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Purpose: To assess the relationships between the electric field (EF) and neural excitation patterns in cochlear implants (CIs) and explore their associations with the cochlear diameter, patient age and gender, and postoperative speech recognition., Method: The intraoperative transimpedance matrix (TIM) and spread of excitation (SOE) measures were computed to obtain their 50 % widths corresponding to six electrode contacts of a lateral-wall electrode array. The measures were then analyzed for intercorrelations, associations with the cochlear diameter, as well as age and gender-related differences. The relationships between the computed intraoperative measures and postimplant speech recognition were also studied., Results: The TIM and SOE 50 % widths present moderate correlations and exhibit differences between adults and children. The TIM 50 % widths show additional associations with the cochlear diameter and partly vary with the implantee's gender. Speech recognition was found to have a significant relationship with the exponential spread coefficients (ESCs) obtained for individual electrode contacts., Conclusion: Although interrelated, the EF and neural excitation measures of the CI are associated with different variables. The ESC, derived from computations of the TIM , is the only measure linked to postoperative speech recognition., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Otoscopes and otomicroscopes are the most commonly used instruments for visualizing the ear. Digital otoscopy (DO) could be used to improve diagnostics in primary health care by utilizing image enlargement. The aim of the study was to explore the possibilities of DO in remote consultations., Materials and Methods: Based on real-life referrals, 45 otologic outpatients were recruited. DO was performed followed by an attending otologist's appointment, serving as the gold standard. Twenty-four patient cases were analyzed on a digital platform as remote consultation cases containing the given referral information supplemented with DO videos (DOVs). A total of 71 evaluations were performed by five otologists. The quality of the DOVs, their suitability for remote consultations, the accuracy of diagnoses and the usefulness of remote consultations were determined., Results: The average DOV quality was judged to be 7.4 ± 0.3 (mean ± standard error of the mean; scale of 1-10). The diagnosis was correct in 79% of the cases. In 59% of the patients, the otologists considered that remote consultation could have replaced an in-person visit., Conclusions: In our simulated remote consultation setup, DOV quality was sufficient for diagnostic purposes, DO improved diagnostics and treatment planning in most cases and could be used to reduce the need for in-person visits. DO-aided remote consultation may improve diagnostics and access to care.Level of evidence: 3., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Objectives: Sinonasal inverted papilloma (IP) has a locally destructive growth pattern, can relapse, and can undergo malignant transformation (IP-associated sinonasal squamous cell carcinoma (IP-SNSCC)). Human papillomaviruses (HPV)-6 and -16 are frequently detected in IPs. To clarify the possible roles of other DNA viruses in IPs, we explored viruses not studied in this context before. With the setting of pre- and post-malignant transformation samples, we investigated HPV genomes in depth to assess the integration of HPV into the human genome and the presence of minor intratypic variants., Materials and Methods: We analyzed 35 IP samples representing 28 individuals, of which six had IP-SNSCC. For virus screening, we applied qPCR to detect 16 different DNA viruses in three virus families, comprising herpesviruses, parvoviruses, and polyomaviruses. In addition, targeted next generation sequencing (NGS) was used for detailed HPV analysis., Results: We detected herpes-, parvo-, and polyomaviruses in 13/28 (46%) patients, with codetections of multiple viruses in six (21%) patients. NGS revealed HPV16 DNA in 2/6 IP-SNSCC and in their respective earlier benign IP samples, as well as in a plasma sample from one of these patients. HPV6 was detected in two IP samples without subsequent malignant transformation. We identified sequence reads containing junctions of HPV6 and HPV16 and host genome suggestive of viral integration. HPV6 and HPV16 minor intratypic variants were present across pre- and post-malignant transformation, with mostly nonsynonymous mutations., Conclusions: Multiple DNA viruses were present in IPs. HPV16 was detected only in IP-SNSCCs or in tumors that later underwent malignant transformation., Level of Evidence: 3 Laryngoscope, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: Sinonasal lymphoma (SL) is a rare lymphatic neoplasm of the nasal cavities, paranasal sinuses and nasopharynx. Whereas some risk factors for SL subtypes have been identified, their aetiology is unknown. Along with other predisposing factors, the viral association of lymphomas, such as Epstein-Barr virus (EBV) and Burkitt and Hodgkin lymphomas, is well-established. Modern molecular biology techniques have enabled the discovery of novel human viruses, exemplified by the protoparvovirus cutavirus (CuV), associated with cutaneous T-cell lymphoma. These findings, and the anatomical location of the sinonasal tract with its rich microbiome and infectious agents, justify in-depth studies among SL., Methods: We analysed the presence of 20 viruses of Orthoherpesviridae, Parvoviridae, and Polyomaviridae by qPCR in 24 SL tumours. We performed RNAscope in situ hybridisation (RISH) to localize the viruses. Parvovirus-specific IgG was analysed by enzyme immunoassay and targeted next-generation sequencing (NGS) was applied to detect CuV in plasma., Results: We detected viral DNA in 15/24 (63%) tumours; nine of EBV, six of human herpesvirus (HHV) -7, four each of HHV-6B and parvovirus B19, two of cytomegalovirus, and one each of CuV and Merkel-cell polyomavirus. We found tumours with up to four viruses per tumour, and localized CuV and EBV DNAs by RISH. Two of the ten plasma samples exhibited CuV IgG, and one plasma sample demonstrated CuV viremia by NGS., Conclusion: Viruses were frequent findings in SL. The EBV detection rate was high in diffuse large B-cell lymphoma, and co-detections with other viruses were prevalent., (© 2024. The Author(s).)

