Long-term follow-up results of facial nerve schwannoma with good facial nerve function: a multicenter study.

PURPOSE: Facial nerve schwannomas (FNSs) are rare intracranial tumors, and the optimal management of these tumors remains unclear. We investigated the long-term follow-up results of FNS with good facial nerve function. METHODS: At nine medical centers in the Korean Facial Nerve Study Group, 43 patients undergoing observation periods longer than 12 months for FNS with good facial nerve function (House-Brackmann grade ≤ II) were enrolled, and clinical and radiographic data were obtained for these cases. RESULTS: The mean follow-up period was 63 months. In the majority of cases, tumors involved multiple segments (81.4%) and only eight cases were confined to a single site. There were no cases where the tumor was confined to the extratemporal region. Tumor size increased slightly, with an average estimated change of 0.48 mm/year. Twenty (46.5%) of 43 patients showed no change in tumor size. Seven patients (16.3%) showed worsening House-Brackmann (H-B) grade, of which two patients deteriorated from H-B grade I to II, four worsened to grade III, and one deteriorated to grade IV. The remaining 36 patients (83.7%) showed no change in facial nerve function. There was no difference in H-B grade according to tumor size at the time of diagnosis or change in tumor size. CONCLUSION: We conducted a large-scale observational study of FNS with good facial nerve function. Our study showed that many patients maintained facial nerve function during long-term follow-up. Conservative management with regular examination and imaging can be an appropriate option for managing FNS with good facial nerve function.

Assessing the accuracy and reliability of application-based audiometry for hearing evaluation.

Pure-tone audiometry (PTA) is the gold standard for assessing hearing loss. However, traditional PTA tests require specialized equipment, trained personnel, and a soundproof environment. Recently, smartphone-based PTA tests have been developed as an alternative method for hearing assessment. The aim of this study was to validate the accuracy and reliability of a smartphone application-based audiometry test. This study was conducted to assess the performance of application-based audiometry from November 2021 to January 2022. Pure-tone thresholds were measured using a smartphone application-based PTA test and compared with results obtained using a traditional audiometer in a sound-treated booth. The smartphone application used in this study was the "Care4Ear (Care4ear, version 1.0.6, MIJ Co., Ltd.)". Hearing thresholds less than 35 dB HL were classified as group A, 35-64 dB HL as group B, and 65 dB HL or greater as group C for the classification of hearing levels. We evaluated the accuracy of smartphone audiometry for each group and compared the results of frequency-specific hearing tests. Additionally, we examined the results of smartphone audiometry in individuals (n = 27) with asymmetric hearing loss. Seventy subjects completed both conventional audiometry and smartphone application-based hearing tests. Among the ears assessed, 55.7% were classified as group A, while 25.7% and 18.6% were classified as group B and group C, respectively. The average hearing threshold obtained from conventional pure-tone audiometry was 37.7 ± 25.2 dB HL, whereas the application-based hearing test yielded thresholds of 21.0 ± 23.0 dB HL. A significant correlation (r = 0.69, p < 0.01) was found between the average hearing thresholds obtained from the application-based and conventional pure-tone audiometry tests. The application-based test achieved a 97.4% hit rate for classifying hearing thresholds as class A, but lower rates of 22.2% for class B and 38.5% for class C. Notably, a discrepancy was observed between the hearing threshold measured by the application and the conventional audiometry for the worse ear with asymmetric hearing. The smartphone-based audiometry is a feasible method for hearing evaluation especially in persons with normal hearing. In cases of hearing loss or asymmetric hearing loss, the results of the application-based audiometry may be inaccurate, limiting its diagnostic utility.

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.

Infiltrative fibrous lesion of the facial nerve mimicking a facial nerve tumor.

