Hierarchical neural processing in γ oscillations for syntactic and semantic operations accounts for first- and second-language epistemology.

Introduction: We discuss event-related power differences (ERPDs) in low- and broadband-γ oscillations as the embedded-clause edge is processed in wh-dependencies such as Which decision regarding/about him/her did Paul say that Lydie rejected without hesitation? in first (L1) and second language (L2) French speakers. Methods: The experimental conditions manipulated whether pronouns appeared in modifiers (Mods; regarding him/her) or in noun complements (Comps; about him/her) and whether they matched or mismatched a matrix-clause subject in gender. Results: Across L1 and L2 speakers, we found that anaphora-linked ERPDs for Mods vs. Comps in evoked power first arose in low γ and then in broadband γ. Referential elements first seem to be retrieved from working memory by narrowband processes in low γ and then referential identification seems to be computed in broadband-γ output. Interactions between discourse- and syntax-based referential processes for the Mods vs. Comps in these ERPDs furthermore suggest that multidomain γ-band processing enables a range of elementary operations for discourse and semantic interpretation. Discussion: We argue that a multidomain mechanism enabling operations conditioned by the syntactic and semantic nature of the elements processed interacts with local brain microcircuits representing features and feature sets that have been established in L1 or L2 acquisition, accounting for a single language epistemology across learning contexts.

The role of Bifidobacterium in longevity and the future of probiotics.

This review explores the role and health impacts of probiotics, focusing specifically on Bifidobacterium spp. It highlights the functionalities that Bifidobacteria can provide, underscored by the historical evolution of definitions and technological advancements related to probiotics. By examining the association between Bifidobacteria and longevity, this review suggests new avenues for health enhancement. Highlighting case studies of centenarians, it presents examples related to human aging, illuminating the potential links to longevity through research on Bifidobacterium strains found in centenarians. This review not only emphasizes the importance of current research but also advocates for further investigation into the health benefits of Bifidobacteria, underlining the necessity for continuous study in the nutraceutical field.

Comparative analysis of reduced toxicity conditioning regimens between fludarabine plus melphalan and fludarabine plus busulfex in adult patients with acute lymphoblastic leukemia.

Reduced-toxicity conditioning (RTC) regimens aim to mitigate regimen-related toxicity while maintaining anti-leukemic efficacy in allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed outcomes of RTC regimens utilizing melphalan versus intravenous busulfan combined with fludarabine in adult acute lymphoblastic leukemia (ALL) patients. A retrospective analysis was conducted with 149 consecutive adult ALL patients (median age 51, range 18-60) in remission undergoing allo-HSCT. Patients received either fludarabine 150 mg/BSA plus 2 days of melphalan 70 mg/BSA (FM140, n = 76) from 2009 to 2015 or fludarabine plus 3 days of busulfan 3.2 mg/kg (FB9.6, n = 73) from 2016 to 2021. At 5 years post-HSCT, FM140 demonstrated superior disease-free survival (53.4% vs. 30.5%, p = 0.007) and lower cumulative relapse (27.4% vs. 46.8%, p = 0.026) than FB9.6. Five-year overall survival and non-relapse mortality did not significantly differ. FM140 exhibited a higher incidence of acute graft-versus-host disease (GVHD) grades II-IV (49.3% vs. 30.3%, p = 0.016), though rates of acute GVHD grades III-IV and chronic GVHD were similar. Multivariate analysis identified Philadelphia chromosome and minimal residual disease positive status, and FB9.6 conditioning as predictors of increased relapse and poorer disease-free survival. FM140 RTC regimen displayed significantly reduced relapse and superior disease-free survival compared to FB9.6 in ALL patients undergoing allo-HSCT, highlighting its current clinical utility.

Harnessing biotechnology for penicillin production: Opportunities and environmental considerations.

