On the High Frequency Transfer of Mechanical Stimuli from the Surface of the Head to the Macular Neuroepithelium of the Mouse

Vestibular macular sensors are activated by a shearing motion between the otoconial membrane and underlying receptor epithelium. Shearing motion and sensory activation in response to an externally induced head motion do not occur instantaneously. The mechanically reactive elastic and inertial properties of the intervening tissue introduce temporal constraints on the transfer of the stimulus to sensors. Treating the otoconial sensory apparatus as an overdamped second-order mechanical system, we measured the governing long time constant (Τ_L) for stimulus transfer from the head surface to epithelium. This provided the basis to estimate the corresponding upper cutoff for the frequency response curve for mouse otoconial organs. A velocity step excitation was used as the forcing function. Hypothetically, the onset of the mechanical response to a step excitation follows an exponential rise having the form Vel_shear = U(1-e^−t/TL), where U is the applied shearing velocity step amplitude. The response time of the otoconial apparatus was estimated based on the activation threshold of macular neural responses to step stimuli having durations between 0.1 and 2.0 ms. Twenty adult C57BL/6 J mice were evaluated. Animals were anesthetized. The head was secured to a shaker platform using a non-invasive head clip or implanted skull screws. The shaker was driven to produce a theoretical forcing step velocity excitation at the otoconial organ. Vestibular sensory evoked potentials (VsEPs) were recorded to measure the threshold for macular neural activation. The duration of the applied step motion was reduced systematically from 2 to 0.1 ms and response threshold determined for each duration (nine durations). Hypothetically, the threshold of activation will increase according to the decrease in velocity transfer occurring at shorter step durations. The relationship between neural threshold and stimulus step duration was characterized. Activation threshold increased exponentially as velocity step duration decreased below 1.0 ms. The time constants associated with the exponential curve were Τ_L = 0.50 ms for the head clip coupling and T_L = 0.79 ms for skull screw preparation. These corresponded to upper −3 dB frequency cutoff points of approximately 318 and 201 Hz, respectively. T_L ranged from 224 to 379 across individual animals using the head clip coupling. The findings were consistent with a second-order mass-spring mechanical system. Threshold data were also fitted to underdamped models post hoc. The underdamped fits suggested natural resonance frequencies on the order of 278 to 448 Hz as well as the idea that macular systems in mammals are less damped than generally acknowledged. Although estimated indirectly, it is argued that these time constants reflect largely if not entirely the mechanics of transfer to the sensory apparatus. The estimated governing time constant of 0.50 ms for composite data predicts high frequency cutoffs of at least 318 Hz for the intact otoconial apparatus of the mouse.     

Enhanced Vestibulo-ocular Reflex to Electrical Vestibular Stimulation in Meniere’s Disease

Meniere’s disease is characterized by sporadic episodes of vertigo, nystagmus, fluctuating sensorineural hearing loss, tinnitus and aural pressure. Since Meniere’s disease can affect different regions of the vestibular labyrinth, we investigated if electrical vestibular stimulation (EVS) which excites the entire vestibular labyrinth may be useful to reveal patchy endorgan pathology. We recorded three-dimensional electrically evoked vestibulo-ocular reflex (eVOR) to transient EVS using bilateral, bipolar 100-ms current steps at intensities of 0.9, 2.5, 5.0, 7.5 and 10.0 mA with dual-search coils in 12 unilateral Meniere’s patients. Their results were compared to 17 normal subjects. Normal eVOR had tonic and phasic spatiotemporal properties best described by the torsional component, which was four times larger than horizontal and vertical components. At EVS onset and offset of 8.9 ms latency, there were phasic eVOR initiation (M = 1,267 °/s²) and cessation (M = −1,675 °/s²) acceleration pulses, whereas during the constant portion of the EVS, there was a maintained tonic eVOR (M = 9.1 °/s) at 10 mA. However in Meniere’s disease, whilst latency of EVS onset and offset was normal at 9.0 ms, phasic eVOR initiation (M = 1,720 °/s²) and cessation (M = −2,523 °/s²) were enlarged at 10 mA. The initiation profile was a bimodal response, whilst the cessation profile frequently did not return to baseline. The tonic eVOR (M = 20.5 °/s) exhibited a ramped enhancement of about twice normal at 10 mA. Tonic eVOR enhancement was present for EVS >0.9 mA and disproportionately enhanced the torsional, vertical and horizontal components. These eVOR abnormalities may be a diagnostic indicator of Meniere’s disease and may explain the vertigo attacks in the presence of declining mechanically evoked vestibular responses.     

