Shelley Batts
Scientific Writer/Proposal Development Officer, OHNS/Otology & Neurotology Division
All Publications
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Comparison of the rates of emergent otologic adverse events following mRNA COVID-19 versus influenza vaccination: a matched cohort analysis.
Frontiers in neurology
2025; 16: 1637870
Abstract
Otologic adverse events (AEs) have been occasionally reported as sequalae of COVID-19 vaccination, although their incidence in comparison with that of preexisting vaccines with high uptake remains unclear. This study compared the rates of new-onset otologic AEs among matched adults receiving mRNA COVID-19 vaccination versus influenza vaccination.This retrospective cohort study used electronic health records (EHR) data from Stanford Health Care to identify adults aged 50-89 years with no history of otologic disorders prior to first Pfizer/Moderna COVID-19 vaccine (December 2020-January 2022) or any pre-pandemic influenza vaccine (January 2016-December 2019). Patients were categorized by vaccination into FluVax or COVIDVax cohorts. A 90-day history pre-vaccination (baseline period) and ≥6 months follow-up post-vaccination were required. Event rates of new-onset hearing loss (HL), sudden HL, tinnitus, vertigo/dizziness, aural fullness, and otalgia in the 6 months post-vaccination were compared between groups after high-dimensional propensity score (hdPS) matching. A sensitivity analysis was conducted among patients with no COVID-19 infection at any time. Odds ratios (ORs) were calculated using logistic regression for the hdPS matched cohorts.After hdPS matching, 20,325 patients were included into the FluVax and COVIDVax cohorts, respectively (mean age: 65.5 and 65.2 years; 53.1 and 53.8% females). The rates of otologic AEs in the 6 months post-vaccination were similarly low for the FluVax and COVIDVax cohorts: 1.16% vs. 1.16% for any HL, 0.01% vs. 0.02% for sudden HL, 0.41% vs. 0.47% for tinnitus, 1.96% vs. 1.59% for vertigo, 0.27% vs. 0.25% for otalgia, and 0.09% vs. 0.2% for aural fullness. COVIDVax patients had lower odds of vertigo [OR 95% CI: 0.81 (0.70, 0.94)] and higher odds of aural fullness [2.16 (1.25-3.72)] than the FluVax patients (both p < 0.05). The results of the sensitivity analysis limited to patients with no COVID-19 infection at any time (N = 17,530 each cohort) were consistent with the primary results, but aural fullness was the only AE with statistically higher risk in the COVIDVax vs. FluVax cohort [OR (95% CI): 1.90 (1.09-3.31); p = 0.021].New-onset otologic AEs were rare among a large cohort of hdPS-matched patients who received mRNA COVID-19 or pre-pandemic flu vaccination at a single institution. Although aural fullness was statistically more common in the COVIDVax vs. FluVax cohort, regardless of COVID-19 infection status, it remained extremely rare (<0.22%) in any cohort. These results indicate a similar otologic safety profile of the two vaccines, although future research is recommended in larger EHR databases to corroborate the findings.
View details for DOI 10.3389/fneur.2025.1637870
View details for PubMedID 40852523
View details for PubMedCentralID PMC12367506
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The State of High-Resolution Imaging of the Human Inner Ear: A Look Into the Black Box.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
2025: e00556
Abstract
Unlike most medical fields, otology has not benefited from the transformative impact of high-resolution, cellular-level imaging. The sensorineural cells required for human hearing-located within the cochlea-are just 10-50 µm, placing them outside the resolution of magnetic resonance imaging, computed tomography, and positron emission tomography. These cells are highly mechano- and chemo-sensitive, and their death or dysfunction underlie the vast majority of hearing loss. Further, the cochlea is only 4-7 mm in diameter, has complex anatomy, and is deeply embedded in bone. Cochlear blood flow is partially separated by a blood barrier, limiting access to radiotracers or fluorophores. These and other features have left the human cochlea as a "black box" that cannot be assessed with high precision in vivo, limiting the development of novel hearing loss therapies. The benefits and drawbacks of existing medical imaging techniques used to diagnose disorders of the human inner ear are discussed, as well as those of emerging technologies that may help overcome challenges to access, resolution, and functional detail. A comprehensive and up-to-date discussion is provided on research efforts to improve and adapt current clinical imaging methods and introduce recent innovations that have shown exciting promise for deriving both structural and metabolic information from cochlear cells.