PURPOSE: To report three cases of facial nerve lesions that were clinically expected to be facial nerve tumors but showed fibrotic infiltration without any apparent signs of a specific tumor on histopathological findings. We also aimed to investigate the clinical characteristics of these cases. METHODS: Medical records of patients who underwent surgery for facial nerve lesions were reviewed. RESULTS: All three cases initially had House-Brackmann (HB) grade IV-V facial nerve palsy. On radiological imaging, schwannoma or glomus tumor originating from the facial nerve was suspected. All patients underwent complete surgical removal of the neoplasm followed by facial nerve reconstruction using the sural nerve. The lesions were histologically confirmed as infiltrative fibrous lesions without tumor cells. In two cases, facial nerve palsy improved to HB grade III by nine months post-surgery, and there were no signs of recurrence on follow-up MRI. The other case, after 1 year of follow-up, showed persistence of HB grade V facial nerve palsy without any evidence of recurrence. CONCLUSION: Fibrotic lesions of the facial nerve could mimic primary facial nerve tumors. Clinicians should consider this condition even when a facial nerve tumor is suspected.

Diabetes Mellitus and Acute Facial Palsy: A Nationwide Population-Based Study.

INTRODUCTION: Acute facial palsy, characterized by sudden hemifacial weakness, significantly impacts an individual's quality of life. Despite several predisposing factors identified for acute facial palsy, the specific relationship between diabetes mellitus (DM) and acute facial palsy has not been comprehensively explored in recent studies. The aim of the study was to assess the risk of acute facial palsy in patients with DM using a nationwide population sample cohort. METHODS: DM cohort and non-DM cohort were built using the Korean National Health Insurance Service-Sample Cohort which represents the entire population of the Republic of Korea from January 2002 to December 2019. The DM cohort comprised 92,872 patients with a record of medication and a diagnosis of DM. Individuals who had facial palsy before the diagnosis of DM were excluded. A comparison cohort comprised 1,012,021 individuals without DM matched sociodemographically in a 1:4 ratio. The incidence of Bell's palsy (BP) and Ramsay Hunt syndrome (RHS) were evaluated in both cohorts. The risk factors for acute facial palsy were also assessed. RESULTS: Among the 92,868 patients in the DM cohort, the incidence rate (IR) of BP and RHS were 31.42 (confidence interval [CI], 30.24-32.63) and 4.58 per 10,000 person-years (CI, 4.14-5.05), respectively. Among the 371,392 individuals in the non-DM cohort, the IR of BP was 22.11 per 10,000 person-years (CI, 21.62-22.59) and the IR of RHS was 2.85 per 10,000 person-years (CI, 2.68-3.02). IR ratios for BP and RHS were 1.42 (CI, 1.36-1.48) and 1.61 (CI, 1.43-1.80). In multivariate analysis, DM (hazard ratio [HR] 1.428), age (HR 1.008), and high comorbidity score (HR 1.051) were associated with increased risk of BP, and male (HR 0.803) and living in metropolis (HR 0.966) decreased the risk of BP. And DM (HR 1.615), high comorbidity score (HR 1.078), and living in metropolis (HR 1.201) were associated with increased risk for RHS. CONCLUSION: This study suggests that patients with DM had an increased risk of acute facial palsy including BP and RHS.

A prognostic value of estimated pulse wave velocity in idiopathic sudden sensorineural hearing loss.

PURPOSE: Arterial stiffness, represented by estimated pulse wave velocity (ePWV), is the independent surrogate marker for cardiovascular event. The aim of the study was to investigate the significance of ePWV in the treatment outcome of idiopathic sudden sensorineural hearing loss (SSNHL). METHODS: One hundred and ten patients with idiopathic SSNHL who hospitalized between April 2019 and March 2022 were evaluated. Arterial stiffness was calculated with formula for ePWV and other cardiovascular parameters of body mass index (BMI), and serum lipid level was determined. All patients received systemic high-dose steroid therapy and intratympanic steroid injections as a salvage management. Treatment outcome was assessed at 6 months after treatment, and classified as recovery and nonrecovery groups according to hearing recovery. RESULTS: The initial pure-tone hearing threshold was 72.6 ± 23.8 dB and final hearing threshold was 52.63 ± 31.10 dB. After treatment, 60 (54.5%) patients included in recovery group and other 50 (45.5%) were classified as nonrecovery group. Age, days of onset to treatment, BMI, waist circumference, and ePWV were higher in the nonrecovery group compared to recovery group in univariate analysis (p = 0.039, p = 0.049, p = 0.003, p = 0.004, p = 0.007, respectively). In multivariate analysis, days of onset to treatment, BMI, and ePWV were associated with recovery (p = 0.030, p = 0.007, p = 0.022). CONCLUSION: Higher ePWV, a measure of arterial stiffness, was associated with a poor hearing recovery of SSNHL.

