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OBJECTIVE: The dynamic range (DR) available to the patient is a central parameter to determine speech intelligibility in quiet. DESIGN: In this retrospective study, the DR for the Vibrant Soundbridge implanted in individual patients was calculated using in situ thresholds of the patients and technical data of the implant system. The average DR across frequencies (0.5, 1, 2, 4 kHz) was correlated with the patients' assigned word recognition score (WRS) in quiet. STUDY SAMPLE: A data set of 66 cases (4 bilateral and 2 revised cases) from 60 implanted patients between 14.3-81.8 years were analysed. RESULTS: The relationship between DR and WRS was described by a sigmoidal growth function with R2=0.6371 and a maximum WRS (upper asymptote) of 93.5%. Word recognition scores in quiet improved with increasing DR. A significant shift in performance was detected from DR bin 2 (10-20 dB, median WRS 55%) to bin 3 (20-30 dB, median WRS 80%) and from DR bin 4 (30-40 dB, median WRS 82.5%) to bin 5 (40-50 dB, median WRS 90%). CONCLUSION: A minimum DR of 20 dB can yield sufficient speech intelligibility in quiet in implanted patients, however, an optimum DR is suggested to be 40 dB.
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Hearing crucially depends on cochlear ion homeostasis as evident from deafness elicited by mutations in various genes encoding cation or anion channels and transporters. Ablation of ClCK/barttin chloride channels causes deafness by interfering with the positive electrical potential of the endolymph, but roles of other anion channels in the inner ear have not been studied. Here we report the intracochlear distribution of all five LRRC8 subunits of VRAC, a volume-regulated anion channel that transports chloride, metabolites, and drugs such as the ototoxic anti-cancer drug cisplatin, and explore its physiological role by ablating its subunits. Sensory hair cells express all LRRC8 isoforms, whereas only LRRC8A, D and E were found in the potassium-secreting epithelium of the stria vascularis. Cochlear disruption of the essential LRRC8A subunit, or combined ablation of LRRC8D and E, resulted in cochlear degeneration and congenital deafness of Lrrc8a-/- mice. It was associated with a progressive degeneration of the organ of Corti and its innervating spiral ganglion. Like disruption of ClC-K/barttin, loss of VRAC severely reduced the endocochlear potential. However, the mechanism underlying this reduction seems different. Disruption of VRAC, but not ClC-K/barttin, led to an almost complete loss of Kir4.1 (KCNJ10), a strial K+ channel crucial for the generation of the endocochlear potential. The strong downregulation of Kir4.1 might be secondary to a loss of VRAC-mediated transport of metabolites regulating inner ear redox potential such as glutathione. Our study extends the knowledge of the role of cochlear ion transport in hearing and ototoxicity.
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Proteínas de la Membrana , Ratones Noqueados , Animales , Ratones , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Audición , Cóclea/metabolismo , Cóclea/patología , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/patología , Estría Vascular/metabolismo , Estría Vascular/patología , Sordera/metabolismo , Sordera/patología , Sordera/genética , Canales Aniónicos Dependientes del Voltaje/metabolismo , Canales Aniónicos Dependientes del Voltaje/genéticaRESUMEN
In recent years, tools for early detection of irreversible trauma to the basilar membrane during hearing preservation cochlear implant (CI) surgery were established in several clinics. A link with the degree of postoperative hearing preservation in patients was investigated, but patient populations were usually small. Therefore, this study's aim was to analyze data from intraoperative extracochlear electrocochleography (ECochG) recordings for a larger group.During hearing preservation CI surgery, extracochlear recordings were made before, during, and after CI electrode insertion using a cotton wick electrode placed at the promontory. Before and after insertion, amplitudes and stimulus response thresholds were recorded at 250, 500, and 1000 Hz. During insertion, response amplitudes were recorded at one frequency and one stimulus level. Data from 121 patient ears were analyzed.The key benefit of extracochlear recordings is that they can be performed before, during, and after CI electrode insertion. However, extracochlear ECochG threshold changes before and after CI insertion were relatively small and did not independently correlate well with hearing preservation, although at 250 Hz they added some significant information. Some tendencies-although no significant relationships-were detected between amplitude behavior and hearing preservation. Rising amplitudes seem favorable and falling amplitudes disadvantageous, but constant amplitudes do not appear to allow stringent predictions.Extracochlear ECochG measurements seem to only partially realize expected benefits. The questions now are: do gains justify the effort, and do other procedures or possible combinations lead to greater benefits for patients?
