Optimal electrode position for abdominal functional electrical stimulation

Abdominal functional electrical stimulation (abdominal FES) improves respiratory function. Despite this, clinical use remains low, possibly due to lack of agreement on the optimal electrode position. This study aimed to ascertain the optimal electrode position for abdominal FES, assessed by expiratory twitch pressure. Ten able-bodied participants received abdominal FES using electrodes placed: 1) on the posterolateral abdominal wall and at the motor points of 2) the external oblique muscles plus rectus abdominis muscles, and 3) the external obliques alone. Gastric (Pga) and esophageal (Pes) twitch pressures were measured using a gastroesophageal catheter. Single-stimulation pulses were applied at functional residual capacity during step increments in stimulation current to maximal tolerance or until Pga plateaued. Stimulation applied on the posterolateral abdominal wall led to a 71% and 53% increase in Pga and Pes, respectively.compared with stimulation of the external oblique and rectus abdominis muscles (P < 0.001) and a 95% and 56% increase in Pga and Pes, respectively.compared with stimulation of the external oblique muscles alone (P < 0.001). Stimulation of both the external oblique and rectus abdominis muscles led to an 18.3% decrease in Pg.compared with stimulation of only the external oblique muscles (P = 0.040), with inclusion of the rectus abdominis having no effect on Pes (P = 0.809). Abdominal FES applied on the posterolateral abdominal wall generated the highest expiratory twitch pressures. As expiratory pressure is a good indicator of expiratory muscle strength and, thus, cough efficacy, we recommend this electrode position for all therapeutic applications of abdominal FES. NEW & NOTEWORTHY While abdominal functional electrical stimulation (abdominal FES) can improve respiratory function, clinical use remains low. This is at least partly due to lack of agreement on the optimal electrode position. Therefore, this study aimed to ascertain the optimal electrode position for abdominal FES. We show that electrodes placed on the posterolateral abdominal wall generated the highest expiratory twitch pressures. As such, we recommend this electrode position for all therapeutic applications of abdominal FES

The detection and sensory perception of inspiratory resistive loads in people with chronic tetraplegia

This study investigated sensations of breathing following tetraplegia. Fifteen people with chronic tetraplegia and fifteen healthy able-bodied controls matched for age, sex, height, and weight participated. Sensations of breathing were quantified by determining the threshold for detecting an added resistance during inspiration. In a separate task, the perceived magnitudes of six suprathreshold resistive loads were determined with a modified Borg scale. The detection threshold of 0.34 cmH2O/L/s [standard deviation (SD) 0.14] in the tetraplegia group was higher than the 0.23 cmH2O/L/s (SD 0.10) threshold for able-bodied controls (P = 0.004). Both participant groups perceived larger loads to be more effortful, with the Borg effort rating increasing linearly with the peak inspiratory pressure generated at each load. The relationship between Borg effort rating and peak inspiratory pressure was steeper in participants with tetraplegia than in able-bodied controls (P = 0.001), but there was no difference when pressure was divided by maximal inspiratory pressure (P = 0.95). Despite a higher detection threshold, the findings suggest that the perceived magnitude of a suprathreshold inspiratory load is not impaired in chronic tetraplegia and that load magnitude perception is related to the maximal, and not absolute, inspiratory muscle force. NEW & NOTEWORTHY Sensations of breathing are thought to be impaired following chronic tetraplegia. The detection threshold for an added resistive load during inspiration was higher in people with tetraplegia than in healthy able-bodied participants. However, for inspiratory loads above the detection threshold, the perceived magnitude of a resistive load as a function of the peak inspiratory pressure was greater in tetraplegia. Load magnitude perception was comparable between participant groups when peak pressure was divided by maximal inspiratory pressure

The reliability of inspiratory resistive load magnitude and detection testing

Objectives: To assess the test-retest reliability of inspiratory load detection and load magnitude perception tests in healthy volunteers. Design: Cohort of convenience. Setting: Respiratory physiology laboratory. Participants: Twenty healthy adults. Interventions: On two separate occasions participants performed tests of inspiratory loading. Participants breathed through custom made resistive tubing and were asked to indicate when they detected a different resistance during inspiration. In a second test participants rated the magnitude of presented inspiratory loads using the modified Borg score. Main Outcome Measures: Intra-class Correlation Coefficient (ICC2,1) values for repeated tests of inspiratory load detection threshold and load magnitude rating. Results: ICC2,1 values ranged from 0.657–0.786 for load detection testing and 0.739 to 0.969 for rating of load magnitude. Conclusions: The tests are simple and reliable measures of inspiratory load detection and magnitude rating. They can be used in future research to determine the effectiveness of interventions to reduce the effort of breathing in health and disease

Abdominal functional electrical stimulation to augment respiratory function in spinal cord injury