Background: The etiology behind different types of chronic sialadenitis (CS), some of which exhibit IgG4 overexpression, is unknown. Further, IgG4-related disease (IgG4-RD) commonly affects the submandibular gland, but its relationship to IgG4-overexpressing CS, and the antigen triggering IgG4 overexpression, remain unknown., Materials and Methods: By qPCR, we assessed the presence of 21 DNA-viruses causing IgG4 overexpression in submandibular gland tissue from patients with IgG4-positive and IgG4-negative CS. Healthy submandibular glands and glands with sialolithiasis without CS were used as controls. We examined the distribution of HHV-7, HHV-6B and B19V DNA, within virus PCR-positive tissues with RNAscope in-situ hybridization (RISH)., Results: We detected DNA from seven viruses in 48/61 samples. EBV DNA was more prevalent within the IgG4-positive samples (6/29; 21%) than the IgG4-negative ones (1/19; 5.3%). B19V DNA was more prevalent within the IgG4-negative samples (5/19; 26%) than the IgG4-positive ones (4/29; 14%). The differences in virus prevalence were not statistically significant. Of the IgG4-RD samples ( n  = 3) one contained HHV-6B DNA. RISH only showed signals of HHV-7., Conclusions: None of the studied viruses are implicated as triggering IgG4-overexpression in CS. Although our results do not confirm viral etiology in the examined conditions, they provide valuable information on the prevalence of viruses in both diseased and healthy submandibular gland tissue., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: In otosurgical training, cadaveric temporal bones are primarily used to provide a realistic tactile experience. However, using cadaveric temporal bones is challenging due to their limited availability, high cost, and potential for infection. Utilizing current three-dimensional (3D) technologies could overcome the limitations associated with cadaveric bones. This study focused on how a 3D-printed middle ear model can be used in otosurgical training., Methods: A cadaveric temporal bone was imaged using microcomputed tomography (micro-CT) to generate a 3D model of the middle ear. The final model was printed from transparent photopolymers using a laser-based 3D printer (vat photopolymerization), yielding a 3D-printed phantom of the external ear canal and middle ear. The feasibility of this phantom for otosurgical training was evaluated through an ossiculoplasty simulation involving ten otosurgeons and ten otolaryngology-head and neck surgery (ORL-HNS) residents. The participants were tasked with drilling, scooping, and placing a 3D-printed partial ossicular replacement prosthesis (PORP). Following the simulation, a questionnaire was used to collect the participants' opinions and feedback., Results: A transparent photopolymer was deemed suitable for both the middle ear phantom and PORP. The printing procedure was precise, and the anatomical landmarks were recognizable. Based on the evaluations, the phantom had realistic maneuverability, although the haptic feedback during drilling and scooping received some criticism from ORL-HNS residents. Both otosurgeons and ORL-HNS residents were optimistic about the application of these 3D-printed models as training tools., Conclusions: The 3D-printed middle ear phantom and PORP used in this study can be used for low-threshold training in the future. The integration of 3D-printed models in conventional otosurgical training holds significant promise., (© 2024. The Author(s).)

