A preliminary case study of the effect of shoe-wearing on the biomechanics of a horse’s foot

Horse racing is a multi-billion-dollar industry that has raised welfare concerns due to injured and euthanized animals. Whilst the cause of musculoskeletal injuries that lead to horse morbidity and mortality is multifactorial, pre-existing pathologies, increased speeds and substrate of the racecourse are likely contributors to foot disease. Horse hooves have the ability to naturally deform during locomotion and dissipate locomotor stresses, yet farriery approaches are utilised to increase performance and protect hooves from wear. Previous studies have assessed the effect of different shoe designs on locomotor performance; however, no biomechanical study has hitherto measured the effect of horseshoes on the stresses of the foot skeleton in vivo. This preliminary study introduces a novel methodology combining three-dimensional data from biplanar radiography with inverse dynamics methods and finite element analysis (FEA) to evaluate the effect of a stainless steel shoe on the function of a Thoroughbred horse's forefoot during walking. Our preliminary results suggest that the stainless steel shoe shifts craniocaudal, mediolateral and vertical GRFs at mid-stance. We document a similar pattern of flexion-extension in the PIP (pastern) and DIP (coffin) joints between the unshod and shod conditions, with slight variation in rotation angles throughout the stance phase. For both conditions, the PIP and DIP joints begin in a flexed posture and extend over the entire stance phase. At mid-stance, small differences in joint angle are observed in the PIP joint, with the shod condition being more extended than the unshod horse, whereas the DIP joint is extended more in the unshod than the shod condition. We also document that the DIP joint extends more than the PIP after midstance and until the end of the stance in both conditions. Our FEA analysis, conducted solely on the bones, shows increased von Mises and Maximum principal stresses on the forefoot phalanges in the shod condition at mid-stance, consistent with the tentative conclusion that a steel shoe might increase mechanical loading. However, because of our limited sample size none of these apparent differences have been tested for statistical significance. Our preliminary study illustrates how the shoe may influence the dynamics and mechanics of a Thoroughbred horse's forefoot during slow walking, but more research is needed to quantify the effect of the shoe on the equine forefoot during the whole stance phase, at faster speeds/gaits and with more individuals as well as with a similar focus on the hind feet. We anticipate that our preliminary analysis using advanced methodological approaches will pave the way for new directions in research on the form/function relationship of the equine foot, with the ultimate goal to minimise foot injuries and improve animal health and welfare

Forelimb muscle and joint actions in Archosauria: insights from Crocodylus johnstoni (Pseudosuchia) and Mussaurus patagonicus (Sauropodomorpha)

Many of the major locomotor transitions during the evolution of Archosauria, the lineage including crocodiles and birds as well as extinct Dinosauria, were shifts from quadrupedalism to bipedalism (and vice versa). Those occurred within a continuum between more sprawling and erect modes of locomotion and involved drastic changes of limb anatomy and function in several lineages, including sauropodomorph dinosaurs. We present biomechanical computer models of two locomotor extremes within Archosauria in an analysis of joint ranges of motion and the moment arms of the major forelimb muscles in order to quantify biomechanical differences between more sprawling, pseudosuchian (represented the crocodile Crocodylus johnstoni) and more erect, dinosaurian (represented by the sauropodomorph Mussaurus patagonicus) modes of forelimb function. We compare these two locomotor extremes in terms of the reconstructed musculoskeletal anatomy, ranges of motion of the forelimb joints and the moment arm patterns of muscles across those ranges of joint motion. We reconstructed the three-dimensional paths of 30 muscles acting around the shoulder, elbow and wrist joints. We explicitly evaluate how forelimb joint mobility and muscle actions may have changed with postural and anatomical alterations from basal archosaurs to early sauropodomorphs. We thus evaluate in which ways forelimb posture was correlated with muscle leverage, and how such differences fit into a broader evolutionary context (i.e. transition from sprawling quadrupedalism to erect bipedalism and then shifting to graviportal quadrupedalism). Our analysis reveals major differences of muscle actions between the more sprawling and erect models at the shoulder joint. These differences are related not only to the articular surfaces but also to the orientation of the scapula, in which extension/flexion movements in Crocodylus (e.g. protraction of the humerus) correspond to elevation/depression in Mussaurus. Muscle action is highly influenced by limb posture, more so than morphology. Habitual quadrupedalism in Mussaurus is not supported by our analysis of joint range of motion, which indicates that glenohumeral protraction was severely restricted. Additionally, some active pronation of the manus may have been possible in Mussaurus, allowing semi-pronation by a rearranging of the whole antebrachium (not the radius against the ulna, as previously thought) via long-axis rotation at the elbow joint. However, the muscles acting around this joint to actively pronate it may have been too weak to drive or maintain such orientations as opposed to a neutral position in between pronation and supination. Regardless, the origin of quadrupedalism in Sauropoda is not only linked to manus pronation but also to multiple shifts of forelimb morphology, allowing greater flexion movements of the glenohumeral joint and a more columnar forelimb posture

