A hybrid sensory feedback system for thermal nociceptive warning and protection in prosthetic hand.

Background: Advanced prosthetic hands may embed nanosensors and microelectronics in their cosmetic skin. Heat influx may cause damage to these delicate structures. Protecting the integrity of the prosthetic hand becomes critical and necessary to ensure sustainable function. This study aims to mimic the sensorimotor control strategy of the human hand in perceiving nociceptive stimuli and triggering self-protective mechanisms and to investigate how similar neuromorphic mechanisms implemented in prosthetic hand can allow amputees to both volitionally release a hot object upon a nociceptive warning and achieve reinforced release via a bionic withdrawal reflex. Methods: A steady-state temperature prediction algorithm was proposed to shorten the long response time of a thermosensitive temperature sensor. A hybrid sensory strategy for transmitting force and a nociceptive temperature warning using transcutaneous electrical nerve stimulation based on evoked tactile sensations was designed to reconstruct the nociceptive sensory loop for amputees. A bionic withdrawal reflex using neuromorphic muscle control technology was used so that the prosthetic hand reflexively opened when a harmful temperature was detected. Four able-bodied subjects and two forearm amputees randomly grasped a tube at the different temperatures based on these strategies. Results: The average prediction error of temperature prediction algorithm was 8.30 ± 6.00%. The average success rate of six subjects in perceiving force and nociceptive temperature warnings was 86.90 and 94.30%, respectively. Under the reinforcement control mode in Test 2, the median reaction time of all subjects was 1.39 s, which was significantly faster than the median reaction time of 1.93 s in Test 1, in which two able-bodied subjects and two amputees participated. Results demonstrated the effectiveness of the integration of nociceptive sensory strategy and withdrawal reflex control strategy in a closed loop and also showed that amputees restored the warning of nociceptive sensation while also being able to withdraw from thermal danger through both voluntary and reflexive protection. Conclusion: This study demonstrated that it is feasible to restore the sensorimotor ability of amputees to warn and react against thermal nociceptive stimuli. Results further showed that the voluntary release and withdrawal reflex can work together to reinforce heat protection. Nevertheless, fusing voluntary and reflex functions for prosthetic performance in activities of daily living awaits a more cogent strategy in sensorimotor control.

Precision Control of Fingertip Force by a Biorealistic Hand with a Pair of Neuromorphic Muscles.

In this paper, the ability of precision control of fingertip forces was investigated in an antagonistic cable-driven prosthetic hand with neuromorphic twin of muscles. Surface electromyography (sEMG) signals collected from able-bodied subjects' forearm were processed and used as alpha motor commands to drive the neuromorphic muscle models. A pair of antagonistic muscles were cascaded by two servo motors to control the index finger. Force control performance was tested by pressing a spring with a fixed stiffness using the fingertip, where forces with varying target levels were regulated with visual feedback. Two able-bodied subjects performed the precision force control task with the prosthetic index finger by sEMG signals and the intact hand. One subject was tested with force level changes of 0.1N, and another subject with force level changes of 0.2N. The ability of force regulation by the prosthetic finger was compared to that of the intact finger. Results showed that the overall root-mean-squares (RMS) error of the prosthetic finger was low, although significantly higher than the intact finger, 75% higher in subject 1 and 57% in subject 2. However, the correlation coefficient between the forces of prosthetic finger and intact finger was high, 75% for subject 1 and 84% for subject 2, respectively. This preliminary study is encouraging, illustrating the feasibility of accurate and stable control of different levels of fingertip forces by the prosthetic finger, which is comparable to that of the intact finger. This capability may allow the prosthetic hand for fine manipulation tasks, such as grasping brittle objects, or response to object slip during grasp.Clinical Relevance-This work attempts to restore the ability of a prosthetic hand for precision fingertip force control that may enrich the functionality for users in activities of daily living.

Predictive Warning of Nociceptive Temperature during Prosthetic Hand Prehension.

Grasping hot objects may be harmful, and a warning of nociceptive temperature should be provided to prevent prosthetic hands from damage. This study developed a fast algorithm to predict the steady state temperature of grasped objects based on a thermoresistant sensor, and verified a bi-state sensory encoding strategy to inform either contact force or nociceptive temperature at prosthetic finger. Below the threshold, a buzz percept was used to encode fingertip force, and above the threshold, a tingling pain sensation was induced to warn harmful temperature. This sensory encoding mechanism was tested in one able-bodied subject with a psychophysical experimental paradigm. Results indicated that fast identification of the steady state temperature could be achieved in 0.75±0.00 s with an error of 8.3±6.0%. The subject was able to recognize whether the object temperature was above or below the threshold of nociceptive temperature with an average success rate of 98.2% and 97.0%, respectively. The action to release the tube could be executed in 0.80±0.32 s. The reaction time of successful identification and execution was 1.55 ± 0.32 s. The probability that a release reaction was triggered at the threshold of 60.0°C was calculated with tube temperatures varying from 30.0°C to 80.0°C. The 50% percentile point on the fitted stimulus-response curve corresponded to a temperature of 59.5°C, nearly identical to the internally set threshold. The psychophysical behavior test verified the sensory function to recognize and notify unsafe temperatures in real time.Clinical Relevance-The method of identifying and alerting nociceptive temperatures may restore the sensory ability of amputees to avoid potential damage of grasping hot objects with a prosthetic hand in activities of daily life.