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Audiometría de Respuesta Evocada , Umbral Auditivo , Cóclea , Implantación Coclear , Implantes Cocleares , Audición , Humanos , Audiometría de Respuesta Evocada/métodos , Estudios Retrospectivos , Implantación Coclear/instrumentación , Femenino , Persona de Mediana Edad , Masculino , Anciano , Adulto , Audición/fisiología , Cóclea/cirugía , Cóclea/fisiopatología , Resultado del Tratamiento , Adolescente , Valor Predictivo de las Pruebas , Adulto Joven , Niño , Audiometría de Tonos Puros , Anciano de 80 o más Años , Preescolar , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/fisiopatología , Pérdida Auditiva/cirugía , Pérdida Auditiva/rehabilitaciónRESUMEN
OBJECTIVE: The frequency specific maximum output (MO) of active middle ear implants is the most crucial parameter for speech intelligibility. We determined individual MO from clinical routine data in round window (RW) coupling of the Vibrant Soundbridge (VSB). DESIGN: Monocentric, retrospective analysis. STUDY SAMPLE: 68 ears implanted with the VSB at the RW were analysed. Using bone conduction and direct threshold, MO was determined for combinations of implants (VORP502, VORP503) and processors (Samba, Amadé). Coupling modes were: (A) without coupler (N = 28), (B) spherical coupler (N = 19), (C) soft coupler (N = 10) or (D) custom-made "Hannover coupler" (N = 11). RESULTS: The MO frequency dependence was similar for coupling types (A-D) with a maximum at 1.5 kHz. No differences between groups were observed, although the average MO of the soft coupler was 10 dB lower. The average MO (0.5, 1.0, 2.0, 4.0 kHz) was (A) 77.6 ± 15.0 dB HL, (B) 81.0 ± 11.1 dB HL, (C) 67.6 ± 17.9 dB HL (C), and (D) 79.6 ± 11.7 dB HL (D). CONCLUSION: The individual MO can be determined from patients' clinical data. It permits in-depth analyses of patient outcomes and definition of evidence-based indication and decision criteria.
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The feasibility of low frequency pure tone generation in the inner ear by laser-induced nonlinear optoacoustic effect at the round window was demonstrated in three human cadaveric temporal bones (TB) using an integral pulse density modulation (IPDM). Nanosecond laser pulses with a wavelength in the near-infrared (NIR) region were delivered to the round window niche by an optical fiber with two spherical lenses glued to the end and a viscous gel at the site of the laser focus. Using IPDM, acoustic tones with frequencies between 20 Hz and 1 kHz were generated in the inner ear. The sound pressures in scala tympani and vestibuli were recorded and the intracochlear pressure difference (ICPD) was used to calculate the equivalent sound pressure level (eq. dB SPL) as an equivalent for perceived loudness. The results demonstrate that the optoacoustic effect produced sound pressure levels ranging from 140 eq. dB SPL at low frequencies ≤ 200 Hz to 90 eq. dB SPL at 1 kHz. Therefore, the produced sound pressure level is potentially sufficient for patients requiring acoustic low frequency stimulation. Hence, the presented method offers a potentially viable solution in the future to provide the acoustic stimulus component in combined electro-acoustic stimulation with a cochlear implant.