Since the discovery of antibiotics, penicillin has remained the top choice in clinical medicine. With continuous advancements in biotechnology, penicillin production has become cost-effective and efficient. Genetic engineering techniques have been employed to enhance biosynthetic pathways, leading to the production of new penicillin derivatives with improved properties and increased efficacy against antibiotic-resistant pathogens. Advances in bioreactor design, media formulation, and process optimization have contributed to higher yields, reduced production costs, and increased penicillin accessibility. While biotechnological advances have clearly benefited the global production of this life-saving drug, they have also created challenges in terms of waste management. Production fermentation broths from industries contain residual antibiotics, by-products, and other contaminants that pose direct environmental threats, while increased global consumption intensifies the risk of antimicrobial resistance in both the environment and living organisms. The current geographical and spatial distribution of antibiotic and penicillin consumption dramatically reveals a worldwide threat. These challenges are being addressed through the development of novel waste management techniques. Efforts are aimed at both upstream and downstream processing of antibiotic and penicillin production to minimize costs and improve yield efficiency while lowering the overall environmental impact. Yield optimization using artificial intelligence (AI), along with biological and chemical treatment of waste, is also being explored to reduce adverse impacts. The implementation of strict regulatory frameworks and guidelines is also essential to ensure proper management and disposal of penicillin production waste. This review is novel because it explores the key remaining challenges in antibiotic development, the scope of machine learning tools such as Quantitative Structure-Activity Relationship (QSAR) in modern biotechnology-driven production, improved waste management for antibiotics, discovering alternative path to reducing antibiotic use in agriculture through alternative meat production, addressing current practices, and offering effective recommendations.

Association between knee osteoarthritis and the risk of cardiovascular disease and the synergistic adverse effects of lack of exercise.

We aimed to determine whether knee OA is associated with CVD risk and all-cause death and to evaluate whether the association differs by exercise behavior. We used Korea National Health Insurance Service (KNHIS) database and included 201,466 participants (7572 subjects diagnosed with knee OA) who underwent health screening between 2009 and 2015. Those who had been diagnosed with knee OA or CVD before the index year were excluded. Cox proportional hazard models were used after adjusting for sociodemographic and CVD risk factors to evaluate the association between knee OA and CVD risk and all-cause death. Stratification analysis was further performed to determine the effect of exercise behavior on this relationship. During a median follow-up of 7.06 ± 2.24 years, 8743 CVD (2510 MI and 6553 stroke) cases developed. Individuals with knee OA had increased risks of CVD [hazard ratio (HR) 1.26, 95% confidence interval (CI) 1.15-1.38], myocardial infarction (MI) (HR 1.20, 95% CI 1.00-1.44), and stroke (HR 1.29, 95% CI 1.16-1.43) compared with those without knee OA. Those with knee OA who did not exercise had an increased risk of CVD (HR 1.25, 95% CI 1.11-1.40), whereas no significant increased CVD risk was observed in those with knee OA who exercised at least once a week (HR 1.11, 95% CI 0.96-1.28). There was no association between knee osteoarthritis and all-cause death. Knee OA was independently associated with an increased risk of CVD. Lack of exercise might have a synergistic adverse effect on the association between knee OA and CVD.

Cardiac Muscle Training-A New Way of Recognizing and Supporting Recovery for LVAD Patients in the Pediatric Population.

Patients with refractory heart failure due to chronic progressive cardiac myopathy (CM) may require mechanical circulatory support as a bridge to transplantation. A few patients can be weaned from support devices if recovery can be achieved. The identification of these patients is of great importance as recovery may be missed if the heart is unloaded by the ventricular assist device (VAD). Testing the load-bearing capacity of the supported left ventricle (LV) by temporarily and gradually reducing mechanical support during cardiac exercise can help identify responders and potentially aid the recovery process. An exercise training protocol was used in 3 patients (8 months, 18 months and 8 years old) with histological CM findings and myocarditis. They were monitored regularly using clinical information and functional imaging with VAD support. Echocardiographic examination included both conventional real-time 3D echocardiography (RT3DE) and speckle tracking (ST). A daily temporary reduction in pump rate (phase A) was followed by a permanent reduction in rate (phase B). Finally, pump stops of up to 30 min were performed once a week (phase C). The final decision on explantation was based on at least three pump stops. Two patients were weaned and successfully removed from the VAD. One of them was diagnosed with acute viral myocarditis. The other had chronic myocarditis with dilated myopathy and mild interstitial fibrosis. The noninvasive assessment of cardiac output and strain under different loading conditions during VAD therapy is feasible and helps identify candidates for weaning despite severe histological findings. The presented protocol, which incorporates new echocardiographic techniques for determining volume and deformation, can be of great help in positively guiding the process of individual recovery, which may be essential for selecting and increasing the number of patients to be weaned from VAD.

