Vertebral artery strains during high-speed, low amplitude cervical spinal manipulation

Spinal manipulative therapy (SMT) has been recognized as an effective treatment modality for many back, neck and musculoskeletal problems. One of the major issues of the use of SMT is its safety, especially with regards to neck manipulation and the risk of stroke. The vast majority of these accidents involve the vertebro-basilar system, specifically the vertebral artery (VA) between C2/C1. However, the mechanics of this region of the VA during SMT are unexplored. Here, we present first ever data on the mechanics of this region during cervical SMT performed by clinicians. VA strains obtained during SMT are significantly smaller than those obtained during diagnostic and range of motion testing, and are much smaller than failure strains. We conclude from this work that cervical SMT performed by trained clinicians does not appear to place undue strain on VA, and thus does not seem to be a factor in vertebro-basilar injuries.     

Biomechanical quantification of experimental spinal cord trauma

An apparatus is described that produces experimental contusion of the spinal cord and completely defines the mechanical parameters of the trauma. The data provided includes a continuous record of the force, displacement, velocity of deformation, and acceleration of deformation of the spinal cord and the underlying thorax.     

Biomechanical implications of lumbar spinal ligament transection

Many lumbar spine surgeries either intentionally or inadvertently damage or transect spinal ligaments. The purpose of this work was to quantify the previously unknown biomechanical consequences of isolated spinal ligament transection on the remaining spinal ligaments (stress transfer), vertebrae (bone remodelling stimulus) and intervertebral discs (disc pressure) of the lumbar spine. A finite element model of the full lumbar spine was developed and validated against experimental data and tested in the primary modes of spinal motion in the intact condition. Once a ligament was removed, stress increased in the remaining spinal ligaments and changes occurred in vertebral strain energy, but disc pressure remained similar. All major biomechanical changes occurred at the same spinal level as the transected ligament, with minor changes at adjacent levels. This work demonstrates that iatrogenic damage to spinal ligaments disturbs the load sharing within the spinal ligament network and may induce significant clinically relevant changes in the spinal motion segment.     

Biomechanical analysis of the anterior cervical fusion

This paper presents a biomechanical analysis of the cervical C5-C6 functional spine unit before and after the anterior cervical discectomy and fusion. The aim of this work is to study the influence of the medical procedure and its instrumentation on range of motion and stress distribution. First, a three-dimensional finite element model of the lower cervical spine is obtained from computed tomography images using a pipeline of image processing, geometric modelling and mesh generation software. Then, a finite element study of parameters' influence on motion and a stress analysis at physiological and different post-operative scenarios were made for the basic movements of the cervical spine. It was confirmed that the results were very sensitive to intervertebral disc properties. The insertion of an anterior cervical plate influenced the stress distribution at the vertebral level as well as in the bone graft. Additionally, stress values in the graft decreased when it is used together with a cage.     

Biomechanical analysis of the anterior cervical fusion

This paper presents a biomechanical analysis of the cervical C5–C6 functional spine unit before and after the anterior cervical discectomy and fusion. The aim of this work is to study the influence of the medical procedure and its instrumentation on range of motion and stress distribution. First, a three-dimensional finite element model of the lower cervical spine is obtained from computed tomography images using a pipeline of image processing, geometric modelling and mesh generation software. Then, a finite element study of parameters' influence on motion and a stress analysis at physiological and different post-operative scenarios were made for the basic movements of the cervical spine. It was confirmed that the results were very sensitive to intervertebral disc properties. The insertion of an anterior cervical plate influenced the stress distribution at the vertebral level as well as in the bone graft. Additionally, stress values in the graft decreased when it is used together with a cage.     

Magnetic manipulation of nanorods in the nucleus of living cells

The organization of chromatin in the cell nucleus is crucial for gene expression regulation. However, physically probing the nuclear interior is challenging because high forces have to be applied using minimally invasive techniques. Here, magnetic nanorods embedded in the nucleus of living cells are subjected to controlled rotational forces, producing micron-sized displacements in the nuclear interior. The resulting time-dependent rotation of the nanorods is analyzed in terms of viscoelastic parameters of the nucleus, in wild-type and Lamin A/C deficient cells. This method and analysis reveal that Lamin A/C knockout, together perhaps with other changes that result from the knockout, induce significant decreases in the nuclear viscosity and elasticity.     

Performance based objective outcome measures and spinal manipulation

This paper provides a general overview of performance based outcome measures used in an attempt to objectively measure the ramifications of spinal manipulation. While not a systematic or exhaustive review it serves to categorize, and provide insight into the background, successes and shortcomings of measurement techniques used. The outcome measures are drawn from the full spectrum of approaches to research and are broken down into the following sections: (1) biomechanically constrained motor performance measures, (2) neurologically constrained performance measures and (3) perceptual, perceptual motor, and complex task constrained performance measures. The paper concludes with some future research directions to enhance the understanding of the impact of spinal manipulation, and how to objectively measure its mechanical and physiological effects on the human system.     

