Changing the Face of Health Education via Health Interventions: Social Ecological Perspectives on New Media Technologies and Elementary Nutrition Education.

The relationship between media use, family dynamics, and school environments on a child's likelihood to be overweight or obese is an area of research with limited empirical evidence; however, reports have indicated that children are increasingly developing more negative habits related to their health. The purpose of the present study was to employ a social ecological perspective in determining the effectiveness of a longitudinal health literacy/health intervention program on children's nutritional knowledge, attitudes toward healthy eating and exercise, food preferences, and eating behavior. Using a sample of elementary school children initially in Grades 2 and 3 and then in Grades 3 and 4, a field experiment was conducted using a new media technology to record their food intake at home and at school. Results from the study suggest that the health literacy program was successful with positive increases observed for cognition, attitudes, and behavior. From a perspective of social ecological model, the findings suggest that children's eating behaviors need to be considered at the intersection of children's health literacy/attitudes, community efforts, and media/screen time use.

Effect of body position and oxygen tension on foramen ovale recruitment.

While there is an increased prevalence of stroke at altitude in individuals who are considered to be low risk for thrombotic events, it is uncertain how venous thrombi reach the brain. The patent foramen ovale (PFO) is a recruitable intracardiac shunt between the right and left atrium. We aimed to determine whether body position and oxygen tension affect blood flow through the PFO in healthy adults. We hypothesized that hypoxia and body positions that promote right atrial filling would independently recruit the PFO. Subjects with a PFO (n = 11) performed 11 trials, combining four different fractions of inhaled oxygen (FiO2) (1.0, 0.21, 0.15, and 0.10) and three positions (upright, supine, and 45° head down), with the exception of FiO2 = 0.10, while 45° head down. After 5 min in each position, breathing the prescribed oxygen tension, saline bubbles were injected into an antecubital vein and a four-chamber echocardiogram was obtained to evaluate PFO recruitment. We observed a high incidence of PFO recruitment in all conditions, with increased recruitment in response to severe hypoxia and some contribution of body position at moderate levels of hypoxia. We suspect that increased pulmonary vascular pressure, secondary to hypoxia-induced pulmonary vasoconstriction, increased right atrial pressure enough to recruit the PFO. Additionally, we hypothesize that the minor increase in breathing resistance that was added by the mouthpiece, used during experimental trials, affected intrathoracic pressure and venous return sufficiently to recruit the PFO.

Efficacy of bronchoscopic thermal vapor ablation and lobar fissure completeness in patients with heterogeneous emphysema.

BACKGROUND: Bronchoscopic thermal vapor ablation (BTVA) ablates emphysematous tissue through a localized inflammatory response followed by contractive fibrosis and tissue shrinkage leading to lung volume reduction that should not be influenced by collateral ventilation. OBJECTIVES: To determine the correlation of clinical data from a trial of BTVA with fissure integrity visually assessed by computed tomography (CT). METHODS: We conducted a single-arm study of patients with upper lobe-predominant emphysema (n = 44). Patients received BTVA either to the right upper lobe or left upper lobe, excluding the lingula. Primary efficacy outcomes were forced expiratory volume in 1 s (FEV(1)) and St. George's Respiratory Questionnaire (SGRQ) at 6 months. Lobar volume reduction from CT was another efficacy outcome measurement. The fissure of the treated lobe was analyzed visually on preinterventional CT. Incompleteness of the small fissure, the upper half of the right large fissure and the whole left large fissure were estimated visually in 5% increments, and the relative amount of fissure incompleteness was calculated. Pearson correlation coefficients were calculated for the association between fissure incompleteness and change in efficacy outcomes (baseline to 6 months) of BTVA. RESULTS: A total of 38 out of 44 patients (86%) had incompleteness in the relevant fissure. Calculated relevant fissure incompleteness was a mean of 13% of fissure integrity (range 0-63). Correlation coefficients for the association of incompleteness with outcomes were as follows: FEV(1) = 0.17; lung volume reduction = -0.27; SGRQ score = -0.10; 6-min walk distance = 0.0; residual volume (RV) = -0.18, and RV/total lung capacity = -0.14. CONCLUSIONS: Lobar fissure integrity has no or minimal influence on BTVA-induced lung volume reduction and improvements in clinical outcomes.

Use of computed tomography in the emergency department for the diagnosis of pediatric peritonsillar abscess.