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Ventana Redonda , Sonido , Humanos , Estimulación Acústica , Ventana Redonda/fisiología , Rampa Timpánica/fisiología , Rayos Láser , Cóclea/fisiologíaRESUMEN
OBJECTIVES: The maximum output provided by a bone conduction (BC) device is one of the main factors that determines the success when treating patients with conductive or mixed hearing loss. Different approaches such as sound pressure measurements using a probe microphone in the external auditory canal or a surface microphone on the forehead have been previously introduced to determine the maximum output of active transcutaneous BC devices that are not directly accessible after implantation. Here, we introduce a method to determine the maximum output hearing level (MOHL) of a transcutaneous active BC device using patients' audiometric data. DESIGN: We determined the maximum output in terms of hearing level MOHL (dB HL) of the Bonebridge using the audiometric and direct BC threshold of the patient together with corresponding force levels at hearing threshold and the maximum force output of the device. Seventy-one patients implanted with the Bonebridge between 2011 and 2020 (average age 45 ± 19 years ranging from 5 to 84 years) were included in this study. The analyses of MOHLs were performed by (1) dividing patients into two groups with better or worse average audiometric BC threshold (0.5, 1, 2, 4 kHz), on the ipsilateral side or (2) by separating the MOHLs based on better or worse frequency-by-frequency specific audiometric BC thresholds on the ipsilateral (implanted) side. RESULTS: When using a frequency-by-frequency analysis obtained average ipsilateral MOHLs were in the range between 51 and 73 dB HL for frequencies from 0.5 to 6 kHz in the group with better audiometric BC threshold on the ipsilateral ears. The average contralateral MOHLs in the group with better contralateral hearing were in the range from 43 to 67 dB HL. The variability of the data was approximately 6 to 11 dB (SDs) across measured frequencies (0.5 to 6 kHz). The average MOHLs were 4 to 8 dB higher across frequencies in the group with better audiometric BC threshold on the ipsilateral ears than in the group with better audiometric BC threshold on the contralateral ears. The differences between groups were significant across measured frequencies ( t test; p < 0.05). CONCLUSIONS: Our proposed method demonstrates that the individual frequency-specific MOHL on the ipsilateral and contralateral side of individual patients with a transcutaneous BC device can be determined mainly using direct and audiometric BC threshold data of the patients from clinical routine. The average MOHL of the implant was found 4 to 8 dB higher on the ipsilateral (implanted) side than on the contralateral side.
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Sordera , Audífonos , Pérdida Auditiva , Humanos , Adulto , Persona de Mediana Edad , Conducción Ósea , Pérdida Auditiva Conductiva , Audición , Umbral AuditivoRESUMEN
OBJECTIVES: Test feasibility of a means to distinguish artifact from relevant signal in an experimental method for pre-clinical assessment of bone conduction (BC) stimulation efficiency based on measurement of intracochlear pressure (ICP). METHODS: Experiments were performed on fresh-frozen human temporal bones and cadaver heads. In a first step, fiber optic pressure sensors inserted into the cochlea through cochleostomies were intentionally vibrated to generate relative motion versus the stationary specimen, and the resulting ICP artifact recorded, before and after attaching the sensor fiber to the bone with glue. In a second step, BC stimulation was applied in the conventional location for a commercial bone anchored implant, as well as two alternative locations closer to the otic capsule. Again, ICP was recorded and compared with an estimated artifact, calculated from the previous measurements with intentional vibration of the fiber. RESULTS: Intentional vibration of the sensor fiber creates relative motion between fiber and bone, as intended, and causes an ICP signal. The stimulus does not create substantial promontory vibration, indicating that the measured ICP is all artifact, i.e. would not occur if the sensor were not in place. Fixating the sensor fiber to the bone with glue reduces the ICP artifact by at least 20 dB. BC stimulation also creates relative motion between sensor fiber and bone, as expected, from which an estimated ICP artifact level can be calculated. The ICP signal measured during BC stimulation is well above the estimated artifact, at least in some specimens and at some frequencies, indicating "real" cochlear stimulation, which would result in an auditory percept in a live subject. Stimulation at the alternative locations closer to the otic capsule appear to result in higher ICP (no statistical analysis performed), indicating a trend towards more efficient stimulation than at the conventional location. CONCLUSIONS: Intentional vibration of the fiber optic sensor for measurement of ICP can be used to derive an estimate of the artifact to be expected when measuring ICP during BC stimulation, and to characterize the effectiveness of glues or other means of reducing the artifact caused by relative motion of fiber and bone.
