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

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

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 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

Mental health symptoms in children and adolescents during COVID-19 in Australia

OBJECTIVE: COVID-19 has led to disruptions to the lives of Australian families through social distancing, school closures, a temporary move to home-based online learning, and effective lockdown. Understanding the effects on child and adolescent mental health is important to inform policies to support communities as they continue to face the pandemic and future crises. This paper sought to report on mental health symptoms in Australian children and adolescents during the initial stages of the pandemic (May to November 2020) and to examine their association with child/family characteristics and exposure to the broad COVID-19 environment. METHODS: An online baseline survey was completed by 1327 parents and carers of Australian children aged 4 to 17 years. Parents/carers reported on their child’s mental health using five measures, including emotional symptoms, conduct problems, hyperactivity/inattention, anxiety symptoms and depressive symptoms. Child/family characteristics and COVID-related variables were measured. RESULTS: Overall, 30.5%, 26.3% and 9.5% of our sample scored in the high to very high range for emotional symptoms, conduct problems and hyperactivity/inattention, respectively. Similarly, 20.2% and 20.4% of our sample scored in the clinical range for anxiety symptoms and depressive symptoms, respectively. A child’s pre-existing mental health diagnosis, neurodevelopmental condition and chronic illness significantly predicted parent-reported child and adolescent mental health symptoms. Parental mental health symptoms, having a close contact with COVID-19 and applying for government financial assistance during COVID-19, were significantly associated with child and adolescent mental health symptoms. CONCLUSION: Our findings show that Australian children and adolescents experienced considerable levels of mental health symptoms during the initial phase of COVID-19. This highlights the need for targeted and effective support for affected youth, particularly for those with pre-existing vulnerabilities

Disfluency in dialogue:an intentional signal from the speaker?

Disfluency is a characteristic feature of spontaneous human speech, commonly seen as a consequence of problems with production. However, the question remains open as to why speakers are disfluent: Is it a mechanical by-product of planning difficulty, or do speakers use disfluency in dialogue to manage listeners' expectations? To address this question, we present two experiments investigating the production of disfluency in monologue and dialogue situations. Dialogue affected the linguistic choices made by participants, who aligned on referring expressions by choosing less frequent names for ambiguous images where those names had previously been mentioned. However, participants were no more disfluent in dialogue than in monologue situations, and the distribution of types of disfluency used remained constant. Our evidence rules out at least a straightforward interpretation of the view that disfluencies are an intentional signal in dialogue. © 2012 Psychonomic Society, Inc

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe

The effect of intervertebral cartilage on neutral posture and range of motion in the necks of sauropod dinosaurs

The necks of sauropod dinosaurs were a key factor in their evolution. The habitual posture and range of motion of these necks has been controversial, and computer-aided studies have argued for an obligatory sub-horizontal pose. However, such studies are compromised by their failure to take into account the important role of intervertebral cartilage. This cartilage takes very different forms in different animals. Mammals and crocodilians have intervertebral discs, while birds have synovial joints in their necks. The form and thickness of cartilage varies significantly even among closely related taxa. We cannot yet tell whether the neck joints of sauropods more closely resembled those of birds or mammals. Inspection of CT scans showed cartilage:bone ratios of 4.5% for Sauroposeidon and about 20% and 15% for two juvenile Apatosaurus individuals. In extant animals, this ratio varied from 2.59% for the rhea to 24% for a juvenile giraffe. It is not yet possible to disentangle ontogenetic and taxonomic signals, but mammal cartilage is generally three times as thick as that of birds. Our most detailed work, on a turkey, yielded a cartilage:bone ratio of 4.56%. Articular cartilage also added 11% to the length of the turkey's zygapophyseal facets. Simple image manipulation suggests that incorporating 4.56% of neck cartilage into an intervertebral joint of a turkey raises neutral posture by 15°. If this were also true of sauropods, the true neutral pose of the neck would be much higher than has been depicted. An additional 11% of zygapophyseal facet length translates to 11% more range of motion at each joint. More precise quantitative results must await detailed modelling. In summary, including cartilage in our models of sauropod necks shows that they were longer, more elevated and more flexible than previously recognised

Combinatorial Roles of Heparan Sulfate Proteoglycans and Heparan Sulfates in Caenorhabditis elegans Neural Development

Heparan sulfate proteoglycans (HSPGs) play critical roles in the development and adult physiology of all metazoan organisms. Most of the known molecular interactions of HSPGs are attributed to the structurally highly complex heparan sulfate (HS) glycans. However, whether a specific HSPG (such as syndecan) contains HS modifications that differ from another HSPG (such as glypican) has remained largely unresolved. Here, a neural model in C. elegans is used to demonstrate for the first time the relationship between specific HSPGs and HS modifications in a defined biological process in vivo. HSPGs are critical for the migration of hermaphrodite specific neurons (HSNs) as genetic elimination of multiple HSPGs leads to 80% defect of HSN migration. The effects of genetic elimination of HSPGs are additive, suggesting that multiple HSPGs, present in the migrating neuron and in the matrix, act in parallel to support neuron migration. Genetic analyses suggest that syndecan/sdn-1 and HS 6-O-sulfotransferase, hst-6, function in a linear signaling pathway and glypican/lon-2 and HS 2-O-sulfotransferase, hst-2, function together in a pathway that is parallel to sdn-1 and hst-6. These results suggest core protein specific HS modifications that are critical for HSN migration. In C. elegans, the core protein specificity of distinct HS modifications may be in part regulated at the level of tissue specific expression of genes encoding for HSPGs and HS modifying enzymes. Genetic analysis reveals that there is a delicate balance of HS modifications and eliminating one HS modifying enzyme in a compromised genetic background leads to significant changes in the overall phenotype. These findings are of importance with the view of HS as a critical regulator of cell signaling in normal development and disease

Recombination rate and selection strength in HIV intra-patient evolution

The evolutionary dynamics of HIV during the chronic phase of infection is driven by the host immune response and by selective pressures exerted through drug treatment. To understand and model the evolution of HIV quantitatively, the parameters governing genetic diversification and the strength of selection need to be known. While mutation rates can be measured in single replication cycles, the relevant effective recombination rate depends on the probability of coinfection of a cell with more than one virus and can only be inferred from population data. However, most population genetic estimators for recombination rates assume absence of selection and are hence of limited applicability to HIV, since positive and purifying selection are important in HIV evolution. Here, we estimate the rate of recombination and the distribution of selection coefficients from time-resolved sequence data tracking the evolution of HIV within single patients. By examining temporal changes in the genetic composition of the population, we estimate the effective recombination to be r=1.4e-5 recombinations per site and generation. Furthermore, we provide evidence that selection coefficients of at least 15% of the observed non-synonymous polymorphisms exceed 0.8% per generation. These results provide a basis for a more detailed understanding of the evolution of HIV. A particularly interesting case is evolution in response to drug treatment, where recombination can facilitate the rapid acquisition of multiple resistance mutations. With the methods developed here, more precise and more detailed studies will be possible, as soon as data with higher time resolution and greater sample sizes is available.Comment: to appear in PLoS Computational Biolog