Anatomically-Inspired Robotic Finger with SMA Tendon Actuation for Enhanced Biomimetic Functionality.

This research introduces an advanced robotic finger designed for future generalist robots, closely mimicking the natural structure of the human finger. The incorporation of rarely discussed anatomical structures, including tendon sheath, ligaments, and palmar plates, combined with the usage of anatomically proven 3D models of the finger, give rise to the highly accurate replication of human-like soft mechanical fingers. Benefiting from the accurate anatomy of muscle insertions with the utilization of Shape Memory Alloy (SMA) wires' muscle-like actuation properties, the bonding in-between the flexor tendons and extensor tendons allows for the realization of the central and lateral band of the finger anatomy. Evaluated using the computer vision method, the proposed robotic finger demonstrates a range of motion (ROM) equivalent to 113%, 87% and 88% of the human dynamic ROM for the DIP, PIP and MCP joints, respectively. The proposed finger possesses a soft nature when relaxed and becomes firm when activated, pioneering a new approach in biomimetic robot design and offering a unique contribution to the future of generalist humanoid robots.

An SMA Transducer for Sensing Tactile Sensation Focusing on Stroking Motion.

The authors have developed a micro-vibration actuator using filiform SMA wire electrically driven by periodic electric current. While applying the SMA actuators to tactile displays, we discovered a phenomenon that the deformation caused by a given stress to an SMA wire generated a change in the electrical resistance. With this characteristic, the SMA wire works as a micro-force sensor with high sensitivity, while generating micro-vibration. In this paper, the micro-force sensing ability of an SMA transducer is described and discussed. Experiments are conducted by sliding the SMA sensor on the surface of different objects with different speeds, and the sensing ability is evaluated to be related with human tactile sensation.

Analysis of different self-propulsion types of oil droplets based on electrostatic interaction effects.

This study aims to investigate electrical effects in self-propelled oil droplets and analyze the motion caused by electrical interactions between two droplets. We examine the motion of self-propelled oil droplets in terms of electrical effects; no similar analyses have been reported to date. When an oleic acid droplet is introduced into a surfactant solution, oleic acid is adsorbed at the droplet surface; as a result, the surface becomes negatively charged. However, the electrostatic interaction between oil droplets has not been studied so far. We focus on the chargeability of self-propelled oil droplets, and propose that their motion can be controlled by changing the charge state at the oil/water interface. This is realized by controlling the pH of the surfactant solution. We prepared several aqueous solutions with slightly different pH values, and introduced two oil droplets into each solution to investigate the relationship between the pH value and the correlated motion of the oil droplets. In an aqueous solution at pH 12.00, the two oil droplets showed two types of motion (follow-up and parallel motion), while in an aqueous solution at pH 12.10 they exhibited only one type of motion, i.e., repulsive motion. In order to analyze the three types of motion, we investigated electrical effects on the surface of the oil droplets. First, we measured the zeta potentials of aqueous solutions at pH 12.00 and 12.10, and analyzed the relationship between pH and charge. Furthermore, we calculated the amount of charge and the repulsive force generated on the surface of the oil droplets. For the pH 12.10 solution, the charge of one oil droplet and the repulsive force generated by the charge were found to be -30.79 pC and 282 nN, respectively. Taking into account the driving forces controlling the motion of oil droplets reported in previous studies, this repulsive force could be the driving force of the observed repulsive motion. Based on the experimental results, we inferred that the three types of self-propulsive motion were controlled by electrical effects at the oil/water interface. To further examine these motions, we analyzed the time dependences of the total distance traveled by a droplet and of the distance between oil droplets, as well as the droplet velocities and images of internal convection of oil droplets.

A Wearable Assistive Device for Blind Pedestrians Using Real-Time Object Detection and Tactile Presentation.

Nowadays, improving the traffic safety of visually impaired people is a topic of widespread concern. To help avoid the risks and hazards of road traffic in their daily life, we propose a wearable device using object detection techniques and a novel tactile display made from shape-memory alloy (SMA) actuators. After detecting obstacles in real-time, the tactile display attached to a user's hands presents different tactile sensations to show the position of the obstacles. To implement the computation-consuming object detection algorithm in a low-memory mobile device, we introduced a slimming compression method to reduce 90% of the redundant structures of the neural network. We also designed a particular driving circuit board that can efficiently drive the SMA-based tactile displays. In addition, we also conducted several experiments to verify our wearable assistive device's performance. The results of the experiments showed that the subject was able to recognize the left or right position of a stationary obstacle with 96% accuracy and also successfully avoided collisions with moving obstacles by using the wearable assistive device.

