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Background: The indications for transcanal endoscopic ear surgery (TEES) for middle ear cholesteatoma have expanded for cases involving mastoid extension. However, TEES is not indicated for all cases with mastoid extension. In addition, predicting the extent of external auditory canal (EAC) removal needed for cholesteatoma resection is not always easy. The purpose of this study was to use augmented reality (AR) to project the lesion onto an intraoperative endoscopic image to predict EAC removal requirements and select an appropriate surgical approach. Methods: In this study, patients showing mastoid extension were operated on using a navigation system with an AR function (Stryker). Results: The results showed that some cases with lesions slightly extending into the antrum required extensive resection of the EAC, while cases with lesions extending throughout the antrum required smaller resection of the EAC, indicating TEES. Conclusions: By predicting the extent of the needed EAC removal, it is possible to determine whether TEES (a retrograde approach) or canal wall-up mastoidectomy, which preserves as much of the EAC as possible, should be performed. We believe that our findings will contribute to the success of middle ear surgeries and the implementation of robotic surgery in the future. [ABSTRACT FROM AUTHOR]

Sinonasal inverted papilloma (IP) is at risk of recurrence and malignancy, and early diagnosis using nasal endoscopy is essential. We thus developed a diagnostic system using artificial intelligence (AI) to identify nasal sinus papilloma. Endoscopic surgery videos of 53 patients undergoing endoscopic sinus surgery were edited to train and evaluate deep neural network models and then a diagnostic system was developed. The correct diagnosis rate based on visual examination by otolaryngologists was also evaluated using the same videos and compared with that of the AI diagnostic system patients. Main outcomes evaluated included the percentage of correct diagnoses compared to AI diagnosis and the correct diagnosis rate for otolaryngologists based on years of practice experience. The diagnostic system had an area under the curve of 0.874, accuracy of 0.843, false positive rate of 0.124, and false negative rate of 0.191. The average correct diagnosis rate among otolaryngologists was 69.4%, indicating that the AI was highly accurate. Evidently, although the number of cases was small, a highly accurate diagnostic system was created. Future studies with larger samples to improve the accuracy of the system and expand the range of diseases that can be detected for more clinical applications are warranted. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the efficacy and safety of 1.5% levofloxacin (LVFX) otic solution for the treatment of patients with otitis media. This multicenter, randomized, double-blind, parallel-group, placebo-controlled phase 3 trial was conducted at 34 institutions in Japan. A total of 202 patients with chronic suppurative otitis media (CSOM) or acute otitis media (AOM) were randomized into either the LVFX group or placebo group. A total of 6–10 drops of 1.5% otic solution of LVFX or its matching placebo were administered in the diseased ear twice daily, in the morning and evening for up to 10 days. Images corresponding to three clinical findings—purulent otorrhea, hyperemia (redness), and granulation tissue formation in the middle ear and tympanic membrane—for each diseased ear were evaluated using digital endoscopy by a blinded central independent review committee (BICRC) at each visit after treatment administration. In total, the data of 201 participants (LVFX group, 99; placebo group, 102) were analyzed. The proportion of patients with disappearance (improvement rate) of all three clinical findings at the end of treatment or discontinuation by the BICRC was 46.5% (46/99) in the LVFX group and 23.5% (24/102) in the placebo group, and the difference (95% confidence interval) between the groups was 22.0% (8.7, 34.2), with a significantly higher improvement rate in the LVFX group than in the placebo group (p = 0.001; Cochran–Mantel–Haenszel test), demonstrating the efficacy of LVFX. The bacterial eradication rates were 93.9% (77/82) and 12.5% (11/88) in the LVFX and placebo groups, respectively, and the rate was significantly higher in the LVFX group than in the placebo group (p < 0.001). Treatment-related adverse events (AEs) occurred in 5.1% (5/99) and 7.8% (8/102) of the patients in the LVFX and placebo groups, respectively, and no significant difference was noted in incidence rate between the groups. The clinical efficacy of 1.5% LVFX otic solution for CSOM and AOM was demonstrated by the resolution of inflammation in the middle ear and tympanic membrane as well as through the high bacterial eradication rate observed. No deaths or serious treatment-related AEs were observed. The study provided confirmation that 1.5% LVFX otic solution is a safe, well-tolerated, and effective treatment for CSOM and AOM. [ABSTRACT FROM AUTHOR]

Recent studies have suggested that speech perception outcomes after cochlear implantation (CI) in prelingually deafened adults have improved with advances in CI technology and speech processing strategies. However, the outcomes vary from case to case. Communication mode has been reported in many studies as the factor that related to the post CI outcomes. This study aimed at investigating the post CI outcomes and the progress during 2 years for each communication mode. The subjects were 17 prelingually deafened adults undergoing CI at our hospital between April 2013 and March 2019. We investigated preoperative factors affecting post CI outcomes. Also we analyzed post CI outcomes for each communication mode and compared preoperative factors for each communication mode. Communication mode and preoperative discrimination score were the factor affecting on postoperative discrimination score. The speech perception score after CI improved significantly in the oral and lip-reading group and total communication group. The speech perception scores in postlingually deafened adults improved significantly during the first six months and became to plateau after CI. On the other hand, the scores of prelingually deafened adults tended to improve gradually after six months postoperatively. Furthermore, the degree of improvement and progress differed by each communication mode. The communication mode is important factors in predicting outcomes in prelingually deafened adults after CI. Long-term auditory training is important for prelingually deafened adults who use visual information as their preoperative method of communication. [ABSTRACT FROM AUTHOR]

Purpose: In most stapes surgeries, the posterior ear canal is enlarged and a piston is inserted posterior to the chorda tympani nerve (post-chorda tympani approach; Post C). Although reports vary, some indicate that more than 60% of the patients experience lingual symptoms following surgery. Endoscopic surgery may permit an anterior approach to the nerve (pre-chorda tympani approach; Pre C). Herein, we propose a suitable approach for endoscopic stapes surgery based on the classification of the chorda tympani nerve. Methods: We retrospectively reviewed the medical records of 23 patients who underwent endoscopic stapes surgery at our institution between 2019 and 2021. The nerve classification previously reported, the modified nerve classification (attached long type is divided into Category 1: lenticular process is visible with 0° endoscope and Category 2: not visible), selected approach (Pre C or Post C), use of a 30° endoscope, and manipulation of the nerve (number of contacts and traction, with or without suction, with or without malposition or extension and amputation, and damage score) were evaluated. Results: The damage score was significantly lower in the Pre C group (p < 0.05); however, using this approach for all cases is not desirable owing to the high risk of damage to the nerve during posterior malpositioning. Conclusion: The Post C should be used for the detached and attached long 1 types, while the Pre C with a 30° endoscope should be used for the attached long 2, attached short, ultrashort, and external auditory canal types. [ABSTRACT FROM AUTHOR]

