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(2021). Thirty Years of Translational Research Behind MED-EL. Acta Oto-Laryngologica: Vol. 141, Thirty Years of Translational Research Behind MED-EL, pp. (i)-(cxcvi).

Optimal matching of an electrode array to the cochlear anatomy plays a key role in bringing the best benefit of CI technology to the users. Even within the category of normal anatomy cochlea, the size variation is huge justifying MED-EL's FLEX electrode array to be available in five different lengths. Within the malformed inner-ear category the anatomical variation is huge, convincing MED-EL to custom-design the electrode array as per the request from the operating surgeons. Thanks to G. Bredberg, M. Beltrame, L. Sennaroglu, J. Gavilan, S. Plontke, T. Lenarz, J. Müller, and few others for their valuable suggestions on unique electrode designs satisfying various needs. Translational research efforts at MED-EL in cooperation with CI surgeons from across the world led to the implantation of a variety of electrode array designs in patients with special cochlear needs.

The Auditory Brainstem Implant (ABI) is based on the classic cochlear implant (CI) but uses a different stimulation electrode. At MED-EL, the early development activities on ABI started in the year 1994, with the suggestion coming from J. Helms and J. Müller from Würzburg, Germany in collaboration with the Univ. of Innsbruck Austria. The first ABI surgery in a neuro-fibromatosis (NF2) patient with the MED-EL device took place in the year 1997. Later, the indication of ABI was expanded to non-NF2 patients with severe inner-ear malformation, for whom a regular CI will not be beneficial. Key translational research activities at MED-EL in collaboration with numerous clinics investigating the factors that affect the hearing performance amongst ABI patients, importance of early ABI implantation in children, tools in pre-operative assessment of ABI candidates and new concepts that were pursued with the MED-EL ABI device. The CE-mark for the MED-EL ABI to be used in adults and children down to the age of 12 months without NF-2 was granted in 2017 mainly based on two long-term clinical studies in the pediatric population. This article covers the milestones of translational research from the first concept to the widespread clinical use of ABI in association with MED-EL.

Electric-acoustic stimulation (EAS) is a special treatment modality for those patients who are profoundly deaf in the high-frequency (HF) region and retain usable hearing in the low-frequency (LF) region. Combining the electric stimulation with cochlear implant (CI) in the HF and acoustic amplification of residual hearing using a conventional hearing aid (HA) in the LF region defines EAS. The EAS concept was first proposed by C. von Ilberg from Frankfurt, Germany in the year 1997. In association with MED-EL, all the necessary safety studies were performed in non-human subjects before the first patient received it in 1997. In association with MED-EL, all the necessary safety studies were performed in non-human subjects before the first patient received it in 1999. For the patient to successfully use the EAS concept, the residual hearing needs to be preserved to a high extent and for several years. This requires a highly flexible electrode array in safeguarding the intra-cochlear structures during and after the CI electrode array insertion. Combining the HA unit with the audio processor unit of the CI was necessary for the convenient wearing of the unified audio processor. Fitting of the unified audio processor is another important factor that contributes to the overall success of the EAS treatment. The key translational research efforts at MED-EL were on the development of flexible electrodes, a unified audio processor, innovations in the fitting process, intra-operative monitoring of cochlear health during electrode insertion, pre-operative soft-ware tool to evaluate the cochlear size and electrode selection and some new innovations tried within EAS topic. This article covers the milestones of translational research from the first concept to the widespread clinical use of EAS.

