Trends in Distributions of Hearing Threshold Levels by Ages: A Comparison of the ISO 7029 and Newly Available Country-Specific Data.

Hearing thresholds provide essential information and references about the human auditory system. This study aimed to identify changing trends in distributions of hearing threshold levels across ages by comparing the International Organization for Standardization (ISO) 7029 and newly available data after publishing ISO 7029. To compare ISO 7029 and newly available hearing threshold data after publishing ISO 7029, four country-specific datasets that presented average hearing threshold levels under conditions similar to ISO 7029 were utilized. For frequencies between 125 Hz and 8,000 Hz, the deviations of hearing threshold values by ages from the hearing threshold of the youngest age group for each data point were utilized. For frequencies from 9,000 Hz to 12,500 Hz, the median threshold information was utilized. Hearing threshold data reported after publishing ISO 7029 from the four countries were mostly similar to the ISO 7029 data but tended to deviate in some age groups and sexes. As national hearing threshold trends change, the following ISO 7029 revision suggests the need to integrate hearing threshold data from different countries.

Auditory Brainstem Response Data Preprocessing Method for the Automatic Classification of Hearing Loss Patients.

Auditory brainstem response (ABR) is the response of the brain stem through the auditory nerve. The ABR test is a method of testing for loss of hearing through electrical signals. Basically, the test is conducted on patients such as the elderly, the disabled, and infants who have difficulty in communication. This test has the advantage of being able to determine the presence or absence of objective hearing loss by brain stem reactions only, without any communication. This paper proposes the image preprocessing process required to construct an efficient graph image data set for deep learning models using auditory brainstem response data. To improve the performance of the deep learning model, we standardized the ABR image data measured on various devices with different forms. In addition, we applied the VGG16 model, a CNN-based deep learning network model developed by a research team at the University of Oxford, using preprocessed ABR data to classify the presence or absence of hearing loss and analyzed the accuracy of the proposed method. This experimental test was performed using 10,000 preprocessed data, and the model was tested with various weights to verify classification learning. Based on the learning results, we believe it is possible to help set the criteria for preprocessing and the learning process in medical graph data, including ABR graph data.

Improving Accuracy and Reliability of Hearing Tests: An Exploration of International Standards.

This study explores the internal standards for hearing tests and benefits of implementing international standard protocols, including the International Organization for Standardization (ISO) and International Electrotechnical Commission (IEC), and discusses how ISO and IEC standards provide a framework for designing, calibrating, assessing hearing test instruments and methods, and exchanging and comparing data globally. ISO and IEC standards for hearing tests improve accuracy, reliability, and consistency of test results by applying standardized methods and environments. Moreover, they promote international harmonization and data interoperability, enabling information exchange and research collaboration. Those standards for hearing tests are beneficial but have challenges and limitations, such as variation in equipment and calibration, lag in updating standards, variation in implementation and compliance, and lack of coverage of clinical aspects, cultural diversity, and linguistic diversity. These affect the quality and interpretation of test results. Adapting ISO or IEC standards locally would improve their applicability and acceptability, while balancing customization and compatibility with global standards.

Lactobacillus plantarum Reduces Low-Grade Inflammation and Glucose Levels in a Mouse Model of Chronic Stress and Diabetes.

This study aimed to examine the effects of Lactobacillus plantarum, a lactic acid bacteria strain isolated from kimchi, on the development of low-grade inflammation and type 2 diabetes mellitus (T2DM) exacerbated by chronic stress. C57BL/6 mice were fed either a high-fat diet (HFD) and randomized into an HFD group or a group that was fed an HFD and subjected to chronic cold exposure-related stress (HFDS), or mice were fed a normal diet (ND) and randomized into an ND group or a group that was fed an ND and subjected to chronic cold exposure-related stress (NDS). Lactobacillus plantarum LRCC5310 (108, 1010 CFU) and LRCC5314 (108, 1010 CFU) as well as L. gasseri BNR17 (108 CFU), as a positive control, were administered orally twice every day to all the mice for 12 weeks. The expression of Glut4 and adiponectin, main glucose transporter-related genes, was upregulated in the LRCC5310- and LRCC5314-treated groups. Levels of serum proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6]) and of mRNAs of proinflammatory genes (Tnf-α, Il-6, Ccl2, leptin) were elevated in HFDS mice. The expression of proinflammatory genes was downregulated in LRCC5310- and LRCC5314-treated groups; this was not the case for Tnf-α expression in HFDS mice. Levels of serum corticosterone and mRNA levels of stress-related genes (Npy, Y2r) were decreased in lactic acid bacteria (LAB)-fed groups, with only LRCC5314 downregulating Npy expression in HFDS mice. These results suggest that the LAB strains can normalize the expression of metabolic genes, inhibit inflammatory responses, and suppress stress in HFDS mice.

