Cochlear Microphonic and Summating Potential Responses from Click-Evoked Auditory Brain Stem Responses in High-Risk and Normal Infants.

BACKGROUND: Examination of cochlear and neural potentials is necessary to assess sensory and neural status in infants, especially those cared for in neonatal intensive care units (NICU) who have high rates of hyperbilirubinemia and thus are at risk for auditory neuropathy (AN). PURPOSE: The purpose of this study was to determine whether recording parameters commonly used in click-evoked auditory brain stem response (ABR) are useful for recording cochlear microphonic (CM) and Wave I in infants at risk for AN. Specifically, we analyzed CM, summating potential (SP), and Waves I, III, and V. The overall aim was to compare latencies and amplitudes of evoked responses in infants cared for in NICUs with infants in a well-baby nursery (WBN), both of which passed newborn hearing screening. RESEARCH DESIGN: This is a prospective study in which infants who passed ABR newborn hearing screening were grouped based on their birth history (WBN and NICU). All infants had normal hearing status when tested with diagnostic ABR at about one month of age, corrected for prematurity. STUDY SAMPLE: Thirty infants (53 ears) from the WBN [mean corrected age at test = 5.0 weeks (wks.)] and thirty-two infants (59 ears) from the NICU (mean corrected age at test = 5.7 wks.) with normal hearing were included in this study. In addition, two infants were included as comparative case studies, one that was diagnosed with AN and another case that was diagnosed with bilateral sensorineural hearing loss (SNHL). DATA COLLECTION AND ANALYSIS: Diagnostic ABR, including click and tone-burst air- and bone-conduction stimuli were recorded. Peak Waves I, III, and V; SP; and CM latency and amplitude (peak to trough) were measured to determine if there were differences in ABR and electrocochleography (ECochG) variables between WBN and NICU infants. RESULTS: No significant group differences were found between WBN and NICU groups for ABR waveforms, CM, or SP, including amplitude and latency values. The majority (75%) of the NICU group had hyperbilirubinemia, but overall, they did not show evidence of effects in their ECochG or ABR responses when tested at about one-month corrected age. These data may serve as a normative sample for NICU and well infant ECochG and ABR latencies at one-month corrected age. Two infant case studies, one diagnosed with AN and another with SNHL demonstrated the complexity of using ECochG and otoacoustic emissions to assess the risk of AN in individual cases. CONCLUSIONS: CM and SPs can be readily measured using standard click stimuli in both well and NICU infants. Normative ranges for latency and amplitude are useful for interpreting ECochG and ABR components. Inclusion of ECochG and ABR tests in a test battery that also includes otoacoustic emission and acoustic reflex tests may provide a more refined assessment of the risks of AN and SNHL in infants.

Optimizing Clinical Interpretation of Distortion Product Otoacoustic Emissions in Infants.