Hyperpolarization-Activated Current (I h) in Vestibular Calyx Terminals: Characterization and Role in Shaping Postsynaptic Events

Calyx afferent terminals engulf the basolateral region of type I vestibular hair cells, and synaptic transmission across the vestibular type I hair cell/calyx is not well understood. Calyces express several ionic conductances, which may shape postsynaptic potentials. These include previously described tetrodotoxin-sensitive inward Na⁺ currents, voltage-dependent outward K⁺ currents and a K(Ca) current. Here, we characterize an inwardly rectifying conductance in gerbil semicircular canal calyx terminals (postnatal days 3–45), sensitive to voltage and to cyclic nucleotides. Using whole-cell patch clamp, we recorded from isolated calyx terminals still attached to their type I hair cells. A slowly activating, noninactivating current (I_h) was seen with hyperpolarizing voltage steps negative to the resting potential. External Cs⁺ (1–5 mM) and ZD7288 (100 μM) blocked the inward current by 97 and 83 %, respectively, confirming that I_h was carried by hyperpolarization-activated, cyclic nucleotide gated channels. Mean half-activation voltage of I_h was −123 mV, which shifted to −114 mV in the presence of cAMP. Activation of I_h was well described with a third order exponential fit to the current (mean time constant of activation, τ, was 190 ms at −139 mV). Activation speeded up significantly (τ = 136 and 127 ms, respectively) when intracellular cAMP and cGMP were present, suggesting that in vivo I_h could be subject to efferent modulation via cyclic nucleotide-dependent mechanisms. In current clamp, hyperpolarizing current steps produced a time-dependent depolarizing sag followed by either a rebound afterdepolarization or an action potential. Spontaneous excitatory postsynaptic potentials (EPSPs) became larger and wider when I_h was blocked with ZD7288. In a three-dimensional mathematical model of the calyx terminal based on Hodgkin–Huxley type ionic conductances, removal of I_h similarly increased the EPSP, whereas cAMP slightly decreased simulated EPSP size and width.     

Characterization and Inflammatory Response of Perivascular-Resident Macrophage-Like Melanocytes in the Vestibular System

A large number of perivascular cells expressing both macrophage and melanocyte characteristics (named perivascular-resident macrophage-like melanocytes, PVM/Ms), previously found in the intra-strial fluid–blood barrier, are also found in the blood–labyrinth barrier area of the vestibular system in normal adult cochlea, including in the three ampullae of the semicircular canals (posterior, superior, and horizontal), utricle, and saccule. The cells were identified as PVM/Ms, positive for the macrophage and melanocyte marker proteins F4/80 and GSTα4. Similar to PVM/Ms present in the stria vascularis, the PVM/Ms in the vestibular system are closely associated with microvessels and structurally intertwined with endothelial cells and pericytes, with a density in normal (unstimulated) utricle of 225 ± 43/mm²; saccule 191 ± 25/mm²; horizontal ampullae 212 ± 36/mm²; anterior ampullae 238 ± 36/mm²; and posterior ampullae 223 ± 64/mm². Injection of bacterial lipopolysaccharide into the middle ear through the tympanic membrane causes the PVM/Ms to activate and arrange in an irregular pattern along capillary walls in all regions within a 48-h period. The inflammatory response significantly increases vascular permeability and leakage. The results underscore the morphological complexity of the blood barrier in the vestibular system, with its surrounding basal lamina, pericytes, as well as second line of defense in PVM/Ms. PVM/Ms may be important to maintain blood barrier integrity and initiating local inflammatory response in the vestibular system.     

