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[ "Acta", "Crystallographica", "Section", "E", "Structure", "Reports", "Online", "ISSN", "1600-5368", "Bis{4-chloro-N0", "-[phenyl(2-pyridyl)-", "2", "methylidene]benzohydrazidato-j", "N0,O}-", "cobalt(III)", "nitrate", "methanol", "disolvate", "Genhua", "Wu,", "Hui", "Ye", "and", "Dayu", "Wu*", "Anhui", "Key", "Laboratory", "of", "Functional", "Coordination", "Compounds,", "School", "of", "Chemistry", "and", "Chemical", "Engineering,", "Anqing", "Teachers", "College,", "Anqing,", "246011", "Anhui,", "People’s", "Republic", "of", "China", "Correspondence", "e-mail:", "wudayu_nju@yahoo.com.cn", "Received", "3", "August", "2010;", "accepted", "11", "August", "2010", "Key", "indicators:", "single-crystal", "X-ray", "study;", "T", "=", "293", "K;", "mean", "(C–C)", "=", "0.005", "A˚;", "R", "factor", "=", "0.051;", "wR", "factor", "=", "0.156;", "data-to-parameter", "ratio", "=", "13.3.", "In", "the", "title", "compound,", "[Co(C19H13ClN3O)2]NO3", "2CH3OH,", "the", "central", "CoIII", "atom", "in", "the", "cation", "is", "surrounded", "by", "two", "tridentate", "ligands", "in", "a", "distorted", "octahedral", "fashion", "by", "four", "N", "and", "two", "O", "atoms.", "Classical", "O—H", "O", "hydrogen", "bonds", "link", "both", "methanol", "solvent", "molecules", "with", "the", "nitrate", "anion.", "Related", "literature", "For", "related", "work", "on", "the", "mononuclear", "cobalt", "compound,", "see:", "Herchel", "&", "Boca", "(2005).", "For", "a", "dimetallic", "dicobalt(II)", "complex,", "see:", "Gavrilova", "et", "al.", "(2002).", "For", "a", "spin-crossover", "FeII", "complex,", "see:", "Wu", "et", "al.", "(2009).", "Experimental", "Crystal", "data", "[Co(C19H13ClN3O)2]NO3", "2CH4O", "Mr", "=", "854.57", "Monoclinic,", "P21=c", "a", "=", "12.914", "(8)", "A˚", "b", "=", "17.423", "(11)", "A˚", "c", "=", "17.451", "(11)", "A˚", "=", "93.031", "(8)", "Acta", "Cryst.", "(2010).", "E66,", "m1121", "V", "=", "3921", "(4)", "A˚3", "Z", "=", "4", "Mo", "K", "radiation", "=", "0.63", "mm", "1", "T", "=", "293", "K", "0.31", "0.23", "0.21", "mm", "Data", "collection", "Bruker", "SMART", "APEXII", "CCD", "area-detector", "diffractometer", "Absorption", "correction:", "scan", "(SADABS;", "Bruker,", "1997)", "Tmin", "=", "0.839,", "Tmax", "=", "0.875", "Refinement", "R[F", "2", ">", "2", "(F", "2)]", "=", "0.051", "wR(F", "2)", "=", "0.156", "S", "=", "1.07", "6859", "reflections", "Table", "1", "Selected", "bond", "lengths", "(A˚", ").", "Co1—N2", "Co1—N5", "Co1—O2", "metal-organic", "compounds", "18168", "measured", "reflections", "6859", "independent", "reflections", "4829", "reflections", "with", "I", ">", "2", "(I)", "Rint", "=", "0.033", "516", "parameters", "H-atom", "parameters", "constrained", "max", "=", "0.48", "e", "A˚", "3", "min", "=", "0.39", "e", "A˚", "3", "1.909", "(3)", "1.915", "(2)", "1.921", "(3)", "D—H", "A", "167", "142", "150", "1.853", "(3)", "1.859", "(3)", "1.899", "(2)", "Co1—N4", "Co1—O1", "Co1—N1", "Table", "2", "Hydrogen-bond", "geometry", "(A˚", ",", ").", "D—H", "A", "O39—H39D", "O40—H40D", "O40—H40D", "O3", "O3", "O5", "D—H", "0.82", "0.85", "0.85", "H", "1.94", "2.16", "2.20", "A", "D", "A", "2.747", "(11)", "2.873", "(12)", "2.963", "(12)", "Data", "collection:", "SMART", "(Bruker,", "1997);", "cell", "refinement:", "SAINT", "(Bruker,", "1997);", "data", "reduction:", "SAINT;", "program(s)", "used", "to", "solve", "structure:", "SHELXS97", "(Sheldrick,", "2008);", "program(s)", "used", "to", "refine", "structure:", "SHELXL97", "(Sheldrick,", "2008);", "molecular", "graphics:", "SHELXTL", "(Sheldrick,", "2008);", "software", "used", "to", "prepare", "material", "for", "publication:", "SHELXL97", "and", "PLATON", "(Spek,", "2009).", "This", "work", "was", "supported", "by", "Anhui", "Provincial", "Office", "of", "Science", "and", "Technology", "(project:", "Photo-induced", "Spin", "Cross-", "over", "Cluster", "and", "Photomagnetic", "Devices).", "Supplementary", "data", "and", "figures", "for", "this", "paper", "are", "available", "from", "the", "IUCr", "electronic", "archives", "(Reference:", "SI2285).", "References", "Bruker", "(1997).", "SMART,", "SAINT", "and", "SADABS.", "Bruker", "AXS", "Inc.,", "Madison,", "Wisconsin,", "USA.", "Gavrilova,", "A.,", "Qin,", "C.", "J.,", "Sommer,", "R.,", "Rheingold,", "A.", "&", "Bosnich,", "B.", "(2002).", "J.", "Am.", "Chem.", "Soc.", "124,", "1714–1722.", "Herchel,", "R.", "&", "Boca,", "R.", "(2005).", "Dalton", "Trans.", "pp.", "1352–1353.", "Sheldrick,", "G.", "M.", "(2008).", "Acta", "Cryst.", "A64,", "112–122.", "Spek,", "A.", "L.", "(2009).", "Acta", "Cryst.", "D65,", "148–155.", "Wu,", "D.-Y.,", "Sato,", "O.,", "Einaga,", "Y.", "&", "Duan,", "C.-Y.", "(2009).", "Angew.", "Chem.", "Int.", "Ed.", "48,", "1475–1478.", "doi:10.1107/S1600536810032241", "Wu", "et", "al.", "m1121" ]