OBJECTIVE: The objective of this study was to review our pediatric emergency department's (ED's) utilization of computed tomography (CT) in the diagnosis of peritonsillar abscess (PTA) and treatment outcomes. METHODS: This study used case series with chart review. RESULTS: From January 2007 to January 2009, 148 patients were seen in our ED for possible PTA. Mean age at presentation was 11.8 years (range, 10 months to 18 years); 81 (54.7%) of 148 were females. Computed tomography was ordered in 96 (64.9%) of 148 patients, of which 73 (49.3%) 148 were confirmed to have PTA. Mean age of patients who underwent CT was younger when compared with those who did not have CT performed (mean, 11 vs 13 years; P = 0.02). Unilateral PTA was found in 65 (43.9%) of 148, bilateral in 8 (5.4%) of 148, and intratonsillar in 25 patients (16.9%). Concomitant CT findings of parapharyngeal space involvement were found in 19 (12.8%), and retropharyngeal space involvement in 11 (7.4%). Admission was necessary for 104 (71.2%) of 148 patients, whereas 42 were discharged from the ED. Transoral needle aspiration and/or incision and drainage were performed in the ED in 41 patients, with purulence identified in 33 (80.5%) of 41. Rapid strep testing was positive in 40 (32%) of 124 patients tested. Operative treatment was necessary in 44 patients (29.7%), 34 underwent incision and drainage, and 10 underwent quinsy tonsillectomy. CONCLUSIONS: Computed tomography is commonly utilized in the ED for the evaluation of PTA and is ordered more often in younger children.

A retrospective study on the acceptability, feasibility, and effectiveness of LoveYourBrain Yoga for people with traumatic brain injury and caregivers.

PURPOSE: To conduct a mixed methods, pre-post, retrospective study on the feasibility, acceptability, and effectiveness of the LoveYourBrain Yoga program. MATERIALS AND METHODS: People were eligible if they were a traumatic brain injury survivor or caregiver, age 15-70, ambulatory, and capable of gentle exercise and group discussion. We analyzed attendance, satisfaction, and mean differences in scores on Quality of Life After Brain Injury Overall scale (QOLIBRI-OS) and four TBI-QOL/Neuro-QOL scales. Content analysis explored perceptions of benefits and areas of improvement. RESULTS: 1563 people (82.0%) participated ≥1 class in 156 programs across 18 states and 3 Canadian provinces. Mean satisfaction was 9.3 out of 10 (SD 1.0). Mixed effects linear regression found significant improvements in QOLIBRI-OS (B 9.70, 95% CI: 8.51, 10.90), Resilience (B 1.30, 95% CI: 0.60, 2.06), Positive Affect and Well-being (B 1.49, 95% CI: 1.14, 1.84), and Cognition (B 1.48, 95% CI: 0.78, 2.18) among traumatic brain injury survivors (n = 705). No improvement was found in Emotional and Behavioral Dysregulation, however, content analysis revealed better ability to regulate anxiety, anger, stress, and impulsivity. Caregivers perceived improvements in physical and psychological health. CONCLUSIONS: LoveYourBrain Yoga is feasible and acceptable and may be an effective mode of community-based rehabilitation.IMPLICATIONS FOR REHABILITATIONPeople with traumatic brain injury and their caregivers often experience poor quality of life and difficulty accessing community-based rehabilitation services.Yoga is a holistic, mind-body therapy with many benefits to quality of life, yet is largely inaccessible to people affected by traumatic brain injury in community settings.Participants in LoveYourBrain Yoga, a six-session, community-based yoga with psychoeducation program in 18 states and 3 Canadian provinces, experienced significant improvements in quality of life, resilience, cognition, and positive affect.LoveYourBrain Yoga is feasible and acceptable when implemented on a large scale and may be an effective mode of, or adjunct to, community-based rehabilitation.

Haemaphysalis longicornis: the life-cycle on dogs and cattle, with confirmation of its vector status for Theileria orientalis in Australia.

