The Influence of Hearing Aids on Balance Control: A Systematic Review.

AIM: To assess the current opinion on the effects of hearing loss treatment by hearing aids (HAs) and the benefits of HA use on imbalance. METHODS: PRISMA-compliant systematic review was done, including observational studies in patients affected by mild to severe sensorineural hearing loss with HAs, investigating the benefits of HAs on balance. Electronic searches were performed through Medline, Cochrane, Embase, Web of Science, and Scopus. RESULTS: A total of 200 patients in 8 studies were included in this systematic review. Four studies were cross-sectional, 3 cross-sectional controlled and 1 prospective nonrandomized study. Static and dynamic balance in the aided condition improved in patients assessed using clinical investigations including Romberg test and Functional Ambulation Performance/mini-BESTest, respectively. Variable outcomes were found measuring static and dynamic balance during the aided condition with objective tests (computerized posturography, Mobility Lab device). Improved quality of life outcomes and self-confidence were noted, while subjective measurements of balance had conflicting results. CONCLUSION: Although an improvement in balance in patients with HAs has been shown in certain conditions, the overall benefit is still unclear and it is only possible to speculate that HAs may also improve static, dynamic, or subjective perception of balance function in adults affected by hearing loss.

Establishing Reproducibility and Correlation of Cochlear Microphonic Amplitude to Implant Electrode Position Using Intraoperative Electrocochleography and Postoperative Cone Beam Computed Tomography.

OBJECTIVES: The primary objective of this study was to establish the reproducibility of cochlear microphonic (CM) recordings obtained from a cochlear implant (CI) electrode contact during and immediately after insertion. This was achieved by evaluating the insertion angle and calculating the position of the apical electrode contact during insertion, using postoperative cone beam computed tomography (CBCT). The secondary objective was to create individualized patient maps of electrode contacts located within acoustically sensitive regions by correlating the CM amplitude to the electrode position determined using CBCT. METHODS: CMs were recorded from a CI electrode contact during and immediately after insertion in 12 patients (n = 14 ears). Intraoperative recordings were made for a 0.5 kHz tone burst stimulus and were recorded from the apical electrode contact. Postinsertion recordings were made from the odd-numbered electrode contacts (1-15) along the array, using a range of stimulus frequencies (from 0.125 to 2 kHz). The time point at which each electrode contact passed through the round window was noted throughout the insertion, and the CM amplitude at this point was correlated to postoperative CBCT. This correlation was then used to estimate the CM amplitude at particular points within the cochlea, which was in turn compared with the amplitudes recorded from each electrode postoperatively to assess the reproducibility of the recordings. RESULTS: Significant correlation was shown between intraoperative insertion and postinsertion angles at two amplitude events (maximum amplitude: 29° mean absolute error, r = 0.77, p = 0.006; 10% of maximum amplitude: 52° mean absolute error, r = 0.85, p = 0.002). CONCLUSION: We have developed a novel method to demonstrate the reproducibility of the CM responses recorded from a CI electrode during insertion. By correlating the CM amplitude with the postoperative CBCT, we have also been able to create individualized maps of CM responses, categorizing the cochlea into acoustically responsive and unresponsive regions. If the electrode contacts within the acoustically sensitive regions are shown to be associated with improved loudness discrimination, it could have implications for optimal electrode mapping and placement.

Longitudinal economic analysis of Bonebridge 601 versus percutaneous bone-anchored hearing devices over a 5-year follow-up period.