OBJECTIVES: The purpose of this study was to analyze distortion product otoacoustic emission (DPOAE) level and signal to noise ratio in a group of infants from birth to 4 months of age to optimize prediction of hearing status. DPOAEs from infants with normal hearing (NH) and hearing loss (HL) were used to predict the presence of conductive HL (CHL), sensorineural HL (SNHL), and mixed HL (MHL). Wideband ambient absorbance was also measured and compared among the HL types. DESIGN: This is a prospective, longitudinal study of 279 infants with verified NH and HL, including conductive, sensorineural, and mixed types that were enrolled from a well-baby nursery and two neonatal intensive care units in Cincinnati, Ohio. At approximately 1 month of age, DPOAEs (1-8 kHz), wideband absorbance (0.25-8 kHz), and air and bone conduction diagnostic tone burst auditory brainstem response (0.5-4 kHz) thresholds were measured. Hearing status was verified at approximately 9 months of age with visual reinforcement audiometry (0.5-4 kHz). Auditory brainstem response air conduction thresholds were used to assign infants to an NH or HL group, and the efficacy of DPOAE data to classify ears as NH or HL was analyzed using receiver operating characteristic (ROC) curves. Two summary statistics of the ROC curve were calculated: the area under the ROC curve and the point of symmetry on the curve at which the sensitivity and specificity were equal. DPOAE level and signal to noise ratio cutoff values were defined at each frequency as the symmetry point on their respective ROC curve, and DPOAE results were combined across frequency in a multifrequency analysis to predict the presence of HL. RESULTS: Single-frequency test performance of DPOAEs was best at mid to high frequencies (3-8 kHz) with intermediate performance at 1.5 and 2 kHz and chance performance at 1 kHz. Infants with a conductive component to their HL (CHL and MHL combined) displayed significantly lower ambient absorbance values than the NH group. No differences in ambient absorbance were found between the NH and SNHL groups. Multifrequency analysis resulted in the best prediction of HL for the SNHL/MHL group with poorer sensitivity values when infants with CHL were included. CONCLUSIONS: Clinical interpretation of DPOAEs in infants can be improved by using age-appropriate normative ranges and optimized cutoff values. DPOAE interpretation is most predictive at higher F2 test frequencies in young infants (2-8 kHz) due to poor test performance at 1 to 1.5 kHz. Multifrequency rules can be used to improve sensitivity while balancing specificity. Last, a sensitive middle ear measure such as wideband absorbance should be included in the test battery to assess possibility of a conductive component to the HL.

Longitudinal Development of Distortion Product Otoacoustic Emissions in Infants With Normal Hearing.

OBJECTIVES: The purpose of this study was to describe normal characteristics of distortion product otoacoustic emission (DPOAE) signal and noise level in a group of newborns and infants with normal hearing followed longitudinally from birth to 15 months of age. DESIGN: This is a prospective, longitudinal study of 231 infants who passed newborn hearing screening and were verified to have normal hearing. Infants were enrolled from a well-baby nursery and two neonatal intensive care units (NICUs) in Cincinnati, OH. Normal hearing was confirmed with threshold auditory brainstem response and visual reinforcement audiometry. DPOAEs were measured in up to four study visits over the first year after birth. Stimulus frequencies f1 and f2 were used with f2/f1 = 1.22, and the DPOAE was recorded at frequency 2f1-f2. A longitudinal repeated-measure linear mixed model design was used to study changes in DPOAE level and noise level as related to age, middle ear transfer, race, and NICU history. RESULTS: Significant changes in the DPOAE and noise levels occurred from birth to 12 months of age. DPOAE levels were the highest at 1 month of age. The largest decrease in DPOAE level occurred between 1 and 5 months of age in the mid to high frequencies (2 to 8 kHz) with minimal changes occurring between 6, 9, and 12 months of age. The decrease in DPOAE level was significantly related to a decrease in wideband absorbance at the same f2 frequencies. DPOAE noise level increased only slightly with age over the first year with the highest noise levels in the 12-month-old age range. Minor, nonsystematic effects for NICU history, race, and gestational age at birth were found, thus these results were generalizable to commonly seen clinical populations. CONCLUSIONS: DPOAE levels were related to wideband middle ear absorbance changes in this large sample of infants confirmed to have normal hearing at auditory brainstem response and visual reinforcement audiometry testing. This normative database can be used to evaluate clinical results from birth to 1 year of age. The distributions of DPOAE level and signal to noise ratio data reported herein across frequency and age in normal-hearing infants who were healthy or had NICU histories may be helpful to detect the presence of hearing loss in infants.

HUMA: A platform for the analysis of genetic variation in humans.

The completion of the human genome project at the beginning of the 21st century, along with the rapid advancement of sequencing technologies thereafter, has resulted in exponential growth of biological data. In genetics, this has given rise to numerous variation databases, created to store and annotate the ever-expanding dataset of known mutations. Usually, these databases focus on variation at the sequence level. Few databases focus on the analysis of variation at the 3D level, that is, mapping, visualizing, and determining the effects of variation in protein structures. Additionally, these Web servers seldom incorporate tools to help analyze these data. Here, we present the Human Mutation Analysis (HUMA) Web server and database. HUMA integrates sequence, structure, variation, and disease data into a single, connected database. A user-friendly interface provides click-based data access and visualization, whereas a RESTful Web API provides programmatic access to the data. Tools have been integrated into HUMA to allow initial analyses to be carried out on the server. Furthermore, users can upload their private variation datasets, which are automatically mapped to public data and can be analyzed using the integrated tools. HUMA is freely accessible at https://huma.rubi.ru.ac.za.

