Arm-support exoskeleton reduces shoulder muscle activity in ceiling construction.

The objective of this study was to assess the efficacy and user's impression of an arm-support exoskeleton in complex and realistic ceiling construction tasks. 11 construction workers performed 9 tasks. We determined objective and subjective efficacy of the exoskeleton by measuring shoulder muscle activity and perceived exertion. User's impression was assessed by questionnaires on expected support, perceived support, perceived hindrance and future intention to use the exoskeleton. Wearing the exoskeleton yielded persistent reductions in shoulder muscle activity of up to 58% and decreased perceived exertion. Participants reported limited perceived hindrance by the exoskeleton, as also indicated by no increase in antagonistic muscle activity. The findings demonstrate the high potential of an arm-support exoskeleton for unloading the shoulder muscles when used in the dynamic and versatile working environment of a ceiling construction worker, which is in line with the consistent intention of the workers to use the exoskeleton in the future.Practitioner Summary: The majority of research focuses on the effect of using an arm-support exoskeleton during isolated postures and prescribed movements. We investigated the efficacy of an exoskeleton during a complex and realistic work, namely ceiling construction. Shoulder muscle activity was lower in almost all tasks when wearing the exoskeleton.

Field study on the use and acceptance of an arm support exoskeleton in plastering.

Exoskeleton use in day-to-day plastering may face several challenges. Not all plasterer's tasks comprise of movements that will be supported by the exoskeleton and might even be hindered. Furthermore, use in practice might be jeopardised by time pressure, colleagues being negative, discomfort, or any other hindrance of the exoskeleton. We set up a field study, in which 39 plasterers were equipped with an exoskeleton for six weeks, to study exoskeleton usage. Moreover, we studied workload and fatigue, behaviour, productivity and quality, advantages and disadvantages, and acceptance. Exoskeleton use was dependent on the task performed but did not change over the course of the six weeks. For three tasks, higher exoskeleton use was associated with lower perceived loads, although differences were small. Advantages outweighed disadvantages for the majority of our population. This study shows that a majority of plasterers will wear the exoskeleton and is enthusiastic about the load reducing effect. Practitioner summary: For exoskeletons to make an impact on the health and well-being of workers, they need to be applicable in real work situations and accepted by the users. This study shows that 65% of the plasterers in this study want to use the exoskeleton in the future, for specific tasks.

What about the human in human robot collaboration?

In this review we address the human in human robot collaboration (HRC). Although there are different hypotheses on potential effects of HRC on job quality, defined as the quality of the working environment and its effect on the employee's well-being, a comprehensive theory is still lacking. How does HRC influence job quality on an individual level and how can we adapt HRC to boost positivity at work? We identified four job quality related factors that are of relevance in HRC: (1) Cognitive Workload, (2) Collaboration Fluency, (3) Trust, and (4) Acceptance and Satisfaction. Increasing awareness and being able to adapt the robot to the individual operator are crucial to improve the aforementioned factors. Implementing predictable robots, that offer a clear advantage to the human and take into account operators' preferences, will bring us closer to a human-centered collaboration. Practitioner Summary: The effect of human robot collaboration (HRC) on job quality is still under debate. Design characteristics of HRC, such as collaboration design, robot design, and workplace design affect job quality related factors. Using a participatory design approach, as to align robot capabilities to end-users' preferences, will enhance HRC and improve job quality. Abbreviations: HRC: human robot collaboration; OECD: organisation for economic co-operation and development.

Passive Trunk Exoskeleton Acceptability and Effects on Self-efficacy in Employees with Low-Back Pain: A Mixed Method Approach.

Purpose Determinants of successfully introducing passive exoskeletons in the working environment to decrease mechanical loading on the back, are acceptability of the device to management and employees, including self-efficacy of employees when using the device. Therefore, the aim of this study was to assess self-efficacy of employees with low-back pain when using an exoskeleton and the acceptability of such a device to these employees and their managers. Methods We used a mixed method approach. We quantitatively assessed the change in self-efficacy of 17 employees with low-back pain when performing daily activity tasks with the exoskeleton, using the modified spinal function sort (M-SFS). Qualitatively, we conducted a focus group with employees and a double interview with two managers to add more insight and understandings into changes in self-efficacy and to discuss challenges of implementing an exoskeleton in the working environment. Results Self-efficacy significantly increased by 7% when using the exoskeleton. Employees acknowledged the flexibility of the exoskeleton being advantageous to current static external lifting devices, which confirmed the increase of self-efficacy in both static and dynamic tasks. Individual data showed that the increase in self-efficacy was largest for participants, being greatly restricted by their low-back pain. In the focus group, employees confirmed that they are mostly open to wearing the exoskeleton if they suffer from low-back pain. Conclusion If potential challenges, e.g. visibility and potential refusal of wearing an exoskeleton are considered in the implementation strategy, acceptability of and self-efficacy in using the passive trunk exoskeleton would be further improved, potentially contributing to reduced risk of low-back pain.