Dynamic Displacement of Normal and Detached Semicircular Canal Cupula

The dynamic displacement of the semicircular canal cupula and modulation of afferent nerve discharge were measured simultaneously in response to physiological stimuli in vivo. The adaptation time constant(s) of normal cupulae in response to step stimuli averaged 36 s, corresponding to a mechanical lower corner frequency for sinusoidal stimuli of 0.0044 Hz. For stimuli equivalent to 40–200 deg/s of angular head velocity, the displacement gain of the central region of the cupula averaged 53 nm per deg/s. Afferents adapted more rapidly than the cupula, demonstrating the presence of a relaxation process that contributes significantly to the neural representation of angular head motions by the discharge patterns of canal afferent neurons. We also investigated changes in time constants of the cupula and afferents following detachment of the cupula at its apex—mechanical detachment that occurs in response to excessive transcupular endolymph pressure. Detached cupulae exhibited sharply reduced adaptation time constants (300 ms–3 s, n = 3) and can be explained by endolymph flowing rapidly over the apex of the cupula. Partially detached cupulae reattached and normal afferent discharge patterns were recovered 5–7 h following detachment. This regeneration process may have relevance to the recovery of semicircular canal function following head trauma.     

Rapid Increase in Neural Conduction Time in the Adult Human Auditory Brainstem Following Sudden Unilateral Deafness

Individuals with sudden unilateral deafness offer a unique opportunity to study plasticity of the binaural auditory system in adult humans. Stimulation of the intact ear results in increased activity in the auditory cortex. However, there are no reports of changes at sub-cortical levels in humans. Therefore, the aim of the present study was to investigate changes in sub-cortical activity immediately before and after the onset of surgically induced unilateral deafness in adult humans. Click-evoked auditory brainstem responses (ABRs) to stimulation of the healthy ear were recorded from ten adults during the course of translabyrinthine surgery for the removal of a unilateral acoustic neuroma. This surgical technique always results in abrupt deafferentation of the affected ear. The results revealed a rapid (within minutes) reduction in latency of wave V (mean pre = 6.55 ms; mean post = 6.15 ms; p < 0.001). A latency reduction was also observed for wave III (mean pre = 4.40 ms; mean post = 4.13 ms; p < 0.001). These reductions in response latency are consistent with functional changes including disinhibition or/and more rapid intra-cellular signalling affecting binaurally sensitive neurons in the central auditory system. The results are highly relevant for improved understanding of putative physiological mechanisms underlying perceptual disorders such as tinnitus and hyperacusis.     

Current Steering with Partial Tripolar Stimulation Mode in Cochlear Implants

The large spread of excitation is a major cause of poor spectral resolution for cochlear implant (CI) users. Partial tripolar (pTP) mode has been proposed to reduce current spread by returning an equally distributed fraction (0.5 × σ) of current to two flanking electrodes and the rest to an extra-cochlear ground. This study tested the efficacy of incorporating current steering into pTP mode to add spectral channels. Different proportions of current [α × σ and (1 − α) × σ] were returned to the basal and apical flanking electrodes respectively to shape the electric field. Loudness and pitch perception with α from 0 to 1 in steps of 0.1 was simulated with a computational model of CI stimulation and tested on the apical, middle, and basal electrodes of six CI subjects. The highest σ allowing for full loudness growth within the implant compliance limit was chosen for each main electrode. Pitch ranking was measured between pairs of loudness-balanced steered pTP stimuli with an α interval of 0.1 at the most comfortable level. Results demonstrated that steered pTP stimuli with α around 0.5 required more current to achieve equal loudness than those with α around 0 or 1, maybe due to more focused excitation patterns. Subjects usually perceived decreasing pitches as α increased from 0 to 1, somewhat consistent with the apical shift of the center of gravity of excitation pattern in the model. Pitch discrimination was not better with α around 0.5 than with α around 0 or 1, except for some subjects and electrodes. For three subjects with better pitch discrimination, about half of the pitch ranges of two adjacent main electrodes overlapped with each other in steered pTP mode. These results suggest that current steering with focused pTP mode may improve spectral resolution and pitch perception with CIs.     