View details for DOI 10.1002/advs.202500556
View details for PubMedID 40470704
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Dynamic micro-optical coherence tomography enables structural and metabolic imaging of the mammalian cochlea.
Frontiers in molecular neuroscience
2024; 17: 1436837
Abstract
Sensorineural hearing loss (SNHL) is caused by damage to the mechanosensory hair cells and auditory neurons of the cochlea. The development of imaging tools that can directly visualize or provide functional information about a patient's cochlear cells is critical to identify the pathobiological defect and determine the cells' receptiveness to emerging SNHL treatments. However, the cochlea's small size, embedded location within dense bone, and sensitivity to perturbation have historically precluded high-resolution clinical imaging. Previously, we developed micro-optical coherence tomography (μOCT) as a platform for otologic imaging in animal models and human cochleae. Here we report on advancing μOCT technology to obtain simultaneously acquired and co-localized images of cell viability/metabolic activity through dynamic μOCT (DμOCT) imaging of intracellular motion. DμOCT obtains cross-sectional images of ATP-dependent movement of intracellular organelles and cytoskeletal polymerization by acquiring sequential μOCT images and computing intensity fluctuation frequency metrics on a pixel-wise basis. Using a customized benchtop DμOCT system, we demonstrate the detailed resolution of anatomical and metabolic features of cells within the organ of Corti, via an apical cochleostomy, in freshly-excised adult mouse cochleae. Further, we show that DμOCT is capable of capturing rapid changes in cochlear cell metabolism following an ototoxic insult to induce cell death and actin stabilization. Notably, as few as 6 frames can be used to reconstruct cochlear DμOCT images with sufficient detail to discern individual cells and their metabolic state. Taken together, these results motivate future development of a DμOCT imaging probe for cellular and metabolic diagnosis of SNHL in humans.
View details for DOI 10.3389/fnmol.2024.1436837
View details for PubMedID 39449964
View details for PubMedCentralID PMC11499234
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Tinnitus prevalence, associated characteristics, and related healthcare use in the United States: a population-level analysis.
Lancet regional health. Americas
2024; 29: 100659
Abstract
Tinnitus is a potentially disabling condition with few treatments. We examined the prevalence and characteristics of tinnitus among demographic groups in the United States (US) and assessed associated factors and tinnitus-related healthcare.We included adults with and without bothersome tinnitus from the nationally representative 2014 National Health Interview Survey (NHIS; raw n = 36,697), the latest year with tinnitus data. We evaluated tinnitus prevalence and characteristics (frequency, severity, duration) overall and among groups defined by sex and race/ethnicity. Logistic regression with adjusted Wald tests were used for comparisons in NHIS-weighted populations by sex and race/ethnicity, and to evaluate associations between demographic/medical characteristics and noise exposure on tinnitus risk.The US prevalence of tinnitus was 11.2% (95% CI: 10.8%, 11.7%; ∼27 million people) in 2014. Of those with tinnitus, 41.2% always had symptoms and 28.3% had ≥15 years symptom duration; the rates were significantly higher among men vs. women and non-Hispanic (nHW) vs. Hispanic Whites (HW), Blacks, or other ethnicity. Significantly more women vs. men and HW vs. nHW reported severe tinnitus. Sex and race/ethnicity, except Asian, were not significantly associated with tinnitus when age, otologic/medical disorders, and noise exposure were included in the model. Significantly lower rates of all minority groups discussed tinnitus with a doctor compared to nHW, and among those who did, Blacks were significantly less likely to receive tinnitus evaluation than nHWs.Tinnitus prevalence varies across US demographic groups and racial differences were identified in the delivery of tinnitus-related healthcare.Rich Robbins, Bertarelli Foundation Endowed Professorship.
View details for DOI 10.1016/j.lana.2023.100659
View details for PubMedID 38269207
View details for PubMedCentralID PMC10806285
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Immune Profiling of Secreted Factors from Human Vestibular Schwannoma Cells and Tumor-associated Macrophages.