SPEXOR passive spinal exoskeleton decreases metabolic cost during symmetric repetitive lifting.

PURPOSE: Besides mechanical loading of the back, physiological strain is an important risk factor for low-back pain. Recently a passive exoskeleton (SPEXOR) has been developed to reduce loading on the low back. We aimed to assess the effect of this device on metabolic cost of repetitive lifting. To explain potential effects, we assessed kinematics, mechanical joint work, and back muscle activity. METHODS: We recruited ten male employees, working in the luggage handling department of an airline company and having ample experience with lifting tasks at work. Metabolic cost, kinematics, mechanical joint work and muscle activity were measured during a 5-min repetitive lifting task. Participants had to lift and lower a box of 10 kg from ankle height with and without the exoskeleton. RESULTS: Metabolic cost was significantly reduced by 18% when wearing the exoskeleton. Kinematics did not change significantly, while muscle activity decreased by up to 16%. The exoskeleton took over 18-25% of joint work at the hip and L5S1 joints. However, due to large variation in individual responses, we did not find a significant reduction of joint work around the individual joints. CONCLUSION: Wearing the SPEXOR exoskeleton decreased metabolic cost and might, therefore, reduce fatigue development and contribute to prevention of low-back pain during repetitive lifting tasks. Reduced metabolic cost can be explained by the exoskeleton substituting part of muscle work at the hip and L5S1 joints and consequently decreasing required back muscle activity.

The effect of a passive trunk exoskeleton on metabolic costs during lifting and walking.

The objective of this study was to assess how wearing a passive trunk exoskeleton affects metabolic costs, movement strategy and muscle activation during repetitive lifting and walking. We measured energy expenditure, kinematics and muscle activity in 11 healthy men during 5 min of repetitive lifting and 5 min of walking with and without exoskeleton. Wearing the exoskeleton during lifting, metabolic costs decreased as much as 17%. In conjunction, participants tended to move through a smaller range of motion, reducing mechanical work generation. Walking with the exoskeleton, metabolic costs increased up to 17%. Participants walked somewhat slower with shortened steps while abdominal muscle activity slightly increased when wearing the exoskeleton. Wearing an exoskeleton during lifting decreased metabolic costs and hence may reduce the development of fatigue and low back pain risk. During walking metabolic costs increased, stressing the need for a device that allows disengagement of support depending on activities performed. Practitioner summary: Physiological strain is an important risk factor for low back pain. We observed that an exoskeleton reduced metabolic costs during lifting, but had an opposite effect while walking. Therefore, exoskeletons may be of benefit for lifting by decreasing physiological strain but should allow disengagement of support when switching between tasks. Abbreviations: COM: centre of mass; EMG: electromyography; LBP: low back pain; MVC: maximum voluntary isometric contraction; NIOSH: National Institute for Occupational Safety and Health; PLAD: personal lift augmentation device; PWS: preferred walking speed without exoskeleton; PWSX: preferred walking speed with exoskeleton; ROM: range of motion; RER: respiratory exchange ratio; V ̇O2max: maximum rate of oxygen consumption.

The effect of a passive trunk exoskeleton on functional performance in healthy individuals.

The objective of this study was to assess the effect of a passive trunk exoskeleton on functional performance for various work related tasks in healthy individuals. 18 healthy men performed 12 tasks. Functional performance in each task was assessed based on objective outcome measures and subjectively in terms of perceived task difficulty, local and general discomfort. Wearing the exoskeleton tended to increase objective performance in static forward bending, but decreased performance in tasks, such as walking, carrying and ladder climbing. A significant decrease was found in perceived task difficulty and local discomfort in the back in static forward bending, but a significant increase of perceived difficulty in several other tasks, like walking, squatting and wide standing. Especially tasks that involved hip flexion were perceived more difficult with the exoskeleton. Design improvements should include provisions to allow full range of motion of hips and trunk to increase versatility and user acceptance.

