Pain after Whole-Body Vibration Exposure is Frequency Dependent and Independent of the Resonant Frequency: Lessons from an in vivo Rat Model

This is the author accepted manuscript. The final version is available from ASME via the DOI in this recordData Availability: Supporting datasets have been uploaded as part of the supplementary material.Occupational whole-body vibration (WBV) increases the risk of developing low back and neck pain; yet, there has also been an increased use of therapeutic WBV in recent years. Although the resonant frequency (fr) of the spine decreases as the exposure acceleration increases, effects of varying the vibration profile, including peak-to-peak displacement (sptp), root mean squared acceleration (arms) and frequency (f), on pain onset are not known. An established in-vivo rat model of WBV was used to characterize the resonance of the spine using sinusoidal sweeps. The relationship between arms and fr was defined and implemented to assess behavioral sensitivity - a proxy for pain. Five groups were subjected to a single 30-minute exposure, each with a different vibration profile, and a sham group underwent only anaesthesia exposure. The behavioral sensitivity was assessed at baseline and for 7 days following WBV-exposure. Only WBV at 8Hz induced behavioral sensitivity, and the higher arms exposure at 8Hz led to a more robust pain response. These results suggest that the development of pain is frequency-dependent, but further research into the mechanisms leading to pain are warranted to fully understand which WBV profiles may be detrimental or beneficial.Department of DefenseCatherine Sharpe Foundatio

Influence of testing environment and loading rate on intervertebral disc compressive mechanics: An assessment of repeatability at three different laboratories

In vitro mechanical testing of intervertebral discs is crucial for basic science and pre-clinical testing. Generally, these tests aim to replicate in vivo conditions, but simplifications are necessary in specimen preparation and mechanical testing due to complexities in both structure and the loading conditions required to replicate in vivo conditions. There has been a growing interest in developing a consensus of testing protocols within the spine community to improve comparison of results between studies. The objective of this study was to perform axial compression experiments on bovine bone-disc-bone specimens at three institutions. No differences were observed between testing environment being air, with PBS soaked gauze, or a PBS bath (P > .206). A 100-fold increase in loading rate resulted in a small (2%) but significant increase in compressive mechanics (P < .017). A 7% difference in compressive stiffness between Labs B and C was eliminated when values were adjusted for test system compliance. Specimens tested at Lab A, however, were found to be stiffer than specimens from Lab B and C. Even after normalizing for disc geometry and adjusting for system compliance, an ∼35% difference was observed between UK based labs (B and C) and the USA based lab (A). Large differences in specimen stiffness may be due to genetic differences between breeds or in agricultural feed and use of growth hormones; highlighting significant challenges in comparing mechanics data across studies. This research provides a standardized test protocol for the comparison of spinal specimens and provides steps towards understanding how location and test set-up may affect biomechanical results

Viscoelastic properties of biopolymer hydrogels determined by Brillouin spectroscopy: a probe of tissue micromechanics

This is the final version. Available on open access from the American Association for the Advancement of Science via the DOI in this recordData and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.Many problems in mechanobiology urgently require characterisation of the micromechanical properties of cells and tissues. Brillouin light scattering has been proposed as a new optical elastography technique to meet this need. However, the information contained in the Brillouin spectrum is still a matter of debate due to fundamental problems in understanding the role of water in biomechanics and in relating the Brillouin data to low-frequency macroscopic mechanical parameters. Here we investigate this question using gelatin as a model system in which the macroscopic physical properties can be manipulated to mimic all the relevant biological states of matter, ranging from the liquid to the gel and the glassy phase. We demonstrate that Brillouin spectroscopy is able to reveal both the elastic and viscous properties of biopolymers that are central to the structure and function of biological tissues.Engineering and Physical Sciences Research Council (EPSRC)Cancer Research UKEU COST Action BioBrilloui

Realtime monitoring of thrombus formation in vivo using a self-reporting vascular access graft

Background: Chronic kidney disease (CKD) affects 10% of the global population costing over a hundred billion dollars per annum and leading to increased risk of cardiovascular disease. Many patients with CKD require regular haemodialyses. Synthetic arteriovenous grafts (AVG) are increasingly used to provide rapid vascular connection for dialysis. Initially, they have excellent patency rates but are critically limited by neointimal hyperplasia at the venous anastomosis, which drives subsequent thrombosis, graft failure and death. Methods: Here, we describe a system in which electrical impedance spectroscopy sensors are incorporated circumferentially into the wall of a synthetic arteriovenous graft. This is combined with an implantable radiotelemetry system for data transmission outside the patient. The system was tested using monolayers of endothelial and smooth muscle cells as well as swine blood and clots with explanted human carotid artery plaques. Sensor testing was then performed in vitro and the device was implanted in vivo in female swine. Results: The device can wirelessly report the accumulation of biological material, both cells and blood. Differences are also detected when comparing controls with pathological atheroma. In swine differences between blockage formation in a graft were remotely obtained and wireless reported. Conclusions: Combining electrical impedance spectroscopy and an implantable radiotelemetry system enables graft surveillance. This has the potential to be used for early detection of venous stenosis and blood clot formation in real-time in vivo. In principle, the concept could apply to other cardiovascular diseases and vascular implantable devices