The Laryngoscope
2023
Abstract
This study compared the immune-related secretory capacity of human vestibular schwannoma (VS) and tumor-assisted macrophages (TAMs) with their normal counterparts (Schwann cells [SC] and peripheral blood monocyte-derived macrophages [Mo-MFs], respectively), and examined relationships with presurgical hearing and tumor size.VS tumors (n = 16), auditory nerve (n = 1), blood (n = 9), and great auricular nerves (n = 3) were used. SCs (S100B+ ) and TAMs (CD68+ ) were isolated from VS tissue for culture. The secreted levels of 65 immune-related factors were measured and compared using unpaired t-tests with Welch correction (schwannoma vs. SCs) or Mann-Whitney tests (TAMs and Mo-MFs). Associations between factor concentration and word recognition (WR), pure-tone average (PTA), and tumor size were evaluated with Spearman correlation.Secreted factors with significantly higher concentrations in schwannoma versus SC supernatants included IL-2 and BAFF, whereas MMP-1, IL-6, FGF-2, VEGF-A, MIP-3α, and GRO-α concentrations were significantly higher in TAMs versus Mo-MFs (all p < 0.05). Worse WR was significantly associated with higher secretion of fractalkine, eotaxin-3, CD30, and IL-16 by VS cells; IP-10, eotaxin-3, multiple interleukins, GM-CSF, SCF, and CD30 by TAMs; and TNF-α and MIP-1α by Mo-MFs (all p < 0.05). Worse PTA was significantly correlated with higher secretion of IL-16 by VS cells (p < 0.05). Larger tumor size was significantly correlated with higher secretion of eotaxin by VS cells, and of IL-7, IL-21, and LIF by TAMs (all p = 0.017).Differential secretion of immune-related factors was observed in schwannoma versus normal SCs and in TAMs versus Mo-MFs, some of which were correlated with worse hearing and larger VS tumors.N/A Laryngoscope, 2023.
View details for DOI 10.1002/lary.31067
View details for PubMedID 37776249
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Potential Ototoxicity of Insulin-like Growth Factor 1 Receptor Signaling Inhibitors: An In Silico Drug Repurposing Study of the Regenerating Cochlear Neuron Transcriptome.
Journal of clinical medicine
2023; 12 (10)
Abstract
Spiral ganglion neurons (SGNs) connect cochlear hair cells with higher auditory pathways and their degeneration due to drug toxicity (ototoxicity) contributes to hearing loss. This study aimed to identify drug classes that are negatively correlated with the transcriptome of regenerating SGNs. Human orthologs of differentially expressed genes within the regenerating neonatal mouse SGN transcriptome were entered into CMap and the LINCS unified environment and perturbation-driven gene expression was analyzed. The CMap connectivity scores ranged from 100 (positive correlation) to -100 (negative correlation). Insulin-like growth factor 1/receptor (IGF-1/R) inhibitors were highly negatively correlated with the regenerating SGN transcriptome (connectivity score: -98.87). A systematic literature review of clinical trials and observational studies reporting otologic adverse events (AEs) with IGF-1/R inhibitors identified 108 reports (6141 treated patients). Overall, 16.9% of the treated patients experienced any otologic AE; the rate was highest for teprotumumab (42.9%). In a meta-analysis of two randomized placebo-controlled trials of teprotumumab, there was a significantly higher risk of hearing-related (pooled Peto OR [95% CI]: 7.95 [1.57, 40.17]) and of any otologic AEs (3.56 [1.35, 9.43]) with teprotumumab vs. a placebo, whether or not dizziness/vertigo AEs were included. These results call for close audiological monitoring during IGF-1-targeted treatment, with prompt referral to an otolaryngologist should otologic AEs develop.
View details for DOI 10.3390/jcm12103485
View details for PubMedID 37240591
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Comparative Transcriptomic Analysis of Archival Human Vestibular Schwannoma Tissue from Patients with and without Tinnitus.