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[ "6568–6584", "Nucleic", "Acids", "Research,", "2011,", "Vol.", "39,", "No.", "15", "doi:10.1093/nar/gkr340", "Published", "online", "16", "May", "2011", "Ultrafine", "anaphase", "bridges,", "broken", "DNA", "and", "illegitimate", "recombination", "induced", "by", "a", "replication", "fork", "barrier", "Sevil", "Sofueva,", "Fekret", "Osman,", "Alexander", "Lorenz,", "Roland", "Steinacher,", "Stefania", "Castagnetti,", "Jennifer", "Ledesma", "and", "Matthew", "C.", "Whitby*", "Department", "of", "Biochemistry,", "University", "of", "Oxford,", "South", "Parks", "Road,", "Oxford,", "OX1", "3QU,", "UK", "Received", "November", "25,", "2010;", "Revised", "April", "13,", "2011;", "Accepted", "April", "21,", "2011", "ABSTRACT", "Most", "DNA", "double-strand", "breaks", "(DSBs)", "in", "S-", "and", "G2-phase", "cells", "are", "repaired", "accurately", "by", "Rad51-", "dependent", "sister", "chromatid", "recombination.", "However,", "a", "minority", "give", "rise", "to", "gross", "chromosome", "rearrangements", "(GCRs),", "which", "can", "result", "in", "disease/", "death.", "What", "determines", "whether", "a", "DSB", "is", "repaired", "accurately", "or", "inaccurately", "is", "currently", "unclear.", "We", "provide", "evidence", "that", "suggests", "that", "perturbing", "replication", "by", "a", "non-programmed", "protein–DNA", "replication", "fork", "barrier", "results", "in", "the", "persistence", "of", "replication", "intermediates", "(most", "likely", "regions", "of", "unreplicated", "DNA)", "into", "mitosis,", "which", "results", "in", "anaphase", "bridge", "formation", "and", "ultimately", "to", "DNA", "breakage.", "However,", "unlike", "previously", "chara-", "cterised", "replication-associated", "DSBs,", "these", "breaks", "are", "repaired", "mainly", "by", "Rad51-independent", "pro-", "cesses", "such", "as", "single-strand", "annealing,", "and", "are", "therefore", "prone", "to", "generate", "GCRs.", "These", "data", "high-", "light", "how", "a", "replication-associated", "DSB", "can", "be", "predisposed", "to", "give", "rise", "to", "genome", "rearrangements", "in", "eukaryotes.", "INTRODUCTION", "The", "path", "to", "complete", "genome", "duplication", "is", "littered", "with", "obstacles", "that", "can", "impede", "the", "progression", "of", "the", "replica-", "tion", "fork", "(1).", "These", "replication", "fork", "barriers", "(RFBs)", "include", "natural", "programmed", "RFBs,", "which", "are", "designed", "to", "ensure", "unidirectional", "replication", "of", "a", "given", "locus,", "as", "well", "as", "numerous", "accidental", "RFBs,", "including", "various", "DNA", "lesions,", "secondary", "structures", "in", "the", "template", "DNA,", "and", "protein–DNA", "complexes", "(2).", "Cells", "appear", "to", "have", "a", "variety", "of", "mechanisms", "for", "coping", "with", "RFBs,", "and", "it", "is", "thought", "that", "the", "nature", "of", "the", "barrier", "determines", "which", "is", "used", "in", "any", "given", "situation", "(1).", "In", "many", "cases", "it", "appears", "that", "the", "response", "is", "to", "protect", "the", "fork", "and", "its", "protein", "components", "(the", "replisome),", "until", "such", "time", "as", "the", "block", "has", "been", "removed", "and", "DNA", "syn-", "thesis", "can", "resume,", "or", "replication", "is", "completed", "by", "the", "arrival", "of", "the", "opposing", "fork", "(3).", "However,", "when", "fork", "pro-", "tection", "fails", "or", "the", "barrier", "proves", "persistent", "homologous", "recombination", "(HR)", "can", "be", "used", "to", "enable", "template", "switching", "to", "bypass", "the", "RFB", "or", "to", "promote", "replication", "restart", "if", "the", "fork", "has", "collapsed", "(=", "dissociation", "of", "the", "replisome", "from", "DNA)", "or", "broken", "(4,5).", "This", "recombin-", "ation", "typically", "occurs", "between", "equivalent", "DNA", "sequences", "on", "the", "sister", "chromatids,", "however", "occasionally", "HR", "acts", "between", "allelic", "or", "ectopic", "sites", "and", "consequently", "can", "result", "in", "changes", "to", "the", "genome", "such", "as", "loss", "of", "heterozy-", "gosity", "(LOH)", "and", "gross", "chromosome", "rearrangements", "(GCRs)", "including", "deletions,", "duplications,", "inversions", "and", "translocations", "that", "in", "humans", "can", "promote", "diseases", "such", "as", "cancer", "(5–8).", "Whether", "this", "misdirected", "recombination", "is", "solely", "stochastic", "or", "can", "be", "driven", "by", "the", "nature", "of", "the", "fork", "impediment", "is", "unknown.", "A", "key", "requirement", "in", "HR", "is", "the", "presence", "of", "a", "stretch", "of", "single-stranded", "(ss)", "DNA", "that", "is", "bound", "by", "recombinases,", "such", "as", "Rad51", "and", "Rad52,", "which", "then", "promote", "either", "strand", "invasion", "of", "a", "homologous", "duplex", "DNA", "or", "anneal-", "ing", "to", "a", "complementary", "DNA", "strand", "(9).", "Replication", "forks", "naturally", "contain", "a", "region", "of", "ssDNA", "on", "the", "lagging", "template", "strand,", "and", "it", "is", "thought", "that", "this", "can", "become", "accessible", "to", "recombinases", "following", "fork", "stalling.", "Alternatively,", "the", "stalled", "fork", "can", "be", "remodelled", "through", "a", "process", "of", "fork", "reversal,", "which", "causes", "the", "nascent", "DNA", "strands", "to", "anneal", "to", "each", "other", "forming", "a", "duplex", "DNA", "end", "that", "can", "be", "resected", "to", "produce", "a", "*To", "whom", "correspondence", "should", "be", "addressed.", "Tel:", "44", "1865", "613239;", "Fax:", "44", "1865", "613343;", "Email:", "matthew.whitby@bioch.ox.ac.uk", "Present", "address:", "Sevil", "Sofueva,", "UCL", "Cancer", "Institute,", "72", "Huntley", "Street,", "London,", "WC1E", "6BT,", "UK.", "The", "authors", "wish", "it", "to", "be", "known", "that,", "in", "their", "opinion,", "the", "first", "three", "authors", "should", "be", "regarded", "as", "joint", "First", "Authors.", "The", "Author(s)", "2011.", "Published", "by", "Oxford", "University", "Press.