A Genome-Wide Association Study of Chronic Otitis Media with Effusion and Recurrent Otitis Media Identifies a Novel Susceptibility Locus on Chromosome 2

Chronic otitis media with effusion (COME) and recurrent otitis media (ROM) have been shown to be heritable, but candidate gene and linkage studies to date have been equivocal. Our aim was to identify genetic susceptibility factors using a genome-wide association study (GWAS). We genotyped 602 subjects from 143 families with 373 COME/ROM subjects using the Illumina Human CNV370-Duo DNA Bead Chip (324,748 SNPs). We carried out the GWAS scan and imputed SNPs at the regions with the most significant associations. Replication genotyping in an independent family-based sample was conducted for 53 SNPs: the 41 most significant SNPs with P < 10⁻⁴ and 12 imputed SNPs with P < 10⁻⁴ on chromosome 15 (near the strongest signal). We replicated the association of rs10497394 (GWAS discovery P = 1.30 × 10⁻⁵) on chromosome 2 in the independent otitis media population (P = 4.7 × 10⁻⁵; meta-analysis P = 1.52 × 10⁻⁸). Three additional SNPs had replication P values < 0.10. Two were on chromosome 15q26.1 including rs1110060, the strongest association with COME/ROM in the primary GWAS (P = 3.4 ×10⁻⁷) in KIF7 intron 7 (P = 0.072), and rs10775247, a non-synonymous SNP in TICRR exon 2 (P = 0.075). The third SNP rs386057 was on chromosome 5 in TPPP intron 1 (P = 0.045). We have performed the first GWAS of COME/ROM and have identified a SNP rs10497394 on chromosome 2 is significantly associated with COME/ROM susceptibility. This SNP is within a 537 kb intergenic region, bordered by CDCA7 and SP3. The genomic and functional significance of this newly identified locus in COME/ROM pathogenesis requires additional investigation.     

Auditory Cortex Signs of Age-Related Hearing Loss

Age-related hearing loss, or presbyacusis, is a major public health problem that causes communication difficulties and is associated with diminished quality of life. Limited satisfaction with hearing aids, particularly in noisy listening conditions, suggests that central nervous system declines occur with presbyacusis and may limit the efficacy of interventions focused solely on improving audibility. This study of 49 older adults (M = 69.58, SD = 8.22 years; 29 female) was designed to examine the extent to which low and/or high frequency hearing loss was related to auditory cortex morphology. Low and high frequency hearing constructs were obtained from a factor analysis of audiograms from these older adults and 1,704 audiograms from an independent sample of older adults. Significant region of interest and voxel-wise gray matter volume associations were observed for the high frequency hearing construct. These effects occurred most robustly in a primary auditory cortex region (Te1.0) where there was also elevated cerebrospinal fluid with high frequency hearing loss, suggesting that auditory cortex atrophies with high frequency hearing loss. These results indicate that Te1.0 is particularly affected by high frequency hearing loss and may be a target for evaluating the efficacy of interventions for hearing loss.     