Antagonistic Control of a Cable-Driven Prosthetic Hand with Neuromorphic Model of Muscle Reflex.

In this paper, a novel prototype of a cable-driven prosthetic hand with biorealisitic muscle property was developed. A pair of antagonistic muscles controlled the flexion and extension of the prosthetic index finger. Biorealistic properties of muscle were emulated using a neuromorphic model of muscle reflex in real time. The model output was coupled to a servo motor that tracked the computed muscle force. The servo motor was able to track model output within a frequency range from 0 to 8.29 (Hz) with a phase shift from 2 to 205 (deg). Surface electromyography signals collected from the amputee's forearm were used as α commands to drive the muscle model. With this prototype system, we evaluated its characteristics for force and stiffness control. Results of the force variability test showed that the standard deviation of fingertip force was linear to the mean fingertip force, indicating that force variability was proportional to the background force. At different levels of antagonistic co-contraction, the index finger and muscles displayed different levels of stiffness corresponding to the degree of co-activation. This prototype system showed the similar compliant behaviors of human limbs actuated with biological muscles. In further studies, this prototype system would be thoroughly evaluated for its biorealistic properties, and integrated with sensors to investigate feedback strategies of various sensory information for individuals with amputation. Clinical Relevance- This article established an antagonistic control of a cable-driven prosthetic hand with biorealistic properties of muscle reflex for application to individuals with amputation.

Serine active site containing protein 1 depletion alters lipid metabolism and protects against high fat diet-induced obesity in mice.

OBJECTIVE: Although the serine active site containing 1 (SERAC1) protein is essential for cardiolipin remodeling and cholesterol transfer, its physiological role in whole-body energy metabolism remains unclear. Thus, we investigated the role of SERAC1 in lipid distribution and metabolism in mice. METHODS: CRISPR/Cas9 was used to create homozygous Serac1 knockout mice. A range of methods, including electron microscopy, histological analysis, DNA sequencing, glucose and insulin tolerance tests, and biochemical analysis of serum lipid levels, were used to assess lipid distribution and rates of lipid synthesis in mice. RESULTS: We found that Serac1 depletion in mice prevented high-fat diet-induced obesity but did not affect energy expenditure. The liver was affected by Serac1 depletion, but adipose tissues were not. Serac1 depletion was shown to impair cholesterol transfer from the liver to the serum and led to an imbalance in cholesterol distribution. The livers from mice with Serac1 depletion showed increased cholesterol synthesis because the levels of cholesterol synthesis enzymes were upregulated. Moreover, the accumulation of hepatic lipid droplets in mice with Serac1 depletion were decreased, suggesting that SERAC1 depletion may decrease the risk for hepatic steatosis in high fat diet-induced mice. CONCLUSION: Our findings demonstrate that SERAC1 can serve as a potential target for the treatment or prevention of diet-induced hepatic lipid metabolic disorders.

SERAC1 is a component of the mitochondrial serine transporter complex required for the maintenance of mitochondrial DNA.

SERAC1 deficiency is associated with the mitochondrial 3-methylglutaconic aciduria with deafness, (hepatopathy), encephalopathy, and Leigh-like disease [MEGD(H)EL] syndrome, but the role of SERAC1 in mitochondrial physiology remains unknown. Here, we generated Serac1-/- mice that mimic the major diagnostic clinical and biochemical phenotypes of the MEGD(H)EL syndrome. We found that SERAC1 localizes to the outer mitochondrial membrane and is a protein component of the one-carbon cycle. By interacting with the mitochondrial serine transporter protein SFXN1, SERAC1 facilitated and was required for SFXN1-mediated serine transport from the cytosol to the mitochondria. Loss of SERAC1 impaired the one-carbon cycle and disrupted the balance of the nucleotide pool, which led to primary mitochondrial DNA (mtDNA) depletion in mice, HEK293T cells, and patient-derived immortalized lymphocyte cells due to insufficient supply of nucleotides. Moreover, both in vitro and in vivo supplementation of nucleosides/nucleotides restored mtDNA content and mitochondrial function. Collectively, our findings suggest that MEGD(H)EL syndrome shares both clinical and molecular features with the mtDNA depletion syndrome, and nucleotide supplementation may be an effective therapeutic strategy for MEGD(H)EL syndrome.