OBJECTIVES: Percutaneous bone-anchored hearing devices (pBAHDs) are the most commonly used bone conduction implants (BCI). Concerns surround the long-term complications, notably skin-related, in patients with percutaneous abutments. The active transcutaneous BCI Bonebridge system can help avoid some of these pitfalls but is often considered a second-line option due to various factors including perceived increased overall costs. DESIGN: Longitudinal economic analysis of Bonebridge BCI 601 versus pBAHD over a 5-year follow-up period. SETTING: A specialist hearing implant centre. PARTICIPANTS: Adult patients (≥16 years) with conductive hearing loss, mixed hearing loss or single-sided deafness, who received a Bonebridge or pBAHD implant between 1/7/2013 and 1/12/2018 with a minimum 12-month follow-up. MAIN OUTCOME MEASURES: We compared the mean costs per implanted patient for both implants at 1, 3 and 5 years postoperative time points. Clinical effectiveness was evaluated using objective and patient-reported outcome measures. RESULTS: The mean total cost per patient of Bonebridge was significantly higher than pBAHD at 1-year post-implantation (£8512 standard deviation [SD] £715 vs £5590 SD £1394, P < .001); however, by 5-years post-implantation this difference was no longer statistically significant (£12 453 SD £2159 vs £12 575 SD £3854, P > .05). The overall cost convergence was mainly accounted for by the increased long-term complications, revision surgery rates and higher cost of the pBAHD external processor compared to Bonebridge. CONCLUSIONS: Long-term costs of Bonebridge to healthcare providers are comparable to pBAHDs, whilst offering lower complication rates, comparable audiological benefit and patient satisfaction. Bonebridge should be considered as a first-line BCI option in appropriate cases.

Two-Dimensional Mass Spectrometry for Proteomics, a Comparative Study with Cytochrome c.

Two-dimensional Fourier transform ion cyclotron resonance mass spectrometry (2D FT-ICR MS) allows the correlation between precursor and fragment ions in tandem mass spectrometry without the need to isolate the precursor ion beforehand. 2D FT-ICR MS has been optimized as a data-independent method for the structural analysis of compounds in complex samples. Data processing methods and denoising algorithms have been developed to use it as an analytical tool. In the present study, the capabilities of 2D FT-ICR MS are explored with a tryptic digest of cytochrome c with both ECD and IRMPD as fragmentation modes. The 2D mass spectra showed useful fragmentation patterns of peptides over a dynamic range of almost 400. By using a quadratic calibration, fragment ion peaks could be successfully assigned. The correlation between precursor and fragment ions in the 2D mass spectra was more accurate than in MS/MS spectra after quadrupole isolation, due to the limitations of quadrupole isolation. The use of the second dimension allowed for successful fragment assignment from precursors that were separated by only m/z 0.0156. The resulting cleavage coverage of cytochrome c almost matched data provided by high-resolution FT-ICR MS/MS analysis, but the 2D FT-ICR MS method required only one experimental scan.

Self-Assessment of Cochlear Health by New Cochlear Implant Recipients: Daily Impedance, Electrically Evoked Compound Action Potential and Electrocochleography Measurements Over the First Three Postoperative Months.

HYPOTHESES: In newly implanted cochlear implant (CI) users, electrically evoked compound action (eCAPs) and electrocochleography (ECochGs) will remain stable over time. Electrode impedances will increase immediately postimplantation due to the initial inflammatory response, before decreasing after CI switch-on and stabilizing thereafter. BACKGROUND: The study of cochlear health (CH) has several applications, including explaining variation in CI outcomes, informing CI programming strategies, and evaluating the safety and efficacy of novel biological treatments for hearing loss. Very early postoperative CH patterns have not previously been intensively explored through longitudinal daily testing. Thanks to technological advances, electrode impedances, eCAPs, and ECochGs can be independently performed by CI users at home to monitor CH over time. METHODS: A group of newly implanted CI users performed daily impedances, eCAPs, and ECochGs for 3 months at home, starting from the first day postsurgery (N = 7) using the Active Insertion Monitoring system by Advanced Bionics. RESULTS: Measurement validity of 93.5, 93.0, and 81.6% for impedances, eCAPs, and ECochGs, respectively, revealed high participant compliance. Impedances increased postsurgery before dropping and stabilizing after switch-on. eCAPs showed good stability, though statistical analyses revealed a very small but significant increase in thresholds over time. Most ECochG thresholds did not reach the liberal signal-to-noise criterion of 2:1, with low threshold stability over time. CONCLUSION: Newly implanted CI recipients can confidently and successfully perform CH recordings at home, highlighting the valuable role of patients in longitudinal data collection. Electrode impedances and eCAPs are promising objective measurements for evaluating CH in newly implanted CI users.

Improved optimization of the Fourier transform ion cyclotron resonance mass spectrometry phase correction function using a genetic algorithm.