Predicting cardiovascular stent complications using self-reporting biosensors for noninvasive detection of disease

Self-reporting implantable medical devices are the future of cardiovascular healthcare. Cardiovascular complications such as blocked arteries that lead to the majority of heart attacks and strokes are frequently treated with inert metal stents that reopen affected vessels. Stents frequently re-block after deployment due to a wound response called in-stent restenosis (ISR). Herein, an implantable miniaturized sensor and telemetry system are developed that can detect this process, discern the different cell types associated with ISR, distinguish sub plaque components as demonstrated with ex vivo samples, and differentiate blood from blood clot, all on a silicon substrate making it suitable for integration onto a vascular stent. This work shows that microfabricated sensors can provide clinically relevant information in settings closer to physiological conditions than previous work with cultured cells

Feasibility of comparing medical management and surgery (with neurosurgery or stereotactic radiosurgery) with medical management alone in people with symptomatic brain cavernoma - protocol for the Cavernomas: A Randomised Effectiveness (CARE) pilot trial.

INTRODUCTION: The top research priority for cavernoma, identified by a James Lind Alliance Priority setting partnership was 'Does treatment (with neurosurgery or stereotactic radiosurgery) or no treatment improve outcome for people diagnosed with a cavernoma?' This pilot randomised controlled trial (RCT) aims to determine the feasibility of answering this question in a main phase RCT. METHODS AND ANALYSIS: We will perform a pilot phase, parallel group, pragmatic RCT involving approximately 60 children or adults with mental capacity, resident in the UK or Ireland, with an unresected symptomatic brain cavernoma. Participants will be randomised by web-based randomisation 1:1 to treatment with medical management and with surgery (neurosurgery or stereotactic radiosurgery) versus medical management alone, stratified by prerandomisation preference for type of surgery. In addition to 13 feasibility outcomes, the primary clinical outcome is symptomatic intracranial haemorrhage or new persistent/progressive focal neurological deficit measured at 6 monthly intervals. An integrated QuinteT Recruitment Intervention (QRI) evaluates screening logs, audio recordings of recruitment discussions, and interviews with recruiters and patients/parents/carers to identify and address barriers to participation. A Patient Advisory Group has codesigned the study and will oversee its progress. ETHICS AND DISSEMINATION: This study was approved by the Yorkshire and The Humber-Leeds East Research Ethics Committee (21/YH/0046). We will submit manuscripts to peer-reviewed journals, describing the findings of the QRI and the Cavernomas: A Randomised Evaluation (CARE) pilot trial. We will present at national specialty meetings. We will disseminate a plain English summary of the findings of the CARE pilot trial to participants and public audiences with input from, and acknowledgement of, the Patient Advisory Group. TRIAL REGISTRATION NUMBER: ISRCTN41647111

Morphometric Analysis of Human Second Cervical Vertebrae (Axis)

Possessing an odontoid process and unique superior articular facets, the axis vertebra morphometry significantly differs from morphometry of other cervical vertebrae. The fractures of axis, especially its dens, are very common and surgeries highly risky. Knowledge of the axis dimensions is essential not only for preclinical studies, diagnosis of spinal cord diseases, planning of the surgeries but also for correct selection and insertion of surgical instruments or vertebral implants design. Many quantitative studies of the second cervical vertebra have been performed, yet still lacking the area parameters determination and precision of three-dimension in vivo measurement. Vertebral dimensions are reported to vary among populations, although there are very little studies examining Caucasian specimen.This study aims to provide three-dimensional in vivo morphometric analysis of the axis vertebra as well as comparison to the previous studies. The clinically relevant vertebral dimensions were measured on the threedimensional model reconstruction of CT scans providing high accuracy. Five human second cervical vertebrae were investigated (Caucasian males) and linear, area and angular dimensions were measured.The data on vertebral body dimensions were best fitting Doherty and Naderi measurement. The vertebra body anterior height was established to be 26.2 mm and the posterior height 21.4 mm. The dens parameters were similar to those presented by Doherty. Doherty also reported large variation in the dens sagittal angle which was observed in the present study as well. The dens height was determined to be 17.8 mm which is significantly greater compared to the previous studies. The smallest height among specimens was reported to be 17.0 mm. The smallest anteroposterior or transverse diameter of the dens measured was the upper depth, 9.4 mm. The smallest and biggest areas of dens were measured to be 79.0 mm2 and 121.6 mm2. The superior articular facet area with mean value 211.2 mm2 was observed to be significantly bigger than the inferior area, 141.2 mm2. The mean sagittal angle of the inferior facet area was assessed to be 42.1° and the mean frontal angle of the superior articular facet 69.3°. The parameters of articular facets measured by Xu correspond to the present study. Due to the vertebral body enlargement in the inferior part of vertebra, the spinal canal superior depth,18.0 mm, was observed to be bigger than its inferior depth, 16.2 mm. In case of the spinal canal depth, Sengul measured values considerably greater than other studies. However, Singla, Gosavi and Xu presented the parameters very similar to the present study. Spinal canal width was measured to be 24.4 mm supporting the measurement done by Sengul which is 24.7 mm.The measured vertebral dimensions can be used either for development of instrumentation, preclinical planning of surgeries, implant design or as the reference values for evaluation and diagnosis of various clinical conditions