Background: Tympanoplasty using the interlay technique has rarely been reported in transcanal endoscopic ear surgery, unlike the underlay technique. This is because many surgeons find it challenging to detach the epithelial layer of the tympanic membrane using only one hand. However, the epithelial layer can be easily detached from the inferior part of the tympanic membrane. Another key point is to actively improve anteroinferior visibility even if the overhang is slight because most perforations and postoperative reperforations are found in the anteroinferior quadrant of the tympanic membrane. We report the application of the interlay technique in endoscopic tympanoplasty type I for tympanic perforations. Methods: We retrospectively reviewed the medical records of 51 patients who had undergone tympanoplasty using the interlay technique without ossiculoplasty between 2017 and 2020. We then compared the data with those of patients who underwent microscopic surgery (MS) using the underlay technique between 1998 and 2009 (n = 104). No other technique was used in each group during this period. Repair of tympanic membrane perforation and hearing outcomes were assessed for > 1 year postoperatively. Results: The perforation sites were limited to the anterior, posterior, and anterior–posterior quadrants in 23, 1, and 27 ears, respectively. Perforations were closed in 50 of the 51 ears (98.0%), and the postoperative hearing was good (average air-bone [A-B] gap was 6.8 ± 5.8 dB). The surgical success rate for the repair of tympanic membrane perforation was not significantly different from the MS group (93.3%, P = 0.15). The average postoperative average A-B gap in the group that underwent the interlay technique was significantly different from that in the MS group (10.1 ± 6.6 dB, P < 0.01). Conclusion: The interlay technique should be considered as one of the treatment methods in endoscopic surgery for tympanic perforations. Further study of the postoperative outcomes of this procedure should be conducted to establish the optimal surgical procedure for tympanic perforations. Trial registration: This study was retrospectively approved by the Institutional Review Board of the Jikei University, Tokyo, Japan (approval number: 32-205 10286). EHU69PToR4KkpCPbQtPHKe Video abstract [ABSTRACT FROM AUTHOR]

Cholesteatoma is a progressive middle ear disease that can only be treated surgically but with a high recurrence rate. Depending on the extent of the disease, a surgical approach, such as microsurgery with a retroarticular incision or transcanal endoscopic surgery, is performed. However, the current examination cannot sufficiently predict the progression before surgery, and changes in approach may be made during the surgery. Large amounts of data are typically required to train deep neural network models; however, the prevalence of cholesteatomas is low (1-in-25, 000). Developing analysis methods that improve the accuracy with such a small number of samples is an important issue for medical artificial intelligence (AI) research. This paper presents an AI-based system to automatically detect mastoid extensions using CT. This retrospective study included 164 patients (80 with mastoid extension and 84 without mastoid extension) who underwent surgery. This study adopted a relatively lightweight neural network model called MobileNetV2 to learn and predict the CT images of 164 patients. The training was performed with eight divided groups for cross-validation and was performed 24 times with each of the eight groups to verify accuracy fluctuations caused by randomly augmented learning. An evaluation was performed by each of the 24 single-trained models, and 24 sets of ensemble predictions with 23 models for 100% original size images and 400% zoomed images. Fifteen otolaryngologists diagnosed the images and compared the results. The average accuracy of predicting 400% zoomed images using ensemble prediction model was 81.14% (sensitivity = 84.95%, specificity = 77.33%). The average accuracy of the otolaryngologists was 73.41% (sensitivity, 83.17%; specificity, 64.13%), which was not affected by their clinical experiences. Noteworthily, despite the small number of cases, we were able to create a highly accurate AI. These findings represent an important first step in the automatic diagnosis of the cholesteatoma extension. [ABSTRACT FROM AUTHOR]

Aims/Introduction: To investigate the association between cardiovascular autonomic neuropathy (CAN) assessed by the coefficient of variation of the R‐R interval and the reduction in the estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes. Materials and methods: This retrospective observational cohort study enrolled type 2 diabetes patients who had their coefficient of variation of the R‐R interval measured on an electrocardiogram from January 2005 to December 2018. CAN was defined using the reference coefficient of variation of the R‐R interval value based on age and sex. The primary outcome was set as a 40% eGFR decline from baseline. Regression analyses using the Cox proportional hazards model were carried out to evaluate the association. Results: Of the 831 patients, 118 (14.2%) were diagnosed with CAN. In the analysis of the primary outcome, the median follow‐up period was 5.3 years, and 25 (21.2%) patients with CAN and 78 (10.9%) patients without CAN developed a 40% eGFR decline. In the univariate regression analysis, CAN was significantly associated with a 40% eGFR decline (hazard ratio 2.42, 95% confidence interval 1.54–3.80). In the multivariate analysis, CAN remained almost significant after adjusting for the prognostic risk factors for CAN and the decline in the renal function, and an interaction with proteinuria was found. In analyses for the interaction effect between CAN and proteinuria, the presence of CAN synergistically increased the risk of an eGFR decline in patients with macroproteinuria. Conclusions: CAN strongly increased the risk of a 40% eGFR decline from baseline, especially in type 2 diabetes patients with macroproteinuria. [ABSTRACT FROM AUTHOR]

Objective: Eosinophilic otitis media (EOM) is an intractable middle ear disease recognized by an eosinophil enriched middle ear effusion and mucosa. Although precise pathogenesis of EOM remains unclear, it is characterized by type 2 inflammation. Since IgG4 is an IgG subclass induced by type 2 cytokines such as IL-4 and IL-13, we sought to characterize and compare local IgG4 expression in patients with and without EOM.Methods: Twelve patients with bilateral profound hearing loss, 9 of which underwent a cochlear implant surgery, were enrolled in this study (6 with EOM and 6 without EOM). The surgical specimens were harvested during surgery and were subjected to IgG4 immunostaining.Result: The middle ear mucosa showed the presence of a large number of IgG4-positive cells in patients with EOM, which was significantly higher than that in patients without EOM.Conclusion: Local IgG4 expression was observed in patients with EOM in comparison to those without EOM, suggesting that IgG4 contributes to EOM pathogenesis. [ABSTRACT FROM AUTHOR]

Background: 30° and 45° endoscopes are commonly used, but there are few reports about the use of 70° endoscopes for ear surgery. Methods: The use of 70° endoscopes made it possible to resect cholesteatomas without removing extensive regions of the external ear canal, which facilitated reconstruction, as the areas that needed to be reconstructed were smaller. Conclusion: None of the 34 patients who underwent this procedure for pars flaccida cholesteatoma suffered recurrence. Therefore, we consider that the procedure is useful. A further study of the postoperative outcomes of this procedure should be conducted. [ABSTRACT FROM AUTHOR]