[Confocal microscope examination of the corneal nerve plexus as biomarker for systemic diseases : View from the corneal nerve plexus on diabetes mellitus disease]. / Konfokal mikroskopisch sichtbarer kornealer Nervenplexus als Biomarker für systemische Erkrankungen : Blick vom kornealen Nervenplexus auf die Erkrankung Diabetes mellitus.

It is estimated that approximately 50% of patients with diabetes mellitus suffer from polyneuropathy, which is frequently diagnosed too late. Consequently, the question arises whether imaging procedures of the eye, namely optical coherence tomography of the retina and confocal microscopy of the cornea are suitable for the diagnostics and follow-up control of neurodegenerative changes in patients with diabetes mellitus. De Clerck and co-workers could demonstrate this by a systematic review of studies. Of these studies 11 were further evaluated with respect to corneal confocal microscopy. Approximately 15 years after juvenile type 1 diabetes a reduction of corneal nerve fiber length and density was observed, although clinical signs of neuropathy were absent. At this stage an examination seems reasonable. Type 2 diabetes mellitus in the elderly is often associated with a metabolic syndrome and its time of manifestation remains unknown; therefore, corneal confocal microscopy should be implemented at the time of diagnosis of type 2 diabetes. Patients with long disease duration and significant changes in the corneal nerve plexus already showed clinical signs of polyneuropathy and often suffered from proliferative retinopathy. The accessibility of the eye for non-invasive optical modalities should be used more often in the treatment of patients with diabetes mellitus for early identification of patients at risk. Further longitudinal studies are highly necessary.

[Ophthalmological Monitoring of Diabetic Neuropathy in a Mouse Model]. / Ophthalmologisches Monitoring der diabetischen Neuropathie am Mausmodell.

Patients with diabetes mellitus suffer from late damage, including microvascular and macrovascular complications and diabetic polyneuropathy, even though blood glucose is well controlled and the HbA1c value normalised. Peripheral nerves are affected, and when these are damaged, this can result in disturbed sensation and pain. Such nerves are mainly Aδ und C fibres, which are present in the skin, but also in the subbasal nerve plexus of the cornea. Imaging of the subbasal nerve plexus using microscopic techniques allows a very early and objective view of neuropathy, which is only possible invasively by skin biopsy. We have used a thy1-YFP mouse strain in which the peripheral nerves are detectable by fluorescence excitation. Using two photon microscopy, we produced high resolution three dimensional images of the corneal subbasal nerve plexus of these mice. We induced diabetes mellitus in thy1-YFP mice by injection of streptocotocin. We showed that the increase in blood glucose was accompanied by a loss of subbasal nerve fibres, mainly in the centre of the cornea. Subsequent treatment of the animals with insulin normalised blood glucose and was accompanied by an increase in subbasal nerve fibres. Thus, this model is highly suited to investigate the pathogenesis of diabetic polyneuropathy, with the aim of developing new causal strategies to treat the disease.

Cellular characterisation of the GCKR P446L variant associated with type 2 diabetes risk.

AIMS/HYPOTHESIS: Translation of genetic association signals into molecular mechanisms for diabetes has been slow. The glucokinase regulatory protein (GKRP; gene symbol GCKR) P446L variant, associated with inverse modulation of glucose- and lipid-related traits, has been shown to alter the kinetics of glucokinase (GCK) inhibition. As GCK inhibition is associated with nuclear sequestration, we aimed to determine whether this variant also alters the direct interaction between GKRP and GCK and their intracellular localisation. METHODS: Fluorescently tagged rat and human wild-type (WT)- or P446L-GCKR and GCK were transiently transfected into HeLa cells and mouse primary hepatocytes. Whole-cell and nuclear fluorescence was quantified in individual cells exposed to low- or high-glucose conditions (5.5 or 25 mmol/l glucose, respectively). Interaction between GCK and GKRP was measured by sensitised emission-based fluorescence resonance energy transfer (FRET) efficiency. RESULTS: P446L-GKRP had a decreased degree of nuclear localisation, ability to sequester GCK and direct interaction with GCK as measured by FRET compared with WT-GKRP. Decreased interaction was observed between WT-GKRP and GCK at high compared with low glucose, but not between P446L-GKRP and GCK. Rat WT-GKRP and P446L-GKRP behaved quite differently: both variants responded to high glucose by diminished sequestration of GCK but showed no effect of the P446L variant on nuclear localisation or GCK sequestration. CONCLUSIONS/INTERPRETATION: Our study suggests the common human P446L-GKRP variant protein results in elevated hepatic glucose uptake and disposal by increasing active cytosolic GCK. This would increase hepatic lipid biosynthesis but decrease fasting plasma glucose concentrations and provides a potential mechanism for the protective effect of this allele on type 2 diabetes risk.