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/", "by-nc/3.0),", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Fibroblast", "Growth", "Factor", "22", "Is", "Not", "Essential", "for", "Skin", "Development", "and", "Repair", "but", "Plays", "a", "Role", "in", "Tumorigenesis", "Monika", "Jarosz1,", "Luisa", "Robbez-Masson", "1", ",", "Athina-Myrto", "Chioni1,", "Barbara", "Cross2,", "Ian", "Rosewell2,", "Richard", "Grose1*", "1", "Centre", "for", "Tumour", "Biology,", "Barts", "Cancer", "Institute", "–", "a", "Cancer", "Research", "UK", "Centre", "of", "Excellence,", "Queen", "Mary", "University", "of", "London,", "London,", "United", "Kingdom,", "2", "Biological", "Services,", "Clare", "Hall", "Laboratories,", "Cancer", "Research", "UK", "London", "Research", "Institute,", "South", "Mimms,", "Herts,", "United", "Kingdom", "Abstract", "Fibroblast", "Growth", "Factors", "play", "critical", "roles", "during", "development,", "tissue", "homeostasis", "and", "repair", "by", "controlling", "cell", "proliferation,", "survival,", "migration", "and", "differentiation.", "Of", "the", "22", "mammalian", "FGFs,", "FGF22,", "a", "member", "of", "the", "FGF7/10/22", "subfamily,", "has", "been", "shown", "to", "have", "a", "clear", "role", "in", "synaptogenesis,", "but", "its", "roles", "in", "other", "tissues", "have", "not", "been", "studied.", "We", "have", "investigated", "the", "in", "vivo", "functions", "of", "FGF22", "in", "mice.", "Fgf22", "null", "animals", "were", "viable,", "fertile", "and", "did", "not", "display", "any", "obvious", "abnormalities.", "Despite", "the", "known", "expression", "profile", "of", "FGF22", "in", "the", "skin,", "no", "differences", "in", "either", "skin", "or", "pelage", "were", "observed,", "demonstrating", "that", "FGF22", "is", "dispensable", "during", "embryogenesis", "and", "in", "unchallenged", "adult", "skin.", "Mice", "lacking", "FGF22", "were", "able", "to", "heal", "acute", "wounds", "just", "as", "efficiently", "as", "wild", "type", "mice.", "However,", "classical", "two-step", "skin", "carcinogenesis", "challenge", "revealed", "that", "FGF22", "null", "mice", "developed", "fewer", "papillomas", "than", "wild", "type", "controls,", "suggesting", "a", "potential", "pro-oncogenic", "role", "for", "FGF22", "in", "the", "skin.", "Citation:", "Jarosz", "M,", "Robbez-Masson", "L,", "Chioni", "A-M,", "Cross", "B,", "Rosewell", "I,", "et", "al.", "(2012)", "Fibroblast", "Growth", "Factor", "22", "Is", "Not", "Essential", "for", "Skin", "Development", "and", "Repair", "but", "Plays", "a", "Role", "in", "Tumorigenesis.", "PLoS", "ONE", "7(6):", "e39436.", "doi:10.1371/journal.pone.0039436", "Editor:", "Zhongjun", "Zhou,", "The", "University", "of", "Hong", "Kong,", "Hong", "Kong", "Received", "November", "29,", "2011;", "Accepted", "May", "21,", "2012;", "Published", "June", "21,", "2012", "Copyright:", "2012", "Jarosz", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "research", "was", "funded", "by", "Cancer", "Research", "UK,", "The", "Wellcome", "Trust", "(076678/Z/05/Z)", "and", "the", "Trustees", "of", "St", "Barts", "and", "The", "London", "Charitable", "Foundation.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "r.p.grose@qmul.ac.uk", "Introduction", "Fibroblast", "Growth", "Factors", "(FGFs)", "are", "a", "large", "family", "of", "22", "signalling", "molecules,", "responsible", "for", "regulating", "a", "range", "of", "cellular", "processes", "including", "proliferation,", "survival,", "migration,", "differentia-", "tion", "and", "response", "to", "injury", "[1].", "Their", "various", "roles", "have", "been", "delineated", "through", "a", "large", "number", "of", "genetically", "modified", "mouse", "studies", "(reviewed", "in", "[2]).", "They", "act,", "for", "the", "most", "part,", "as", "secreted", "growth", "factors,", "which", "bind", "to", "receptor", "tyrosine", "kinases", "on", "nearby", "cells.", "FGFs", "can", "be", "grouped", "into", "subfamilies,", "based", "on", "sequence", "similarity", "and", "receptor", "specificity", "[1,3,4].", "The", "biological", "activities", "of", "FGFs", "are", "mediated", "by", "high", "affinity", "cell", "surface", "tyrosine", "kinase", "receptors.", "FGF7/10/22", "subfamily", "members", "activate", "two", "main", "receptors:", "FGFR1b", "and", "FGFR2b,", "although", "they", "signal", "preferentially,", "and", "exclusively", "in", "the", "case", "of", "FGF7,", "via", "FGFR2b", "[4,5].", "Striking", "phenotypic", "similarities", "between", "fgf10", "and", "fgfr2b", "knockout", "mice", "[6,7,8],", "together", "with", "rather", "modest", "phenotypes", "of", "fgf7", "[9]", "and", "fgfr1b", "[10]", "knockout", "mice,", "have", "