Excitation Patterns of Standard and Steered Partial Tripolar Stimuli in Cochlear Implants

Current steering in partial tripolar (pTP) mode has been shown to improve pitch perception and spectral resolution with cochlear implants (CIs). In this mode, a fraction (σ) of the main electrode current is returned within the cochlea and steered between the basal and apical flanking electrodes (with a proportion of α and 1 − α, respectively). Pitch generally decreases when α increases from 0 to 1, although the salience of pitch change varies across CI users. This study aimed to identify the mechanism of pitch changes with pTP-mode current steering and the factors contributing to the intersubject variability in pitch-ranking sensitivity. The electrical fields were measured for steered pTP stimuli on the same main electrode with α = 0, 0.5, and 1 in five implanted ears using electrical field imaging (EFI). The related excitation patterns were also measured physiologically using evoked compound action potential (ECAP) and psychophysically using psychophysical forward masking (PFM). Consistent with the pitch-ranking results in this study, the EFI, ECAP, and PFM centroids shifted apically with increasing α. An apical shift was also observed for the PFM peak but not for the EFI or ECAP peak. The pattern width was similar with different α values within a given measure (e.g., EFI, ECAP, or PFM), but the ECAP patterns were broader than the EFI and PFM patterns, possibly because ECAP was measured with smaller σ values than EFI and PFM. The amount of pattern shift with α depended on σ (i.e., the total amount of current used for steering) but was not correlated with the pitch-ranking sensitivity across subjects. The results revealed that the pitch changes elicited by pTP-mode current steering were not only driven by the shifts of excitation centroid.     

Speech Perception in Noise with a Harmonic Complex Excited Vocoder

A cochlear implant (CI) presents band-pass-filtered acoustic envelope information by modulating current pulse train levels. Similarly, a vocoder presents envelope information by modulating an acoustic carrier. By studying how normal hearing (NH) listeners are able to understand degraded speech signals with a vocoder, the parameters that best simulate electric hearing and factors that might contribute to the NH-CI performance difference may be better understood. A vocoder with harmonic complex carriers (fundamental frequency, f₀ = 100 Hz) was used to study the effect of carrier phase dispersion on speech envelopes and intelligibility. The starting phases of the harmonic components were randomly dispersed to varying degrees prior to carrier filtering and modulation. NH listeners were tested on recognition of a closed set of vocoded words in background noise. Two sets of synthesis filters simulated different amounts of current spread in CIs. Results showed that the speech vocoded with carriers whose starting phases were maximally dispersed was the most intelligible. Superior speech understanding may have been a result of the flattening of the dispersed-phase carrier’s intrinsic temporal envelopes produced by the large number of interacting components in the high-frequency channels. Cross-correlogram analyses of auditory nerve model simulations confirmed that randomly dispersing the carrier’s component starting phases resulted in better neural envelope representation. However, neural metrics extracted from these analyses were not found to accurately predict speech recognition scores for all vocoded speech conditions. It is possible that central speech understanding mechanisms are insensitive to the envelope-fine structure dichotomy exploited by vocoders.     

Evaluation of the structure of the otoconial layer using micro-computed tomography

ObjectiveEstrogen deficiency caused by bilateral ovariectomy (OVX) has been reported to lead to morphological changes in otoconia. Thus, we examined the morphological changes in the otoconial layer after OVX. We also investigated whether micro-computed tomography (µCT) is useful for the detection of morphological changes in the otoconial layer.MethodsThe otic capsules of C57BL/6 J mice were removed and evaluated using histological techniques and µCT at 2, 4, and 8 weeks after OVX or sham surgery. The volume of the utricle otoconial layer was measured and compared between the OVX and sham groups. The µCT scan and histological study results were also compared.ResultsThe volume of the utricle otoconial layer was significantly increased 4 weeks after OVX compared to the sham group in both histological and µCT studies (p < 0.05). The volume of the otoconial layer measured using µCT was significantly correlated with the histological study results (p < 0.05).ConclusionThe volume of the utricle otoconial layer increased after OVX. These morphological changes could be detected by µCT.     