The intracellular protozoal parasite Theileria orientalis ikeda has rapidly spread across South-eastern Australia since 2006, causing deaths and production losses in cattle. The 3-host "bush tick" Haemaphysalis longicornis (Neumann) appears the principal biological vector in the endemic regions. To generate sufficient numbers of ticks to produce stabilate for infection to confirm vector competency and for acaricide trials, the optimal conditions and stage-specific intervals for the generational life-cycle of H.longicornis was defined on two dogs and two steers. To determine whether H.longicornis was a definitive host for Theileria orientalis, nymphal stages were fed on a steer infected with T.orientalis and moulted adults were permitted to feed for 3 days on an uninfected calf prior to harvest. Subsequent detection of infection after inoculation of four naïve calves with stabilate produced from ground-up adult ticks or dissected salivary glands confirmed H.longicornis as one final (definitive) host for T.orientalis in Australia.

Haemaphysalis longicornis: the life-cycle on dogs and cattle, with confirmation of its vector status for Theileria orientalis in Australia.

The intracellular protozoal parasite Theileria orientalis ikeda has rapidly spread across South-eastern Australia since 2006, causing deaths and production losses in cattle. The 3-host "bush tick" Haemaphysalis longicornis (Neumann) appears the principal biological vector in the endemic regions. To generate sufficient numbers of ticks to produce stabilate for infection to confirm vector competency and for acaricide trials, the optimal conditions and stage-specific intervals for the generational life-cycle of H.longicornis was defined on two dogs and two steers. To determine whether H.longicornis was a definitive host for Theileria orientalis, nymphal stages were fed on a steer infected with T.orientalis and moulted adults were permitted to feed for 3 days on an uninfected calf prior to harvest. Subsequent detection of infection after inoculation of four naïve calves with stabilate produced from ground-up adult ticks or dissected salivary glands confirmed H.longicornis as one final (definitive) host for T.orientalis in Australia.

Integration of health solutions into government systems: a tool for assessing readiness.

Government partnerships are essential for many health solutions to sustain impact at scale, particularly in low-resource settings where strengthening health systems is critical for Universal Health Coverage. Many non-governmental organizations (NGOs) and funders ultimately want solutions to be integrated into public health systems by transitioning solution ownership, management and/or operation to government. However, NGOs and their government partners have limited guidance on how to effectively determine when a solution is ready to transition in a way that will maintain impact long term. To address this need, VillageReach developed the Transition Readiness Assessment (TRA) based on our transition to government theoretical framework. The framework was developed to define both factors related to a solution, as well as external influences that affect a solution's success.  The framework identifies seven dimensions of solution readiness: the political, economic, and social context; solution design; resource availability; financial management; government strategy; government policy and regulations; and organizational management. The TRA measures those dimensions and assigns each one a readiness score. We developed the framework and TRA for VillageReach solutions, as well as to share with government partners and stakeholders. This Open Letter outlines the TRA development, details empirical examples from applying the tool on two VillageReach solutions, and presents recommendations based on our lessons learned. Stakeholders working to transition solutions to government can utilize both the TRA and our lessons.

Increased aortic stiffness and elevated blood pressure in response to exercise in adult survivors of prematurity.

OBJECTIVES: Adults born prematurely have an increased risk of early heart failure. The impact of prematurity on left and right ventricular function has been well documented, but little is known about the impact on the systemic vasculature. The goals of this study were to measure aortic stiffness and the blood pressure response to physiological stressors; in particular, normoxic and hypoxic exercise. METHODS: Preterm participants (n = 10) were recruited from the Newborn Lung Project Cohort and matched with term-born, age-matched subjects (n = 12). Aortic pulse wave velocity was derived from the brachial arterial waveform and the heart rate and blood pressure responses to incremental exercise in normoxia (21% O2 ) or hypoxia (12% O2 ) were evaluated. RESULTS: Aortic pulse wave velocity was higher in the preterm groups. Additionally, heart rate, systolic blood pressure, and pulse pressure were higher throughout the normoxic exercise bout, consistent with higher conduit artery stiffness. Hypoxic exercise caused a decline in diastolic pressure in this group, but not in term-born controls. CONCLUSIONS: In this first report of the blood pressure response to exercise in adults born prematurely, we found exercise-induced hypertension relative to a term-born control group that is associated with increased large artery stiffness. These experiments performed in hypoxia reveal abnormalities in vascular function in adult survivors of prematurity that may further deteriorate as this population ages.

Employment and work disability in systemic lupus erythematosus: a systematic review.