A content analysis of YouTube videos on tinnitus in South Korea.

More people use the internet for medical information, especially YouTube. Nevertheless, no study has been conducted to analyze the quality of YouTube videos about tinnitus in Korea. This study aims to review the contents and quality of YouTube videos on tinnitus. The top 100 Korean YouTube videos on tinnitus were reviewed by a tinnitus expert. This study assessed video details: title, creator, length, and popularity indicators-subscribers, views, and likes. The contents of the video clips were analyzed to determine the relevance, understandability, actionability, and quality of information. Out of 100 tinnitus videos, 27 were created by otolaryngologists, 25 by traditional Korean medicine doctors, 25 by other medical professionals, and 3 by lay persons. Sensorineural tinnitus was frequently dealt, and hearing loss, stress, and noise were introduced as main causes of tinnitus. Otolaryngologists' videos covered verified treatments, but others suggested unproven therapies including herbal medicine or acupressure. Otolaryngologists' videos showed significantly higher understandability and quality of information compared to others (p < 0.001). This study found that tinnitus YouTube videos frequently present low-quality and incorrect material, which could have an adverse effect on patients. Results highlight the need for tinnitus specialists to provide accurate information.

Findings of Intravenous Gadolinium Inner Ear Magnetic Resonance Imaging in Patients With Acute Low-Tone Sensorineural Hearing Loss.

OBJECTIVES: Acute low-tone sensorineural hearing loss (ALHL) is thought to have a different etiology from that of idiopathic sudden sensorineural hearing loss. We hypothesized that endolymphatic hydrops (EH) in the inner ear organ contributes to ALHL, even in patients without vertigo. This study investigated the presence of EH in ALHL and compared the clinical characteristics of patients with or without EH. METHODS: We retrospectively reviewed 38 patients diagnosed with ALHL without vertigo from January 2017 to March 2022. EH was measured in all patients using inner ear magnetic resonance imaging (MRI). In addition, we selected patients who showed only mid- or high-frequency hearing loss and had available MRI data as a control group and compared the ALHL and control groups. RESULTS: After treatment, the pure-tone average at low frequencies significantly improved compared to the initial hearing (P<0.001). Hearing recovery was observed in 63.1% of patients; however, the recovery rate did not differ based on the treatment method. During the follow-up period, six patients (15.8%) progressed to Meniere's disease, and 18 (47.4%) experienced recurrence. In the ALHL group, the cochlear hydrops ratio on the affected side (0.34±0.09) was significantly higher than on the contralateral side (0.29±0.12) (P=0.005), and most patients showed hydrops in the apex area of the cochlea. Compared with the control group (0.25±0.15), the ALHL group showed a significantly higher cochlear hydrops ratio (P=0.043). The correlation analysis showed a tendency for hearing thresholds at low frequencies to increase as the hydrops ratio increased, albeit without statistical significance. CONCLUSION: The cochlear hydrops ratio, especially in the apex area on the affected side, was significantly higher in patients with ALHL, suggesting that EH in the cochlea contributes to the pathogenesis of ALHL.

Structural changes in the retina after implantation of subretinal three-dimensional implants in mini pigs.