Journal of clinical medicine
2023; 12 (7)
Abstract
Vestibular schwannoma (VS) is an intracranial tumor that commonly presents with tinnitus and hearing loss. To uncover the molecular mechanisms underlying VS-associated tinnitus, we applied next-generation sequencing (Illumina HiSeq) to formalin-fixed paraffin-embedded archival VS samples from nine patients with tinnitus (VS-Tin) and seven patients without tinnitus (VS-NoTin). Bioinformatic analysis was used to detect differentially expressed genes (DEG; i.e., ≥two-fold change [FC]) while correcting for multiple comparisons. Using RNA-seq analysis, VS-Tin had significantly lower expression of GFAP (logFC = -3.04), APLNR (logFC = -2.95), PREX2 (logFC = -1.44), and PLVAP (logFC = -1.04; all p < 0.01) vs. VS-NoTin. These trends were validated by using real-time RT-qPCR. At the protein level, immunohistochemistry revealed a trend for less PREX2 and apelin expression and greater expression of NLRP3 inflammasome and CD68-positive macrophages in VS-Tin than in VS-NoTin, suggesting the activation of inflammatory processes in VS-Tin. Functional enrichment analysis revealed that the top three protein categories-glycoproteins, signal peptides, and secreted proteins-were significantly enriched in VS-Tin in comparison with VS-NoTin. In a gene set enrichment analysis, the top pathway was allograft rejection, an inflammatory pathway that includes the MMP9, CXCL9, IL16, PF4, ITK, and ACVR2A genes. Future studies are needed to examine the importance of these candidates and of inflammation in VS-associated tinnitus.
View details for DOI 10.3390/jcm12072642
View details for PubMedID 37048724
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Noise-Induced Hearing Loss.
Journal of clinical medicine
2023; 12 (6)
Abstract
Noise-induced hearing loss (NIHL) is the second most common cause of sensorineural hearing loss, after age-related hearing loss, and affects approximately 5% of the world's population. NIHL is associated with substantial physical, mental, social, and economic impacts at the patient and societal levels. Stress and social isolation in patients' workplace and personal lives contribute to quality-of-life decrements which may often go undetected. The pathophysiology of NIHL is multifactorial and complex, encompassing genetic and environmental factors with substantial occupational contributions. The diagnosis and screening of NIHL are conducted by reviewing a patient's history of noise exposure, audiograms, speech-in-noise test results, and measurements of distortion product otoacoustic emissions and auditory brainstem response. Essential aspects of decreasing the burden of NIHL are prevention and early detection, such as implementation of educational and screening programs in routine primary care and specialty clinics. Additionally, current research on the pharmacological treatment of NIHL includes anti-inflammatory, antioxidant, anti-excitatory, and anti-apoptotic agents. Although there have been substantial advances in understanding the pathophysiology of NIHL, there remain low levels of evidence for effective pharmacotherapeutic interventions. Future directions should include personalized prevention and targeted treatment strategies based on a holistic view of an individual's occupation, genetics, and pathology.
View details for DOI 10.3390/jcm12062347
View details for PubMedID 36983347
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Associations of Tinnitus Incidence with Use of Tumor Necrosis Factor-Alpha Inhibitors among Patients with Autoimmune Conditions.
Journal of clinical medicine
2023; 12 (5)
Abstract
Tumor necrosis factor-alpha (TNFalpha) may promote neuroinflammation prompting tinnitus. This retrospective cohort study evaluated whether anti-TNFalpha therapy influences incident tinnitus risk among adults with autoimmune disorders and no baseline tinnitus selected from a US electronic health records database (Eversana; 1 January 2010-27 January 2022). Patients with anti-TNFalpha had ≥90-day history pre-index (first autoimmune disorder diagnosis) and ≥180-day follow-up post-index. Random samples (n = 25,000) of autoimmune patients without anti-TNFalpha were selected for comparisons. Tinnitus incidence was compared among patients with or without anti-TNFalpha therapy, overall and among at-risk age groups or by anti-TNFalpha category. High-dimensionality propensity score (hdPS) matching was used to adjust for baseline confounders. Compared with patients with no anti-TNFalpha, anti-TNFalpha was not associated with tinnitus risk overall (hdPS-matched HR [95% CI]: 1.06 [0.85, 1.33]), or between groups stratified by age (30-50 years: 1 [0.68, 1.48]; 51-70 years: 1.18 [0.89, 1.56]) or anti-TNFalpha category (monoclonal antibody vs. fusion protein: 0.91 [0.59, 1.41]). Anti-TNFalpha was not associated with tinnitus risk among those treated for ≥6 months (hdPS-matched HR [95% CI]: 0.96 [0.69, 1.32]) or ≥12 (1.03 [0.71, 1.5]), or those with RA (1.16 [0.88, 1.53]). Thus, in this US cohort study, anti-TNFalpha therapy was not associated with tinnitus incidence among patients with autoimmune disorders.