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Artefactos , Vibración , Humanos , Estimulación Acústica/métodos , Cóclea/fisiología , Conducción Ósea/fisiología , CadáverRESUMEN
OBJECTIVE: Rabbit snuffles is one of the most common challenges in veterinary practice. The aim of the present study was to evaluate nasal samples of rabbits submitted between 2015-2019, with regard to bacterial distribution and antimicrobial resistance. MATERIAL AND METHODS: Each sample was plated on four different agar plates and enriched in a non-selective broth. Isolates were identified by MALDI Biotyper® (MBT) (Bruker Daltonik GmbH, Bremen, Germany) and antimicrobial susceptibility was performed by broth microdilution method in accordance with the Clinical and Laboratory Standards Institute (CLSI, Wayne, PA, USA). RESULTS: A total of 1261 samples were evaluated. Among the samples that tested positive (n=941), one bacterial species was detected in 79.1% of the cases, and more than one bacterial species (mixed culture) was found in 20.9% of the cases. A total of 150 species from 14 families were identified. Isolates belonging to the family Pasteurellaceae were identified most frequently, followed by Enterobacteriaceae, Pseudomonadaceae and Staphylococcaceae.A total of 467 antibiograms of the most common pathogens with possible clinical relevance (Pasteurella multocida [14.6%], Pasteurella species [10.0%], Staphylococcus aureus [5.9%], Pseudomonas aeruginosa [5.4%] and Bordetella bronchiseptica [4.8%]) were evaluated. Quinolones showed the highest efficacy and clindamycin the lowest. Furthermore, among S. aureus, MRSA were most frequently detected in 2016 reaching 23.1% of cases. CONCLUSIONS AND CLINICAL RELEVANCE: Since the causal bacteria for rabbit snuffles are mostly found in the deeper areas of the nose and the nasal vestibule is often contaminated with ubiquitous and coliform bacteria, it would make sense to take samples from the depth of the nasal cavity, ideally via nasal lavage. Due to the demonstrated pathogen diversity and long-term therapy associated with the disease, bacterial culture and sensitivity testing is recommended as part of the management. In the absence of an antibiogram, enrofloxacin is the drug of first choice due to its favorable resistance pattern and tolerability. However, since quinolones are considered as "critically important" antibiotics, their use should be limited to a minimum.
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Quinolonas , Staphylococcus aureus , Conejos , Animales , Cavidad Nasal , Estudios Retrospectivos , Bacterias , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana/veterinaria , Farmacorresistencia BacterianaRESUMEN
The aim of this work is to generate defined tones that cover the human hearing range in aqueous media for a later application in middle or inner ear implants. In our experiments, we investigated the characteristics of single laser pulses and pulse trains with different laser repetition rates of nanosecond laser pulses that were focused into aqueous media in a small volume. The frequency of the generated tones was limited by the spectral properties of the single acoustic pulses, which depended on the medium. Tones with fundamental frequencies above 8 kHz were generated using laser pulses focused into water. By replacing water with gel, tones between 500 Hz and 20 kHz could be produced. The generation of tones in the low-frequency range was only possible when laser pulse trains with pulse density modulated pulse patterns were applied in gel. This enabled the generation of tones between 20 Hz and 2 kHz. Consequently, the combination of different pulse patterns for the different frequency ranges allows generating optoacoustic tones between 20 Hz and 20 kHz in gel. Thus, we can cover the complete range of human hearing through optoacoustically generated tones.
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Acústica , Audición , Humanos , Rayos Láser , AguaRESUMEN
Introduction: The Hannover Coupler version 2 (HC2) was designed to (1) adapt the coupler geometry to the round window (RW) niche (2) to stabilize the floating mass transducer, and (3) to control static coupling forces to the RW. First audiological outcomes with a custom-made HC2 are reported here. Material and Methods: Ten patients were enrolled in our site-initiated, prospective study. To assess audiological outcomes up to 6 months, preoperative and postoperative hearing thresholds, word recognition score (WRS) at 65 dB SPL and the speech recognition threshold in quiet and noise were performed. The effective gain (EG) and the coupling efficiency were calculated. Results: One revision surgery had to be performed during the study period and a significant, but clinically not relevant bone conduction thresholds change was observed at 4 and 6 kHz at 6-month follow-up. At 6 months, the median WRS (n = 10) improved significantly from 0% to 80%. The median speech reception threshold in noise improved significantly from 11.6 to -2.4 dB SNR, and in quiet significantly from 79.6 to 44.4 dB SPL. The average EG of -1.3 dB indicated a closure of the air bone gap. The determined average coupling efficiency of 23.3 dB was within the acceptance range suggested by the manufacturer. Conclusion: For patients with mixed hearing loss and multiple ear surgeries, the HC2 provided good and stable speech recognition results exceeding published results of RW coupling without a coupler or coupling with the RW soft coupler.
