Exciting innovations for the spinally injured

Spinal injury can be devastating, resulting, as it often does, in some paralysis and loss of sensation. Engineering plays an important role in spinal cord injury rehabilitation. Here, the authors survey current research into the uses of functional electrical stimulation to improve the quality of life of spinally injured people. Touching on the area of spinal cord repair and nerve regeneration, they also consider the question of whether technology can help paraplegics to take steps again

Upper-limb exercise in tetraplegia using functional electrical stimulation

Cervical spinal cord injury can result in dysfunction in both the lower and upper limbs (tetraplegia), andmay be accompanied by a range of secondary complications. The degree of upper-limb dysfunctiondepends upon the level and completeness of the lesion; in this paper we consider tetraplegics with a neurological level in the range C4-C6. A person with a C5- or C6-level injury will generally retain control of the shoulder and elbow flexor muscles biceps), but will have no control of the hand, wrist or elbow extensors (triceps).With a complete C4 injury voluntary control of the entire arm is lost. Thus, we propose that functional electrical stimulation (FES) of the biceps and triceps muscles may enhance the efficacy of cyclical upper-limb exercise. Alternatives for partial restoration of function include tendon transfer surgery or mechanical orthoses1. Previous FES research for C4-C6 tetraplegics has focused on systems for hand function2,3 and improved working area (i.e. overhead reach)4,5,6,7, but the provision of upper-limb exercise modalities using FES assistance has been neglected. This is important because the lack of effective exercise can lead rapidly to severe cardiopulmonary deconditioning in this population

Automatic electrical stimulation of abdominal wall muscles increases tidal volume and cough peak flow in tetraplegia

<p>Paralysis of the respiratory muscles in people with tetraplegia affects their ability to breathe and contributes to respiratory complications. Surface functional electrical stimulation (FES) of abdominal wall muscles can be used to increase tidal volume (V_{T}) and improve cough peak flow (CPF) in tetraplegic subjects who are able to breathe spontaneously.</p> <p>This study aims to evaluate the feasibility and effectiveness of a novel abdominal FES system which generates stimulation automatically, synchronised with the subjects' voluntary breathing activity. Four subjects with complete tetraplegia (C4-C6), breathing spontaneously, were recruited.</p> <p>The automatic stimulation system ensured that consistent stimulation was achieved. We compared spirometry during unassisted and FES-assisted quiet breathing and coughing, and measured the effect of stimulation on end-tidal CO_2 (EtCO_2) during quiet breathing.</p> <p>The system dependably recognised spontaneous respiratory effort, stimulating appropriately, and was well tolerated by patients. Significant increases in V_T during quiet breathing (range 0.05–0.23 L) and in CPF (range 0.04–0.49 L/s) were observed. Respiratory rate during quiet breathing decreased in all subjects when stimulated, whereas minute ventilation increased by 1.05–2.07 L/min. The changes in EtCO_2 were inconclusive.</p> <p>The automatic stimulation system augmented spontaneous breathing and coughing in tetraplegic patients and may provide a potential means of respiratory support for tetraplegic patients with reduced respiratory capacity.</p&gt

Arm-cranking exercise assisted by Functional Electrical Stimulation in C6 tetraplegia: a pilot study

Tetraplegic volunteers undertook progressive exercise training, using novel systems for arm-cranking exercise assisted by Functional Electrical Stimulation (FES). The main aim was to determine potential training effects of FES-assisted arm-crank ergometry (FES-ACE) on upper limb strength and cardiopulmonary {fitness} in tetraplegia. Surface FES was applied to the biceps and triceps during exercise on an instrumented ergometer. Two tetraplegic volunteers with C6 Spinal Cord Injury (SCI) went through muscle strengthening, baseline exercise testing and three months of progressive FES-ACE training. Repeat exercise tests were carried out every four weeks during training, and post-training, to monitor upper-limb strength and cardiopulmonary fitness. At each test point, an incremental test was carried out to determine peak work rate, peak oxygen uptake, gas exchange threshold and oxygen uptake-work rate relationship during FES-ACE. Peak oxygen uptake for Subject A increased from 0.7 l/min to 1.1 l/min, and peak power output increased from 7 W to 38 W after FES-ACE training. For Subject B, peak oxygen uptake was unchanged, but peak power output increased from 3 W to 8 W. These case studies illustrate potential benefits of FES-ACE in tetraplegia, but also the differences in exercise responses between individuals. Keywords: electrical stimulation; spinal cord injury; cardiopulmonary fitness; rehabilitation; tetraplegi

Production of alkenes and novel secondary products by P450 OleT JE using novel H2O2-generating fusion protein systems

Jeotgalicoccus sp. 8456 OleTJE (CYP152L1) is a fatty acid decarboxylase cytochrome P450 that uses hydrogen peroxide (H2O2) to catalyse production of terminal alkenes, which are industrially important chemicals with biofuel applications. We report enzyme fusion systems in which Streptomyces coelicolor alditol oxidase (AldO) is linked to OleTJE. AldO oxidizes polyols (including glycerol), generating H2O2 as a co-product and facilitating its use for efficient OleTJE-dependent fatty acid decarboxylation. AldO activity is regulatable by polyol substrate titration, enabling control over H2O2 supply to minimise oxidative inactivation of OleTJE and prolong activity for increased alkene production. We also use these fusion systems to generate novel products from secondary turnover of 2-OH and 3-OH myristic acid primary products, expanding the catalytic repertoire of OleTJE

Methods and protocols for incremental exercise testing in tetraplegia, using arm-crank ergometry assisted by Functional Electrical Stimulation