MD-TASK: a software suite for analyzing molecular dynamics trajectories.

SUMMARY: Molecular dynamics (MD) determines the physical motions of atoms of a biological macromolecule in a cell-like environment and is an important method in structural bioinformatics. Traditionally, measurements such as root mean square deviation, root mean square fluctuation, radius of gyration, and various energy measures have been used to analyze MD simulations. Here, we present MD-TASK, a novel software suite that employs graph theory techniques, perturbation response scanning, and dynamic cross-correlation to provide unique ways for analyzing MD trajectories. AVAILABILITY AND IMPLEMENTATION: MD-TASK has been open-sourced and is available for download from https://github.com/RUBi-ZA/MD-TASK , implemented in Python and supported on Linux/Unix. CONTACT: o.tastanbishop@ru.ac.za.

Wideband acoustic immittance in children with Down syndrome: prediction of middle-ear dysfunction, conductive hearing loss and patent PE tubes.

OBJECTIVE: The purpose of this study was to evaluate pressurised wideband acoustic immittance (WAI) tests in children with Down syndrome (DS) and in typically developing children (TD) for prediction of conductive hearing loss (CHL) and patency of pressure equalising tubes (PETs). DESIGN: Audiologic diagnosis was determined by audiometry in combination with distortion-product otoacoustic emissions, 0.226 kHz tympanometry and otoscopy. WAI results were compared for ears within diagnostic categories (Normal, CHL and PET) and between groups (TD and DS). STUDY SAMPLE: Children with DS (n = 40; mean age 6.4 years), and TD children (n = 48; mean age 5.1 years) were included. RESULTS: Wideband absorbance was significantly lower at 1-4 kHz in ears with CHL compared to NH for both TD and DS groups. In ears with patent PETs, wideband absorbance and group delay (GD) were larger than in ears without PETs between 0.25 and 1.5 kHz. Wideband absorbance tests were performed similarly for prediction of CHL and patent PETs in TD and DS groups. CONCLUSIONS: Wideband absorbance and GD revealed specific patterns in both TD children and those with DS that can assist in detection of the presence of significant CHL, assess the patency of PETs, and provide frequency-specific information in the audiometric range.

Role of Structural Bioinformatics in Drug Discovery by Computational SNP Analysis: Analyzing Variation at the Protein Level.

With the completion of the human genome project at the beginning of the 21st century, the biological sciences entered an unprecedented age of data generation, and made its first steps toward an era of personalized medicine. This abundance of sequence data has led to the proliferation of numerous sequence-based techniques for associating variation with disease, such as genome-wide association studies and candidate gene association studies. However, these statistical methods do not provide an understanding of the functional effects of variation. Structure-based drug discovery and design is increasingly incorporating structural bioinformatics techniques to model and analyze protein targets, perform large scale virtual screening to identify hit to lead compounds, and simulate molecular interactions. These techniques are fast, cost-effective, and complement existing experimental techniques such as high throughput sequencing. In this paper, we discuss the contributions of structural bioinformatics to drug discovery, focusing particularly on the analysis of nonsynonymous single nucleotide polymorphisms. We conclude by suggesting a protocol for future analyses of the structural effects of nonsynonymous single nucleotide polymorphisms on proteins and protein complexes.

Structure-Based Analysis of Single Nucleotide Variants in the Renin-Angiotensinogen Complex.