Glucokinase mediates coupling of glycolysis to mitochondrial metabolism but not to beta cell damage at high glucose exposure levels.

AIMS/HYPOTHESIS: Glucose is the main stimulus of insulin secretion in pancreatic beta cells. However, high glucose has also been considered to damage beta cells. In this study we examined, with special emphasis on the role of the glucose sensor enzyme glucokinase, whether elevated glucose metabolism evokes toxicity to beta cells. METHODS: RINm5F-R-EYFP-GK cells, producing glucokinase in response to a synthetic inducer, and rat beta cells were incubated at different glucose concentrations. Glucokinase enzyme activity, insulin secretion, cell viability and mitochondrial metabolism were analysed. RESULTS: Glucokinase production evoked a concentration-dependent increase in glucose-induced insulin secretion from RINm5F-R-EYFP-GK cells without reducing cell viability. Pre-culture at high glucose (30 mmol/l) in the absence of high concentrations of NEFA neither reduced viability nor significantly increased apoptosis in RINm5F-R-EYFP-GK cells and rat beta cells. The integrity of the mitochondrial respiratory chain and mitochondrial dynamics, namely fusion and fission, were not impaired by high glucose pre-culture. As previously demonstrated in mouse beta cells, pre-culture at high glucose significantly decreased the mitochondrial membrane potential heterogeneity in RINm5F-R-EYFP-GK cells. Indeed, after starvation, in response to glucose, rat beta cells and RINm5F-R-EYFP-GK cells with glucokinase production pre-cultured for 48 h at high glucose showed the fastest increase in the mitochondrial membrane potential. CONCLUSIONS/INTERPRETATION: Our experiments do not support the hypothesis that glucokinase and the glucose metabolism on its own act as a mediator of beta cell toxicity. By contrast, rather a beneficial effect on glucose-induced insulin secretion after glucokinase production was observed, based on an improved coupling of the glucose stimulus to the mitochondrial metabolism.

Do insulinotropic glucose-lowering drugs do more harm than good? The hypersecretion hypothesis revisited.

Significant progress has been made in recent years in the characterisation of the signal pathways of beta cell dysfunction and death in the pathogenesis of type 2 diabetes. Glucolipotoxicity acts as an exogenous factor whereas oxidative stress and endoplasmic reticulum stress may result from the processes of signal recognition and stimulated secretion within the beta cell. The pharmacological stimulation of secretion may thus appear to be a double-edged sword: it counteracts hyperglycaemia, but may do so at the expense of beta cell mass. So, in the long run, insulinotropic glucose-lowering drugs might do more harm than good. However, much of this logic is derived by analogy from the long-held assumption that beta cell hypersecretion imposed by insulin resistance causes the absolute secretion deficit in the later course of type 2 diabetes. In this concept the beta cell has a secondary role and loss of beta cell mass is necessary for the manifestation of type 2 diabetes. Recent studies have shown that a secretion deficit can exist well before insulin resistance and that major genetic risk factors concern beta cell function. Also, the evidence for a beta cell toxic effect of insulinotropic drugs is currently inconclusive. Assuming that the insulin secretion deficit is of pathogenetic importance in a network with insulin resistance as an aggravating factor, an insulinotropic glucose-lowering drug may do more good than harm if it relieves the beta cell from the stress of glucose overstimulation and does so without inducing hypoglycaemia.

Kinetics of insulin secretion from MIN6 pseudoislets after encapsulation in a prototype device of a bioartificial pancreas.

