The C57BL/6J (B6) mouse strain carries a cadherin23 mutation (Cdh23753A, also known as Ahl), which affects inner ear structures and results in age-related hearing loss. The B6.CAST strain harbors the wild type Cdh23 gene and hence the influence of Ahl is absent. The purpose of the present study was to characterize the effect of age and gender on gravity receptor function in B6 and B6.CAST strains and to compare functional aging between auditory and vestibular modalities. Auditory sensitivity declined at significantly faster rates than gravity receptor sensitivity for both strains. Indeed, vestibular functional aging was minimal for both strains. The comparatively smaller loss of macular versus cochlear sensitivity in both the B6 and B6.CAST strains suggests that the contribution of Ahl to the aging of the vestibular system is minimal, and thus very different than its influence on aging of the auditory system. Alternatively, there exist unidentified genes or gene modifiers that serve to slow the degeneration of gravity receptor structures and maintain gravity receptor sensitivity into advanced age.

A/J mice develop progressive hearing loss that begins before one month of age and is attributed to cochlear hair cell degeneration. Screening tests indicated this strain also develops early onset vestibular dysfunction and has otoconial deficits. The purpose of this study was to characterize the vestibular dysfunction and macular structural pathology over the lifespan of A/J mice. Vestibular function was measured using linear vestibular evoked potentials (VsEPs). Macular structural pathology was evaluated using light microscopy, SEM, TEM, confocal microscopy and Western blotting. Individually, vestibular functional deficits in mice ranged from mild to profound. On average, A/J mice had significantly reduced vestibular sensitivity (elevated VsEP response thresholds and smaller amplitudes), whereas VsEP onset latency was prolonged compared to age-matched controls (C57BL/6J). A limited age-related vestibular functional loss was also present. Structural analysis identified marked age-independent otoconial abnormalities in concert with some stereociliary bundle defects. Macular epithelia were incompletely covered by otoconial membranes with significantly reduced opacity and often contained abnormally large or giant otoconia as well as normal appearing otoconia. Elevated expression of key otoconins [i.e., otoconin 90, otolin and keratin sulfate proteoglycan] ruled out the possibility of reduced levels contributing to otoconial dysgenesis. The phenotype of A/J was partially replicated in a consomic mouse strain (C57BL/6J-Chr 17A/J/NaJ), thus indicating that Chr 17A/J contained a trait locus for a new gene variant responsible to some extent for the A/J vestibular phenotype. Quantitative trait locus analysis identified additional epistatic influences associated with chromosomes 1, 4, 9 and X. Results indicate that the A/J phenotype represents a complex trait and the A/J mouse strain presents a new model for the study of mechanisms underlying otoconial formation and maintenance.

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Participation in syringe exchange programs (SEPs) is associated with many individual and public health benefits, but may have little impact on reducing drug use without concurrent treatment engagement. The present study evaluated rates of drug use, other risk behaviors, and illegal activities in newly registered SEP participants (n = 240) enrolled versus not enrolled in substance abuse treatment over a 4-month observation window, and examined the effect of days in treatment on these outcomes. After controlling for baseline differences, SEP registrants enrolled in treatment (n = 113) reported less days of opioid and cocaine use, injection drug use, illegal activities, and incarceration than those not enrolled in treatment (n=127). For those enrolled in treatment, days of treatment was strongly correlated with each of these outcomes. These findings provide good evidence for a dose-response effect of treatment in syringe exchangers, and suggest that substance abuse treatment significantly expands the harm reduction benefits of SEP participation.Keywords syringe exchange; substance abuse treatment; injection drug use; HIV risk behaviors; harm reduction I.0 IntroductionCommunity syringe exchange programs (SEPs) are consistently associated with reduced rates of injection equipment sharing and reduced rates of HIV infection (e.g., Bluthenthal, Kral, Gee, Erringer, & Edlin, 2000;Des Jarlais et al., 1996;Des Jarlais, McKnight, Goldblatt, & Purchase, 2009;Gibson et al., 2002;Huo & Ouellet, 2007; see Wodak & Cooney, 2006 for a review). The fact that syringe exchange participation does not fully suppress the sharing of injection equipment is most likely related to the high rates of continuing drug injection in this subgroup of substance users (e.g., Des Jarlais, Braine, Yi, & Turner, 2007;Fisher, Fenaughty, Cagle, & Wells, 2003;Wood et al., 2002). Interventions that fully suppress drug injection would clearly enhance the harm reduction benefits of syringe exchanges. A recent study by Van Den Berg, Smit, Van Brussel, Coutinho, & Prins (2007) reached this conclusion in a study of 714 injection drug users in Amsterdam. Subjects in that study that concurrently participated in syringe exchange and substance Phone for First Author: Phone: (410) 550-0006, Fax: (410) 550-2957, mkidorf@jhmi.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. While several studies have reported on promising strategies to bridge syringe exchange and substance abuse treatment participation (Kidorf et al., 2009;Kuo et al., 2003;Strathdee et al., 2006), little is known about the responsiveness of syringe...

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