Cervical spinal cord injury (SCI) leads to tetraplegia, with paralysis and loss of sensation in the upper and lower limbs. The associated sedentary lifestyle results in an increased risk of cardiovascular disease. To address this, we require the design of exercise modalities aimed specifically at tetraplegia and methods to assess their efficacy. This paper describes methods for arm-crank ergometry (ACE) assisted by Functional Electrical Stimulation (FES) applied to the biceps and triceps. The instrumented ergometer enables work-rate control during exercise, implemented here for incremental exercise testing during FES-ACE. Detailed protocols for the tests are given. Experimental data collected during exercise tests with tetraplegic volunteers are provided to illustrate the feasibility of the proposed approach to testing and data analysis. Incremental tests enabled calculation of peak power output and peak oxygen uptake. We propose that the high-precision exercise testing protocols described here are appropriate to assess the efficacy of the novel exercise modality, FES-ACE, in tetraplegia

Comparison of stimulation patterns for FES-cycling using measures of oxygen cost and stimulation cost

<b>Aim</b><p></p> The energy efficiency of FES-cycling in spinal cord injured subjects is very much lower than that of normal cycling, and efficiency is dependent upon the parameters of muscle stimulation. We investigated measures which can be used to evaluate the effect on cycling performance of changes in stimulation parameters, and which might therefore be used to optimise them. We aimed to determine whether oxygen cost and stimulation cost measurements are sensitive enough to allow discrimination between the efficacy of different activation ranges for stimulation of each muscle group during constant-power cycling. <p></p> <b>Methods</b><p></p> We employed a custom FES-cycling ergometer system, with accurate control of cadence and stimulated exercise workrate. Two sets of muscle activation angles (“stimulation patterns”), denoted “P1” and “P2”, were applied repeatedly (eight times each) during constant-power cycling, in a repeated measures design with a single paraplegic subject. Pulmonary oxygen uptake was measured in real time and used to determine the oxygen cost of the exercise. A new measure of stimulation cost of the exercise is proposed, which represents the total rate of stimulation charge applied to the stimulated muscle groups during cycling. A number of energy-efficiency measures were also estimated. <p></p> <b>Results</b><p></p> Average oxygen cost and stimulation cost of P1 were found to be significantly lower than those for P2 (paired <i>t</i>-test, <i>p</i> < 0.05): oxygen costs were 0.56 ± 0.03 l min<sup>−1</sup> and 0.61 ± 0.04 l min<sup>−1</sup>(mean ± S.D.), respectively; stimulation costs were 74.91 ± 12.15 mC min<sup>−1</sup> and 100.30 ± 14.78 mC min<sup>−1</sup> (mean ± S.D.), respectively. Correspondingly, all efficiency estimates for P1 were greater than those for P2. <p></p> <b>Conclusion</b><p></p> Oxygen cost and stimulation cost measures both allow discrimination between the efficacy of different muscle activation patterns during constant-power FES-cycling. However, stimulation cost is more easily determined in real time, and responds more rapidly and with greatly improved signal-to-noise properties than the ventilatory oxygen uptake measurements required for estimation of oxygen cost. These measures may find utility in the adjustment of stimulation patterns for achievement of optimal cycling performance. <p></p&gt

Tragedy revisited

“Freedom in a commons brings ruin to all.” So argued ecologist Garrett Hardin in “The Tragedy of the Commons” in the 13 December 1968 issue of Science (1). Hardin questioned society's ability to manage shared resources and avoid an environmentally and socially calamitous free-for-all. In the 50 years since, the essay has influenced discussions ranging from climate change (see page 1217) to evolution, from infectious disease to the internet, and has reached far beyond academic literature—but not without criticism. Considerable work, notably by Nobelist Elinor Ostrom (2), has challenged Hardin, particularly his emphasis on property rights and government regulatory leviathans as solutions. Instead, research has documented contexts, cases, and principles that reflect the ability of groups to collectively govern common resources. To mark this anniversary and celebrate the richness of research and practice around commons and cooperation, Science invited experts to share some contemporary views on such tragedies and how to avert them. —Brad Wibl

Proteomic Analysis Reveals Age-related Changes in Tendon Matrix Composition, with Age- and Injury-specific Matrix Fragmentation

Energy storing tendons, such as the human Achilles and equine superficial digital flexor tendon (SDFT), are highly prone to injury, the incidence of which increases with aging. The cellular and molecular mechanisms that result in increased injury in aged tendons are not well established but are thought to result in altered matrix turnover. However, little attempt has been made to fully characterize the tendon proteome nor determine how the abundance of specific tendon proteins changes with aging and/or injury. The aim of this study was, therefore, to assess the protein profile of normal SDFTs from young and old horses using label-free relative quantification to identify differentially abundant proteins and peptide fragments between age groups. The protein profile of injured SDFTs from young and old horses was also assessed. The results demonstrate distinct proteomic profiles in young and old tendon, with alterations in the levels of proteins involved in matrix organization and regulation of cell tension. Furthermore, we identified several new peptide fragments (neopeptides) present in aged tendons, suggesting that there are age-specific cleavage patterns within the SDFT. Proteomic profile also differed between young and old injured tendon, with a greater number of neopeptides identified in young injured tendon. This study has increased the knowledge of molecular events associated with tendon aging and injury, suggesting that maintenance and repair of tendon tissue may be reduced in aged individuals and may help to explain why the risk of injury increases with aging

Technical summary

Human interference with the climate system is occurring. Climate change poses risks for human and natural systems. The assessment of impacts, adaptation, and vulnerability in the Working Group II contribution to the IPCC's Fifth Assessment Report (WGII AR5) evaluates how patterns of risks and potential benefits are shifting due to climate change and how risks can be reduced through mitigation and adaptation. It recognizes that risks of climate change will vary across regions and populations, through space and time, dependent on myriad factors including the extent of mitigation and adaptation