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Baro-challenge-induced Eustachian tube dysfunction (ETD) manifests due to inadequate Eustachian tube (ET) function during rapid ambient pressure changes, although ET function may be normal in normobaric situations. This systematic review and retrospective cohort study aimed to evaluate the effectiveness of balloon Eustachian tuboplasty (BET) for the treatment of baro-challenge-induced ETD.PubMed, the Cochrane Library, Scopus, and Helsinki University Hospital cohort.A systematic literature search was conducted in November 2020 and resulted in 174 articles. Eight articles fulfilled the inclusion criteria. Data was available altogether from 74 adult baro-challenge-induced ETD patients. In addition, we retrospectively evaluated 39 BET operations at Helsinki University Hospital from 2011 to 2020. Data from these 39 patients were collected from medical charts, and a questionnaire was sent to the patients. Meta-analysis was used to evaluate subjective symptom improvement, changes in ETD Questionnaire-7 (ETDQ-7) scores, and Valsalva maneuver performance.In the systematic review, the outcome parameters varied between studies. Improvement was reported in subjective symptoms, Valsalva maneuver, ETDQ-7, tubomanometry, and pressure chamber test. Response rate for the Helsinki University Hospital cohort study was 72% (28/39). Mean follow-up time from the BET to the questionnaire was 4 years 8 months (SD 26months). Of those patients 93% (26/28) found the operation beneficial. Meta-analysis including up to 113 patients showed improvement in Valsalva maneuver, ETDQ-7, and improvement in subjective symptoms. Overall improvement in symptoms was noted in 81% of the patients.BET seems to be effective in the majority of patients with baro-challenge-induced ETD.

Background Multi slice computed tomography (MSCT) is the most common used method in middle ear imaging. However, MSCT lacks the ability to distinguish the ossicular chain microstructures in detail resulting in poorer diagnostic outcomes. Novel cone beam computed tomography (CBCT) devices’ image resolution is, on the other hand, better than MSCT resolution. The aim of this study was to optimize imaging parameters of a novel full body CBCT device to obtain optimal contrast to noise ratio (CNR) with low effective dose, and to optimize its clinical usability. Methods Imaging of five anonymous excised human cadaver temporal bones, the acquisition of the effective doses and the CNR measurements were performed for images acquired on using Planmed XFI® full body CBCT device (Planmed Oy, Helsinki, Finland) with a voxel size of 75 µm. All images acquired from the specimens using 10 different imaging protocols varying from their tube current exposure time product (mAs) and tube voltage (kVp) were analyzed for eight anatomical landmarks and evaluated by three evaluators. Results With the exception of protocol with 90 kVp 100 mAs, all other protocols used are competent to image the finest structures. With a moderate effective dose (86.5 µSv), protocol with 90 kV 450 mAs was chosen the best protocol used in this study. A significant correlation between CNR and clinical image quality of the protocols was observed in linear regression model. Using the optimized imaging parameters, we were able to distinguish even the most delicate middle ear structures in 2D images and produce accurate 3D reconstructions. Conclusions In this ex vivo experiment, the new Planmed XFI® full body CBCT device produced excellent 2D resolution and easily created 3D reconstructions in middle ear imaging with moderate effective doses. This device would be suitable for middle ear diagnostics and for e.g., preoperative planning. Furthermore, the results of this study can be used to optimize the effective dose by selecting appropriate exposure parameters depending on the diagnostic task.

Funding Information: We want to thank M.Sc. (Tech) Pekka Paavola for photo stacking technique photographing. We also want to thank Ph.D. Jukka Kuva (Geological Survey of Finland, Espoo, Finland) for collaboration with regard to micro-CT imaging. X-ray tomography was supported by the Academy of Finland via RAMI infrastructure project (#293109). Funding Information: This study has been funded by the Tauno Palva Foundation, the Helsinki University Hospital Research Fund and the Academy of Finland Grant 325509. Publisher Copyright: © 2023 Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution License, permitting distribution and reproduction in any medium, provided the original work is properly cited. Despite advances in prosthesis materials, operating microscopes and surgical techniques during the last 50 years, long-lasting hearing improvement remains a challenge in ossicular chain reconstruction. Failures in the reconstruction are mainly due to inadequate length or shape of the prosthesis, or defects in the surgical procedure. 3D-printed middle ear prosthesis might offer a solution to individualize treatment and obtain better results. The aim of the study was to study the possibilities and limitations of 3D-printed middle ear prostheses. Design of the 3D-printed prosthesis was inspired by a commercial titanium partial ossicular replacement prosthesis. 3D models of different lengths (1.5–3.0 mm) were created with Solidworks 2019–2021 software. The prostheses were 3D-printed with vat photopolymerization using liquid photopolymer Clear V4. Accuracy and reproducibility of 3D printing were evaluated with micro-CT imaging. The acoustical performance of the prostheses was determined in cadaver temporal bones with laser Doppler vibrometry. In this paper, we present an outline of individualized middle ear prosthesis manufacturing. 3D printing accuracy was excellent when comparing dimensions of the 3D-printed prostheses and their 3D models. Reproducibility of 3D printing was good if the diameter of the prosthesis shaft was 0.6 mm. 3D-printed partial ossicular replacement prostheses were easy to manipulate during surgery even though they were a bit stiffer and less flexible than conventional titanium prostheses. Their acoustical performance was similar to that of a commercial titanium partial ossicular replacement prosthesis. It is possible to 3D print functional individualized middle ear prostheses made of liquid photopolymer with good accuracy and reproducibility. These prostheses are currently suitable for otosurgical training. Further research is needed to explore their usability in a clinical setting. In the future, 3D printing of individualized middle ear prostheses may provide better audiological outcomes for patients.

Background Ear canal and middle ear tumors are rare and exhibit variability in histology and clinical manifestation. Surgical resection remains the treatment of choice, but individualized approach is needed to preserve function when possible. Aims/objectives To review the management and outcome of ear canal and middle ear tumors at an academic referral center. Materials and methods Helsinki University Hospital (HUS) patient files were searched for clinically and histologically confirmed ear canal and middle ear tumors over a 14-year period. The minimum follow-up time was 2 years. Results Eighty-seven patients with 88 tumors were identified. There were 20 (23%) benign external auditory canal (EAC), 36 (41%) benign middle ear space (MES), 29 (33%) malignant EAC, and 3 (3%) malignant MES tumors. Most (92%) tumors were managed with primary resection. Thirty-five percent of the operatively managed patients had a residual or a recurrent tumor. Conclusions and significance EAC and MES tumors show great diagnostic and histologic heterogeneity with need for individualized investigative and treatment approaches. In benign tumors, we advocate aggressive local surgical control without sacrificing vital structures. In malignant tumors, we recommend local surgical control with or without adjunct RT.

