SoftHand at the CYBATHLON: a user's experience.

BACKGROUND: Roughly one-quarter of upper limb prosthesis users reject their prosthesis. Reasons for rejection range from comfort, to cost, aesthetics, function, and more. This paper follows a single user from training with and testing of a novel upper-limb myoelectric prosthesis (the SoftHand Pro) for participation in the CYBATHLON rehearsal to training for and competing in the CYBATHLON 2016 with a figure-of-nine harness controlled powered prosthesis (SoftHand Pro-H) to explore the feasibility and usability of a flexible anthropomorphic prosthetic hand. METHODS: The CYBATHLON pilot took part in multiple in-lab training sessions with the SoftHand Pro and SoftHand Pro-H; these sessions focused on basic control and use of the prosthetic devices and direct training of the tasks in the CYBATHLON. He used these devices in competition in the Powered Arm Prosthesis Race in the CYBATHLON rehearsal and 2016 events. RESULTS: In training for the CYBATHLON rehearsal, the subject was able to quickly improve performance with the myoelectric SHP despite typically using a body-powered prosthetic hook. The subject improved further with additional training using the figure-of-nine harness-controlled SHPH in preparation for the CYBATHLON. The Pilot placed 3rd (out of 4) in the rehearsal. In the CYBATHLON, he placed 5th (out of 12) and was one of only two pilots who successfully completed all tasks in the competition, having the second-highest score overall. CONCLUSIONS: Results with the SoftHand Pro and Pro-H suggest it to be a viable alternative to existing anthropomorphic hands and show that the unique flexibility of the hand is easily learned and exploited.

Aminopeptidase substrate preference affects HIV epitope presentation and predicts immune escape patterns in HIV-infected individuals.

Viruses evade immune detection partly through immune-associated mutations. Analyses of HIV sequences derived from infected individuals have identified numerous examples of HLA-associated mutations within or adjacent to T cell epitopes, but the potential impact of most mutations on epitope production and presentation remains unclear. The multistep breakdown of proteins into epitopes includes trimming of N-extended peptides into epitopes by aminopeptidases before loading onto MHC class I molecules. Definition of sequence signatures that modulate epitope production would lead to a better understanding of factors driving viral evolution and immune escape at the population level. In this study, we identified cytosolic aminopeptidases cleavage preferences in primary cells and its impact on HIV Ag degradation into epitopes in primary human cell extracts by mass spectrometry and on epitope presentation to CTL. We observed a hierarchy of preferred amino acid cleavage by cytosolic aminopeptidases. We demonstrated that flanking mutations producing more or less cleavable motifs can increase or decrease epitope production and presentation by up to 14-fold. We found that the efficiency of epitope production correlates with cleavability of flanking residues. These in vitro findings were supported by in vivo population-level analyses of clinically derived viral sequences from 1134 antiretroviral-naive HIV-infected individuals: HLA-associated mutations immune pressures drove the selection of residues that are less cleavable by aminopeptidases predominantly at N-flanking sites, leading to reduced epitope production and immune recognition. These results underscore an important and widespread role of Ag processing mutations in HIV immune escape and identify molecular mechanisms underlying impaired epitope presentation.

The SoftHand Pro: Functional evaluation of a novel, flexible, and robust myoelectric prosthesis.

Roughly one quarter of active upper limb prosthetic technology is rejected by the user, and user surveys have identified key areas requiring improvement: function, comfort, cost, durability, and appearance. Here we present the first systematic, clinical assessment of a novel prosthetic hand, the SoftHand Pro (SHP), in participants with transradial amputation and age-matched, limb-intact participants. The SHP is a robust and functional prosthetic hand that minimizes cost and weight using an underactuated design with a single motor. Participants with limb loss were evaluated on functional clinical measures before and after a 6-8 hour training period with the SHP as well as with their own prosthesis; limb-intact participants were tested only before and after SHP training. Participants with limb loss also evaluated their own prosthesis and the SHP (following training) using subjective questionnaires. Both objective and subjective results were positive and illuminated the strengths and weaknesses of the SHP. In particular, results pre-training show the SHP is easy to use, and significant improvement in the Activities Measure for Upper Limb Amputees in both groups following a 6-8 hour training highlights the ease of learning the unique features of the SHP (median improvement: 4.71 and 3.26 and p = 0.009 and 0.036 for limb loss and limb-intact groups, respectively). Further, we found no difference in performance compared to participant's own commercial devices in several clinical measures and found performance surpassing these devices on two functional tasks, buttoning a shirt and using a cell phone, suggesting a functional prosthetic design. Finally, improvements are needed in the SHP design and/or training in light of poor results in small object manipulation. Taken together, these results show the promise of the SHP, a flexible and adaptive prosthetic hand, and pave a path forward to ensuring higher functionality in future.