BACKGROUND: The renin-angiotensin system (RAS) plays an important role in regulating blood pressure and controlling sodium levels in the blood. Hyperactivity of this system has been linked to numerous conditions including hypertension, kidney disease, and congestive heart failure. Three classes of drugs have been developed to inhibit RAS. In this study, we provide a structure-based analysis of the effect of single nucleotide variants (SNVs) on the interaction between renin and angiotensinogen with the aim of revealing important residues and potentially damaging variants for further inhibitor design purposes. OBJECTIVES: To identify SNVs that have functional and potentially damaging effects on the renin-angiotensinogen complex and to use computational approaches to investigate how SNVs might have damaging effects. METHODS: A comprehensive set of all known SNVs in the renin and angiotensinogen proteins was extracted from the HUMA database. This dataset was filtered by removing synonymous and missense variants and using the VAPOR pipeline to predict which variants were likely to be deleterious. Variants in the filtered dataset were modeled into the renin-angiotensinogen complex using MODELLER and subjected to molecular dynamics simulations using GROMACS. The residue interaction networks of the resultant trajectories were analyzed using graph theory. CONCLUSIONS: This research identified important SNVs in the interface of RAS and showed how they might affect the function of the proteins. For instance, the mutant complex containing the variant P40L in angiotensinogen caused instability in the complex, indicating that this mutation plays an important role in disrupting the interaction between renin and angiotensinogen. The mutant complex containing the SNV A188V in renin was shown to have significantly increased fluctuation in the residue interaction networks. D104N in renin, associated with renal tubular dysgenesis, caused increased rigidity in the protein complex comparison to the wild type, which probably in turn negatively affects the function of RAS.

Development of Bioinformatics Infrastructure for Genomics Research.

BACKGROUND: Although pockets of bioinformatics excellence have developed in Africa, generally, large-scale genomic data analysis has been limited by the availability of expertise and infrastructure. H3ABioNet, a pan-African bioinformatics network, was established to build capacity specifically to enable H3Africa (Human Heredity and Health in Africa) researchers to analyze their data in Africa. Since the inception of the H3Africa initiative, H3ABioNet's role has evolved in response to changing needs from the consortium and the African bioinformatics community. OBJECTIVES: H3ABioNet set out to develop core bioinformatics infrastructure and capacity for genomics research in various aspects of data collection, transfer, storage, and analysis. METHODS AND RESULTS: Various resources have been developed to address genomic data management and analysis needs of H3Africa researchers and other scientific communities on the continent. NetMap was developed and used to build an accurate picture of network performance within Africa and between Africa and the rest of the world, and Globus Online has been rolled out to facilitate data transfer. A participant recruitment database was developed to monitor participant enrollment, and data is being harmonized through the use of ontologies and controlled vocabularies. The standardized metadata will be integrated to provide a search facility for H3Africa data and biospecimens. Because H3Africa projects are generating large-scale genomic data, facilities for analysis and interpretation are critical. H3ABioNet is implementing several data analysis platforms that provide a large range of bioinformatics tools or workflows, such as Galaxy, the Job Management System, and eBiokits. A set of reproducible, portable, and cloud-scalable pipelines to support the multiple H3Africa data types are also being developed and dockerized to enable execution on multiple computing infrastructures. In addition, new tools have been developed for analysis of the uniquely divergent African data and for downstream interpretation of prioritized variants. To provide support for these and other bioinformatics queries, an online bioinformatics helpdesk backed by broad consortium expertise has been established. Further support is provided by means of various modes of bioinformatics training. CONCLUSIONS: For the past 4 years, the development of infrastructure support and human capacity through H3ABioNet, have significantly contributed to the establishment of African scientific networks, data analysis facilities, and training programs. Here, we describe the infrastructure and how it has affected genomics and bioinformatics research in Africa.

PRIMO: An Interactive Homology Modeling Pipeline.