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OBJECTIVES: The output performance of a novel semi-implantable transcutaneous bone conduction device was compared to an established percutaneous bone-anchored hearing system device using cadaver heads. The influence of actuator position, tissue growth below the actuator and mounting it on the surface or in a flattened bone bed on the performance of the implanted actuator was investigated. MATERIALS AND METHODS: The percutaneous and the new transcutaneous device were sequentially implanted at two sites in five human cadaver heads: 55 mm superior-posterior to the ear canal opening (position A) and, closer to the cochlea, about 20 mm inferior-posterior to the ear canal opening behind the pinna on the mastoid (position B). The ipsi- and contralateral cochlear promontory (CP) velocity magnitude responses to percutaneous and transcutaneous stimulation were measured using laser Doppler vibrometry. In addition, the CP vibration of the transcutaneous device placed directly on the skull bone surface was compared with the placement in a flattened bone bed at a depth of about 3 mm. Finally, the influence of placing a thin silicone interposition layer under the implanted transducer was also explored. RESULTS: The percutaneous device provided about an 11 dB higher average CP vibration level than the transcutaneous device at frequencies between 0.5 and 10 kHz. The ipsilateral CP vibration responses with stimulations at position B were on average 13 dB higher compared to stimulation at position A. The placement of the transcutaneous transducer at position B provided similar or higher average vibration magnitudes than the percutaneous transducer at position A. The 3 mm deep flattened bone bed had no significant effects on the output performance. Placing a thin silicone layer under the transcutaneous transducer had no significant influence on the output of the transcutaneous device. CONCLUSIONS: Our results using the CP vibration responses show that at frequencies above 500 Hz the new transcutaneous device at position B provides similar output levels as the percutaneous device at position A. The results also indicated that neither a bone bed for the placement of the transcutaneous transducer nor a simulated tissue growth between the actuator and the bone affect the output performance of the device.
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Conducción Ósea , Audífonos , Conducción Ósea/fisiología , Cadáver , Cóclea/fisiología , Humanos , Siliconas , VibraciónRESUMEN
BACKGROUND: Fibroblast growth factors (Fgfs) are required for survival and organ formation during embryogenesis. Fgfs often execute their functions redundantly. Previous analysis of Fgf3 mutants revealed effects on inner ear formation and embryonic survival with incomplete penetrance. RESULTS: Here, we show that presence of a neomycin resistance gene (neo) replacing the Fgf3 coding region leads to reduced survival during embryogenesis and an increased penetrance of inner ear defects. Fgf3neo/neo mutants showed reduced expression of Fgf4, which is positioned in close proximity to the Fgf3 locus in the mouse genome. Conditional inactivation of Fgf4 during inner ear development on a Fgf3 null background using Fgf3/4 cis mice revealed a redundant requirement between these Fgfs during otic placode induction. In contrast, inactivation of Fgf3 and Fgf4 in the pharyngeal region where both Fgfs are also co-expressed using a Foxg1-Cre driver did not affect development of the pharyngeal arches. However, these mutants showed reduced perinatal survival. CONCLUSIONS: These results highlight the importance of Fgf signaling during development. In particular, different members of the Fgf family act redundantly to guarantee inner ear formation and embryonic survival.