OBJECTIVES: Many studies have provided information on employment and work disability (WD) rates in patients with SLE, yet are often limited by small sample sizes, poor generalizability or fail to examine the risks and outcomes of WD. Our objective was to systematically review the literature on WD in SLE to identify a more generalizable point estimate and range of WD in SLE patients. METHODS: A search was conducted using Medline, EMBase, PubMed and Cochrane databases to identify publications related to SLE and employment and/or WD. Characteristics of the study samples and employment/WD data were extracted. Descriptive statistics, a test for heterogeneity and random effects models were performed to obtain pooled estimates of employment and WD rates for all patients. RESULTS: Twenty-six studies with a total of 9886 SLE patients were found; however, not all patients were reviewed for WD. Larger studies demonstrated the prevalence of WD at 20-40%, and pooled estimates found that 46% (95% CI 40%, 52%) were employed with SLE and 34% (95% CI 24%, 44%) had WD. WD was related to psychosocial and disease-related factors including age, race, socioeconomic status (SES), education, disease activity and duration, pain, fatigue, anxiety and neurocognitive involvement. CONCLUSIONS: This study provides strong evidence that costs of SLE may be very high due to job loss at a younger age in SLE patients, and identifies some risk factors associated with WD, which should be targeted by interventions aimed at preventing job loss.

Laboratory evaluations of the 3-month efficacy of oral lotilaner (Credelio™) against experimental infestations of dogs with the Australian paralysis tick, Ixodes holocyclus.

BACKGROUND: From three days following host attachment, the Australian paralysis tick, Ixodes holocyclus, secretes a neurotoxin that annually causes paralysis in approximately 10,000 domestic pets. Lotilaner, a novel isoxazoline formulated in a chewable flavoured tablet (CredelioTM), produces rapid onset of acaricidal activity in dogs, with an efficacy duration of at least one month. Two studies were performed to determine the efficacy of lotilaner against I. holocyclus infestations over 3 months. METHODS: Both studies included 16 dogs, ranked according to I. holocyclus counts on Day -5 (from infestations on Day -8) and blocked into pairs. One dog in each pair was randomized to be a sham-treated control, the other to receive lotilaner at a minimum dose rate of 20 mg/kg on Day 0. Dogs were dosed in a fed state. Infestations were performed in both studies on Days -8 (to determine the tick carrying capacity of each dog) -1, 28, 56, 70, 77 and 84, and additionally in Study 1 on Day 91, in Study 2 on Days 14 and 42. In Study 1, ticks were counted and assessed as alive or dead at 24, 48 and 72 h post-initial infestation and post-subsequent re-infestations. In study 2, ticks were counted at 24, 48 and 72 h post-dosing or post-re-infestation. Efficacy was determined by the percent reduction in live attached tick counts in the lotilaner group compared to control. RESULTS: Within 48 h post-treatment in Study 1 and within 72 h post-treatment in Study 2 all lotilaner-group dogs were free of live ticks. By 72 h post-infestation, efficacy in Study 1 remained at 100% through Day 87, except on Day 31 when a single tick was found on one dog, and through Day 59 in Study 2. Efficacy exceeded 95% through the final assessment in each study (Days 94 and 87 in Studies 1 and 2, respectively). CONCLUSION: These results demonstrate that lotilaner quickly kills existing I. holocyclus infestations. By providing 95.3-100.0% protection through at least 87 days post-treatment, lotilaner can be a valuable tool in reducing the risk of tick paralysis in dogs.

Inspiratory and expiratory resistance cause right-to-left bubble passage through the foramen ovale.

A patent foramen ovale (PFO) is linked to increased risk of decompression illness in divers. One theory is that venous gas emboli crossing the PFO can be minimized by avoiding lifting, straining and Valsalva maneuvers. Alternatively, we hypothesized that mild increases in external inspiratory and expiratory resistance, similar to that provided by a SCUBA regulator, recruit the PFO. Nine healthy adults with a Valsalva-proven PFO completed three randomized trials (inspiratory, expiratory, and combined external loading) with six levels of increasing external resistance (2-20 cmH2 O/L/sec). An agitated saline contrast echocardiogram was performed at each level to determine foramen ovale patency. Contrary to our hypothesis, there was no relationship between the number of subjects recruiting their PFO and the level of external resistance. In fact, at least 50% of participants recruited their PFO during 14 of 18 trials and there was no difference between the combined inspiratory, expiratory, or combined external resistance trials (P > 0.05). We further examined the relationship between PFO recruitment and intrathoracic pressure, estimated from esophageal pressure. Esophageal pressure was not different between participants with and without a recruited PFO. Intrasubject variability was the most important predictor of PFO patency, suggesting that some individuals are more likely to recruit their PFO in the face of even mild external resistance. Right-to-left bubble passage through the PFO occurs in conditions that are physiologically relevant to divers. Transthoracic echocardiography with mild external breathing resistance may be a tool to identify divers that are at risk of PFO-related decompression illness.

