WITHDRAWN:Comparison of the Efficacy of Epidural Balloon Neuroplasty Versus Percutaneous Epidural Neuroplasty Using a Catheter for Lumbar Central Spinal Stenosis.

This article was withdrawn by the Neurospine editorial board's decision due to the author's ethical problem.

Neuron Stimulation Device Integrated with Silicon Nanowire-Based Photodetection Circuit on a Flexible Substrate.

This paper proposes a neural stimulation device integrated with a silicon nanowire (SiNW)-based photodetection circuit for the activation of neurons with light. The proposed device is comprised of a voltage divider and a current driver in which SiNWs are used as photodetector and field-effect transistors; it has the functions of detecting light, generating a stimulation signal in proportion to the light intensity, and transmitting the signal to a micro electrode. To show the applicability of the proposed neural stimulation device as a high-resolution retinal prosthesis system, a high-density neural stimulation device with a unit cell size of 110 × 110 µ m and a resolution of 32 × 32 was fabricated on a flexible film with a thickness of approximately 50 µm. Its effectiveness as a retinal stimulation device was then evaluated using a unit cell in an in vitro animal experiment involving the retinal tissue of retinal Degeneration 1 (rd1) mice. Experiments wherein stimulation pulses were applied to the retinal tissues successfully demonstrate that the number of spikes in neural response signals increases in proportion to light intensity.

Gintonin stimulates gliotransmitter release in cortical primary astrocytes.

Lysophosphatidic acid (LPA) is a simple and minor phospholipid, but serves as a lipid-derived neurotransmitter via activation of G protein-coupled LPA receptors. Astrocytes abundantly express LPA receptors and contain gliotransmitters that modulate astrocyte-neuron interactions. Gintonin is a novel ginseng-derived G protein-coupled LPA receptor ligand. Gintonin induces [Ca(2+)]i transients in neuronal and non-neuronal cells via activation of LPA receptors, which regulate calcium-dependent ion channels and receptors. A line of evidence shows that neurotransmitter-mediated [Ca(2+)]i elevations in astrocytes are coupled with gliotransmitter release. However, little is known about whether gintonin-mediated [Ca(2+)]i transients are coupled to gliotransmitter release in astrocytes. In the present study, we examined the effects of gintonin on adenosine triphosphate (ATP) and glutamate release in mouse cortical primary astrocytes. Application of gintonin to astrocytes induced [Ca(2+)]i transients in a concentration-dependent and reversible manner. However, ginsenosides, other active ingredients in ginseng, had no effect on [Ca(2+)]i transients. The induction of gintonin-mediated [Ca(2+)]i transients was attenuated/blocked by the LPA1/3 receptor antagonist Ki16425, a phospholipase C inhibitor, an inositol 1,4,5-triphosphate receptor antagonist, and an intracellular Ca(2+) chelator. Gintonin treatment on astrocytes increased ATP and glutamate release in a concentration- and time-dependent manner. BAPTA and Ki16425 attenuated gintonin-mediated ATP and glutamate release in astrocytes. The present study shows that gintonin-mediated [Ca(2+)]i transients are coupled to gliotransmitter release via LPA receptor activation. Finally, gintonin-mediated [Ca(2+)]i transients and gliotransmitter release from astrocytes via LPA receptor activation might explain one mechanism of gintonin-mediated neuromodulation in the central nervous system.

Current stimulator IC with adaptive supply regulator for visual prostheses.

The current stimulation method is preferred over the voltage stimulation method in the visual prostheses based on functional electrical stimulation (FES) due to its accurate charge control property. Previous current stimulators are generally implemented using a static high supply voltage, because current stimulations require high output voltage compliance. This high static supply voltage, however, may harm the tissues or damage the electrodes. This paper proposes a novel integrated circuit (IC) current stimulator with adaptive supply regulator (ASR). In the proposed circuit, the internal power supply voltage is not static, but adaptively regulated to the minimum required voltage for stimulation. The current feedback loop in the ASR adaptively increases the internal supply voltage when the monitored current is smaller than the desired current, and reduces the internal supply voltage when the monitored current is higher than the desired current. With this method, the internal supply voltage of the stimulator is minimized, and potential damages of the tissues due to high voltage (HV) stimulation can be reduced. Also the current feedback loop in ASR enhances the accuracy of the output current and the robustness to the load impedance. The stimulator IC is fabricated using 0.35 micro m bipolar-CMOS-DMOS (BCDMOS) process, and the size of the chip is 2000 micro m by 1500 micro m.