RATIONALE: Fourier Transform Ion Cyclotron Resonance mass spectra exhibit improved resolving power, mass accuracy and signal-to-noise ratio when presented in absorption mode; a process which requires calculation of a phase correction function. Mass spectrometric images can contain many thousands of pixels; hence methods of decreasing the time required to solve for a phase correction function will result in significant improvements in this application. METHODS: A genetic algorithm approach for optimizing the phase correction function has been developed and compared with a previously described convergent iteration technique. RESULTS: The genetic algorithm method has been shown to offer a five-fold improvement in processing speed compared with the previous iterative approach used in the Autophaser algorithm, while maintaining the levels of accuracy. This translates to an 11 hour improvement in processing for a 20 000 pixel mass spectrometric image. CONCLUSIONS: The genetic algorithm method described in this manuscript offers significant processing speed advantages over the previously described convergent iteration technique. This improvement is key to allowing the future routine use of absorption mode mass spectrometric images.

Classification of Acoustic Hearing Preservation After Cochlear Implantation Using Electrocochleography.

The objective to preserve residual hearing during cochlear implantation has recently led to the use of intracochlear electrocochleography (ECochG) as an intraoperative monitoring tool. Currently, a decrease in the amplitude of the difference between responses to alternating-polarity stimuli (DIF response), predominantly reflecting the hair cell response, is used for providing feedback. Including other ECochG response components, such as phase changes and harmonic distortions, could improve the accuracy of surgical feedback. The objectives of the present study were (1) to compare simultaneously recorded stepwise intracochlear and extracochlear ECochG responses to 500 Hz tone bursts, (2) to explore patterns in features extracted from the intracochlear ECochG recordings relating to hearing preservation or hearing loss, and (3) to design support vector machine (SVM) and random forest (RF) classifiers of acoustic hearing preservation that treat each subject as a sample and use all intracochlear ECochG recordings made during electrode array insertion for classification. Forty subjects undergoing cochlear implant (CI) surgery at the Oslo University Hospital, St. Thomas' Hearing Implant Centre, or the University Hospital of Zurich were prospectively enrolled. In this cohort, DIF response amplitude decreases did not relate to postoperative acoustic hearing preservation. Exploratory analysis of the feature set extracted from the ECochG responses and preoperative audiogram showed that the features were not discriminative between outcome classes. The SVM and RF classifiers that were trained on these features could not distinguish cases with hearing loss and hearing preservation. These findings suggest that hearing loss following CI surgery is not always reflected in intraoperative ECochG recordings.

The development and clinical use of the Guy's and St Thomas' quality of life questionnaire (GAST) for adult cochlear implant patients.

OBJECTIVES: To Review the benefit of the GAST questionnaire (Tilston, S. 2003. Assessing the quality of life in adult cochlear implant users. MSc dissertation. London: City University.) to measure hearing related quality of life for adults pre and post-cochlear implantation. To develop a scoring methodology as to what score constitutes a significantly 'good' or 'poor' change to better target rehabilitation to those most in need. DESIGN: The GAST Questionnaire was developed using a robust cycle of validation and reliability analyses using the Statistical Package for the Social Sciences (Norusis, M. 1993. SPSS for windows: professional statistics. release 6.0. Chicago: SPSS Inc.). The scoring methodology was developed by dividing 83 patient full data sets into quintiles for the delta of quality of life improvement and the 9-12 month post-implantation GAST score. RESULTS: The GAST questionnaire design was deemed robust. The scoring methodology used led to the 20th percentile score highlighting individuals requiring further support and the 80th percentiles for those suitable for partial booking. CONCLUSION: The GAST questionnaire is a useful way of identifying the patients in need of support as well as to measure patient reported quality of life improvements following cochlear implantation.

Self-assessment of cochlear health by cochlear implant recipients.