View details for DOI 10.3390/jcm12051935
View details for PubMedID 36902722
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miR-431 secreted by human vestibular schwannomas increases the mammalian inner ear's vulnerability to noise trauma.
Frontiers in neurology
2023; 14: 1268359
Abstract
Introduction: Vestibular schwannoma (VS) is an intracranial tumor that arises on the vestibular branch of cranial nerve VIII and typically presents with sensorineural hearing loss (SNHL). The mechanisms of this SNHL are postulated to involve alterations in the inner ear's microenvironment mediated by the genetic cargo of VS-secreted extracellular vesicles (EVs). We aimed to identify the EV cargo associated with poor hearing and determine whether its delivery caused hearing loss and cochlear damage in a mouse model in vivo.Methods: VS tissue was collected from routinely resected tumors of patients with good (VS-GH) or poor (VS-PH) pre-surgical hearing measured via pure-tone average and word recognition scores. Next-generation sequencing was performed on RNA isolated from cultured primary human VS cells and EVs from VS-conditioned media, stratified by patients' hearing ability. microRNA expression levels were compared between VS-PH and VS-GH samples to identify differentially expressed candidates for packaging into a synthetic adeno-associated viral vector (Anc80L65). Viral vectors containing candidate microRNA were infused to the semicircular canals of mice to evaluate the effects on hearing, including after noise exposure.Results: Differentially expressed microRNAs included hsa-miR-431-5p (enriched in VS-PH) and hsa-miR-192-5p (enriched in VS-GH). Newborn mice receiving intracochlear injection of viral vectors over-expressing hsa-miR-431-GFP, hsa-miR-192-GFP, or GFP only (control) had similar hearing 6weeks post-injection. However, after acoustic trauma, the miR-431 group displayed significantly worse hearing, and greater loss of synaptic ribbons per inner hair cell in the acoustically traumatized cochlear region than the control group.Conclusion: Our results suggest that miR-431 contributes to VS-associated hearing loss following cochlear stress. Further investigation is needed to determine whether miR-431 is a potential therapeutic target for SNHL.
View details for DOI 10.3389/fneur.2023.1268359
View details for PubMedID 37885485
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Micro-optical coherence tomography of the mammalian cochlea
SCIENTIFIC REPORTS
2016; 6: 33288
Abstract
The mammalian cochlea has historically resisted attempts at high-resolution, non-invasive imaging due to its small size, complex three-dimensional structure, and embedded location within the temporal bone. As a result, little is known about the relationship between an individual's cochlear pathology and hearing function, and otologists must rely on physiological testing and imaging methods that offer limited resolution to obtain information about the inner ear prior to performing surgery. Micro-optical coherence tomography (μOCT) is a non-invasive, low-coherence interferometric imaging technique capable of resolving cellular-level anatomic structures. To determine whether μOCT is capable of resolving mammalian intracochlear anatomy, fixed guinea pig inner ears were imaged as whole temporal bones with cochlea in situ. Anatomical structures such as the tunnel of Corti, space of Nuel, modiolus, scalae, and cell groupings were visualized, in addition to individual cell types such as neuronal fibers, hair cells, and supporting cells. Visualization of these structures, via volumetrically-reconstructed image stacks and endoscopic perspective videos, represents an improvement over previous efforts using conventional OCT. These are the first μOCT images of mammalian cochlear anatomy, and they demonstrate μOCT's potential utility as an imaging tool in otology research.
