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Brody C.M.,Touro University California | Brody C.M.,University of California at Berkeley | Bellows N.,Independent Consultant | Campbell M.,Venture Strategies for Health and Development | Potts M.,University of California at Berkeley
Global Public Health | Year: 2013

One approach to delivering healthcare in developing countries is through voucher programmes, where vouchers are distributed to a targeted population for free or subsidised health care. Using inclusion/exclusion criteria, a search of databases, key journals and websites review was conducted in October 2010. A narrative synthesis approach was taken to summarise and analyse five outcome categories: targeting, utilisation, cost efficiency, quality and health outcomes. Sub-group and sensitivity analyses were also performed. A total of 24 studies evaluating 16 health voucher programmes were identified. The findings from 64 outcome variables indicates: modest evidence that vouchers effectively target specific populations; insufficient evidence to determine whether vouchers deliver healthcare efficiently; robust evidence that vouchers increase utilisation; modest evidence that vouchers improve quality; no evidence that vouchers have an impact on health outcomes; however, this last conclusion was found to be unstable in a sensitivity analysis. The results in the areas of targeting, utilisation and quality indicate that vouchers have a positive effect on health service delivery. The subsequent link that they improve health was found to be unstable from the data analysed; another finding of a positive effect would result in robust evidence. Vouchers are still new and the number of published studies is limiting. © 2013 Copyright Taylor and Francis Group, LLC.

Holden P.M.,State University of New York at Stony Brook | Allen W.J.,State University of New York at Stony Brook | Gochin M.,Touro University California | Gochin M.,University of California at San Francisco | Rizzo R.C.,State University of New York at Stony Brook
Bioorganic and Medicinal Chemistry | Year: 2014

A highly-conserved binding pocket on HIVgp41 is an important target for development of anti-viral inhibitors. Holden et al. (Bioorg. Med. Chem. Lett. 2012, 22, 3011) recently reported 7 experimentally-verified leads identified through a computational screen to the gp41 pocket in conjunction with a new DOCK scoring method (termed FPS scoring) developed in our laboratory. The method employs molecular footprints based on per-residue van der Waals interactions, electrostatic interactions, or the sum. In this work, we critically examine the gp41 screening results, prioritized using different scoring methods, in terms of two main criteria: (1) ligand pose properties which include footprint and energy score decompositions, MW, number of rotatable bonds, ligand efficiency, formal charge, and volume overlap, and (2) ligand pose stability which includes footprint stability (changes in footprint overlap) and rmsd stability (changes in geometry). Relative to standard DOCK scoring, pose property analyses demonstrate how FPS scoring can be used to identify ligands that mimic a known reference (derived here from the native gp41 substrate), while pose stability analyses demonstrate how FPS scoring can be used to enrich for compounds with greater overall stability during molecular dynamics (MD) simulations. Compellingly, of the 115 compounds tested experimentally, the 7 active compounds, as a group, more closely mimic the footprints made by the reference and show greater MD stability compared to the inactive group. Extensive studies using 116 protein-ligand complexes as controls reveal that ligands in their crystallographic binding pose also maintain higher FPS scores and smaller rmsds than do accompanying decoys, confirming that native poses are indeed 'stable' under the same conditions and that monitoring FPS variability during compound prioritization is likely to be beneficial. Overall, the results suggest the new scoring method will complement current virtual screening approaches for both the identification (FPS-ranking) and prioritization (FPS-stability) of target-compatible molecules in a quantitative and logical way. © 2013 Published by Elsevier Ltd. All rights reserved.

Kemnade J.O.,Baylor College of Medicine | Seethammagari M.,Baylor College of Medicine | Collinson-Pautz M.,Baylor College of Medicine | Kaur H.,Touro University California | And 2 more authors.
Vaccine | Year: 2014

Over the past 20 years, dendritic cells (DCs) have been utilized to activate immune responses capable of eliminating cancer cells. Currently, ex vivo DC priming has been the mainstay of DC cancer immunotherapies. However, cell-based treatment modalities are inherently flawed due to a lack of standardization, specialized facilities and personnel, and cost. Therefore, direct modes of DC manipulation, circumventing the need for ex vivo culture, must be investigated. To facilitate the development of next-generation, in vivo targeted DC vaccines, we characterized the DC interaction and activation potential of the Tobacco Mosaic virus (TMV), a plant virus that enjoys a relative ease of production and the ability to deliver protein payloads via surface conjugation. In this study we show that TMV is readily taken up by mouse bone marrow-derived DCs, in vitro. Footpad injection of fluorophore-labeled TMV reveals preferential uptake by draining lymph node resident DCs in vivo. Uptake leads to activation, as measured by the upregulation of key DC surface markers. When peptide antigen-conjugated TMV is injected into the footpad of mice, DC-mediated uptake and activation leads to robust antigen-specific CD8+ T cell responses, as measured by antigen-specific tetramer analysis. Remarkably, TMV priming induced a greater magnitude T cell response than Adenovirus (Ad) priming. Finally, TMV is capable of boosting either Ad-induced or TMV-induced antigen-specific T cell responses, demonstrating that TMV, uniquely, does not induce neutralizing self-immunity. Overall, this study elucidates the in vivo DC delivery and activation properties of TMV and indicates its potential as a vaccine vector in stand alone or prime-boost strategies. © 2014 Elsevier Ltd.

Cai L.,Beijing Institute of Pharmacology and Toxicology | Cai L.,Touro University California | Gochin M.,Touro University California | Gochin M.,University of California at San Francisco | Liu K.,Beijing Institute of Pharmacology and Toxicology
Chemical Communications | Year: 2011

Liquid surface curvature variations in microplate wells due to different liquid surface tension cause significant signal change in spectroscopic measurement using a plate reader with a vertical detecting light beam. The signals have been quantitated and used to develop a method for facile surfactant critical micelle concentration determination. © 2011 The Royal Society of Chemistry.

Zhou G.,Touro University California | Wu D.,Touro University California | Snyder B.,Southern Research Institute | Ptak R.G.,Southern Research Institute | And 3 more authors.
Journal of Medicinal Chemistry | Year: 2011

Nonpeptide inhibition of fusion remains an important goal in anti-HIV research, due to its potential for low cost prophylaxis or prevention of cell-cell transmission of the virus. We report here on a series of indole compounds that have been identified as fusion inhibitors of gp41 through a structure-based drug design approach. Experimental binding affinities of the compounds for the hydrophobic pocket were strongly correlated to fusion inhibitory data (R 2 = 0.91), and corresponding inhibition of viral replication confirmed the hydrophobic pocket as a valid target for low molecular weight fusion inhibitors. The most active compound bound to the hydrophobic pocket and inhibited cell-cell fusion and viral replication at submicromolar levels. A common binding mode for the inhibitors in this series was established by carrying out docking studies using structures of gp41 in the Protein Data Bank. The molecules were flexible enough to conform to the contours of the pocket, and the most active compound was able to adopt a structure mimicking the hydrophobic contacts of the D-peptide PIE7. The results enhance our understanding of indole compounds as inhibitors of gp41. © 2011 American Chemical Society.

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