Nimodipine and Steroid Combination Therapy for Idiopathic Sudden Sensorineural Hearing Loss.

OBJECTIVE: To evaluate the treatment outcomes of nimodipine and steroid combination therapy for idiopathic sudden sensorineural hearing loss (ISSNHL). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Seventy-eight patients who were diagnosed with ISSNHL were divided into two group based on the treatment strategies used: steroid+nimodipine (SN, n = 36) and steroid only (SO, n = 42) groups. Based on the level of hearing loss before treatment, subgroup analysis (<90 dB HL, SN-S versus SO-S groups; ≥90 dB HL, SN-P versus SO-P groups) was performed. INTERVENTIONS: Nimodipine+dexamethasone versus dexamethasone alone. MAIN OUTCOME MEASURES: Hearing thresholds and complete/partial recovery rate after treatment. RESULTS: Hearing thresholds after treatment were not significantly different between the SN and SO groups (46.8 ±â€Š29.4 versus 54.8 ±â€Š27.6 dB HL, p = 0.218). However, the complete recovery rate was significantly higher in the SN group than in the SO group (41.7% versus 16.8%, p = 0.014). In subgroup analysis, the complete recovery rate was significantly higher in the SN-S group than in the SO-S group (60.9% versus 19.2%, p = 0.003), whereas the difference between the SN-P and SO-P groups was not significant (7.7% versus 12.5%, p = 0.672). The cumulative incidence of complete recovery was significantly higher in SN-S group than in the SO-S group (p = 0.005); the mean recovery time was 4.4 weeks (95% confidence interval [CI], 2.8-6.1) in the SN-S group and 8.8 weeks (95% CI, 7.0-10.5) in the SO-S group. CONCLUSIONS: The results of this study suggest that nimodipine and steroid combination therapy for ISSNHL results in a higher complete recovery rate than steroid alone in patients with moderate to severe hearing loss.

Potential benefits of salvage intratympanic dexamethasone injection in profound idiopathic sudden sensorineural hearing loss.

PURPOSES: To compare hearing recovery levels after initial treatment or salvage intratympanic dexamethasone injection (ITDI), and to find the prognostic factor on salvage ITDI therapy in profound ISSNHL. METHODS: We retrospectively reviewed 115 patients with profound ISSNHL. All patients were treated with combination or systemic steroid therapy as the initial treatment. Next, we used salvage ITDI therapy on patients who showed slight or no improvement according to Siegel's criteria. To find the prognostic factors for the effectiveness of salvage ITDI therapy, we analyzed clinical data, such as, age, sex, vertigo, symptom duration, diabetes, hypertension, initial PTA, pre-salvage PTA, and treatment methods, using multiple regression analyses. RESULTS: The rate of serviceable hearing recovery were 10.4% (12/115) in the initial-treatment group and 20.4% (21/103) in the salvage group. The difference was statistically significant (p = 0.041). Pre-salvage PTA, diabetes mellitus, and symptom duration were affective factors for the effectiveness of salvage ITDI therapy in profound ISSNHL refractory to initial treatment, with odds ratios of 1.169 (95% confidence interval, 1.088-1.256), 0.069 (95% confidence interval, 0.005-0.889), and 9.242 (95% confidence interval, 1.079-79.146). CONCLUSIONS: Salvage therapy should be considered for profound ISSNHL, which is expected to result in poor prognosis or hearing recovery: ITSI therapy might be an effective treatment as salvage therapy.