The retinal structural changes after subretinal implantation of three-dimensional (3D) microelectrodes were investigated in a mini pig. Three types of electrode were implanted into the subretinal spaces of nine mini pigs: 75-µm-high 3D electrodes on a 200-µm-thick right-angled polydimethylsiloxane (PDMS) substrate (group 1); a 140-µm-thick sloped PDMS substrate without electrodes (group 2); and a 140-µm-thick sloped PDMS substrate with 20-µm-high 3D electrodes (group 3). One mini pig was used as a control. Spectral domain-optical coherence tomography (SD-OCT) images were obtained at baseline and 2, 6, and 12 weeks post-surgery. Retinal specimens were immunostained using a tissue-clearing method 3 months post-implantation. The 75-µm-high 3D electrodes progressively penetrated the inner nuclear layer (INL) and touched the inner plexiform layer (IPL) 2 weeks post-surgery. At 6 weeks post-operatively, the electrodes were in contact with the nerve-fiber layer, accompanied by a severe fibrous reaction. In the other groups, the implants remained in place without subretinal migration. Immunostaining showed that retinal ganglion and bipolar cells were preserved without fibrosis over the retinal implants in groups 2 and 3 during the 12-week implantation period. In summary, SD-OCT and immunohistology results showed differences in the extent of reactions, such as fibrosis over the implants and penetration of the electrodes into the inner retinal layer depending on different types of electrodes. A sloped substrate performed better than a right-angled substrate in terms of retinal preservation over the implanted electrodes. The 20-µm-high electrodes showed better structural compatibility than the 75-µm-high 3D electrodes. There was no significant difference between the results of sloped implants without electrodes and 20-µm-high 3D electrodes, indicating that the latter had no adverse effects on retinal tissue.

Possible Existence of Cochlear Synaptopathy in Patients Completely Recovered from Idiopathic Sudden Sensorineural Hearing Loss.

Cochlear synaptopathy refers to a subclinical hearing pathology which could potentially explain hearing difficulties within the normal hearing threshold; it is also called "hidden hearing loss". We hypothesized that a temporary threshold shift in sudden sensorineural hearing loss (ISSNHL) also affects the function in the synapse. The aim of the study was to evaluate the presence of cochlear synaptopathy in patients who had completely recovered from unilateral SSNHL Nineteen patients who had completely recovered from ISSNHL from January 2018 to June 2021 were assessed. Complete recovery was established by pure tone audiometry (PTA) 3 months after treatment, according to the American Academy of Otolaryngology-Head and Neck Surgery criteria. Subjects completed the pure tone audiometry, speech audiometry and auditory brain stem response (ABR) test, and completed a questionnaire regarding hearing loss after hearing recovery. The ABR amplitudes of wave I and wave V, and the ratio of wave I/V of both ears (recovered side and healthy side) were assessed. A visual analog scale (VAS) and a hidden hearing loss questionnaire were used to evaluate subjective hearing difficulty. The ABR waves I of the recovered ears had a significantly lower amplitude (p = 0.002) than those of the healthy side, whereas there was no difference in wave V (p = 0.985) or in the ratio of wave I/V (p = 0.107). Some patients still felt mild hearing difficulty although their PTA results were normal, but there was no clear relationship between the VAS score, wave I amplitude and speech recognition scores. The present findings point to the possible existence of cochlear synaptopathy in ears that have completely recovered from unilateral sudden sensorineural hearing loss. We suggest that the causes of cochlear synaptopathy and of idiopathic sudden hearing loss may have something in common.

Vestibular mapping assessment in idiopathic sudden sensorineural hearing loss.

OBJECTIVE: The aim of this study was to investigate patterns of semicircular canal (SCC) and otolith organ dysfunction by vestibular mapping, and to determine the clinical implications of treatment outcomes in idiopathic sudden sensorineural hearing loss (ISSNHL). METHODS: We retrospectively reviewed 135 consecutive patients diagnosed with ISSNHL from January 2016 to December 2020. Patients underwent video-head impulse tests (vHIT) for each SCC, cervical vestibular-evoked myogenic potential test for the saccules, ocular vestibular-evoked myogenic potential test for the utricles, and hearing tests. Hearing outcomes were evaluated according to the American Academy of Otolaryngology-Head and Neck Surgery criteria and factors associated with prognosis were assessed. We also conducted vestibular mapping assessments and hierarchical cluster analysis. RESULTS: Overall, utricular impairment (76, 56.3%) was the most frequent diagnosis in the 135 ISSNHL patients, followed by saccular impairment (59, 43.7%) and posterior SCC impairment (30, 22.2%). The mean number of affected end organs was 1.37 ± 1.24, with higher numbers in the complete recovery group than in the partial/no recovery groups. In a multivariate analysis, higher initial hearing level and abnormal vHIT results in the posterior SCC were associated with poor prognosis in ISSNHL. In hierarchical cluster analysis, horizontal SCC and anterior SCC showed the highest similarity but were in different clusters than posterior SCC, and the saccule and utricle were in separate clusters from the three SCCs. CONCLUSIONS: The vestibular end organ showed various patterns of dysfunction in patients with ISSNHL. Of the five vestibular end organs, only abnormal posterior SCC was associated with poor prognosis for hearing recovery.

