Development of a method to identify foot strike on an arena surface: application to jump landing

Foot strike can be difficult to determine using kinematics alone, particularly when studying equine activities on more compliant surfaces, so this study was done with the aim of developing and validating a method to determine foot strike on an arena surface that can be used in conjunction with kinematics alone, and of applying the method in the context of measuring foot strike during jump landing on an arena surface. A low-cost contact mat was developed. The timing of the contact mat switching ‘on’ was compared to the timing of a force platform onset of 20 N, load and loading rate at foot strike. Two groups of 25 participants were used in two separate studies to validate the contact mat: the first measured the difference in timing with respect to two different activities (running and stepping down from a box), and the second measured the difference in timing with respect to 1- and 2-cm depths of an arena surface during running. In a third study, the mat was used to measure leading limb foot strike of six horses during jump landing, and these data were compared to kinematics from a palmar marker on the hoof wall. All data were recorded at 500 Hz. A consistent difference in delay was found between the mat and force platform onset, and as a result, no significant differences (P>0.05) in timing delay between different loading rates or depths were found. During jump landing, foot strike (determined from the mat) occurred after the vertical velocity minima and the acceleration maxima for the hoof marker, but it occurred before the point where the rate of vertical displacement began to reduce. In conclusion, further work is needed to enhance these techniques, but these preliminary results indicate that this method may be effective in determining foot strike for field-based applications

Natriuretic peptide receptors regulate cytoprotective effects in a human ex vivo 3D/bioreactor model

© 2013 Peake et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

C-Type Natriuretic Peptide: A Multifaceted Paracrine Regulator in the Heart and Vasculature

C-type natriuretic peptide (CNP) is an autocrine and paracrine mediator released by endothelial cells, cardiomyocytes and fibroblasts that regulates vital physiological functions in the cardiovascular system. These roles are conveyed via two cognate receptors, natriuretic peptide receptor B (NPR-B) and natriuretic peptide receptor C (NPR-C), which activate different signalling pathways that mediate complementary yet distinct cellular responses. Traditionally, CNP has been deemed the endothelial component of the natriuretic peptide system, while its sibling peptides, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), are considered the endocrine guardians of cardiac function and blood volume. However, accumulating evidence indicates that CNP not only modulates vascular tone and blood pressure, but also governs a wide range of cardiovascular effects including the control of inflammation, angiogenesis, smooth muscle and endothelial cell proliferation, atherosclerosis, cardiomyocyte contractility, hypertrophy, fibrosis, and cardiac electrophysiology. This review will focus on the novel physiological functions ascribed to CNP, the receptors/signalling mechanisms involved in mediating its cardioprotective effects, and the development of therapeutics targeting CNP signalling pathways in different disease pathologies

C-type natriuretic peptide is a pivotal regulator of metabolic homeostasis

Thermogenesis and adipogenesis are tightly regulated mechanisms that maintain lipid homeostasis and energy balance; dysfunction of these critical processes underpins obesity and contributes to cardiometabolic disease. C-type natriuretic peptide (CNP) fulfills a multimodal protective role in the cardiovascular system governing local blood flow, angiogenesis, cardiac function, and immune cell reactivity. Herein, we investigated a parallel, preservative function for CNP in coordinating metabolic homeostasis. Global inducible CNP knockout mice exhibited reduced body weight, higher temperature, lower adiposity, and greater energy expenditure in vivo. This thermogenic phenotype was associated with increased expression of uncoupling protein-1 and preferential lipid utilization by mitochondria, a switch corroborated by a corresponding diminution of insulin secretion and glucose clearance. Complementary studies in isolated murine and human adipocytes revealed that CNP exerts these metabolic regulatory actions by inhibiting sympathetic thermogenic programming via G(i)-coupled natriuretic peptide receptor (NPR)-C and reducing peroxisome proliferator-activated receptor-γ coactivator-1α expression, while concomitantly driving adipogenesis via NPR-B/protein kinase-G. Finally, we identified an association between CNP/NPR-C expression and obesity in patient samples. These findings establish a pivotal physiological role for CNP as a metabolic switch to balance energy homeostasis. Pharmacological targeting of these receptors may offer therapeutic utility in the metabolic syndrome and related cardiovascular disorders

Intrinsic defence capacity and therapeutic potential of natriuretic peptides in pulmonary hypertension associated with lung fibrosis

This work was supported by the British Lung Foundation. C.J.S. is supported by a Medical Research Council Fellowship

