Development of a Rapid Assay for Prolyl Hydroxylase in Mouse Lung

The National Institute for Occupational Safety and Health is conducting research on the effects of respiratory exposure to carbon nanotubes. Exposure to some kinds of carbon nanotubes has been associated with a fibrogenic response in lungs that has negative effects on lung physiology and human health. A thorough understanding of the molecular events leading to fibrosis could offer prophylactic or therapeutic approaches to avoid the fibrosis. Several different enzymes are associated with fiber formation in the lung ,and one of interest is prolyl hydroxylase (PH-4). Current protocols for measuring PH-4 activity are expensive, cumbersome, and time-consuming. A rapid assay protocol would aid in our understanding of the regulation on the enzyme’s activity. To prepare the tissue for assay, it was homogenized and then microsomes were prepared by differential centrifugation. Then, a surfactant was used to solubilize the protein, allowing substrate access. The incubation occurred in stoppered vials. The vials were placed in a 37 degree C water bath with shaking. A radioactive co-substrate for the reaction, 2-oxo[1-14C]-glutarate, was incubated in the presence and absence of a synthetic peptide containing proline and the liberated 14CO2 was captured. The reaction was terminated by adding pH 5 phosphate buffer to the reaction vial. Radioactivity was determined using liquid scintillation spectrometry. The peptide-dependent 14CO2 captured was used to estimate enzyme activity. This assay has been determined to be linear with respect to enzyme concentration as well as incubation time. This is a useful method as it can be completed in a matter of hours and requires no previous preparation of tissue or substrate. This rapid assay will be used to assess PH-4 in mouse lung from mice exposed or not exposed to carbon nanotubes. PH-4 regulation, or a lack thereof, after nanotube exposure suggests the molecular pathway by which the fibrogenic response associated with carbon nanotube exposure is elicited

Differential impact of disfiguring facial features on overt and covert attention

Observers can form negative impressions about faces that contain disfiguring features (e.g., scars). Previous research suggests that this might be due to the ability of disfiguring features to capture attention — as evidenced by contrasting observers’ responses to faces with or without disfiguring features. This, however, confounds the effects of salience and perceptual interpretation, i.e. whether the feature is seen as integral to the face, or separate from it. Furthermore, it remains unclear to what extent disfiguring features influence covert as well as overt attention. We addressed these issues by studying attentional effects by photographs of unfamiliar faces containing a unilateral disfigurement (a skin discoloration) or a visually similar control feature that was partly occluding the face. Disfiguring and occluding features were first matched for salience (Experiment 1). Experiments 2 and 3 assessed the effect of these features on covert attention in two cueing tasks involving discrimination of a (validly or invalidly cued) target in the presence of, respectively, a peripheral or central distractor face. In both conditions, disfigured and occluded faces did not differ significantly in their impact on response-time costs following invalid cues. In Experiment 4 we compared overt attention to these faces by analysing patterns of eye fixations during an attractiveness rating task. Critically, faces with disfiguring features attracted more fixations on the eyes and incurred a higher number of recurrent fixations compared to faces with salience-matched occluding features. Together, these results suggest a differential impact of disfiguring facial features on overt and covert attention, which is mediated both by the visual salience of such features and by their perceptual interpretation

Metabolic response during high-intensity interval exercise and resting vascular and mitochondrial function in CrossFit participants

High-intensity functional training (HIFT) can play a major role in preventing cardiometabolic disease. The majority of HIFT interventions incorporate CrossFit (CF) training. We measured aerobic capacity, metabolic response during high-intensity interval exercise (HIIE), resting mitochondrial oxidative capacity, and resting vascular function in adults who participated in CF training (> one year) vs. a sedentary group completing one year (SED). Twenty-one participants were recruited (CF n = 13 vs. SED n = 8). CF participants had a 33.0% greater relative VO2 peak (p.200). CF participants had greater mitochondrial oxidative capacity (p=.014). There were no differences in large artery function, but CF participants had greater baseline arterial diameter (p=.004) and faster reperfusion following arterial occlusion (p<.05). These data support HIFT programs’ effectiveness in improving fitness, weight status, and metabolic, mitochondrial, and vascular function

Assessing fatigue in adults with Axial Spondyloarthritis : a systematic review of the quality and acceptability of patient-reported outcome measures

