The short form of the Glasgow Composite Measure Pain Scale in post-operative analgesia studies in dogs: a scoping review

The measurement and treatment of acute pain in animals are essential from a welfare perspective. Valid pain-related outcome measures are also crucial for ensuring reliable and translatable findings in veterinary clinical trials. The short form of the Glasgow Composite Measure Pain Scale (GCMPS-SF) is a multi-item behavioural pain assessment tool, developed and validated using a psychometric approach, to measure acute pain in the dog. The psychometric approach refers to a scientific method used to develop tools intended to measure complex and multifaceted constructs like pain. Relevant words and expressions related to pain are collected, refined, and classified into domains and associated categories through a multi-step approach that involves the participation of a large sample of pain sufferers (or observers for non-verbal patients) and a pool of experts in the field. Ultimately, the instrument developed is tested by clinical studies to assess its validity, reliability, and responsiveness. While this approach has been widely adopted to reliably assess pain in humans, the GCMPS-SF is at present the only validated tool to measure acute pain in dogs developed using this methodology. The GCMPS-SF comprises four sections (section A: observation of resting behaviours from a distance, section B and C: evaluation of interactive behaviours, section D: assessment of the overall attitude of the patient), with instructions for completion provided at the beginning of each section. The questionnaire encompasses two categories within each section, incorporating a total of six behavioural categories. These categories are associated with multiple descriptive expressions of pain, assigned an individual score each and ordered in an increased level of severity within the category. We conducted a scoping review through systematic search of the literature to identify prospective research studies that have used the GCMPS-SF. We aimed to describe the contexts in which it has been used, verify the correct use of the scale, examine whether these studies are well-designed and adequately powered, and determine whether statistically significant differences in GCMPS-SF scores appear clinically relevant. We identified 114 eligible studies, indicating widespread use of the scale. We documented a limited number of modifications to the scale and intervention level, which would alter its validity, and a variety of methods to analyse the data derived from the scale. We also documented many deficiencies in reporting of experimental design in terms of the observers used, the underlying hypothesis of the research, the statement of primary outcome, the use of a priori sample size calculations, blinding and randomisation strategies. These deficiencies in reporting and study design may predispose to both Type I and Type II statistical errors in the small animal pain literature. Results of our analyses also suggest that methodological factors affected study outcomes in our dataset. The probability of finding a statistically significant difference was 7 times higher in studies that used negative control groups, 3 times higher when the GCMPS-SF scores were used as a primary outcome, and 12 times higher if the pain scale was modified. Finally, we documented a wide range (1.00 to 11.0) of actual effect sizes in GCMPS-SF scores, with approximately 30% of the values below 1.60, and a median largest actual effect size of 2.00 in trials that declared statistical significance. With the consideration that clinical relevance is perhaps more anchored to the intervention level with the GCMPS-SF, rather than to a minimum difference in pain scores, we question whether some of the differences detected, albeit statistically significant, are clinically relevant without accounting for their position on the scale. Based on our findings, we encourage methodologically sound study design, high quality of reporting, and a more robust use of the scale and derived data to ensure attainment of reliable and translatable outcomes

Assessment of Magnetic Resonance Imaging Artefacts Caused By Equine Anaesthesia Equipment:A Cadaver Study

Acquisition of magnetic resonance images of the equine limb is still sometimes conducted under general anaesthesia. Despite low-field systems allow the use of standard anaesthetic equipment, possible interferences of the extensive electronic componentry of advanced anaesthetic machines on image quality is unknown. This prospective, blinded, cadaver study investigated the effects of 7 standardised conditions [Tafonius positioned as in clinical cases, Tafonius on the boundaries of the controlled area, anaesthetic monitoring only, Mallard anaesthetic machine, Bird ventilator, complete electronic silence in the room (negative control), source of electronic interference (positive control)] on image quality through the acquisition of 78 sequences using a 0.31T equine MRI scanner. Images were graded with a 4-point scoring system, where 1 denoted absence of artefacts and 4 major artefacts requiring repetition in a clinical setting. A lack of STIR fat suppression was commonly reported (16/26). Ordinal logistic regression showed no statistically significant differences in image quality between the negative control and either the non-Tafonius or the Tafonius groups (p = 0.535 and p = 0.881, respectively), and with the use of Tafonius compared to the other anaesthetic machines (p = 0.578). The only statistically significant differences in scores were observed between the positive control and the non-Tafonius (p = 0.006) and the Tafonius groups (p = 0.017). Our findings suggest that anaesthetic machines and monitoring do not appear to affect MRI scan quality and support the use of Tafonius during acquisition of images with a 0.31T MRI system in a clinical context