Impaired Glycolysis Promotes AlcoholExposure-Induced Apoptosis in HEI-OC1 Cells via Inhibition of EGFR Signaling.

Glucose metabolism is an important metabolic pathway in the auditory system. Chronic alcohol exposure can cause metabolic dysfunction in auditory cells during hearing loss. While alcohol exposure has been linked to hearing loss, the mechanism by which impaired glycolysis promotes cytotoxicity and cell death in auditory cells remains unclear. Here, we show that the inhibition of epidermal growth factor receptor (EGFR)-induced glycolysis is a critical mechanism for alcohol exposure-induced apoptosis in HEI-OC1 cells. The cytotoxicity via apoptosis was significantly increased by alcohol exposure in HEI-OC1 cells. The glycolytic activity and the levels of hexokinase 1 (HK1) were significantly suppressed by alcohol exposure in HEI-OC1 cells. Mechanistic studies showed that the levels of EGFR and AKT phosphorylation were reduced by alcohol exposure in HEI-OC1 cells. Notably, HK1 expression and glycolytic activity was suppressed by EGFR inhibition in HEI-OC1 cells. These results suggest that impaired glycolysis promotes alcohol exposure-induced apoptosis in HEI-OC1 cells via the inhibition of EGFR signaling.

Clinical characteristics and associated factors of canal switch in benign paroxysmal positional vertigo.

BACKGROUND: Canal switch benign paroxysmal positional vertigo (CS-BPPV) is a transition of BPPV involving one canal to another canal during or after canalith repositioning procedures (CRP). OBJECTIVE: To investigate the clinical characteristics of CS-BPPV and its associated factors. METHODS: The data of 2,303 patients with BPPV involving the lateral canal (LC) or posterior canal (PC) were retrospectively analyzed. Demographics, etiologies, and various clinical parameters related to CRP were compared between patients with and without CS-BPPV. RESULTS: Sixty-eight (2.95%) patients exhibited CS-BPPV. For patients with CS-BPPV from the PC to the LC, as well as those with CS-BPPV from the LC to the PC, the CRP number for the original canal in CS-BPPV was significantly greater than in non-CS-BPPV (P = 0.002). More CRP cycles were required to treat CS-BPPV than non-CS-BPPV involving the same canal. Multivariate analysis showed that CS-BPPV from the LC to the PC was significantly associated with multiple CRP cycles and use of the Gufoni maneuver (P = 0.038 and P < 0.001, respectively). CONCLUSIONS: The use of multiple cycles of CRP and the Gufoni maneuver were significantly associated with the onset of CS-BPPV. Furthermore, more CRP cycles were needed for the treatment of CS-BPPV than for non-CS-BPPV involving the same canal.

Cisplatin-Induced Ototoxicity in Rats Is Driven by RIP3-Dependent Necroptosis.

Cisplatin-induced early-onset ototoxicity is linked to hearing loss. The mechanism by which cisplatin causes ototoxicity remains unclear. The purpose of this study was to identify the involvement of receptor-interacting protein kinase (RIP)3-dependent necroptosis in cisplatin-induced ototoxicity in vitro and in vivo. Sprague-Dawley rats (SD, 8 week) were treated via intraperitoneal (i.p.) injection with cisplatin (16 mg/kg for 1 day), and their hearing thresholds were measured by the auditory brainstem response (ABR) method. Hematoxylin and eosin (H & E) staining, immunohistochemistry, and western blots were performed to determine the effect of cisplatin-induced ototoxicity on cochlear morphology. Inhibitor experiments with necrostatin 1 (Nec-1) and Z-VAD were also performed in HEI-OC1 cell line. H&E stains revealed that the necroptotic changes were increased in the organ of Corti (OC) and spiral ganglion neurons (SGNs). Moreover, immunohistochemistry and western blot analysis showed that cisplatin treatment increased the protein levels of RIP3 in both OCs and SGNs. The treatment of Nec-1, a selective RIP1 inhibitor, resulted in markedly suppression of cisplatin-induced cell death in HEI-OC1 cells, whereas Z-VAD treatment did not change the cisplatin-induced cell death. Our results suggest that RIP3-dependent necroptosis was substantial in cisplatin-induced ototoxicity; inner cochlear regions, the OCs, and SGNs were especially sensitive to necroptosis.