Long-termin-vivorecording performance of flexible penetrating microelectrode arrays.

Objective. Neural interfaces are an essential tool to enable the human body to directly communicate with machines such as computers or prosthetic robotic arms. Since invasive electrodes can be located closer to target neurons, they have advantages such as precision in stimulation and high signal-to-noise ratio (SNR) in recording, while they often exhibit unstable performance in long-termin-vivoimplantation because of the tissue damage caused by the electrodes insertion. In the present study, we investigated the electrical functionality of flexible penetrating microelectrode arrays (FPMAs) up to 3 months inin-vivoconditions.Approach. Thein-vivoexperiment was performed by implanting FPMAs in five rats. Thein-vivoimpedance as well as the action potential (AP) amplitude and SNR were analyzed over weeks. Additionally, APs were tracked over time to investigate the possibility of single neuron recording.Main results. It was observed that the FPMAs exhibited dramatic increases in impedance for the first 4 weeks after implantation, accompanied by decreases in AP amplitude. However, the increase/decrease in AP amplitude was always accompanied by the increase/decrease in background noise, resulting in quite consistently maintained SNRs. After 4 weeks of implantation, we observed two distinctive issues regarding long-term implantation, each caused by chronic tissue responses or by the delamination of insulation layer. The results demonstrate that the FPMAs successfully recorded neuronal signals up to 12 weeks, with very stably maintained SNRs, reduced by only 16.1% on average compared to the first recordings, although biological tissue reactions or physical degradation of the FPMA were present.Significance. The fabricated FPMAs successfully recorded intracortical signals for 3 months. The SNR was maintained up to 3 months and the chronic function of FPMA was comparable with other silicon based implantable electrodes.

Purple corn extract alleviates 2,4-dinitrochlorobenzene-induced atopic dermatitis-like phenotypes in BALB/c mice.

Zea mays L. (Poaceae), also known as purple corn, is an annual herbaceous plant that is grown as food for human consumption in a variety of forms, including cooking oils and sweeteners in processed food and beverage products. The purpose of this study was to determine whether a novel purple corn extract, FB801, might have an anti-atopic dermatitis (AD) effect on AD-like skin lesions induced by 2,4-dinitrochlorobenzene (DNCB) in BALB/c mice. Topical sensitization (1%) and challenge (0.3%) by DNCB were performed on the dorsal skin and right ear of BALB/c mice to induce AD. Following FB801 and dexamethasone administered orally, the severity of skin lesions was examined macroscopically and histologically. Serum levels of immunoglobulin E (IgE) and various cytokines were determined by enzyme-linked immunosorbent assay. Oral administration of FB801 significantly reduced typical symptoms of AD (erythema/bleeding, swelling, molting/erosion and scaling/drying), scratching frequencies, and the recruitment of inflammatory and mast cells. In addition, FB801 suppressed serum levels of IgE and T helper (Th)2 type cytokines such as interleukin (IL)-4 and IL-10 in DNCB-treated BALB/c mice. Furthermore, FB801 reduced the degradation of inhibitor of nuclear factor-κB proteins (NF-κB) in tumor necrosis factor (TNF)-α-stimulated human keratinocyte (HaCaT) cells. These results suggest that FB801 inhibited the development of the AD-like skin symptoms by regulating Th1 and Th2 responses in the skin lesions in mice and suppressing TNF-α induced NF-κB activation in HaCaT cells, suggesting that FB801 has potential application as an effective alternative therapy for the prevention and management of AD.