Publisher Copyright: © 2023 The Author(s) The electrode-generated intracochlear electrical field (EF) spreads widely along the scala tympani surrounded by poorly-conducting tissue and it can be measured with monopolar transimpedance matrix (TIMmp). Bipolar TIM (TIMbp) allows estimations of local potential differences. With TIMmp, the correct alignment of the electrode array can be assessed, and TIMbp may be useful in more subtle evaluations of the electrode array's intracochlear location. In this temporal bone study, we investigated the effect of the cross-sectional scala area (SA) and the electrode-medial-wall distance (EMWD) on both TIMmp and TIMbp using three types of electrode arrays. Also, multiple linear regressions based on the TIMmp and TIMbp measurements were used to estimate the SA and EMWD. Six cadaver temporal bones were consecutively implanted with a lateral-wall electrode array (Slim Straight) and with two different precurved perimodiolar electrode arrays (Contour Advance and Slim Modiolar) for variation in EMWD. The bones were imaged with cone-beam computed tomography with simultaneous TIMmp and TIMbp measurements. The results from imaging and EF measurements were compared. SA increased from apical to basal direction (r = 0.96, p < 0.001). Intracochlear EF peak negatively correlated with SA (r = –0.55, p < 0.001) irrespective of the EMWD. The rate of the EF decay did not correlate with SA but it was faster in the proximity of the medial wall than in more lateral positions (r = 0.35, p < 0.001). For a linear comparison between the EF decaying proportionally to squared distance and anatomic dimensions, a square root of inverse TIMbp was applied and found to be affected by both SA and EMWD (r = 0.44 and r = 0.49, p < 0.001 for both). A regression model confirmed that together TIMmp and TIMbp can be used to estimate both SA and EMWD (R2 = 0.47 and R2 = 0.44, respectively, p < 0.001 for both). In TIMmp, EF peaks grow from basal to apical direction and EF decay is steeper in the proximity of the medial wall than in more lateral positions. Local potentials measured via TIMbp correlate with both SA and EMWD. Altogether, TIMmp and TIMbp can be used to assess the intracochlear and intrascalar position of the electrode array, and they may reduce the need for intra- and postoperative imaging in the future.

BACKGROUND: Sinus barotraumas are a common condition in aviation medicine, sometimes compromising flight safety and even permanently grounding aircrew. Considering this and the ever-increasing amount of commercial aviation, a thorough examination is required.METHODS: In this survey study, an anonymous, electronic questionnaire was distributed to commercial aircrew of the three major commercial airlines operating in Finland (N = 3799), covering 93% of the target population (i.e., all commercial aircrew operating in Finland, N = 4083). Primary outcomes were self-reported prevalence, clinical characteristics, and health and occupational effects of sinus barotraumas in flight. Secondary outcomes were adjusted odds ratios (OR) for frequency of sinus barotraumas with respect to possible risk factors.RESULTS: Response rate was 47% (N = 1789/3799), with 61% (N = 1088) of the respondents having experienced sinus barotraumas in flight. Of those affected, 59% had used medications, 18% had undergone surgical procedures, and 53% had been on sick leave due to sinus barotraumas (38% during the last year) in flight. Factors associated with sinus barotraumas were female sex [OR, 2.47; 95% confidence interval (CI) 1.35–4.50] and a high number of upper respiratory tract infections (≥3 vs. CONCLUSION: Sinus barotraumas were reported by 61% of commercial aircrew. They caused an increased need for medications, otorhinolaryngology-related surgical procedures, and sickness absence from flight duty. The possible risk factors were female sex and a high number of URTIs/yr.Lindfors OH, Ketola KS, Klockars TK, Leino TK, Sinkkonen ST. Sinus barotraumas in commercial aircrew. Aerosp Med Hum Perform. 2021; 92(11):857–863.

Multiple myeloma (MM), the most common plasmacell neoplasm, manifests relatively often in the head and neck region, but rarely in the ear. We present a patient with fluctuating hearing loss, otalgia, persistent otitis externa and occipital swelling. CT imaging showed a large mass of cranium and the initial radiological diagnosis was plasmacytoma. Multiple osteolytic bone lesions, monoclonal serum protein with serum M component concentration of 35.2 g/L and bone marrow biopsy with abnormal, clonal plasma cells population confirmed the diagnosis of multiple myeloma. Although a rare manifestation in the external ear canal and its surroundings, plasmacytoma or multiple myeloma should be considered as a possible diagnosis in the presence of a scalp mass or a treatment resistant swelling of the external ear canal.

Purpose: An important outcome measure of patient care is the impact on the patient's health-related quality of life (HRQoL). Current ear-specific HRQoL instruments are designed for one diagnosis and emphasize different subdivisions such as symptoms, hearing problems, psychosocial impact, and the need for care. The optimal length of the recall period has not been studied. For these reasons, a new survey is needed that would cover most chronic ear diseases. Methods: A preliminary 24-item survey (EOS-24) was created. Untreated adult patients (included n = 186) with one of seven different chronic otologic conditions from all university hospitals in Finland were recruited to respond to EOS-24 and the 15D general HRQoL instrument. The recruiting otologists evaluated the severity of the disease and the disability caused by it. A control group was recruited. Based on the patients' responses in different diagnosis groups, the items were reduced according to pre-defined criteria. The resulting survey was validated using a thorough statistical analysis. Results: The relevance and necessity of the original 24 items were thoroughly investigated, leading to the exclusion of 8 items and the modification of 1. The remaining 16 items were well-balanced between subdivisions and were useful in all seven diagnosis groups, thus constituting the final instrument, EOS-16. The most suitable recall period was three months. Conclusions: EOS-16 has been created according to the HRQoL survey guidelines with a versatile nationwide patient population. The survey has been validated and can be used for a wide range of chronic ear diseases as a HRQoL instrument. (C) 2021 PLA General Hospital Department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd.

The objective was to evaluate the pure-tone audiogram-based screening protocols in VS diagnostics. We retrospectively analyzed presenting symptoms, pure tone audiometry and MRI finding from 246 VS patients and 442 controls were collected to test screening protocols (AAO-HNS, AMCLASS-A/B, Charing Cross, Cueva, DOH, Nashville, Oxford, Rule3000, Schlauch, Seattle, Sunderland) for sensitivity and specificity. Results were pooled with data from five other studies, and analysis of sensitivity, specificity and positive likelihood ratio (LR+) for each protocol was performed. Our results show that protocols with significantly higher sensitivity (AMCLASS-A/B, Nashville) show also significantly lowest specificity, and tend to have low association (positive likelihood ratio, LR+) to the VS. The highest LR+ was found for protocols AAO-HNS, Rule3000 and Seattle. In conclusions, knowing their properties, screening protocols are simple decision-making tools in VS diagnostic. To use the advantage of the highest sensitivity, protocols AMCLASS-A + B or Nashville can be of choice. For more reasonable approach, applying the protocols with high LR+ (AAO-HNS, Rule3000, Seattle) may reduce the overall number of MRI scans at expense of only few primarily undiagnosed VS. (C) 2020 PLA General Hospital Department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd.

Funding Information: The study was funded by the Academy of Finland (AD Grant No. 333525), State Research Funding of the Kuopio University Hospital (TT Grant No. 5551865, AD Grant No. 5551853), The Finnish ORL-HNS Foundation (TT Grant No. 20210002 and No. 20220027), North Savo Regional Fund (TT Grant No. 65202121, AD Grant No. 65202054), Finnish Cultural Foundation (TT Grant No. 00211098), and The Finnish Society of Ear Surgery. Publisher Copyright: Copyright © 2022 Timonen, Iso-Mustajärvi, Linder, Vrzakova, Sinkkonen, Luukkainen, Laitakari, Elomaa and Dietz. Introduction: In recent decades, the lack of educational resources for cadaveric dissections has complicated the hands-on otological surgical training of otorhinolaryngology residents due to the poor availability of cadaver temporal bones, facilities, and limited hours for practice. Since students must gain adequate and patient-safe surgical skills, novel training methods need to be considered. In this proof-of-concept study, a new virtual reality (VR) software is described; this was used during a national temporal bone dissection course where we investigated its feasibility for otological surgical training. Methods: A total of 11 otorhinolaryngology residents attended the annual 2-day hands-on temporal bone dissection course; they were divided into two groups with similar experience levels. Both groups received a lecture on temporal bone anatomy. A total of 22 cadaver temporal bones were harvested for the course; 11 of these bones were imaged by computed tomography. VR software designed for preoperative planning was then used to create 3D models of the imaged temporal bones. Prior to dissection training, the first group underwent a 30-min VR session, where they identified 24 surgically relevant anatomical landmarks on their individual temporal bone. The second group proceeded directly to dissection training. On the second day, the groups were switched. The feasibility of VR training was assessed with three different metrics: surgical performance evaluation using a modified Hopkins objective structured assessment of technical skill (OSATS), time for the surgical exposure of anatomical landmarks, and the user experience collected with a Likert scale questionnaire. Results: No differences were noted in the overall performance between the groups. However, participants with prior VR training had a lower mean time for surgical exposure of anatomical landmarks (antrum 22.09 vs. 27.64 min, p = 0.33; incus 60.00 vs. 76.00, p = 0.03; PSCC 71.83 vs. 88.50, p = 0.17) during dissection training. The participants considered VR beneficial for anatomy teaching, surgery planning, and training. Conclusion: This study demonstrated the feasibility of implementing VR training in a temporal bone dissection course. The VR training demonstrated that even short expert-guided VR sessions are beneficial, and VR training prior to the dissections has a positive effect on the time needed to perform surgical tasks while maintaining comparable performance scores.