established", "the", "FGF10-FGFR2b", "axis", "as", "a", "key", "ligand-receptor", "partnership", "in", "embryogenesis.", "FGF22", "is", "a", "relatively", "understudied", "member", "of", "the", "FGF7/10/22", "subfamily", "[11].", "In", "the", "skin,", "FGFs", "7,", "10", "and", "22", "act", "predominately", "on", "cells", "of", "epithelial", "origin", "but,", "uniquely,", "FGF22", "is", "expressed", "by", "epithelial", "cells", "[12],", "suggesting", "a", "cell", "autonomous", "role.", "Expression", "of", "FGF22", "is", "relatively", "restricted.", "It", "first", "was", "detected,", "by", "Northern", "blot,", "in", "placenta,", "brain", "and", "skin", "[11].", "In", "murine", "skin,", "expression", "of", "FGF22", "begins", "at", "embryonic", "day", "16.5,", "as", "determined", "by", "RNase", "protection", "assay", "[12].", "In", "adult", "mouse", "skin,", "FGF22", "is", "expressed", "in", "the", "inner", "root", "sheath", "(IRS)", "of", "the", "hair", "follicle", "[11]", "and", "in", "the", "interfollicular", "epidermis", "[12].", "During", "hair", "development,", "the", "dermal", "papilla,", "a", "cluster", "of", "specialised", "mesenchymal", "cells", "within", "the", "dermis,", "signals", "to", "epidermal", "follicular", "stem", "cells", "to", "proliferate", "and", "differentiate", "into", "IRS,", "medulla", "and", "cortex", "cells,", "which", "together", "with", "the", "cuticle", "cells", "undergo", "terminal", "differentiation", "to", "form", "the", "mature", "hair", "fibre", "[13].", "FGF7", "and", "FGF10", "are", "expressed", "in", "the", "dermal", "papilla", "of", "the", "hair", "follicle", "[14]", "and", "fgf7", "knockout", "mice", "displayed", "a", "mild", "hair", "phenotype,", "with", "male", "mice", "developing", "greasy,", "matted", "hair", "with", "age", "[9].", "Furthermore,", "transgenic", "mice", "overexpressing", "FGF7", "in", "the", "epidermis", "demonstrated", "abnormal", "patterns", "of", "hair", "growth", "[15],", "and", "subcutaneous", "or", "intraperitoneal", "injections", "of", "recombinant", "FGF7", "into", "nude", "mice", "stimulated", "hair", "growth", "by", "extending", "the", "anagen", "phase", "of", "the", "hair", "cycle", "[16].", "Since", "both", "fgf10", "and", "fgfr2b", "knockout", "mice", "die", "at", "birth,", "their", "hair", "phenotype", "is", "hard", "to", "study.", "Nevertheless,", "late", "stage", "fgfr2b", "knockout", "embryos", "showed", "a", "reduction", "in", "hair", "follicle", "development,", "with", "significantly", "fewer,", "developmentally", "retarded,", "hair", "follicles", "relative", "to", "wild", "type", "littermates", "[17].", "Skin", "grafting", "studies,", "using", "late", "stage", "fgfr2b", "null", "and", "wild", "type", "foetuses,", "showed", "that", "FGFR2b", "signalling", "was", "crucial", "for", "normal", "epidermal", "growth", "and", "development", "as", "well", "as", "for", "subsequent", "hair", "follicle", "morphogenesis", "[18].", "Transgenic", "mice", "expressing", "dominant-negative", "FGFR2b", "in", "differentiating", "hair", "keratinocytes", "developed", "abnormally", "thin,", "but", "otherwise", "normal,", "hairs", "characterised", "by", "single", "columns", "of", "medulla", "cells", "in", "PLoS", "ONE", "|", "www.plosone.org", "1", "June", "2012", "|", "Volume", "7", "|", "Issue", "6", "|", "e39436" ]

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"pre-eclampsia", "ranges", "from", "3%", "to", "7%", "for", "nulliparas", "and", "1%", "to", "3%", "for", "multiparas.", "Pre-eclampsia", "is", "a", "major", "cause", "of", "maternal", "mortality", "and", "morbidity,", "preterm", "birth,", "perinatal", "death,", "and", "intrauterine", "growth", "restriction.", "Unfortunately,", "the", "pathophysiology", "of", "this", "multisystem", "disorder,", "characterized", "by", "abnormal", "vascular", "response", "to", "placentation,", "is", "still", "unclear.", "Despite", "great", "polymorphism", "of", "the", "disease,", "the", "criteria", "for", "pre-eclampsia", "have", "not", "changed", "over", "the", "past", "decade", "(systolic", "blood", "pressure", ".140", "mmHg", "or", "diastolic", "blood", "pressure", "$90", "mmHg", "and", "24-hour", "proteinuria", "$0.3", "g).", "Clinical", "features", "and", "laboratory", "abnormalities", "define", "and", "determine", "the", "severity", "of", "pre-eclampsia.", "Delivery", "is", "the", "only", "curative", "treatment", "for", "pre-eclampsia.", "Multidisciplinary", "management,", "involving", "an", "obstetrician,", "anesthetist,", "and", "pediatrician,", "is", "carried", "out", "with", "consideration", "of", "the", "maternal", "risks", "due", "to", "continued", "pregnancy", "and", "the", "fetal", "risks", "associated", "with", "induced", "preterm", "delivery.", "Screening", "women", "at", "high", "risk", "and", "preventing", "recurrences", "are", "key", "issues", "in", "the", "management", "of", "pre-eclampsia.", "Keywords:", "pre-eclampsia,", "epidemiology,", "pathophysiology,", "therapeutic", "management", "Introduction", "The", "criteria", "that", "define", "pre-eclampsia", "have", "not", "changed", "over", "the", "past", "decade.1,2", "These", "are:", "onset", "at", ".20", "weeks’", "gestational", "age", "of", "24-hour", "proteinuria", "$30", "mg/day", "or,