Objective Evaluate the quality and acceptability of patient-reported outcome measures used to assess fatigue in patients with Axial Spondyloarthritis. Methods A two-stage systematic review of major electronic databases (1980-2017) to: 1) Identify measures; and 2) Identify evaluative studies. Study and measurement quality was evaluated following international standards. Measurement content was appraised against a conceptual model of RA-fatigue. Results From 387 reviewed abstracts, 23 articles provided evidence for nine fatigue-specific measures: six multi-item and three single-item. No axSpA-fatigue specific measure was identified. Evidence of reliability was limited, but acceptable for the Multi-dimensional Fatigue Inventory (internal consistency, test-retest) and Short Form 36-item Health Survey Vitality subscale (SF-36 VT) (internal consistency). Evidence of construct validity was moderate for the Functional Assessment of Chronic Illness Therapy-Fatigue and 10cm visual analogue scale, limited for the SF-36 VT, and not available for the remaining measures. Responsiveness was rarely evaluated. Evidence of measurement error, content validity or structural validity was not identified. Most measures provide a limited reflection of fatigue; the most comprehensive were the Multi-dimensional Assessment of Fatigue (MAF), MFI-20, FACIT-fatigue and Fatigue Severity Scale (FSS). Conclusion The limited content and often poor quality of the reviewed measures limits any clear recommendation for fatigue-assessment in this population; assessments should be applied with caution until further robust evidence is established. Well developed, patient-derived measures can provide essential evidence of the patient’s perspective to inform clinical research and drive tailored healthcare. The collaborative engagement of key stakeholders must seek to ensure that future fatigue assessment is relevant, acceptable and of high quality

Do facially disfiguring features influence attention and perception of faces?:Evidence from an antisaccade task

Facial disfigurements can influence how observers attend to and interact with the person, leading to disease-avoidance behaviour and emotions (disgust, threat, fear for contagion). However, it is unclear whether this behaviour is reflected in the effect of the facial stigma on attention and perceptual encoding of facial information. We addressed this question by measuring, in a mixed antisaccade task, observers' speed and accuracy of orienting of visual attention towards or away from peripherally presented upright and inverted unfamiliar faces that had either a realistic looking disease-signalling feature (a skin discolouration), a non-disease-signalling control feature, or no added feature. The presence of a disfiguring or control feature did not influence the orienting of attention (in terms of saccadic latency) towards upright faces, suggesting that avoidance responses towards facial stigma do not occur during covert attention. However, disfiguring and control features significantly reduced the effect of face inversion on saccadic latency, thus suggesting an impact on the holistic processing of facial information. The implications of these findings for the encoding and appraisal of facial disfigurements are discussed

The effect of whisker movement on radial distanceestimation: A case study in comparative robotics

Whisker movement has been shown to be under active control in certain specialistanimals such as rats and mice. Though this whisker movement is well characterized,the role and effect of this movement on subsequent sensing is poorly understood. Onemethod for investigating this phenomena is to generate artificial whisker deflections withrobotic hardware under different movement conditions. A limitation of this approachis that assumptions must be made in the design of any artificial whisker actuators,which will impose certain restrictions on the whisker-object interaction. In this paperwe present three robotic whisker platforms, each with different mechanical whiskerproperties and actuation mechanisms. A feature-based classifier is used to simultaneouslydiscriminate radial distance to contact and contact speed for the first time. We showthat whisker-object contact speed predictably affects deflection magnitudes, invariantof whisker material or whisker movement trajectory. We propose that rodent whiskercontrol allows the animal to improve sensing accuracy by regulating contact speed inducedtouch-to-touch variability

Assessing health-related quality of life (HRQoL) in survivors of out-of-hospital cardiac arrest : A systematic review of patient-reported outcome measures

Aim: High quality evidence of out-of-hospital cardiac arrest (OHCA) survivors' health-related quality of life (HRQoL) can measure the long-term impact of CA. The aim of this study was to critically appraise the evidence of psychometric quality and acceptability of measures used in the assessment of HRQoL in cardiac arrest survivors. Methods: Systematic literature searches (2004-2017) and named author searches to identify articles pertaining to the measurement of HRQoL. Data on study quality, measurement and practical properties were extracted and assessed against international standards. Results: From 356 reviewed abstracts, 69 articles were assessed in full. 25 provided evidence for 10 measures of HRQoL: one condition-specific; three generic profile measures; two generic index; and four utility measures. Although limited, evidence for measurement validity was strongest for the HUI3 and SF-36. However, evidence for reliability, content validity, responsiveness and interpretability and acceptability was generally limited or not available in the CA population for all measures. Conclusions: This review has demonstrated that a measure of quality of life specific to OHCA survivors is not available. Limited evidence of validity exists for one utility measure - the HUI3 - and a generic profile - the SF-36. Robust evidence of the quality and acceptability of HRQoL measures in OHCA was limited or not available. Future collaborative research must seek to urgently establish the relevance and acceptability of these measures to OHCA survivors, to establish robust evidence of essential measurement and practical properties over the short and long-term, and to inform future HRQoL assessment in the OHCA population. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe