An Exploratory Investigation on the Use of Closed-Loop Electrical Stimulation to Assist Individuals with Stroke to Perform Fine Movements with Their Hemiparetic Arm.

Stroke is the leading cause of upper limb impairments resulting in disability. Modern rehabilitation includes training with robotic exoskeletons and functional electrical stimulation (FES). However, there is a gap in knowledge to define the detailed use of FES in stroke rehabilitation. In this paper, we explore applying closed-loop FES to the upper extremities of healthy volunteers and individuals with a hemiparetic arm resulting from stroke. We used a set of gyroscopes to monitor arm movements and used a non-linear controller, namely, the robust integral of the sign of the error (RISE), to assess the viability of controlling FES in closed loop. Further, we explored the application of closed-loop FES in improving functional tasks performed by individuals with stroke. Four healthy individuals of ages 27-32 years old and five individuals with stroke of ages 61-83 years old participated in this study. We used the Rehastim FES unit (Hasomed Ltd.) with real-time modulation of pulse width and amplitude. Both healthy and stroke individuals were tested in RISE-controlled single and multi-joint upper limb motions following first a sinusoidal trajectory. Individuals with stroke were also asked to perform the following functional tasks: picking up a basket, picking and placing an object on a table, cutting a pizza, pulling back a chair, eating with a spoon, as well as using a stapler and grasping a pen. Healthy individuals were instructed to keep their arm relaxed during the experiment. Most individuals with stroke were able to follow the sinusoid trajectories with their arm joints under the sole excitation of the closed-loop-controlled FES. One individual with stroke, who was unable to perform any of the functional tasks independently, succeeded in completing all the tasks when FES was used. Three other individuals with stroke, who were unable to complete a few tasks independently, completed some of them when FES was used. The remaining stroke participant was able to complete all tasks with and without FES. Our results suggest that individuals with a low Fugl-Meyer score or a higher level of disability may benefit the most with the use of closed-loop-controlled FES.

Facile fabrication of super-hydrophobic nano-needle arrays via breath figures method.

Super-hydrophobic surfaces which have been fabricated by various methods such as photolithography, chemical treatment, self-assembly, and imprinting have gained enormous attention in recent years. Especially 2D arrays of nano-needles have been shown to have super-hydrophobicity due to their sharp surface roughness. These arrays can be easily generated by removing the top portion of the honeycomb films prepared by the breath figures method. The hydrophilic block of an amphiphilic polymer helps in the fabrication of the nano-needle arrays through the production of well-ordered honeycomb films and good adhesion of the film to a substrate. Anisotropic patterns with water wettability difference can be useful for patterning cells and other materials using their selective growth on the hydrophilic part of the pattern. However, there has not been a simple way to generate patterns with highly different wettability. Mechanical stamping of the nano-needle array with a polyurethane stamp might be the simplest way to fabricate patterns with wettability difference. In this study, super-hydrophobic nano-needle arrays were simply fabricated by removing the top portion of the honeycomb films. The maximum water contact angle obtained with the nano-needle array was 150°. By controlling the pore size and the density of the honeycomb films, the height, width, and density of nano-needle arrays were determined. Anisotropic patterns with different wettability were fabricated by simply pressing the nano-needle array at ambient temperature with polyurethane stamps which were flexible but tough. Mechanical stamping of nano-needle arrays with micron patterns produced hierarchical super-hydrophobic structures.PACS: 05.70.Np, 68.55.am, 68.55.jm.

Interleukin 1 receptor antagonist mediates the beneficial effects of systemic interferon beta in mice: implications for rheumatoid arthritis.

