Detection and characterization of novel luchacoviruses, genus Alphacoronavirus, in saliva and feces of meso-carnivores in the northeastern United States.

IMPORTANCE: Several coronaviruses (CoVs) have been detected in domesticated, farmed, and wild meso-carnivores, causing a wide range of diseases and infecting diverse species, highlighting their important but understudied role in the epidemiology of these viruses. Assessing the viral diversity hosted in wildlife species is essential to understand their significance in the cross-species transmission of CoVs. Our focus here was on CoV discovery in meso-carnivores in the Northeast United States as a potential "hotspot" area with high density of humans and urban wildlife. This study identifies novel alphacoronaviruses circulating in multiple free-ranging wild and domestic species in this area and explores their potential epidemiological importance based on regions of the Spike gene, which are relevant for virus-host interactions.

Detection and characterization of novel luchacoviruses, genus Alphacoronavirus, shed in saliva and feces of meso-carnivores in the northeastern United States.

Small to mid-sized carnivores, or meso-carnivores, comprise a group of diverse mammals, many of which can adapt to anthropogenically disturbed environments. Wild meso-carnivores living in urban areas may get exposed to or spread pathogens to other species, including stray/feral domestic animals. Several coronaviruses (CoVs) have been detected in domesticated and farmed meso-carnivores, but knowledge of CoVs circulating in free-ranging wild meso-carnivores remains limited. In this study, we analyzed 321 samples collected between 2016 and 2022 from 9 species of free-ranging wild meso-carnivores and stray/feral domestic cats in the northeastern United States. Using a pan-CoV PCR, we screened tissues, feces, and saliva, nasal, and rectal swabs. We detected CoV RNA in fecal and saliva samples of animals in four species: fisher (Pekania pennanti), bobcat (Lynx rufus), red fox (Vulpes vulpes), and domestic cat (Felis catus). Next-generation sequencing revealed that all these viruses belonged to the Luchacovirus subgenus (Alphacoronavirus genus), previously reported only in rodents and lagomorphs (i.e., rabbits). Genetic comparison of the 3'-end of the genome (~12,000bp) revealed that although the viruses detected group with, and have a genetic organization similar to other luchacoviruses, they are genetically distinct from those from rodents and lagomorphs. Genetic characterization of the spike protein revealed that the meso-carnivore luchacoviruses do not have an S1/S2 cleavage motif but do have highly variable structural loops containing cleavage motifs similar to those identified in certain pathogenic CoVs. This study highlights the importance of characterizing the spike protein of CoVs in wild species for further targeted epidemiologic monitoring.

Multiple symptom illness in New Zealand contemporary veterans.

AIMS: To describe patterns of multiple symptom illness (MSI) in New Zealand military veterans, defined as clusters of "medically unexplained" symptoms not fitting within a specific medical diagnosis, and to investigate the relationship with exposure to traumatic events. METHODS: We designed an online cross-sectional survey. The participants of interest were the 3,874 currently serving veterans who had been deployed to a conflict zone, but all veterans were eligible to participate. A modified Centers for Disease Control (CDC) 54-item symptom checklist identified MSI, the post-traumatic checklist-military version (PCL-M) identified symptoms of post-traumatic stress disorder (PTSD) and the brief trauma scale assessed "war zone" service. Factor analysis was used to identify unobserved "latent factors" in the data, factor severity scores and the number of symptoms being calculated for each respondent. RESULTS: The CDC questionnaire was completed by 1,819 veterans, with 1,672 completing the PCL-M. The factor analysis revealed three factors, explaining 86% of the variation in the data. Factor 1 symptoms were of an arthro-neuromuscular nature, Factor 2 cognitive and Factor 3 psycho-physiological. Discriminant function analysis showed that the factors could discriminate between those with and without PTSD but could not discriminate between those who did and did not serve in a war zone. CONCLUSIONS: In veterans, multiple symptoms including pain, sleep disorders, cognitive problems and avoidance, especially when severe, may be worthy of further investigation by health professionals because of the possible association with PTSD.

Opportunities for preventing subsequent injuries: a qualitative study exploring perspectives of people who have experienced injuries.

