TCT-480 National Trend in Multivessel Percutaneous Coronary Intervention in Patients with Diabetes Mellitus in the United States

Abstract available through the Journal of the American College of Cardiology

Organic electrode coatings for next-generation neural interfaces

Traditional neuronal interfaces utilize metallic electrodes which in recent years have reached a plateau in terms of the ability to provide safe stimulation at high resolution or rather with high densities of microelectrodes with improved spatial selectivity. To achieve higher resolution it has become clear that reducing the size of electrodes is required to enable higher electrode counts from the implant device. The limitations of interfacing electrodes including low charge injection limits, mechanical mismatch and foreign body response can be addressed through the use of organic electrode coatings which typically provide a softer, more roughened surface to enable both improved charge transfer and lower mechanical mismatch with neural tissue. Coating electrodes with conductive polymers or carbon nanotubes offers a substantial increase in charge transfer area compared to conventional platinum electrodes. These organic conductors provide safe electrical stimulation of tissue while avoiding undesirable chemical reactions and cell damage. However, the mechanical properties of conductive polymers are not ideal, as they are quite brittle. Hydrogel polymers present a versatile coating option for electrodes as they can be chemically modified to provide a soft and conductive scaffold. However, the in vivo chronic inflammatory response of these conductive hydrogels remains unknown. A more recent approach proposes tissue engineering the electrode interface through the use of encapsulated neurons within hydrogel coatings. This approach may provide a method for activating tissue at the cellular scale, however, several technological challenges must be addressed to demonstrate feasibility of this innovative idea. The review focuses on the various organic coatings which have been investigated to improve neural interface electrodes

Allotransplanted Neurons Used to Repair Peripheral Nerve Injury Do Not Elicit Overt Immunogenicity

A major problem hindering the development of autograft alternatives for repairing peripheral nerve injuries is immunogenicity. We have previously shown successful regeneration in transected rat sciatic nerves using conduits filled with allogeneic dorsal root ganglion (DRG) cells without any immunosuppression. In this study, we re-examined the immunogenicity of our DRG neuron implanted conduits as a potential strategy to overcome transplant rejection. A biodegradable NeuraGen® tube was infused with pure DRG neurons or Schwann cells cultured from a rat strain differing from the host rats and used to repair 8 mm gaps in the sciatic nerve. We observed enhanced regeneration with allogeneic cells compared to empty conduits 16 weeks post-surgery, but morphological analyses suggest recovery comparable to the healthy nerves was not achieved. The degree of regeneration was indistinguishable between DRG and Schwann cell allografts although immunogenicity assessments revealed substantially increased presence of Interferon gamma (IFN-γ) in Schwann cell allografts compared to the DRG allografts by two weeks post-surgery. Macrophage infiltration of the regenerated nerve graft in the DRG group 16 weeks post-surgery was below the level of the empty conduit (0.56 fold change from NG; p<0.05) while the Schwann cell group revealed significantly higher counts (1.29 fold change from NG; p<0.001). Major histocompatibility complex I (MHC I) molecules were present in significantly increased levels in the DRG and Schwann cell allograft groups compared to the hollow NG conduit and the Sham healthy nerve. Our results confirmed previous studies that have reported Schwann cells as being immunogenic, likely due to MHC I expression. Nerve gap injuries are difficult to repair; our data suggest that DRG neurons are superior medium to implant inside conduit tubes due to reduced immunogenicity and represent a potential treatment strategy that could be preferable to the current gold standard of autologous nerve transplant

Concomitant differentiation of a population of mouse embryonic stem cells into neuron‐like cells and schwann cell–like cells in a slow‐flow microfluidic device

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135245/1/dvdy24466_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135245/2/dvdy24466.pd

Botulinum Neurotoxin for Pain Management: Insights from Animal Models

The action of botulinum neurotoxins (BoNTs) at the neuromuscular junction has been extensively investigated and knowledge gained in this field laid the foundation for the use of BoNTs in human pathologies characterized by excessive muscle contractions. Although much more is known about the action of BoNTs on the peripheral system, growing evidence has demonstrated several effects also at the central level. Pain conditions, with special regard to neuropathic and intractable pain, are some of the pathological states that have been recently treated with BoNTs with beneficial effects. The knowledge of the action and potentiality of BoNTs utilization against pain, with emphasis for its possible use in modulation and alleviation of chronic pain, still represents an outstanding challenge for experimental research. This review highlights recent findings on the effects of BoNTs in animal pain models

Techniques for designing robust and reliable analog circuits

Recent decades have seen an influx of electronics into high volume safety-critical applications such as automotive. These applications differ from the conventional safety-critical applications like aircrafts in that they operate in a price sensitive market and are available to mass consumers. This makes it difficult to use traditional robustness and reliability mechanisms like redundancy and exhaustive testing. Techniques that can help improve the robustness and reliability of integrated circuits (ICs) to be used in these high-volume safety-critical applications are at the forefront of industrial and academic discussions. Unlike digital designs, which have managed to achieve very low defects per million, required for the automotive sector, analog designs lag far behind. In fact, analog designs are responsible for the majority of in-field failures observed in any mixed signal system on chip (SoC). The conventional technique of adding design margins to account for the robustness and reliability is running out of steam. Therefore, techniques such as on-chip functional testing, on-chip transistor degradation monitoring, and lowering AMS test costs in general or through the use of already available on-chip resources is the way forward to deal with these robustness and reliability issues. In this this dissertation all these techniques have been touched upon. Spectral testing and linearity testing are two primary test categories performed on data converters. On-chip testing of these specifications can help reduce test costs and, improve functional safety through in-field testing. A low cost on-chip sine wave generator for spectral testing has been designed and measurement results obtained in the 40nm bulk CMOS technology. Taking advantage of the fact that modern SoCs have both ADCs and DACs, an algorithm that can enable co-linearity testing of these data converters without the need for any external equipment has been developed. The algorithm removes the need for requiring a high accuracy signal source or measurement device for the ADC/DAC testing. A monolithic, fast, large dynamic range gate leakage current monitor has been developed to enable on-chip monitoring/characterization of time dependent dielectric breakdown (TDDB). The developed sensor is sensitive to currents as low as 200pA and directly measures the degrading parameters, that is the gate leakage current unlike previously published designs. An algorithm to enable high-speed low-cost jitter segregation in pulse amplitude modulation-4 (PAM4) links is also discussed. Level shifters are an essential component of any modern SoC. Level shifters targeted to charge constraint applications have also been discussed in this thesis