Does subchondral bone of the equine proximal phalanx adapt to race training?

Sagittal fractures of the first phalanx are a common, potentially catastrophic injury in racehorses. These fractures are often linked to an acute, one time, biomechanical event; however, recent evidence implies that chronic exposure to stress can lead to the accumulation of bony changes that affect the structural integrity of the bone and increase the likelihood of fracture. The aim of the study was to compare variations of two common metrics of bone adaptation – subchondral bone density and thickness across the proximal articular surface of the first phalanx in Thoroughbred horses that (1) raced but never experienced a first phalanx fracture (Raced Control); (2) raced and had experienced fracture of the contralateral first phalanx (Contralateral to Fracture); (3) had never raced or experienced a first phalanx fracture (Unraced Control). A total of 22 first phalangeal bones were sampled post‐mortem and imaged using micro‐computed tomography calibrated for mineral density measures. Measurements of volumetric subchondral bone mineral density and thickness were taken from images at five sites from medial to lateral, in three coronal planes (25, 50 and 75% dorsal‐palmar). At each of the 15 sites, measurements were repeated and averaged across 10 adjacent micro‐computed tomography slices of bone, spanning 0.75 mm. The magnitude and variance of these measurements were compared between sites and between cohorts with non‐parametric statistical tests. Across the proximal osteochondral surface of the first phalanx, the pattern of subchondral bone volumetric bone mineral density and thickness varied with each coronal section studied. The subchondral bone thickness was greater for the central and dorsal coronal sections, compared with the palmar section. For the race‐fit groups (Raced Control and Contralateral to Fracture), the highest volumetric bone mineral density was in the central sagittal groove. The volumetric bone mineral density was significantly greater in the sagittal groove in the central coronal section in the raced than the unraced group. The Contralateral to Fracture group demonstrated significantly greater variance of volumetric bone mineral density compared with the Raced Control and Unraced Control (P < 0.0001), with no difference in variance noted between the Raced Control and Unraced Control groups. There was a small (R rank = 0.3) but significant correlation between subchondral bone volumetric bone mineral density and thickness in the Contralateral to Fracture group (P = 0.005). The findings demonstrate that differences exist in subchondral bone volumetric bone mineral density and thickness across the proximal osteochondral surface of the equine first phalanx in horses with different training histories. The findings also demonstrate that the subchondral bone of the sagittal groove of the equine first phalanx adapts to race‐training in the race‐fit groups (Raced Control and Contralateral to Fracture) with an increase in volumetric bone mineral density relative to unraced controls. Within the race‐trained groups, the Contralateral to Fracture bones had a greater variance of volumetric bone mineral density, suggesting that stress‐induced bone adaptation had become more erratic, potentially contributing to the aetiology of sagittal fractures of the first phalanx in the Thoroughbred racehorse

Moving singing for lung health online in response to COVID-19: experience from a randomised controlled trial

Introduction: Singing for lung health (SLH) is a popular arts-in-health activity for people with long-term respiratory conditions. Participants report biopsychosocial benefits, however, research on impact is limited. The ‘SLH: Improving Experiences of Lung Disease trial’, a randomised controlled, single (assessor) blind, trial of 12 weeks SLH versus usual care for people with chronic obstructive pulmonary disease (COPD) (n=120) was setup to help to address this. The first group (n=18, nine singing and nine controls) started face-to-face (five sessions) before changing to online delivery (seven sessions) due to COVID-19-related physical distancing measures. As such, the experience of this group is here reported as a pilot study to inform further research in this area. Methods: We conducted semistructured interviews and thematic analysis regarding barriers, facilitators and key considerations for transitioning from face-to-face to online delivery. Pilot quantitative outcomes include attendance, premeasures and postmeasures of quality of life and disease impact (Short Form 36 Health Survey, COPD Assessment Test score), breathlessness (Medical Research Council breathlessness scale, Dyspnoea-12), depression (Patient Health Questionnaire-9, PHQ-9), anxiety (Generalised Anxiety Disorder-7), balance confidence (Activity specific Balance Confidence, ABC scale) and physical activity (clinical visit PROactive physical activity in COPD tool, combining subjective rating and actigraphy). Results: Attendance was 69% overall, (90% of the face-to-face sessions, 53% online sessions). Analysis of semistructured interviews identified three themes regarding participation in SLH delivered face to face and online, these where (1) perceived benefits; (2) digital barriers (online) and (3) digital facilitators (online). Findings were summarised into key considerations for optimising transitioning singing groups from face-to-face to online delivery. Pilot quantitative data suggested possible improvements in depression (treatment effect −4.78 PHQ-9 points, p<0.05, MCID 5) and balance confidence (treatment effect +17.21 ABC scale points, p=0.04, MCID 14.2). Discussion: This study identifies key considerations regarding the adaptation of SLH from face-to-face to online delivery. Pilot data suggest online group singing for people with COPD may deliver benefits related to reducing depression and improved balance confidence.National Institute for Health Research; Imperial College; Wellcome Trust; UK NIHR