View details for DOI 10.1038/srep33288
View details for Web of Science ID 000383331800001
View details for PubMedID 27633610
View details for PubMedCentralID PMC5025881
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Notch signaling and Atoh1 expression during hair cell regeneration in the mouse utricle
HEARING RESEARCH
2010; 267 (1-2): 61-70
Abstract
The mammalian vestibular epithelium has a limited capacity for spontaneous hair cell regeneration. The mechanism underlying the regeneration is not well understood. Because the Notch signaling pathway mediates the formation of the sensory epithelial mosaic patterning during ear development, it may also play a role in hair cell regeneration in the mature mammalian vestibular epithelium after a lesion. To investigate the process of spontaneous regeneration in the vestibular epithelium vis-à-vis changes in Notch signaling, we induced a unilateral lesion by infusing streptomycin into the mouse posterior semicircular canal, and examined Notch signaling molecules and their mRNA expression levels by immunohistochemistry and quantitative real-time polymerase chain reaction (qRTPCR), respectively. We detected Jagged1 in supporting cells in both normal and lesioned utricles. Atoh1, a marker for early developing hair cells, was absent in the intact mature tissue, but re-appeared after the lesion. Many cells were either positive for both Atoh1 and myosin VIIa, or for one of them. qRTPCR data showed a post trauma decrease of Hes5 and an increase in Atoh1. Atoh1 up-regulation may either be a result of Hes5 down-regulation or mediated by another signaling pathway.
View details for DOI 10.1016/j.heares.2010.03.085
View details for Web of Science ID 000280351700008
View details for PubMedID 20433915
View details for PubMedCentralID PMC2902641
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Visualization of spiral ganglion neurites within the scala tympani with a cochlear implant in situ.
Journal of neuroscience methods
2009; 179 (2): 201-7
Abstract
Current cochlear histology methods do not allow in situ processing of cochlear implants. The metal components of the implant preclude standard embedding and mid-modiolar sectioning, and whole mounts do not have the spatial resolution needed to view the implant within the scala tympani. One focus of recent auditory research is the regeneration of structures within the cochlea, particularly the ganglion cells and their processes, and there are multiple potential benefits to cochlear implant users from this work. To facilitate experimental investigations of auditory nerve regeneration performed in conjunction with cochlear implantation, it is critical to visualize the cochlear tissue and the implant together to determine if the nerve has made contact with the implant. This paper presents a novel histological technique that enables simultaneous visualization of the in situ cochlear implant and neurofilament-labeled nerve processes within the scala tympani, and the spatial relationship between them.
View details for DOI 10.1016/j.jneumeth.2009.01.034
View details for PubMedID 19428528
View details for PubMedCentralID PMC2680747
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Brain lesions and their implications in criminal responsibility.
Behavioral sciences & the law
2009; 27 (2): 261-72
Abstract
For over 200 years, Western courts have considered pleas of "not guilty by reason of insanity" (NGRI) for defendants in possession of a mental defect rendering them unable to understand the wrongfulness of their act. Until recently, determining the mental state of a defendant has fallen largely upon the shoulders of court psychologists and experts in psychiatry for qualitative assessments related to NGRI pleas and mitigation at sentencing. However, advances in neuroscience--particularly neurological scanning techniques such as magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), computed tomography scanning (CT), and positron emission tomography scanning (PET)--may provide additional, pertinent biological evidence as to whether an organically based mental defect exists. With increasing frequency, criminal defense attorneys are integrating neuroimaging data into hearings related to determinations of guilt and sentencing mitigation. This is of concern, since not all brain lesions and abnormalities indicate a compromised mental state that is relevant to knowing whether the act was wrong at the time of commission, and juries may be swayed by neuroscientific evidence that is not relevant to the determination of the legal question before them. This review discusses historical and modern cases involving the intersection of brain lesions and criminality, neuroscientific perspectives of how particular types of lesions may contribute to a legally relevant mental defect, and how such evidence might best be integrated into a criminal trial.
View details for DOI 10.1002/bsl.857
View details for PubMedID 19319837
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Notch signaling and Hes labeling in the normal and drug-damaged organ of Corti.