AIM: This study aims to examine opportunities for subsequent injury prevention from the perspectives of people who have recently experienced subsequent injury events. METHODS: This qualitative study involved individual semi-structured interviews with people who had >2 injury events in the previous 12 months. Interviews were audio-recorded, transcribed verbatim and thematic analysis undertaken. RESULTS: Sixteen interviews were completed with participants who had experienced a range of index and subsequent injury types. Potential opportunities raised were wide-ranging. Some related to individuals, e.g., motivation to carry out prevention strategies. Other opportunities were related to healthcare providers and the health system. For instance, increasing consultation times to allow a focus on subsequent injury prevention, building rapport and tailoring their approach to the individual, proactively referring people to a range of healthcare providers, and ensuring people are aware of resources and supports available following injury. Broader environmental and societal opportunities were also suggested, such as ensuring adequate social support following injury, ensuring accessibility to rehabilitation and community facilities and the modification of built environments. CONCLUSION: A broad range of potential opportunities to prevent subsequent injuries were raised. These opportunities are promising and future research to trial interventions raised in this study is warranted to determine their feasibility and effectiveness.

Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse.

Kv3 potassium currents mediate rapid repolarisation of action potentials (APs), supporting fast spikes and high repetition rates. Of the four Kv3 gene family members, Kv3.1 and Kv3.3 are highly expressed in the auditory brainstem and we exploited this to test for subunit-specific roles at the calyx of Held presynaptic terminal in the mouse. Deletion of Kv3.3 (but not Kv3.1) reduced presynaptic Kv3 channel immunolabelling, increased presynaptic AP duration and facilitated excitatory transmitter release; which in turn enhanced short-term depression during high-frequency transmission. The response to sound was delayed in the Kv3.3KO, with higher spontaneous and lower evoked firing, thereby reducing signal-to-noise ratio. Computational modelling showed that the enhanced EPSC and short-term depression in the Kv3.3KO reflected increased vesicle release probability and accelerated activity-dependent vesicle replenishment. We conclude that Kv3.3 mediates fast repolarisation for short precise APs, conserving transmission during sustained high-frequency activity at this glutamatergic excitatory synapse.

Factors associated with self-reported health among New Zealand military veterans: a cross-sectional study.

OBJECTIVE: To identify factors associated with better or poorer self-reported health status in New Zealand military Veterans. DESIGN: A cross-sectional survey. PARTICIPANTS: The participants of interest were the 3874 currently serving Veterans who had been deployed to a conflict zone, but all Veterans were eligible to participate. STUDY VARIABLES: The EQ-5D-5L, asking about problems across five dimensions (mobility, self-care, usual activities, pain or discomfort and anxiety or depression), with five levels of severity (eg, no, slight, moderate, severe or extreme problems), also containing a Visual Analogue Scale (EQ-VAS) to self-assess health state, scaled from 0 (worst) to 100 (best) imagined health.Hypothetical relationships with better health were positive social support, sleep and psychological flexibility; with poorer health, post-traumatic stress, exposure to psychological trauma, distress and hazardous drinking. RESULTS: The EQ5-D-5L was completed by 1767 Veterans, 1009 serving, a response rate of 26% from that group, 1767 completing the EQ5-D, 1458 who had deployed, 288 who had not and the 21 who did not provide deployment data. Of these, 247 were not used in the analysis due to missing values in one or more variables, leaving 1520 for analysis.A significantly higher proportion of Veterans reported 'any problems' rather than 'no problems' with four EQ-5D dimensions: mobility, self-care, usual activities and pain or discomfort, but no difference in anxiety or depression. Age, length of service, deployment, psychological flexibility and better sleep quality were associated with higher EQ-VAS scores; distress with lower EQ-VAS scores. CONCLUSION: In this sample of New Zealand Veterans, psychological flexibility and good sleep are associated with better self-rated health, and distress and poor sleep with diminished health. These factors might be used as sentinel health indicators in assessing Veteran health status, and cognitive-behavioural therapy encompassing these domains may be useful in improving the health of New Zealand Veterans.

Preventing subsequent injury: Healthcare providers' perspectives on untapped potential.