Pharmacodynamics of adenovector distribution within the inner ear tissues of the mouse.

Recent studies have demonstrated that delivery of genes to the inner ear can achieve a variety of effects ranging from support of auditory neuron survival to protection and restoration of hair cells, demonstrating the utility of vector based gene delivery. Translation of these findings to useful experimental systems or even clinical applications requires a detailed understanding of the pharmacokinetics of gene delivery in the inner ear. Ideal gene delivery systems will employ a well tolerated vector which efficiently transduces the appropriate target cells within a tissue, but spare non-target structures. Adenovectors based on serotype 5 (Ad 5) are commonly used vectors, are easy to construct and have a long track record of efficacious gene transfer in the inner ear. In this study we demonstrate that distribution of Ad5 vector occurs in a basal to apical gradient with rapid distribution of vector to the vestibule after delivery via a round window cochleostomy. Transduction of the vector and expression of the delivered transgene occurs by 10 min post vector delivery. At 24 h post delivery only 16% of vector that was initially detectable within the inner ear by quantitative PCR remained. Perilymph sampling was used to determine that vector concentrations in perilymph peaked at 30 min post delivery and then declined rapidly. Understanding these basic distribution patterns and parameters for delivery are important for the design of gene delivery vectors and vital for modeling dose responses to achieve safe efficacious delivery of a therapeutic agent.

Vestibular hair cell regeneration and restoration of balance function induced by math1 gene transfer.

HYPOTHESIS: Delivery of math1 using an adenovector (Admath1.11D) results in vestibular hair cell regeneration and recovery of balance function in ototoxin-treated adult mice. BACKGROUND: Loss of peripheral vestibular function is associated with disease processes such as vestibular neuronitis, aminoglycoside ototoxicity, and aging. Loss of vestibular hair cells is one of the mechanisms underlying balance dysfunction in all of these disorders. Currently, recovery from these diseases relies on central vestibular compensation rather than on local tissue recovery. Overexpression of the mammalian atonal homologue math1 has been demonstrated to induce generation of hair cells in neonatal organ of Corti cultures and in the guinea pig cochlea in vivo and could thus provide an approach to local tissue recovery. METHODS: Admath1.11D was applied to cultures of aminoglycoside-treated macular organs or in vivo in a mouse aminoglycoside ototoxicity model. Outcome measures included histologic examination, immunohistochemistry, swim testing, and evaluation of the horizontal vestibulo-ocular reflex. RESULTS: Delivery of math1 resulted in the generation of vestibular hair cells in vitro after aminoglycoside-mediated loss of hair cells. Math1-treated mice showed recovery of the vestibular neuroepithelium within 8 weeks after Admath1.11D treatment. Assessment of animals after vector infusion demonstrated a recovery of vestibular function compared with aminoglycoside-only-treated mice. CONCLUSION: Molecular replacement of math1 may provide a therapeutic means of restoring vestibular function related to vestibular hair cell loss.

Drug delivery to the inner ear using gene therapy.

The last 10 years have seen the development of numerous strategies for the delivery of genes to the inner ear. Besides being a useful research tool,gene therapy has significant promise as a potential clinical treatment. The human inner ear is easily accessible through either the round window or the stapes footplate. It is now possible to choose a variety of vectors to target a variety of different tissues. Modification of promoters yields different expression patterns as well as differences in degree of expression. Several animal studies have also demonstrated that expression of exogenous genes in the cochlea does not result in loss of hearing function. A variety of potential clinical applications are already evident from these early studies. Protective strategies such as prevention of neuronal degeneration and protection of auditory hair cells from oxidative stress are potential examples where gene therapy may be useful. As the understanding of gene therapy improves, investigators will be able to move toward targeted single-gene replacement to treat disorders such as connexin mutations and applying gene therapy to sensory cell replacement.