The development of automated servers to predict the three-dimensional structure of proteins has seen much progress over the years. These servers make calculations simpler, but largely exclude users from the process. In this study, we present the PRotein Interactive MOdeling (PRIMO) pipeline for homology modeling of protein monomers. The pipeline eases the multi-step modeling process, and reduces the workload required by the user, while still allowing engagement from the user during every step. Default parameters are given for each step, which can either be modified or supplemented with additional external input. PRIMO has been designed for users of varying levels of experience with homology modeling. The pipeline incorporates a user-friendly interface that makes it easy to alter parameters used during modeling. During each stage of the modeling process, the site provides suggestions for novice users to improve the quality of their models. PRIMO provides functionality that allows users to also model ligands and ions in complex with their protein targets. Herein, we assess the accuracy of the fully automated capabilities of the server, including a comparative analysis of the available alignment programs, as well as of the refinement levels used during modeling. The tests presented here demonstrate the reliability of the PRIMO server when producing a large number of protein models. While PRIMO does focus on user involvement in the homology modeling process, the results indicate that in the presence of suitable templates, good quality models can be produced even without user intervention. This gives an idea of the base level accuracy of PRIMO, which users can improve upon by adjusting parameters in their modeling runs. The accuracy of PRIMO's automated scripts is being continuously evaluated by the CAMEO (Continuous Automated Model EvaluatiOn) project. The PRIMO site is free for non-commercial use and can be accessed at https://primo.rubi.ru.ac.za/.

JMS: An Open Source Workflow Management System and Web-Based Cluster Front-End for High Performance Computing.

Complex computational pipelines are becoming a staple of modern scientific research. Often these pipelines are resource intensive and require days of computing time. In such cases, it makes sense to run them over high performance computing (HPC) clusters where they can take advantage of the aggregated resources of many powerful computers. In addition to this, researchers often want to integrate their workflows into their own web servers. In these cases, software is needed to manage the submission of jobs from the web interface to the cluster and then return the results once the job has finished executing. We have developed the Job Management System (JMS), a workflow management system and web interface for high performance computing (HPC). JMS provides users with a user-friendly web interface for creating complex workflows with multiple stages. It integrates this workflow functionality with the resource manager, a tool that is used to control and manage batch jobs on HPC clusters. As such, JMS combines workflow management functionality with cluster administration functionality. In addition, JMS provides developer tools including a code editor and the ability to version tools and scripts. JMS can be used by researchers from any field to build and run complex computational pipelines and provides functionality to include these pipelines in external interfaces. JMS is currently being used to house a number of bioinformatics pipelines at the Research Unit in Bioinformatics (RUBi) at Rhodes University. JMS is an open-source project and is freely available at https://github.com/RUBi-ZA/JMS.

SANCDB: a South African natural compound database.

BACKGROUND: Natural products (NPs) are important to the drug discovery process. NP research efforts are expanding world-wide and South Africa is no exception to this. While freely-accessible small molecule databases, containing compounds isolated from indigenous sources, have been established in a number of other countries, there is currently no such online database in South Africa. DESCRIPTION: The current research presents a South African natural compound database, named SANCDB. This is a curated and fully-referenced database containing compound information for 600 natural products extracted directly from journal articles, book chapters and theses. There is a web interface to the database, which is simple and easy to use, while allowing for compounds to be searched by a number of different criteria. Being fully referenced, each compound page contains links to the original referenced work from which the information was obtained. Further, the website provides a submission pipeline, allowing researchers to deposit compounds from their own research into the database. CONCLUSIONS: SANCDB is currently the only web-based NP database in Africa. It aims to provide a useful resource for the in silico screening of South African NPs for drug discovery purposes. The database is supported by a submission pipeline to allow growth by entries from researchers. As such, we currently present SANCDB the starting point of a platform for a community-driven, curated database to further natural products research in South Africa. SANCDB is freely available at https://sancdb.rubi.ru.ac.za/.

Air and Bone Conduction Click and Tone-Burst Auditory Brainstem Thresholds Using Kalman Adaptive Processing in Nonsedated Normal-Hearing Infants.