Introduction: Middle ear barotrauma (MEBt) is the most common medical complication in diving, posing a serious risk to dive safety. Given this prevalence and the continuing growth of the diving industry, a comprehensive overview of the condition is warranted. Methods: This was a survey study. An anonymous, electronic questionnaire was distributed to 7,060 recipients: professional divers of the Finnish Border Guard, the Finnish Rescue Services, and the Finnish Heritage agency; and recreational divers registered as members of the Finnish Divers’ Association reachable by e-mail (roughly two-thirds of all members and recreational divers in Finland). Primary outcomes were self-reported prevalence, clinical characteristics, and health effects of MEBt while diving. Secondary outcomes were adjusted odds ratios (OR) for frequency of MEBt with respect to possible risk factors. Results: A total of 1,881 respondents participated in the study (response rate 27%). In total, 81% of the respondents had experienced MEBt while diving. Of those affected, 38% had used medications and 1% had undergone otorhinolaryngology-related surgical procedures due to MEBt. Factors most associated with MEBt were poor subjective success in Valsalva (‘occasionally’ versus ‘always’ successful: OR 11.56; 95% CI 7.24–18.47) and Toynbee (‘occasionally’ versus ‘always’ successful: OR 3.51; 95% CI 1.95–6.30) manoeuvres. Conclusions: MEBt is common in both recreational and professional divers, having affected 81% of the respondents. The main possible risk factors include poor success in pressure equalisation manoeuvres.

Inner ear decompression sickness (IEDCS) is a condition from which only a minority of patients recover completely, the majority ending up with mild to moderate residual symptoms. IEDCS has been reported after deep technical dives using mixed breathing gases, and moderate recreational dives with compressed air as the breathing gas. Considering this and the high proportion of technical diving in Finland, a comparison between IEDCS cases resulting from technical and recreational dives is warranted.This is a retrospective examination of IEDCS patients treated at Hyperbaric Center Medioxygen or National Hyperbaric Centre of Turku University Hospital from 1999 to 2018. Patients were included if presenting with hearing loss, tinnitus, or vertigo and excluded if presenting only with symptoms of middle ear or cerebellar involvement. Patients were divided into technical and recreational divers, based on incident dive.A total of 89 (15.6%) of all DCS patients presented with IEDCS, two-thirds treated during the latter decade. The most common predisposing factors were consecutive days of diving (47.2%), multiple dives per day (53.9%), and factors related to an increase in intrathoracic pressure (27.0%). The symptoms were cochlear in 19.1% and vestibular in 93.3% of cases, symptoms being more common and severe in technical divers. Complete recovery was achieved in 64.5% of technical and 71.4% of recreational divers.The incidence of IEDCS in Finland is increasing, most likely due to changing diving practices. A comprehensive examination should be carried out after an incident of IEDCS in all cases, irrespective of clinical recovery.

BACKGROUND: The etiology of salivary gland tumors is mainly unknown. The anatomical location of the salivary glands, with the mucosal pathway to the oral cavity and its rich microbiome, raises the question of potential viral background. OBJECTIVE: This study focuses on the potential presence of herpes-, polyoma- and parvoviruses in pleomorphic adenoma (PA), recurrent pleomorphic adenoma (RPA) and carcinoma ex pleomorphic adenoma (CaxPA). METHODS: Thirty different viruses were analyzed by PCR-based assays in 68 formalin-fixed paraffin-embedded salivary gland tumors (25 PA, 31 RPA and 12 CaxPA). RESULTS: Virus DNA was detected altogether in 19/68 (28%) tumor samples. Human herpesviruses 6B and 7 (HHV-6B and HHV-7) and Epstein-Barr virus (EBV) were frequently and almost exclusively found in CaxPA (5/12, 7/12, and 3/12, respectively). Within the 7 CaxPA that were virus-positive, 3 samples contained 3, and 1 sample even 4, different viruses. Infrequent viral positivity was shown for parvovirus B19 and cutavirus, as well as Merkel cell and Malawi polyomaviruses. CONCLUSIONS: Our unexpected finding of herpesvirus DNA almost exclusively in CaxPA tissues deserves further in-depth studies.

Objectives: A narrow bony cochlear nerve canal (BCNC), as well as a hypoplastic and aplastic cochlear nerve (CN) have been associated with increased electrically-evoked compound action potential (eCAP) thresholds in some studies, suggesting poorer neural excitability in cochlear implantation. Also, in large cochleae the extent of activated spiral ganglion neurons with electrical stimulation is less than in smaller ones. However, a detailed description of the relationship between eCAP thresholds for a lateral-wall electrode array and dimensions of the inner-ear structures and internal auditory canal (IAC) is missing. Design: The study subjects were 52 pediatric patients with congenital severe-to-profound hearing loss (27 females and 25 males; ages 0.7-2.0 years; 1.0 +/- 0.3 years, mean +/- SD) implanted bilaterally with Cochlear Nucleus CI422, CI522, or CI622 implants with full insertion of the Slim Straight electrode array. Diameters of the cochlea and the BCNC as well as the widths and heights of the IAC and the CN were evaluated from preoperative computed tomography and magnetic resonance images. These anatomical dimensions were compared with each other and with the patients' intraoperative eCAP thresholds. Results: The eCAP thresholds increased from the apical to basal direction (r = 0.89, p < 0.001). After sorting the cochleae into four size categories, higher eCAP thresholds were found in larger than in smaller cochleae (p < 0.001). With similar categorization, the eCAP thresholds were higher in cochleae with a larger BCNC than in cochleae with a smaller BCNC (p < 0.001). Neither IAC nor CN cross-sectional areas affected the eCAP thresholds. Correlations were found between cochlea and BCNC diameters and between IAC and CN cross-sectional areas (r = 0.39 and r = 0.48, respectively, p < 0.001 for both). Conclusions: In the basal part of the electrode array, higher stimulation levels to elicit measurable neural responses (eCAP thresholds) were required than in the apical part. Increased eCAP thresholds associated with a larger cochlear diameter, but contrary to the earlier studies, not with a small size of the BCNC or the CN. Instead, the BCNC diameter correlated significantly with the cochlea diameter.

