Focal stimulation of retinal ganglion cells using subretinal 3D microelectrodes with peripheral electrodes of opposite current.

Subretinal prostheses have been developed to stimulate survived retinal ganglion cells (RGCs), indirectly following the physiological visual pathways. However, current spreading from the prosthesis electrode causes the activation of unintended RGCs, thereby limiting the spatial resolution of artificial vision. This study proposes a strategy for focal stimulation of RGCs using a subretinal electrode array, in which six hexagonally arranged peripheral electrodes surround a stimulating electrode. RGCs in an in-vitro condition were subretinally stimulated using a fabricated electrode array coated with iridium oxide, following the three different stimulation configurations (with no peripheral, six electrodes of opposite current, and six ground). In-vitro experiments showed that the stimulation with six electrodes of opposite current was most effective in controlling RGC responses with a high spatial resolution. The results suggest that the effective utilization of return electrodes, such as by applying an opposite current to them, could help reduce current spreading beyond the local area targeted for stimulation and elicit RGC responses only in the vicinity of the stimulating electrode. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-023-00342-3.

Interaction Between a High-Fat Diet and Tau Pathology in Mice: Implications for Alzheimer's Disease.

BACKGROUND: Obesity is a modifiable risk factor for Alzheimer's disease (AD). However, its relation with tau pathology (i.e., aberrant tau protein behavior in tauopathies such as AD) has been inconclusive. OBJECTIVE: This study investigated the interaction between a high-fat diet (HFD) and tau pathology in adult male mice. METHODS: Transgenic mice overexpressing human P301S Tau (those with the pathology) and wild-type (WT) littermates were subjected to behavioral tests, functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and western blotting analysis to investigate the effects of prolonged HFD versus regular diet during adulthood. RESULTS: HFD increased body weight in both WT and P301S mice but had minimal effect on blood glucose levels. The brain response to HFD was tau genotype-specific. WT mice exhibited decreased recognition memory and enhanced network connectivity in fMRI, while P301S mice exhibited white matter tract disorganization in DTI as the sole significant finding. The reduction of insulin receptor ß, insulin downstream signaling, neuronal nuclear protein, CD68-positive phagocytic activity, and myelin basic protein level were confined to the cortex of WT mice. In contrast to P301S mice, WT mice showed significant changes in the tau protein and its phosphorylation levels along with increased soluble neurofilament light levels in the hippocampus. CONCLUSIONS: HFD-induced brain dysfunction and pathological changes were blunted in mice with the pathology and more profound in healthy mice. Our findings highlight the need to consider this interaction between obesity and tau pathology when tailoring treatment strategies for AD and other tauopathies.

Quantitative non-nutritive sucking measurement as a predictor of oral feeding readiness in newborns.

Background and purpose: The purpose of this study is to examine the relationship between the parameters of a silver nanowire-based flexible pressure sensor developed to measure the non-nutritive sucking (NNS) performance and predict the nutritive sucking status in preterm infants. Methods: Preterm infants who were referred for feeding difficulty during the transition period from tubal feeding to oral feeding were enrolled in our study. A flexible pressure sensor was used to measure the non-nutritive sucking parameters of neonates. The evaluator stimulated the infants' lips and tongue with a pacifier integrated with a sucking pressure sensor, to check whether non-nutritive sucking had occurred. When the sucking reflex was induced, it was measured. The infants' sucking characteristics were subdivided into classifications according to the NOMAS criteria and full oral feeding (FOF) status. Quantitative NNS measurement according to the feeding state was compared between groups. Results: When comparing the quantitative NNS measurement by feeding characteristics, the average sucking pressure was significantly higher in infants in the FOF capable group than those in the incomplete FOF group. In addition, the maximum and average sucking pressure was significantly higher in infants with a normal sucking pattern compared to those with a disorganized sucking pattern. The average NNS pressure was divided over the range of 0-3 kPa and the same weight was assigned to each item. When the optimal cut-off value for the sensitivity and specificity of the average NNS pressure to estimate the FOF was set, a pressure of 1.5 kPa yielded the highest sensitivity (84.62%) and specificity (67.65%) on the receiver operating characteristic (ROC) curve. The area under the curve (AUC) was 0.786, and this result was statistically significant. Conclusions: This study presents a quantitative parameter for non-nutritive sucking in preterm infants with the use of a flexible pressure sensor. Results show possible quantitative indicators that can aid in predicting when preterm infants can transition to oral feeding and their prognosis. This will serve as a basis for future research on determining the feeding transition period of newborns with health conditions that affect oral feeding.