Objectives To study the changes in the coiled configuration of electrode excess lead in the mastoid cavity in the cochlear implant recipients over time. Methods Post-operative CT scans at two different appointments of fourteen patients with cochlear implants (CI) were retrospectively analyzed using a DICOM viewer software (3D-slicer). Mastoid thickness (MT) was measured in the oblique coronal plane from the round window (RW) entrance to the mastoid edge and inter-cochlear distance (ICD) was measured in the axial plane at the fundus level between two ears. 3D segmentation of the entire inner ear of both sides and coiled electrode excess lead was performed to visually compare the changes in coiled configuration between the two CT scan time points. Result MT and ICD increased logarithmically with the patient’s age, as has been measured from both the 1st and the 2nd CT scans and a weak linear correlation between MT and ICD was observed. Growth in MT and ICT measured between the time of 1st and 2nd CT scans showed a strong linear correlation. In eight cases, changes in the electrode excess lead have been observed in the 2nd CT scan, either a change in the coiling configuration of electrode excess lead or shifted laterally toward the mastoid edge. The ICD growth between the 1st and the 2nd CT scans was >2 mm in only seven cases and all of them were children. All other six cases had no observed changes in the coiled electrode lead. In addition, the mastoid growth between the 1st and the 2nd CT scan was >2.5 mm in only 4 cases. Conclusion Coiled configuration of electrode excess lead could change when the MT and ICD increased over time.

The NA23_RS08100 gene of Fervidobacterium islandicum AW-1 encodes a keratin-degrading β-aspartyl peptidase (FiBAP) that is highly expressed under starvation conditions. Herein, we expressed the gene in Escherichia coli, purified the recombinant enzyme to homogeneity, and investigated its function. The 318 kDa recombinant FiBAP enzyme exhibited maximal activity at 80°C and pH 7.0 in the presence of Zn2+. Size-exclusion chromatography revealed that the native enzyme is an octamer comprising a tetramer of dimers; this was further supported by determination of its crystal structure at 2.6 Å resolution. Consistently, the structure of FiBAP revealed three additional salt bridges in each dimer, involving 12 ionic interactions that might contribute to its high thermostability. In addition, the co-crystal structure containing the substrate analog N-carbobenzoxy-β-Asp-Leu at 2.7 Å resolution revealed binuclear Zn2+-mediated substrate binding, suggesting that FiBAP is a hyperthermophilic type-I IadA, in accordance with sequence-based phylogenetic analysis. Indeed, complementation of a Leu auxotrophic E. coli mutant strain (ΔiadA and ΔleuB) with FiBAP enabled the mutant strain to grow on isoAsp-Leu peptides. Remarkably, LC-MS/MS analysis of soluble keratin hydrolysates revealed that FiBAP not only cleaves the C-terminus of isoAsp residues but also has a relatively broad substrate specificity toward α-peptide bonds. Moreover, heat shock-induced protein aggregates retarded bacterial growth, but expression of BAP alleviated the growth defect by degrading damaged proteins. Taken together, these results suggest that the viability of hyperthermophiles under stressful conditions may rely on the activity of BAP within cellular protein repair systems.

In prokaryotes, toxin-antitoxin (TA) systems are commonly found. They likely reflect the adaptation of pathogenic bacteria or extremophiles to various unfavorable environments by slowing their growth rate. Genomic analysis of the extremophile Deinococcus radiodurans R1 revealed the presence of eight type II TA systems, including the genes dr0417, dr0660, dr1530, dr0690, and dr1807. Expression of these toxin genes led to inhibition of Escherichia coli growth, whereas their antidote antitoxins were able to recover the growth defect. Remarkably, Dr0417 (DrMazF) showed endoribonuclease activity toward rRNAs as well as mRNAs, as determined by in vivo and in vitro RNA cleavage assays, and this activity was inhibited by Dr0416 (DrMazE). It was also found that the expression of dr0416-0417 module is directly regulated by the DrMazE-MazF complex. Furthermore, this TA module was induced under stress conditions and plays an important role in survival. To understand the regulatory mechanism at the molecular level, we determined the first high-resolution structures of DrMazF alone and of the DrMazE-MazF complex. In contrast with the hetero-hexameric state of typical MazE-MazF complexes found in other species, DrMazE-MazF crystal structure consists of a hetero-trimer, with the DNA-binding domain of DrMazE undergoing self-cleavage at the flexible linker loop. Our structure revealed that the unique residue R54 provides an additional positive charge to the substrate-binding pocket of DrMazF, its mutation significantly affects the endonuclease activity. Thus, our work reports the unique structural and biochemical features of the DrMazE-MazF system.