OBJECTIVES: To study normative thresholds and latencies for click and tone-burst auditory brainstem response (TB-ABR) for air and bone conduction in normal infants and those discharged from neonatal intensive care units, who passed newborn hearing screening and follow-up distortion product otoacoustic emission. An evoked potential system (Vivosonic Integrity) that incorporates Bluetooth electrical isolation and Kalman-weighted adaptive processing to improve signal to noise ratios was employed for this study. Results were compared with other published data. DESIGN: One hundred forty-five infants who passed two-stage hearing screening with transient-evoked otoacoustic emission or automated auditory brainstem response were assessed with clicks at 70 dB nHL and threshold TB-ABR. Tone bursts at frequencies between 500 and 4000 Hz were used for air and bone conduction auditory brainstem response testing using a specified staircase threshold search to establish threshold levels and wave V peak latencies. RESULTS: Median air conduction hearing thresholds using TB-ABR ranged from 0 to 20 dB nHL, depending on stimulus frequency. Median bone conduction thresholds were 10 dB nHL across all frequencies, and median air-bone gaps were 0 dB across all frequencies. There was no significant threshold difference between left and right ears and no significant relationship between thresholds and hearing loss risk factors, ethnicity, or gender. Older age was related to decreased latency for air conduction. Compared with previous studies, mean air conduction thresholds were found at slightly lower (better) levels, while bone conduction levels were better at 2000 Hz and higher at 500 Hz. Latency values were longer at 500 Hz than previous studies using other instrumentation. Sleep state did not affect air or bone conduction thresholds. CONCLUSIONS: This study demonstrated slightly better wave V thresholds for air conduction than previous infant studies. The differences found in the present study, while statistically significant, were within the test step size of 10 dB. This suggests that threshold responses obtained using the Kalman weighting software were within the range of other published studies using traditional signal averaging, given step-size limitations. Thresholds were not adversely affected by variable sleep states.

Cast saw noise does not reach occupational hazard levels.

BACKGROUND: The purpose of our study was to measure the sound level generated by selected commercially available cast saws. These levels were then compared with the level of everyday sounds and to accepted intensities by Safety Administrations to see whether the mandatory use of hearing protection should be recommended to prevent noise-induced hearing loss. METHODS: We assessed the sound levels generated by the Quiet Cast Removal System (QCR; OrthoPediatrics Corp., Warsaw, IN), Stryker 986 Cast Vac (Stryker Corp.), and the Stryker 840 Cast Cutter (Stryker Corp.). The sound generated by these saws was measured with a sound level meter at the source and at 6, 12, and 36 inches. The sound level from each device was assessed both while operating alone and while cutting casts for a total of 3 repetitions at each of the distances tested and analyzed statistically. RESULTS: The maximal mean sound intensity of the Stryker 986 and Stryker 840 saws was 90.7 and 88.6 dBA at 36 inches, respectively while cutting a cast, whereas the QCR System produced 50.1 dBA at this distance. At 6 inches, the mean sound intensity was 99.4, 96.4, and 64.5 dBA for the Stryker 840, 986, and QCR, respectively. Statistically significant differences in sound intensity between Stryker and QCR saws were noted under all testing scenarios (P<0.0001). CONCLUSIONS: None of the cast saws produced intensities exceeding recommended standards for a single exposure or intensities reaching occupational hazard levels. The QCR saw was significantly quieter than both the Stryker 840 and 986 under all scenarios. The need for a recommendation of mandatory usage of hearing protection for patients and office personal could not be demonstrated. CLINICAL RELEVANCE: Cast saw noise is common in orthopaedic clinics. Our study demonstrates sound levels from commercially available saws do not reach occupational hazards but are sufficiently high that practical methods to reduce intensity may be warranted.

The North American Listening in Spatialized Noise-Sentences test (NA LiSN-S): normative data and test-retest reliability studies for adolescents and young adults.

