing TEMPO radical groups has been characterised by ESR and cyclic voltammetry; electrodes modified with this polymer display high electroactivity for amine oxidation.</p

    Obstacle avoidance task.

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    <p>(A.) The visual display in a portable format including: depth camera, goggle mounted LEDs, laptop and cooling packs. (B.) A photo of one configuration of the obstacle course and top-down schematics of all ten configurations. (C.) Graphs showing the three main outcome measures averaged across all subjects for each of the ten randomly assigned courses. The total time to completion shows a logarithmic decrease from an average of 112 seconds for the Trial 1 down to 52 seconds by Trial 10 (R<sup>2</sup> = 0.91). Median velocity increased linearly across trials from 17 to 31 cm/s (R<sup>2</sup> = 0.86). The average number of collisions decreased linearly across trials from 3.9 at Trial 1 to 1.7 at Trial 10 (R<sup>2</sup> = 0.68). Bars represent one standard error.</p

    Head-mounted search task with sight impaired individuals.

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    <p>(A.) A pair of ski goggles carrying an array of LEDs and digital gyroscope (IMU-3000, Sparkfun) connected to a computer. An example of the stimuli (a binocular set of illuminated 2×2 squares) is visible on the display. (B.) Six representative sets of head position data from blind individuals orienting towards stimuli appearing between ±60 degrees. As the participant turns to face each new target, the blue head position trace approaches zero. Several undetected targets are apparent at high eccentricities. (C.) This graph from a sight impaired participant shows the linear relationship between target eccentricity and the time to orient. Fitting a line through these points allows a predicted time for a target appearing at 30° to be estimated. (D.) Response times from all participants and a sighted control (in red) to orient towards a target at 30° vs total DLTV score. The majority of those tested performed similarly to the control. Conspicuous outliers above 10 seconds were found in three participants who had extremely constricted fields of view due to retinitis pigmentosa (RP).</p

    Distributing a depth image across the binocular display.

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    <p>(A.) A single frame from the depth camera showing several chairs and obstacles. In order to generate a correctly proportioned display, only the central strip was presented (B.). This was divided into two binocular viewpoints (C. and D.) where the central portion (2) was shared between both eyes and unique thirds (1 and 3) were presented in the periphery of each display.</p

    Depth-to-brightness imaging and prototype headset.

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    <p>The role of the software was to transform a depth map into a viewable image by converting distance into brightness, such that closer images appear brighter (A. and B.). In the example above two large forms easily identifiable as a person and a small partitioned wall. Increasing distances are represented as a gradual darkening towards a pre-set depth limit. The prototype visual display designed for use in this study consisted of a depth camera and a horizontal array of LEDs mounted on ski goggles (C. and D.). The display was split binocularly with 12×8 LEDs per eye. The individual in this figure has given written informed consent, as outlined in the PLOS consent form, to publication of their photograph.</p
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