", "if", "not", "available,", "a", "protein", "concentration", "$30", "mg", "($1+", "on", "dipstick)", "in", "a", "minimum", "of", "two", "random", "urine", "samples", "collected", "at", "least", "4–6", "hours", "but", "no", "more", "than", "7", "days", "apart,", "a", "systolic", "blood", "pressure", ".140", "mmHg", "or", "diastolic", "blood", "pressure", "$90", "mmHg", "as", "measured", "twice,", "using", "an", "appropriate", "cuff,", "4–6", "hours", "and", "less", "than", "7", "days", "apart,", "and", "disappearance", "of", "all", "these", "abnormalities", "before", "the", "end", "of", "the", "6th", "week", "postpartum.", "Nonetheless,", "some", "presentations", "of", "pregnancy-related", "hypertension", "combined", "with", "clinical", "or", "laboratory", "abnormalities", "or", "intrauterine", "growth", "restriction", "should", "also", "be", "considered", "as", "potential", "pre-eclampsia.1", "Epidemiology", "Pre-eclampsia", "is", "a", "multisystem", "disorder", "that", "complicates", "3%–8%", "of", "pregnancies", "in", "Western", "countries", "and", "constitutes", "a", "major", "source", "of", "morbidity", "and", "mortality", "worldwide.3,4", "Overall,", "10%–15%", "of", "maternal", "deaths", "are", "directly", "associated", "with", "pre-", "eclampsia", "and", "eclampsia.4", "Some", "epidemiological", "findings", "support", "the", "hypothesis", "of", "a", "genetic", "and", "immunological", "etiology.", "The", "risk", "of", "pre-eclampsia", "is", "2-fold", "to", "5-fold", "higher", "in", "pregnant", "women", "with", "a", "maternal", "history", "of", "this", "disorder.", "Depending", "on", "ethnicity,", "the", "incidence", "of", "pre-eclampsia", "ranges", "from", "3%", "to", "7%", "in", "healthy", "nulliparas", "and", "1%", "to", "3%", "submit", "your", "manuscript", "|", "www.dovepress.com", "Dovepress", "http://dx.doi.org/10.2147/VHRM.S20181", "Vascular", "Health", "and", "Risk", "Management", "2011:7", "467–474", "©", "2011", "Uzan", "et", "al,", "publisher", "and", "licensee", "Dove", "Medical", "Press", "Ltd.", "This", "is", "an", "Open", "Access", "article", "which", 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[ "RESEARCH", "PREPAREDNESS", "AND", "RESPONSE", "Body", "Temperature", "Monitoring", "and", "SARS", "Fever", "Hotline,", "Taiwan", "S.", "Cornelia", "Kaydos-Daniels,*†", "Babatunde", "Olowokure,‡§", "Hong-Jen", "Chang,¶", "Rachel", "S.", "Barwick,†", "Jou-Fang", "Deng,#", "Ming-Liang", "Lee,**", "Steve", "Hsu-Sung", "Kuo,††", "Ih-Jen", "Su,‡‡", "Kow-Tong", "Chen,††", "Susan", "A.", "Maloney,†", "and", "the", "SARS", "International", "Field", "Team1", "In", "Taiwan,", "a", "temperature-monitoring", "campaign", "and", "hotline", "for", "severe", "acute", "respiratory", "syndrome", "(SARS)", "fever", "were", "implemented", "in", "June", "2003.", "Among", "1,966", "calls,", "fever", "was", "recorded", "in", "19%", "(n", "=", "378);", "18", "persons", "at", "high", "risk", "for", "SARS", "were", "identified.", "In", "a", "cross-sectional", "telephone", "sur-", "vey,", "95%", "(n", "=", "1,060)", "of", "households", "knew", "about", "the", "cam-", "paign", "and", "7", "households", "reported", "fever.", "Fsyndrome", "(SARS)", "(1–3).", "Persons", "with", "fevers", "initially", "ever", "is", "one", "of", "the", "first", "signs", "of", "severe", "acute", "respiratory", "attributed", "to", "other", "illnesses", "have", "caused", "outbreaks", "of", "SARS", "in", "hospitals", "and", "the", "community", "(1–7).", "This", "finding", "highlights", "the", "need", "for", "early", "recognition", "of", "cases.", "On", "June", "1,", "2003,", "in", "Taiwan,", "a", "National", "Temperature", "Monitoring", "Campaign", "and", "SARS", "fever", "hotline", "were", "launched.", "These", "were", "intended", "to", "raise", "public", "awareness", "about", "SARS", "(and", "fever", "as", "an", "early", "sign", "of", "SARS),", "improve", "early", "detection", "of", "possible", "SARS", "cases,", "and", "prevent", "SARS", "transmission.", "In", "the", "campaign,", "fever", "was", "defined", "as", "fore-", "head", "or", "axillary", "temperature", ">37°C,", "oral", "temperature", ">37.5°C,", "or", "tympanic", "or", "rectal", "temperature", ">38°C", "(8).2", "In", "conjunction", "with", "this", "campaign,", "persons", "with", "fevers", "were", "encouraged", "to", "call", "a", "toll-free", "SARS", "fever", "hotline.", "The", "hotline", "objectives", "were", "to", "appropriately", "triage", "persons", "with", "fever,", "reduce", "clinic", "visits", "by", "the", "“worried", "well,”", "identify", "persons", "at", "high", "risk", "for", "SARS,", "reduce", "opportunities", "for", "SARS", "exposure,", "and", "increase", "the", "public’s", "sense", "of", "security.", "Both", "the", "body-temperature", "monitoring", "campaign", "and", "the", "hotline", "were", "publicized", "through", "television,", "posters,", "fliers,", "radio,", "the", "Internet,", "magazines,", "and", "newspapers.", "We", "*West", "Virginia", "Bureau", "for", "Public", "Health,", "Charleston,", "West", "Virginia,", "USA;", "†Centers", "for", "Disease", "Control", "and", "Prevention,", "Atlanta,", "Georgia,", "USA;", "‡World", "Health", "Organization,", "Geneva,", "Switzerland;", "§Health", "Protection", "Agency,", "Regional", "Surveillance", "Unit", "West", "Midlands,", "Birmingham,", "United", "Kingdom;", "¶Bureau", "of", "National", "Health", "Insurance,", "Taiwan;", "#Taipei", "Medical", "Association,", "Taipei,", "Taiwan;", "**Tzu-Chi", "University,", "Hualien,", "Taiwan;", "††Taipei", "Economic", "and", "Cultural", "Representative", "Office,", "Washington,", "DC,", "USA;", "and", "‡‡Center", "for", "Disease", "Control,", "Taiwan", "describe", "and", "evaluate", "the", "body-temperature", "monitoring", "campaign", "and", "the", "SARS", "fever", "hotline.", "Methods", "Our", "investigation", "evaluated", "the", "community-wide", "body-", "temperature", "monitoring", "campaign", "and", "SARS", "fever", "hotline", "in", "the", "city", "of", "Taipei,", "which", "makes", "up", "11.8%", "of", "the", "popula-", "tion", "of", "Taiwan", "(population", "of", "Taiwan,", "22.51", "million", "[9]).", "We", "analyzed", "data", "from", "three", "sources:", "hotline", "call", "data", "reported", "to", "the", "Bureau", "of", "National", "Health", "Insurance", "for", "all", "of", "Taiwan;", "hotline", "call", "data", "for", "Taipei;", "and", "data", "from", "a", "telephone", "survey", "of", "Taipei", "residents.", "Data", "were", "evaluated", "for", "the", "period", "June", "1–10,", "2003,", "corresponding", "to", "the", "dura-", "tion", "of", "the", "body-temperature", "monitoring", "campaign", "as", "well", "as", "the", "first", "10", "days", "of", "the", "hotline.2", "SARS", "Fever", "Hotline", "Data", "Throughout", "Taiwan,", "each", "local", "medical", "association", "responsible", "for", "operating", "the", "fever", "hotline", "in", "its", "city", "or", "county", "provided", "daily", "reports", "to", "the", "Bureau", "of", "National", "Health", "Insurance.", "The", "total", "number", "of", "calls", "and", "the", "advice", "given", "to", "the", "caller", "were", 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[ "Pediatr", "Radiol", "(2010)", "40:1789–1793", "DOI", "10.1007/s00247-010-1725-4", "ORIGINAL", "ARTICLE", "Starreveld", "scoring", "method", "in", "diagnosing", "childhood", "constipation", "Fredericus", "T.", "Kokke", "&", "Judith", "S.", "Sittig", "&", "Annemiek", "de", "Bruijn", "&", "Tjeerd", "Wiersma", "&", "Rick", "R.", "Van", "Rijn", "&", "Jan", "L.", "Limpen", "&", "Roderick", "H.", "Houwen", "&", "Kathelijn", "Fischer", "&", "Marc", "A.", "Benninga", "Received:", "21", "December", "2009", "/", "Revised:", "18", "March", "2010", "/", "Accepted:", "25", "April", "2010", "/", "Published", "online:", "1", "July", "2010", "#", "The", "Author(s)", "2010.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "Background", "Four", "scoring", "methods", "exist", "to", "assess", "severity", "of", "fecal", "loading", "on", "plain", "abdominal", "radiographs", "in", "constipated", "patients", "(Barr-,", "Starreveld-,", "Blethyn-", "and", "Leech).", "So", "far,", "the", "Starreveld", "score", "was", "used", "only", "in", "adult", "patients.", "Objective", "To", "determine", "accuracy", "and", "intra-", "and", "inter-observ-", "er", "agreement", "of", "the", "Starreveld", "scoring", "method", "in", "the", "diagnosis", "of", "functional", "constipation", "among", "pediatric", "patients.", "In", "F.", "T.", "Kokke", "(*)", "Pediatric", "Gastroenterology,", "Wilhelmina", "Childrens", "Hospital,", "KE", "1.144.3,", "PO", "Box", "85090,", "Utrecht", "3508", "AB,", "The", "Netherlands", "e-mail:", "f.t.m.kokke@umcutrecht.nl", "J.", "S.", "Sittig", ":", "J.", "L.", "Limpen", "Pediatrics", "Wilhelmina", "Childrens", "Hospital,", "Utrecht,", "The", "Netherlands", "A.", "de", "Bruijn", ":", "T.", "Wiersma", "Radiology,", "Rijnstate", "Hospital,", "Arnhem,", "The", "Netherlands", "R.", "H.", "Houwen", "Pediatric", "Gastroenterology,", "Wilhelmina", "Childrens", "Hospital,", "Utrecht,", "The", "Netherlands", "R.", "R.", "Van", "Rijn", "Radiology,", "Academic", "Medical", "Center", "Amsterdam,", "Amsterdam,", "The", "Netherlands", "K.", "Fischer", "Epidemiology,", "Center", "for", "Health", "Sciences", "and", "Primary", "Care,", "Utrecht,", "The", "Netherlands", "M.", "A.", "Benninga", "Pediatric", "Gastroenterology,", "Emma", "Children’s", "Hospital/Academic", "Medical", "Center,", "Amsterdam,", "The", "Netherlands", "addition,", "we", "compared", "the", "Starreveld", "with", "the", "Barr", "scoring", "method.", "Materials", "and", "methods", "Thirty-four", "constipated", "and", "34", "non-constipated", "children", "were", "included.", "Abdominal", "radiographs,", "obtained", "before", "treatment,", "were", "rated", "(Star-", "reveld-", "and", "Barr)", "by", "4", "observers.", "A", "second", "observation", "after", "4", "weeks", "was", "done", "by", "3", "observers.", "Cut-off", "level", "for", "the", "Starreveld", "score,", "accuracy", "as", "measured", "by", "the", "area", "under", "the", "receiver", "operator", "characteristics", "curve,", "and", "inter-", "and", "intra-observer", "agreement", "were", "calculated.", "Results", "Cut-off", "value", "for", "the", "Starreveld", "score", "was", "10.", "AUC", "for", "Starreveld", "score", "was", "0.54", "and", "for", "Barr", "score", "0.38,", "indicating", "poor", "discriminating", "power.", "Inter-observer", "agree-", "ment", "was", "0.49-0.52