Biomechanical characterisation of ovine spinal facet joint cartilage

The spinal facet joints are known to be an important component in the kinematics and the load transmission of the spine. The articular cartilage in the facet joint is prone to degenerative changes which lead to back pain and treatments for the condition have had limited long term success. There is currently a lack of information on the basic biomechanical properties of the facet joint cartilage which is needed to develop tissue substitution or regenerative interventions. In the present study, the thickness and biphasic properties of ovine facet cartilage were determined using a combination of indentation tests and computational modelling. The equilibrium biphasic Young's modulus and permeability were derived to be 0.76±0.35 MPa and 1.61±1.10×10^?15 m⁴/(Ns) respectively, which were within the range of cartilage properties characterised from the human synovial joints. The average thickness of the ovine facet cartilage was 0.52±0.10 mm, which was measured using a needle indentation test. These properties could potentially be used for the development of substitution or tissue engineering interventions and for computational modelling of the facet joint. Furthermore, the developed method to characterise the facet cartilage could be used for other animals or human donors.     

Isolation, characterization and manipulation of cellulase genes

The complete hydrolysis of cellulose requires a number of different enzymes including endoglucanase, exoglucanase and beta-glucosidase. These enzymes function in concert as part of a 'cellulase'complex called a cellulosome. In order (i) to develop a better understanding of the biochemical nature of the cellulase complex as well as the genetic regulation of its integral components and (ii) to utilize cellulases either as purified enzymes or as part of an engineered organism for a variety of purposes, researchers have, as a first step, used recombinant DNA technology to isolate the genes for these enzymes from a variety of organisms. This review provides some perspective on the current status of the isolation, characterization and manipulation of cellulase genes and specifically discusses (i) strategies for the isolation of endoglucanase, exoglucanase and beta-glucosidase genes; (ii) DNA sequence characterization of the cellulase genes and their accompanying regulatory elements; (iii) the expression of cellulase genes in heterologous host organisms and (iv) some of the proposed uses for isolated cellulase genes.     

Biomechanical design of load simulation in multiple spinal segments]

Multisegmental biomechanical studies on the lumbar spine are steadily increasing in importance. Only in this way can we acquire knowledge about the physiological behaviour of the entire lumbar spine. Furthermore, these studies allow us to analyse in vitro the biomechanics of manipulated lumbar spines after various surgical operations on the spine. A load simulator was developed to investigate multisegmental lumbar spine mobility, and its function was investigated in an initial study on 19 fresh--frozen specimens of human lumbar spine. After x-ray examination and determination of the bone mineral density, the specimens were loaded up to 10 Nm in the automatic electromechanical loading system under flexion/extension, lateral bending and axial rotation. An ultrasound-based motion analysis system was used to measure the displacements of the vertebrae involved.     

Biomechanical characterization of a desminopathy in primary human myoblasts

Heterozygous mutations of the human desmin gene on chromosome 2q35 cause hereditary and sporadic myopathies and cardiomyopathies. The expression of mutant desmin brings about partial disruption of the extra sarcomeric desmin cytoskeleton and abnormal protein aggregation in the sarcoplasm of striated muscle cells. The precise molecular pathways and sequential steps that lead from a desmin gene defect to progressive muscle damage are still unclear. We tested whether mutant desmin changes the biomechanical properties and the intrinsic mechanical stress response of primary cultured myoblasts derived from a patient carrying a heterozygous R350P desmin mutation. Compared to wildtype controls, undifferentiated mutant desmin myoblasts revealed increased cell death and substrate detachment in response to cyclic stretch on flexible membranes. Moreover, magnetic tweezer microrheometry of myoblasts using fibronectin-coated beads showed increased stiffness of diseased cells. Our findings provide the first evidence that altered mechanical properties may contribute to the progressive striated muscle pathology in desminopathies. We postulate that the expression of mutant desmin leads to increased mechanical stiffness, which results in excessive mechanical stress in response to strain and consecutively to increased mechanical vulnerability and damage of muscle cells.     

Reporter gene imaging of protein-protein interactions in living subjects

In the past few years there has been a veritable explosion in the field of reporter gene imaging, with the aim of determining the location, duration and extent of gene expression within living subjects. An important application of this approach is the molecular imaging of interacting protein partners, which could pave the way to functional proteomics in living animals and might provide a tool for the whole-body evaluation of new pharmaceuticals targeted to modulate protein-protein interactions. Three general methods are currently available for imaging protein-protein interactions in living subjects using reporter genes: a modified mammalian two-hybrid system, a bioluminescence resonance energy transfer (BRET) system, and split reporter protein complementation and reconstitution strategies. In the future, these innovative approaches are likely to enhance our appreciation of entire biological pathway systems and their pharmacological regulation.     