Compassionate open-label use of rituximab following a randomised clinical trial against neuromyelitis optica (RIN-2 study): B cell monitoring-based administration.

OBJECTIVE: The aim of the RIN-2 study was a compassionate use of rituximab (RTX) for patients who completed the RIN-1 study, a multicentre, randomised, double-blind, placebo-controlled trial of RTX. We also investigated the long-term safety and efficacy of RTX. METHODS: A study design was a prospective open-label extension study following the RIN-1 study. RTX was infused repeatedly under monthly monitoring of CD19-positive and CD 20-positive B cell lymphocyte subsets from 24 weeks after an infusion. RESULTS: Thirty-three (87%) of 38 patients of the RIN-1 study were enrolled from February 2016 to March 2019 at six sites in Japan. In RIN-2, RTX was administered three times (median, range 1-5 times), and the interval of RTX administrations were 9.5 [2.5] months (mean [SD]). The observation period was 20.5 [10.1] months. During the trial, three patients dropped out due to two withdrawals and one adverse event. During the study, 28 (90%) of 31 patients were treated with RTX monotherapy. Neuromyelitis optica (NMO) relapses were observed in two patients. The annualized relapse rate (ARR) was 0.035 counts per person-years, ∼1/10th compared with 0.321 in the placebo arm of the RIN-1 study. We observed 14 severe adverse events in six (18%) and 156 adverse events, of which 135 were grade 1, 11 were grade 2 and 10 were grade 3. CONCLUSIONS: Under B cell monitoring, the interval of RTX re-infusion was elongated to nine months, and NMO relapses were suppressed with 0.035 of ARR.

Older-onset levodopa-responsive parkinsonism with normal DAT-SPECT and pterin hypometabolism.

Pterin species participate in dopamine biosynthesis, and abnormal pteridine metabolism contributes to reduced dopamine. GTP cyclohydrolase 1 (GCH-1) deficiency, which triggers pteridine hypometabolism and normally develops in childhood, can mediate an adult-onset decrease in levodopa production and dopa-responsive dystonia (DRD), with normal dopamine transporter single-photon emission computed tomography (DAT-SPECT). A recent study described normal DAT-SPECT in adult-onset cases with GCH-1 mutations, clinically diagnosed with Parkinson's disease, which raises the possibility that the abnormal metabolism of pteridine may be a differential diagnosis for adult-onset parkinsonism. We report an older patient with levodopa-responsive parkinsonism with normal DAT-SPECT, or scans without evidence of dopamine deficit (SWEDD), whose biochemical analysis showed pterin hypometabolism, which occurs in GCH-1-deficient DRD. Surprisingly, this patient presented no dystonia or GCH-1 gene mutation or deletion. This case suggests that low pterin metabolism should be considered in older-onset levodopa-responsive parkinsonism with normal DAT-SPECT, even without GCH-1 mutations or deletions.

Early-start vs delayed-start donepezil against cognitive decline in Parkinson disease: a randomized clinical trial.

BACKGROUND: Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS: The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS: A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × Îµ4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS: Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.