Introduction: Balloon Eustachian tuboplasty (BET) is used to treat obstructive Eustachian tube dysfunction (OETD) and recurrent otitis media with effusion (OME). However, there are no indisputable evidence of its efficacy. Here, we present a multicenter, double-blinded, randomized, placebo-controlled trial (MDRCT) design to evaluate the efficacy of BET, and the results of a pilot trial with 3- and 12-months' follow-up., Material and Methods: This was a prospective MDRCT. For a pilot study, OETD (n = 10) and OME (n = 5) patients were recruited and followed. Detailed inclusion and exclusion criteria were used. Participants were randomized at beginning of the operation to active or sham surgery. All procedures were performed under local anesthesia. Controls were performed in double-blinded manner (both patient and physician), at 3 and 12 months after the procedure., Results: Altogether, 20 ears were treated and followed for 12 months, including 14 active BETs and 6 sham surgeries. Both the active and sham surgery were performed under local anesthesia without problems or deviations from the protocol. There were no differences in the preoperative symptoms (ETDQ-7) or objective measures (tympanometry, Valsalva and Toynbee maneuvers, tubomanometry, Eustachian tube score) between active and sham surgery arms. During follow-up, we noticed largely similar reduction in subjective symptoms and improvement in Eustachian tube score both in active and sham surgery arms., Conclusions: The pilot study demonstrates that our MDRCT protocol is feasible, and that blinded RCTs are dearly needed to objectively measure the efficacy of BET., Level of Evidence: 2 Laryngoscope, 134:1874-1881, 2024., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Plants have unique responses to fluctuating light conditions. One such response involves chloroplast photorelocation movement, which optimizes photosynthesis under weak light by the accumulation of chloroplasts along the periclinal side of the cell, which prevents photodamage under strong light by avoiding chloroplast positioning toward the anticlinal side of the cell. This light-responsive chloroplast movement relies on the reorganization of chloroplast actin (cp-actin) filaments. Previous studies have suggested that CHLOROPLAST UNUSUAL POSITIONING 1 (CHUP1) is essential for chloroplast photorelocation movement as a regulator of cp-actin filaments. In this study, we conducted comprehensive analyses to understand CHUP1 function. Functional, fluorescently tagged CHUP1 colocalized with and was coordinately reorganized with cp-actin filaments on the chloroplast outer envelope during chloroplast movement in Arabidopsis thaliana. CHUP1 distribution was reversibly regulated in a blue light- and phototropin-dependent manner. X-ray crystallography revealed that the CHUP1-C-terminal domain shares structural homology with the formin homology 2 (FH2) domain, despite lacking sequence similarity. Furthermore, the CHUP1-C-terminal domain promoted actin polymerization in the presence of profilin in vitro. Taken together, our findings indicate that CHUP1 is a plant-specific actin polymerization factor that has convergently evolved to assemble cp-actin filaments and enables chloroplast photorelocation movement., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Properly patterned cell walls specify cellular functions in plants. Differentiating protoxylem and metaxylem vessel cells exhibit thick secondary cell walls in striped and pitted patterns, respectively. Cortical microtubules are arranged in distinct patterns to direct cell wall deposition. The scaffold protein MIDD1 promotes microtubule depletion by interacting with ROP GTPases and KINESIN-13A in metaxylem vessels. Here we show that the phase separation of MIDD1 fine-tunes cell wall spacing in protoxylem vessels in Arabidopsis thaliana. Compared with wild-type, midd1 mutants exhibited narrower gaps and smaller pits in the secondary cell walls of protoxylem and metaxylem vessel cells, respectively. Live imaging of ectopically induced protoxylem vessels revealed that MIDD1 forms condensations along the depolymerizing microtubules, which in turn caused massive catastrophe of microtubules. The MIDD1 condensates exhibited rapid turnover and were susceptible to 1,6-hexanediol. Loss of ROP abolished the condensation of MIDD1 and resulted in narrow cell wall gaps in protoxylem vessels. These results suggest that the microtubule-associated phase separation of MIDD1 facilitates microtubule arrangement to regulate the size of gaps in secondary cell walls. This study reveals a new biological role of phase separation in the fine-tuning of cell wall patterning., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Salivary pleomorphic adenoma is histopathologically characterized by its colorful stroma with myxoid, chondroid, and hyaline appearances, due to enhanced biosynthesis of extracellular matrix (ECM) molecules and poor vascularity. Thus, pleomorphic adenoma cells embedded in the stroma typically survive under hypoxic conditions. We determined the expression kinetics of ECM molecules, such as perlecan and fibronectin (FN), under hypoxia in SM-AP1 cells which are duct epithelial differentiated cells, and in SM-AP4 cells, which are myoepithelial differentiated cells, cloned from pleomorphic adenoma of the parotid gland. We investigated hypoxia-inducible factor-1α (HIF-1α)-inducing pathways through a variety of ECM molecules in association with their cellular proliferation and migration. We observed that hypoxic conditions with elevated HIF-1α protein levels induced increased expression of perlecan and FN in SM-AP cells than in controls. Moreover, perlecan and FN knockdown reduced the proliferation of SM-AP1 and SM-AP4 cells under hypoxia. Further, SM-AP1 cell migration was enhanced by both perlecan and FN knockdown, whereas SM-AP4 cell migration was increased by perlecan knockdown and inhibited by fibronectin knockdown. The results indicated that pleomorphic adenoma cells can survive under hypoxic conditions by promoting cell proliferation via enhanced synthesis of ECM molecules. Overall, ECM molecules may be a new anti-tumor target under hypoxic conditions.

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 (TIM mp ). Bipolar TIM (TIM bp ) allows estimations of local potential differences. With TIM mp , the correct alignment of the electrode array can be assessed, and TIM bp 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 TIM mp and TIM bp using three types of electrode arrays. Also, multiple linear regressions based on the TIM mp and TIM bp 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 TIM mp and TIM bp 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 TIM bp 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 TIM mp and TIM bp can be used to estimate both SA and EMWD (R 2  = 0.47 and R 2  = 0.44, respectively, p < 0.001 for both). In TIM mp , 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 TIM bp correlate with both SA and EMWD. Altogether, TIM mp and TIM bp 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., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Microsurgical resection of vestibular schwannoma (VS) is highly challenging, especially because surgical treatment nowadays is mainly reserved for larger (Koos grade 3 and 4) tumors., Objective: To assess the performance of three-dimensional exoscope use in VS resection in comparison with the operative microscope., Methods: Duration of surgery and clinical and radiological results were collected for 13 consecutive exoscopic schwannoma surgeries. Results were compared with 26 preceding microsurgical resections after acknowledging similar surgical complexity between groups by assessment of tumor size (maximum diameter and Koos grade), the presence of meatal extension or cystic components, and preoperative hearing and facial nerve function., Results: Total duration of surgery was comparable between microscopically and exoscopically operated patients (264 minutes ± 92 vs 231 minutes ± 84, respectively; P = .276). However, operative time gradually decreased in consecutive exoscopic cases and in a multiple regression model predicting duration of surgery, and exoscope use was associated with a reduction of 58.5 minutes (95% CI -106.3 to -10.6; P = .018). Tumor size was identified as the main determinant of duration of surgery (regression coefficient = 5.50, 95% CI 3.20-7.80) along meatal extension and the presence of cystic components. No differences in postoperative hearing preservation and facial nerve function were noted between the exoscope and the microscope., Conclusion: Resection of VS using a foot switch-operated three-dimensional exoscope is safe and leads to comparable clinical and radiological results as resection with the operative microscope., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