Recent technological advances in cochlear implant (CI) telemetry have enabled, for the first time, CI users to perform cochlear health (CH) measurements through self-assessment for prolonged periods of time. This is important to better understand the influence of CH on CI outcomes, and to assess the safety and efficacy of future novel treatments for deafness that will be administered as adjunctive therapies to cochlear implantation. We evaluated the feasibility of using a CI to assess CH and examined patterns of electrode impedances, electrically-evoked compound action potentials (eCAPs) and electrocochleography (ECochGs), over time, in a group of adult CI recipients. Fifteen subjects were trained to use the Active Insertion Monitoring tablet by Advanced Bionics, at home for 12 weeks to independently record impedances twice daily, eCAPs once weekly and ECochGs daily in the first week, and weekly thereafter. Participants also completed behavioral hearing and speech assessments. Group level measurement compliance was 98.9% for impedances, 100% for eCAPs and 99.6% for ECochGs. Electrode impedances remained stable over time, with only minimal variation observed. Morning impedances were significantly higher than evening measurements, and impedances increased toward the base of the cochlea. eCAP thresholds were also highly repeatable, with all subjects showing 100% measurement consistency at, at least one electrode. Just over half of all subjects showed consistently absent thresholds at one or more electrodes, potentially suggesting the existence of cochlear dead regions. All subjects met UK NICE guidelines for cochlear implantation, so were expected to have little residual hearing. ECochG thresholds were, unsurprisingly, highly erratic and did not correlate with audiometric thresholds, though lower ECochG thresholds showed more repeatability over time than higher thresholds. We conclude that it is feasible for CI users to independently record CH measurements using their CI, and electrode impedances and eCAPs are promising measurements for objectively assessing CH.

Levels of [(3)H]pirenzepine binding in Brodmann's area 6 from subjects with schizophrenia is not associated with changes in the transcription factor SP1 or BACE1.

Decreased muscarinic M1 receptor (CHRM1) mRNA has been reported in Brodmann's area (BA) 6 from subjects with schizophrenia. We have extended this study by measuring levels of CHRM1 ([(3)H]pirenzepine binding), CHRM3 ([(3)H]4-DAMP binding), the transcription factor SP1 and the CHRM1 downstream target beta-site APP-cleaving enzyme 1 (BACE1) in BA 6 from 19 subjects with schizophrenia and 19 control subjects. Radioligand binding was quantified using either in situ radioligand binding with autoradiography or, in cohorts of 10 control subjects and 10 subjects with schizophrenia, membrane enriched fraction (MEF) CNS ([(3)H]pirenzepine binding only). Levels of SP1 and BACE1 were measured by Western blotting. [(3)H]pirenzepine binding to tissue sections was in two layers, binding to tissue sections (Binding layer 1: p<0.01; Binding layer 2: p<0.001) and MEF (p<0.05) were decreased in schizophrenia. Levels of [(3)H]4-DAMP binding, SP1 and BACE1 were not altered in subjects with the disorder. This study shows a decrease in levels of CHRM1 in BA 6 from subjects with schizophrenia; as CHRM1 and BA 6 are important in maintaining normal cognitive function, these data support the hypothesis that decreased levels of cortical CHRM1 may contribute to the cognitive deficits associated with schizophrenia. Our findings on BACE1 suggest that the schizophrenia phenotype reported in BACE(-/-) mice is not simply due to lack of that protein in the cortex.

2D FT-ICR MS of Calmodulin: A Top-Down and Bottom-Up Approach.

Two-dimensional Fourier transform ion cyclotron resonance mass spectrometry (2D FT-ICR MS) allows data-independent fragmentation of all ions in a sample and correlation of fragment ions to their precursors through the modulation of precursor ion cyclotron radii prior to fragmentation. Previous results show that implementation of 2D FT-ICR MS with infrared multi-photon dissociation (IRMPD) and electron capture dissociation (ECD) has turned this method into a useful analytical tool. In this work, IRMPD tandem mass spectrometry of calmodulin (CaM) has been performed both in one-dimensional and two-dimensional FT-ICR MS using a top-down and bottom-up approach. 2D IRMPD FT-ICR MS is used to achieve extensive inter-residue bond cleavage and assignment for CaM, using its unique features for fragment identification in a less time- and sample-consuming experiment than doing the same thing using sequential MS/MS experiments. Graphical Abstract ᅟ.

Does deamidation cause protein unfolding? A top-down tandem mass spectrometry study.