INTRODUCTION: Many individuals who experience an injury go on to have subsequent injuries. This study examined the views of health professionals about potential opportunities to prevent subsequent injuries. METHODS: Semi-structured individual interviews were held with a range of health professionals involved in treating injuries. Interviews examined opportunities for the prevention of subsequent injuries, particularly opportunities that may be implemented by health professionals. A thematic analysis of the data was undertaken. RESULTS: Thirteen health professionals were interviewed, including physiotherapists, occupational therapists, and emergency department staff. Opportunities to prevent subsequent injuries aligned with the Dahlgren-Whitehead model of health determinants, representing opportunities to focus on demographic factors (e.g. older adults), individual lifestyle factors (e.g. alcohol consumption), social and community networks (e.g. social isolation), living and working conditions (e.g. access to preventive healthcare), and general socioeconomic, cultural, and environmental conditions (e.g. changes in legislation). CONCLUSIONS: Health professionals identified a number of opportunities for subsequent injury prevention, ranging from individually oriented interventions to broader societal interventions. Within their roles, health professionals highlighted potential opportunities to provide education, modify attitudes, engage in multi-disciplinary teamwork, and serve as advocates. Use of these strategies could help to reduce the disability burden presented by subsequent injuries.

The Girls' Leadership Academy: A Promising, Empowerment-Based Approach to the Prevention of Sexual Violence.

Sexual violence (SV) is a pernicious issue that disproportionally impacts girls and women. Although few initiatives have demonstrated effectiveness in leading to reductions in SV, global health organizations have identified empowerment-based programs as a promising approach to SV prevention. The purpose of this article is to discuss the Girls Leadership Academy (GLA), a program of the Nebraska's Women's Center for Advancement, which is a "homegrown," theoretically grounded, practice-based SV prevention program for adolescent girls. More specifically, we discuss previous research relevant to the GLA; the theoretical underpinnings of the GLA; and the history, context, and content of the GLA.

Prospective Outcomes of Injury Study 10 Years on (POIS-10): An Observational Cohort Study.

Injury is a leading cause of disability and is costly. This prospective cohort study extension aims to improve disability, health, and wellbeing outcomes for injured New Zealanders, including for Maori. We will identify predictors and modifiable risk factors of long-term outcomes (positive and negative), and develop an Injury Early Care Tool (INJECT) to inform the implementation of effective interventions to improve outcomes. In the Prospective Outcomes of Injury Study (POIS), 2856 people participated following an injury (occurring between 2007 and 2009) registered with New Zealand's no-fault accident compensation scheme (ACC). POIS-10 will invite 2121 people (including 358 Maori) who completed a 24-month POIS interview and agreed to follow-up, anticipating 75% participation (n = 1591). Interviews will collect sociodemographic characteristics, life events, comorbidities, and new injuries since participants' 24-month interview, as well as key disability, health, and wellbeing outcomes 12 years post-injury. Injury-related data will be collected from ACC and hospitalisation records 12 years post-injury. Regression models for the main outcomes will examine the direct effects of predictor variables after adjustment for a wide range of confounders. POIS-10 is enhanced by our partnership with ACC, and expert advisors and will benefit injured people, including Maori, through increased understanding of mechanisms and interventions to improve long-term post-injury outcomes.

Prevalence and predictors of psychological distress following injury: findings from a prospective cohort study.

BACKGROUND: Research examining psychological distress in people who have experienced an injury has focused on those with serious injuries or specific injury types, and has not involved long-term follow up. The aims of this investigation were to describe the prevalence of, and factors contributing to, psychological distress in a cohort of people with a broad range of injuries. METHODS: The Prospective Outcomes of Injury Study (POIS) is a longitudinal cohort study of 2856 injured New Zealanders recruited from a national insurance entitlement claims register between 2007 and 2009. Participants were interviewed approximately 3, 12, and 24 months after their injury. The Kessler Psychological Distress Scale (K6) was used to measure psychological distress at each interview. RESULTS: 25% of participants reported clinically relevant distress (K6 ≥ 8) 3 months post-injury, 15% reported distress at 12 months, and 16% reported distress at 24 months. Being 45 years or older, Maori or Pacific ethnicity, experiencing pre-injury mental health conditions, having inadequate pre-injury income, reporting poor pre-injury health or trouble accessing healthcare, having a severe injury or an injury resulting from assault, and reporting clinically relevant distress 3 months post-injury were independently associated with an increased risk of distress 12 months post-injury. The majority of these associations were also evident with respect to distress 24 months post-injury. CONCLUSIONS: Distress is common after injury among people with a broad range of injury types and severities. Screening for distress early after injury is important to identify individuals in need of targeted support.