INTRODUCTION: Inner ear barotrauma (IEBt) and inner ear decompression sickness (IEDCS) are the two dysbaric inner ear injuries associated with diving. Both conditions manifest as cochleovestibular symptoms, causing difficulties in differential diagnosis and possibly delaying (or leading to inappropriate) treatment. METHODS: This was a systematic review of IEBt and IEDCS cases aiming to define diving and clinical variables that help differentiate these conditions. The search strategy consisted of a preliminary search, followed by a systematic search covering three databases (PubMed, Medline, Scopus). Studies were included when published in English and adequately reporting one or more IEBt or IEDCS patients in diving. Concerns regarding missing and duplicate data were minimised by contacting original authors when necessary. RESULTS: In total, 25 studies with IEBt patients (n = 183) and 18 studies with IEDCS patients (n = 397) were included. Variables most useful in differentiating between IEBt and IEDCS were dive type (free diving versus scuba diving), dive gas (compressed air versus mixed gas), dive profile (mean depth 13 versus 43 metres of seawater), symptom onset (when descending versus when ascending or surfacing), distribution of cochleovestibular symptoms (vestibular versus cochlear) and absence or presence of other DCS symptoms. Symptoms of difficult middle ear equalisation or findings consistent with middle ear barotrauma could not be reliably assessed in this context, being insufficiently reported in the IEDCS literature. CONCLUSIONS: There are multiple useful variables to help distinguish IEBt from IEDCS. Symptoms of difficult middle ear equalisation or findings consistent with middle ear barotrauma require further study as means of distinguishing IEBt and IEDCS.

Otitis media (OM) is a common childhood infection that may result in bacterial meningitis (BM). However, OM-associated BM remains poorly characterized. We aimed to study the occurrence, clinical presentation and outcome of this type of childhood BM in Luanda, Angola.Five hundred twelve children from our previous clinical BM trial, with the ear meticulously examined, were analyzed whether they had or not OM, and according to their age, ≤12 month old and12 month old. Prospectively collected clinical data, laboratory test results and outcome for these groups were assessed.Sixty-two children (12%) had OM-associated BM, of whom 39 had otorrhea. Ear discharge was more common in older children (median age 45 months old vs. 12 months old; P0.001). Children with OM often showed an additional infectious focus (n = 20, 32% vs. n = 82, 18%; P = 0.016), were dehydrated (n = 16, 26% vs. n = 66, 15%; P = 0.04), and showed higher odds of complicated clinical course or death (odds ratios 2.27, 95% CI: 1.004-5.15, P = 0.049) compared with children without OM. The12-month-old children with OM often arrived in poor clinical condition with coma and/or ptosis. Otorrhea was associated with HIV positivity. Infants with otorrhea frequently lived under poor socioeconomic conditions.Children with OM-associated BM were prone to many problems, such as being especially ill at presentation, undergoing a difficult clinical course and showing a higher risk of complicated or fatal outcome. HIV infection and malnutrition were common in children with otorrhea, which was also associated with low socioeconomic status.

The nonsteroidal anti-inflammatory drug (NSAID) niflumic acid, a fenamate in structure, has many molecular targets, one of them being specific subtypes of the main inhibitory ligand-gated anion channel, the GABA(A) receptor. Here, we report on the effects of other fenamates and other classes of NSAIDs on brain picrotoxinin-sensitive GABA A receptors, using an autoradiographic assay with [S-35]TBPS as a ligand on mouse brain sections. We found that the other fenamates studied (flufenamic acid, meclofenamic acid, mefenamic acid and tolfenamic acid) affected the autoradiographic signal at low micromolar concentrations in a facilitatory-like allosteric fashion, i.e., without having affinity to the [S-35]TBPS binding site. Unlike niflumic acid that shows clear preference for inhibiting cerebellar granule cell layer GABA(A) receptors, the other fenamates showed little brain regional selectivity, indicating that their actions are not receptor-subtype selective. Of the non-fenamate NSAIDs studied at 100 mu M concentration, diclofenac induced the greatest inhibition of the binding, which is not surprising as it has close structural similarity with the potent fenamate meclofenamic acid. Using two-electrode voltage-clamp assays on Xenopus oocytes, the effect of niflumic acid was found to be dependent on the beta subunit variant and the presence of gamma 2 subunit in rat recombinant alpha 1 beta and alpha 1 beta gamma 2 GABA(A) receptors, with the beta 1 allowing the niflumic acid inhibition and beta 3 the stimulation of the receptor-mediated currents. In summary, the fenamate NSAID5 constitute an interesting class of compounds that could be used for development of potent GABA(A) receptor allosteric agonists with other targets to moderate inflammation, pain and associated anxiety/depression.

BACKGROUND: Middle ear (ME) barotraumas are the most common condition in aviation medicine, sometimes seriously compromising flight safety. Considering this and the ever-increasing amount of commercial aviation, a detailed overview is warranted.METHODS: In this survey study, an anonymous, electronic questionnaire was distributed to commercial aircrew of the three major commercial airlines operating in Finland (N 3799), covering 93% of the target population (i.e., all commercial aircrew operating in Finland, N 4083). Primary outcomes were self-reported prevalence, clinical characteristics, and health and occupational effects of ME barotraumas in flight. Secondary outcomes were adjusted odds ratios (OR) for frequency of ME barotraumas with respect to possible risk factors.RESULTS: Response rate was 47% (N 1789/3799), with 85% (N 1516) having experienced ME barotraumas in flight. Of those affected, 60% had used medications, 5% had undergone surgical procedures, and 48% had been on sick leave due to ME barotraumas (40% during the last year). Factors associated with ME barotraumas included a high number of upper respiratory tract infections [3 URTIs/yr vs. 0 URTIs/yr: OR, 9.02; 95% confidence interval (CI) 3.9920.39] and poor subjective performance in Valsalva (occasionally vs. always successful: OR, 7.84; 95% CI 3.9715.51) and Toynbee (occasionally vs. always successful: OR, 9.06; 95% CI 2.6730.78) maneuvers.CONCLUSION: ME barotraumas were reported by 85% of commercial aircrew. They lead to an increased need for medications, otorhinolaryngology-related surgical procedures, and sickness absence from flight duty. Possible risk factors include a high number of URTIs and poor performance in pressure equalization maneuvers.Lindfors OH, Ketola KS, Klockars TK, Leino TK, Sinkkonen ST. Middle ear barotraumas in commercial aircrew. Aerosp Med Hum Perform. 2021; 92(3):182189.

In angiosperms, endosperm development comprises a series of developmental transitions controlled by genetic and epigenetic mechanisms that are initiated after double fertilization. Polycomb repressive complex 2 (PRC2) is a key component of these mechanisms that mediate histone H3 lysine 27 trimethylation (H3K27me3); the action of PRC2 is well described in Arabidopsis thaliana but remains uncertain in cereals. In this study, we demonstrate that mutation of the rice (Oryza sativa) gene EMBRYONIC FLOWER2a (OsEMF2a), encoding a zinc-finger containing component of PRC2, causes an autonomous endosperm phenotype involving proliferation of the central cell nuclei with separate cytoplasmic domains, even in the absence of fertilization. Detailed cytological and transcriptomic analyses revealed that the autonomous endosperm can produce storage compounds, starch granules, and protein bodies specific to the endosperm. These events have not been reported in Arabidopsis. After fertilization, we observed an abnormally delayed developmental transition in the endosperm. Transcriptome and H3K27me3 ChIP-seq analyses using endosperm from the emf2a mutant identified downstream targets of PRC2. These included >100 transcription factor genes such as type-I MADS-box genes, which are likely required for endosperm development. Our results demonstrate that OsEMF2a-containing PRC2 controls endosperm developmental programs before and after fertilization.

