Faculty Bibliography

Accurate assessment of neonatal hearing screening performance is impossible without knowledge of the true status of hearing, a prohibitive requirement that necessitates a complete diagnostic evaluation on all babies screened. The purpose of this study was to circumvent this limitation by integrating two types of screening measures obtained near simultaneously on every baby. Peripheral auditory function was defined by otoacoustic emission results. A complete diagnostic evaluation was performed on every baby who received a "Refer" outcome for auditory brainstem response screening. The integrated results for auditory brainstem response screening in an unselected group of 300 newborns estimated sensitivity at 100%, specificity at 99.7%, overall referral rate at 2.0%, and a positive predictive value of 83.3%. Conductive loss associated with amniotic fluid in the middle ear can persist several weeks after birth; conductive loss can produce a "Refer" outcome for auditory brainstem response screening; and auditory neuropathy can be detected with screening measures. Prevalence results were consistent with the published literature. The implications of this study are that otoacoustic emissions and auditory brainstem measures provide much more information than either alone and that both are needed for a comprehensive hearing screening program.

Molecular methodologies have become useful techniques for the identification of pathogenic Nocardia species and for the recognition of novel species that are capable of causing human disease. Two isolates recovered from immunocompromised patients were characterized as Nocardia nova by biochemical and susceptibility testing results. The restriction fragment length polymorphism (RFLP) patterns obtained by restriction endonuclease analysis (REA) of an amplified portion of the heat shock protein gene were identical to those obtained with the type strain of N. nova. REA of an amplified portion of the 16S rRNA gene showed RFLP patterns that were unlike those obtained for the type strain of N. nova but that were similar to those obtained for the type strains of N. africana and N. veterana. Subsequent sequencing of a portion of the 16S rRNA gene produced identical results for the two patient isolates. Sequence analysis of 1,352-bp portions of the 16S rRNA gene indicated that these isolates were 99.8% similar to the recently described species N. veterana but were only 99.3, 98.1, and 98.1% similar to the type strains of N. africana, N. nova, and N. vaccinii, respectively. DNA-DNA hybridization studies confirmed that the two patient isolates belonged to the same species but were not closely related to N. africana, N. nova, N. vaccinii, or N. veterana. The patient isolates have been designated N. kruczakiae sp. nov. Because N. africana, N. veterana, and the new species are not readily differentiated from N. nova by phenotypic methods alone, the designation "N. nova complex" can be used to designate isolates such as these that phenotypically resemble N. nova but that have not been definitively characterized by 16S rRNA gene sequencing or DNA-DNA hybridization.

The inhibitory neurons of the thalamic reticular nucleus (TRN) contribute to the generation of widespread oscillations in the thalamocortical system. Some TRN neurons are interconnected by electrical synapses, and here we tested the possibility that electrical synapses mediate rhythmic synchrony in juvenile rats. Both the incidence and strength of electrical coupling between pairs of TRN neurons were a steep function of intersomatic distance, and coupling was absent at distances >40 microm. Presynaptic spike bursts evoked much larger electrical postsynaptic potentials than did single presynaptic spikes. Activation of metabotropic glutamate receptors (mGluRs) with a bath-applied agonist or an endogenous ligand released during tetanic stimulation induced robust rhythms of the subthreshold membrane potential, with a mean frequency of approximately 10 Hz. In the absence of fast chemical synaptic transmission, subthreshold rhythms and the action potentials that they evoked were well synchronized between closely spaced, electrically coupled pairs; rhythms in noncoupled cells were not synchronized. The results suggest that electrical synapses can coordinate spindle-frequency rhythms among small clusters of mGluR-activated TRN cells.

Many neurons in the mammalian central nervous system communicate through electrical synapses, defined here as gap junction-mediated connections. Electrical synapses are reciprocal pathways for ionic current and small organic molecules. They are often strong enough to mediate close synchronization of subthreshold and spiking activity among clusters of neurons. The most thoroughly studied electrical synapses occur between excitatory projection neurons of the inferior olivary nucleus and between inhibitory interneurons of the neocortex, hippocampus, and thalamus. All these synapses require the gap junction protein connexin36 (Cx36) for robust electrical coupling. Cx36 appears to interconnect neurons exclusively, and it is expressed widely along the mammalian neuraxis, implying that there are undiscovered electrical synapses throughout the central nervous system. Some central neurons may be electrically coupled by other connexin types or by pannexins, a newly described family of gap junction proteins. Electrical synapses are a ubiquitous yet underappreciated feature of neural circuits in the mammalian brain.

Interaction between an electronic and a biological circuit has been investigated for a pair of electrically connected nonlinear oscillators, with a spontaneously oscillating olivary neuron as the single-cell biological element. By varying the coupling strength between the oscillators, we observe a range of behaviors predicted by model calculations, including a reversible low-energy dissipation "amplitude death" where the oscillations in the coupled system cease entirely.