Grasp Performance of a Soft Synergy-Based Prosthetic Hand: A Pilot Study.

Current prosthetic hands are frequently rejected in part due to limited functionality and versatility. We assessed the feasibility of a novel prosthetic hand, the SoftHand Pro (SHP), whose design combines soft robotics and hand postural synergies. Able-bodied subjects ( ) tracked cursor motion by opening and closing the SHP and performed a grasp-lift-hold-release (GLHR) task with a sensorized cylindrical object of variable weight. The SHP control was driven by electromyographic (EMG) signals from two antagonistic muscles. Although the time to perform the GLHR task was longer for the SHP than native hand for the first few trials (10.2 ± 1.4 s and 2.13 ± 0.09 s, respectively), performance was much faster on subsequent trials (~5 s). The SHP steady-state grip force was significantly modulated as a function of object weight ( ). For the native hand, however, peak and steady-state grip forces were modulated to a greater extent (+68% and +91%, respectively). These changes were mediated by the modulation of EMG amplitude and co-contraction. These data suggest that the SHP has a promise for prosthetic applications and point-to-design modifications that could improve the SHP.

Evaluation of HEXORR Tone Assistance Mode Against Spring Assistance.

Robots are a promising tool for rehabilitation, and research suggests combining assistance with subject participation to maintain motivation and engagement. In this study, we compare two different types of robotic assistance for hand rehabilitation: Tone, a novel method designed to directly compensate for the user's hypertonia, and Spring, a commonly used method simulating a spring-like force attracting the subject to the target position. Eight chronic stroke subjects played a Gate Game, where they guide a ball through a sweeping, on-screen gate. Each subject was exposed to 5 modes: unassisted, assisted by the Spring and Tone modes, and "delay" modes where the assistance was provided after a period without assistance. Compared to unassisted trials, subjects produced less positive work and more negative work with all types of assistance but also reached a larger ROM and scored higher on the game. Notably, subjects produced more positive work overall with Tone compared to Spring. Further, subjects produced positive work over a significantly shorter range with Spring compared to Unassisted, while there was no difference between Tone and Unassisted. While both modes were effective at enabling the training of a larger workspace, these results suggest Tone assistance maintains a greater level of subject engagement and participation, likely making it a useful tool for hand rehabilitation.

Clinical effects of using HEXORR (Hand Exoskeleton Rehabilitation Robot) for movement therapy in stroke rehabilitation.

OBJECTIVE: The goals of this pilot study were to quantify the clinical benefits of using the Hand Exoskeleton Rehabilitation Robot for hand rehabilitation after stroke and to determine the population best served by this intervention. DESIGN: Nine subjects with chronic stroke (one excluded from analysis) completed 18 sessions of training with the Hand Exoskeleton Rehabilitation Robot and a preevaluation, a postevaluation, and a 90-day clinical evaluation. RESULTS: Overall, the subjects improved in both range of motion and clinical measures. Compared with the preevaluation, the subjects showed significant improvements in range of motion, grip strength, and the hand component of the Fugl-Meyer (mean changes, 6.60 degrees, 8.84 percentage points, and 1.86 points, respectively). A subgroup of six subjects exhibited lower tone and received a higher dosage of training. These subjects had significant gains in grip strength, the hand component of the Fugl-Meyer, and the Action Research Arm Test (mean changes, 8.42 percentage points, 2.17 points, and 2.33 points, respectively). CONCLUSIONS: Future work is needed to better manage higher levels of hypertonia and provide more support to subjects with higher impairment levels; however, the current results support further study into the Hand Exoskeleton Rehabilitation Robot treatment.