Cytomegalovirus-Specific Immunotherapy for Glioblastoma Treatments.

Over the last two decades, numerous studies have investigated the presence of human cytomegalovirus (CMV) within glioblastoma or gliomas; however, the results are severely conflicting. While a few researchers have suggested the potential benefits of cytotoxic T lymphocyte or dendritic cell-based vaccines for recurrent or newly diagnosed glioblastoma patients, several studies did not at all agree with the existence of CMV in glioblastoma cells. In this review, we summarized the conflicting results and issues about the detection of CMV in glioblastoma or glioma patients. We also provided the clinical data of published and unpublished clinical trials using CMV-specific immunotherapy for glioblastomas.

Radio Communications on Family Planning: Case of West Africa.

Sub-Saharan Africa will accommodate more population this century by having a multitude of births across the continent. Family planning methods provide women with techniques to manage their health and wellbeing. This study investigated how radio communications in family planning changed the perception of Ghanaian, Liberian, and Senegalese mothers toward having fewer children. Univariate and multivariate linear regression results after coarsened exact matching (CEM) with selected covariates for 15- to 49-year-old mothers from demographic and health survey (DHS) data implied the effectiveness of radio communications. This effort supports the need for further research on tailored communication methods for West African mothers over time.

In vivo and in vitro assessment of the bleaching effectiveness of a brush-off patch containing 3.0% hydrogen peroxide.

OBJECTIVES: To evaluate the efficacy of a brush-off patch containing 3.0% hydrogen peroxide, which is a new over-the-counter (OTC) product for tooth whitening, and determine the optimal protocol for use. MATERIALS AND METHODS: We performed an in vitro study using hydroxyapatite specimens and a clinical trial involving 140 volunteers. The brush-off patch was applied to the specimens (in vitro) or the maxillary anterior teeth (in vivo; 14 days) for 10 min twice daily (case 10 group) or 30 min once daily (case 30 group). We also included control groups in both experiments. Lightness (L*), redness (a*), and yellowness (b*) values were measured using a colorimeter. In the in vivo study, color changes were measured at baseline and 7 and 14 days after the start of patch application. The overall color change (ΔE) was statistically analyzed. RESULTS: In the in vitro study, the color change (ΔE*) after the experiment was significantly different between the two case groups and the control group (p < 0.001). In the in vivo study, the case groups showed color changes at both 7 and 14 days after patch application. In particular, the change in the case 30 group was significantly more prominent on day 14 than on day 7 (p < 0.05). CONCLUSION: Our findings suggest that brush-off patches containing 3.0% hydrogen peroxide are effective OTC products for tooth whitening. CLINICAL RELEVANCE: For best results, brush-off patches containing 3.0% hydrogen peroxide can be applied once daily for 30 min.

Penetration of an antimicrobial zinc-sugar alcohol complex into Streptococcus mutans biofilms.