Contrast Enhanced Micro-Computed Tomography Resolves the 3-Dimensional Morphology of the Cardiac Conduction System in Mammalian Hearts

The general anatomy of the cardiac conduction system (CCS) has been known for 100 years, but its complex and irregular three-dimensional (3D) geometry is not so well understood. This is largely because the conducting tissue is not distinct from the surrounding tissue by dissection. The best descriptions of its anatomy come from studies based on serial sectioning of samples taken from the appropriate areas of the heart. Low X-ray attenuation has formerly ruled out micro-computed tomography (micro-CT) as a modality to resolve internal structures of soft tissue, but incorporation of iodine, which has a high molecular weight, into those tissues enhances the differential attenuation of X-rays and allows visualisation of fine detail in embryos and skeletal muscle. Here, with the use of a iodine based contrast agent (I2KI), we present contrast enhanced micro-CT images of cardiac tissue from rat and rabbit in which the three major subdivisions of the CCS can be differentiated from the surrounding contractile myocardium and visualised in 3D. Structures identified include the sinoatrial node (SAN) and the atrioventricular conduction axis: the penetrating bundle, His bundle, the bundle branches and the Purkinje network. Although the current findings are consistent with existing anatomical representations, the representations shown here offer superior resolution and are the first 3D representations of the CCS within a single intact mammalian heart

Widespread Translocation from Autosomes to Sex Chromosomes Preserves Genetic Variability in an Endangered Lark

Species that pass repeatedly through narrow population bottlenecks (<100 individuals) are likely to have lost a large proportion of their genetic variation. Having genotyped 92 Raso larks Alauda razae, a Critically Endangered single-island endemic whose world population in the Cape Verdes over the last 100 years has fluctuated between about 15 and 130 pairs, we found variation at 7 of 21 microsatellite loci that successfully amplified, the remaining loci being monomorphic. At 6 of the polymorphic loci variation was sex-linked, despite the fact that these microsatellites were not sex-linked in the other passerine birds where they were developed. Comparative analysis strongly suggests that material from several different autosomes has been recently transferred to the sex chromosomes in larks. Sex-linkage might plausibly allow some level of heterozygosity to be maintained, even in the face of persistently small population sizes

The shear viscosity of carbon fibre suspension and its application for fibre length measurement

The viscosity of short carbon fibre suspensions in glycerol aqueous solution was measured using a bespoke vane-in-cup viscometer, where the carbon fibre has an aspect ratio from 450 to 2209. In the semi-concentrated regime, nL3 ranging from 20 to 4400, the suspensions demonstrated strong shear-thinning characteristics particularly at higher concentrations. The shear-thinning characteristic is strongly related to the crowding factor proposed by Kerekes, indicating that non-hydrodynamic interactions occur in the suspensions. The influence of fibre bending on viscosity emerges when the bending ratio is lower than 0.0028. An empirical model based on transient network formation and rupture was proposed and used to correlate the relative viscosity with fibre concentration nL3 and shear rate. Based on the model, a viscosity method is established to analyse the fibre length by measuring the viscosity of the fibre suspension using a bespoke vane-in-cup viscometer

High resolution 3-Dimensional imaging of the human cardiac conduction system from microanatomy to mathematical modeling