Geometry Diagnostics of a Stellar Flare from Fluorescent X-rays

We present evidence of Fe fluorescent emission in the Chandra HETGS spectrum of the single G-type giant HR 9024 during a large flare. In analogy to solar X-ray observations, we interpret the observed Fe K$\alpha$ line as being produced by illumination of the photosphere by ionizing coronal X-rays, in which case, for a given Fe photospheric abundance, its intensity depends on the height of the X-ray source. The HETGS observations, together with 3D Monte Carlo calculations to model the fluorescence emission, are used to obtain a direct geometric constraint on the scale height of the flaring coronal plasma. We compute the Fe fluorescent emission induced by the emission of a single flaring coronal loop which well reproduces the observed X-ray temporal and spectral properties according to a detailed hydrodynamic modeling. The predicted Fe fluorescent emission is in good agreement with the observed value within observational uncertainties, pointing to a scale height $\lesssim 0.3$\rstar. Comparison of the HR 9024 flare with that recently observed on II Peg by Swift indicates the latter is consistent with excitation by X-ray photoionization.Comment: accepted for publication on the Astrophysical Journal Letter

A Crosstalk Between Brain Cholesterol Oxidation and Glucose Metabolism in Alzheimer’s Disease

In Alzheimer’s disease (AD), both cholesterol and glucose dysmetabolism precede the onset of memory deficit and contribute to the disease’s progression. It is indeed now believed that oxidized cholesterol in the form of oxysterols and altered glucose uptake are the main triggers in AD affecting production and clearance of Aβ, and tau phosphorylation. However, only a few studies highlight the relationship between them, suggesting the importance of further extensive studies on this topic. Recently, a molecular link was demonstrated between cholesterol oxidative metabolism and glucose uptake in the brain. In particular, 27-hydroxycholesterol, a key linker between hypercholesterolemia and the increased AD risk, is considered a biomarker for reduced glucose metabolism. In fact, its excess increases the activity of the renin-angiotensin system in the brain, thus reducing insulin-mediated glucose uptake, which has a major impact on brain functioning. Despite this important evidence regarding the role of 27-hydroxycholesterol in regulating glucose uptake by neurons, the involvement of other cholesterol oxidation products that have been clearly demonstrated to be key players in AD cannot be ruled out. This review highlights the current understanding of the potential role of cholesterol and glucose dysmetabolism in AD progression, and the bidirectional crosstalk between these two phenomena

A Dietary Mixture of Oxysterols Induces In Vitro Intestinal Inflammation through TLR2/4 Activation: The Protective Effect of Cocoa Bean Shells

Background: Exaggerated Toll-like receptor (TLR)-mediated immune and inflammatory responses play a role in inflammatory bowel diseases. This report deals with the ability of a mixture of oxysterols widely present in cholesterol-rich foods to induce in vitro intestinal inflammation through TLR up-regulation. The anti-inflammatory action of four cocoa bean shell (CBS) extracts with different polyphenol content, was tested. Methods: Differentiated intestinal CaCo-2 cells were treated with a dietary oxysterol mixture (Oxy-mix) (60 µM). The expression and activation of TLR2 and TLR4, as well as the production of their downstream signaling effectors IL-8, IFNβ and TNFα were analyzed in the presence or absence of TLR antibodies. Honduras CBS extracts were characterized for their polyphenol contents; their anti-inflammatory action was analyzed in CaCo-2 cells treated with Oxy-mix. Results: Oxysterol-dependent TLR-2 and TLR4 over-expression and activation together with cytokine induction were abolished by blocking TLRs with specific antibodies. Polyphenol-rich CBS extracts consisting of high quantities of (−)-epicatechin and tannins also prevented TLR induction. Conclusions: TLR2 and TLR4 mainly contribute to inducing oxysterol-dependent intestinal inflammation. The fractionation method of CBS allowed the recovery of fractions rich in (−)-epicatechin and tannins able to counteract oxysterol-induced inflammation, thus highlighting the beneficial biological potential of specific CBS extracts