", "4", "(Starreveld)", "and", "0.44", "(Barr),", "which", "is", "considered", "moderate.", "Intra-observer", "agreement", "was", "0.52-", "0.71", "(Starreveld)", "and", "0.62-", "0.76", "(Barr).", "Conclusion", "The", "Starreveld", "scoring", "method", "to", "assess", "fecal", "loading", "on", "a", "plain", "abdominal", "radiograph", "is", "of", "limited", "value", "in", "the", "diagnosis", "of", "childhood", "constipation.", "Keywords", "Constipation", ".", "Scoring", ".", "Abdominal", "radiograph", ".", "Child", "Introduction", "Constipation", "is", "a", "common", "gastrointestinal", "complaint", "in", "children", "with", "a", "prevalence", "ranging", "from", "0.77%", "to", "29.6%", "both", "in", "Western", "and", "non-Western", "countries", "[1].", "The", "symp-", "toms", "may", "vary", "from", "mild", "and", "short-lived", "to", "severe", "chronic", "constipation", "with", "faecal", "impaction", "and", "the", "involuntary", "loss", "of", "faeces.", "Medical", "history", "together", "with", "a", "thorough", "physical", "examination", "is", "generally", "sufficient", "for", "diagnosis", "and", "treat-", "ment", "of", "most", "children", "with", "constipation.", "However,", "many", "clinicians", "additionally", "order", "a", "plain", "abdominal", "radiograph", "to" ]

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[ "Open", "Access", "Kuo", "BMC", "Ophthalmology", "2011,", "11:11", "http://www.biomedcentral.com/1471-2415/11/11", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Trends", "in", "refractive", "surgery", "at", "an", "academic", "center:", "2007-2009", "Irene", "C", "Kuo", "Abstract", "Background:", "The", "United", "States", "officially", "entered", "a", "recession", "in", "December", "2007,", "and", "it", "officially", "exited", "the", "recession", "in", "December", "2009,", "according", "to", "the", "National", "Bureau", "of", "Economic", "Research.", "Since", "the", "economy", "may", "affect", "not", "only", "the", "volume", "of", "excimer", "laser", "refractive", "surgery,", "but", "also", "the", "clinical", "characteristics", "of", "patients", "undergoing", "surgery,", "our", "goal", "was", "to", "compare", "the", "characteristics", "of", "patients", "completing", "excimer", "laser", "refractive", "surgery", "and", "the", "types", "of", "procedures", "performed", "in", "the", "summer", "quarter", "in", "2007", "and", "the", "same", "quarter", "in", "2009", "at", "an", "academic", "center.", "A", "secondary", "goal", "was", "to", "determine", "whether", "the", "volume", "of", "astigmatism-", "or", "presbyopia-correcting", "intraocular", "lenses", "(IOLs)", "has", "concurrently", "changed", "because", "like", "laser", "refractive", "surgery,", "these", "“premium”", "IOLs", "involve", "out-of-pocket", "costs", "for", "patients.", "Methods:", "Retrospective", "case", "series.", "Medical", "records", "were", "reviewed", "for", "all", "patients", "completing", "surgery", "at", "the", "Wilmer", "Laser", "Vision", "Center", "in", "the", "summer", "quarter", "of", "2007", "and", "the", "summer", "quarter", "of", "2009.", "Outcome", "measures", "were", "the", "proportions", "of", "treated", "refractive", "errors,", "the", "proportion", "of", "photorefractive", "keratectomy", "(PRK)", "vs.", "laser-assisted", "in-situ", "keratomileusis", "(LASIK),", "and", "the", "mean", "age", "of", "patients", "in", "each", "quarter.", "Chi-square", "test", "was", "used", "to", "compare", "the", "proportions", "of", "treated", "refractive", "errors", "and", "the", "proportions", "of", "procedures;", "two-tailed", "t-test", "to", "compare", "the", "mean", "age", "of", "patients;", "and", "two-tailed", "z-test", "to", "compare", "proportions", "of", "grouped", "refractive", "errors", "in", "2007", "vs.", "2009;", "alpha", "=", "0.05", "for", "all", "tests.", "Refractive", "errors", "were", "grouped", "by", "the", "spherical", "equivalent", "of", "the", "manifest", "refraction", "and", "were", "considered", "“low", "myopia”", "for", "6", "diopters", "(D)", "of", "myopia", "or", "less,", "“high", "myopia”", "for", "more", "than", "6", "D,", "and", "“hyperopia”", "for", "any", "hyperopia.", "Billing", "data", "were", "reviewed", "to", "obtain", "the", "volume", "of", "premium", "IOLs.", "Results:", "Volume", "of", "laser", "refractive", "procedures", "decreased", "by", "at", "least", "30%.", "The", "distribution", "of", "proportions", "of", "treated", "refractive", "errors", "did", "not", "change", "(p", "=", "0.10).", "The", "proportion", "of", "high", "myopes,", "however,", "decreased", "(p", "=", "0.05).", "The", "proportions", "of", "types", "of", "procedure", "changed,", "with", "an", "increase", "in", "the", "proportion", "of", "PRK", "between", "2007", "and", "2009", "(p", "=", "0.02).", "The", "mean", "age", "of", "patients", "did", "not", "change", "[42.4", "±", "14.4", "(standard", "deviation)", "years", "in", "2007", "vs.", "39.6", "±", "14.5", "years", "in", "2009;", "p", "=", "0.4].", "Astigmatism-correcting", "IOL", "and", "presbyopia-correcting", "IOL", "volumes", "increased", "15-fold", "and", "three-fold,", "respectively,", "between", "2007", "and", "2009.", "Conclusions:", "Volume", "of", "excimer", "laser", "refractive", "surgery", "decreased", "