Significance of 1 kHz Pure-tone Threshold in Acute Low-frequency Sensorineural Hearing Loss.

OBJECTIVES: To analyze risk factors for acute low-frequency hearing loss (ALFHL), and compare treatment outcomes in the presence or absence of such risk factors. STUDY DESIGN: A case series featuring retrospective chart review. SETTING: An academic university hospital. PATIENTS: We included 170 ALFHL patients without vertigo. All of the patients received one of four treatments: low-dose steroid (LD-steroid), high-dose steroid (HD-steroid), LD-steroid and diuretics (LD-combination therapy), and ITDI (intratympanic dexamethasone injection) and diuretics (ITDI-combination therapy). To identify risk factors, we reviewed the clinical features of patients such as age, sex, chief complaint, accompanying symptoms, diabetes, hypertension, time from disease onset, the extent of hearing loss, treatment methods, and 1 kHz involvement. INTERVENTIONS: ALFHL was diagnosed based on the average hearing loss >30 dB at 250 and 500 Hz. RESULTS: The overall rates of hearing recovery were 70-80% in the four treatment groups. In terms of the prognosis of ALFHL patients, we found that a longer time from disease onset and 1 kHz involvement were independent risk factors for poor prognosis. In addition, we compared treatment outcomes of four treatment methods in the presence or absence of risk factors. In ALFHL patients with risk factors, we found statistically significant differences (p = 0.042) among treatment methods; effectiveness ranged in the order if ITDI-combination therapy, LD-combination therapy, HD-steroid, and LD-steroid. CONCLUSIONS: Risk factors for poor hearing recovery in ALFHL included longer symptom duration and 1 kHz involvement. In ALFHL with such risk factors, combination therapy was more effective than oral steroid therapy.

Potential Risk Factors Affecting Repeated Canalith Repositioning Procedures in Benign Paroxysmal Positional Vertigo.

OBJECTIVE: To define the risk factors and adverse effects associated with repeated canalith repositioning procedures (CRPs). STUDY DESIGN: A case series featuring chart review. SETTING: An academic university hospital. PATIENTS: We retrospectively reviewed 1900 patients (average age, 54.9 years; range, 11-88 years) diagnosed with benign paroxysmal positional vertigo (BPPV). All underwent repeated CRPs. We recorded clinical features including age, gender, BPPV cause (idiopathic or secondary), symptom duration, the canal involved, the number of sessions of CRP, recurrence, follow-up duration, and complications. We compared these factors using Pearson's chi-squared test and multiple linear regression analysis with dummy variables. INTERVENTIONS: BPPV was diagnosed based on the results of the head roll and Dix-Hallpike tests. RESULTS: The overall BPPV resolution rate for patients treated with repeated CRPs was 96.4%. The risk factors for the need for multiple CRPs in BPPV were the duration of vertigo before treatment (ß = 0.326, p < 0.001), the type of canal involved (ß = 0.130, p < 0.001), and age (ß = 0.040, p = 0.040). The explanatory power of the regression model attained 46.0% (F = 172.510, p < 0.001). The failure rate of repeated CRPs was 3.6% and complications included canal conversion (3.1%), nausea (46.4%), vomiting (4.9%), head heaviness (50.8%), imbalance (31.9%), and hypotension or palpitations (8.6%). However, almost all patients recovered. CONCLUSION: The risk factors associated with the need for Multiple CRPs were as follows: longer duration of vertigo before treatment, bilateral or multiple canal involved, and age >50 years.

Differences in clinical characteristics and prognosis of sudden low- and high-frequency hearing loss.