Deamidation is a nonenzymatic post-translational modification of asparagine to aspartic acid or glutamine to glutamic acid, converting an uncharged amino acid to a negatively charged residue. It is plausible that deamidation of asparagine and glutamine residues would result in disruption of a proteins' hydrogen bonding network and thus lead to protein unfolding. To test this hypothesis Calmodulin and B2M were deamidated and analyzed using tandem mass spectrometry on a Fourier transform ion cyclotron resonance mass spectrometer (FTICR-MS). The gas phase hydrogen bonding networks of deamidated and nondeamidated protein isoforms were probed by varying the infra-red multi-photon dissociation laser power in a linear fashion and plotting the resulting electron capture dissociation fragment intensities as a melting curve at each amino acid residue. Analysis of the unfolding maps highlighted increased fragmentation at lower laser powers localized around heavily deamidated regions of the proteins. In addition fragment intensities were decreased across the rest of the proteins which we propose is because of the formation of salt-bridges strengthening the intramolecular interactions of the central regions. These results were supported by a computational flexibility analysis of the mutant and unmodified proteins, which would suggest that deamidation can affect the global structure of a protein via modification of the hydrogen bonding network near the deamidation site and that top down FTICR-MS is an appropriate technique for studying protein folding.

Differentiating Fragmentation Pathways of Cholesterol by Two-Dimensional Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.

Two-dimensional Fourier transform ion cyclotron resonance mass spectrometry is a data-independent analytical method that records the fragmentation patterns of all the compounds in a sample. This study shows the implementation of atmospheric pressure photoionization with two-dimensional (2D) Fourier transform ion cyclotron resonance mass spectrometry. In the resulting 2D mass spectrum, the fragmentation patterns of the radical and protonated species from cholesterol are differentiated. This study shows the use of fragment ion lines, precursor ion lines, and neutral loss lines in the 2D mass spectrum to determine fragmentation mechanisms of known compounds and to gain information on unknown ion species in the spectrum. In concert with high resolution mass spectrometry, 2D Fourier transform ion cyclotron resonance mass spectrometry can be a useful tool for the structural analysis of small molecules. Graphical Abstract ᅟ.

Unexpected crosslinking and diglycation as advanced glycation end-products from glyoxal.

Glyoxal-derived advanced glycation end-products (AGEs) are formed in physiological systems affecting protein/peptide function and structure. These AGEs are generated during aging and chronic diseases such as diabetes and are considered arginine glycating agents. Thus, the study of glyoxal-derived AGEs in lysine residues and amino acid competition is addressed here using acetylated and non-acetylated undecapeptides, with one arginine and one lysine residue available for glycation. Tandem mass spectrometry results from a Fourier transform ion cyclotron resonance mass spectrometer showed glycated species at both the arginine and lysine residues. One species with the mass addition of 116.01096 Da is formed at the arginine residue. A possible structure is proposed to explain this finding (Nδ-[2-(dihydroxymethyl)-2H,3aH,4H,6aH-[1,3]dioxolo[5,6-d]imidazolin-5-yl]-L-ornithine-derived AGE). The second species corresponded to intramolecular crosslink involving the lysine residue and its presence is checked with ion-mobility mass spectrometry.

The occurrence of a deficit in contextual fear extinction in adult amyloid-over-expressing TASTPM mice is independent of the strength of conditioning but can be prevented by mild novel cage stress.

In the amyloid over-expressing TASTPM mouse model of Alzheimer's disease, impaired contextual fear memory occurs early, and is preceded, at 4 months of age, by a deficit in extinction of contextual fear that is resistant to improvement by repeated mild novel cage stress. The first aim of this study was thus to establish whether the extinction deficit could be prevented if the novel cage procedure was applied prior to its onset. The second aim was to establish whether the occurrence of the extinction deficit was dependent on the robustness of the conditioning protocol. We first compared 3-month-old wild-type and TASTPM mice for acquisition, retention and extinction of contextual fear and then, looked at the impact of 5 weeks of novel cage stress (4 x 1 h/week) applied from 3 months onwards, on age-related changes in these behaviours evaluated at 4.5 months of age. In another experiment, we compared 4-month-old TASTPM and wild-type mice for the impact of a 2 and 5-pairing conditioning procedure on the three phases of contextual fear conditioning. In 4.5-month-old TASTPM mice, the deficit in extinction was alleviated by repeated novel cage stress, applied from prior to its onset at 3 months. At 4 months of age, the occurrence of an extinction deficit was independent of the strength of the conditioning procedure, in TASTPM mice, which even showed an increase in aversive memory under the 2-pairing condition. The robust early impairment in the extinction of contextual fear seen in adult TASTPM mice suggests that a deficit in cognitive flexibility is the first sign of behavioural pathology in this model of Alzheimer's disease.