Secondary health conditions and disability among people with spinal cord injury: A prospective cohort study.

Objective: To examine how secondary health conditions (SHCs) that develop early after a spinal cord injury (SCI) are related to disability over time.Design: Prospective cohort study.Setting: Two spinal units in New Zealand (Burwood Spinal Unit and Auckland Spinal Rehabilitation Unit).Participants: Between 2007 and 2009, 91 people participated in three telephone interviews approximately 6, 18, and 30 months after the occurrence of a SCI.Outcome measures: SHCs were measured using 14 items derived from the Secondary Complications Survey. Disability was measured using the 12-item World Health Organization Disability Assessment Schedule 2.0. Linear regression analyses were performed to investigate associations between SHCs at 6 months and disability at each assessment point.Results: The most prevalent SHCs were leg spasms, constipation, back pain, pain below the level of SCI, and shoulder pain. Constipation, urinary tract infection, and headaches at 6 months post-SCI were associated with significantly higher levels of disability at each subsequent follow-up, independent of age, sex and SCI impairment. Back pain, and pain below the SCI, at 6 months were associated with significantly greater disability at 18 months, and difficulty coughing at 6 months was associated with significantly greater disability at 30 months.Conclusion: The experience of specific SHCs in the first 6 months after an SCI is related to greater long-term disability. In order to reduce the disability burden of people with SCI, efforts should be directed toward early prevention of these SHCs.

Preanalytical variables affecting the measurement of serum paraoxonase-1 activity in horses.

Paraoxonase-1 (PON-1) activity is a new inflammatory and oxidative marker. Technical effects and biological factors could affect the accuracy of PON-1 activity measurement. We investigated the effects of storage at different temperatures, repeated freeze-thaw cycles, interferences from hemolytic, lipemic, and icteric samples, and seasonal effects on PON-1 activity in horses. We evaluated 2 substrates with an automated spectrophotometer. Ten equine serum samples were stored under different conditions. Although storage at room (21°C) or refrigeration (4°C) temperature induced a statistically significant decrease (p < 0.05) in PON-1 activity, this is not diagnostically relevant. PON-1 activity in frozen samples (-20°C) was stable for short-term storage; diagnostically significant (p < 0.01) fluctuations were observed after 1 mo. Four repeated freeze-thaw cycles were assessed, and all cycles affected PON-1 activity (p < 0.01); however, this was diagnostically significant only after the 4th cycle. Hemolysis induced an overestimation of PON-1 activity; lipemia and hyperbilirubinemia did not change PON-1 activity. Thirty-four horses were sampled monthly for 1 y, and PON-1 activity was higher in autumn (p < 0.05) and winter (p < 0.05) than in spring and summer.

Effect of virtual reality simulation training on real-life cataract surgery complications: systematic literature review.

Virtual reality simulation (VRS) has become progressively popular as a training tool in ophthalmology. However, debate continues as to whether VRS has resulted in better outcomes for patients after cataract surgery. Accordingly, a qualitative systematic literature review was conducted to identify whether VRS training results in a reduced complication rate after real-life cataract surgery. Included studies measured the effect of VRS on real-life patient outcomes after cataract surgery. Databases searched included MEDLINE (Ovid), The Cochrane Library, Web of Science, PubMed, and CINAHL. A total of 1917 studies were identified, of which 10 studies were included, spanning from 2011 to 2020. The studies comprised 471 ophthalmological residents, with their complication rates assessed after 30 462 cataract surgery procedures. This systematic literature review indicates that VRS seems to be most helpful in reducing the rate of posterior capsular rupture or errant curvilinear capsulorrhexis and had limited evidence in reducing the rate of other complications.

A systematic scoping review of interventions to integrate physical and mental healthcare for people with serious mental illness and substance use disorders.