A Biorealistic Computational Model Unfolds Human-Like Compliant Properties for Control of Hand Prosthesis.

Objective: Human neuromuscular reflex control provides a biological model for a compliant hand prosthesis. Here we present a computational approach to understanding the emerging human-like compliance, force and position control, and stiffness adaptation in a prosthetic hand with a replica of human neuromuscular reflex. Methods: A virtual twin of prosthetic hand was constructed in the MuJoCo environment with a tendon-driven anthropomorphic hand structure. Biorealistic mathematic models of muscle, spindle, spiking-neurons and monosynaptic reflex were implemented in neuromorphic chips to drive the virtual hand for real-time control. Results: Simulation showed that the virtual hand acquired human-like ability to control fingertip position, force and stiffness for grasp, as well as the capacity to interact with soft objects by adaptively adjusting hand stiffness. Conclusion: The biorealistic neuromorphic reflex model restores human-like neuromuscular properties for hand prosthesis to interact with soft objects.

[Traditional medicinal plants for arthropod-borne diseases of five countries in Lancang-Mekong region:a review].

Arthropod-borne diseases, such as malaria and dengue fever, have frequently beset five countries(Cambodia, Vietnam, Laos, Myanmar, and Thailand) in the tropical rainy Lancang-Mekong region, which pose a huge threat to social production and daily life. As a resort to such diseases, chemical drugs risk the resistance in plasmodium, non-availability for dengue virus, and pollution to the environment. Traditional medicinal plants have the multi-component, multi-target, and multi-pathway characteristics, which are of great potential in drug development. Exploring potential medicinals for arthropod-borne diseases from traditional medicinal plants has become a hot spot. This study summarized the epidemiological background of arthropod-borne diseases in the Lancang-Mekong region and screened effective herbs from the 350 medicinal plants recorded in CHINA-ASEAN Traditional Medicine. Based on CNKI, VIP, and PubMed, the plants for malaria and dengue fever and those for killing and repelling mosquitoes were respectively sorted out. Their pharmacological effects and mechanisms were reviewed and the material basis was analyzed. The result is expected to serve as a reference for efficient utilization of medicinal resources, development of effective and safe drugs for malaria and dengue fever, and the further cooperation between China and the other five countries in the Lancang-Mekong region.

A novel mitochondrial m.14430A>G (MT-ND6, p.W82R) variant causes complex I deficiency and mitochondrial Leigh syndrome.

Objectives Leigh syndrome (LS) is one of the most common mitochondrial diseases and has variable clinical symptoms. However, the genetic variant spectrum of this disease is incomplete. Methods Next-generation sequencing (NGS) was used to identify the m.14430A > G (p.W82R) variant in a patient with LS. The pathogenesis of this novel complex I (CI) variant was verified by determining the mitochondrial respiration, assembly of CI, ATP, MMP and lactate production, and cell growth rate in cybrids with and without this variant. Results A novel m.14430A > G (p.W82R) variant in the NADH dehydrogenase 6 (ND6) gene was identified in the patient; the mutant loads of m.14430A > G (p.W82R) in the patient were much higher than those in his mother. Although the transmitochondrial cybrid-based study showed that mitochondrial CI assembly remains unaffected in cells with the m.14430G variant, control cells had significantly higher endogenous and CI-dependent mitochondrial respiration than mutant cells. Accordingly, mutant cells had a lower ATP, MMP and higher extracellular lactate production than control cells. Notably, mutant cells had impaired growth in a galactose-containing medium when compared to wild-type cells. Conclusions A novel m.14430A > G (p.W82R) variant in the ND6 gene was identified from a patient suspected to have LS, and this variant impaired mitochondrial respiration by decreasing the activity of mitochondrial CI.

The synthesis of CeO2 nanospheres with different hollowness and size induced by copper doping.

In this paper, copper-doped ceria oxides with different hollowness and size are fabricated by changing the Cu(2+) doping concentration in the mixed water-glycol system. Results show that the copper-doped CeO2 oxides undergo a morphology transformation from the solid nanospheres to core-shell, then to hollow nanospheres with the increase of the Cu(2+) doping concentration. The corresponding size becomes smaller during this transfer process. The Cu(2+) doping induced acceleration in the nucleation and growth process is further investigated. The resultant Cu(2+)-doped CeO2 oxides exhibit enhanced CO conversion performance and better reduction behaviors.