Publications

The present study provides an implementation fidelity, process, and immediate outcomes evaluation of Project Towards No Drug Abuse (TND), a drug prevention program targeting continuation high school youth (n=1426) at risk for drug abuse. A total of 24 schools participated in three randomized conditions: TND Only, TND and motivational interviewing follow-up, and no treatment control. Fidelity was high: across program schools the curriculum was implemented as intended and was received favorably by students. Relative to controls, intervention conditions produced effects on hypothesized mediators, including greater gains in program related knowledge, greater reductions in drug use intentions, and positive changes in motivation. However, few generalizations to attitudes and intentions regarding risky sexual behavior were found. The pattern of results suggests that the experimental manipulations worked as intended.

In 2008, diagnosis and investigation of 2 multidrug-resistant tuberculosis cases with matching genotypes led to identification of an outbreak among foreign-born persons who performed short-term seafood production work in Alaska during 2006. Tuberculosis control programs should consider the possibility of domestic transmission even among foreign-born patients.

BACKGROUND AND PURPOSE

Intracellular pharmacokinetics of anticancer drugs in multi-drug resistance (MDR) cancer cells is hugely important in the evaluation and improvement of drug efficacy. By using adriamycin as a probe drug in MDR cancer cells, we developed a cellular pharmacokinetic-pharmacodynamic (PK-PD) model to reveal the correlation between cellular pharmacokinetic properties and drug resistance. In addition, the ability of 20(S)-ginsenoside Rh2 (20(S)-Rh2) to reverse MDR was further investigated.

EXPERIMENTAL APPROACH

The cellular pharmacokinetics of adriamycin were analysed visually and quantitatively in human breast cancer cells MCF-7 and in adriamycin-resistant MCF-7 (MCF-7/Adr) cells. Mitochondria membrane potential was assayed to evaluate the apoptotic effect of adriamycin. Subsequently, a PK-PD model was developed via MATLAB.

KEY RESULTS

Visual and quantitative data of the dynamic subcellular distribution of adriamycin revealed that it accumulated in cells, especially nuclei, to a lesser and slower extent in MCF-7/Adr than in MCF-7 cells. 20(S)-Rh2 increased the rate and amount of adriamycin entering cellular/subcellular compartments in MCF-7/Adr cells through inhibition of P-glycoprotein (P-gp) activity, in turn augmenting adriamycin-induced apoptosis. The integrated PK-PD model mathematically revealed the pharmacokinetic mechanisms of adriamycin resistance in MCF-7/Adr cells and its reversal by 20(S)-Rh2.

CONCLUSIONS AND IMPLICATIONS

P-gp, which is overexpressed and functionally active at cellular/subcellular membranes, influences the cellular pharmacokinetic and pharmacological properties of adriamycin in MCF-7/Adr cells. Inhibition of P-gp activity represents a key mechanism by which 20(S)-Rh2 attenuates adriamycin resistance. Even more importantly, our findings provide a new strategy to explore the in-depth mechanisms of MDR and evaluate the efficacy of MDR modulators.

The development of HIV-1 integrase strand transfer inhibitors (INSTIs) has been a major therapeutic breakthrough in the management of HIV-1 infection. The first HIV-1 integrase inhibitor, raltegravir, was licensed in 2007 and was subsequently approved for use in treatment-naive patients. Since then, newer members of the INSTI class have been developed, including elvitegravir (EVG), which is in advanced clinical development and is being developed for use in both treatment-naive and treatment-experienced patients. EVG utilizes pharmacokinetic boosting to achieve adequate serum levels with once-daily dosing. Boosting agents with which it is being studied include ritonavir and cobicistat. In addition, EVG is being studied as a once-daily INSTI in a coformulated fixed-dose combination pill with the agents tenofovir disoproxil fumarate, emtricitabine and cobicistat (QUAD pill), which has the additional potential benefit of convenient once-daily dosing. The in vitro activity, pharmacokinetic and pharmacodynamic properties, results of Phase I-III clinical trials, resistance profile and drug-drug interactions of EVG will be reviewed in this article.

BACKGROUND

Global health education (GHE) at undergraduate medical institutions has expanded significantly over the last 30 years, but many questions remain regarding the best practices for the development and implementation of global health programs.

AIM

To identify key themes essential to the development of GHE programs.

METHOD

We discuss five themes relevant to GHE in the context of existing literature and practice.

RESULTS

The following themes are essential to the development of GHE programs: the definition and scope of GHE, student competencies in global health, the challenges and opportunities associated with inter-institutional relationships, principles for GHE student placements, and the evaluation of GHE programs. We place these themes in the context of current literature and practice, and provide practical guidance on how these themes might be successfully implemented by institutions seeking to develop or refine GHE programs.

CONCLUSIONS

Institutions developing or evaluating GHE programs should focus on these themes as they build their global health curricula.