Musculoskeletal Geometry, Muscle Architecture and Functional Specialisations of the Mouse Hindlimb

Mice are one of the most commonly used laboratory animals, with an extensive array of disease models in existence, including for many neuromuscular diseases. The hindlimb is of particular interest due to several close muscle analogues/homologues to humans and other species. A detailed anatomical study describing the adult morphology is lacking, however. This study describes in detail the musculoskeletal geometry and skeletal muscle architecture of the mouse hindlimb and pelvis, determining the extent to which the muscles are adapted for their function, as inferred from their architecture. Using I2KI enhanced microCT scanning and digital segmentation, it was possible to identify 39 distinct muscles of the hindlimb and pelvis belonging to nine functional groups. The architecture of each of these muscles was determined through microdissections, revealing strong architectural specialisations between the functional groups. The hip extensors and hip adductors showed significantly stronger adaptations towards high contraction velocities and joint control relative to the distal functional groups, which exhibited larger physiological cross sectional areas and longer tendons, adaptations for high force output and elastic energy savings. These results suggest that a proximo-distal gradient in muscle architecture exists in the mouse hindlimb. Such a gradient has been purported to function in aiding locomotor stability and efficiency. The data presented here will be especially valuable to any research with a focus on the architecture or gross anatomy of the mouse hindlimb and pelvis musculature, but also of use to anyone interested in the functional significance of muscle design in relation to quadrupedal locomotion

Anatomical and biomechanical traits of broiler chickens across ontogeny. Part II. Body segment inertial properties and muscle architecture of the pelvic limb

In broiler chickens, genetic success for desired production traits is often shadowed by welfare concerns related to musculoskeletal health. Whilst these concerns are clear, a viable solution is still elusive. Part of the solution lies in knowing how anatomical changes in afflicted body systems that occur across ontogeny influence standing and moving. Here, to demonstrate these changes we quantify the segment inertial properties of the whole body, trunk (legs removed) and the right pelvic limb segments of five broilers at three different age groups across development. We also consider how muscle architecture (mass, fascicle length and other properties related to mechanics) changes for selected muscles of the pelvic limb. All broilers used had no observed lameness, but we document the limb pathologies identified post mortem, since these two factors do not always correlate, as shown here. The most common leg disorders, including bacterial chondronecrosis with osteomyelitis and rotational and angular deformities of the lower limb, were observed in chickens at all developmental stages. Whole limb morphology is not uniform relative to body size, with broilers obtaining large thighs and feet between four and six weeks of age. This implies that the energetic cost of swinging the limbs is markedly increased across this growth period, perhaps contributing to reduced activity levels. Hindlimb bone length does not change during this period, which may be advantageous for increased stability despite the increased energetic costs. Increased pectoral muscle growth appears to move the centre of mass cranio-dorsally in the last two weeks of growth. This has direct consequences for locomotion (potentially greater limb muscle stresses during standing and moving). Our study is the first to measure these changes in the musculoskeletal system across growth in chickens, and reveals how artificially selected changes of the morphology of the pectoral apparatus may cause deficits in locomotion

Morphine activates neuroinflammation in a manner parallel to endotoxin

Opioids create a neuroinflammatory response within the CNS, compromising opioid-induced analgesia and contributing to various unwanted actions. How this occurs is unknown but has been assumed to be via classic opioid receptors. Herein, we provide direct evidence that morphine creates neuroinflammation via the activation of an innate immune receptor and not via classic opioid receptors. We demonstrate that morphine binds to an accessory protein of Toll-like receptor 4 (TLR4), myeloid differentiation protein 2 (MD-2), thereby inducing TLR4 oligomerization and triggering proinflammation. Small-molecule inhibitors, RNA interference, and genetic knockout validate the TLR4/MD-2 complex as a feasible target for beneficially modifying morphine actions. Disrupting TLR4/MD-2 protein–protein association potentiated morphine analgesia in vivo and abolished morphine-induced proinflammation in vitro, the latter demonstrating that morphine-induced proinflammation only depends on TLR4, despite the presence of opioid receptors. These results provide an exciting, nonconventional avenue to improving the clinical efficacy of opioids.Xiaohui Wang, Lisa C. Loram, Khara Ramos, Armando J. de Jesus, Jacob Thomas, Kui Cheng, Anireddy Reddy, Andrew A. Somogyi, Mark R. Hutchinson, Linda R. Watkins and Hang Yi

Musculoskeletal modelling of an ostrich (Struthio camelus) pelvic limb: influence of limb orientation on muscular capacity during locomotion