Mature biofilms are highly resistant to antimicrobial agents due to the presence of extracellular polymeric substances (EPS), which inhibit the penetration of external molecules. In this study, we developed a coordination compound consisting of zinc chloride and erythritol that exhibits penetrating and bactericidal activity against Streptococcus mutans biofilms. An in vitro biofilm model was established in microplates, and bactericidal activity against biofilms was evaluated using an Alamar blue assay. The cause of the antimicrobial activity of the zinc-erythritol mixture on mature biofilms was demonstrated using fast atom bombardment-mass spectrometry, confocal laser scanning microscopy and atomic force microscopy. We demonstrated that zinc chloride spontaneously formed cationic complexes with erythritol in water. The zinc-erythritol complexes reduced intra- and inter-molecular interactions between bacterial exopolysaccharides, a major component of EPS. This activity was confirmed by measuring the attenuation of the hardness of dried polysaccharides isolated from S. mutans biofilms. The reduction in the interactions between polysaccharides allowed the complexes to penetrate into biofilms and kill the embedded bacteria. While approximately 13% of biofilm-associated microbes were killed by a 10 min treatment with 6.6 mM zinc chloride, 45% were killed when a solution containing 19.8 mM erythritol and 6.6 mM zinc chloride was used. This strategy of leveraging the coordination properties of metal ions with sugar alcohols provides a simple way to effectively remove mature biofilms using only conventional substances without the need for intricate chemical synthesis processes.

Remote quantification of Cochlodinium polykrikoides blooms occurring in the East Sea using geostationary ocean color imager (GOCI).

Accurate and timely quantification of widespread harmful algal bloom (HAB) distribution is crucial to respond to the natural disaster, minimize the damage, and assess the environmental impact of the event. Although various remote sensing-based quantification approaches have been proposed for HAB since the advent of the ocean color satellite sensor, there have been no algorithms that were validated with in-situ quantitative measurements for the red tide occurring in the Korean seas. Furthermore, since the geostationary ocean color imager (GOCI) became available in June 2010, an algorithm that exploits its unprecedented observation frequency (every hour during the daytime) has been highly demanded to better track the changes in spatial distribution of red tide. This study developed a novel red tide quantification algorithm for GOCI that can estimate hourly chlorophyll-a (Chl a) concentration of Cochlodinium (Margalefidinium) polykrikoides, one of the major red tide species around Korean seas. The developed algorithm has been validated using in-situ Chl a measurements collected from a cruise campaign conducted in August 2013, when a massive C. polykrikoides bloom devastated Korean coasts. The proposed algorithm produced a high correlation (R2=0.92) with in-situ Chl a measurements with robust performance also for high Chl a concentration (300mg/m3) in East Sea areas that typically have a relatively low total suspended particle concentration (<0.5mg/m3).

Tooth wear and cleaning effect of an abrasive-free dentifrice.

BACKGROUND/PURPOSE: To evaluate the degree of wear on human teeth and the cleaning effect of abrasive-free dentifrice. A sodium pyrophosphate and cellulose-containing abrasive-free dentifrice and calcium carbonate-containing control dentifrice were evaluated. MATERIALS AND METHODS: Dentin and enamel specimens were subjected to 109,500 successive double strokes and 5480 double strokes in pH-cycling condition. A profilometer measured abrasion depth. The cleaning effect of dentifrices on artificial stain was evaluated by cleaning power (modified Stookey method) and by removal of colored stain on artificial tooth. RESULTS: The experimental results were evaluated using Mann-Whitney U test. The abrasion depth in dentin specimens was 13.97-26.73 times smaller with abrasive-free dentifrice than with control dentifrice. The abrasion depth of enamel specimen was 2.17 ± 0.66 µm with control dentifrice. The values for abrasive-free dentifrice were too small to measure. In pH-cycling conditions using dentin specimens, abrasion depth was 14.28-19.00 times smaller with abrasive-free dentifrice than with control dentifrice. The cleaning power and removing effect of colored stain were statistically insignificant between abrasive-free dentifrice and control dentifrice (P > 0.05). CONCLUSION: The abrasive-free dentifrice was as effective as control dentifrice in its cleaning effect on artificial stain and can significantly reduce tooth wear more than control dentifrice.

Indoor Air Quality Analysis Using Deep Learning with Sensor Data.

