Hypoxic regulation of ion channel function and expression

Acute hypoxia regulates the activity of specific ion channels in a rapid and reversible manner. Such effects underlie appropriate cellular responses to hypoxia which are designed to initiate cardiorespiratory reflexes and contribute importantly to other tissue responses, all of which are designed to improve tissue O2 supply. These responses include excitation of chemoreceptors as well as pulmonary vasoconstriction and systemic vasodilatation. However, such responses may also contribute to the adverse responses to hypoxia, such as excitotoxicity in the central nervous system. Whilst numerous ion channel types are known to be modulated by acute hypoxia, the nature of the O2 sensor in most tissues remains to be identified. Prolonged (chronic) hypoxia regulates functional expression of ion channels, and so remodels excitability of various cell types. Whilst this may contribute to adaptive responses such as high-altitude acclimatization, such altered channel expression may also contribute to the onset of pathological disorders, including Alzheimer's disease. Indeed, evidence is emerging that production of pathological peptides associated with Alzheimer's disease is increased during prolonged hypoxia. Such effects may account for the known increased incidence of this disease in patients who have previously endured hypoxic episodes, such as congestive heart failure and stroke. Identification of the mechanisms coupling hypoxia to the increased production of these peptides is likely to be of therapeutic benefit

Interactions of chemostimuli at the single cell level: studies in a model system

The responses of afferent chemosensory fibres of the carotid body to individual chemostimuli have long been established. However, the mechanisms underlying the multiplicative interactions of these stimuli (i.e. how the combined effects of hypoxia and hypercapnia exert a greater effect on afferent nerve discharge than the sum of their individual effects) have not been elucidated. Using the membrane hypothesis for carotid body chemoreception, in which chemostimuli inhibit type I cell K+ channels, leading to depolarization, voltage-gated Ca2+ entry and hence the triggering of exocytosis, this article considers data acquired in isolated type I carotid body cells and model chemoreceptor (PC12) cells to attempt to explain stimulus interactions. Whilst stimulus interactions are not clearly evident at the level of K+ channel inhibition or rises of [Ca2+](i), they are apparent at the level of transmitter release. Thus, it is clear that individual chemoreceptor cells can sense multiple stimuli, and that interactions of these stimuli can produce greater than additive effects in terms of transmitter release

Acute oxygen sensing: diverse but convergent mechanisms in airway and arterial chemoreceptors

Airway neuroepithelial bodies sense changes in inspired O2, whereas arterial O2 levels are monitored primarily by the carotid body. Both respond to hypoxia by initiating corrective cardiorespiratory reflexes, thereby optimising gas exchange in the face of a potentially deleterious O2 supply. One unifying theme underpinning chemotransduction in these tissues is K+ channel inhibition. However, the transduction components, from O2 sensor to K+ channel, display considerable tissue specificity yet result in analogous end points. Here we highlight how emerging data are contributing to a more complete understanding of O2 chemosensing at the molecular level

Performance and Usability Evaluation Scheme for Mobile Manipulator Teleoperation

This article presents a standardized human–robot teleoperation interface (HRTI) evaluation scheme for mobile manipulators. Teleoperation remains the predominant control type for mobile manipulators in open environments, particularly for quadruped manipulators. However, mobile manipulators, especially quadruped manipulators, are relatively novel systems to be implemented in the industry compared to traditional machinery. Consequently, no standardized interface evaluation method has been established for them. The proposed scheme is the first of its kind in evaluating mobile manipulator teleoperation. It comprises a set of robot motion tests, objective measures, subjective measures, and a prediction model to provide a comprehensive evaluation. The motion tests encompass locomotion, manipulation, and a combined test. The duration for each trial is collected as the response variable in the objective measure. Statistical tools, including mean value, standard deviation, and T-test, are utilized to cross-compare between different predictor variables. Based on an extended Fitts' law, the prediction model employs the time and mission difficulty index to forecast system performance in future missions. The subjective measures utilize the NASA-task load index and the system usability scale to assess workload and usability. Finally, the proposed scheme is implemented on a real-world quadruped manipulator with two widely-used HRTIs, the gamepad and the wearable motion capture system

A pragmatic benchmarking study of an evidence-based personalised approach in 1938 adolescents with high-risk idiopathic scoliosis

Combining evidence-based medicine and shared decision making, current guidelines support an evidence-based personalised approach (EBPA) for idiopathic scoliosis in adolescents (AIS). EBPA is considered important for adolescents\u2019 compliance, which is particularly difficult in AIS. Benchmarking to existing Randomised Controlled Trials (RCTs) as paradigms of single treatments, we aimed to check the effectiveness and burden of care of an EBPA in high-risk AIS. This study\u2019s design features a retrospective observation of a prospective database including 25,361 spinal deformity patients < 18 years of age. Participants consisted of 1938 AIS, 11\u201345\u25e6 Cobb, Risser stage 0\u20132, who were studied until the end of growth. EBPA included therapies classified for burdensomeness according to current guidelines. Using the same inclusion criteria of the RCTs on exercises, plastic, and elastic bracing, out of the 1938 included, we benchmarked 590, 687, and 884 participants, respectively. We checked clinically significant results and burden of care, calculating Relative Risk of success (RR) and Number Needed to Treat (NNT) for efficacy (EA) and intent-to-treat analyses. At the end of growth, 19% of EBPA participants progressed, while 33% improved. EBPA showed 2.0 (1.7\u20132.5) and 2.9 (1.7\u20134.9) RR of success versus Weinstein and Coillard\u2019s studies control groups, respectively. Benchmarked to plastic or elastic bracing, EBPA had 1.4 (1.2\u20131.5) and 1.7 (1.2\u20132.5) RR of success, respectively. The EBPA treatment burden was greater than RCTs in 48% of patients, and reduced for 24% and 42% versus plastic and elastic bracing, respectively. EBPA showed to be from 40% to 70% more effective than benchmarked individual treatments, with low NNT. The burden of treatment was frequently reduced, but it had to be increased even more frequently