Ratiometric Zinc Biosensor Based on Bioluminescence Resonance Energy Transfer: Trace Metal Ion Determination with Tunable Response.

Determination of metal ions such as zinc in solution remains an important task in analytical and biological chemistry. We describe a novel zinc ion biosensing approach using a carbonic anhydrase-Oplophorus luciferase fusion protein that employs bioluminescence resonance energy transfer (BRET) to transduce the level of free zinc as a ratio of emission intensities in the blue and orange portions of the spectrum. In addition to high sensitivity (below nanomolar levels) and selectivity, this approach allows both quantitative determination of "free" zinc ion (also termed "mobile" or "labile") using bioluminescence ratios and determination of the presence of the ion above a threshold simply by the change in color of bioluminescence, without an instrument. The carbonic anhydrase metal ion sensing platform offers well-established flexibility in sensitivity, selectivity, and response kinetics. Finally, bioluminescence labeling has proven an effective approach for molecular imaging in vivo since no exciting light is required; the expressible nature of this sensor offers the prospect of imaging zinc fluxes in vivo.

Transtheoretical model intervention for adherence to lipid-lowering drugs.

An estimated 60% of individuals prescribed lipid-lowering medications are nonadherent. Failure to adhere increases morbidity, mortality, healthcare utilization, and healthcare costs. This study examined the effectiveness of a population-based, individualized Transtheoretical Model (TTM) expert system intervention to improve adherence and increase exercise and diet in a randomized 18-month trial involving 404 adults. Compared to usual care, treatment participants who started in a pre-action stage were significantly more likely to be in the Action and Maintenance (A/M) stages for adherence at end of treatment (55.3% versus 40%, z = 2.11, p < 0.05, h = 0.31) and at 18-months (56% versus 37.8%, z = 2.38, p < 0.01, h = 0.36). The treatment group scored significantly better on two measures of adherence at six and 12 months post-treatment (all p < 0.05, odds ratios [OR] 1.49-3.67). Among those who began in A/M, treatment participants were significantly more likely to remain in A/M at 18 months (85.2% versus 55.6%, z = 2.63, p < 0.01, h = 0.67). Those receiving treatment were significantly more likely to progress to A/M for exercise and dietary fat reduction (43.3% versus 24.7% for exercise, and 24.7% versus 12.5% for diet). TTM expert system interventions can have a significant impact on entire populations for adherence. Results for dietary fat and exercise suggest covariation of treatment effects.

Effectiveness of cognitive--behavioral treatment for panic disorder versus treatment as usual in a managed care setting.

Eighty clients enrolled in a managed care health plan who identified panic disorder as their primary presenting problem were randomly assigned to treatment by a therapist recently trained in a manual-based empirically supported psychotherapy or a therapist conducting treatment as usual (TAU). Participants in both conditions showed significant change from pre- to posttreatment on a number of measures. Those receiving panic control therapy (PCT) showed greater levels of change than those receiving TAU. Among treatment completers, an average of 42.9% of those in PCT and 18.8% in TAU achieved clinically significant change across measures. The results are discussed with reference to the dissemination of PCT and other evidence-based psychotherapies to clinical practice settings.