Background: Functional electrical stimulation (FES) is the application of electrical pulses to a nerve to achieve a functional muscle contraction. Surface electrical stimulation of the nerves that innervate the abdominal muscles, termed abdominal FES, can cause the abdominal muscles to contract, even when paralysed after spinal cord injury. As the abdominal muscles are the major expiratory muscles, and commonly partially or completely paralysed in tetraplegia, abdominal FES offers a promising method of improving respiratory function for this patient group. Objective: The aim of the article is to provide readers with a better understanding of how abdominal FES can be used to improve the health of the spinal cord–injured population. Methods: A narrative review of the abdominal FES literature was performed. Results: Abdominal FES can achieve an immediate effective cough in patients with tetraplegia, while the repeated application over 6 weeks of abdominal FES can improve unassisted respiratory function. Ventilator duration and tracheostomy cannulation time can also be reduced with repeated abdominal FES. Conclusion: Abdominal FES is a noninvasive method to achieve functional improvements in cough and respiratory function in acute and chronically injured people with tetraplegia. Potential practical outcomes of this include reduced ventilation duration, assisted tracheostomy decannulation, and a reduction in respiratory complications. All of these outcomes can contribute to reduced morbidity and mortality, improved quality of life, and significant potential cost savings for local health care providers

Inspiratory muscle responses to sudden airway occlusion in chronic obstructive pulmonary disease

Brief airway occlusion produces a potent reflex inhibition of inspiratory muscles that is thought to protect against aspiration. Its duration is prolonged in asthma and obstructive sleep apnea. We assessed this inhibitory reflex (IR) in chronic obstructive pulmonary disease (COPD). Reflex responses to brief (250 ms) inspiratory occlusions were measured in 18 participants with moderate to severe COPD (age 73 ± 11 yr) and 17 healthy age-matched controls (age 72 ± 6 yr). We compared the incidence and properties of the IR between groups. Median eupneic preocclusion electromyographic activity was higher in the COPD group than controls (9.4 μV vs. 5.2 μV, P = 0.001). Incidence of the short-latency IR was higher in the COPD group compared with controls (15 participants vs. 7 participants, P = 0.010). IR duration for scalenes was similar for the COPD and control groups [73 ± 37 ms (means ± SD) and 90 ± 50 ms, respectively] as was the magnitude of inhibition. IRs in the diaphragm were not detected in the controls but were present in 9 participants of the COPD group (P = 0.001). The higher incidence of the IR in the COPD group than in the age-matched controls may reflect the increased inspiratory neural drive in the COPD group. This higher drive counteracts changes in chest wall and lung mechanics. However, when present, the reflex was similar in size and duration in the two groups. The relation between the IR in COPD and swallowing function could be assessed. NEW & NOTEWORTHY A potent short-latency reflex inhibition of inspiratory muscles produced by airway occlusion was tested in people with COPD and age-matched controls. The reflex was more prevalent in COPD, presumably due to an increased neural drive to breathe. When present, the reflex was similar in duration in the two groups, longer than historical data for younger control groups. The work reveals novel differences in reflex control of inspiratory muscles due to aging as well as COPD

The frequency of bowel and bladder problems in multiple sclerosis and its relation to fatigue: A single centre experience

Background Bowel and bladder problems affect more than 50% of people with Multiple Sclerosis (MS). These problems have a large impact on quality of life and place a significant burden on health systems. Objectives This study aimed to ascertain the frequency of bladder and bowel problems in a select Australian MS cohort and to investigate the relationships between level of disability, bladder and bowel problems, and fatigue. Methods Questionnaires on the nature and severity of MS symptoms were distributed to clients attending an Australian MS centre. Log-binomial regression and multiple linear regression models were used to investigate relationships between disability, fatigue, and bladder and bowel problems. Results and conclusions Of 167 questionnaires distributed, 136 were completed. Bladder problems were reported by 87 (74.4%) respondents, whilst 66 (48.9%) experienced functional constipation and 43 (31.9%) faecal incontinence. This frequency in our select Australian MS population is similar to that reported globally. There was a significant correlation between level of disability and: bladder problems (p = 0.015), faecal incontinence (p = 0.001), fatigue (p<0.001) and constipation (p = 0.016, relative risk: 1.16). Further investigation into the causal relationships between various MS symptoms may be beneficial in the development of novel therapeutic strategies for people with MS

Impact of respiratory muscle training on respiratory muscle strength, respiratory function and quality of life in individuals with tetraplegia: A randomised clinical trial