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Oído Interno , Factores de Crecimiento de Fibroblastos , Animales , Ectodermo/metabolismo , Femenino , Factor 3 de Crecimiento de Fibroblastos/genética , Factor 3 de Crecimiento de Fibroblastos/metabolismo , Factor 4 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/metabolismo , Factores de Transcripción Forkhead/genética , Ratones , Familia de Multigenes , Proteínas del Tejido Nervioso/genética , EmbarazoRESUMEN
OBJECTIVE: The Cochlear™ Osia® System (Osia) is an active transcutaneous bone conduction implant system intended for patients with conductive and mixed hearing loss but can also be used in cases of single-sided deafness (SSD) for the contralateral routing of signal (CROS). The Osia implant is placed subcutaneously under the intact skin behind the ear with the piezoelectric actuator connected to an osseointegrated BI300 implant - a titanium screw used for a 2-stage Baha surgery - on the mastoid. The external processor is magnetically attached to the subcutaneous implant receiver coil. As the Osia has recently been CE certified and is new on the market, with limited patient outcome data for SSD available, the objective of this study was the evaluation of surgical procedure, audiological results, and patient satisfaction for the Osia in SSD patients. STUDY DESIGN: In a prospective, monocentric clinical observation study, 6 patients (18 years of age or older) with SSD and bone conduction thresholds pure tone average 0.5, 1, 2, and 4 kHz ≤25 dB HL on the contralateral side were implanted with an Osia. Analysis of clinical outcome data with respect to surgical technique, adverse events, audiological measurement, and subjective benefit for SSD patients was conducted. Audiological measurements performed included hearing thresholds, sound field thresholds, word recognition scores (WRS; in %) in quiet, and speech recognition thresholds in noise (in dB SNR). All tests were performed unaided and aided with the Osia. The subjective benefit with the Osia was determined by using 2 questionnaires; the Abbreviated Profile of Hearing Aid Benefit (APHAB) and the Bern Benefit in Single-Sided Deafness (BBSSD). RESULTS: Preliminary results indicate a straightforward surgical procedure with a low rate of complications and an improvement in speech perception in quiet, listening performance in everyday situations and patient satisfaction. However, in one of 6 subjects, a revision surgery had to be performed. CONCLUSION: Provided that SSD patients are open for CROS hearing, they can benefit from the Osia by reduced head shadow effects and better speech recognition. Special caution should be given to the skin at the site of implantation to avoid complications.
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Prótesis Anclada al Hueso , Sordera , Audífonos , Percepción del Habla , Adolescente , Adulto , Conducción Ósea , Pérdida Auditiva Conductiva/cirugía , Humanos , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Direct acoustic cochlear stimulation uses piston motion to substitute for stapes footplate (SFP) motion. The ratio of piston to stapes footplate motion amplitude, to generate the same loudness percept, is an indicator of stimulation efficiency. We determined the relationship between piston displacement to perceived loudness, the achieved maximum power output and investigated stapes fixation and obliteration as confounding factors. The electro-mechanical transfer function of the actuator was determined preoperatively on the bench and intraoperatively by laser Doppler vibrometry. Clinically, perceived loudness as a function of actuator input voltage was calculated from bone conduction thresholds and direct thresholds via the implant. The displacement of a 0.4 mm diameter piston required for a perception equivalent to 94 dB SPL at the tympanic membrane compared to normal SFP piston displacement was 27.6-35.9 dB larger, consistent with the hypothesis that the ratio between areas is responsible for stimulation efficiency. Actuator output was 110 ± 10 eq dB SPLFF @1Vrms ≤ 3 kHz and decreased to 100 eq dB SPLFF at 10 kHz. Output was significantly higher for mobile SFPs but independent from obliteration. Our findings from clinical data strongly support the assumption of a geometrical dependency on piston diameter at the biological interface to the cochlea.
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Estimulación Acústica , Oído Interno/fisiología , Prótesis Osicular , Anciano , Algoritmos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Teóricos , Estribo , Resultado del TratamientoRESUMEN
Tobramycin is a broad-spectrum aminoglycoside antibiotic agent. The compound is obtained from the base-catalyzed hydrolysis of carbamoyltobramycin (CTB), which is naturally produced by the actinomycete Streptoalloteichus tenebrarius. However, the strain uses the same precursors to synthesize several structurally related aminoglycosides. Consequently, the production yields of tobramycin are low, and the compound's purification is very challenging, costly, and time-consuming. In this study, the production of the main undesired product, apramycin, in the industrial isolate Streptoalloteichus tenebrarius 2444 was decreased by applying the fermentation media M10 and M11, which contained high concentrations of starch and dextrin. Furthermore, the strain was genetically engineered by the inactivation of the aprK gene (∆aprK), resulting in the abolishment of apramycin biosynthesis. In the next step of strain development, an additional copy of the tobramycin biosynthetic gene cluster (BGC) was introduced into the ∆aprK mutant. Fermentation by the engineered strain (∆aprK_1-17L) in M11 medium resulted in a 3- to 4-fold higher production than fermentation by the precursor strain (∆aprK). The phenotypic stability of the mutant without selection pressure was validated. The use of the engineered S. tenebrarius 2444 facilitates a step-saving, efficient, and, thus, more sustainable production of the valuable compound tobramycin on an industrial scale.