Epigenetic gene silencing by aberrant DNA methylation leads to loss of key cellular pathways in tumorigenesis. In order to analyze the effects of DNA methylation on prostate cancer, we established LNCaP-derived human prostate cancer cells that can pharmacologically induce global reactivation of hypermethylated genes by the methyl-CpG targeted transcriptional activation (MeTA) method. The MeTA suppressed the growth of LNCaP-derived cells and induced apoptosis. Microarray analysis indicated that PYCARD (PYD and CARD domain containing) encoding an apoptosis-inducing factor was upregulated by 65-fold or more after treatment with MeTA. We analyzed DNA methylation statuses using 50 microdissected primary prostate cancer tissues and found an extremely high frequency of tumor-specific promoter hypermethylation of PYCARD (90%, 45/50). Moreover, DNA methylation status was significantly associated with Gleason score (P = 0.0063); the frequency of tumor-specific hypermethylation was 96% (44/46) in tumors with Gleason score ≥ 7 , whereas that in tumors with Gleason score 6 was 25% (1/4). Immunohistochemical analyses using these 50 cases indicated that only 8% (4/50) of cancerous tissues expressed PYCARD, whereas 80% (40/50) of corresponding normal prostate epithelial and/or basal cells expressed PYCARD. In addition, there was no relationship between PYCARD immunostaining and the Gleason score in cancerous tissue and surrounding normal tissue. Inducible expression of PYCARD inhibited cell proliferation by induction of apoptosis. These results suggest that aberrant methylation of PYCARD is a distinctive feature of prostate cancers with Gleason score ≥ 7 and may play an important role in escaping from apoptosis in prostatic tumorigenesis. [ABSTRACT FROM AUTHOR]

Epigenetic gene silencing by aberrant DNA methylation leads to loss of key cellular pathways in tumorigenesis. In order to analyze the effects of DNA methylation on prostate cancer, we established LNCaP-derived human prostate cancer cells that can pharmacologically induce global reactivation of hypermethylated genes by the methyl-CpG targeted transcriptional activation (MeTA) method. The MeTA suppressed the growth of LNCaP-derived cells and induced apoptosis. Microarray analysis indicated that PYCARD (PYD and CARD domain containing) encoding an apoptosis-inducing factor was upregulated by 65-fold or more after treatment with MeTA. We analyzed DNA methylation statuses using 50 microdissected primary prostate cancer tissues and found an extremely high frequency of tumor-specific promoter hypermethylation of PYCARD (90%, 45/50). Moreover, DNA methylation status was significantly associated with Gleason score (P = 0.0063); the frequency of tumor-specific hypermethylation was 96% (44/46) in tumors with Gleason score ≥ 7 , whereas that in tumors with Gleason score 6 was 25% (1/4). Immunohistochemical analyses using these 50 cases indicated that only 8% (4/50) of cancerous tissues expressed PYCARD, whereas 80% (40/50) of corresponding normal prostate epithelial and/or basal cells expressed PYCARD. In addition, there was no relationship between PYCARD immunostaining and the Gleason score in cancerous tissue and surrounding normal tissue. Inducible expression of PYCARD inhibited cell proliferation by induction of apoptosis. These results suggest that aberrant methylation of PYCARD is a distinctive feature of prostate cancers with Gleason score ≥ 7 and may play an important role in escaping from apoptosis in prostatic tumorigenesis. [ABSTRACT FROM AUTHOR]

Detailed studies have not been conducted on sound localization and speech perception in noise in patients with unilateral congenital aural atresia (UCAA). To evaluate the benefits of the use of the Vibrant Soundbridge (VSB) for UCAA by performing audiometric and sound localization tests. Four children with UCAA underwent VSB (VORP 503) implantation from 2018 to 2019. Speech perception tests in noise were conducted using the Japanese monosyllable test. The spatial configuration for speech testing consisted of speech presented from the front and noise presented into the normal ear (S0N90). The sound localization test was conducted using nine loudspeakers equally distributed in a semicircle. The children's speech perception in noise 6 months after VSB activation was significantly better than before activation (p <.05). Additionally, the children's sound localization ability after VSB activation was significantly better than before VSB activation. The benefits of VSB use in children with UCAA were revealed using audiometric and sound localization tests. [ABSTRACT FROM AUTHOR]

Background and objective: Dipeptidyl peptidase-4 (DPP-4) inhibitors have been suggested to have pancreatic beta-cell preserving effect according to studies using homeostatic model of assessment for beta-cell function (HOMA-β). However, whether HOMA-β is a suitable biomarker for comparisons between hypoglycemic drugs with different mechanisms of action remains unclear. Therefore, we conducted a meta-analysis to compare the effects of DPP-4 inhibitors and other classes of hypoglycemic drugs on HOMA-β and proinsulin-to-insulin ratio (PIR). Methods: We searched MEDLINE, CENTRAL, and Ichushi-web for the period of 1966 to May 2020. We collected randomized, controlled clinical trials in patients with type 2 diabetes mellitus comparing DPP-4 inhibitors and other classes of hypoglycemic agents [α-glucosidase inhibitors (α-GIs), glucagon-like peptide-1 (GLP-1) analogues, metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, sulfonylureas, or thiazolidinediones]. Weighted mean differences and 95% confidence intervals of changes in HOMA-β or PIR during study periods were calculated for pairwise comparisons. Results: Thirty-seven and 21 relevant trials were retrieved for comparisons of HOMA-β and PIR, respectively. HOMA-β and PIR consistently showed superiority of DPP-4 inhibitors compared with α-GIs. Both biomarkers consistently supported inferiority of DPP-4 inhibitors compared with GLP-1 analogues. However, PIR showed inferiority of DPP-4 inhibitors compared with metformin, and superiority compared with SGLT2 inhibitors, whereas HOMA-β showed no significant differences between DPP-4 inhibitors and the two other agents. Conclusion: DPP-4 inhibitors appear to be superior to α-GIs but inferior to GLP-1 analogues in preservation of beta-cell function assessed by either HOMA-β or PIR. DPP-4 inhibitors seem to be superior to SGLT2 inhibitors but inferior to metformin on islet function assessed only by PIR. Because HOMA-β and PIR may indicate different aspects of beta-cell function, results of beta-cell function preserving effects of hypoglycemic agents should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Herein, gallium nitride (GaN) samples implanted with magnesium (Mg) and fluorine (F) ions are investigated by photoluminescence (PL) measurements. In low‐temperature PL measurements, the characteristic green luminescence (GL) band attributable to nitrogen vacancies (VN) is observed in Mg‐ion‐implanted GaN. As VN are likely to act as donors, suppressing their formation is essential to realizing p‐type conductivity. The energy required for a F impurity to replace VN in GaN and eventually form F on a N site decreases when the Fermi level approaches the valence band maximum, and therefore F is employed as a subsequent implantation element to compensate for VN. The GL band peak disappears upon implanting Mg and F ions at a high temperature and adjusting the F concentration to an appropriate value. This result suggests that VN generated by Mg ion implantation can be suppressed using an element with a lower formation energy than that of VN. [ABSTRACT FROM AUTHOR]