We developed a three-dimensional, biomechanical computer model of the 36 major pelvic limb muscle groups in an ostrich (Struthio camelus) to investigate muscle function in this, the largest of extant birds and model organism for many studies of locomotor mechanics, body size, anatomy and evolution. Combined with experimental data, we use this model to test two main hypotheses. We first query whether ostriches use limb orientations (joint angles) that optimize the moment-generating capacities of their muscles during walking or running. Next, we test whether ostriches use limb orientations at mid-stance that keep their extensor muscles near maximal, and flexor muscles near minimal, moment arms. Our two hypotheses relate to the control priorities that a large bipedal animal might evolve under biomechanical constraints to achieve more effective static weight support. We find that ostriches do not use limb orientations to optimize the moment-generating capacities or moment arms of their muscles. We infer that dynamic properties of muscles or tendons might be better candidates for locomotor optimization. Regardless, general principles explaining why species choose particular joint orientations during locomotion are lacking, raising the question of whether such general principles exist or if clades evolve different patterns (e.g., weighting of muscle force–length or force–velocity properties in selecting postures). This leaves theoretical studies of muscle moment arms estimated for extinct animals at an impasse until studies of extant taxa answer these questions. Finally, we compare our model’s results against those of two prior studies of ostrich limb muscle moment arms, finding general agreement for many muscles. Some flexor and extensor muscles exhibit self-stabilization patterns (posture-dependent switches between flexor/extensor action) that ostriches may use to coordinate their locomotion. However, some conspicuous areas of disagreement in our results illustrate some cautionary principles. Importantly, tendon-travel empirical measurements of muscle moment arms must be carefully designed to preserve 3D muscle geometry lest their accuracy suffer relative to that of anatomically realistic models. The dearth of accurate experimental measurements of 3D moment arms of muscles in birds leaves uncertainty regarding the relative accuracy of different modelling or experimental datasets such as in ostriches. Our model, however, provides a comprehensive set of 3D estimates of muscle actions in ostriches for the first time, emphasizing that avian limb mechanics are highly three-dimensional and complex, and how no muscles act purely in the sagittal plane. A comparative synthesis of experiments and models such as ours could provide powerful synthesis into how anatomy, mechanics and control interact during locomotion and how these interactions evolve. Such a framework could remove obstacles impeding the analysis of muscle function in extinct taxa

Modeling the initiation of others into injection drug use, using data from 2,500 injectors surveyed in Scotland during 2008-2009

The prevalence of injection drug use has been of especial interest for assessment of the impact of blood-borne viruses. However, the incidence of injection drug use has been underresearched. Our 2-fold aim in this study was to estimate 1) how many other persons, per annum, an injection drug user (IDU) has the equivalent of full responsibility (EFR) for initiating into injection drug use and 2) the consequences for IDUs' replacement rate. EFR initiation rates are strongly associated with incarceration history, so that our analysis of IDUs' replacement rate must incorporate when, in their injecting career, IDUs were first incarcerated. To do so, we have first to estimate piecewise constant incarceration rates in conjunction with EFR initiation rates, which are then combined with rates of cessation from injecting to model IDUs' replacement rate over their injecting career, analogous to the reproduction number of an epidemic model. We apply our approach to Scotland's IDUs, using over 2,500 anonymous injector participants who were interviewed in Scotland's Needle Exchange Surveillance Initiative during 2008-2009. Our approach was made possible by the inclusion of key questions about initiations. Finally, we extend our model to include an immediate quit rate, as a reasoned compensation for higher-than-expected replacement rates, and we estimate how high initiates' quit rate should be for IDUs' replacement rate to be 1

High-throughput in-situ characterization and modelling of precipitation kinetics in compositionally graded alloys

The development of new engineering alloy chemistries is a time consuming and iterative process. A necessary step is characterization of the nano/microstructure to provide a link between the processing and properties of each alloy chemistry considered. One approach to accelerate the identification of optimal chemistries is to use samples containing a gradient in composition, ie. combinatorial samples, and to investigate many different chemistries at the same time. However, for engineering alloys, the final properties depend not only on chemistry but also on the path of microstructure development which necessitates characterization of microstructure evolution for each chemistry. In this contribution we demonstrate an approach that allows for the in-situ, nanoscale characterization of the precipitate structures in alloys, as a function of aging time, in combinatorial samples containing a composition gradient. The approach uses small angle x-ray scattering (SAXS) at a synchrotron beamline. The Cu-Co system is used for the proof-of-concept and the combinatorial samples prepared contain a gradient in Co from 0% to 2%. These samples are aged at temperatures between 450{\textdegree}C and 550{\textdegree}C and the precipitate structures (precipitate size, volume fraction and number density) all along the composition gradient are simultaneously monitored as a function of time. This large dataset is used to test the applicability and robustness of a conventional class model for precipitation that considers concurrent nucleation, growth and coarsening and the ability of the model to describe such a large dataset.Comment: Published in Acta Materiali