Xenotransplantation of insulin-secreting cells from nonhuman sources is an alternative therapeutic approach to bypass the shortage of human pancreatic islet tissue for transplantation in order to treat insulin deficiency in type 1 diabetes mellitus. Therefore, we studied the suitability of pseudoislets generated from insulin-secreting MIN6 tissue culture cells to serve as a surrogate for replacement of pancreatic islets after encapsulation in a minicell, representing a prototype of a new bioartificial pancreas device. MIN6 pseudoislets showed an excellent insulin secretory responsiveness with a typical biphasic secretory pattern to glucose stimulation. When encapsulated in the minicell, insulin release from the pseudoislets in response to glucose stimulation was reduced. The initial first phase insulin secretory response was greatly attenuated. In contrast, the first phase insulin secretory response of the encapsulated pseudoislets was restored on stimulation with the sulfonylurea drug tolbutamide. Our results indicate that the reason for the attenuated first phase of release is the restricted permeability of the pores in the separating membrane in the minicell for the hydrophilic glucose molecule rather than a limited permeability for the secretion product insulin. The reduced release of insulin from the encapsulated pseudoislets could be compensated by overexpression of glucokinase in MIN6 cells, which resulted in an increased glucose responsiveness of the pseudoislets for stimulation with glucose. Thus, this minicell is a well-suited miniature test system for the evaluation of the feasibility of encapsulation of insulin-secreting cells and allows the testing of permeability properties of separating membranes in bioartificial pancreas devices.

Monitoring of glucose-regulated single insulin secretory granule movement by selective photoactivation.

AIMS/HYPOTHESIS: Fluorescence microscopy opens new perspectives for the analysis of insulin secretory granule movement. In this study, we examined whether recently developed photoactivatable/photoconvertible proteins are a useful tool for studying this process at the single granule level in insulin-secreting cells after glucose stimulation. METHODS: Plasmids were generated for expression of fusion proteins of the granule membrane phosphatase phogrin or the granule cargo protein neuropeptide Y (NPY) with the photoactivatable green fluorescent protein mutant A206K (PA-GFP-A206K), the photoconvertible protein Dendra2 and the fluorescent protein mCherry. Transfected insulin-secreting MIN6 cells were analysed by fluorescence microscopy. RESULTS: Point-resolved 405 nm light exposure during image acquisition of MIN6 cells transiently transfected with Phogrin-PA-GFP-A206K or NPY-PA-GFP-A206K as well as of stable MIN6-Phogrin-Dendra2 cells resulted in selective visualisation of few granules by green or red fluorescence, respectively. Movement of these granules was analysed by an automated tracking method from confocal 3D image series. The high spatiotemporal resolution facilitated an elongated tracking of single granules. Interestingly, the track speed and track displacement of granules after 1 h starvation and subsequent glucose stimulation was lower in cells pre-cultured for 48 h at 3 mmol/l glucose than in cells pre-cultured at 25 mmol/l glucose. CONCLUSIONS/INTERPRETATION: Targeting of the granule membrane or its cargo with a photoactivatable/photoconvertible protein allows in-depth visualisation and tracking of single insulin granules in dependence upon glucose. This technique may also open the way to elucidating the regulation of granule movement velocity within the pancreatic beta cell with respect to secretory defects in type 2 diabetes.

Characterization of glucokinase-binding protein epitopes by a phage-displayed peptide library. Identification of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase as a novel interaction partner.

The low affinity glucose-phosphorylating enzyme glucokinase shows the phenomenon of intracellular translocation in beta cells of the pancreas and the liver. To identify potential binding partners of glucokinase by a systematic strategy, human beta cell glucokinase was screened by a 12-mer random peptide library displayed by the M13 phage. This panning procedure revealed two consensus motifs with a high binding affinity for glucokinase. The first consensus motif, LSAXXVAG, corresponded to the glucokinase regulatory protein of the liver. The second consensus motif, SLKVWT, showed a complete homology to the bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2), which acts as a key regulator of glucose metabolism. Through yeast two-hybrid analysis it became evident that the binding of glucokinase to PFK-2/FBPase-2 is conferred by the bisphosphatase domain, whereas the kinase domain is responsible for dimerization. 5'-Rapid amplification of cDNA ends analysis and Northern blot analysis revealed that rat pancreatic islets express the brain isoform of PFK-2/FBPase-2. A minor portion of the islet PFK-2/FBPase-2 cDNA clones comprised a novel splice variant with 8 additional amino acids in the kinase domain. The binding of the islet/brain PFK-2/ FBPase-2 isoform to glucokinase was comparable with that of the liver isoform. The interaction between glucokinase and PFK-2/FBPase-2 may provide the rationale for recent observations of a fructose-2,6-bisphosphate level-dependent partial channeling of glycolytic intermediates between glucokinase and glycolytic enzymes. In pancreatic beta cells this interaction may have a regulatory function for the metabolic stimulus-secretion coupling. Changes in fructose-2,6-bisphosphate levels and modulation of PFK-2/FBPase-2 activities may participate in the physiological regulation of glucokinase-mediated glucose-induced insulin secretion.