OBJECTIVES: Interferon beta (IFNß) therapy is effective in multiple sclerosis and murine models of arthritis. Surprisingly, systemic IFNß treatment induces only minimal improvement in rheumatoid arthritis (RA). To explain this paradox, the authors evaluated the mechanism of IFNß benefit in passive K/BxN arthritis and the effect of IFNß treatment on RA synovium. METHODS: Interleukin 10 (IL-10) null, IL-1 receptor antagonist (IL-1Ra) null, IL-1Ra transgenic and wild-type mice were administered K/BxN serum and in some cases treated with IFNß or normal saline. Clinical response and histological scores were assessed. Gene expression was measured by quantitative PCR. Serum IL-1Ra and IL-6 were measured by ELISA. Paired synovial biopsy specimens from RA patients pre-IFNß and post-IFNß treatment (purified natural fibroblast IFNß (Frone) subcutaneously three times weekly 6 million IU, 12 million IU or 18 million IU) were immunostained for IL-1Ra and IL-10. RESULTS: Il1rn transgenic mice had an attenuated course of arthritis, whereas Il1rn(-/-) and Il10(-/-) mice had more severe serum transfer arthritis than wild-type mice. Daily IFNß treatment significantly decreased arthritis severity in Il10(-/-) but not Il1rn(-/-) mice. IFNß treatment did not reduce the histological scores in Il1rn(-/-) mice or gene expression of articular cytokines and chemokines. Paired synovial biopsy specimens from RA patients treated with IFNß demonstrated a trend towards increased IL-1Ra and reduced IL-10 expression on day 85 levels compared with pretreatment specimens. CONCLUSIONS: The anti-inflammatory effects of IFNß in passive K/BxN arthritis are dependent on IL-1Ra, but not IL-10. Systemic IFNß treatment in RA increases synovial IL-1Ra production, but also decreases IL-10 production.

The loss of PIN1 deregulates cyclin E and sensitizes mouse embryo fibroblasts to genomic instability.

During the G0/G1-S phase transition, the timely synthesis and degradation of key regulatory proteins is required for normal cell cycle progression. Two of these proteins, c-Myc and cyclin E, are recognized by the Cdc4 E3 ligase of the Skp1/Cul1/Rbx1 (SCF) complex. SCF(Cdc4) binds to a similar phosphodegron sequence in c-Myc and cyclin E proteins resulting in ubiquitylation and degradation of both proteins via the 26 S proteosome. Since the prolyl isomerase Pin1 binds the c-Myc phosphodegron and participates in regulation of c-Myc turnover, we hypothesized that Pin1 would bind to and regulate cyclin E turnover in a similar manner. Here we show that Pin1 regulates the turnover of cyclin E in mouse embryo fibroblasts. Pin1 binds to the cyclin E-Cdk2 complex in a manner that depends on Ser384 of cyclin E, which is phosphorylated by Cdk2. The absence of Pin1 results in an increased steady-state level of cyclin E and stalling of the cells in the G1/S phase of the cell cycle. The cellular changes that result from the loss of Pin1 predispose Pin1 null mouse embryo fibroblasts to undergo more rapid genomic instability when immortalized by conditional inactivation of p53 and sensitizes these cells to more aggressive Ras-dependent transformation and tumorigenesis.

T cell homeostasis requires G protein-coupled receptor-mediated access to trophic signals that promote growth and inhibit chemotaxis.

Signals that regulate T cell homeostasis are not fully understood. G protein-coupled receptors (GPCR), such as the chemokine receptors, may affect homeostasis by direct signaling or by guiding T cell migration to distinct location-restricted signals. Here, we show that blockade of Galphai-associated GPCR signaling by treatment with pertussis toxin led to T cell atrophy and shortened life-span in T cell-replete hosts and prevented T cell homeostatic growth and proliferation in T cell-deficient hosts. In vitro, however, neither GPCR inhibition nor chemokine stimulation affected T cell atrophy, survival, or proliferation. These findings suggest that GPCR signals are not trophic stimuli, but instead may be required for migration to distinct trophic signals, such as IL-7 or self-peptide/MHC. Surprisingly, while chemokines did not affect atrophy, atrophic T cells displayed increased chemokine-induced chemotaxis that was prevented by IL-7 and submitogenic anti-CD3 antibody treatment. This increase in migration was associated with increased levels of GTP-bound Rac and the ability to remodel actin. These data suggest a novel mechanism of T cell homeostasis wherein GPCR may promote T cell migration to distinct location-restricted homeostatic trophic cues for T cell survival and growth. Homeostatic trophic signals, in turn, may suppress chemokine sensitivity and cytoskeletal remodeling, to inhibit further migration.