Low dose oxidative stress induces mitochondrial damage in hair cells.

Oxidative stress has been implicated as a cause of hair cell damage after ischemia reperfusion injury, noise trauma, and ototoxic injury. Oxidative stress can induce both apoptosis or necrosis depending on the degree of exposure. To study how reactive oxygen species (ROS) interacts with hair cells, we have developed an in vitro model of oxidative stress using organ of Corti cultures exposed to physiologically relevant concentrations of hydrogen peroxide (H(2) O(2) ). Treatment of organ of Corti cultures with low concentrations of H(2) O(2) results in loss of outer hair cells in the basal turn of the explant. Higher concentrations of peroxide result in more extensive outer hair cell injury as well as loss of inner hair cells. Early outer hair cell death appears to occur though apoptosis as demonstrated by staining of activated caspase. The effect of oxidative stress on mitochondrial function is a key determinant of degree of damage. Oxidative stress results in reduction of the mitochondrial membrane potential and reduction of mitochondrial produced antioxidants. Low doses of oxidative stress induce changes in mitochondrial gene expression and induce mitochondrial DNA deletions. Recurrent oxidative stress or inhibition of mitochondrial function significantly enhanced hair cell death. This tissue culture model of oxidative hair cell injury maintains a pattern of injury similar to what is observed in vivo after oxidative injury and can be used to study the effects of ROS on hair cells over the time period of the culture.

Adenovector-mediated hair cell regeneration is affected by promoter type.

CONCLUSION: Replacement of vestibular hair cells induced by atoh1 driven by the tissue-specific GFAP promoter was significantly more efficient than use of the cBA or hCMV promoter. OBJECTIVE: To test whether expression level, persistence, or selectivity from adenovirus vectors delivered in the inner ear can be altered by changing the adenovector backbone or by using different cellular and viral promoters. MATERIALS AND METHODS: Adenovector and promoter modifications were tested for differences in transgene expression in adult macular organs. The effect of using an E1/E3 deleted vector was compared to E1/E3/E4 deleted vectors. The effect of using viral and cellular promoters to modify transgene expression was tested in explanted adult mouse macular organs. Based on these results three different promoters were tested for efficacy of atonal gene. RESULTS: Use of adenovectors containing human CMV, the hybrid cBA and ubiquitin promoters driving transgene expression resulted in different types of transgene expression. While several viral and cellular promoters provided broad cell type expression, expression driven by the GFAP promoter was limited to vestibular supporting cells, demonstrating the specificity of this promoter.

Repair of the vestibular system via adenovector delivery of Atoh1: a potential treatment for balance disorders.

Loss of auditory and vestibular hair cells is a common cause of hearing loss and balance disorders. A variety of strategies have been proposed to restore function to damaged inner ear neuroepithelium. Delivery of the atonal homolog, atoh1, has been demonstrated to induce recovery of auditory and vestibular hair cells using a variety of delivery methods and model systems. We have developed a mouse model of vestibular aminoglycoside ototoxicity and demonstrated that delivery of an advanced generation adenovector that expresses atoh1 results in the regeneration of vestibular hair cells. Additionally, mice treated with atoh1 recover balance function. Currently vestibular diseases have few treatment options and several lines of evidence suggest that regeneration of hair cells may be more easily accomplished in the vestibular system. Development of atoh1-based gene therapy for vestibular hair cell loss may provide an initial opportunity for developing gene therapy for inner ear disease.

Hearing preservation after inner ear gene therapy: the effect of vector and surgical approach.

Over seventy studies have examined the potential of gene therapy in the inner ear. For the most part, they have focused on adenoviral vectors and delivery into the cochlea. Most studies have emphasized looking at the expression of marker genes driven by a CMV promoter and have used first-generation adenoviral constructs. E1/E3/E4 deleted adenoviral vectors carrying the green fluorescent protein (GFP) gene were injected into the round window, the basal turn of the cochlea (via a cochleostomy) or into the superior semicircular canal. Hearing was then tested 24 h after viral gene transfer. Large vector titers in small volumes of fluid were well tolerated with the round window approach resulting in complete hearing preservation with transfer of GFP to hair cells and spiral ganglion cells. Injection of comparable doses of vector into a basal turn cochleostomy resulted in high-frequency hearing loss. Addition of a pancaspase inhibitor protected hearing when larger volumes of fluid were administered to the inner ear.