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Actinobacteria/genética , Antibacterianos/biosíntesis , Tobramicina/biosíntesis , Aminoglicósidos/biosíntesis , Fermentación/genética , Ingeniería Genética/métodos , Familia de Multigenes/genética , Nebramicina/análogos & derivados , Nebramicina/biosíntesisRESUMEN
INTRODUCTION: This study aims to investigate the performance of an active middle ear implant actuator for various coupling configurations. Actuator output and conductive losses were measured, and the stability of coupling was evaluated by challenging the link between actuator and ossicles through pressure events in magnitudes that occur in daily life. METHODS: Actuator coupling efficiency and the occurrence of conductive losses were measured in 10 temporal bones through laser Doppler vibrometry on the stapes footplate for various coupling types (incus short process with and without laser hole, incus long process, stapes head). To test the stability of coupling, actuator output was measured before and after daily-life pressure events that were simulated; Valsalva maneuvers (500 cycles of -40 to +60 hPa) and jumping into a swimming pool and diving 3 m deep (a step change of 300 hPa). RESULTS: Actuator output was similarly high for all types of coupling to the incus (short process and long process) and most efficient for coupling to the stapes head. Conductive losses occurred in two temporal bones (TBs) for short process coupling but for seven TBs for coupling to the incus long process. All coupling types were stable and did not lose efficiency after pressure events in the low-frequency range (<1âkHz). Losses in output of 13 to 24âdB were observed in one TB at frequencies from 3 to 6âkHz. CONCLUSION: Actuator output was similarly high for all types of coupling to the incus but coupling to the incus long process led to a higher occurrence of conductive losses. All three coupling configurations connected the actuator securely to the ossicular chain, under variations of barometric pressure that can be expected in daily life.
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Prótesis Osicular , Oído Medio/cirugía , Humanos , Yunque/cirugía , Estribo , Hueso Temporal/cirugía , VibraciónRESUMEN
OBJECTIVE: Investigation of long-term safety and performance of an active, transcutaneous bone conduction implant in adults and children up to 36âmonths post-implantation. STUDY DESIGN: Prospective, single-subject repeated-measures design. SETTING: Otolaryngology departments of eight German and Austrian hospitals.∗§||¶#∗∗ Affiliations listed above that did not participate in the study.§§||||¶¶. PATIENTS: Fifty seven German-speaking patients (49 adults and eight children) suffering from conductive or mixed hearing loss, with an upper bone conduction threshold limit of 45âdB HL at frequencies between 500 and 3000âHz. INTERVENTION: Implantation of the Bonebridge transcutaneous bone conduction hearing implant (tBCI). MAIN OUTCOME MEASURES: Patients' audiometric pure tone averages (PTA4) (0.5, 1, 2, 4 kHz) thresholds (air conduction, bone conduction, and sound field) and speech perception (word recognition scores [WRS] and speech reception thresholds [SRT50%]) were tested preoperatively and up to 36âmonths postoperatively. Patients were also monitored for adverse events and administered quality-of-life questionnaires. RESULTS: Speech perception (WRS: pre-op: 17.60%, initial activation [IA]: 74.23%, 3M: 83.65%, 12M: 83.46%, 24M: 84.23%, 36M: 84.42%; SRT50%: pre-op: 65.56âdB SPL, IA: 47.67âdB SPL, 3M: 42.61âdB SPL, 12M: 41.11âdB SPL, 24M: 41.74âdB SPL, 36M: 42.43âdB SPL) and sound field thresholds (pre-op: 57.66âdB HL, IA: 33.82âdB HL, 3M: 29.86âdB HL, 12M: 28.40âdB HL, 24M: 28.22âdB HL, 36M: 28.52âdB HL) improved significantly at all aided postoperative visits. Air and bone conduction thresholds showed no significant changes, confirming preservation of patients' residual unaided hearing. All adverse events were resolved by the end of the study. CONCLUSIONS: Safety and performance of the tBCI was demonstrated in children and adults 36âmonths postoperatively.