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., (© 2023. The Author(s).)

With computed tomography (CT), the delicate structures of the inner ear may be hard to visualise, which a cochlear implant (CI) electrode array can further complicate. The usefulness of a novel cone-beam CT device in CI recipient's inner ear imaging was evaluated and the exposure parameters were optimised to attain adequate clinical image quality at the lowest effective dose (ED). Six temporal bones were implanted with a Cochlear Slim Straight electrode array and imaged with six different imaging protocols. Contrast-to-noise ratio was calculated for each imaging protocol, and three observers evaluated independently the image quality of each imaging protocol and temporal bone. The overall image quality of the inner ear structures did not differ between the imaging protocols and the most relevant inner ear structures of CI recipient's inner ear can be visualised with a low ED. To visualise the most delicate structures in the inner ear, imaging protocols with higher radiation exposure may be required., (© The Author(s) 2023. Published by Oxford University Press.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright: © 2023, Heikkinen A-K, Lähde S, Rissanen V, et al.)

Etiology of vestibular schwannoma (VS) is unknown. Viruses can infect and reside in neural tissues for decades, and new viruses with unknown tumorigenic potential have been discovered. The presence of herpesvirus, polyomavirus, parvovirus, and anellovirus DNA was analyzed by quantitative PCR in 46 formalin-fixed paraffin-embedded VS samples. Five samples were analyzed by targeted next-generation sequencing. Viral DNA was detected altogether in 24/46 (52%) tumor samples, mostly representing anelloviruses (46%). Our findings show frequent persistence of anelloviruses, considered normal virome, in VS. None of the other viruses showed an extensive presence, thereby suggesting insignificant role in VS., (© 2023. The Author(s).)

A limiting factor of cochlear implant (CI) technology is the electrode-contact overlapping spread of the electrode-generated intracochlear electrical field (EF). While the extent of the spread can be reduced with intracochlear ground electrodes, the stimulation level must be increased to reach similar loudness as with monopolar stimulation utilizing an extracochlear ground. In this study, we investigated the relationship between the monopolar intracochlear EF and the minimum stimulation level required for a measurable neural response assessed with electrically evoked compound action potential (eCAP) thresholds in intraoperative settings. Also, the effect of cochlear diameter on the intracochlear EF was evaluated, as narrower intracochlear EFs were found from larger than smaller cochleae in an earlier study. A total of 171 ears of severely-to-profoundly hearing-impaired patients (ages 0.7-89 years; 42.5 ± 27.8 years, mean ± SD) implanted with a Cochlear Nucleus CI522 or CI622 implant and Slim Straight electrode array or with a Med-El Synchrony implant and Flex 28 electrode array were included in the study. Normal anatomy was established and cochlear diameter was measured for all patients from preoperative imaging. Intraoperative intracochlear EF and eCAP threshold measurements were measured for both Cochlear and Med-El devices with the CIs' back-telemetry options, and EF and eCAP were compared for Cochlear devices. The peak and width of the intracochlear EF correlated with each other ( r = 0.46, p < 0.001), and both had an inverse relationship with eCAP thresholds ( r = -0.41, p < 0.001 and r = -0.29, p < 0.001, respectively). The peak amplitudes of the intracochlear EF increased towards the apical part of the electrode array with both Cochlear ( r = 0.97, p < 0.001) and Med-El ( r = 0.80, p = 0.002) devices. The peak amplitudes of the intracochlear EF were shallower across the electrode array in large than in small cochleae ( p < 0.05). Our results indicate that the responsiveness of the cochlear nerve is not only dependent on neural health but is also affected by the physical environment of the electrode array, which can be assessed by measuring the intracochlear EF. Further studies are warranted to investigate the detailed characteristics of the intracochlear current spread in CI recipients with varying anatomical features of the cochlea and with electrode arrays with different locations in the scalae or related to the modiolus in the cochleae., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Objectives: Currently, there is no consensus regarding the best protocol for diagnosing Eustachian tube dysfunction (ETD). We aimed to evaluate how patient characteristics affect tubomanometry (TMM) results. If an association between patient characteristics and TMM results exists, this should be considered in TMM interpretation. We also wanted to study if TMM correlates with other diagnostic tools of ETD., Methods: A retrospective chart review was conducted on all patients with TMM results available from November 2011 to October 2020 at a tertiary referral center, including 432 ears from 219 patients. An association between diagnostic tests and patient characteristics was assessed using regression models. Spearman's rank correlation was used to analyze correlations between diagnostic tests., Results: None of the studied patient characteristics (age, gender, body mass index, smoking, sinonasal disease) was associated with TMM results except for pollen allergy (OR 1.74, 95% CI 1.15-2.63, P = 0.009). TMM results correlated with Valsalva maneuver performance (P < 0.001, ρ = 0.31) and otomicroscopic signs of inadequate middle ear ventilation (P < 0.001, ρ = 0.28). The Eustachian tube dysfunction questionnaire-7 (ETDQ-7) score did not correlate with any diagnostic method., Conclusions: TMM results are unaffected by patient characteristics other than pollen allergy. Thus, TMM may be used in ETD diagnostics in a wide variety of patients with straightforward interpretation. TMM correlates with other diagnostic tests studied but not with ETDQ-7. ETDQ-7 does not seem to correlate with other diagnostic tests and appears nonspecific in ETD diagnostics., (© 2022. The Author(s).)