OBJECTIVES Tubomanometry (TMM) is an objective method for investigating Eustachian tube (ET) function, but difficulties in technique and interpretation may reduce its usability. The objective of our study was to investigate common difficulties with TMM in different ET dysfunction (ETD) patient groups and at different pressures (30, 40, and 50 mbars) when first introducing TMM to otologic practice. Furthermore, we wanted to investigate whether it would be possible to perform TMM at only one pressure and obtain a representative result. METHODS A retrospective chart review of a 2-year cohort of 114 patients with a history of ETD treated at a tertiary referral center. Primary outcome was the success rate of TMM, secondary the reasons for unsuccessful measurements. Tertiary outcome was the correlation of TMM results at adjacent pressures. RESULTS TMM success rate was 91%, varying 81 to 94% in different ETD patient groups and 87 to 94% at different pressures. Unsuccessful measurements resulted from air-leaks from the external ear canal, abnormal ear canal pressure curves (R

Introduction: Sinus barotrauma is a common occurrence in diving and subaquatic medicine, potentially compromising dive safety. To gain a more thorough understanding of the condition, an in-depth investigation is justified. Methods: This was a survey study. An anonymous, electronic questionnaire was distributed to 7,060 recipients: professional divers of the Finnish Border Guard, the Finnish Rescue Services, and the Finnish Heritage agency, as well as recreational divers registered as members of the Finnish Divers’ Association reachable by email (roughly two-thirds of all members and recreational divers in Finland). Primary outcomes were self-reported prevalence, clinical characteristics, and health effects of sinus barotrauma while diving. Secondary outcomes were adjusted odds ratios (OR) for frequency of sinus barotrauma with respect to possible risk factors. Results: In total, 1,881 respondents participated in the study (response rate 27%). A total of 49% of the respondents had experienced sinus barotrauma while diving and of those affected, 32% had used medications to alleviate their symptoms. The factors associated with sinus barotrauma were pollen allergies (OR 1.59; 95% CI 1.10–2.29), regular smoking (OR 2.04; 95% CI 1.07–3.91) and a high number of upper respiratory tract infections per year (≥ 3 vs. < 3 infections per year: OR 2.76; 95% CI 1.79–4.24). Conclusions: Sinus barotrauma is the second most common condition encountered in diving medicine, having affected 49% of the respondents. Possible risk factors include allergies to pollen, regular smoking, and a high number of URTIs per year.

SUMMARYPlants have evolved unique responses to fluctuating light conditions in their environment. One such response, chloroplast photorelocation movement, optimizes photosynthesis under weak light and prevents photodamage under strong light. CHLOROPLAST UNUSUAL POSITIONING 1 (CHUP1) plays a pivotal role in the light-responsive chloroplast movements, which are driven by dynamic reorganization of chloroplast actin (cp-actin) filaments. In this study, we demonstrated that fluorescently tagged CHUP1 colocalized and was coordinately reorganized with cp-actin filaments during chloroplast movement in Arabidopsis thaliana. The resulting asymmetric distribution of CHUP1 was reversibly regulated by the blue light receptor phototropin. X-ray crystallography indicated that the CHUP1 C-terminal domain shares structural similarity with the formin homology 2 (FH2) domain, although there is no sequence similarity between the two domains. The CHUP1 C-terminal domain stimulated actin polymerization in the presence of profilin. We conclude that CHUP1 is a novel, plant-specific actin nucleator that functions in cp-actin-based chloroplast movement.HighlightsBlue light changes the distribution pattern of CHUP1Formin FH2 and CHUP1 C-terminal domains are structurally similar but not homologousCHUP1 nucleates and severs actin filaments in vitroCHUP1 is a novel, plant-specific actin nucleator for chloroplast movement

Objective To study whether balloon Eustachian tuboplasty (BET) is a feasible and safe procedure under local anesthesia. Study design Prospective multicenter case-control study. Methods Patients undergoing either BET (n = 13) or endoscopic sinus surgery (ESS) (n = 12) under local anesthesia, with the possibility of sedation and analgesia, were monitored during the procedure and recovery period for possible adverse effects. After the procedure, the patients responded to a questionnaire assessing their experience. Results No adverse effects were detected in the BET group. Patients in the BET group reported similar Visual Analog Scale scores for pain during the operation as the ESS group (5.0 ± 0.7 vs. 3.2 ± 0.7, mean ± standard error of the mean). However, patients in the BET group experienced more discomfort (4.2 ± 0.6 vs. 2.5 ± 0.3, respectively, P = 0.049). Seventy-seven and 92% of the patients in the BET and ESS groups, respectively, considered the anesthesia and pain relief to be sufficient. Patients from both the BET and ESS groups were almost devoid of pain 1 to 2 hours postoperatively (0.8 ± 0.2 and 1.4 ± 0.3, respectively). In total, 12 of 13 patients in the BET group, and all 12 patients in the ESS group, would choose local anesthesia with sedation and analgesia if they needed to undergo the same procedure again. Conclusion BET is a safe and feasible procedure under monitored anesthesia care, including local anesthesia along with sedation and analgesia. There is need for further methodological improvement to reduce pain and discomfort during the operation. Level of evidence 4. Laryngoscope, 127:1021-1025, 2017.

OBJECTIVES/HYPOTHESIS This study compares image quality and appropriateness for teleconsultations for three different otological conditions. STUDY DESIGN Web-based survey. METHODS We compared four digital otoscopes via a Web-based questionnaire distributed to all Finnish ear, nose, and throat (ENT) specialists and residents. The survey consisted of three fictional patient cases, each of which was presented with images taken using the otoscopes studied. Respondents assessed the image quality on a visual analog scale (VAS), assessing its appropriateness for teleconsultations and comparing images taken using different otoscopes to one another. RESULTS In total, 98 individuals responded, consisting of 81 ENT specialists and 17 ENT residents. The CellScope Oto and Digital MacroView received higher VAS scores for image quality and appropriateness for teleconsultations than the FireFly and Delfino otoscopes (P

There is no unanimous consensus for indications of eustachian tube balloon dilation (ETBD). Nordic countries have relatively similar hospital organizations and treatment guidelines. Therefore, it was logical to organize a consensus meeting of ETBD. The symposium: Nordic Experiences on Eustachian Tube Balloon Dilation, in Copenhagen, 30–31 March, 2017. The panellists from Denmark, Finland, Norway and Sweden and the attendees of the meeting agreed a consensus on the following issues: Candidates, Definition of Eustachian Tube Dysfunction, Diagnostic Work up, Differential Diagnosis, Contraindications, ETBD Procedure, Complications, Follow-up, and Outcomes. The article also presents the status for ETBD in each of these countries. Thereafter the consensus statement has been discussed in the national societies and meetings for ear surgeons in each of these countries. It can be assumed that surgeons in the hospitals of these Nordic countries generally follow the recommendations from the consensus meeting. Keywords: Eustachian tube, Eustachian tube dysfunction, Balloon dilation, Nordic consensus

The nonsteroidal anti-inflammatory drug (NSAID) niflumic acid, a fenamate in structure, has many molecular targets, one of them being specific subtypes of the main inhibitory ligand-gated anion channel, the GABA

Plants and animals express multiple actin isoforms in a manner that is dependent on tissues, organs and the stage of development. Previous genetic analyses suggested that individual actin isoforms have specific roles in cells, but there is little biochemical evidence to support this hypothesis. In this study, we purified four recombinant Arabidopsis actin isoforms, two major vegetative actin isoforms, ACT2 and ACT7, and two major reproductive isoforms, ACT1 and ACT11, and characterized them biochemically. Phalloidin bound normally to the filaments of the two reproductive actins as well as to the filaments of skeletal muscle actin. However, phalloidin bound only weakly to ACT7 filaments and hardly at all to ACT2 filaments, despite the conserved sequence of the phalloidin-binding site. Polymerization and phosphate release rates among these four actin isoforms were also significantly different. Moreover, interactions with profilin (PRF) were also different among the four Arabidopsis actin isoforms. PRF1 and PRF2 inhibited the polymerization of ACT1, ACT11 and ACT7, while ACT2 was only weakly affected. Plant actin isoforms have different biochemical properties. This result supports the idea that actin isoforms play specific roles to achieve multiple cell functions.

