Adaptation to family-based treatment for Medicaid-insured youth with anorexia nervosa in publicly-funded settings: Protocol for a mixed methods implementation scale-out pilot study.

BACKGROUND: Family-based treatment (FBT) for anorexia nervosa is an evidence-based treatment, but its effectiveness is untested among socioeconomically disadvantaged and racially diverse youth. Adapting FBT may facilitate "scale-out" for Medicaid-insured youth served in publicly-funded settings and potentially improve outcomes for more diverse populations. METHODS: This mixed methods effectiveness-implementation Hybrid Type 3 pilot study protocol included a planning period in collaboration with the San Francisco Department of Public Health, culminating in a two-day in-person FBT training for 25 therapists in the county, followed by the opportunity to engage in one year of weekly supervision. The training incorporated FBT adaptations intended to improve fit for low-income families within community-based settings. Treatment appropriateness and acceptability will be measured immediately post-training. Following the training, cases referred for FBT will only be assigned to the trained clinicians who voluntarily opted into long-term group supervision. Clinicians treating at least one FBT case during the supervision period will report on implementation, adaptations, and patient weight gain. Finally, semi-structured interviews with clinician participants will be conducted, focused on implementation challenges and facilitators, local treatment adaptations, and overall satisfaction with FBT. DISCUSSION: Learning about clinician adaptations will advance knowledge about treatment of eating disorders in publicly-funded community clinics, which serve a racially/ethnically and socioeconomically diverse group of youth. This project is designed to accelerate FBT implementation in publicly-funded mental health systems, and inform service improvements for underserved youth with eating disorders.

Internet Use and Adolescent Binge Drinking: Findings from the Monitoring the Future Study.

OBJECTIVE: To investigate the relation between Internet use and binge drinking during early and middle adolescence. METHODS: This is a cross-sectional study of a sub-sample of 8th and 10th graders from the Monitoring the Future (MtF) study, which annually surveys a nationally representative sample of U.S. youth on their attitudes, behaviors, and values. This study includes data from 21,170 8th and 24,362 10th graders who participated between 2007 and 2012 and were asked questions about Internet use and binge drinking. RESULTS: In fully adjusted models, we found a dose response relation between hours of recreational Internet use (i.e. outside work or school) and binge drinking which was stronger for 8th than 10th graders. Compared to <1 h of Internet use per week, odds ratios estimates for 1-5 h/week, 6-19 h/week, and 20 or more h/week were 1.24 (99% CI: 0.85, 1.82), 1.83 (1.28, 2.61), and 2.78 (1.99, 3.87) for 8th graders, respectively. For 10th graders, this same association was attenuated [estimated OR=1.06 (99% CI: 0.96, 1.16); 1.20 (1.03, 1.40); and 1.30 (1.07, 1.58), respectively]. CONCLUSIONS: Drawing on a nationally representative sample of U.S. youth, we find a significant, dose-response relation between Internet use and binge drinking. This relation was stronger in 8th graders versus 10th graders. Given that alcohol is the most abused substance among adolescents and binge drinking confers many health risks, longitudinal studies designed to examine the mediators of this relation are necessary to inform binge drinking prevention strategies, which may have greater impact if targeted at younger adolescents.

Release and elementary mechanisms of nitric oxide in hair cells.

The enzyme nitric oxide (NO) synthase, that produces the signaling molecule NO, has been identified in several cell types in the inner ear. However, it is unclear whether a measurable quantity of NO is released in the inner ear to confer specific functions. Indeed, the functional significance of NO and the elementary cellular mechanism thereof are most uncertain. Here, we demonstrate that the sensory epithelia of the frog saccule release NO and explore its release mechanisms by using self-referencing NO-selective electrodes. Additionally, we investigated the functional effects of NO on electrical properties of hair cells and determined their underlying cellular mechanism. We show detectable amounts of NO are released by hair cells (>50 nM). Furthermore, a hair-cell efferent modulator acetylcholine produces at least a threefold increase in NO release. NO not only attenuated the baseline membrane oscillations but it also increased the magnitude of current required to generate the characteristic membrane potential oscillations. This resulted in a rightward shift in the frequency-current relationship and altered the excitability of hair cells. Our data suggest that these effects ensue because NO reduces whole cell Ca(2+) current and drastically decreases the open probability of single-channel events of the L-type and non L-type Ca(2+) channels in hair cells, an effect that is mediated through direct nitrosylation of the channel and activation of protein kinase G. Finally, NO increases the magnitude of Ca(2+)-activated K(+) currents via direct NO nitrosylation. We conclude that NO-mediated inhibition serves as a component of efferent nerve modulation of hair cells.

Molecular identity and functional properties of a novel T-type Ca2+ channel cloned from the sensory epithelia of the mouse inner ear.

The molecular identity of non-Cav1.3 channels in auditory and vestibular hair cells has remained obscure, yet the evidence in support of their roles to promote diverse Ca2+-dependent functions is indisputable. Recently, a transient Cav3.1 current that serves as a functional signature for the development and regeneration of hair cells has been identified in the chicken basilar papilla. The Cav3.1 current promotes spontaneous activity of the developing hair cell, which may be essential for synapse formation. Here, we have isolated and sequenced the full-length complementary DNA of a distinct isoform of Cav3.1 in the mouse inner ear. The channel is derived from alternative splicing of exon14, exon25A, exon34, and exon35. Functional expression of the channel in Xenopus oocytes yielded Ca2+ currents, which have a permeation phenotype consistent with T-type channels. However, unlike most multiion channels, the T-type channel does not exhibit the anomalous mole fraction effect, possibly reflecting comparable permeation properties of divalent cations. The Cav3.1 channel was expressed in sensory and nonsensory epithelia of the inner ear. Moreover, there are profound changes in the expression levels during development. The differential expression of the channel during development and the pharmacology of the inner ear Cav3.1 channel may have contributed to the difficulties associated with identification of the non-Cav1.3 currents.

Expression and functional phenotype of mouse ERG K+ channels in the inner ear: potential role in K+ regulation in the inner ear.

An outcome of the intricate K+ regulation in the cochlear duct is the endocochlear potential (EP), approximately 80 mV, the "battery" that runs hair-cell transduction; however, the detailed molecular mechanisms for the generation of the EP remain unclear. We provide strong evidence indicating that the intermediate cells (ICs) of the stria vascularis (StV) express outward K+ current that rectifies inwardly at positive potentials. The channel belongs to the ether-a-go-go-related gene (erg) family of K+ channels. We cloned an ERG1a channel in the mouse inner ear (MERG1a). The cellular distribution of MERG1a in the cochlea displayed the highest levels of immunoreactivity in the ICs and modest reactivity in the marginal cells as well as in several extrastrial cells (e.g., hair cells). Functional expression of the StV-specific MERG1a channel reveals a current that activates at relatively negative potentials (approximately-50 mV) and shows rapid inactivation reflected as inward rectification at depolarized potentials. The current was sensitive to the methanesulfonanilide drug E-4031 (IC50, approximately 165 nM) and the recombinant peptide rBeKm-1 (IC50, approximately 16 nM), and the single-channel conductance in symmetrical K+ was approximately 14 pS. The site of expression of MERG1a and its functional phenotype (e.g., modulation of the current by external K+ make it one of the most likely candidates for establishing the high throughput of K+ ions across ICs to generate EP. In addition, the property of the channel that produces marked K+ extrusion in increased external K+ may be important in shaping the dynamics of K+ cycling in the inner ear.