Objective: 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., Data Sources: PubMed, the Cochrane Library, Scopus, and Helsinki University Hospital cohort., Methods: 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., Results: 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., Conclusion: BET seems to be effective in the majority of patients with baro-challenge-induced ETD., Competing Interests: The authors disclose no financial and conflicts of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

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., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

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.

Background: We previously introduced the Five-Parameter System (FPS), which exclusively evaluates keratinized cellular findings, for use in cytology examinations of oral well-differentiated squamous cell carcinoma (SCC) and carcinoma in situ (CIS) specimens, as they occasionally lack nuclear atypia and can be challenging for categorization by The Bethesda System (TBS). This study was conducted to determine whether FPS parameters are detectable even in oral SCC/CIS specimens with apparent nuclear atypia., Summary: Oral cytology specimens were obtained together with biopsy tissue samples. They were obtained from 59 malignant (HSIL and SCC) and 29 not-definitely malignant (NILM to ASC-H) specimens diagnosed using TBS. Following re-confirmation of the original TBS categorization, the specimens were re-evaluated using FPS. One or more of the FPS parameters were noted in 69 of 70 malignant specimens examined, of which 11 had been diagnosed by TBS as not-definitely malignant. The remaining one malignant specimen was diagnosed as SCC with only TBS. FPS parameters #1 (concentric arrangement), #2 (large cell number), #3 (bizarre-shaped cells), #4 (keratoglobules), and #5 (uneven filamentous cytoplasm) were observed only in malignant cases, while none were revealed in not-definitely malignant specimens. Finally, TBS supplemented with FPS achieved sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 100%., Key Messages: FPS parameters are included in most examinations of oral cytology specimens. Thus, FPS is highly recommended for use in cytology examinations of oral SCC regardless of differentiation degree to confirm judgment based on TBS, a mandatory standard, as well as to cover its limitation of mainly evaluating nuclear atypia. FPS is considered to be an important diagnostic tool for oral cytology, especially in triage cases, which are challenging for TBS. Cytopathology should not be limited to only nuclear findings but be based on whole-cell morphology., (© 2022 S. Karger AG, Basel.)

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., (Copyright: This article is the copyright of the authors who grant Diving and Hyperbaric Medicine a non-exclusive licence to publish the article in electronic and other forms.)

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) 1.354.50] and a high number of upper respiratory tract infections (3 vs. <3 URTIs/yr: OR, 3.61; 95% CI 2.654.93). 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 .

Background: Gelsolin amyloidosis (AGel amyloidosis) is a hereditary form of systemic amyloidosis featuring ophthalmological, neurological and cutaneous symptoms. Previous studies based mainly on patients' self-reporting have indicated that hearing impairment might also be related to the disease, considering the progressive cranial neuropathy characteristic for AGel amyloidosis. In order to deepen the knowledge of possible AGel amyloidosis-related hearing problems, a clinical study consisting of the Speech, Spatial and Qualities of Hearing Scale (SSQ) questionnaire, clinical examination, automated pure-tone audiometry and a speech-in-noise test was designed., Results: Of the total 46 patients included in the study, eighteen (39%) had self-reported hearing loss. The mean scores in the SSQ were 8.2, 8.3 and 8.6 for the Speech, Spatial and Qualities subscales, respectively. In audiometry, the mean pure tone average (PTA) was 17.1 (SD 12.2) and 17.1 (SD 12.3) dB HL for the right and left ears, respectively, with no difference to gender- and age-matched, otologically normal reference values. The average speech reception threshold in noise (SRT) was - 8.2 (SD 1.5) and - 8.0 (SD 1.7) dB SNR for the right and left ears, respectively, which did not differ from a control group with a comparable range in PTA thresholds., Conclusion: Although a significant proportion of AGel amyloidosis patients experience subjective difficulties in hearing there seems to be no peripheral or central hearing impairment at least in patients up to the age of 60 years., (© 2021. The Author(s).)