Background Respiratory complications remain a leading cause of morbidity and mortality in people with acute and chronic tetraplegia. Respiratory muscle weakness following spinal cord injury-induced tetraplegia impairs lung function and the ability to cough. In particular, inspiratory muscle strength has been identified as the best predictor of the likelihood of developing pneumonia in individuals with tetraplegia. We hypothesised that 6 weeks of progressive respiratory muscle training (RMT) increases respiratory muscle strength with improvements in lung function, quality of life and respiratory health. Methods Sixty-two adults with tetraplegia participated in a double-blind randomised controlled trial. Active or sham RMT was performed twice daily for 6 weeks. Inspiratory muscle strength, measured as maximal inspiratory pressure (PImax) was the primary outcome. Secondary outcomes included lung function, quality of life and respiratory health. Between-group comparisons were obtained with linear models adjusting for baseline values of the outcomes. Results After 6 weeks, there was a greater improvement in PImax in the active group than in the sham group (mean difference 11.5 cmH 2 O (95% CI 5.6 to 17.4), p<0.001) and respiratory symptoms were reduced (St George Respiratory Questionnaire mean difference 10.3 points (0.01-20.65), p=0.046). Significant improvements were observed in quality of life (EuroQol-Five Dimensional Visual Analogue Scale 14.9 points (1.9-27.9), p=0.023) and perceived breathlessness (Borg score 0.64 (0.11-1.17), p=0.021). There were no significant improvements in other measures of respiratory function (p=0.126-0.979). Conclusions Progressive RMT increases inspiratory muscle strength in people with tetraplegia, by a magnitude which is likely to be clinically significant. Measurement of baseline PImax and provision of RMT to at-risk individuals may reduce respiratory complications after tetraplegia. Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN 12612000929808)

Inspiratory muscle reflex control after incomplete cervical spinal cord injury

In healthy individuals, loading inspiratory muscles by brief inspiratory occlusion produces a short-latency inhibitory reflex (IR) in the electromyographic (EMG) activity of scalene and diaphragm muscles. This IR may play a protective role to prevent aspiration and airway collapse during sleep. In people with motor and sensory complete cervical spinal cord injury (cSCI), who were able to breathe independently, this IR was predominantly absent. Here, we investigated the reflex response to brief airway occlusion in 16 participants with sensory incomplete cSCI [American spinal injury association impairment scale (AIS) score B or C]. Surface EMG was recorded from scalene muscles and the lateral chest wall (overlying diaphragm). The airway occlusion evoked a small change in mouth pressure resembling a physiological occlusion. The short-latency IR was present in 10 (63%) sensory incomplete cSCI participants; significantly higher than the IR incidence observed in complete cSCI participants in our previous study (14%; P = 0.003). When present, mean IR latency across all muscles was 58 ms (range 29-79 ms), and mean rectified EMG amplitude decreased to 37% preocclusion levels. Participants without an IR had untreated severe obstructive sleep apnea (OSA), in contrast to those with an IR, who had either had no, mild, or treated OSA (P = 0.002). Insufficient power did not allow statistical comparison between IR presence or absence and participant clinical characteristics. In conclusion, spared sensory connections or intersegmental connections may be necessary to generate the IR. Future studies to establish whether IR presence is related to respiratory morbidity in the tetraplegic population are required. NEW & NOTEWORTHY Individuals with incomplete cSCI were tested for the presence of a short latency reflex inhibition of inspiratory muscles, by brief airway occlusion. The reflex was 4.5 times more prevalent in this group compared with those with complete cSCI and is similar to the incidence in able-bodied people. Participants without this reflex all had untreated severe OSA, in contrast to those with an IR, who either had no, mild, or treated OSA. This work reveals novel differences in the reflex control of inspiratory muscles across the cSCI population

Non-Invasive Imaging of Cysteine Cathepsin Activity in Solid Tumors Using a 64Cu-Labeled Activity-Based Probe

The papain family of cysteine cathepsins are actively involved in multiple stages of tumorigenesis. Because elevated cathepsin activity can be found in many types of human cancers, they are promising biomarkers that can be used to target radiological contrast agents for tumor detection. However, currently there are no radiological imaging agents available for these important molecular targets. We report here the development of positron emission tomography (PET) radionuclide-labeled probes that target the cysteine cathepsins by formation of an enzyme activity-dependent bond with the active site cysteine. These probes contain an acyloxymethyl ketone (AOMK) functional group that irreversibly labels the active site cysteine of papain family proteases attached to a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) tag for labeling with 64Cu for PET imaging studies. We performed biodistribution and microPET imaging studies in nude mice bearing subcutaneous tumors expressing various levels of cysteine cathepsin activity and found that the extent of probe uptake by tumors correlated with overall protease activity as measured by biochemical methods. Furthermore, probe signals could be reduced by pre-treatment with a general cathepsin inhibitor. We also found that inclusion of a Cy5 tag on the probe increased tumor uptake relative to probes lacking this fluorogenic dye. Overall, these results demonstrate that small molecule activity-based probes carrying radio-tracers can be used to image protease activity in living subjects

Climate change drives microevolution in a wild bird

To ensure long-term persistence, organisms must adapt to climate change, but an evolutionary response to a quantified selection pressure driven by climate change has not been empirically demonstrated in a wild population. Here, we show that pheomelanin-based plumage colouration in tawny owls is a highly heritable trait, consistent with a simple Mendelian pattern of brown (dark) dominance over grey (pale). We show that strong viability selection against the brown morph occurs, but only under snow-rich winters. As winter conditions became milder in the last decades, selection against the brown morph diminished. Concurrent with this reduced selection, the frequency of brown morphs increased rapidly in our study population during the last 28 years and nationwide during the last 48 years. Hence, we show the first evidence that recent climate change alters natural selection in a wild population leading to a microevolutionary response, which demonstrates the ability of wild populations to evolve in response to climate change