BACKGROUND: The Listening in Spatialized Noise-Sentences test (LiSN-S; Cameron and Dillon, 2009) was originally developed to assess auditory stream segregation skills in children aged 6 to 11 yr with suspected central auditory processing disorder. The LiSN-S creates a three-dimensional auditory environment under headphones. A simple repetition-response protocol is used to assess a listener's speech reception threshold (SRT) for target sentences presented in competing speech maskers. Performance is measured as the improvement in SRT in dB gained when either pitch, spatial, or both pitch and spatial cues are incorporated in the maskers. A North American-accented version of the LiSN-S (NA LiSN-S) is available for use in the United States and Canada. PURPOSE: To develop normative data for adolescents and adults on the NA LiSN-S, to compare these data with those of children aged 6 to 11 yr as documented in Cameron et al (2009), and to consolidate the child, adolescent, and adult normative and retest data to allow the software to be used with a wider population. RESEARCH DESIGN: In a descriptive design, normative data and test-retest reliability data were collected. STUDY SAMPLE: One hundred and twenty normally hearing participants took part in the normative data study (67 adolescents aged 12 yr, 1 mo, to 17 yr, 10 mo, and 53 adults aged 19 yr, 10 mo, to 30 yr, 30 mo). Forty-nine participants returned between 1 and 4 mo after the initial assessment for retesting. Participants were recruited from sites in Cincinnati, Dallas, and Calgary. RESULTS: When combined with data collected from children aged 6 to 11 yr, a trend of improved performance as a function of increasing age was found across performance measures. ANOVA (analysis of variance) revealed a significant effect of age on performance. Planned contrasts revealed that there were no significant differences between adults and children aged 13 yr and older on the low-cue SRT; 14 yr and older on talker and spatial advantage; 15 yr and older on total advantage; and 16 yr and older on the high-cue SRT. Mean test-retest differences on the various NA LiSN-S performance measures for the combined child, adult, and adolescent data ranged from 0.05 to 0.5 dB. Paired comparisons revealed test-retest differences were not significant on any measure of the NA LiSN-S except low-cue SRT. Test-retest differences across measures did not differ as a function of age. Test and retest scores were significantly correlated for all NA LiSN-S measures. CONCLUSIONS: The ability to use either spatial or talker cues in isolation becomes adultlike by about 14 yr of age, whereas the ability to combine spatial and talker cues does not fully mature until closer to adulthood. By consolidating child, adolescent, and adult normative and retest data the NA LiSN-S can now been utilized to assess auditory processing skills in a wider population.

Power spectrum auditory brainstem response: novel approach to the evaluation of patients with unilateral auditory symptoms.

BACKGROUND: Unilateral hearing loss and audiovestibular symptoms are common in the population and can be associated with retrocochlear tumours such as acoustic neuroma (AN). In order to rule out AN, many patients with asymmetric hearing loss are referred for magnetic resonance imaging (MRI). Recent work with modifications of auditory brainstem response (ABR) protocols has improved the ability of ABR to detect small acoustic tumours. This study presents our initial results using the power spectrum ABR (PSABR) as another tool in detecting patients at higher risk for AN. METHODS: A prospective, observational cohort design was employed and a total of 53 subjects were recruited (19 subjects were normal controls and 34 subjects were patients with unilateral audiovestibular symptoms). All subjects underwent complete auditory testing, standard ABR, stacked ABR, and power spectrum ABR. The 34 patients also underwent gadolinium enhanced MRI. RESULTS: Using logistic regression, our data showed that wave I-V latency was most highly predictive of tumour presence or absence. However, both stacked ABR and power spectrum ABR were predictive. Stacked ABR was also able to differentiate symptomatic patients with tumours from those without. CONCLUSIONS: This study was not designed to compare PSABR to other more established methods. Rather, our intent was to establish PSABR as a valid and practical addition to other ABR tools. More research is needed to optimize PSABR algorithms, and the method also needs to be tested and validated in larger populations of patients. Early results do indicate that PSABR could be a valid and reliable method of identifying subgroups of patients with unilateral auditory dysfunction who would best benefit from MRI.

Macrophage inflammatory proteins in cytomegalovirus-related inner ear injury.