Deglacial to postglacial palaeoenvironments of the Celtic Sea: Lacustrine conditions versus a continuous marine sequence

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Recent work on the last glaciation of the British Isles has led to an improved understanding of the nature and timing of the retreat of the British-Irish Ice Sheet (BIIS) from its southern maximum (Isles of Scilly), northwards into the Celtic and Irish seas. However, the nature of the deglacial environments across the Celtic Sea shelf, the extent of subaerial exposure and the existence (or otherwise) of a contiguous terrestrial linkage between Britain and Ireland following ice retreat remains ambiguous. Multiproxy research, based on analysis of 12 BGS vibrocores from the Celtic Deep Basin (CDB), seeks to address these issues. CDB cores exhibit a shell-rich upward fining sequence of Holocene marine sand above an erosional contact cut in laminated muds with infrequent lonestones. Molluscs, in situ Foraminifera and marine diatoms are absent from the basal muds, but rare damaged freshwater diatoms and foraminiferal linings occur. Dinoflagellate cysts and other non-pollen palynomorphs evidence diverse, environmentally incompatible floras with temperate, boreal and Arctic glaciomarine taxa co-occurring. Such multiproxy records can be interpreted as representing a retreating ice margin, with reworking of marine sediments into a lacustrine basin. Equally, the same record may be interpreted as recording similar conditions within a semi-enclosed marine embayment dominated by meltwater export and deposition of reworked microfossils. As assemblages from these cores contrast markedly with proven glaciomarine sequences from outside the CDB, a glaciolacustrine interpretation is favoured for the laminated sequence, truncated by a Late Weichselian transgressive sequence fining upwards into fully marine conditions. Reworked rare intertidal molluscs from immediately above the regional unconformity provide a minimum date c.13.9cal. ka BP for commencement of widespread marine erosion. Although suggestive of glaciolacustrine conditions, the exact nature and timing of laminated sediment deposition within the CDB, and the implications this has on (pen)insularity of Ireland following deglaciation, remain elusive. © 2013 The Boreas Collegium.Funded by NERC PhD research studentship grant. Grant Number: GT04/97/289/ES; two NSERC-funded radiocarbon allocations. Grant Numbers: 746/0898, 814/0999; MacEwan Universit

Raised arterial blood pressure in neurokinin-1 receptor-deficient mice (NK1R−/−): evidence for a neural rather than a vascular mechanism

NEW FINDINGS: What is the central question of this study? Does genetic ablation of neurokinin-1 receptors alter arterial blood pressure? What is the main finding and its importance? NK1R(-/-) mice have increased mean arterial blood pressure, but without a concomitant change in vascular reactivity. This finding suggests that neurokinin-1 receptors play a role in the neural regulation of blood pressure. Mice with functional ablation of the neurokinin-1 receptor gene, Tacr1, (NK1R(-/-) ) express behavioural abnormalities equivalent to those seen in attention deficit hyperactivity disorder (ADHD). An established model of ADHD is the spontaneously hypertensive rat, which exhibits high blood pressure owing to increased central sympathetic drive. In light of the evidence that the neurokinin-1 receptor (NK1R) also influences cardiovascular haemodynamics, we have investigated whether NK1R(-/-) mice exhibit raised blood pressure. Cardiovascular parameters were recorded for 24 h in conscious mice using radiotelemetry. Vascular function was assessed in mesenteric resistance arteries by wire myography. The NK1R(-/-) mice exhibited a higher blood pressure than wild-type animals throughout the 24 h period. Heart rate and locomotor activity in NK1R(-/-) mice were higher than in wild-type mice during the night period (active phase), consistent with an ADHD-like phenotype, but not during the day. Mesenteric and renal arteries from NK1R(-/-) mice exhibited normal vascular function; the responses to vasoconstrictors (U46619 and phenylephrine) and the endothelium-dependent vasodilator, acetylcholine, were not altered in these animals, suggesting that the NK1R does not regulate vascular tone. Analysis of heart rate variability revealed a higher low-frequency to high-frequency ratio in NK1R(-/-) mice, indicative of increased cardiac sympathetic activity. We propose that the raised blood pressure in NK1R(-/-) mice could be due to a neural mechanism rather than a change in vascular reactivity. Further studies are required to understand this mechanism and to establish whether a subgroup of ADHD patients with polymorphism of the equivalent (TACR1) gene are affected in a similar way

Multidrug resistance proteins preferentially regulate natriuretic peptide-driven cGMP signalling in the heart & vasculature.