Influence of fiber posts on the fracture resistance of endodontically treated premolars with different dental defects

This study aimed to evaluate the influence of quartz fiber post placement on the fracture resistance of endodontically treated premolars with different dental defects under dynamic loading.Fifty extracted single-rooted mandibular premolars were randomized into five groups.Each group was prepared according to numbers of residual walls ranged from 0 to 4.Then each group was divided into two subgroups with one restored with quartz fiber posts and the other without posts.In no-post groups,gutta percha point 2 mm below cemento-enamel junction was removed.Composite resin was adapted to the well and used to shape the core directly.Each tooth was restored with a complete metal crown.Dynamic loading was carried out in a masticatory simulator with a nominal load of 50 N at 2 Hz for 300 000 loading cycles.Then a quasi-statically load was applied in a universal testing machine 306 to the long axis with a crosshead speed of 1 mm？min21until fracture.Data were analyzed with one-way analysis of variance and pairwise comparison（P,0.05）.No specimens failed during dynamic loading.The fracture resistance enhanced with the increase of numbers of coronal walls and the differences were significant（P,0.05）.Placement of fiber posts had a significant effect when fewer than two walls remained（P,0.05）,but it had no significant influence in groups with two,three or four walls（P.0.05）.Fiber post did not change failure mode,and the fracture pattern was mainly favorable.More dentin walls need to be retained in clinic.When no less than two walls remained,a fiber post is not always necessary.     

Directional Plasticity Rapidly Improves 3D Vestibulo-Ocular Reflex Alignment in Monkeys Using a Multichannel Vestibular Prosthesis

Bilateral loss of vestibular sensation can be disabling. We have shown that a multichannel vestibular prosthesis (MVP) can partly restore vestibular sensation as evidenced by improvements in the 3-dimensional angular vestibulo-ocular reflex (3D VOR). However, a key challenge is to minimize misalignment between the axes of eye and head rotation, which is apparently caused by current spread beyond each electrode’s targeted nerve branch. We recently reported that rodents wearing a MVP markedly improve 3D VOR alignment during the first week after MVP activation, probably through the same central nervous system adaptive mechanisms that mediate cross-axis adaptation over time in normal individuals wearing prisms that cause visual scene movement about an axis different than the axis of head rotation. We hypothesized that rhesus monkeys would exhibit similar improvements with continuous prosthetic stimulation over time. We created bilateral vestibular deficiency in four rhesus monkeys via intratympanic injection of gentamicin. A MVP was mounted to the cranium, and eye movements in response to whole-body passive rotation in darkness were measured repeatedly over 1 week of continuous head motion-modulated prosthetic electrical stimulation. 3D VOR responses to whole-body rotations about each semicircular canal axis were measured on days 1, 3, and 7 of chronic stimulation. Horizontal VOR gain during 1 Hz, 50 °/s peak whole-body rotations before the prosthesis was turned on was <0.1, which is profoundly below normal (0.94 ± 0.12). On stimulation day 1, VOR gain was 0.4–0.8, but the axis of observed eye movements aligned poorly with head rotation (misalignment range ∼30–40 °). Substantial improvement of axis misalignment was observed after 7 days of continuous motion-modulated prosthetic stimulation under normal diurnal lighting. Similar improvements were noted for all animals, all three axes of rotation tested, for all sinusoidal frequencies tested (0.05–5 Hz), and for high-acceleration transient rotations. VOR asymmetry changes did not reach statistical significance, although they did trend toward slight improvement over time. Prior studies had already shown that directional plasticity reduces misalignment when a subject with normal labyrinths views abnormal visual scene movement. Our results show that the converse is also true: individuals receiving misoriented vestibular sensation under normal viewing conditions rapidly adapt to restore a well-aligned 3D VOR. Considering the similarity of VOR physiology across primate species, similar effects are likely to occur in humans using a MVP to treat bilateral vestibular deficiency.     