OBJECTIVES/HYPOTHESIS: We compared the clinical characteristics between acute low- and high-frequency hearing loss (LF and HF, respectively) patients, and the efficacy of three different treatment protocols (systemic steroids, intratympanic steroid injection, and combination therapy). STUDY DESIGN: Prospective, randomized controlled study. METHODS: A total of 111 patients diagnosed with LF or HF were treated on an outpatient basis. Each group was randomly divided into three equal subgroups based on therapy: oral steroid, intratympanic dexamethasone injection (IT), and combination therapy. Hearing gain was estimated by comparing pre- and post-treatment pure-tone averages. Recovery rate was assessed by Clinical Practice Guideline: Sudden Hearing Loss from the American Academy of Otolaryngology-Head and Neck Surgery. RESULTS: In comparison of chief complaints, ear fullness and hearing loss were more common in the LF and HF group, respectively (P = .033 and P = .001, respectively). Hearing recovery rates were significantly different between the two groups (i.e., 74.1% [40/54] in the LF group and 45.6% [26/57] in the HF group; P < .001). Oral steroid therapy was most effective in the LF group (P = .017). In the HF group, all three modalities showed similar results, although IT tended to be the most effective (P = .390). CONCLUSIONS: There were differences in chief complaints and treatment responses between LF and HF patients. Although they showed similar partial damage in the cochlea, the pathophysiology of LF and HF may be quite different. LEVEL OF EVIDENCE: 1b. Laryngoscope, 127:1878-1884, 2017.

Effect of low frequency on speech performance with bimodal hearing in bilateral severe hearing loss.

OBJECTIVES/HYPOTHESIS: Unilateral cochlear implantation has emerged as a widely accepted procedure to treat severe to profound hearing loss, but many studies have reported benefits in terms of speech comprehension when listeners with residual low-frequency hearing in the nonimplanted ear use a hearing aid. STUDY DESIGN: Retrospective study. METHODS: In this study, we analyzed the speech performance and satisfaction of bimodal hearing according to the residual low-frequency hearing level in the nonimplanted ear. Based on low-frequency pure-tone audiometry (average of 250 Hz and 500 Hz) in the nonimplanted ear, we classified individuals into three groups as follows: group A (under 70 dB), group B (71-90 dB), and group C (over 91 dB). Listeners were tested using the Word Recognition Score, the Korea-Central Institute for Deaf sentence recognition test, and the Korean version of the Hearing Handicap Inventory for the Elderly questionnaire. RESULTS: We observed a bimodal benefit when the residual low-frequency threshold was less than 70 dB HL and a greater satisfaction with bimodal hearing compared to cochlear implant alone, when the residual low-frequency threshold was less than 70 dB HL. CONCLUSIONS: This study supports the benefits of bimodal hearing in listeners with bilateral severe to profound sensorineural hearing loss as standard clinical practice, when the residual low-frequency hearing threshold is under 70 dB in the nonimplanted ear. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:2817-2822, 2016.

Potential Benefits of Combination Therapy as Primary Treatment for Sudden Sensorineural Hearing Loss.

OBJECTIVE: We analyzed the effectiveness of combination therapy (CT) for idiopathic sudden sensorineural hearing loss (ISSNHL) and the utility of intratympanic dexamethasone injection (ITDI) reapplication as salvage treatment for ISSNHL refractory to CT. STUDY DESIGN: Case series with chart review. SETTING: Academic university hospital. SUBJECTS AND METHODS: We reviewed 229 patients with ISSNHL and divided these patients into 2 groups according to treatment: systemic steroid therapy (SST) and CT groups. The SST group received prednisolone therapy. The CT group also received ITDI daily. Patients who demonstrated no recovery (<10 dB) after initial treatment were defined as refractory and received salvage ITDI therapy: ITDI reapplication in the CT group and ITDI application in the SST group. RESULTS: Hearing recovery rates were 77.8% (77/99) in the CT group and 60.8% (79/130) in the SST group. The difference was statistically significant (P = .011). Initial pure-tone audiometry and vertigo were affective factors on hearing recovery rates in the CT group. After salvage therapy, hearing improvement of 10 dB or greater was noted in 6 of the 22 (27.3%) patients in the CT group and 16 of the 51 (31.4%) patients in the SST group. The difference in efficacy of salvage therapy between the CT and SST groups was simply not significant (P = .612). CONCLUSIONS: Combination therapy was more effective for ISSNHL in achieving hearing gain than SST alone. Furthermore, ITDI reapplication for ISSNHL refractory to CT was as effective as salvage ITDI for ISSNHL refractory to SST.