Recent advancements in the electric vehicle charging stations are aiding the power system in case of reliability and cost efficiency. Since the transfer switch power supply is an interconnection of various power sources, the system to be analyzed consists of solar as a renewable resource. During peak hours the power demand will be increased, which can be minimized by alternate use of supply. In this project a database is created for efficient power usage (between electrical grid and EV's) and transactions made easier. Efficient usage of power and hazel free transactions is attained using cloud data. Quick response code is used to automatically pay tolls. This paper analyses the electric vehicle considering battery ratings such as voltage and current. The aim is to charge the vehicle automatically when it is plugged in and during peak hours the power demand should be satisfied. The software used for analysis is IOTA tangle.

The question of why pre-curved modiolar hugging (MH) electrodes only cover the basal turn of the cochlea and not beyond that is unanswered yet in the CI field. Therefore the aim of this article is to show what the practical limitations are with the pre-curved MH electrode design in not being able to fabricate beyond one full turn. Every CI electrode design needs a metal mold with grooves for placing the platinum wires and for injecting with the silicone elastomer. Limitations in making a mold with groove that goes beyond one full turn of curvature along with the mechanical deformation of the curved silicone elastomer, prevents making a pre-curved MH electrode beyond one full turn. Electrode tip fold-over, electrode scalar deviation and the inconsistent electrode to modiolus wall proximity are the reported issues with this electrode type which does not help by any means to the operating surgeon and the pediatric candidates especially. If intra-operative imaging is recommended to confirm the proper placement of the electrode for one particular electrode design, then how many clinics in the world may have this facility and is it ethical to put the patient under more radiation risk are the natural questions that needs to be answered in the interest of the patient. Every CI brand should come out of their marketing philosophy and innovate what is essential in bringing the full benefit of the device to the patients.

Objective: Determine the occurrence rate of cochlear implant (CI) electrode tip fold-over and electrode scalar deviation as reported in patient cases with different commercial electrode types. Data-sources: PubMed search for identifying peer-reviewed articles published till 2018 on CI electrode tip fold-over and scalar deviation. Key-words for searching were “Cochlear electrode tip fold-over”, “Cochlear electrode scalar position” and “Cochlear electrode scalar location”. Articles-selection: Only if electrode related issues were investigated in patient cases. 38 articles met the inclusion-criteria. Results: 13 articles on electrode tip fold-over issue covering 3177 implanted ears, out of which 50 ears were identified with electrode tip fold-over with an occurrence rate of 1.57%. Out of 50 ears, 43 were implanted with pre-curved electrodes and the remaining 7 with lateral-wall electrodes. One article reported on both tip fold-over and scalar deviation. 26 articles reported on the electrode scalar deviation covering an overall number of 2046 ears out of which, 458 were identified with electrode scalar deviation at a rate of 22.38%. After removing the studies that did not report on the number of electrodes per electrode type, it was 1324 ears implanted with pre-curved electrode and 507 ears with lateral-wall electrode. Out of 1324 pre-curved electrode implanted ears, 424 were reported with scalar deviation making an occurrence rate of 32%. Out of 507 lateral-wall electrode implanted ears, 43 were associated with scalar deviation at an occurrence rate of 6.7%. Conclusion: This literature review revealing the fact of higher rate of electrode insertion trauma associated with pre-curved electrode type irrespective of CI brand is one step closer to obsolete it from the clinical practice in the interest of patient's cochlear health. Keywords: Electrode tip fold-over, Scalar deviation, Pre-curved electrode, Straight electrode

The objective of this study was to determine the shape of cochlear basal turn through basic cochlear parameters measurement. The secondary aim was to overlay an image of the precurved electrode array on top of the three-dimensional (3D) image of the cochlea to determine which shape of the cochlear basal turn gives optimal electrode-to-modiolus proximity.Computed tomography (CT) preoperative image-data sets of 117 ears were made available for the measurements of cochlear parameters retrospectively. Three-dimensional slicer was used in the visualization and measurement of cochlear parameters from both 3D and 2D (2-dimensional) images of the inner ear. Cochlear parameters including basal turn diameter (The cochlear size as measured byAccurate measurement of cochlear parameters adds value to the overall understanding of the cochlear geometry before a cochlear implantation procedure. The shape of cochlear basal turn could have clinical implications when comes to