Integrated care approaches have been recommended to remove barriers to healthcare and improve the physical health outcomes of people living with serious mental illness (SMI) and/or substance use disorders (SUDs). The aim of this systematic scoping review was to describe empirical investigations of interventions designed to integrate physical, mental, and addiction healthcare for this population. An iterative and systematic search of five electronic databases (Medline (Ovid), PsycINFO, CINAHL, Embase (Ovid) and Scopus) was conducted to identify peer-reviewed articles published between January 2000 and April 2019. Two reviewers independently screened publications in two successive stages of title and abstract screening, followed by full-text screening of eligible publications. Data from each included publication were extracted independently by two reviewers using a standardised spreadsheet. A total of 28 eligible publications were identified, representing 25 unique studies. Over half of the included studies investigated the use of case managers to provide self-management skills or to coordinate mental and physical healthcare (n = 14). Other interventions examined the co-location of services (n = 9) and the implementation of screening and referral pathways to specialist treatment (n = 2). Less than half of the included studies described a framework, theory or model that was underpinning the intervention tested. While some aspects of integrated care have been identified and addressed by interventions, other key dimensions have not been considered, such as shared decision-making. Identification of a comprehensive model of integrated care is recommended to inform the development and evaluation of future interventions for people with SMI/SUDs.

A systems approach delivers a functional microRNA catalog and expanded targets for seizure suppression in temporal lobe epilepsy.

Temporal lobe epilepsy is the most common drug-resistant form of epilepsy in adults. The reorganization of neural networks and the gene expression landscape underlying pathophysiologic network behavior in brain structures such as the hippocampus has been suggested to be controlled, in part, by microRNAs. To systematically assess their significance, we sequenced Argonaute-loaded microRNAs to define functionally engaged microRNAs in the hippocampus of three different animal models in two species and at six time points between the initial precipitating insult through to the establishment of chronic epilepsy. We then selected commonly up-regulated microRNAs for a functional in vivo therapeutic screen using oligonucleotide inhibitors. Argonaute sequencing generated 1.44 billion small RNA reads of which up to 82% were microRNAs, with over 400 unique microRNAs detected per model. Approximately half of the detected microRNAs were dysregulated in each epilepsy model. We prioritized commonly up-regulated microRNAs that were fully conserved in humans and designed custom antisense oligonucleotides for these candidate targets. Antiseizure phenotypes were observed upon knockdown of miR-10a-5p, miR-21a-5p, and miR-142a-5p and electrophysiological analyses indicated broad safety of this approach. Combined inhibition of these three microRNAs reduced spontaneous seizures in epileptic mice. Proteomic data, RNA sequencing, and pathway analysis on predicted and validated targets of these microRNAs implicated derepressed TGF-ß signaling as a shared seizure-modifying mechanism. Correspondingly, inhibition of TGF-ß signaling occluded the antiseizure effects of the antagomirs. Together, these results identify shared, dysregulated, and functionally active microRNAs during the pathogenesis of epilepsy which represent therapeutic antiseizure targets.

A systematic review of studies measuring health-related quality of life of general injury populations: update 2010-2018.

BACKGROUND: Studies examining the impact of injury on health-related quality of life (HRQL) over time are necessary to understand the short- and long-term consequences of injury for population health. The aim of this systematic review was to provide an evidence update on studies that have measured HRQL over time in general injury populations using a generic (general) health state measure. METHODS: Studies conducted between 2010 and 2018 that assessed HRQL at more than one time point among general injury populations were eligible for inclusion. Two reviewers independently extracted information from each study on design, HRQL measure used, method of HRQL measure administration, timing of assessment(s), predictive variables, ability to detect change, and findings. Quality appraisals of each study were also completed by two reviewers using items from the RTI Item Bank on Risk of Bias and Precision of Observational Studies and the Guidelines for the Conduction of Follow-up Studies Measuring Injury-Related Disability. RESULTS: Twenty-nine studies (44 articles) that met the inclusion criteria were identified. HRQL was measured using 14 different generic measures; the SF-36, SF-12, and EQ-5D were used most frequently. A varying number of follow-up assessments were undertaken, ranging from one to five. Follow-up often occurred 12 months post-injury. Fewer studies (n = 11) examined outcomes two or more years post-injury, and only one to 10 years post-injury. While most studies documented improvements in HRQL over time since the injury event, study populations had not returned to pre-injury status or reached general population norm HRQL values at post-injury follow-ups. CONCLUSIONS: Since 2010 there has been a substantial increase in the number of studies evaluating the HRQL of general injury populations. However, significant variability in study design continues to impede quantification of the impact of injury on population health over time. Variation between studies is particularly evident with respect to timing and number of follow-up assessments, and selection of instruments to evaluate HRQL.

Risk and protective factors for post-traumatic stress among New Zealand military personnel: A cross sectional study.