Safety and efficacy of rituximab in neuromyelitis optica spectrum disorders (RIN-1 study): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Pharmacological prevention against relapses in patients with neuromyelitis optica spectrum disorder (NMOSD) is developing rapidly. We aimed to investigate the safety and efficacy of rituximab, an anti-CD20 monoclonal antibody, against relapses in patients with NMOSD. METHODS: We did a multicentre, randomised, double-blind, placebo-controlled clinical trial at eight hospitals in Japan. Patients aged 16-80 years with NMOSD who were seropositive for aquaporin 4 (AQP4) antibody, were taking 5-30 mg/day oral steroids, and had an Expanded Disability Status Scale (EDSS) score of 7·0 or less were eligible for the study. Individuals taking any other immunosuppressants were excluded. Participants were randomly allocated (1:1) either rituximab or placebo by a computer-aided dynamic random allocation system. The doses of concomitant steroid (converted to equivalent doses of prednisolone) and relapses in previous 2 years were set as stratification factors. Participants and those assessing outcomes were unaware of group assignments. Rituximab (375 mg/m2) was administered intravenously every week for 4 weeks, then 6-month interval dosing was done (1000 mg every 2 weeks, at 24 weeks and 48 weeks after randomisation). A matching placebo was administered intravenously. Concomitant oral prednisolone was gradually reduced to 2-5 mg/day, according to the protocol. The primary outcome was time to first relapse within 72 weeks. Relapses were defined as patient-reported symptoms or any new signs consistent with CNS lesions and attributable objective changes in MRI or visual evoked potential. The primary analysis was done in the full analysis set (all randomly assigned patients) and safety analyses were done in the safety analysis set (all patients who received at least one infusion of assigned treatment). The primary analysis was by intention-to-treat principles. This trial is registered with the UMIN clinical trial registry, UMIN000013453. FINDINGS: Between May 10, 2014, and Aug 15, 2017, 38 participants were recruited and randomly allocated either rituximab (n=19) or placebo (n=19). Three (16%) patients assigned rituximab discontinued the study and were analysed as censored cases. Seven (37%) relapses occurred in patients allocated placebo and none were recorded in patients assigned rituximab (group difference 36·8%, 95% CI 12·3-65·5; log-rank p=0·0058). Eight serious adverse events were recorded, four events in three (16%) patients assigned rituximab (lumbar compression fracture and infection around nail of right foot [n=1], diplopia [n=1], and uterine cancer [n=1]) and four events in two (11%) people allocated to placebo (exacerbation of glaucoma and bleeding in the right eye chamber after surgery [n=1], and visual impairment and asymptomatic white matter brain lesion on MRI [n=1]); all patients recovered. No deaths were reported. INTERPRETATION: Rituximab prevented relapses for 72 weeks in patients with NMOSD who were AQP4 antibody-positive. This study is limited by its small sample size and inclusion of participants with mild disease activity. However, our results suggest that rituximab could be useful maintenance therapy for individuals with NMOSD who are AQP4 antibody-positive. FUNDING: Japanese Ministry of Health, Labour and Welfare, Japan Agency for Medical Research and Development, and Zenyaku Kogyo.

α-Synuclein oligomers mediate the aberrant form of spike-induced calcium release from IP3 receptor.

Emerging evidence implicates α-synuclein oligomers as potential culprits in the pathogenesis of Lewy body disease (LBD). Soluble oligomeric α-synuclein accumulation in cytoplasm is believed to modify neuronal activities and intraneural Ca2+ dynamics, which augment the metabolic burden in central neurons vulnerable to LBD, although this hypothesis remains to be fully tested. We evaluated how intracellular α-synuclein oligomers affect the neuronal excitabilities and Ca2+ dynamics of pyramidal neurons in neocortical slices from mice. Intracellular application of α-synuclein containing stable higher-order oligomers (αSNo) significantly reduced spike frequency during current injection, elongated the duration of spike afterhyperpolarization (AHP), and enlarged AHP current charge in comparison with that of α-synuclein without higher-order oligomers. This αSNo-mediated alteration was triggered by spike-induced Ca2+ release from inositol trisphosphate receptors (IP3R) functionally coupled with L-type Ca2+ channels and SK-type K+ channels. Further electrophysiological and immunochemical observations revealed that α-synuclein oligomers greater than 100 kDa were directly associated with calcium-binding protein 1, which is responsible for regulating IP3R gating. They also block Ca2+-dependent inactivation of IP3R, and trigger Ca2+-induced Ca2+ release from IP3R during multiple spikes. This aberrant machinery may result in intraneural Ca2+ dyshomeostasis and may be the molecular basis for the vulnerability of neurons in LBD brains.

Directional and velocity control of active droplets using a rigid-frame.

This paper introduces a novel directional control method of self-propelled oil droplets. Oil droplets locomote spontaneously with surfactant action. This self-propulsion is caused by Marangoni convection within the oil droplet due to differences in the surfactant concentration at the droplet surface. Recent studies have reported that self-propelled oil droplets change their locomotion style depending on their shapes. We confirm that spherical oil droplets move randomly, including straight motion, bending motion, and rotation. In particular, we discover that boomerang-shaped oil droplets exhibit only straight motion. In this study, we introduce an exoskeleton for the directional and velocity control of oil droplets. A droplet shaped as a boomerang by an exoskeleton locomotes in the direction from a concave region to a convex region. Through experimental studies, we found that the stability of the velocity and locomotion direction depended on the boomerang shape. Self-propelled oil droplets with exoskeletons were then applied to a transporting robot driven only by the energy obtained from chemical reactions. We demonstrate the robot pushes and transports an object floating on water.

