Otolaryngology - Research Publications
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ItemHybrid optogenetic and electrical stimulation for greater spatial resolution and temporal fidelity of cochlear activation(IOP PUBLISHING LTD, 2020-10)OBJECTIVE: Compared to electrical stimulation, optogenetic stimulation has the potential to improve the spatial precision of neural activation in neuroprostheses, but it requires intense light and has relatively poor temporal kinetics. We tested the effect of hybrid stimulation, which is the combination of subthreshold optical and electrical stimuli, on spectral and temporal fidelity in the cochlea by recording multiunit activity in the inferior colliculus of channelrhodopsin (H134R variant) transgenic mice. APPROACH: Pulsed light or biphasic electrical pulses were delivered to cochlear spiral ganglion neurons of acutely deafened mice, either as individual stimuli or as hybrid stimuli for which the timing of the electrical pulse had a varied delay relative to the start of the optical pulse. Response thresholds, spread of activation and entrainment data were obtained from multi-unit recordings from the auditory midbrain. MAIN RESULTS: Facilitation occurred when subthreshold electrical stimuli were applied at the end of, or up to 3.75 ms after subthreshold optical pulses. The spread of activation resulting from hybrid stimulation was significantly narrower than electrical-only and optical-only stimulation (p < 0.01), measured at equivalent suprathreshold levels of loudness that are relevant to cochlear implant users. Furthermore, temporal fidelity, measured as maximum following rates to 300 ms pulse trains bursts up to 240 Hz, was 2.4-fold greater than optical-only stimulation (p < 0.05). SIGNIFICANCE: By significantly improving spectral resolution of electrical- and optical-only stimulation and the temporal fidelity of optical-only stimulation, hybrid stimulation has the potential to increase the number of perceptually independent stimulating channels in a cochlear implant.
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ItemEar, nose and throat surgery: All you need to know about the surgical approach to the management of middle-ear effusions in Australian Indigenous and non-Indigenous children(WILEY, 2017-11)Otitis media (OM) is a common condition in Australia. It represents a spectrum of diseases from otitis media with effusion (OME) to chronic suppurative otitis media. For all the OM diagnoses, Australian Indigenous children have higher rates of early onset, severe and persistent disease. OME is the most common form of OM and often occurs after an upper respiratory tract infection. It can be difficult to diagnose (and often goes unrecognised). Hearing loss is the most important complication. The middle-ear effusion impedes the movement of the tympanic membrane and causes a conductive hearing loss of around 25 dB. Around 20% will have a hearing loss exceeding 35 dB. Children with early onset, persistent, bilateral OME and hearing loss (or speech delay) are most likely to benefit from interventions. However, the impact of all the effective treatment options is modest. Giving advice about effective communication strategies for young children is always appropriate. The best evidence from randomised trials supports not using antihistamines and/or decongestants, considering a trial of antibiotics and referral for tympanostomy tubes. Despite the availability of evidence-based guidelines, giving advice about treatment is a challenge because recommendations vary according to condition, age, risk of complications and parental preference. While most children with OME can be effectively managed in primary care, we need to get children who meet the criteria for simple ear, nose and throat procedures that improve hearing on to ear, nose and throat surgery waiting lists. Long delays in hearing support may contribute to life-long social and economic disadvantage.
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ItemEffect of cochlear implantation on middle ear function: A three-month prospective study(WILEY, 2018-05)OBJECTIVES/HYPOTHESIS: To determine if cochlear implantation has a delayed effect on the middle ear conductive hearing mechanism by measuring laser Doppler vibrometry (LDV) of the tympanic membrane (TM) in both implanted and contralateral control ears preoperatively and 3 months postoperatively, and then comparing the relative change in LDV outcome measures between implanted and control ears. STUDY DESIGN: Prospective cohort study. METHODS: Eleven preoperative adult unilateral cochlear implant recipients in previously unoperated ears with normal anatomy and aerated temporal bones were included in this study. The magnitude and phase angle of umbo velocity transfer function in response to air- conduction (AC) stimulus, and the magnitude of umbo velocity in response to bone- conduction (BC) stimulus were measured in the implant ear and the contralateral control ear preoperatively and 3 months postoperatively and compared. RESULTS: No significant changes in the magnitude or phase angle of TM velocity in response to either AC or BC stimulus were observed in the implanted ear relative to the contralateral control ear 3 months following cochlear implantation. CONCLUSIONS: From the results of LDV measurements, it can be said that cochlear implantation has no significant delayed effect on the middle ear conductive mechanism. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1207-1212, 2018.