BACKGROUND: Post-traumatic stress (PTS) is prevalent among military personnel. Knowledge of the risk and protective factors associated with PTS in this population may assist with identifying personnel who would benefit from increased or targeted support. AIMS: To examine factors associated with PTS among New Zealand military personnel. METHODS: For this cross-sectional study, currently serving and retired military personnel were invited to complete a questionnaire. The questionnaire included a measure of PTS (the Military Post-traumatic Stress Disorder Checklist; PCL-M), where scores ≥30 indicate the experience of significant PTS symptoms and scores ≥45 indicate a presumptive clinical diagnosis of post-traumatic stress. Potential risk and protective factors associated with PTS were examined using logistic regression modelling. RESULTS: 1817 military personnel completed the questionnaire. PCL-M scores were ≥30 for 549 (30%) participants and ≥45 for 179 (10%) participants. Factors associated with higher PCL-M scores were trauma exposure, older age, male sex, and Maori ethnicity. Factors associated with lower PCL-M scores were greater length of service, psychological flexibility, and better quality sleep. CONCLUSIONS: PTS was found to be prevalent among New Zealand military personnel. The experience of trauma was strongly associated with PTS. However, factors such as psychological flexibility (the ability to adapt to changes in circumstances) and good sleep were protective, suggesting that these factors could be key targets for interventions designed to reduce PTS among military personnel in New Zealand.

Kv3.1 and Kv3.3 subunits differentially contribute to Kv3 channels and action potential repolarization in principal neurons of the auditory brainstem.

KEY POINTS: Kv3.1 and Kv3.3 subunits are highly expressed in the auditory brainstem, with little or no mRNA for Kv3.2 or Kv3.4. Changes in Kv3 currents and action potential (AP) firing were analysed from wild-type, Kv3.1 and Kv3.3 knockout (KO) mice. Both Kv3.1 and Kv3.3 immunostaining was present and western blots confirmed loss of subunit protein in the respective KO. Medial nucleus of the trapezoid body (MNTB) AP repolarization utilized Kv3.1 and/or Kv3.3; while in the lateral superior olive (LSO) Kv3.3 was essential. Voltage-gated calcium currents were unchanged between the genotypes. But APs evoked higher [Ca2+ ]i in LSO than MNTB neurons; and were highest in the Kv3.3KO, consistent with longer AP durations. High frequency stimulation increased AP failure rates and AP latency in LSO neurons from the Kv3.3KO, underlining the physiological consequences for binaural integration. LSO neurons require Kv3.3 for functional Kv3 channels, while MNTB neurons can utilize either Kv3.1 or Kv3.3 subunits. ABSTRACT: Kv3 voltage-gated potassium channels mediate action potential (AP) repolarization. The relative importance of Kv3.1 and Kv3.3 subunits for assembly of functional channels in neurons of the auditory brainstem was examined from the physiological perspective that speed and precision of AP firing are crucial for sound source localization. High levels of Kv3.1 and Kv3.3 mRNA and protein were measured, with no evidence of compensation by Kv3.2 or Kv3.4 in the respective knockout (KO) mouse. Using the KOs, composition of Kv3 channels was constrained to either Kv3.1 or Kv3.3 subunits in principal neurons of the medial nucleus of the trapezoid body (MNTB) and lateral superior olive (LSO); while TEA (1 mm) was employed to block Kv3-mediated outward potassium currents in voltage- and current clamp experiments. MNTB neuron APs (half-width 0.31 ± 0.08 ms, n = 25) were fast, reliable, and showed no distinction between channels assembled from Kv3.1 or Kv3.3 subunits (in the respective KO). LSO AP half-widths were also fast, but absolutely required Kv3.3 subunits for fast repolarization (half-widths: 0.25 ± 0.08 ms, n = 19 wild-type, 0.60 ± 0.17 ms, n = 21 Kv3.3KO, p = 0.0001). The longer AP duration increased LSO calcium influx and AP failure rates, and increased AP latency and jitter during high frequency repetitive firing. Both Kv3.1 and Kv3.3 subunits contribute to Kv3 channels in the MNTB (and compensate for each other in each KO); in contrast, LSO neurons require Kv3.3 subunits for fast repolarization and to sustain AP firing during high frequency stimulation. In conclusion, Kv3 channels exhibit both redundancy and Kv3.3 dominance between the brainstem nuclei involved in sound localization.