Magnetic stimulation of the sciatic nerve using an implantable high-inductance coil with low-intensity current.

Objective.Magnetic stimulation using implantable devices may offer a promising alternative to other stimulation methods such as transcranial magnetic stimulation (TMS) or electric stimulation using implantable devices. This alternative may increase the selectivity of stimulation compared to TMS, and eliminate the need to expose tissue to metals in the body, as is required in electric stimulation using implantable devices. However, previous studies of magnetic stimulation of the sciatic nerve used large coils, with a diameter of several tens of mm, and a current intensity in the order of kA.Approach.Since such large coils and high current intensity are not suitable for implantable devices, we investigated the feasibility of using a smaller implantable coil and lower current to elicit neuronal responses. A coil with a diameter of 3 mm and an inductance of 1 mH was used as the implantable stimulator.Main results.Beforein vivoexperiments, we used 3D computational models to estimate the minimum stimulus intensity required to elicit neuronal responses, resulting in a threshold current above 3.5 A. Inin vivoexperiments, we observed successful nerve stimulation via compound muscle action potentials elicited in hind-limb muscles when the applied current was above 3.8 A, a significantly reduced current than that used in conventional magnetic stimulation.Significance.We report the feasibility of magnetic stimulation using an implantable millimeter-sized coil and low current of a few amperes to elicit neural responses in peripheral nerves. The proposed method is expected to be an alternative to TMS, with the merit of improved selectivity in stimulation, and to electrical stimulation based on implantable devices, with the merit of avoiding the exposure of conducting metals to neural tissues.

A Microfluidic System for Stable and Continuous EEG Monitoring from Multiple Larval Zebrafish.

Along with the increasing popularity of larval zebrafish as an experimental animal in the fields of drug screening, neuroscience, genetics, and developmental biology, the need for tools to deal with multiple larvae has emerged. Microfluidic channels have been employed to handle multiple larvae simultaneously, even for sensing electroencephalogram (EEG). In this study, we developed a microfluidic chip capable of uniform and continuous drug infusion across all microfluidic channels during EEG recording. Owing to the modular design of the microfluidic channels, the number of animals under investigation can be easily increased. Using the optimized design of the microfluidic chip, liquids could be exchanged uniformly across all channels without physically affecting the larvae contained in the channels, which assured a stable environment maintained all the time during EEG recording, by eliminating environmental artifacts and leaving only biological effects to be seen. To demonstrate the usefulness of the developed system in drug screening, we continuously measured EEG from four larvae without and with pentylenetetrazole application, up to 60 min. In addition, we recorded EEG from valproic acid (VPA)-treated zebrafish and demonstrated the suppression of seizure by VPA. The developed microfluidic system could contribute to the mass screening of EEG for drug development to treat neurological disorders such as epilepsy in a short time, owing to its handy size, cheap fabrication cost, and the guaranteed uniform drug infusion across all channels with no environmentally induced artifacts.

An EEG system to detect brain signals from multiple adult zebrafish.

Zebrafish has been widely used as an experimental animal in many biological processes to study brain functions, neurological disorders and drug toxicity. Electroencephalogram (EEG), which directly measures brain activities, has been used to diagnose and study neurological disorders. Previous studies have recorded EEG signals from adult zebrafish, but the recordings have been only possible from a single individual. In this study, we developed a system to record EEG of multiple adult zebrafish simultaneously. To secure multiple zebrafish in a stable condition for a certain time, perfusion and recording systems were mechanically separated, which allowed effective immobilization of the fish. We recorded EEG signals from pentylenetetrazole (PTZ)-induced seizure models and valproic acid (VPA)-treated models to demonstrate the performance of the developed system in validation of the effect of anti-epileptic drugs. The developed system effectively measured individual EEG signals from more than three zebrafish out of four simultaneously on average. Seizure induction by PTZ and seizure suppression by VPA were successfully detected through EEG recording. The scheme of the EEG recording system developed in this study has a potential for expansion and could be further applied to mass drug screening in a short time.

A Batteryless, Wireless Strain Sensor Using Resonant Frequency Modulation.