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ItemType-I interferons mediate the neuroinflammatory response and neurotoxicity induced by rotenone(WILEY, 2017-04)Evidence from post-mortem human brains, animal studies and cell culture models has implicated neuroinflammation in the aetiology of chronic neuropathologies including Alzheimer's and Parkinson's diseases. Although the neuroinflammatory response is considered detrimental in contributing to these pathologies, the underlying mechanisms are still not well understood. The type-I interferons (IFNs) have been well characterised in the periphery and are known to initiate/modulate the immune response. Recently, they have been implicated in ageing and we have also demonstrated increased type-I IFN expression in post-mortem human Alzheimer's and Parkinson's disease brains. We hypothesise that the type-I IFNs are key drivers of the damaging, self-perpetuating pro-inflammatory response that contributes to these chronic neuropathologies. In support of this, we have recently confirmed in models of Alzheimer's and Parkinson's disease that mice lacking the type-I IFN receptor (IFNAR1), display an attenuated neuroinflammatory response with subsequent neuroprotection. To further investigate type-I IFN-mediated neuroinflammation and the specific CNS cell types involved, this study treated primary cultured wild-type and IFNAR1-/- neurons or mixed glia with the mitochondrial complex I inhibitor, rotenone. Wild-type neurons and glia treated with 3 nM and 25 nM rotenone, respectively, exhibited a pro-inflammatory response, including increased type-I IFN expression that was attenuated in cells lacking IFNAR1. Reduced type-I IFN signalling in IFNAR1-/- neurons also conferred protection against caspase-3-mediated rotenone-induced cell death. Further, this reduced pro-inflammatory response in the IFNAR1-/- glia subsequently diminished their neurotoxic effects to wild-type neurons. In support of this, we confirmed that therapeutically targeting the type-I IFN glial response to rotenone through a specific IFNAR1 blocking monoclonal antibody was neuroprotective. Our data has confirmed that both neurons and glia contribute to the pro-inflammatory response induced by rotenone with attenuation of this response beneficial in reducing neuronal cell death. Read the Editorial Comment for this article on page 9.
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ItemPostauricular-submental approach endoscopic thyroidectomy(WILEY, 2018-04)
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ItemType-1 Interferons Contribute to the Neuroinflammatory Response and Disease Progression of the MPTP Mouse Model of Parkinson's Disease(WILEY, 2016-09)Type-1 interferons (IFNs) are pleiotropic cytokines with a critical role in the initiation and regulation of the pro-inflammatory response. However, the contribution of the type-1 IFNs to CNS disorders, specifically chronic neuropathologies such as Parkinson's disease is still unknown. Here, we report increased type-1 IFN signaling in both post mortem human Parkinson's disease samples and in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model. In response to MPTP, mice lacking the type-1 IFN receptor (IFNAR1(-/-) ) displayed decreased type-1 IFN signaling, an attenuated pro-inflammatory response and reduced loss of dopaminergic neurons. The neuroprotective potential of targeting the type-1 IFN pathway was confirmed by reduced neuroinflammation and DA cell death in mice treated with a blocking monoclonal IFNAR1 (MAR-1) antibody. The MPTP/MAR-1 treated mice also displayed increased striatal dopamine levels and improved behavioural outcomes compared to their MPTP/IgG controls. These data, implicate for the first time, a deleterious role for the type-1 IFNs as key modulators of the early neuroinflammatory response and therefore the neuronal cell death in Parkinson's disease. GLIA 2016;64:1590-1604.