Human Yaw Rotation Aftereffects with Brief Duration Rotations Are Inconsistent with Velocity Storage

In many sensory systems, perception of stimuli is influenced by previous stimulus exposure such that subsequent stimuli may be perceived as more neutral. This phenomenon is known as an aftereffect and has been studied for vision, audition, and some vestibular stimuli including roll and translation. Previous data on yaw rotation perception has focused on low-frequency stimuli on the order of a minute which may not be directly applicable to frequencies during ambulation. The aim of the current study is to look at the influence of yaw rotation on subsequent perception near 1 Hz, the predominant frequency of yaw rotation during human ambulation. Humans were rotated with 12 ° whole body adapting stimulus over 1 or 1.5 s. After an interstimulus interval (ISI) of 0.5, 1.0, 1.5, or 3 s, a test stimulus the same duration as the adapting stimulus was presented, and subjects pushed a button to identify the direction of the test stimulus as right or left. The direction and magnitude of the test stimulus was adjusted based on prior responses to find the stimulus at which no rotation was perceived. Experiments were conducted both in darkness and with a visual fixation point. The presence of a fixation point did not influence the aftereffect which was largest at 0.5 s with an average size of 0.78 ± 0.18 °/s (mean ± SE). The aftereffect diminished with a time constant of ~1 s. Thresholds were elevated after the adapting stimulus and also decreased with a time constant of ~1 s. These findings demonstrate that short adapting stimuli can induce significant aftereffects in yaw rotation perception and that these aftereffects are independent from the previously described velocity storage.     

Behavioral Estimates of the Contribution of Inner and Outer Hair Cell Dysfunction to Individualized Audiometric Loss

Differentiating the relative importance of the various contributors to the audiometric loss (HL_TOTAL) of a given hearing impaired listener and frequency region is becoming critical as more specific treatments are being developed. The aim of the present study was to assess the relative contribution of inner (IHC) and outer hair cell (OHC) dysfunction (HL_IHC and HL_OHC, respectively) to the audiometric loss of patients with mild to moderate cochlear hearing loss. It was assumed that HL_TOTAL = HL_OHC + HL_IHC (all in decibels) and that HL_OHC may be estimated as the reduction in maximum cochlear gain. It is argued that the latter may be safely estimated from compression threshold shifts of cochlear input/output (I/O) curves relative to normal hearing references. I/O curves were inferred behaviorally using forward masking for 26 test frequencies in 18 hearing impaired listeners. Data suggested that the audiometric loss for six of these 26 test frequencies was consistent with pure OHC dysfunction, one was probably consistent with pure IHC dysfunction, 13 were indicative of mixed IHC and OHC dysfunction, and five were uncertain (one more was excluded from the analysis). HL_OHC and HL_IHC contributed on average 60 and 40 %, respectively, to the audiometric loss, but variability was large across cases. Indeed, in some cases, HL_IHC was up to 63 % of HL_TOTAL, even for moderate losses. The repeatability of the results is assessed using Monte Carlo simulations and potential sources of bias are discussed.     

Examining the Electro-Neural Interface of Cochlear Implant Users Using Psychophysics,CT Scans,and Speech Understanding

This study examines the relationship between focused-stimulation thresholds, electrode positions, and speech understanding in deaf subjects treated with a cochlear implant (CI). Focused stimulation is more selective than monopolar stimulation, which excites broad regions of the cochlea, so may be more sensitive as a probe of neural survival patterns. Focused thresholds are on average higher and more variable across electrodes than monopolar thresholds. We presume that relatively high focused thresholds are the result of larger distances between the electrodes and the neurons. Two factors are likely to contribute to this distance: (1) the physical position of electrodes relative to the modiolus, where the excitable auditory neurons are normally located, and (2) the pattern of neural survival along the length of the cochlea, since local holes in the neural population will increase the distance between an electrode and the nearest neurons. Electrode-to-modiolus distance was measured from high-resolution CT scans of the cochleae of CI users whose focused-stimulation thresholds were also measured. A hierarchical set of linear models of electrode-to-modiolus distance versus threshold showed a significant increase in threshold with electrode-to-modiolus distance (average slope = 11 dB/mm). The residual of these models was hypothesized to reflect neural survival in each subject. Consonant–Nucleus–Consonant (CNC) word scores were significantly correlated with the within-subject variance of threshold (r² = 0.82), but not with within-subject variance of electrode distance (r² = 0.03). Speech understanding also significantly correlated with how well distance explained each subject’s threshold data (r² = 0.63). That is, subjects with focused thresholds that were well described by electrode position had better speech scores. Our results suggest that speech understanding is highly impacted by individual patterns of neural survival and that these patterns manifest themselves in how well (or poorly) electrode position predicts focused thresholds.     

