Background: Uganda's national community health worker program involves volunteer Village Health Teams (VHTs) delivering basic health services and education. Evidence demonstrates their positive impact on health outcomes, particularly for Ugandans who would otherwise lack access to health services. Despite their impact, VHTs are not optimally supported and attrition is a growing problem.
View Article and Find Full Text PDFHospital-acquired infections pose both a major risk to patient wellbeing and an economic burden on global healthcare systems, with the problem compounded by the emergence of multidrug resistant and biocide tolerant bacterial pathogens. Many inanimate surfaces can act as a reservoir for infection, and adequate disinfection is difficult to achieve and requires direct intervention. In this study we demonstrate the preparation and performance of materials with inherent photodynamic, surface-active, persistent antimicrobial properties through the incorporation of photosensitizers into high density poly(ethylene) (HDPE) using hot-melt extrusion, which require no external intervention except a source of visible light.
View Article and Find Full Text PDFA series of four related phenol derivatives, with 2,2'-dipicolylamine substituents at the ortho positions, were prepared and their Zn coordination complexes studied by spectroscopic methods. X-ray crystal diffraction analysis of a dinuclear zinc complex with two bridging acetate anions showed a ternary structure with highly charged interior and lipophilic exterior, which helps explain why this class of water-soluble complexes can effectively diffuse through cell membranes. The stability of the dinuclear zinc complexes in aqueous solution was found to be strongly anion dependent; that is, bridging oxyanions, such as acetate and pyrophosphate, lock the two Zn cations to the surrounding ligand and greatly enhance ligand/zinc affinity.
View Article and Find Full Text PDFA series of fluorescent phosphatidylserine and phosphatidylcholine derivatives were prepared and evaluated by cell microscopy for ability to translocate across mammalian plasma membranes via the putative aminophospholipid flippase. Phosphatidylserine derivatives, with either a neutral 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) or a coumarin fluorophore appended to the 2-acyl chain, entered the cytosol of all three cell lines tested and control experiments showed that the translocation was due to flippase activity. In contrast, a phosphatidylserine conjugate containing a charged and polar carboxyfluorescein was not translocated and remained in the cell plasma membrane.
View Article and Find Full Text PDFA new type of synthetic membrane transporter is described and shown to operate in vesicles by a relay mechanism. The transporter structure is a phosphatidylcholine derivative with a urea group appended to the end of its sn-2 acyl chain. The urea can bind a chloride ion at the membrane surface via hydrogen bonds and then relay it through the bilayer interior to an acceptor molecule located in the opposite membrane leaflet.
View Article and Find Full Text PDFThe syntheses of phosphatidylserine (PS) conjugates are described, including fluorescent derivatives for potential cellular delivery and bioimaging applications. Installation of terminal functional groups (amine, thiol, or alkyne) onto the sn-2 chain provides reactive sites for bio-orthogonal conjugation of cargo with suitably protected PS derivatives. An amine-containing PS forms amide bonds with peptidic cargo, a thiol derivative is designed for conjugation to cargo that contain alpha-halo carbonyls or Michael acceptors, and the terminal alkyne PS analogue permits "click" conjugation with any azide-tagged molecule.
View Article and Find Full Text PDFMolecular probes with zinc(II)-(2,2'-dipicolylamine) coordination complexes associate with oxyanions in aqueous solution and target biomembranes that contain anionic phospholipids. This study examines a new series of coordination complexes with 2,6-bis(zinc(II)-dipicolylamine)phenoxide as the molecular recognition unit. Two lipophilic analogues are observed to partition into the membranes of zwitterionic and anionic vesicles and induce the transport of phospholipids and hydrophilic anions (carboxyfluorescein).
View Article and Find Full Text PDFThe copper-catalyzed azide alkyne cycloaddition is employed to modify phosphatidylcholine precursors with sn-2 acyl chains containing terminal alkyne or azide groups. Although the reactions are conducted as biphasic dispersions, the yields are essentially quantitative. Bolaamphiphiles are formed by simply clicking together two phosphatidylcholine alkyne precursors to a central bisazide scaffold.
View Article and Find Full Text PDF[reaction: see text] Tyrosine-derived Zn(2+) coordination complexes and their fluorescent NBD conjugates are synthesized in a short, high-yielding procedure. The Zn(2+) complexes are highly water soluble, but in the presence of sodium laurate they readily transfer into an octanol layer. Furthermore, the NBD-labeled bis-Zn(2+) complex can partition into vesicle membranes containing anionic phospholipids.
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