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ItemThe Effect of Interdevice Interval on Speech Perception Performance Among Bilateral, Pediatric Cochlear Implant Recipients(WILEY-BLACKWELL, 2016-10)OBJECTIVES/HYPOTHESIS: To determine if prolongation of the interdevice interval in children receiving bilateral cochlear implants adversely affects speech perception outcomes. STUDY DESIGN: Retrospective chart review. METHODS: Retrospective review of our pediatric cochlear implant database was performed. Children who had undergone revision surgery or had less than 12 months listening experience with either the first or second implant were excluded. The interdevice interval, best Phonetically Balanced Kindergarten word lists (PBK) score from each ear, and demographic data about each patient were collected. A ratio of PBK was generated (PBK second side/PBK first side) to minimize potential confounding from other individual patient factors that affect speech outcomes. RESULTS: Two hundred forty children met the study criteria. Mean age at first cochlear implantation (CI) was 3.2 years (0.6-17.9), and the second was 6.6 years (0.8-22.4). Mean best PBK score from the first CI side was 83.8% (0-100), and the second was 67.5% (0-100) (P < .001). When the PBK ratio was plotted against interdevice interval, R(2) was 0.47 (P < .001). When analyzed for hearing stability, those with a progressive loss history demonstrated less influence of prolonged interdevice interval on performance. Multivariate analysis did not identify other factors influencing the ratio. A line of best fit for those with stable hearing loss suggested best outcomes were with an interdevice interval less than 3 to 4 years. Beyond 7 to 8 years, very few achieved useful speech recognition from the second CI. CONCLUSIONS: Where possible, the second implant should be received within 3 to 4 years of the first to maximize outcome in those with stable, severe to profound sensorineural hearing loss. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:2389-2394, 2016.
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ItemStreet Sign Recognition Using Histogram of Oriented Gradients and Artificial Neural Networks(MDPI, 2019-04)Street sign identification is an important problem in applications such as autonomous vehicle navigation and aids for individuals with vision impairments. It can be especially useful in instances where navigation techniques such as global positioning system (GPS) are not available. In this paper, we present a method of detection and interpretation of Malaysian street signs using image processing and machine learning techniques. First, we eliminate the background from an image to segment the region of interest (i.e., the street sign). Then, we extract the text from the segmented image and classify it. Finally, we present the identified text to the user as a voice notification. We also show through experimental results that the system performs well in real-time with a high level of accuracy. To this end, we use a database of Malaysian street sign images captured through an on-board camera.
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ItemThe Vulval Disease Quality of Life Index in women with vulval lichen sclerosus correlates with clinician and symptom scores(WILEY, 2020-05)BACKGROUND/OBJECTIVES: The Vulval disease Quality of Life Index (VQLI) is a new tool that assesses the burden of vulval disease on quality of life (QoL). Our objective was to assess the correlation between VQLI score and clinician-rated severity scores, overall patient itch/discomfort, disease duration, sexual activity, and age, in vulval lichen sclerosus (VLS) at a vulval disorders clinic. METHODS: A retrospective case note review, including consecutive women with VLS who attended the clinic between April and October 2018. Outcome measures include the VQLI score, clinician-rated severity score, and patient symptom score. RESULTS: A total of 109 women with VLS were included. On multivariable analysis, there was evidence of a positive relationship between VQLI scores and the total clinician-rated score (mean increase in VQLI score per unit increase in clinician score 1.34, 95% confidence interval [CI] 0.31, 2.38; P = 0.01); the relationship was stronger for the cutaneous component. There was little evidence for relationships of the VQLI with the patient's age, sexual activity or time since onset of symptoms. There was strong evidence for a positive relationship between VQLI score and overall itch/discomfort score (mean increase 2.38, 95% CI 1.88, 2.88; P < 0.001). New and follow-up data were obtained on sequential visits for 12 women, among whom the VQLI score dropped a mean -2.75 points between visits (95% CI -6.05, 0.55; P = 0.094). CONCLUSION: The clinician-rated severity correlates with the impact of VLS on QoL. The VQLI captures information included in a patient itch/discomfort score, which can be easily incorporated into routine assessment.