Self-Assembled 3D Actuator Using the Resilience of an Elastomeric Material.

Self-folding technologies have been studied by many researchers for applications to various engineering fields. Most of the self-folding methods that use the physical properties of materials require complex preparation, and usually take time to complete. In order to solve these problems, we focus on the elasticity of a material, and propose a model for forming a 3D structure using its characteristics. Our proposed model achieves high-speed and high-precision self-folding with a simple structure, by attaching rigid frames to a stretchable elastomer. The self-folded structure is applied to introduce a self-assembled actuator by exploiting a dielectric elastomer actuator (DEA). We develop the self-assembled actuator driven with the voltage application by attaching stretchable electrodes on the both side of the elastomer. We attempt several experiments to investigate the basic characteristics of the actuator. We also propose an application of the self-assembled actuator as a gripper based on the experimental results. The gripper has three joints with the angle of 120°, and successfully grabs objects by switching the voltage.

Sensory ganglionopathy associated with drug-induced hypersensitivity syndrome caused by mexiletine.

Although various causes are reported for sensory ganglionopathy, drug-induced hypersensitivity syndrome (DIHS) has not been considered a possibility. We describe a 70-year-old woman, previously administered mexiletine hydrochloride for 4 weeks, who presented with systemic oedematous erythema and subacute progressive gait disturbance. Evaluation revealed lymphadenopathy with atypical lymphocytosis and eosinophilia, and human herpesvirus 6 (HHV-6) reactivation. Neurological examination indicated the almost complete loss of joint positional sense in her extremities; her tendon reflex was lost and there was marked pseudoathetosis and Romberg's sign. Skin biopsy revealed spongiosis with lymphocyte infiltration. Based on these findings, we diagnosed acute sensory ganglionopathy secondary to DIHS. Although her DIHS-induced symptoms subsided after methylprednisolone treatment, partial remission of sensory ganglionopathy occurred, even after subsequent intravenous immunoglobulin therapy. This case suggests the possibility that reactivation of HHV-6 may be involved in the pathomechanism of sensory ganglionopathy.

Early use of donepezil against psychosis and cognitive decline in Parkinson's disease: a randomised controlled trial for 2 years.

OBJECTIVES: Brain acetylcholine is decreased even in patients with cognitively preserved Parkinson's disease (PD). We investigated whether early and long-term use of donepezil prevents psychosis in non-demented PD patients. METHODS: A double-blinded, placebo-controlled trial was conducted. A total of 145 non-demented PD patients were randomly assigned to receive 5 mg/day donepezil (n=72) or placebo (n=73) for 96 weeks. Medications for PD were not restricted, but antipsychotic drugs were not permitted throughout the study. The primary outcome measure was survival time to psychosis that was predefined by Parkinson's Psychosis Questionnaire (PPQ) B score ≥2 or C score ≥2. Secondary outcome measures included psychosis developing within 48 weeks, total PPQ score, Mini-Mental State Examination (MMSE), Wechsler Memory Scale (WMS) and subgroup analysis by apolipoprotein ε4 genotyping. RESULTS: Kaplan-Meier curves for psychosis development were very similar between the two groups, and the Cox proportional hazard model revealed an adjusted HR of 0.87 (95%CI 0.48 to 1.60). The changes in MMSE and WMS-1 (auditory memory) were significantly better with donepezil than in placebo. In the subgroup analysis, donepezil provided an HR of 0.31 (0.11-0.86) against psychosis in 48 weeks for apolipoprotein ε4 non-carriers. CONCLUSIONS: Although donepezil provided beneficial effects on PPQ, MMSE and auditory WMS score changes in 2 years, it had no prophylactic effect on development of psychosis in PD. Apolipoprotein ε4 may suppress the antipsychotic effect of donepezil. TRIAL REGISTRATION NUMBER: UMIN000005403.

Pharmacological interventions for anxiety in Parkinson's disease sufferers.