Indoor air quality analysis is of interest to understand the abnormal atmospheric phenomena and external factors that affect air quality. By recording and analyzing quality measurements, we are able to observe patterns in the measurements and predict the air quality of near future. We designed a microchip made out of sensors that is capable of periodically recording measurements, and proposed a model that estimates atmospheric changes using deep learning. In addition, we developed an efficient algorithm to determine the optimal observation period for accurate air quality prediction. Experimental results with real-world data demonstrate the feasibility of our approach.

Tyrphostin A9 improves blastocyst development in porcine embryos through induction of dynamin-related protein 1-dependent mitochondrial fission.

Mitochondrial dynamics are associated with the development of porcine embryos. However, little is known about the effects of mitochondrial dynamics-related genes (Drp1 and pDrp1-Ser616) on early porcine embryo development. Here, we investigated the effect of Drp1-dependent mitochondrial fission signaling on the development of porcine embryos using the mitochondrial fission inducer, tyrphostin A9 (TA9). We determined that TA9 (1µM) treated embryos were increased the mitochondrial functions, blastocyst development rate and quality, as well as decreased mitochondria-specific superoxide and mitochondrial apoptosis. Thus, TA9-induced appropriate mitochondrial fission improved the developmental competence via maintenance of a balance in mitochondrial dynamics in porcine embryo.

Ganglioside GD1a promotes oocyte maturation, furthers preimplantation development, and increases blastocyst quality in pigs.

Gangliosides are key lipid molecules required for the regulation of cellular processes such as proliferation, differentiation, and cell signaling, including signaling of epidermal growth factor receptor (EGFR). Epidermal growth factor (EGF) has long been considered a potential regulator of meiotic and cytoplasmic maturation in mammalian oocytes. However, there is no report on the direct effect of ganglioside GD1a in porcine oocyte maturation. In this study, we first investigated a functional link between GD1a and meiotic maturation during in vitro maturation (IVM) of porcine embryos. Moreover, we confirmed the effect of exogenous GD1a treatment on blastocyst development, quality, and fertilization rate in early embryonic development. First, we observed that the protein level of ST3GAL2, a GD1a synthesizing enzyme, significantly increased (P < 0.01) in cumulus-oocyte-complexes (COCs) during IVM progress. The proportion of arrested germinal vesicles (GV) increased in oocytes treated with EGF+GD1a (41.6 ± 1.5%) at the IVM I stage. Upon completion of meiotic maturation, the proportion of metaphase II (M II) was significantly higher (P < 0.05) in the EGF+GD1a (89.9 ± 3.6%) treated group. After IVF, the percentage of penetrated oocytes was significantly higher (P < 0.05) in the EGF+GD1a (89.1 ± 2.3%) treated group than in the control group. Furthermore, exogenous GD1a treatment improved the developmental competence and quality of blastocysts during preimplantation embryo development stage. These results suggest that ganglioside GD1a may play an important role in IVM mechanisms of porcine maturation capacity. Furthermore, our findings will be helpful for better promoting the embryo development and blastocyst quality in pigs.

Simple aerosol correction technique based on the spectral relationships of the aerosol multiple-scattering reflectances for atmospheric correction over the oceans.