Multimodality molecular imaging of disease progression in living subjects

The enormous advances in our understanding of the progression of diseases at the molecular level have been supplemented by the new field of ‘molecular imaging’, which provides for in vivo visualization of molecular events at the cellular level in living organisms. Molecular imaging is a noninvasive assessment of gene and protein function, protein–protein interaction and/or signal transduction pathways in animal models of human disease and in patients to provide insights into molecular pathogenesis. Five major imaging techniques are currently available to assess the structural and functional alterations in vivo in small animals. These are (i) optical bioluminescence and fluorescence imaging techniques, (ii) radionuclide-based positron emission tomography (PET) and single photon emitted computed tomography (SPECT), (iii) X-ray-based computed tomography (CT), (iv) magnetic resonance imaging (MRI) and (v) ultrasound imaging (US). Functional molecular imaging requires an imaging probe that is specific for a given molecular event. In preclinical imaging, involving small animal models, the imaging probe could be an element of a direct (‘direct imaging’) or an indirect (‘indirect imaging’) event. Reporter genes are essential for indirect imaging and provide a general integrated platform for many different applications. Applications of multimodality imaging using combinations of bioluminescent, fluorescent and PET reporter genes in unified fusion vectors developed by us for recording events from single live cells to whole animals with high sensitivity and accurate quantification are discussed. Such approaches have immense potential to track progression of metastasis, immune cell trafficking, stem cell therapy, transgenic animals and even molecular interactions in living subjects.     

Quantification of fungiform papillae and taste pores in living human subjects

A method developed to quantify taste buds in living human subjectsto study the relationship between taste sensitivity and tastebud distribution was used to count the taste buds in 10 humansubjects; fungiform papillae were mapped in 12 subjects. Tastebuds were identified by staining taste pores with methyleneblue, and images of the papillae and their taste pores wereobtained with videomicroscopy and an image processor. Fungiformpapillae showed a 3.3-fold range in density, from 22.1 to 73.6papillae/cm² with an average of 41.1 ± 16.8/cm² (s.d.,n = 2). There was a 14-fold range in taste pore density, from36 to 511 pores/cm² among subjects, with an average of 193 ±133/cm² (s.d., n = 10). Fungiform papillae contained from 0to 22 taste pores, with an average per subject of 3.75 ±1.4 taste pores/papilla (s.d., n = 10). We hypothesize thatsome differences in human taste sensitivity may be related tothese variations in taste bud density.     

Biomechanics - Review of approaches for performance training in spinal manipulation

Motor skills development is an inherent part of clinical training in health disciplines. The conscious use of educational theory to ground learning is receiving increasing attention across health care education. There are three distinct, yet overlapping, stages of motor skill learning; the cognitive, the integrative or associative, and the autonomous; in which a contextual framework for learning content may be structured. The learning is associated with a mapping of changes within the central nervous system by the interactive mechanisms of adaptation, use-dependent plasticity and operant reinforcement. Successful skill learning requires a sufficient amount of practice and the implementation of relevant feedback strategies in the form of knowledge of performance (KP) or knowledge of results (KR). There is a natural maturation of skills that may be accelerated by feedback. Several factors contribute to stronger skills development. "Mixture-of-experts" models systematically sequence tasks into logical blocks of theory, practice and student reflection on performance. Feedback should involve both KP and KR that compares performance to a tangible standard. Rehearsals should balance use of simulators and volunteer simulated patients to provide the full range of safe and effective learning opportunities prior to students accepting a role as care givers to the public in any clinical setting.     

Dielectrophoretic manipulation and characterization of herpes simplex virus-1 capsids

The dielectrophoretic behaviour of the capsids of herpes simplex virus type-1 has been measured over a range of conductivities of KCl solutions, with and without the addition of mannitol. The dielectrophoretic response of the capsids was recorded by measuring the frequency corresponding to zero dielectrophoretic force. The data were analysed using a multi-shelled model, and the permittivity and conductivity of the particles estimated. The capsid was modelled as a porous protein shell through which suspending medium passes, an inner chamber containing suspending medium in equilibrium with the outside, and a central core of protein (the scaffold). Capsids suspended in KCl without mannitol exhibited a different behaviour to those suspended in KCl with mannitol.     

Thermoregulatory responses to temperature manipulation of the spinal cord in the marmot

Yellow-bellied marmots (M. flaviventris) acclimated to T_a = 20 °C were implanted with U-shaped polyethylene thermodes in the peridural space of the spinal cord. Decreasing the temperature of the cervical, thoracic, or lumbar areas of the cord increased heart rate, electromyographic activity, and oxygen consumption in the animals. These responses differed qualitatively from those elicited by heating the same cord areas, indicating specificity of the response to the temperature change.Increases in heat production were proportional to the amount of cooling of the cord. The thoracic area was found to be more thermosensitive than the lumbar area. No behavioral or physical thermoregulation was apparent when the spinal cord temperature was changed in these animals.In addition to the conclusion that regulation of spinal cord temperature may be important in the euthermic marmot, it was postulated that the temperature receptors located in the thoracic cord of the marmot may be important in maintaining shivering thermogenesis during arousal from hibernation.