Background: The mastoid air cells are considered to develop better in children with congenital cholesteatoma but only a few quantitative studies have examined. Aims/objectives: The present study was undertaken in order to clarify the relationships between the development of the mastoid air cells in children with congenital cholesteatoma and clinical factors. Materials and methods: Mastoid air cell development was evaluated in 53 children with congenital cholesteatoma. The sizes of the mastoid air cells were measured on computed tomography scans of the temporal bone, and clinical factors, including age, the extent of invasion, and whether it was located close to the eustachian tube were evaluated. Results: The cross-sectional area of the mastoid air cells was significantly smaller on the affected side than on the unaffected side, especially in the older patients. The cases involving invasion into the mastoid portion also had smaller mastoid cells. Whether the cholesteatoma was located close to the eustachian tube had no effect. Conclusions and significance: The mastoid air cells on the affected side were less well developed. Our findings indicate that a high age and the presence of cholesteatoma in the mastoid region might be associated with suppressed mastoid pneumatization. [ABSTRACT FROM AUTHOR]

Highlights • The mechanism underlying the differences in laterality of orofacial clefts. • Whole-genome sequencing results showed no discordant DNA variants in monozygotic twin. • Environmental factors might be a critical factor influencing differences in the cleft side. Abstract Objective The aim of the present study is to explore genetic factors determining difference of cleft side using whole-genome sequencing and evaluation of craniofacial morphology using cephalometric analysis between Japanese monozygotic (MZ) twins with mirror-image cleft lip and palate (CLP). Design We selected a Japanese MZ twin pair (MZ-A and MZ-B) affected with unilateral CLP who are discordant for cleft side (left/right) and conducted whole-genome sequencing to identify genetic factors determining cleft side. Moreover, we compared their craniofacial morphologies using cephalograms. Results Whole-genome sequencing results suggested that no discordant DNA variants were found between MZ-A and MZ-B. The comparison of craniofacial morphology between the MZ twins revealed that MZ-B had maxillary deficiency and slightly more mandibular protrusion than MZ-A. Conclusions It is indicated that environmental factors might be a critical factor that influences the determination of difference of cleft side in orofacial clefts. In addition, we found some differences in craniofacial morphology between MZ-A and MZ-B. Our findings suggest that various environmental factors, such as epigenetics, might be a critical factor that influences the determination of difference of cleft side in CLP rather than inherited genetic factors. [ABSTRACT FROM AUTHOR]

Background: Mastoid development, tympanic sinus depth, and residual disease after surgery for congenital cholesteatoma are probably related, but these relationships have not been examined in detail. Aims/objectives: This study aimed to clarify the relationships between the abovementioned factors. Materials and Methods: The subjects were 31 patients with congenital cholesteatoma (stage III or IV in Potsic's staging system) that underwent mastoidectomy. The cross-sectional area of the mastoid air cells was measured as described previously. Tympanic sinus depth was classified into A–C using Marchioni et al.'s system. Results: Patients with deep tympanic sinuses or residual disease exhibited significantly greater mastoid air cell development. However, little residual disease was found in the mastoid air cells. Conversely, residual disease was observed more frequently in the patients with deep tympanic sinuses. Conclusions and significance: After surgery for congenital cholesteatoma, residual disease is more likely to occur in patients with marked mastoid growth, possibly because they have deep tympanic sinuses. Cases in which congenital cholesteatoma spreads to the mastoid air cells are classified as stage IV in Potsic's system, but our findings indicate that invasion into a deep tympanic sinus is more important than invasion into the mastoid air cells. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Orofacial clefts (OFCs) are common and etiologically complex birth defects. This study explored potential genetic differences in a pair of Japanese monozygotic (MZ) twins with different forms of OFC using whole‐genome sequencing. Subjects and Methods: One co‐twin (MZ‐1) presented with nonsyndromic bilateral cleft lip and palate; the other co‐twin (MZ‐2) had nonsyndromic bilateral cleft lip and unilateral left‐sided cleft alveolus. Neither parent had an OFC. Craniofacial morphologic features and potential genetic differences were compared using standard cephalometry and whole‐genome sequencing, respectively. Results: Morphologically, MZ‐1 had a smaller vertical mandibular height, compared to MZ‐2. However, no discordant genetic differences were detected. Moreover, both twins and their parents harbored rare candidate gene variants (GRHL3; TPM1) considered to be associated with OFCs. Conclusion: The observed differences between MZ‐1 and MZ‐2 in craniofacial morphology assessed by cephalograms might be directly attributable to the effects of the OFC on growth and/or differences in surgical history, given the lack of any differences in genetic background. However, comparisons of discordant MZ twins should continue to identify novel candidates that might control OFC or that might partly explain the missing heritability for this common birth defect, in addition to understanding craniofacial growth and development. [ABSTRACT FROM AUTHOR]

Objective: The preservation of residual hearing after conventional cochlear implantation (CI) is frequently observed when atraumatic soft surgery is adopted. The purpose of this study was to elucidate the predictive factors for residual hearing preservation after atraumatic CI. Patients: This study included 46 patients who underwent CI based on an atraumatic technique using a standard-length flexible electrode implant through a round window approach. Main outcome measure: Cochlear volume was measured using magnetic resonance imaging (MRI). Cochlear duct length (CDL) was taken as the length of the scala media measured using computed tomography (CT). The association between residual hearing preservation and cochlear volume/CDL was then examined. Result: Cochlear volume and CDL were significantly larger in patients with complete hearing preservation than in those with hearing loss. Multivariate logistic regression analysis revealed that cochlear volume was a significant predictive factor for residual hearing preservation. Conclusion: Residual hearing preservation after conventional CI was observed in patients with a larger cochlear volume and longer CDL. Cochlear volume could be a predictive factor for residual hearing preservation after conventional CI. [ABSTRACT FROM AUTHOR]

A hollow fiber degassing membrane (DM) was applied to enhance organic matter degradation and methane gas production of anaerobic granular sludge process by reducing the dissolved hydrogen gas (D-H 2 ) concentration in the liquid phase. DM was installed in the bench-scale anaerobic granular sludge reactors and D-H 2 was removed through DM using a vacuum pump. Degasification improved the organic matter degradation efficiency to 79% while the efficiency was 62% without degasification at 12,000 mg L −1 of the influent T-COD concentration. Measurement of D-H 2 concentrations in the liquid phase confirmed that D-H 2 was removed by degasification. Furthermore, the effect of acetate concentrations on the organic matter degradation efficiency was investigated. At acetate concentrations above 3 g L −1 , organic matter degradation deteriorated. Degasification enhanced the propionate and acetate degradation. These results suggest that degasification reduced D-H 2 concentration and volatile fatty acids concentrations, prevented pH drop, and subsequent enhanced organic matter degradation. [ABSTRACT FROM AUTHOR]