Hypothesis To evaluate the insertion results of a novel straight array (EVO) by detailed imaging and subsequent histology in human temporal bones (TB). Background The main focuses of modern cochlear implant surgery are to prevent damage to the intracochlear structures and to preserve residual hearing. This is often achievable with new atraumatic electrode arrays in combination with meticulous surgical techniques. Methods Twenty fresh-frozen TBs were implanted with the EVO. Pre- and postoperative cone beam computed tomography scans were reconstructed and fused for an artifact-free representation of the electrode. The array's vertical position was quantified in relation to the basilar membrane on basis of which trauma was classified (Grades 0-4). The basilar membrane location was modeled from previous histologic data. The TBs underwent subsequent histologic examination. Results The EVOs were successfully inserted in all TBs. Atraumatic insertion (Grades 0-1) were accomplished in 14 of 20 TBs (70%). There were three apical translocations, and two basal translocations due to electrode bulging. One TB had multiple translocations. The sensitivity and specificity of imaging for detecting insertion trauma (Grades 2-4) was 87.5% and 97.3.0%, respectively. Conclusion Comparable insertion results as reported for other arrays were also found for the EVO. Insertion trauma can be mostly avoided with meticulous insertion techniques to prevent bulging and by limiting the insertion depth angle to 360 degrees. The image fusion technique is a reliable tool for evaluating electrode placement and is feasible for trauma grading.

Flowering plants express multiple actin isoforms. Previous studies suggest that individual actin isoforms have specific functions; however, the subcellular localization of actin isoforms in plant cells remains obscure. Here, we transiently expressed and observed major Arabidopsis vegetative actin isoforms, AtACT2 and AtACT7, as fluorescent-fusion proteins. By optimizing the linker sequence between fluorescent protein and actin, we succeeded in observing filaments that contained these expressed actin isoforms fused with green fluorescent protein (GFP) in Arabidopsis protoplasts. Different colored fluorescent proteins fused with AtACT2 and AtACT7 and co-expressed in Nicotiana benthamiana mesophyll cells co-polymerized in a segregated manner along filaments. In epidermal cells, surprisingly, AtACT2 and AtACT7 tended to polymerize into different types of filaments. AtACT2 was incorporated into thinner filaments, whereas AtACT7 was incorporated into thick bundles. We conclude that different actin isoforms are capable of constructing unique filament arrays, depending on the cell type or tissue. Interestingly, staining patterns induced by two indirect actin filament probes, Lifeact and mTalin1, were different between filaments containing AtACT2 and those containing AtACT7. We suggest that filaments containing different actin isoforms bind specific actin-binding proteins in vivo, since the two probes comprise actin-binding domains from different actin-binding proteins.

There are two classes of myosin, XI and VIII, in higher plants. Myosin XI moves actin filaments at high speed and its enzyme activity is also very high. In contrast, myosin VIII moves actin filaments very slowly with very low enzyme activity. Because most of these enzymatic and motile activities were measured using animal skeletal muscle α-actin, but not plant actin, they would not accurately reflect the actual activities in plant cells. We thus measured enzymatic and motile activities of the motor domains of two Arabidopsis myosin XI isoforms (MYA2, XI-B), and one Arabidopsis myosin VIII isoform (ATM1), by using three Arabidopsis actin isoforms (ACT1, ACT2, and ACT7). The measured activities were different from those measured by using muscle actin. Moreover, Arabidopsis myosins showed different enzymatic and motile activities when using different Arabidopsis actin isoforms. Our results suggest that plant actin should be used for measuring enzymatic and motile activities of plant myosins and that different actin isoforms in plant cells might function as different tracks along which affinities and velocities of each myosin isoform are modulated.

Actin, a major component of microfilaments, is involved in various eukaryotic cellular functions. Over the past two decades, actin fused with fluorescent protein has been used as a probe to detect the organization and dynamics of the actin cytoskeleton in living eukaryotic cells. It is generally assumed that the expression of fusion protein of fluorescent protein does not disturb the distribution of endogenous actin throughout the cell, and that the distribution of the fusion protein reflects that of endogenous actin. However, we noticed that EGFP-β-actin caused the excessive formation of microfilaments in several mammalian cell lines. To investigate whether the position of the EGFP tag on actin affected the formation of filaments, we constructed an expression vector harboring a β-actin-EGFP gene. In contrast to EGFP-β-actin, cells expressing β-actin-EGFP showed actin filaments in a high background from the monomer actin in cytosol. Additionally, the detergent insoluble assay revealed that the majority of the detergent-insoluble cytoskeleton from cells expressing EGFP-β-actin was recovered in the pellet. Furthermore, we found that the expression of EGFP-β-actin affects the migration of NBT-L2b cells and the mechanical stiffness of U2OS cells. These results indicate that EGFP fused to the N-terminus of actin tend to form excessive actin filaments. In addition, EGFP-actin affects both the cellular morphological and physiological phenotypes as compared to actin-EGFP.Key words: actin, GFP, cytoskeleton and probe.

BackgroundUnderstanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function.MethodsA GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function.ResultsThe discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue.ConclusionThe additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies.FundingFor detailed information per study, see Acknowledgments.

Due to their rarity most of the literature concerning head and neck extracranial schwannomas consists of case reports and small patient series. The aim of the study was to describe population-based incidence, presenting signs and symptoms, management and outcome of head and neck extracranial schwannomas in a larger patient group. All the head and neck extracranial schwannoma patients managed during 1987-2008 at the Helsinki University Central Hospital with a referral area of 1.5 million inhabitants were searched. Altogether 47 patients were identified and subjected to retrospective chart review. Population-based incidence of head and neck extracranial schwannomas was 0.14/100,000/year. Eighty-eight percent of the patients had symptoms, which had lasted on average for 11.5 months prior to diagnosis. Presenting signs and symptoms were diverse depending on the affected nerve. Ninety-four percent of the patients were treated surgically. Sixty-four percent of the operations were macroscopically radical. The tumor capsule was intentionally left in place in 9 %. Surgery-related complications were detected in only 7 % of the patients, but 1 month postoperatively 52 % of them had symptoms, majority relating to different nerve deficits. Treatment of extracranial head and neck schwannomas remains challenging. The tumor is benign, and it grows slowly in a vast majority of cases, but its symptoms are highly variable. Correct timing of surgery is essential, as also patients who are preoperatively asymptomatic may suffer severe postoperative morbidity. Preoperative patient counseling needs to address the risks of neurological sequelae.

Heavy meromyosin (HMM) of myosin II and cofilin each binds to actin filaments cooperatively and forms clusters along the filaments, but it is unknown whether the two cooperative bindings are correlated and what physiological roles they have. Fluorescence microscopy demonstrated that HMM-GFP and cofilin-mCherry each bound cooperatively to different parts of actin filaments when they were added simultaneously in 0.2 μM ATP, indicating that the two cooperative bindings are mutually exclusive. In 0.1 mM ATP, the motor domain of myosin (S1) strongly inhibited the formation of cofilin clusters along actin filaments. Under this condition, most actin protomers were unoccupied by S1 at any given moment, suggesting that transiently bound S1 alters the structure of actin filaments cooperatively and/or persistently to inhibit cofilin binding. Consistently, cosedimentation experiments using copolymers of actin and actin-S1 fusion protein demonstrated that the fusion protein affects the neighboring actin protomers, reducing their affinity for cofilin. In reciprocal experiments, cofilin-actin fusion protein reduced the affinity of neighboring actin protomers for S1. Thus, allosteric regulation by cooperative conformational changes of actin filaments contributes to mutually exclusive cooperative binding of myosin II and cofilin to actin filaments, and presumably to the differential localization of both proteins in cells.