INTRODUCTION: Anxiety disorders are a common non-motor symptom of Parkinson's disease (PD) with a reported prevalence ranging from 20% to 50%. Although anxiety is associated with Parkinson's disease, anxiety disorders can begin before the onset of motor symptoms, and have been linked to a possible abnormality of dopaminergic, serotonergic, and adrenergic neurons that precedes motor disturbance. AREAS COVERED: Several studies have reported the pharmacological treatment of depression in PD, but none have been randomized clinical trials with a primary outcome measure of anxiety. Two trials showed that pharmacological intervention with tricyclic antidepressants or selective serotonin reuptake inhibitors proved beneficial in treating anxiety in PD. However, the effect size was modest. Anxiety is associated with off-periods and improved by L-Dopa, especially in patients with high levels of anxiety. EXPERT OPINION: Decreasing off-periods is important for managing anxiety in patients with motor fluctuations. Minor suggestive data indicate that tricyclic antidepressants and selective serotonin reuptake inhibitors can be helpful with modest effect sizes, but the former can cause additional side effects. Only one study has examined the use of benzodiazepines to treat anxiety in PD, and benzodiazepines cannot be recommended because they increase the risk of falling. Further clinical studies for pharmacological intervention against anxiety are required.

Video-fluoroscopic swallowing study scale for predicting aspiration pneumonia in Parkinson's disease.

INTRODUCTION: A number of video-fluoroscopic swallowing study (VFSS) abnormalities have been reported in patients with Parkinson's disease (PD). However, the most crucial finding of subsequent aspiration pneumonia has not been validated fully. We conducted a retrospective and case-control study to determine the clinically significant VFSS findings in this population, and to propose a practical scale for predicting aspiration pneumonia in patients with PD. METHODS: We enrolled 184 PD patients who underwent VFSS because of suspected dysphagia. The patients who developed aspiration pneumonia within six months of the VFSS were assigned as cases and the patients without aspiration pneumonia at six months were designated as controls. Logistic regression analysis was performed to determine the prognostic VFSS features based on the data of swallowing 3 mL of jelly, which were used to make a PD VFSS scale (PDVFS). The validity of the new PDVFS was evaluated by ROC analysis. Additionally, we used the survival time analysis to compare time to death between groups, stratified by the PDVFS score. RESULTS: Twenty-five patients developed aspiration pneumonia. Among the previously-proposed VFSS features, mastication, lingual motility prior to transfer, aspiration, and total swallow time were identified as significant prognostic factors. We combined these factors to form the PDVFS. The PDVFS score ranges from 0 to 12, with 12 being the worst. ROC analysis revealed 92% sensitivity and 82% specificity at a cutoff point of 3. The higher PDVFS group showed shorter time-to-death than the lower PDVFS group (log rank P = 0.001). CONCLUSION: Our newly developed VFSS severity scale (based on jelly swallowing) for patients with PD was easy to rate and could predict subsequent aspiration pneumonia and poor prognosis in patients with PD.

Low body mass index and life prognosis in Parkinson's disease.

INTRODUCTION: Patients with Parkinson's disease (PD) frequently lose weight, even in the early stages of the disease. Our objective was to clarify the association between low body mass index (BMI) and life prognosis in PD. METHODS: We conducted a retrospective cohort study of 651 PD patients (380 females), with a primary endpoint of survival. Because of sex differences in BMI, male and female data were separated. We compared survival times between underweight (BMI < 18.5) and non-underweight (BMI ≥ 18.5) patients and calculated hazard ratios (HRs) adjusted for other relevant factors. To investigate the semi-quantitative relationship between relative risk of death and BMI, we divided patients into lower, middle, and upper thirds of BMI and calculated the HRs of the lower and upper thirds, with reference to the middle third. RESULTS: Seventy-nine patients (41 females) died over a mean (standard deviation) observation period of 39 (26) months. Underweight patients had poorer life prognosis than non-underweight patients and the difference was larger in males than in females (adjusted HR 3.8 (95% confidence interval 1.9-7.9) in males and 1.8 (0.9-3.5) in females). In males, the relationship between survival and BMI was much poorer in the bottom third and slightly poorer in the top third compared with the middle third. In females, the higher the BMI, the better the survival prognosis; however, the difference was not statistically significant. CONCLUSION: Low BMI had a significant impact on the life prognosis of PD patients, especially males.