Expression of an immunocomplex consisting of Fc fragment fused with a consensus dengue envelope domain III in Saccharomyces cerevisiae.

OBJECTIVES: To explore Saccharomyces cerevisiae as an expression platform for dengue oral immune complex vaccine development. RESULTS: Molecular engineering was applied to create a fusion gene construct (scEDIII-PIGS) consisting of a yeast codon optimized sequence encoding for a synthetic consensus dengue envelope domain III (scEDIII) followed by a modified IgG Fc domain (PIGS). Northern blot showed transcription of the target gene, with a temporal expression pattern similar to those from previous work. Western blot showed assembly of various immune complexes from monomer to hexamer. Partial purification of scEDIII-PIGS was also attempted to demonstrate the feasibility of yeast system for immune complex vaccine development. Approximately 1 mg of scEDIII-PIGS can be produced from 1 l culture. CONCLUSION: This work demonstrated for the first time that various immunocomplex structures of our target protein could be efficiently produced in S. cerevisiae for future application in developing oral and injectable vaccines against various pathogens.

Surgical Outcomes and Efficacy of Isthmusectomy in Single Isthmic Papillary Thyroid Carcinoma: A Preliminary Retrospective Study.

BACKGROUND AND OBJECTIVES: The optimal extent of surgery needed for isthmic papillary thyroid carcinoma (PTC) is not well-defined, although total thyroidectomy is usually recommended. This study aimed to evaluate the efficacy of isthmusectomy in the surgical treatment of isthmic PTC. Materials and Methods: We retrospectively studied 121 patients who underwent thyroidectomy with or without central neck dissection (CND) for single isthmic PTC from January 2003 to June 2019. We excluded patients who were clinically suspected to have clinically positive cervical lymph node metastasis and gross extrathyroidal extension or to have cancers at sites other than the thyroid isthmus. Patients were divided into three groups according to the extent of thyroidectomy-total thyroidectomy, lobectomy with isthmusectomy (the lobectomy group), and isthmusectomy. Clinical and pathologic characteristics, surgical outcomes, recurrence rate, and survival were analyzed. Results: Of 121 isthmic PTC patients, 28 were men and 93 were women. Total thyroidectomy, lobectomy with isthmusectomy, and isthmusectomy were performed in 70 (57.8%), 40 (33.1%), and 11 (9.1%) patients, respectively. Prophylactic CND was performed in 104 (86%) patients. In a subgroup analysis, patients who underwent total thyroidectomy showed higher postoperative hypoparathyroidism (p < 0.001) than those who underwent lobectomy and isthmusectomy. However, there were no differences in the recurrence rate or survival between the three groups. Conclusion: Thyroid isthmusectomy may be effective in the surgical treatment of small single isthmic PTC. Further studies are necessary to verify this result.

Ab-interno surgical technique for the implantation of a wireless subretinal prosthesis in mini-pigs.

We sought to describe the surgical techniques required in the ab-interno method to implant subretinal prostheses in mini-pigs and suggest tips to facilitate optimal outcomes. During vitrectomy, the use of valved trocar cannulas was essential to stabilize the detached retina and implanted chip. As a first step in retinal detachment, a 23-gauge cannula with very small amount of viscoelastic material was used to establish the retinal hole and promote retinal detachment. Then, balanced salt solution was applied to increase the retinal detachment and diathermy was used to make opening for subretinal prosthesis. For easy positioning of the subretinal prosthesis, a curved laser probe was adopted when handling the subretinal prosthesis under the retina. After surgery, the sclerotomy sites were tightly sutured to prevent silicone oil leakage. Without special equipment, such as a 41-gauge tip, retinal detachment could be induced easily, while the prosthesis was also successfully inserted and manipulated under the retina without an iatrogenic retinal tear. Two weeks after the operation, the oil fully occupied the intraocular volume without leakage. The subretinal prosthesis remained stable without complication. Understanding the principle of the ab-interno method and considering several tips for improving surgical access may help to enhance surgical success rates of subretinal prostheses implantation.

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.

Heat dissipative mechanical damping properties of EPDM rubber composites including hybrid fillers of aluminium nitride and boron nitride.