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Audífonos , Percepción del Habla , Adulto , Umbral Auditivo , Conducción Ósea , Niño , Audición , Pérdida Auditiva Conductiva/cirugía , Pruebas Auditivas , Humanos , Estudios Prospectivos , Resultado del TratamientoRESUMEN
HYPOTHESIS: Intracochlear pressure measurements in one cochlear scala are sufficient as reference to determine the output of an active middle ear implant (AMEI) in terms of "equivalent sound pressure level" (eqSPL). BACKGROUND: The performance of AMEIs is commonly calculated from stapes velocities or intracochlear pressure differences (PDiff). However, there are scenarios where measuring stapes velocities or PDiff may not be feasible, for example when access to the stapes or one of the scalae is impractical. METHODS: We reanalyzed data from a previous study of our group that investigated the performance of an AMEI coupled to the incus in 10 human temporal bones. We calculated eqSPL based on stapes velocities according to the ASTM standard F2504-05 and based on intracochlear pressures in scala vestibuli, scala tympani, and PDiff. RESULTS: The AMEI produced eqSPL of â¼100 to 120âdB at 1 Vrms. No significant differences were found between using intracochlear pressures in scala vestibuli, scala tympani, or PDiff as a reference. The actuator performance calculated from stapes displacements predicted slightly higher eqSPLs at frequencies above 1000âHz, but these differences were not statistically significant. CONCLUSION: Our findings show that pressure measurements in one scala can be sufficient to evaluate the performance of an AMEI coupled to the incus. The method may be extended to other stimulation modalities of the middle ear or cochlea when access to the stapes or one of the scalae is not possible.
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Cóclea , Sonido , Oído Medio , Humanos , Rampa Timpánica , Escala VestibularRESUMEN
A multitude of new implantable hearing systems and applications creates new options for pathologies which have been difficult to treat in the past. For many of these hearing systems preclinical technical methods to characterize devices and applications are limited. Therefore, clearly structured clinical investigations and trials are necessary to render results of devices and applications comparable for meta-analysis. Beside optimizing results in current applications, this is also essential for comparisons with established treatment options and differential indication criteria. Even during planning and design of studies, the timing of reference measurements and the choice of-on-off vs. pre-post comparisons in audiological testing decides the focus of the study. This applies equally to the choice for a monaural vs. a binaural test design, which decides whether the study will have the device or the overall result of the treatment in focus. Additional measures such as effective gain, coupling efficiency, and maximal possible intelligibility (WRSmax) can be performed with standard methods and equipment and enable better insight into functional principles of devices and applications. However, testing methods have inherent limitations that have to be taken into account for correct and meaningful interpretations. The use of standardized audiological instruments is essential and permits comparison of devices and treatment results. This is equally important for the creation of evidence-based differential indication criteria between different types of devices as well as for choosing the optimal treatment.
Asunto(s)
Conducción Ósea , Audífonos , Pruebas Auditivas , Prótesis e ImplantesRESUMEN
Semi-implantable bone conduction implants (BCI) and active middle ear implants (AMEI) for patients with sensorineural, conductive or mixed hearing loss commonly use an amplitude modulation technology to transmit power and sound signals from an external audio processor to the implant. In patients, the distance dependence of the signal amplitude is of minor importance as the skin thickness is constant and only varies between 3-7 mm. In this range, critical coupling transmission technique sufficiently reduces the variability in amplitude, but fails to provide well-defined amplitudes in many research and clinical applications such as intraoperative integrity tests where the distance range is exceeded by using sterile covers. Here we used the BCI Bonebridge (BB, Med-El, Austria) as an example to develop and demonstrate a system that synthesizes the transmission signal, determines the distance between the transmitter and the receiver implant coil and compensates transmission losses. When compared to an external audio processor (AP304) on an artificial mastoid, our system mainly decreased amplitude variability from over 11 dB to less than 3 dB for audio frequencies (0.1-10 kHz) at distances up to 15 mm, making it adequate for intraoperative and audiometric tests.