Hearing research
2009; 249 (1-2): 15-22
Abstract
During the development of the inner ear, the Notch cell signaling pathway is responsible for the specification of the pro-sensory domain and influences cell fate decisions. It is assumed that Notch signaling ends during maturity and cannot be reinitiated to alter the fate of new or existing cells in the organ of Corti. This is in contrast to non-mammalian species which reinitiate Delta 1-Notch1 signaling in response to trauma in the auditory epithelium, resulting in hair cell regeneration through transdifferentiation and/or mitosis. We report immunohistochemical data and Western protein analysis showing that in the aminoglycoside-damaged guinea pig organ of Corti, there is an increase in proteins involved in Notch activation occurring within 24h of a chemical hair cell lesion. The signaling response is characterized by the increased presence of Jagged1 ligand in pillar and Deiters cells, Notch1 signal in surviving supporting cell nuclei, and the absence of Jagged2 and Delta-like1. The pro-sensory bHLH protein Atoh1 was absent at all time points following an ototoxic lesion, while the repressor bHLH transcription factors Hes1 and Hes5 were detected in surviving supporting cell nuclei in the former inner and outer hair cell areas, respectively. Notch pathway proteins peaked at 2 weeks, decreased at 1 month, and nearly disappeared by 2 months. These results indicate that the mammalian auditory epithelium retains the ability to regulate Notch signaling and Notch-dependent Hes activity in response to cellular trauma and that the signaling is transient. Additionally, since Hes activity antagonizes the transcription of pro-sensory Atoh1, the presence of Hes after a lesion may prohibit the occurrence of transdifferentiation in the surviving supporting cells.
View details for DOI 10.1016/j.heares.2008.12.008
View details for PubMedID 19185606
View details for PubMedCentralID PMC2796274
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Advancing science through conversations: bridging the gap between blogs and the academy.
PLoS biology
2008; 6 (9): e240
Abstract
Blogs have stormed the Internet, providing an interactive medium for rapid and wide-reaching information dispersal. But is there a place for blogs in academia?
View details for DOI 10.1371/journal.pbio.0060240
View details for PubMedID 18816167
View details for PubMedCentralID PMC2553846
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Response of the flat cochlear epithelium to forced expression of Atoh1.
Hearing research
2008; 240 (1-2): 52-6
Abstract
Following hair cell elimination in severely traumatized cochleae, differentiated supporting cells are often replaced by a simple epithelium with cuboidal or flat appearance. Atoh1 (previously Math1) is a basic helix-loop-helix transcription factor critical to hair cell differentiation during mammalian embryogenesis. Forced expression of Atoh1 in the differentiated supporting cell population can induce transdifferentiation leading to hair cell regeneration. Here, we examined the outcome of adenovirus mediated over-expression of Atoh1 in the non-sensory cells of the flat epithelium. We determined that seven days after unilateral elimination of hair cells with neomycin, differentiated supporting cells are absent, replaced by a flat epithelium. Nerve processes were also missing from the auditory epithelium, with the exception of infrequent looping nerve processes above the habenula perforata. We then inoculated an adenovirus vector with Atoh1 insert into the scala media of the deafened cochlea. The inoculation resulted in upregulation of Atoh1 in the flat epithelium. However, two months after the inoculation, Atoh1-treated ears did not exhibit clear signs of hair cell regeneration. Combined with previous data on induction of supporting cell to hair cell transdifferentiation by forced expression of Atoh1, these results suggest that the presence of differentiated supporting cells in the organ of Corti is necessary for transdifferentiation to occur.
View details for DOI 10.1016/j.heares.2008.02.007
View details for PubMedID 18430530
View details for PubMedCentralID PMC2494705
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Transdifferentiation and its applicability for inner ear therapy.
Hearing research
2007; 227 (1-2): 41-7
Abstract
During normal development, cells divide, then differentiate to adopt their individual form and function in an organism. Under most circumstances, mature cells cannot transdifferentiate, changing their fate to adopt a different form and function. Because differentiated cells cannot usually divide, the repair of injuries as well as regeneration largely depends on the activation of stem cell reserves. The mature cochlea is an exception among epithelial cell layers in that it lacks stem cells. Consequently, the sensory hair cells that receive sound information cannot be replaced, and their loss results in permanent hearing impairment. The lack of a spontaneous cell replacement mechanism in the organ of Corti, the mammalian auditory sensory epithelium, has led researchers to investigate circumstances in which transdifferentiation does occur. The hope is that this information can be used to design therapies to replace lost hair cells and restore impaired hearing in humans.
View details for DOI 10.1016/j.heares.2006.08.015
View details for PubMedID 17070000