The retrosigmoid approach for vestibular schwannoma surgery has remained the standard approach by most neurosurgeons. Drilling the posterior wall of the internal auditory meatus (IAM) is an essential step in removing the intrameatal tumor. During IAM drilling, three anatomical structures can be encountered, including the posterior semicircular canal, vestibular aqueduct, and jugular bulb. Any of these can be injured during drilling, especially if the jugular bulb lies above the inferior edge of the IAM. Although IAM drilling is performed in most vestibular schwannoma surgeries, information on how to manage complications such as jugular bulb injury is lacking. Here we use an intraoperative video to demonstrate how to manage the inadvertent injury to the jugular bulb in order to avoid massive blood loss. We present a case of a 39-year-old woman with hearing loss, diagnosed with a cerebellopontine angle mass extending into the IAM. Surgery was required due to tumor progression. We used the retrosigmoid approach to access the tumor. During IAM drilling, the jugular bulb was injured. A thin layer of bone wax was applied under continuous suction. The margins of the wax were then gently compressed with a dissector; great care was taken to avoid pushing the wax into the jugular bulb. Excess bone wax was removed (video 1). A small diamond drill (2 mm) was used for further drilling. Our instructional video shows the surgical approach, microsurgical anatomy, and technical aspects of managing massive bleeding from jugular bulb injury. It should therefore be helpful for young neurosurgeons.

Permanent hearing loss is caused by the irreversible damage of cochlear sensory hair cells and nonsensory supporting cells. In the postnatal cochlea, the sensory epithelium is terminally differentiated, whereas tympanic border cells (TBCs) beneath the sensory epithelium are proliferative. The functions of TBCs are poorly characterized. Using an Axin2lacZ Wnt reporter mouse, we found transient but robust Wnt signaling and proliferation in TBCs during the first 3 postnatal weeks, when the number of TBCs decreases. In vivo lineage tracing shows that a subset of hair cells and supporting cells is derived postnatally from Axin2-expressing TBCs. In cochlear explants, Wnt agonists stimulated the proliferation of TBCs, whereas Wnt inhibitors suppressed it. In addition, purified Axin2lacZ cells were clonogenic and self-renewing in culture in a Wnt-dependent manner, and were able to differentiate into hair cell-like and supporting cell-like cells. Taken together, our data indicate that Axin2-positive TBCs are Wnt responsive and can act as precursors to sensory epithelial cells in the postnatal cochlea.

Background Multiple sclerosis (MS) may affect other cranial nerves besides the optic nerve. Sudden sensorineural hearing loss (SSHL), possibly caused by a deficit in the auditory tract, including the vestibulocochlear nerve, is sometimes associated with MS. Objectives We aimed to assess the incidence of SSHL among MS patients, its frequency as an initial symptom of MS, and magnetic resonance imaging (MRI) findings associated with SSHL in MS. Methods We collected retrospectively all patients diagnosed with MS and SSHL at the Helsinki University Hospital between 2004 and 2014. Patients with both diagnoses were re-evaluated using hospital medical records, audiograms and head MRI scans. Results A total of 2736 patients were diagnosed with MS, 1581 patients with SSHL, and 18 patients (0.7% of all MS patients) with both; two patients presented with SSHL as an initial symptom of MS. The annual incidence of SSHL was 59.8/100 000 (95% confidence interval (CI) 37.7–94.9) in MS patients, and 12.4/100 000 (95% CI 11.8–13.0) in the normal population. Conclusion SSHL is a rare symptom of MS and is even less frequent as an initial symptom. Its incidence in MS patients, however, markedly exceeds that in the normal population.

本研究では，近年の廃棄物溶融炉の増加に伴い排出量が増大しつつある廃棄物溶融スラグ (以下スラグと略記) の新規活用法を検討した。はじめに，スラグの微生物増殖に与える影響を調査した。大腸菌に対しては，振盪培養条件下でのスラグの添加は増殖に有意な影響を与えなかったが，静置培養条件下においては約80%の増殖抑制効果が観察された。同様に，魚飼育水槽由来の水生微生物に対しても静置培養条件下で増殖が約80%が抑制された。以上の結果より，スラグは，水槽や花瓶のような，水が大きく撹拌されない静置条件下において，水防腐剤として活用できる可能性が期待された。次に，実際に熱帯魚飼育水および切り花生け水の防腐剤として活用できるか検討した。その結果，ネオンテトラ飼育水槽にスラグを投入することにより水槽内での藻の発生が3ヶ月以上抑制された。また，キク切り花の生け水に対しては1ヶ月以上の防腐効果が見られ，さらに1.7倍の花持ち延長効果が観察された。また，スラグの投入がネオンテトラの生存率や，今回調査した7品種の切り花の花持ちに悪影響を与えなかったことから，スラグが水槽や花瓶等の防腐剤として有効活用できることが示唆された。

Treatment of jugulotympanic paragangliomas (JTPGLs) remains challenging with no clear guidelines for management or follow-up. The aim of this retrospective case-note study was to assess long-term results of operatively and conservatively managed JTPGLs between years 1974-2013. A total of 36 patients with JTPGLs were identified. Clinical characteristics and management outcomes of patients were reviewed. Data were extracted on demographics, symptoms, timing of diagnosis, tumor location and size, embolization, and management, including pre- and post-operative imaging, analysis of operative techniques, and follow-up. Pulsatile tinnitus and hearing loss were the most common presenting symptoms. Thirty-four (94 %) patients were treated with primary surgical therapy and two (6 %) with radiotherapy. The surgical approaches included endaural approach for Fisch Class A tumors and a variety of approaches for Fisch Class B-D tumors with an increasing predilection for function-preserving surgery. Eight (24 %) patients received subtotal resection. Five (15 %) patients had a local recurrence within 10 years after primary surgery. Two (6 %) patients suffered a permanent cranial nerve (CN) deficit after primary surgery. We advocate radical surgery when tumor resection is possible without compromising CNs. Function-preserving surgery with at least a 10-year follow-up for Fisch Class B-D tumors should be considered if CNs are in danger.

The inner ear arises from multipotent placodal precursors that are gradually committed to the otic fate and further differentiate into all inner ear cell types, with the exception of a few immigrating neural crest-derived cells. The otocyst plays a pivotal role during inner ear development: otic progenitor cells sub-compartmentalize into non-sensory and prosensory domains, giving rise to individual vestibular and auditory organs and their associated ganglia. The genes and pathways underlying this progressive subdivision and differentiation process are not entirely known. The goal of this study was to identify a comprehensive set of genes expressed in the chicken otocyst using the serial analysis of gene expression (SAGE) method. Our analysis revealed several hundred transcriptional regulators, potential signaling proteins, and receptors. We identified a substantial collection of genes that were previously known in the context of inner ear development, but we also found many new candidate genes, such as SOX4, SOX5, SOX7, SOX8, SOX11, and SOX18, which previously were not known to be expressed in the developing inner ear. Despite its limitation of not being all-inclusive, the generated otocyst SAGE library is a practical bioinformatics tool to study otocyst gene expression and to identify candidate genes for developmental studies.