Multi-channel stimulator IC using a channel sharing method for retinal prostheses.

A retinal stimulator is an implantable device restoring vision by supplying a controlled, stimulating electrical signal to people blinded by retinal diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). The resolution requirements of artificial retina systems become increasingly significant in their design as well as their usefulness. At least 32 x 32 pixels are required to provide a minimal visual function. However, a retinal stimulator with a high resolution imposes severe constraints on interface electronics. In this paper, a new stimulator IC (integrated chip) using a channel sharing technique is developed to minimize the circuit size, power consumption, as well as overheating of retina tissues. The proposed current-mode stimulator is fabricated by a 0.35 microm 2-poly/4-metal BCDMOS technology. Attention is given to minimizing the silicon area so that higher channel numbers can be implemented. The stimulator for each channel can provide output current in the range of 0-350 muA. The effective chip area excluding the pads is 1.2 mm x 1.2 mm.

Multiplexed detection of protein markers with silicon nanowire FET and sol-gel matrix.

A new modified top-down based fabrication method has been developed to obtain highly ordered silicon nanowire (SiNW) arrays. With this method, we could produce as many as 500 chips (size dependable) in an 8 inch wafer. The immobilization of multiple proteins on each chip was performed by spotting sol/gel materials encapsulating antibodies on the different regions. The most commonly used protein markers in clinics, such as C-reactive protein (CRP) and prostate specific antigen (PSA), were systematically entrapped in sol-gel materials and used for multiplexed testing. Upon formation, the electrical signal of different concentrations of CRP and PSA could be simultaneously determined in the range of 0.12 ∼ 10 ng/mL and 0.18 ∼ 8.87 ng/mL, respectively.

Measurements of serum C-reactive protein levels in patients with gastric cancer and quantification using silicon nanowire arrays.

We examined the levels of serum alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen in 83 of 400 patients who had undergone surgery for gastric cancer and correlated these markers with stages of the disease. In addition, we measured C-reactive protein (CRP) concentrations in the sera of gastric cancer patients with silicon nanowire field-effect transistors (SiNW FETs) to determine whether SiNW FETs could be used to accurately sense CRP, a marker of inflammation and possible indicator of future progression of the cancer. We designed and fabricated SiNWs to be responsive to CRP. Of the 83 patients examined, six who showed marked elevation of CRP (>3 to 10 mg/dL, according to hospital laboratory measurements) were selected and subjected to measurement with the SiNW FETs. Our findings showed that SiNW-based sensors could be highly sensitive and specific in measuring CRP in the sera of postoperative patients and thus could represent a simple and quick method of prognostic evaluation in patients. FROM THE CLINICAL EDITOR: In this study, silicon nanowire field effect transistors were fabricated to be responsive to C-reactive protein. The new technology resulted in highly sensitive and specific CRP sensors, which may greatly simplify this serum test for a variety of conditions where rapid, accurate and easily repeatable CRP measurements are needed.

Quantitative measurements of C-reactive protein using silicon nanowire arrays.