Nonopioid perioperative analgesia in head and neck cancer surgery: A systematic review

ObjectiveManagement of postoperative pain after head and neck cancer surgery is a complex issue, requiring a careful balance of analgesic properties and side effects. The objective of this review is to discuss the efficacy and safety of multimodal analgesia (MMA) for these patients.MethodsPubmed, Cochrane, Embase, Scopus, and clinicaltrials.gov were systematically searched for all comparative studies of patients receiving MMA (nonsteroidal anti‐inflammatory drugs (NSAIDs), acetaminophen, anticonvulsants, local anesthetics, and corticosteroids) for head and neck cancer surgeries. The primary outcome was additional postoperative opioid usage, and secondary outcomes included subjective pain scores, complications, adverse effects, and 30‐day outcomes.ResultsA total of five studies representing 592 patients (MMA, n = 275; non‐MMA, n = 317) met inclusion criteria. The most commonly used agents were gabapentin, NSAIDs, and acetaminophen (n = 221), NSAIDs (n = 221), followed by corticosteroids (n = 35), dextromethorphan (n = 40), and local nerve block (n = 19). Four studies described a significant decrease in overall postoperative narcotic usage with two studies reporting a significant decrease in hospital time. Subjective pain scores widely varied with two studies reporting reduced pain at postoperative day 3. There were no differences in surgical outcomes, medical complications, adverse effects, or 30‐day mortality and readmission rates.ConclusionMMA is an increasingly popular strategy that may reduce dependence on opioids for the treatment of postoperative pain. A variety of regimens and protocols are available for providers to utilize in the appropriate head and neck cancer patient.     

Influence of acrylamide monomer addition to the acrylic denture-base resins on mechanical and physical properties

The aim of the study was to evaluate the effect of adding acrylamide monomer （AAm） on the characterization, flexural strength, flexural modulus and thermal degradation temperature of poly（methyl methacrylate） （PMMA） denture-base resins. Specimens （n= 10） were fabricated from a conventional heat-activated QC-20 （Qc-） and a microwave heat-activated Acron MC （Ac-） PMMA resins. Powder/ liquid ratio followed the manufacturer＇s instructions for the control groups （Qc-c and Ac-c） and for the copolymer groups, the resins were prepared with 5% （-5）, 10% （- 10）, 15% （- 15） and 20% （-20） acrylamide contents, according to the molecular weight ratio, respectively. The flexural strength and flexural modulus were measured by a three-point bending test. The data obtained were statistically analyzed by Kruskal-Wallis test （a=O.05） to determine significant differences between the groups, The chemical structures of the resins were characterized by the nuclear magnetic resonance spectroscopy. Thermal stabilities were determined by thermogravimetric analysis （TGA） with a heating rate of 10 ~C.min-1 from 35 ~C to 600 ~C. Control groups from both acrylic resins showed the lowest flexural strength values. Qc-15 showed significant increase in the flexural strength when compared to Qc-c （P〈O.01）. Ac-10 and Ac-15 showed significance when compared to Ac-c （P〈O.01）. Acrylamide incorporation increased the elastic modulus in Qc-10, Qc-15 and Qc-20 when compared to Qc-c （P〈0.01）. Also significant increase was observed in Ac-10, Ac-15 and Ac-20 copolymer groups when compared to Ac-c （P〈0.01）. According to the 1H-nuclear magnetic resonance （NMR） results, acrylamide copolymerization was confirmed in the experimental groups. TGA results showed that the thermal stability of PMMA is increased by the insertion of AAm.