Objective: To describe the characteristics, diagnostics, treatment, and outcome of severe acute otitis media (AOM) and acute mastoiditis (AM) caused by group A beta-hemolytic streptococcus (GAS)., Study Design: A retrospective cohort study., Methods: The yearly incidence of inpatient care-needing GAS AOM/AM patients in our hospital catchment area between 2002 and 2018 was investigated. A detailed analysis was performed for cases treated during the last GAS epidemic in 2017-2018. Anamnesis, signs and symptoms, pure-tone audiometry results, treatment, complications, and outcome were collected from medical charts. Patients responded to an otology-specific health-related quality of life survey (EOS-16) 1.5 to 3 years after their treatment., Results: The number of GAS infections peaks at approximately 7-year intervals. During 2017 and 2018, altogether 37 patients (29 adults and 8 children) were hospitalized due to GAS AOM/AM. AM was diagnosed in 14 (38%) patients. The disease progression was typically very rapid. At presentation, all patients had severe ear pain, 68% tympanic membrane perforation and discharge, 43% fever, and 43% vertigo. In pure-tone audiometry, there was usually a marked mixed hearing loss at presentation. There was a significant recovery in both air and bone conduction thresholds; the pure tone average improvement from presentation was 32.3 ± 14.8 dB. Rapid strep tests (RST) proved to be more sensitive than bacterial culture in identifying GAS as a cause of AOM/AM., Conclusion: GAS AOM/AM has a rapid onset. Hearing loss usually includes a sensorineural component, which is usually reversible with adequate treatment. RST seems to be useful in detecting GAS from middle ear discharge., Level of Evidence: 4., Competing Interests: The authors declare no potential conflict of interest., (© 2021 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

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., (© 2020 PLA General Hospital Department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd.)

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., Competing Interests: None. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (© 2021 PLA General Hospital Department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd.)

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., (Copyright: This article is the copyright of the authors who grant Diving and Hyperbaric Medicine a non-exclusive licence to publish the article in electronic and other forms.)

A limiting factor of cochlear implant technology is the spread of electrode-generated intracochlear electrical field (EF) leading to spread of neural excitation (SOE). In this study, we investigated the relation of the spread of the intracochlear EF, assessed via transimpedance matrix (TIM), and SOE. A total of 43 consecutive patients (ages 0.7-82 years; 31.0 ± 25.7 years, mean ± SD) implanted with a Cochlear Nucleus CI522 or CI622 cochlear implant with Slim Straight electrode array (altogether 51 ears) were included in the study. Cochlear nerve was visualized for all patients in preoperative imaging and there were no cochlear anomalies in the study sample. The stimulated electrodes were in the basal, middle, and apical parts of the electrode array (electrode numbers 6, 11, and 19, respectively). The stimulation level was 210 CL on average for the TIM measurement and always 230 CL for the SOE measurement. Approximately 90% of the individual TIM and SOE profiles correlated with each other (p < .05; r = 0.61-0.99). Also, the widths of the TIM and SOE peaks, computed at 50% of the maximum height, exhibited a weak correlation (r = 0.39, p = .007). The 50% widths of TIM and SOE were the same only in the apical part of the electrode array; in the basal part SOE was wider than TIM, and in the middle part TIM was wider than SOE (p < .01 and p = .048, respectively). Within each measurement, TIM 50% widths were different between all three parts of the electrode array, while for SOE, only the basal electrode differed from the middle electrode. Finally, the size of the cochlea and the 50% widths of TIM and SOE had the strongest correlation in the middle part of the electrode array (r = -0.63, and -0.37, respectively). Our results suggest that there is a correlation between the spread of intracochlear EF and neural SOE at least in the apical part of the electrode array used in this study, and that larger cochleae are associated with more focused TIM and SOE., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021. Published by Elsevier B.V.)

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 < 0) and at 50 mbar, difficulties in reaching sufficient nasopharyngeal pressure. TMM results were similar in 88% of cases at 30 and 40 mbars and in 86% of cases at 40 and 50 mbars., Conclusions: TMM success rate seems sufficiently high for clinical diagnostics, and most difficulties may be overcome with proper interpretation during the TMM measurement session, and thus repeating the measurements when necessary. Considering the diagnostic information that would be lost if using only a single, predefined pressure, we suggest using all three pressures., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2021, Otology & Neurotology, Inc.)

Mitochondrial cardiomyopathy can be described as a condition characterized by abnormal heart-muscle structure and/or function, secondary to mutations in nuclear or mitochondrial DNA. Its severity can range from subclinical to critical conditions. We presented three cases of mitochondrial cardiomyopathy with m.3243A > G mutation and compared the clinical manifestations with the histological findings for each of these cases. All cases showed cardiac hypertrophy, juvenile-onset diabetes mellitus, and hearing loss. Case 1 (43-year-old male) showed less cardiac involvement and shorter duration of mitochondrial disease-related symptoms than case 2 (67-year-old female) and case 3 (51-year-old male), who showed the most advanced cardiac condition and longest duration from the manifestation of heart failure. The histological findings revealed that cardiomyocytes from case 1 showed no hypertrophy and mitochondrial degeneration in electron microscopy. Alternatively, cases 2 and 3 showed hypertrophy in their cardiomyocytes, and mitochondrial degeneration (e.g. onion-like lesions, swollen cristae, and lamellar bodies) was most apparent in case 3. These results suggested that mitochondrial degeneration, as evaluated by electron microscopy, might be correlated with impaired heart function in patients with mitochondrial cardiomyopathy.