Cardiac arrhythmias and conduction disturbances are accompanied by structural remodelling of the specialised cardiomyocytes known collectively as the cardiac conduction system. Here, using contrast enhanced micro-computed tomography, we present, in attitudinally appropriate fashion, the first 3-dimensional representations of the cardiac conduction system within the intact human heart. We show that cardiomyocyte orientation can be extracted from these datasets at spatial resolutions approaching the single cell. These data show that commonly accepted anatomical representations are oversimplified. We have incorporated the high-resolution anatomical data into mathematical simulations of cardiac electrical depolarisation. The data presented should have multidisciplinary impact. Since the rate of depolarisation is dictated by cardiac microstructure, and the precise orientation of the cardiomyocytes, our data should improve the fidelity of mathematical models. By showing the precise 3-dimensional relationships between the cardiac conduction system and surrounding structures, we provide new insights relevant to valvar replacement surgery and ablation therapies. We also offer a practical method for investigation of remodelling in disease, and thus, virtual pathology and archiving. Such data presented as 3D images or 3D printed models, will inform discussions between medical teams and their patients, and aid the education of medical and surgical trainees

Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action: Mechanistic Insights from Canine Atrial Models

Anti-arrhythmic drug therapy is a frontline treatment for atrial fibrillation (AF), but its success rates are highly variable. This is due to incomplete understanding of the mechanisms of action of specific drugs on the atrial substrate at different stages of AF progression. We aimed to elucidate the role of cellular, tissue and organ level atrial heterogeneities in the generation of a re-entrant substrate during AF progression, and their modulation by the acute action of selected anti-arrhythmic drugs. To explore the complex cell-to-organ mechanisms, a detailed biophysical models of the entire 3D canine atria was developed. The model incorporated atrial geometry and fibre orientation from high-resolution micro-computed tomography, region-specific atrial cell electrophysiology and the effects of progressive AF-induced remodelling. The actions of multi-channel class III anti-arrhythmic agents vernakalant and amiodarone were introduced in the model by inhibiting appropriate ionic channel currents according to experimentally reported concentration-response relationships. AF was initiated by applied ectopic pacing in the pulmonary veins, which led to the generation of localized sustained re-entrant waves (rotors), followed by progressive wave breakdown and rotor multiplication in both atria. The simulated AF scenarios were in agreement with observations in canine models and patients. The 3D atrial simulations revealed that a re-entrant substrate was typically provided by tissue regions of high heterogeneity of action potential duration (APD). Amiodarone increased atrial APD and reduced APD heterogeneity and was more effective in terminating AF than vernakalant, which increased both APD and APD dispersion. In summary, the initiation and sustenance of rotors in AF is linked to atrial APD heterogeneity and APD reduction due to progressive remodelling. Our results suggest that anti-arrhythmic strategies that increase atrial APD without increasing its dispersion are effective in terminating AF

Exploring miniature insect brains using micro-CT scanning techniques

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High-Resolution Melting Analysis as a Powerful Tool to Discriminate and Genotype Pseudomonas savastanoi Pathovars and Strains

Pseudomonas savastanoi is a serious pathogen of Olive, Oleander, Ash, and several other Oleaceae. Its epiphytic or endophytic presence in asymptomatic plants is crucial for the spread of Olive and Oleander knot disease, as already ascertained for P. savastanoi pv. savastanoi (Psv) on Olive and for pv. nerii (Psn) on Oleander, while no information is available for pv. fraxini (Psf) on Ash. Nothing is known yet about the distribution on the different host plants and the real host range of these pathovars in nature, although cross-infections were observed following artificial inoculations. A multiplex Real-Time PCR assay was recently developed to simultaneously and quantitatively discriminate in vitro and in planta these P. savastanoi pathovars, for routine culture confirmation and for epidemiological and diagnostical studies. Here an innovative High-Resolution Melting Analysis (HRMA)-based assay was set up to unequivocally discriminate Psv, Psn and Psf, according to several single nucleotide polymorphisms found in their Type Three Secretion System clusters. The genetic distances among 56 P. savastanoi strains belonging to these pathovars were also evaluated, confirming and refining data previously obtained by fAFLP. To our knowledge, this is the first time that HRMA is applied to a bacterial plant pathogen, and one of the few multiplex HRMA-based assays developed so far. This protocol provides a rapid, sensitive, specific tool to differentiate and detect Psv, Psn and Psf strains, also in vivo and against other related bacteria, with lower costs than conventional multiplex Real-Time PCR. Its application is particularly suitable for sanitary certification programs for P. savastanoi, aimed at avoiding the spreading of this phytopathogen through asymptomatic plants