Canal Paresis in Benign Paroxysmal Positional Vertigo Secondary to Sudden Sensorineural Hearing Loss.

OBJECTIVES: To review the clinical features of benign paroxysmal positional vertigo (BPPV) secondary to sudden sensorineural hearing loss (SNHL) and to analyze the correlation between canal paresis and the effectiveness of canalith repositioning procedures (CRPs) for the treatment. DESIGN: Study case series with chart review. SETTING: Academic university hospital. PATIENTS: We retrospectively reviewed 277 patients with BPPV. For sudden SNHL with a recent vertigo, patients underwent electronystagmography and bithermal caloric tests. We investigated the clinical characteristics including causes, type of involved semicircular canal, frequency of CRPs, treatment results, and canal paresis (CP). INTERVENTIONS: The diagnosis of BPPV accompanied by same-sided sudden SNHL was based on the results of head roll and Dix-Hallpike tests. RESULTS: Of 277 patients with BPPV, 24 (8.7%) had sudden SNHL. Multiple-canal involvement most commonly developed in post-sudden SNHL BPPV (p < 0.01). Patients with post-sudden SNHL BPPV received a greater number of CRPs (2.95) than those with idiopathic BPPV (1.58) (p = 0.043). In patients with post-sudden SNHL BPPV, the average number of CRPs was 3.31 in the presence of CP and 2.1 sessions in the absence of CP (p = 0.030); the CP value was correlated with the frequency of CRPs (p = 0.020). CONCLUSIONS: In post-sudden SNHL BPPV, the worse the canal paresis becomes, the greater the number of CRPs will be needed for treatment; the simultaneous involvement of the posterior semicircular canal and horizontal semicircular canal is most common.

Tumor-Targeting Co-Delivery of Drug and Gene from Temperature-Triggered Micelles.

Co-delivery strategy using multifunctional nanocarriers is an attractive option for the synergistic and enhanced effects in cancer treatment, but one system integrating multiple functions for controlled release at the target is still challenging. Herein, this study shows the synthesis and characterization of our stimulus-responsive co-delivery system for the controlled release into tumors, which is composed of polyethylenimine (PEI)-linked Pluronic F127 (PF127) and folic acid (FA), called PF127-PEI-FA. PF127-PEI-FA system facilitated drug loading and gene complex formation, and showed controlled release behaviors in response to hitting temperature to hyperthermia. PF127-PEI-FA system was demonstrated to be biocompatible and showed receptor-mediated gene delivery. The results of our multifunctional nanocarrier system that enabled co-delivery suggest a promising potential for controlled drug release at targeted areas. However, further in-depth studies on the use of therapeutic drugs and genes in multiple cell types and the animal response are required.

Structure, biodegradation behavior and cytotoxicity of alkali-containing alkaline-earth phosphosilicate glasses.

We report on the effect of sodium on the structure, chemical degradation and bioactivity of glasses in the CaO-MgO-SiO2-P2O5-CaF2 system. The (29)Si and (31)P magic angle spinning-nuclear magnetic resonance spectroscopy of melt-quenched glasses with varying Na2O/MgO ratios exhibit a silicate glass network with the dominance of Q(2)(Si) units and phosphorus mainly forming orthophosphate species. Sodium incorporation in the glasses did not induce a significant structural change in the silicate network, while it did influence the phosphate environment due to its lower ionic field strength in comparison with that of magnesium. The apatite forming ability of glasses has been investigated by immersion of glass powders in simulated body fluid (SBF) for time durations varying between 1h and 7 days while their chemical degradation has been studied in Tris-HCl in accordance with ISO-10993-14. Increasing Na(+)/Mg(2+) ratio caused a decrease in the chemical durability of glasses and in the apatite forming ability especially during initial steps of interaction between glass and SBF solution. The cellular responses were observed in vitro on bulk glass samples using mouse-derived pre-osteoblastic MC3T3-E1 cell line. The preliminary study suggested that the increasing alkali-concentration in glasses led to cytotoxicity in the cell culture medium.

Targeted disruption of Ataxia-telangiectasia mutated gene in miniature pigs by somatic cell nuclear transfer.