Bilateral cochlear implantation is increasing worldwide. In adults, bilateral cochlear implants (BICI) are often performed sequentially with a time delay between the first (CI1) and the second (CI2) implant. The benefits of BICI have been reported for well over a decade. This study aimed at investigating these benefits for a consecutive sample of adult patients. Improvements in speech-in-noise recognition after CI2 were followed up longitudinally for 12 months with the internationally comparable Finnish matrix sentence test. The test scores were statistically significantly better for BICI than for either CI alone in all assessments during the 12-month period. At the end of the follow-up period, the bilateral benefit for co-located speech and noise was 1.4 dB over CI1 and 1.7 dB over CI2, and when the noise was moved from the front to 90 degrees on the side, spatial release from masking amounted to an improvement of 2.5 dB in signal-to-noise ratio. To assess subjective improvements in hearing and in quality of life, two questionnaires were used. Both questionnaires revealed statistically significant improvements due to CI2 and BICI. The association between speech recognition in noise and background factors (duration of hearing loss/deafness, time between implants) or subjective improvements was markedly smaller than what has been previously reported on sequential BICI in adults. Despite the relatively heterogeneous sample, BICI improved hearing and quality of life.

R2TP is a well-conserved molecular chaperone complex, composed of Pontin, Reptin, RPAP3, and PIH1D, in eukaryotes. Recent studies have suggested an involvement of R2TP in cancer development. However, it remains unclear if it is related to the development of oral squamous cell carcinoma (OSCC), which is the most common type of oral cancer. Here, we identify and investigate the function of R2TP in OSCC development. Immunohistochemical analysis reveals that all of the R2TP components are strongly expressed in normal oral epithelia and OSCC tissues, where actively proliferating cells are abundant. Co-immunoprecipitation assay identifies that R2TP components form a protein complex in OSCC-derived HSC4-cells. Knockdown experiments show that all R2TP components, except for RPAP3, are required for the cell proliferation and migration of HSC-4 cells. Furthermore, we reveal that Pontin contributes to a gain-of-function (GOF) activity of mutp53-R248Q in HSC-4 cells by regulating phosphorylation levels of mutp53 at Ser15 and Ser46. To our knowledge, this study is the first to report the functional involvement of R2TP and its components in the malignant characteristics of OSCC cells., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (Copyright: This article is the copyright of the authors who grant Diving and Hyperbaric Medicine a non-exclusive licence to publish the article in electronic and other forms.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

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.

Introduction: 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., Methods: 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., Results: 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., Conclusion: 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., Competing Interests: The authors of this paper declare no conflicts of interest exist with this submission., (Copyright© Undersea and Hyperbaric Medical Society.)

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.

Introduction: Tinnitus can become a strong stressor for some individuals, leading to imbalance of the autonomous nervous system with reduction of parasympathetic activity. It can manifest itself as sleep disturbances, anxiety and even depression. This condition can be reversed by bioelectrical vagal nerve stimulation (VNS). Conventional invasive VNS is an approved treatment for epilepsy and depression. Transcutaneous VNS (taVNS) stimulating the auricular branch of the vagus nerve has been shown to activate the vagal pathways similarly as an implanted VNS. Therefore, taVNS might also be a therapeutic alternative in health conditions such as tinnitus-related mental stress (TRMS). This retrospective study in 171 TRMS patients reports the clinical features, psychophysiological characteristics, and results of the heart rate variability (HRV) tests before and after test-taVNS. This study also reports the therapy outcomes of 113 TRMS patients treated with taVNS, in combination with standard tinnitus therapy., Methods: Diagnostic tinnitus and hearing profiles were defined. To detect possible cardiac adverse effects, test-taVNS with heart rate monitoring as well as pre- and post-stimulation HRV tests were performed. Daily taVNS home therapy was prescribed thereafter. To assess therapeutic usefulness of taVNS, 1-year follow-up outcome was studied. Results of HRV tests were retrospectively analyzed and correlated to diagnostic data., Results: The large majority of patients with TRMS suffer from associated symptoms such as sleep disturbances and anxiety. Baseline HRV data showed that more than three quarters of the 171 patients had increased sympathetic activity before test-taVNS. Test-taVNS shifted mean values of different HRV parameters toward increased parasympathetic activity in about 80% of patients. Test-taVNS did not cause any cardiac or other side effects. No significant adverse effects were reported in follow-up questionnaires., Conclusion: TRMS is an example of a stress condition in which patients may benefit from taVNS. As revealed by HRV, test-taVNS improved parasympathetic function, most efficiently in patients with a low starting HRV level. Our tinnitus treatment program, including taVNS, effectively alleviated tinnitus stress and handicap. For wider clinical use, there is a great need for more knowledge about the optimal methodology and parameters of taVNS., (Copyright © 2020 Ylikoski, Markkanen, Pirvola, Lehtimäki, Ylikoski, Jing, Sinkkonen and Mäkitie.)