As highly integrated electronic devices and automotive parts are becoming used in high-power and load-bearing systems, thermal conductivity and mechanical damping properties have become critical factors. In this study, we applied two different fillers of aluminium nitride (AlN) and boron nitride (BN), having polygonal and platelet shapes, respectively, into ethylene-propylene-diene monomer (EPDM) rubber to ensure improved thermo-mechanical properties of EPDM composites. These two different shapes are considered advantageous in providing effective pathways of phonon transfer as well as facilitating sliding movement of packed particles. When the volume ratio of AlN : BN was 1 : 1, the thermal conductivity of the hybrid-filler system (EPDM/AlN/BN) increased in comparison to that of the single-filler system (EPDM/AlN) of 3.03 to 4.76 W m-1 K-1. The coefficient of thermal expansion (CTE) and thermal distortion parameter (TDP) substantially decreased from 59.3 ppm °C-1 and 17.5 m K-1 of EPDM/AlN, to 39.7 ppm °C-1 and 8.4 m K-1 of EPDM/AlN/BN, representing reductions of 33 and 52%, respectively. Moreover, the damping coefficient of EPDM/AlN/BN was greatly increased to 0.5 of at 50 °C, compared to 0.03 of neat EPDM. These excellent performances likely stem from the effective packing of AlN/BN hybrid fillers, which could induce facile energy transfer and effective energy dissipation by the sliding movement of the adjacent hybrid fillers in the EPDM matrix.

Sappanchalcone, a flavonoid isolated from Caesalpinia sappan L., induces caspase-dependent and AIF-dependent apoptosis in human colon cancer cells.

The present study examined the apoptotic effects and the underlying mechanism of sappanchalcone, a major bioactive compound isolated from Caesalpinia sappan L. on human colon cancer cells. To achieve this, we used two different colon cancer cell lines, namely HCT116 (as wild-type p53 cells) and SW480 (as p53-mutant cells) cells. Our results illustrated that sappanchalcone treatment decreased the proliferation and further promoted apoptosis in HCT116 cells compared with the findings in SW480 cells. Sappanchalcone triggered phosphorylation of p53, which is involved in the activation of caspases and increased expression of Bax in HCT116 cells. Conversely, sappanchalcone-treated SW480 cells displayed no change in p53 phosphorylation or caspase activation. In addition, sappanchalcone further increased reactive oxygen species (ROS) levels and apoptosis-inducing factor (AIF) release in both HCT116 and SW480 cells. These data suggest that sappanchalcone induces apoptosis through caspase-dependent and caspases-independent mechanisms that were characterized by decreased Bcl-2 expression, mitochondrial targeting, and altered ROS production and AIF translocation to the nuclei.

Fabrication of Subretinal 3D Microelectrodes with Hexagonal Arrangement.

This study presents the fabrication of three-dimensional (3D) microelectrodes for subretinal stimulation, to accommodate adjacent return electrodes surrounding a stimulating electrode. For retinal prosthetic devices, the arrangement of return electrodes, the electrode size and spacing should be considered together, to reduce the undesired dissipation of electric currents. Here, we applied the hexagonal arrangement to the microelectrode array for the localized activation of retinal cells and better visual acuity. To provide stimuli more efficiently to non-spiking neurons, a 3D structure was created through a customized pressing process, utilizing the elastic property of the materials used in the fabrication processes. The diameter and pitch of the Pt-coated electrodes were 150 µm and 350 µm, respectively, and the height of the protruded electrodes was around 20 µm. The array consisted of 98 hexagonally arranged electrodes, supported by a flexible and transparent polydimethylsiloxane (PDMS) base, with a thickness of 140 µm. Also, the array was coated with 2 µm-thick parylene-C, except the active electrode sites, for more focused stimulation. Finally, the electrochemical properties of the fabricated microelectrodes were characterized, resulting in the mean impedance of 384.87 kΩ at 1 kHz and the charge storage capacity (CSC) of 2.83 mC·cm-2. The fabricated microelectrodes are to be combined with an integrated circuit (IC) for additional in vitro and in vivo experiments.