Ataxia telangiectasia (A-T) is a recessive autosomal disorder associated with pleiotropic phenotypes, including progressive cerebellar degeneration, gonad atrophy, and growth retardation. Even though A-T is known to be caused by the mutations in the Ataxia telangiectasia mutated (ATM) gene, the correlation between abnormal cellular physiology caused by ATM mutations and the multiple symptoms of A-T disease has not been clearly determined. None of the existing ATM mouse models properly reflects the extent to which neurological degeneration occurs in human. In an attempt to provide a large animal model for A-T, we produced gene-targeted pigs with mutations in the ATM gene by somatic cell nuclear transfer. The disrupted allele in the ATM gene of cloned piglets was confirmed via PCR and Southern blot analysis. The ATM gene-targeted pigs generated in the present study may provide an alternative to the current mouse model for the study of mechanisms underlying A-T disorder and for the development of new therapies.

Effect of adenotonsillar hypertrophy on right ventricle function in children.

PURPOSE: Chronic upper airway obstruction causes hypoxemic pulmonary vasoconstriction, which may lead to right ventricle (RV) dysfunction. Adenotonsillar hypertrophy (ATH) is the most common cause of upper airway obstruction in children. Therefore, we aimed to evaluate RV function in children with ATH. METHODS: Twenty-one children (male/female, 15/6; mean age, 92.3¡¾39.0 months; age range, 4-15 years) with ATH and 21 healthy age- and gender-matched controls were included in this study. Tricuspid annular plane systolic excursion and RV myocardial performance index were measured by transthoracic echocardiography. Further, the plasma level of N-terminal of probrain natriuretic peptide (NT-proBNP), an indicator of RV function, was determined. RESULTS: The snoring-tiredness during daytime-observed apnea-high blood pressure (STOP) questionnaire was completed by the patients' parents, and loud snoring was noted in the ATH group. The plasma NT-proBNP level was significantly higher in the ATH group than that in the controls (66.44±37.63 pg/mL vs. 27.85±8.89 pg/mL, P=0.001). The echocardiographic parameters were not significantly different between the groups. CONCLUSION: We were unable to confirm the significance of echocardiographic evidence of RV dysfunction in the management of children with ATH. However, the plasma NT-proBNP level was significantly higher in the ATH group than that in the control, suggesting that chronic airway obstruction in children may carry a risk for cardiac dysfunction. Therefore, more patients should be examined using transthoracic echocardiography. In addition, pediatricians and otolaryngologists should consider cardiologic aspects during the management of children with severe ATH.

Differential stimulation of neurotrophin release by the biocompatible nano-material (carbon nanotube) in primary cultured neurons.

In order to develop novel, effective therapies for central nervous system regeneration, it is essential to better understand the role of neurotrophic factors and to design, accordingly, better artificial scaffolds to support both neurite outgrowth and synapse formation. Both nerve growth factor and brain-derived neurotrophic factor are major factors in neural survival, development, synaptogenesis, and synaptic connectivity of primary cultured neurons. As a prime candidate coating material for such neural cultures, carbon nanotubes offer unique structural, mechanical, and electrical properties. In this study, carbon nanotubes coated glass-coverslips were used as the matrix of a primary neural culture system used to investigate the effects of carbon nanotubes on neurite outgrowth and nerve growth factor/brain-derived neurotrophic factor release and expression. For these purposes, we performed comparative analyses of primary cultured neurons on carbon nanotubes coated, non-coated, and Matrigel-coated coverslips. The morphological findings showed definite carbon nanotubes effects on the neurite outgrowths and synaptogenic figures in both cortical and hippocampal neurons when compared with the non-coated negative control. Although the carbon nanotubes did not change neurotrophin expression levels, it stimulated brain-derived neurotrophic factor release into the media from both types of neurons. Accordingly, we suggest a different mechanism of action between carbon nanotubes and Matrigel in relation to the specific neurotrophic factors. Since carbon nanotubes supply long-term extracellular molecular cues for the survival and neurite outgrowths of cultured neurons, the results from this study will contribute to an understanding of carbon nanotubes biological effects and provide new insight into their role in the secretion of neurotrophic factors.