Background: Advancement in both surgical technique and medical equipment has enabled solo surgery. ViKY® Endoscope Positioning System (ViKY®) is a robotic system that remotely controls an endoscope and provides direct vision control to the surgeon. Here, we report our experience with ViKY®-assisted solo surgery.Methods: We retrospectively examined 25 cases of solo surgery TAPP with ViKY®. ViKY® was setup by the surgeon alone, and the setup duration was determined as the time at which the side rail was positioned and that when the endoscope was installed. For assessing the control unit, the number of false movements was counted. We compared the operative results between ViKY®-assisted solo surgery TAPP and the conventional method with an assistant.Results: The average time to set up ViKY® was 7.9 min. The average number of commands for ViKY® during surgery was 98.3, and the average number of errors and no response of control unit was 7.9. The mean duration of surgery was 136 min for the ViKY® group, including the setup time, and 117 min for the conventional method. No case required an assistant during the operation. There was also no difference between the two groups with regard to postoperative complications and the rate of recurrence.Conclusions: ViKY® proved reliable in recognizing orders with very few failures, and the operations were performed safely and were comparable to the conventional operations with assistants. Solo surgery with ViKY® was beneficial in this clinical evaluation. [ABSTRACT FROM AUTHOR]

Highlights: [•] Neural crest-derived cells (NCDCs) exist in adult submandibular glands (SMGs). [•] Sox10 may be a reliable marker for NCDCs in adulthood. [•] NCDCs from adult SMGs expressed Gpr4 and Ednrb at higher levels. [•] NCDCs in adult SMGs have characteristic expression in cell surface molecules. [ABSTRACT FROM AUTHOR]

Abstract: An important goal of synthetic biology is to construct reaction circuits with artificial responses by assembling modulated biological elements into living cells. While many such attempts have been based upon the cellular transcriptional apparatus, the use of the post-translational machinery remains relatively rare. Here we report the reconstruction in Escherichia coli of a protein-based artificial module based upon elements of a eukaryotic cell signaling pathway. The module shows a switch-like ultrasensitive response, using the opposing functions of a protein kinase and a phosphatase. The switch is acutely responsive to the kinase:phosphatase ratio, and can be modulated as a function of the expression level of the substrate. We can theoretically predict the response of this module and can control its steepness based on these predictions. Future work will demonstrate the potential of this controllable protein-based switch to be incorporated into artificial circuits. [Copyright &y& Elsevier]

Abstract: Improved synthesis and reinvestigation of the magnetic properties of triphenylamine bearing three nitronylnitroxide radicals (1) were carried out. Single crystal X-ray crystallographic analysis of 1 established that its molecular shape had a C 3-symmetry. Our newly prepared 1 showed different physical properties from those of reported. SQUID measurements of 1 showed that each of the three spins of 1 behaved independently at room temperature. In contrast, the three spins coupled antiferromagnetically at lower temperature as low as ca. 1.8K. These spin behaviors can be explained by a regular triangular antiferromagnetic model (J/k B =−3.3K) and interpreted as a spin frustration system. [Copyright &y& Elsevier]

Abstract: Objective: The objective of this study was to evaluate the water sorption (Wsp) and ultimate tensile strength (UTS) of HEMA-containing/free one-step self-etch adhesives after long-term water-storage. Methods: Three HEMA-containing one-step self-etch adhesives (Bond Force (BF), Clearfil S3 Bond (S3) and OptiBond All-In-One (OP)), and one HEMA-free one-step self-etch adhesive, G Bond (GB) was used. After the solvents of each adhesive were evaporated, polymerised adhesive disks and dumbbell-shaped specimens of thirty-two each were prepared and divided into four groups of 14-, 90-, 180- and 360-day water-storage. After immersion in water for the designated storage periods, the disks were subjected to measurement of Wsp, and the dumbbell-shaped specimens were subjected to measurement of UTS. The data of Wsp and UTS were statistically analysed using a two-way ANOVA and Bonferroni test. Results: Wsp of BF, S3 and OP increased over time, whereas for GB, there were no significant differences in Wsp among all the storage periods. Wsp of GB was lower than those of BF, S3 and OP in each period. The UTS of BF, S3 and OP decreased over time, whereas for GB, there were no significant differences in UTS among all storage periods. The highest UTS was initially seen in BF>GB=S3=OP, and after 360-day water-storage, seen in BF=GB>OP=S3. Conclusions: For the HEMA-containing adhesives, Wsp increased and UTS decreased over time. On the other hand, for the HEMA-free adhesive, Wsp and UTS did not significantly change even after 360-day water-storage. [Copyright &y& Elsevier]

Abstract: The non-invasive imaging technique of diffusion tensor imaging (DTI) has been used to investigate the microstructural properties of white matter (WM). The present study investigated whether individual differences in the WM structure of normal subjects as measured by fractional anisotropy (FA) values correlate with cognitive performance in terms of sustained attention and working memory. Subjects underwent DTI and performed the Continuous Performance Test (CPT) and N-back task. FA values throughout the brain were correlated with behavioral performance on a voxel-by-voxel basis to investigate relationships between WM microstructure and cognitive function. The discriminability index of CPT correlated positively with FA of the right cingulum. Accuracy of the 2-back task correlated positively with FA in bilateral cerebellar peduncles. WM microstructure of the right cingulum and bilateral cerebellar peduncles appears related to cognitive function such as sustained attention and working memory in the human brain. [Copyright &y& Elsevier]

Objective To assess the effects of two anxiolytics, diazepam and tandospirone, on driving performance from methodological viewpoints taking frequent rear-end collisions into account. Methods In this double-blinded, three-way crossover trial, 18 healthy males received acute doses of 20 mg tandospirone (TSP), 5 mg diazepam (DZP), and placebo (PCB). The subjects were administered three driving tasks—road tracking, car following, and harsh braking—performed using a driving simulator and three cognitive tasks—Wisconsin Card Sorting Test, Continuous Performance Test, and N-back test—at baseline and at 1 and 4 h post-dosing. The Stanford Sleepiness Scale scores were also assessed. Results DZP nonsignificantly increased the percent change of brake reaction time (BRT) as compared to PCB at 4 h post-dosing. TSP nonsignificantly decreased the percent change of BRT as compared to PCB. Consequently, there was a significant difference in the percent change of BRT between DZP and TSP at 4 h post-dosing. For the remaining tasks, no statistically significant effects of treatment were observed. Conclusions Acute doses of DZP significantly impaired the harsh-braking performance as compared to acute doses of TSP. These findings suggest that TSP may be used more safely in patients' driving activities. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Leaf textures of four cabbage cultivars (T-520, Fuyu-nobori, Satsuki-ou, and Kinkei-201) harvested in winter and spring were evaluated. Acoustic vibration signals generated during penetration of four stacked cabbage leaves were measured using a novel texture measurement system. Texture was quantified using a texture index (TI). The TI of T-520 was higher than that of Fuyu-nobori and continually declined during the entire investigation period (between February and May). However, Fuyu-nobori''s TI persisted after early April. This implied that Fuyu-nobori was superior to T-520 in terms of preservation of quality. Satsuki-ou showed either an equivalent or higher TI than T-520 in May. Kinkei-201 had a much lower TI than the other cultivars. TIs of T-520 and Fuyu-nobori stored at a 5°C for 4 weeks were lower than those of samples without storage. This implied that low temperature storage did not effectively retain the texture quality of the cabbages. [Copyright &y& Elsevier]