An estimation of the aerosol multiple-scattering reflectance is an important part of the atmospheric correction procedure in satellite ocean color data processing. Most commonly, the utilization of two near-infrared (NIR) bands to estimate the aerosol optical properties has been adopted for the estimation of the effects of aerosols. Previously, the operational Geostationary Color Ocean Imager (GOCI) atmospheric correction scheme relies on a single-scattering reflectance ratio (SSE), which was developed for the processing of the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) data to determine the appropriate aerosol models and their aerosol optical thicknesses. The scheme computes reflectance contributions (weighting factor) of candidate aerosol models in a single scattering domain then spectrally extrapolates the single-scattering aerosol reflectance from NIR to visible (VIS) bands using the SSE. However, it directly applies the weight value to all wavelengths in a multiple-scattering domain although the multiple-scattering aerosol reflectance has a non-linear relationship with the single-scattering reflectance and inter-band relationship of multiple scattering aerosol reflectances is non-linear. To avoid these issues, we propose an alternative scheme for estimating the aerosol reflectance that uses the spectral relationships in the aerosol multiple-scattering reflectance between different wavelengths (called SRAMS). The process directly calculates the multiple-scattering reflectance contributions in NIR with no residual errors for selected aerosol models. Then it spectrally extrapolates the reflectance contribution from NIR to visible bands for each selected model using the SRAMS. To assess the performance of the algorithm regarding the errors in the water reflectance at the surface or remote-sensing reflectance retrieval, we compared the SRAMS atmospheric correction results with the SSE atmospheric correction using both simulations and in situ match-ups with the GOCI data. From simulations, the mean errors for bands from 412 to 555 nm were 5.2% for the SRAMS scheme and 11.5% for SSE scheme in case-I waters. From in situ match-ups, 16.5% for the SRAMS scheme and 17.6% scheme for the SSE scheme in both case-I and case-II waters. Although we applied the SRAMS algorithm to the GOCI, it can be applied to other ocean color sensors which have two NIR wavelengths.

Vicarious calibration of the Geostationary Ocean Color Imager.

Measurements of ocean color from Geostationary Ocean Color Imager (GOCI) with a moderate spatial resolution and a high temporal frequency demonstrate high value for a number of oceanographic applications. This study aims to propose and evaluate the calibration of GOCI as needed to achieve the level of radiometric accuracy desired for ocean color studies. Previous studies reported that the GOCI retrievals of normalized water-leaving radiances (nLw) are biased high for all visible bands due to the lack of vicarious calibration. The vicarious calibration approach described here relies on the assumed constant aerosol characteristics over the open-ocean sites to accurately estimate atmospheric radiances for the two near-infrared (NIR) bands. The vicarious calibration of visible bands is performed using in situ nLw measurements and the satellite-estimated atmospheric radiance using two NIR bands over the case-1 waters. Prior to this analysis, the in situ nLw spectra in the NIR are corrected by the spectrum optimization technique based on the NIR similarity spectrum assumption. The vicarious calibration gain factors derived for all GOCI bands (except 865nm) significantly improve agreement in retrieved remote-sensing reflectance (Rrs) relative to in situ measurements. These gain factors are independent of angular geometry and possible temporal variability. To further increase the confidence in the calibration gain factors, a large data set from shipboard measurements and AERONET-OC is used in the validation process. It is shown that the absolute percentage difference of the atmospheric correction results from the vicariously calibrated GOCI system is reduced by ~6.8%.

Light-controlled biphasic current stimulator IC using CMOS image sensors for high-resolution retinal prosthesis and in vitro experimental results with rd1 mouse.

Retinal prosthetic devices stimulate retinal nerve cells with electrical signals proportional to the incident light intensities. For a high-resolution retinal prosthesis, it is necessary to reduce the size of the stimulator pixels as much as possible, because the retinal nerve cells are concentrated in a small area of approximately 5 mm × 5 mm. In this paper, a miniaturized biphasic current stimulator integrated circuit is developed for subretinal stimulation and tested in vitro. The stimulator pixel is miniaturized by using a complementary metal-oxide-semiconductor (CMOS) image sensor composed of three transistors. Compared to a pixel that uses a four-transistor CMOS image sensor, this new design reduces the pixel size by 8.3%. The pixel size is further reduced by simplifying the stimulation-current generating circuit, which provides a 43.9% size reduction when compared to the design reported to be the most advanced version to date for subretinal stimulation. The proposed design is fabricated using a 0.35 µm bipolar-CMOS-DMOS process. Each pixel is designed to fit in a 50 µ m × 55 µm area, which theoretically allows implementing more than 5000 pixels in the 5 mm × 5 mm area. Experimental results show that a biphasic current in the range of 0 to 300 µA at 12 V can be generated as a function of incident light intensities. Results from in vitro experiments with rd1 mice indicate that the proposed method can be effectively used for retinal prosthesis with a high resolution.

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.