The major inhibitory neurotransmitter in the brain, gamma-aminobutyric acid (GABA), has only partial efficacy at certain subtypes of GABA(A) receptors. To characterize these minor receptor populations in rat and mouse brains, we used autoradiographic imaging of t-butylbicyclophosphoro[(35)S]thionate ([(35)S]TBPS) binding to GABA(A) receptors in brain sections and compared the displacing capacities of 10mM GABA and 1mM 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), a competitive GABA-site agonist. Brains from GABA(A) receptor alpha1, alpha4, delta, and alpha4+delta subunit knockout (KO) mouse lines were used to understand the contribution of these particular receptor subunits to "GABA-insensitive" (GIS) [(35)S]TBPS binding. THIP displaced more [(35)S]TBPS binding than GABA in several brain regions, indicating that THIP also inhibited GIS-binding. In these regions, GABA prevented the effect of THIP on GIS-binding. GIS-binding was increased in the cerebellar granule cell layer of delta KO and alpha4+delta KO mice, being only slightly diminished in that of alpha1 KO mice. In the thalamus and some other forebrain regions of wild-type mice, a significant amount of GIS-binding was detected. This GIS-binding was higher in alpha4 KO mice. However, it was fully abolished in alpha1 KO mice, indicating that the alpha1 subunit was obligatory for the GIS-binding in the forebrain. Our results suggest that native GABA(A) receptors in brain sections showing reduced displacing capacity of [(35)S]TBPS binding by GABA (partial agonism) minimally require the assembly of alpha1 and beta subunits in the forebrain and of alpha6 and beta subunits in the cerebellar granule cell layer. These receptors may function as extrasynaptic GABA(A) receptors.

L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists increase the threshold for electroshock-induced convulsions. Here, we show that a transgenic mouse line overexpressing cerebellum-restricted gamma-aminobutyric acid type A (GABA(A)) receptor alpha6 subunit in the hippocampal CA1 pyramidal cells (Thy1alpha6 mouse line) exhibits about a 20% increase in the electroshock current intensity inducing tonic hindlimb extension convulsion in 50% of the mice compared with that of their wild-type controls. AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) in patch clamp recordings of CA1 pyramidal neurons in hippocampal slices had decreased amplitudes (8.4 +/- 2.2 pA) in the transgenics compared with the wild types (10.3 +/- 2.5 pA) but showed no change in current decay or frequency. Our results suggest that decreased AMPA-mediated neurotransmission might explain the increased threshold for electroconvulsions and warrant further studies on the regulation between various components of inhibition and excitation in neurons.

[35S]TBPS binding to the GABAA receptor ionophore binding site is anion dependent. Using autoradiography on rat brain sections, we show that permeabilities of anions through the receptor channel correlate with their efficiencies to promote basal [35S]TBPS binding. Phosphate made an exception as it induced more binding than expected from its permeability. Well-permeable anions (chloride, nitrate, formate) allowed [35S]TBPS binding to be effectively displaced by 1 mM GABA, whereas low-permeable anions (acetate, phosphate, propionate) markedly prevented this GABA effect, especially in the thalamus, the transition from the high to the low GABA effect being between formate and acetate. In the presence of phosphate, GABA enhanced [3H]flunitrazepam binding to benzodiazepine site of recombinant alpha1beta2gamma2 receptors with the same efficacy but lower potency as compared to the presence of chloride, whereas [35S]TBPS binding was abnormally modulated by GABA. These results suggest that inorganic phosphate affects coupling between agonist and ionophore sites in GABAA receptors.

GABAA receptors mediate fast phasic inhibitory postsynaptic potentials and participate in slower tonic extrasynaptic inhibition. Thy1alpha6 mice with ectopic forebrain expression of GABAA receptor alpha6 subunits exhibit increased extrasynaptic GABAA receptor-mediated background conductance and reduced synaptic GABAA receptor currents in hippocampal CA1 neurons [W. Wisden et al. (2002) Neuropharmacology 43, 530-549]. Here we demonstrate that isolated CA1 neurons of these mice showed furosemide-sensitivity of GABA-evoked currents, confirming the functional expression of alpha6 subunit. In addition, receptor autoradiography of the CA1 region of Thy1alpha6 brain sections revealed pharmacological features that are unique for alpha6betagamma2 and alpha6beta receptors. The existence of atypical alpha6beta receptors was confirmed after completely eliminating GABAA receptors containing gamma1, gamma2, gamma3 or delta subunits using serial immunoaffinity chromatography on subunit-specific GABAA receptor antibodies. Behaviourally, the Thy1alpha6 mice showed normal features with slightly enhanced startle reflex and struggle-escape behaviours. However, they were more sensitive to GABAA antagonists DMCM (shorter latency to writhing clonus) and picrotoxinin (shorter latency to generalized convulsions). Tiagabine, an antiepileptic GABA-uptake inhibitor that increases brain GABA levels, delayed picrotoxinin-induced convulsions at a low dose of 3.2 mg/kg in Thy1alpha6 mice, but not in control mice; however, the overall effect of higher tiagabine doses on the convulsion latency remained smaller in the Thy1alpha6 mice. Altered balance between extrasynaptic and synaptic receptors thus affects seizure sensitivity to GABAergic convulsants. Importantly, the increased extrasynaptic inhibition, even when facilitated in the presence of tiagabine, was not able fully to counteract enhanced seizure induction by GABAA antagonists.

The influence of excitatory blockade elicited by uncompetitive N-methyl-D-aspartate (NMDA)/glutamate receptor antagonists on inhibitory GABAergic systems is not well understood. Adult male rats were injected i.p. with a single dose of the prototypical uncompetitive antagonist MK-801 (0.2-10 mg/kg) and in situ hybridization was performed to measure mRNA levels of gamma-aminobutyric acid type A (GABAA) receptor subunits (alpha1-6, beta1-3, gamma1-3, delta, and theta). A significant decrease in delta subunit mRNA levels, that reached approximately 70% of saline-treated values, was observed in the hippocampal dentate gyrus following MK-801 administration. Other subunits did not display statistically significant alterations. These data demonstrate selective actions on GABAA receptor subunit levels that result from blockade of excitation by MK-801.

Agonists of the allosteric benzodiazepine site of GABAA receptors bind at the interface of the alpha and gamma subunits. Here, we tested the in vivo contribution of the gamma2 subunit to the actions of zolpidem, an alpha1 subunit selective benzodiazepine agonist, by generating mice with a phenylalanine (F) to isoleucine (I) substitution at position 77 in the gamma2 subunit. The gamma2F77I mutation has no major effect on the expression of GABAA receptor subunits in the cerebellum. The potency of zolpidem, but not that of flurazepam, for the inhibition of [3H]flunitrazepam binding to cerebellar membranes is greatly reduced in gamma2I77/I77 mice. Zolpidem (1 microM) increased both the amplitude and decay of miniature inhibitory postsynaptic currents (mIPSCs) in Purkinje cells of control C57BL/6 (34% and 92%, respectively) and gamma2F77/F77 (20% and 84%) mice, but not in those of gamma2F77I mice. Zolpidem tartrate had no effect on exploratory activity (staircase test) or motor performance (rotarod test) in gamma2I77/I77 mice at doses up to 30 mg/kg (i.p.) that strongly sedated or impaired the control mice. Flurazepam was equally effective in enhancing mIPSCs and disrupting performance in the rotarod test in control and gamma2I77/I77 mice. These results show that the effect of zolpidem, but not flurazepam, is selectively eliminated in the brain by the gamma2F77I point mutation.