Osteoclasts are formed from the monocyte-macrophage lineage in response to receptor activator of nuclear factor kappaB ligand (RANKL) expressed by osteoblasts. Bone is the most common site of breast cancer metastasis, and osteoclasts play roles in the metastasis. The taxane-derived compounds paclitaxel and docetaxel are used for the treatment of malignant diseases, including breast cancer. Here we explored the effects of docetaxel on osteoclastic bone resorption in mouse culture systems. Osteoclasts were formed within 6 days in cocultures of osteoblasts and bone marrow cells treated with 1,25-dihydroxyvitamin D(3) plus prostaglandin E(2). Docetaxel at 10(-8) M inhibited osteoclast formation in the coculture when added for the entire culture period or for the first 3 days. Docetaxel, even at 10(-6) M added for the final 3 days, failed to inhibit osteoclast formation. Osteoprotegerin, a decoy receptor of RANKL, completely inhibited osteoclast formation when added for the final 3 days. Docetaxel at 10(-8) M inhibited the proliferation of osteoblasts and bone marrow cells. RANKL mRNA expression induced by 1,25-dihydroxyvitamin D(3) plus prostaglandin E(2) in osteoblasts was not affected by docetaxel even at 10(-6) M. Docetaxel at 10(-6) M, but not at 10(-8) M, inhibited pit-forming activity of osteoclasts cultured on dentine. Actin ring formation and L: -glutamate secretion by osteoclasts were also inhibited by docetaxel at 10(-6) M. Thus, docetaxel inhibits bone resorption in two different manners: inhibition of osteoclast formation at 10(-8) M and of osteoclast function at 10(-6) M. These results suggest that taxanes have beneficial effects in the treatment of bone metastatic cancers. [ABSTRACT FROM AUTHOR]

Abstract: We investigated time-course changes in the elasticity index (EI) of two melon (Cucumis melo L.) cultivars (“Andes” and “Quincy”) during their postharvest period. The EI was determined using the formula , where f 2 and m were the second resonance frequency and the mass of the sample, respectively. A nondestructive vibrational method with laser Doppler vibrometer (LDV) was used for measuring the second resonance frequency (f 2) of the melon samples. The changes in the EI of both cultivars showed quasi-exponential and biphasic decays. Along with sensory tests, we determined the optimum ripeness for edibility of the melons in terms of their EI to be 4.2–6.3×104 kg2/3 Hz2 (“Andes”) and 4.5–5.6×104 kg2/3 Hz2 (“Quincy”). Therefore, predetermined EI of two melon cultivars enables consumers to predict the time range of optimum ripeness. [Copyright &y& Elsevier]

Objective To assess the effects of antidepressants on driving performance from a different methodological viewpoint in light of the recent traffic accidents. Methods In this double-blinded, 3-way crossover trial, 17 healthy males received acute doses of 10 mg paroxetine, 25 mg amitriptyline, and placebo. The subjects were administered three driving tasks—road tracking, car following, and harsh braking—performed using a driving simulator and three cognitive tasks—Wisconsin Card Sorting Test, Continuous Performance Test, and N-back test at baseline and at 1 h and 4 h post-dosing. The Stanford Sleepiness Scale scores were also assessed. Results At 4 h post-dosing, amitriptyline significantly impaired road-tracking and car-following performance, reduced driver vigilance, and caused subjective somnolence. Paroxetine impaired neither driving performance nor cognitive function. Conclusions Acute doses of amitriptyline significantly impaired driving performance in the context of driving on crowded urban roads at relatively low speeds. This setting is important with respect to skills necessary for daily driving and may be difficult to measure in actual driving tests. This simulator-based study replicated the results of previous studies and could be considered complementary to them. This method may enable easy and safe screening of the driving hazard potential of drugs. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Nitroxide diradicals, in which nitroxides are annelated to m-phenylene forming tricyclic benzo-bisoxazine-like structures, have been synthesized and characterized by X-ray crystallography, magnetic resonance (EPR and ¹H NMR) spectroscopy, as well as magnetic studies in solution and in solid state. For the octamethyl derivative of benzobisoxazine nitroxide diradical, the conformationally constrained nitroxide moieties are coplanar with the m-phenylene, leading to large values of 2J (2 J/k > 200 K in solution and 2 J/k ⪢ 300 K in the solid state). For the diradical, in which all ortho and para positions of the m-phenylene are sterically shielded, distortion of the nitroxide moieties from coplanarity is moderate, such that the singlet-triplet gaps remain large in both solution (2 J/k > 200 K) and the solid state (2J/k ≈ 400-800 K), though an onset of thermal depopulation of the triplet ground state is detectable near room temperature. These diradicals have robust triplet ground states with strong ferromagnetic coupling and good stability at ambient conditions. Magnetic behavior of the nitroxide diradicals at low temperature is best fit to the model of one-dimensional S = 1 Heisenberg chains with intrachain antiferromagnetic coupling. The antiferromagnetic coupling between the S = 1 diradicals may be associated with the methyl nitroxide C-H⋯O contacts, including nonclassical hydrogen bonds. These unprecedented organic S = 1 antiferromagnetic chains are highly isotropic, compared to those of the extensively studied Ni(II)-based chains. [ABSTRACT FROM AUTHOR]

Recent evidence suggested that cyclooxygenase-2 (COX-2) expression in the peripheral nerve early after nerve injury might be involved in the development of neuropathic pain. Although previous investigators have demonstrated that COX-2 is expressed in peripheral nerve at a late phase (2–4 weeks) after nerve injury, COX-2 up-regulation at an early phase after nerve injury has not been determined. Using immunohistochemistry, we observed biphasic increases of COX-2 expression after L5 single spinal nerve injury. The first increment of COX-2 positive cells was noted 1 day after nerve injury and these cells co-expressed the Schwann cell marker S-100. A second increment was noted after 7–14 days and these cells co-expressed the macrophage marker ED-1. These results suggested that the cellular sources of COX-2 expression might be different between the early and late phases after nerve injury. [Copyright &y& Elsevier]

In this paper, the machining phenomena in the electrical discharge machining (EDM) process are investigated through a new method of in-process measurement of gap distance. The aim of this study is to understand the cause of short-circuiting and to improve the machining rate. A pipe electrode is used and the working fluid is supplied to the gap space though a fixed restrictor and the pipe electrode. Since the pressure between the fixed restrictor and the tip of the pipe electrode (fluid pressure) depends on the gap distance, the absolute value of the gap distance can be determined in-process by measuring the fluid pressure. It is found that the gap distance at the moment when the short-circuiting occurs is more than several micrometers. This result indicates that the cause of the short-circuiting is the bridging of the gap space by collected debris. Based on these results, a new gap control method in which the gap distance is kept constant even when short-circuiting occurs is examined. [Copyright &y& Elsevier]