OBJECTIVE: Inner ear inflammation triggered by CMV infection may play a role in CMV-related auditory pathogenesis. The purpose of the study was to determine if a virally encoded macrophage inflammatory protein played a role in CMV-related hearing loss. DESIGN: Mutagenesis was performed with deletion of a guinea pig CMV macrophage inflammatory protein. Intracochlear inoculations were performed on three groups of animals (n = 18). Group 1 received sterile viral media, Group 2 received wild-type CMV virus, and Group 3 received "knockout" (KO) virus with a deleted immunomodulation gene. Baseline and postinoculation ABRs were obtained. ELISA and PCR were performed and temporal bones examined. SUBJECTS: Eighteen guinea pigs. RESULTS: The KO group had significantly better hearing than the WT group. There were no significant differences between the KO and sham groups. The WT group had significant hearing loss at all frequencies. Inflammation and fibrosis were noted in the WT temporal bones only. CONCLUSIONS: Virally encoded macrophage inflammatory proteins appear to play a significant role in CMV-related hearing loss.

The role of CMV inflammatory genes in hearing loss.

HYPOTHESIS: The purpose of this study is to test the hypothesis that virally encoded immunomodulatory genes play a role in cytomegalovirus (CMV)-related hearing loss. OBJECTIVE: Cytomegalovirus is the leading cause of infectious-related congenital sensorineural hearing loss worldwide. Unfortunately, little is known about the pathophysiology of CMV-related injury to the developing ear. METHODS: Viral mutagenesis techniques were developed that allow the deletion of a specific viral immunomodulatory gene, macrophage inflammatory protein (MIP) 1alpha homolog. We assessed the extent to which this gene product contributed to auditory pathologic findings in the guinea pig (GP) model. Eighteen weanling GPs (250-350 g) were used under an Institutional Animal Control and Use Committee-approved protocol. We analyzed preinoculation hearing using auditory brainstem response recordings. Intracochlear inoculations were performed on one group of six GPs with sterile viral media, 6 GPs with wild-type (WT) CMV virus, and 6 GPs with mutant "knockout" (KO) virus (with deleted MIP-1alpha homolog). Auditory brainstem responses were then obtained on postinoculation Days 7, 14, 21, and 28. RESULTS: There was a significant difference in hearing between the KO group and the WT group, with significantly better hearing in the KO group. A comparison of the KO group to the sham group revealed no significant hearing differences between the groups. The WT group had significant threshold shifts by dose at all frequencies meeting our criteria of hearing loss (>30 dB). There were no statistical differences in the sham or KO group. CONCLUSION: Virally encoded immunomodulatory genes such as MIP-1alpha seem to play a significant role in CMV-related hearing loss. This study is the first demonstration of the role of specific viral immune modulation genes in the in vivo pathogenesis of CMV-induced hearing loss in a relevant animal model.

Self-rated health among vulnerable older adults in rural Appalachia.

CONTEXT: Self-rated health (SRH) predicts service use, morbidity, and mortality. Additionally, SRH has been associated with indices of psychological well-being. PURPOSE: The main focus of the study was to investigate important differences among the lower spectrum of SRH (ie, fair and poor) on indices of well-being. METHODS: In-person interviews collected data from 207 (M age = 75.8) older rural adults. Data were used to examine differences between those reporting poor, fair, and good or excellent SRH on measures of demographics, and physical and psychological health. RESULTS: Significant differences emerged between levels of SRH in relation to measures of physical and psychological health. Specifically, individuals with poor SRH were significantly more likely to have (1) illnesses, (2) problems with basic and cognitive tasks of daily living, and (3) depressed affect than individuals reporting good or excellent health. Individuals with poor SRH were significantly more likely to have problems with basic and cognitive tasks of daily living than individuals with fair SRH. No significant differences were found between people reporting fair and good or excellent SRH on illnesses and depressed affect. CONCLUSIONS: Results suggest that future research should investigate the expansion of the lower-end of the SRH measure to more accurately assess SRH among vulnerable, rural older adults. Such efforts would better inform health care providers, practitioners, and policy makers in rural areas as to how SRH affects the well-being of vulnerable older adults.