Although emergence of keratin 17 (K17) and reciprocal loss of K13 are immunohistochemical hallmarks for oral mucosal malignancy, we report here findings of K17-positive (+) speckles, possibly equivalent to Civatte bodies, in benign oral lichen planus. Sixty-two biopsy samples from oral lichen planus cases were subjected to immunohistochemical examinations to analyze the distribution as well as histopathogenesis of Civatte bodies. K17 was irregularly positive among oral lichen planus-affected epithelial cells, and K17-positive (+) filamentous structures were irregularly distributed within the cytoplasm in confocal images. K17+ speckles were identified as Civatte bodies, and they were mainly distributed in the interface between epithelial cells and lymphocytic infiltrates (type A, 52.8%), followed by distribution within the epithelial layer (type B, 24.7%) or within the lamina propria with lymphocytic infiltration (type C, 22.5%). Apoptotic figures were often engulfed by macrophages and clearly distinguished from Civatte bodies by the presence TUNEL signals. These results indicate that K17 is a sensitive immunohistochemical marker for Civatte bodies and useful for differential diagnosis of oral lichen planus from other oral mucosal lesions. Civatte bodies are generated from denucleation of K17+ epithelial cells during the process of cell death via dyskeratosis, which is possibly related to blood capillary collapse.

Apoptotic cell death frequently occurs in human cancer tissues including oral squamous cell carcinoma (SCC), wherein apoptotic tumor cells are phagocytosed not only by macrophages but also by neighboring tumor cells. We previously reported that the engulfment of apoptotic SCC cells by neighboring SCC cells frequently occurs at the invading front. Therefore, we hypothesized that the phagocytosis of these apoptotic cells by tumor cells contributes to disease progression. Herein, using cultured oral SCC cells, we aimed to confirm whether tumor cells actually phagocytose apoptotic cells and to examine whether cellular activities are regulated by the phagocytosis of apoptotic cells. Co-culture experiments showed that living cells could ingest apoptotic cells into phagolysosomes. NSC23766, an inhibitor of Rac1, which is a key regulator of phagocytic cup formation in professional phagocytes, dramatically suppressed the phagocytosis of apoptotic cells by living cells. Additionally, cell migration and the secretion of DKK1, a tumor-promoting protein, were enhanced by co-culture with apoptotic cells, whereas NSC23766 inhibited these effects. These results show that tumor cells can actively phagocytose apoptotic neighbors in a Rac1-dependent manner and that such activity increases their migration. The regulation of apoptotic cell phagocytosis thus represents new directions for therapeutic intervention for oral cancer., Competing Interests: Declaration of competing interest We declare that we have no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

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 < .001 for all comparisons). Respondents considered the CellScope Oto more appropriate for teleconsultations for exostoses than the three other otoscopes. The CellScope Oto and Digital MacroView were equally appropriate in the two other cases (normal ear and perforated tympanic membrane)., Conclusions: Both digital otoscopes and the underlying otological conditions affect the appropriateness of teleconsultations. Moreover, both factors should be considered when evaluating the suitability of otologic teleconsultations. Among the otoscopes evaluated, images taken using the CellScope Oto received the best overall assessments., Level of Evidence: NA Laryngoscope, 130:1572-1576, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: In the present study, we examined the effect of oriented collagen tube (OCT) implantation on the recovery of sensory function of the resected rat sciatic nerve., Materials and Methods: After a 10-mm long portion of the sciatic nerve of a rat was resected, an OCT was placed in the site of nerve defect. Recovery of the sensory function was evaluated using Von Frey test every 3 days after surgery. The regenerated tissue were histologically and ultrastructurally analyzed 2 and 4 weeks after the surgery., Results: The sensory reflexes of the OCT group were restored to the level of that of the intact group after 15 days. Hematoxylin and eosin staining revealed the cross-linking between the proximal and distal stumps after 2 weeks. After 4 weeks, Luxol Fast Blue and immunohistochemical staining revealed the presence of myelin sheath from the proximal to distal region of the regenerated tissue and S100B staining confirmed the presence of Schwann cells. Interestingly, no myelin sheath was ultrastructurally observed around the regenerated axons at the central region after 2 weeks., Conclusions: These results suggest that OCTs facilitate the recovery of sensory function. Additionally, the non-myelinated axons contributed to the recovery of the sensory function., Competing Interests: The authors declare no conflict of interest., (© 2020 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

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., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2019 The Authors.)

Background: 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., Methods: 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 and >12 month old. Prospectively collected clinical data, laboratory test results and outcome for these groups were assessed., Results: 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; P < 0.001). 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. The >12-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., Conclusions: 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 [ 35 S]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 [ 35 S]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 μM 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 β subunit variant and the presence of γ2 subunit in rat recombinant α1β and α1βγ2 GABA A receptors, with the β1 allowing the niflumic acid inhibition and β3 the stimulation of the receptor-mediated currents. In summary, the fenamate NSAIDs 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., (Copyright © 2019. Published by Elsevier B.V.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.