Objective --To elucidate spatial orientation and posture regulation under conditions of microgravity. Material and Methods --Coriolis stimulation was done with five normal subjects on the ground (1 g ) and onboard an aircraft (under conditions of microgravity during parabolic flight). Subjects were asked to tilt their heads forward during rotation at speeds of 0, 50, 100 and 150°/s on the ground and 100°/s during flight. Body sway was recorded using a 3D linear accelerometer and eye movements using an infrared charge-coupled device video camera. Flight experiments were performed on 5 consecutive days, and 11-16 parabolic maneuvers were done during each flight. Two subjects boarded each flight and were examined alternately at least five times. Results --Coriolis stimulation at 1 g caused body sway, nystagmus and a movement sensation in accordance with inertial inputs at 1 g . Neither body sway, excepting a minute sway due to the Coriolis force, nor a movement sensation occurred in microgravity, but nystagmus was recorded. Conclusions --Posture, eye movement and sensation at 1 g are controlled with reference to spatial coordinates that represent the external world in the brain. Normal spatial coordinates are not relevant in microgravity because there is no Z-axis, and the posture regulation and sensation that depend on them collapse. The discrepancy in responses between posture and eye movement under conditions of microgravity may be caused by a different constitution of the effectors which adjust posture and gaze. [ABSTRACT FROM AUTHOR]

A purely organic, high-spin, and durable polyradical molecule was synthesized: It is based on the non-Kekulé- and non-disjoint design of a π-conjugated poly(1,2-phenylenevinylene) backbone pendantly 4-substituted with multiple robust arylaminium radicals. 4-N,N-Bis(4-methoxy- and -tertbutylphenyl)amino-2-bromostyrene 5 were synthesized and polymerized with a palladiumphosphine catalyst to afford the head-to-tail-linked polyradical precursors (1). Oxidation of i with the nitrosonium ion solubilized with a crown ether gave the aminium polyradicals (1+) which were durable (half-life > 1 month) at room temperature in air. A high-spin ground state with an average S = (4.5)/2 for 1a+ was proved even at room temperature by magnetic susceptibility, magnetization, ESR, and NMR measurements. [ABSTRACT FROM AUTHOR]

To clarify the role of cyclooxygenase in the peripheral nerve on the development of neuropathic pain, we investigated the effects of peri-sciatic administration of indomethacin on the development of allodynia in a model of L5 single spinal nerve injury. Peri-sciatic administration of indomethacin (1 mg/kg) was performed 3, 24, or 72 h after nerve injury (n=6/each). In rats with indomethacin 3 or 24 h after nerve injury, ipsi-lateral paw withdrawal thresholds 7–35 days after nerve injury were significantly higher compared with those in the control group (n=6: without peri-sciatic treatment) (P<0.05). However, such efficacy was no longer apparent when indomethacin was administered 72 h after nerve injury. These results suggest that peri-sciatic administration of indomethacin early (less than 24 h) after nerve injury can attenuate the development of allodynia. [Copyright &y& Elsevier]

Primary localized amyloidosis of the mesopharynx is rare. We present the case of a 12-year-old girl; as far as we are aware, our case is the third pediatric case in the English literature. Her chief complaint was a pharyngeal mass identified by the health examination at primary school. Physical examination revealed a mass in the faucial tonsil. Histologically, the lesion was composed of deposition of amyloid and chronic inflammatory cell infiltration. Immunohistochemical studies showed that the lesion was positive for amyloid P component (AP) and negative for amyloid L (AL). No treatments were applied, because she had no symptoms. During the observation period of 24 months, the mesopharyngeal mass showed no remarkable change. [Copyright &y& Elsevier]

The tunnel current (I) to tunnel gap width (s) dependences (the I-s characteristics) of copper(II) phthallocyanine (CuPc)-adsorbed surface of gold under atmosphere were investigated. When the bias voltage of +500mV was applied to the sample, the I-s characteristics began to change, and its slope {-d(log I)/ds} corresponding to the barrier height drastically decreased at higher voltage. Barrier heights evaluated at high voltage region were found to be 1 or 2 orders lower than those at low voltage region. The near infrared spectrum of CuPc in solid state was also found to change at >500mV. The semiconductive nature of CuPc is concluded to be the reason of this change. [ABSTRACT FROM AUTHOR]

BACKGROUND: We report here on the successful surgical treatment of ingrown nails by partial resection of the nail plate and matrix using a carbon dioxide laser. MATERIALS AND METHODS: The subjects of this study were 28 patients (37 cases) who visited our outpatient clinic with the chief complaint of ingrown nails of the great toe between October 1995 and October 1999. They included 12 males and 25 females. Patient age ranged from six to 72 years (mean 26.5 years), and the post operative follow-up period ranged from eight to 48 months (mean 23.2 months). RESULTS: Clinically, this treatment was excellent in terms of operating time reduction, mitigation of mid-operative and post-operative bleeding and pain, and treatment period reduction. Furthermore, no recurrences were observed during the study period. CONCLUSIONS: Judging from the good therapeutic results and improved quality of life of patients, this treatment is expected to be commonly used in the future. [ABSTRACT FROM AUTHOR]

In order to determine the cause of active or passive sensation and action, we studied the effect of perception on gaze and posture control. Normal adults and a patient with bilateral labyrinthine loss underwent whole body rotation seated in a chair (120°/s) or standing on a platform (60°/s), while tilting their head with their vision normal or covered. Eye movements were recorded by a CCD video camera and body sways by a force platform. In normal subjects, gaze and posture became ataxic when head tilting with their vision covered, but they remained skilled under conditions of normal vision. The patient with bilateral labyrinthine loss did not undergo the effect of head tilting with no vision. It seems likely that sensation and action, whether they are skilled or ataxic, are controlled by the perception of an outer world which is integrated from visual and vestibular inputs and functions as a vector in the head. [ABSTRACT FROM AUTHOR]

Examined the synthesis and ferromagnetic spin interaction of a set of pi-conjugated and alternant but non-Kekule-type di- and tri-phenyleneethynylenes. Substitutions with phenoxyl radicals; Synthesis via head-to-tail coupling of benzenes; Coupling effect of the diphenyl ethynylene bridge; Effect of conjugation on alignment.