BACKGROUND & PURPOSE: Cyclic-3',5'-guanosine monophosphate (cGMP) underpins the bioactivity of nitric oxide (NO) and natriuretic peptides and is key to cardiovascular homeostasis. Cyclic GMP-driven responses are terminated primarily by phosphodiesterases but cellular efflux via multidrug resistance proteins (MRPs) might contribute. Herein, the effect of pharmacological blockade of MRPs on cGMP signalling in the heart and vasculature was investigated in vitro and in vivo. EXPERIMENTAL APPROACHES: Proliferation of human coronary artery smooth muscle cells (hCASMC), vasorelaxation of murine aorta and reductions in mean arterial blood pressure (MABP) in response to NO-donors or natriuretic peptides was determined in the absence and presence of the MRP inhibitor MK571. The ability of MRP inhibition to reverse morphological and contractile deficits in a murine model of pressure overload-induced HF was also explored. KEY RESULTS: MK571 attenuated hCASMC growth and enhanced the anti-proliferative effects of NO and ANP. MRP blockade caused concentration-dependent relaxations of murine aorta and augmented responses to ANP (and to a lesser extent NO). MK571 did not decrease MABP, but enhanced the hypotensive actions of ANP and improved structural and functional indices of disease severity in experimental HF. These beneficial actions of MRP inhibition were associated with a greater intra:extra -cellular cGMP ratio in vitro and in vivo. CONCLUSIONS & IMPLICATIONS: MRP blockade promotes the cardiovascular functions of natriuretic peptides in vitro and in vivo, with more modest effects on NO. MRP inhibition may have therapeutic utility in cardiovascular diseases triggered by dysfunctional cGMP signalling, particularly those associated with altered natriuretic peptide bioactivity

Operational temperatures of all-weather thoroughbred racetracks influence surface functional properties

The surface temperature of all-weather racetracks has previously been correlated to speed. However specific functional properties such as grip, cushioning and impact firmness have not been directly compared to environmental conditions. The objective of this study was to assess how temperature influences functional properties of racetracks, and categorise surface wax binders according to first thermal transition peak, and compare responses at different operational temperatures. Functional properties were determined for UK all-weather racetrack surfaces (n = 6) using mechanical testing equipment which assess the loads experienced by the forelimb at gallop (randomised block design). Tests were carried out using latex lined moulds, embedded within a test box with a predefined boundary at 0 °C, 20 °C and 40 °C. Wax binders underwent differential scanning calorimetry to identify thermal transition peaks. Changes in operational temperatures significantly influenced surface responses when a wax binder was part of the composition. Temperature was a factor that significantly contributed to the variation found in horizontal grip (F2, 237 = 65.69, P < 0.001), cushioning (F2, 237 = 58.24, P < 0.001), impact firmness (F2, 237 = 28.02, P < 0.001) and rotational grip (F12, 65 = 9.45, P < 0.001). Using a test box meant individual racetracks were generalised but this enabled conditions to be controlled. Colder temperatures demonstrated higher surface hardness and shear resistance that may increase risk of musculoskeletal injury although this was not measured here. Awareness of the effect temperature has on specific track behaviour allows maintenance protocols to be further developed to improve consistency when temperatures change, with the aim of improving safety

Non-vitamin K antagonist oral anticoagulants and atrial fibrillation guidelines in practice: barriers to and strategies for optimal implementation.

Stroke is a leading cause of morbidity and mortality worldwide. Atrial fibrillation (AF) is an independent risk factor for stroke, increasing the risk five-fold. Strokes in patients with AF are more likely than other embolic strokes to be fatal or cause severe disability and are associated with higher healthcare costs, but they are also preventable. Current guidelines recommend that all patients with AF who are at risk of stroke should receive anticoagulation. However, despite this guidance, registry data indicate that anticoagulation is still widely underused. With a focus on the 2012 update of the European Society of Cardiology (ESC) guidelines for the management of AF, the Action for Stroke Prevention alliance writing group have identified key reasons for the suboptimal implementation of the guidelines at a global, regional, and local level, with an emphasis on access restrictions to guideline-recommended therapies. Following identification of these barriers, the group has developed an expert consensus on strategies to augment the implementation of current guidelines, including practical, educational, and access-related measures. The potential impact of healthcare quality measures for stroke prevention on guideline implementation is also explored. By providing practical guidance on how to improve implementation of the ESC guidelines, or region-specific modifications of these guidelines, the aim is to reduce the potentially devastating impact that stroke can have on patients, their families and their carers