A silicon nanowire-based sensor for biological application showed highly desirable electrical responses to either pH changes or receptor-ligand interactions such as protein disease markers, viruses, and DNA hybridization. Furthermore, because the silicon nanowire can display results in real-time, it may possess superior characteristics for biosensing than those demonstrated in previously studied methods. However, despite its promising potential and advantages, certain process-related limitations of the device, due to its size and material characteristics, need to be addressed. In this article, we suggest possible solutions. We fabricated silicon nanowire using a top-down and low cost micromachining method, and evaluate the sensing of molecules after transfer and surface modifications. Our newly designed method can be used to attach highly ordered nanowires to various substrates, to form a nanowire array device, which needs to follow a series of repetitive steps in conventional fabrication technology based on a vapor-liquid-solid (VLS) method. For evaluation, we demonstrated that our newly fabricated silicon nanowire arrays could detect pH changes as well as streptavidin-biotin binding events. As well as the initial proof-of-principle studies, C-reactive protein binding was measured: electrical signals were changed in a linear fashion with the concentration (1 fM to 1 nM) in PBS containing 1.37 mM of salts. Finally, to address the effects of Debye length, silicon nanowires coupled with antigen proteins underwent electrical signal changes as the salt concentration changed.

Fabrication of suspended silicon nanowire arrays.

A method to fabricate suspended silicon nanowires that are applicable to electronic and electromechanical nanowire devices is reported. The method allows for the wafer-level production of suspended silicon nanowires using anisotropic etching and thermal oxidation of single-crystal silicon. The deviation in width of the silicon nanowire bridges produced using the proposed method is evaluated. The NW field-effect transistor (FET) properties of the device obtained by transferring suspended nanowires are shown to be practical for useful functions.

Hard X-ray microscopy with Zernike phase contrast.

Zernike phase contrast has been added to a full-field X-ray microscope with Fresnel zone plates that was in operation at 6.95 keV. The spatial resolution has also been improved by increasing the magnification of the microscope objective looking at the CsI(Tl) scintillation crystal. Cu no. 2000 meshes and a zone plate have been imaged to see the contrast as well as the spatial resolution. A Halo effect coming from the Zernike phase contrast was clearly visible on the images of meshes.

Increased risk of adefovir resistance in patients with lamivudine-resistant chronic hepatitis B after 48 weeks of adefovir dipivoxil monotherapy.

Although adefovir dipivoxil (ADV) has a unique profile of delayed and infrequent resistance in treatment-naïve chronic hepatitis B patients, the association of ADV resistance with previous lamivudine (LAM) resistance is not well understood. We compared the emergence of the ADV-resistant mutations rtA181V/T and rtN236T between LAM-resistant patients and treatment-naïve patients at 48 weeks of ADV monotherapy. Fifty-seven LAM-resistant patients and 38 treatment-naïve patients were treated with 10 mg/d ADV for more than 48 weeks. Both baseline and 48-week blood samples were analyzed for ADV-resistant mutations via restriction fragment mass polymorphism analysis. Antiviral responses were evaluated according to changes in serum HBV DNA (measured via real-time polymerase chain reaction) and alanine aminotransferase (ALT) levels and loss of hepatitis B e antigen (HBeAg). After 48 weeks, 10 (18%) of the 57 LAM-resistant patients were found to have developed ADV-resistant mutations, whereas none of the 38 treatment-naïve patients developed such mutations (P < .01). Among LAM-resistant patients, the reduction in serum HBV DNA levels was significantly lower in patients with ADV-resistant mutations than in those without such mutations (-1.04 vs. -2.63 log10 copies/mL) (P = .01). However, the rates of serum ALT normalization (60% vs. 55%) and HBeAg loss (14% vs. 21%) were not significantly different between the 2 groups (P > .05). In conclusion, the emergence of the rtA181V/T and rtN236T mutations was more common in LAM-resistant patients than in treatment-naïve patients after 48 weeks of ADV therapy and was associated with reduced antiviral efficacy to drug treatment.

Observations of a human hair shaft with an x-ray microscope.

We observed the internal structures of a human hair shaft using x-ray microscopes with a spatial resolution in the range from a few microns to less than 100 nm. The energy of the x-ray used is 6.95 keV. The Zernike phase contrast together with a spatial resolution better than 100 nm enabled us to see the cuticles of scales, the cortex of macrofibrils and the medulla. All these internal features and more can easily be observed with no sample preparation including staining.