Functional appliances are widely used for promoting mandibular growth by utilizing a construction bite position. We aimed to measure the mechanical load generated by movement of functional appliances and determine the factors influencing this load. Thirteen patients aged 8–12 years were selected for the study, and the load was measured using a previously developed measurement device. To investigate the factors affecting the load, the temporomandibular joint morphology and muscles related to the mandible were examined using cone-beam computed tomography. The standard regression coefficients of the factors affecting the load per millimeter of movement distance were 0.64 and 0.66 for (a) the inclination of the articular eminence and (b) the angle between occlusal plane and posterior temporalis, respectively. Measurement of the occlusal plane to the posterior temporalis and the inclination of the articular eminence were significantly different (p < 0.05). The angle of inclination of the articular eminence emerged as a strong influencing factor. Similarly, the influence of measurements from the occlusal plane to the posterior temporalis was considerable since the posterior temporalis muscle is the most active when the mandible is extended forward. We also found a possible relationship between the occlusal force and load at the construction bite position. To our knowledge, this is the first study to determine the actual load associated with the angle of the temporalis muscle to the occlusal plane, inclination angle of the articular eminence, angle between the occlusal plane and the Frankfort plane, and the angle between the geniohyoid muscle and the occlusal plane. Therefore, mechanical considerations need to be more accurate to facilitate safe orthodontic treatment. [ABSTRACT FROM AUTHOR]

The annealing effect on the optical and magnetic properties of the GaDyN layers was studied. The PL intensities of yellow and green bands as well as the intra-4 f orbital transition of Dy3+ ions were found to decrease for the samples annealed at 900 and 1000 °C. It is supposed that the intra-4 f orbital transition is related to the broad peak luminescence coming from defects. Increasing the annealing temperature, the magnetization becomes smaller. It is considerable that the number of electrons coming from defects was reduced by the annealing treatments and that the ferromagnetism in GaDyN is attributed as carrier induced ferromagnetism. [ABSTRACT FROM AUTHOR]

A questionnaire was devised to quantify and measure four categories: the behavioral characteristics of Type A, self-restraint and escape; the causes of anxiety; means of relaxation; and symptoms incidental to anxiety. Questionnaire analysis was performed in patients (n=60) with Ménière's disease and in a control population (n=936). It was statistically proven that the patient group possessed a stress-causative tendency in behavioral characteristics, felt stronger anxiety and showed more severe symptoms owing to this anxiety. Since the level of anxiety highly correlates with the score of behavioral characteristics and also with severity of symptoms, it seems likely that behavioral characteristics produce the anxiety, which, in turn, results in various symptoms of autonomic nervous disorders. A tendency towards stress-causative behavioral characteristics in Ménière's disease patients may be important in the genesis of endolymphatic hydrops. [ABSTRACT FROM AUTHOR]

Introduction: The multicenter randomized phase III KHBO1401 study (gemcitabine+cisplatin+S-1 [GCS] vs. GC in biliary tract cancers [BTC]) demonstrated that GCS not only prolonged patient survival but also achieved a high response rate and that it should be good for neoadjuvant therapy. Therefore, to explore the possibilities of neoadjuvant therapy, we investigated the tumor shrinkage pattern. Methods: Among the total of 246 patients enrolled in the KHBO1401, the tumor shrinkage pattern and survival were investigated in patients with measurable BTC (n = 183, 74%; GCS, n = 91; GC, n = 92). Results: The tumor shrinkage pattern could be divided into 4 categories based on the response at 100 days after enrollment: categories A (<–30% in size), B (−30–0%), C (0% to +20%), and D (>+20%). The GCS arm included more category A and B cases (61 [67%] vs. 33 [36%], p < 0.0001). Each category predicted the best response and overall survival (p < 0.0001). Category A showed sustained tumor response compared with category B; in GCS, the time to maximum tumor response was 165 ± 76 days in category A and 139 ± 78 in category B. Categories C and D did not achieve tumor shrinkage. The maximum tumor shrinkage size in category A was −53% in the GCS arm and −65% in the GC arm (p = 0.0892). Twenty percent of patients in the GCS showed tumor regrowth 154 ± 143 days later. Conclusion: GCS provided faster and greater tumor shrinkage with better survival in comparison to GC, although 20% of patients showed regrowth after 6 cycles. [ABSTRACT FROM AUTHOR]

Background: Factors related to surgical outcomes of type I tympanoplasty for tympanic membrane (TM) perforation in children are controversial. Objectives: To investigate factors related to anatomical results of type I tympanoplasty for TM perforation 1 year after surgery. Material and methods: We examined 68 ears. Anatomical results were determined based on the presence or absence of re-perforation, atelectasis, and otitis media with effusion. We retrospectively analyzed factors based on age (≤8 and >8 years), cause and size of TM perforation (<50% and ≥50%), history of asthma and cleft palate, and size of mastoid air cell system in bilateral ears before tympanoplasty. Audiological prognosis was evaluated in ears with anatomical success 1 year after surgery. Results: Anatomical success was achieved in 80.9% (55/68) of the ears. No significant differences were observed between these factors and anatomical results. All children with cleft palate had anatomical success. Mean pure-tone average (0.5–4 kHz) was 16.25 dB HL for ears with both TM perforations <50% and ≥50%. Conclusion and significance: We observed no significant relationship between factors considered and surgical outcomes. However, audiological prognosis was favorable for anatomical success regardless of TM perforation size. Accordingly, type I tympanoplasty is considered useful for TM perforation in children. [ABSTRACT FROM AUTHOR]

The PTPRQ gene has been identified as one of the genes responsible for non-syndromic sensorineural hearing loss (SNHL), and assigned as DFNA73 and DFNB84. To date, about 30 causative PTPRQ variants have been reported to cause SNHL. However, the detailed clinical features of PTPRQ-associated hearing loss (HL) remain unclear. In this study, 15,684 patients with SNHL were enrolled and genetic analysis was performed using massively parallel DNA sequencing (MPS) for 63 target deafness genes. We identified 17 possibly disease-causing PTPRQ variants in 13 Japanese patients, with 15 of the 17 variants regarded as novel. The majority of variants identified in this study were loss of function. Patients with PTPRQ-associated HL mostly showed congenital or childhood onset. Their hearing levels at high frequency deteriorated earlier than that at low frequency. The severity of HL progressed from moderate to severe or profound HL. Five patients with profound or severe HL received cochlear implantation, and the postoperative sound field threshold levels and discrimination scores were favorable. These findings will contribute to a greater understanding of the clinical features of PTPRQ-associated HL and may be relevant in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: We aimed to assess the clinical characteristics of extent patterns in congenital cholesteatoma, based on the Japan Otological Society (JOS) staging system.Methods: This was a retrospective chart review that included 80 ears of 80 patients with congenital cholesteatoma who underwent primary surgery at a tertiary academic medical center. The main characteristics and outcomes reviewed were sex, age, clinical background, surgical method, and stage classification according to two staging classifications: the criteria advocated by JOS and Potsic staging system.Results: The age at the time of surgery ranged from 1 to 35 years (average 8.4 years), and there were 54 men and 26 women. According to the JOS staging system, 12 ears were Stage Ia (15%), 7 ears were Stage Ib (9%), 1 ear was Stage Ic (1%), 59 ears were Stage II (74%), and 1 ear was Stage III (1%). In the study of postoperative residual recurrence, there were 4 cases after the primary operation and 3 cases after the staged operation. All 3 ears with residual disease after planned surgery were cholesteatomas that extended to all the tympanomastoid space.Conclusion: We consider the JOS staging system to be more suitable, in terms of anatomical classification and surgical procedure selection for comparison between Europe, the United States, and Asia. Specifically, it was advantageous that the PTAM classification and the S classification are associated with surgical procedure selection and postoperative course. [ABSTRACT FROM AUTHOR]