Isolation of a novel rat neural progenitor clone that expresses Dlx family transcription factors and gives rise to functional GABAergic neurons in culture.

Gamma-aminobutyric acid (GABA) ergic interneurons are lost in conditions including epilepsy and central nervous system injury, but there are few culture models available to study their function. Toward the goal of obtaining renewable sources of GABAergic neurons, we used the molecular profile of a functionally incomplete GABAergic precursor clone to screen 17 new clones isolated from GFP(+) rat E14.5 cortex and ganglionic eminence (GE) that were generated by viral introduction of v-myc. The clones grow as neurospheres in medium with FGF2, and after withdrawal of FGF2, they exhibit varying patterns of differentiation. Transcriptional profiling and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) indicated that one clone (GE6) expresses high levels of mRNAs encoding Dlx1, 2, 5, and 6, glutamate decarboxylases, and presynaptic proteins including neuropeptide Y and somatostatin. Protein expression confirmed that GE6 is a progenitor with restricted differentiation giving rise mostly to neurons with GABAergic markers. In cocultures with hippocampal neurons, GE6 neurons became electrically excitable and received both inhibitory and excitatory synapses. After withdrawal of FGF2 in cultures of GE6 alone, neurons matured to express ßIII-tubulin, and staining for synaptophysin and vesicular GABA transporter were robust after 1-2 weeks of differentiation. GE6 neurons also became electrically excitable and displayed synaptic activity, but synaptic currents were carried by chloride and were blocked by bicuculline. The results suggest that the GE6 clone, which is ventrally derived from the GE, resembles GABAergic interneuron progenitors that migrate into the developing forebrain. This is the first report of a relatively stable fetal clone that can be differentiated into GABAergic interneurons with functional synapses.

Hand function recovery in chronic stroke with HEXORR robotic training: A case series.

After a stroke, many survivors have impaired motor function. Robotic rehabilitation techniques have emerged to provide a repetitive, activity-based therapy at potentially lower cost than conventional methods. Many patients exhibit intrinsic resistance to hand extension in the form of spasticity and/or hypertonia. We have developed a therapy program using the Hand Exoskeleton Rehabilitation Robot (HEXORR) that is capable of compensating for tone to assist patients in opening the paretic hand. The system can move the user's hand, assist movement, allow free movement, or restrict movement to allow static force production. These options combine with an interactive virtual reality game to enhance user motivation. Four chronic stroke subjects received 18 sessions of robot therapy as well as pre and post evaluation sessions. All subjects showed at least modest gains in active finger range of motion (ROM) measured in the robot, and all but one subject had gains in active thumb ROM. Most of these gains carried over to ROM gains outside of the robot. The clinical measures (Fugl-Meyer, Box-and-Blocks) showed clear improvements in two subjects and mixed results in two subjects. Overall, the robot therapy was well received by subjects and shows promising results. We conclude HEXORR therapy is best suited for patients with mild-moderate tone and at least minimal extension.

Differential HIV epitope processing in monocytes and CD4 T cells affects cytotoxic T lymphocyte recognition.

The ability of cytotoxic T lymphocytes (CTLs) to clear virus-infected cells is dependent on the presentation of viral peptides processed intracellularly and displayed by major histocompatibility complex class I. Most CTL functional assays use exogenously added peptides, a practice that does not account for the kinetics and quantity of antigenic peptides produced by infectable cells. Here, we examined the relative ability of 2 major human immunodeficiency virus-infectable cell subsets-CD4 T lymphocytes and monocytes-to produce antigenic peptides, using cytosol as a source of peptidases and mass spectrometry to define the degradation products. We show clear subset-specific differences in the kinetics of peptide production and the ability of the peptides produced to sensitize cells for lysis by CTLs, with primary CD4 T lymphocytes having significantly lower proteolytic activity than monocytes. These differences in epitope processing by cell subsets may affect the efficiency of CTL-mediated clearance of infected subsets and contribute to the establishment of chronic infection.