In this study, we demonstrated the feasibility of a wireless strain sensor using resonant frequency modulation through tensile impedance test and wireless sensing test. To achieve a high stretchability, the sensor was fabricated by embedding a copper wire with high conductivity in a silicone rubber with high stretchability, in which the resonant frequency can be modulated according to changes in strain. The characteristics of the sensor and the behavior of wireless sensing were calculated based on equations and simulated using finite element method. As the strain of the sensor increased, the inductance increased, resulting in the modulation of resonant frequency. In experimental measurement, as the strain of the sensor increased from 0% to 110%, its inductance was increased from 192 nH to 220 nH, changed by 14.5%, and the resonant frequency was shifted from 13.56 MHz to 12.72 MHz, decreased by 6.2%. It was demonstrated that using the proposed sensor, strains up to 110% could be detected wirelessly up to a few centimeters.

Factors associated with satisfaction with pediatric emergency department services in Korea: analysis of Korea Health Panel Data 2010 to 2012.

OBJECTIVE: We aimed to investigate the factors related to satisfaction with the pediatric emergency department service in Korea. METHODS: This study examined data from the Korea Health Panel Data from 2010 to 2012. Pediatric patients who visited the emergency department at least once between 2010 and 2012 in Korea were included. Data were collected on patient satisfaction with the emergency department service, and factors related to the patient characteristics, emergency department service process, and medical institution. We compared the dissatisfied and satisfied groups, and calculated the odds ratios for satisfaction according to each variable. RESULTS: A total of 1,505 emergency department visits from 947 pediatric patients during the 3-year period were analyzed. We estimated that about 79.5% of patients in the population were satisfied. The odds of expressing satisfaction were higher among males than in females, and among patients who were hospitalized after emergency department treatment compared to those who were transferred to another hospital. Conversely, the odds of expressing satisfaction were lower among patients who had a chronic disease, a financial source other than National Health Insurance, experienced hospitalization within 1 year. CONCLUSION: Our study results might be helpful for establishing a satisfactory pediatric emergency medical service system. In the future, further prospective studies evaluating the causal relationships between the relevant factors and patient satisfaction are warranted.

Development of an intrafascicular neural interface for peripheral nerve implantation.

This paper describes an intrafascicular neural interface for peripheral nerve implantation. The flexible penetrating microelectrode array with varying lengths (vl-FPMA), interconnection cable, wireless recording and stimulator modules were designed and fabricated to detect neural signals from the peripheral nerves or to stimulate them. The vl-FPMA consisted of silicon needles and polydimethylsiloxane (PDMS) platform supporting the needles. The length of electrode needles varied from 600 to 1000 µm. The interconnection cable was fabricated as parylene-metal-parylene sandwiched structure. The wireless recording/stimulation modules were also developed and connected with the electrodes. The integrated system was implanted in the sciatic nerve of beagles and the recording capability of the integrated system was demonstrated successfully.

Targeting delivery of tocopherol and doxorubicin grafted-chitosan polymeric micelles for cancer therapy: In vitro and in vivo evaluation.

In this study, we report the development of a novel, redox-sensitive chitosan-based targeted drug delivery system, containing two drugs. We determined whether the synthesized polymeric micelles (HPTOC-DOX) were suitable as a drug carrier. The formation of HPTOC-DOX micelles was confirmed by (1)H NMR. HPTOC-DOX formed micelles of approximately 151.9-311.2nm in size in aqueous solution. Analysis of the drug release profile of HPTOC-DOX in different pH conditions (pH 5.2, 6.2, and 7.4) indicated that DOX was released from HPTOC-DOX micelles at acidic pH (5.2 or 6.2), while almost no DOX was released at pH 7.4. In vitro cell cytotoxicity and hemolysis assays indicated that HPTOC-DOX micelles safely deliver anti-cancer drugs and decrease the cytotoxicity of DOX. In vitro anti-cancer activity assays, confocal laser scanning microscopy analysis of SK-BR-3 cells, and in vivo anti-tumor activity in SK-BR-3-derived tumor-bearing mice were used to evaluate synergistic drug effects and the effect of the targeting peptide (anti-human epidermal growth factor receptor 2 [HER2] target peptide, epitope form; LTVSPWY) on receptor-mediated endocytosis.