by", "at", "least", "30%", "between", "2007", "and", "2009.", "No", "significant", "change", "in", "mean", "age", "or", "in", "the", "distribution", "of", "refractive", "error", "was", "seen,", "although", "the", "proportion", "of", "high", "myopes", "decreased", "between", "summer", "quarters", "of", "2007", "and", "2009.", "PRK", "gained", "as", "a", "proportion", "of", "total", "cases.", "Premium", "IOL", "volume", "increased,", "but", "still", "comprised", "a", "very", "small", "proportion", "of", "total", "IOL", "volume.", "Correspondence:", "ickuo@jhmi.edu", "Wilmer", "Laser", "Vision", "Center,", "Wilmer", "Eye", "Institute,", "Department", "of", "Ophthalmology,", "Johns", "Hopkins", "University", "School", "of", "Medicine,", "Baltimore,", "MD,", "USA", "©", "2011", "Kuo;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Kehl", "et", "al.", "BMC", "Public", "Health", "2010,", "10:424", "http://www.biomedcentral.com/1471-2458/10/424", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "A", "descriptive", "analysis", "of", "relations", "between", "parents’", "self-reported", "smoking", "behavior", "and", "infants’", "daily", "exposure", "to", "environmental", "tobacco", "smoke", "Doris", "Kehl1*,", "Jochen", "R", "Thyrian2,", "Jan", "Lüdemann3,", "Matthias", "Nauck3,", "Ulrich", "John4", "Abstract", "Background:", "The", "aims", "of", "the", "present", "study", "were", "to", "examine", "relations", "between", "parents’", "self-reported", "smoking", "behavior", "and", "infants’", "daily", "exposure", "to", "environmental", "tobacco", "smoke,", "as", "assessed", "by", "urinary", "cotinine-to-creatinine", "ratio", "(CCR),", "and", "to", "describe", "the", "CCR", "over", "seven", "days", "among", "infants", "at", "home.", "Methods:", "A", "convenience", "sample", "of", "27", "households", "was", "drawn.", "Each", "household", "had", "to", "have", "at", "least", "one", "daily", "tobacco", "smoker", "and", "one", "child", "up", "to", "three", "years", "of", "age.", "Over", "a", "seven-day", "period,", "urine", "samples", "were", "obtained", "from", "the", "child", "daily.", "To", "examine", "relations", "between", "parents’", "self-reported", "smoking", "and", "infants’", "daily", "CCR,", "generalized", "estimating", "equation", "(GEE)", "analysis", "was", "used.", "Results:", "The", "data", "revealed", "that", "infants", "from", "households", "with", "indoor", "smoking", "had", "higher", "CCRs", "than", "infants", "in", "households", "with", "outdoor", "smoking.", "CCRs", "were", "higher", "in", "girls", "than", "in", "boys.", "Older", "infants", "had", "lower", "CCRs", "than", "younger", "infants.", "Smoking", "outside", "the", "home", "versus", "inside", "the", "home,", "infant’s", "gender,", "and", "infants’", "age", "accounted", "for", "68%", "of", "the", "variance", "in", "CCR", "in", "a", "GEE", "data", "analysis", "model.", "No", "increase", "or", "decrease", "of", "CCR", "over", "time", "was", "found.", "Conclusion:", "The", "findings", "suggest", "that", "parents’", "self-reported", "smoking", "indoors", "at", "home", "versus", "outdoors", "is", "predictive", "of", "CCR", "among", "infants", "three", "and", "younger.", "Higher", "CCR", "concentrations", "in", "girls’", "urine", "need", "further", "examination.", "Furthermore,", "significant", "fluctuations", "in", "daily", "CCR", "were", "not", "apparent", "in", "infants", "over", "a", "seven-day", "time", "period.", "Background", "Exposure", "to", "environmental", "tobacco", "smoke", "(ETS)", "is", "an", "important", "health", "risk", "among", "infants", "[1].", "Infants", "lack", "mobility", "and", "independence", "and", "are", "unable", "to", "complain", "about", "or", "avoid", "ETS", "[2].", "In", "homes", "where", "tobacco", "smok-", "ing", "occurs,", "infants", "are", "exposed", "during", "their", "regular", "daily", "activities", "[3].", "Many", "studies", "have", "shown", "strong", "and", "consistent", "associations", "between", "ETS,", "particularly", "from", "parental", "smoking,", "and", "numerous", "childhood", "diseases", "such", "as", "respiratory", "infection,", "asthma,", "middle", "ear", "infec-", "tions,", "and", "sudden", "infant", "death", "syndrome.", "*", "Correspondence:", "doris.kehl@uni-greifswald.de", "1Ernst-Moritz-Arndt-University", "Greifswald,", "Institute", "of", "Psychology,", "Department", "Health", "and", "Prevention,", "Robert-Blum-Str.", "13,", "D-17487", "Greifswald,", "Germany", "Infant’s", "exposure", "to", "ETS", "at", "home", "may", "be", "expected", "to", "differ", "according", "to", "the", "amount", "of", "tobacco", "smoke", "and", "the", "distance", "of", "tobacco", "smoke", "in", "relation", "to", "the", "air", "that", "the", "child", "breathes.", "Research", "suggests", "less", "exposure", "to", "ETS", "in", "homes", "with", "a", "home", "smoking", "ban", "than", "in", "homes", "without", "such", "a", "ban", "[4,5].", "However,", "children", "are", "exposed", "to", "ETS", "across", "different", "environments", "[6,7].", "Parents", "may", "not", "be", "aware", "of", "ETS", "exposure", "that", "occurs", "outside", "the", "home", "[8].", "Cotinine", "has", "been", "suggested", "as", "the", "biomarker", "of", "choice", "for", "measuring", "exposure", "to", "ETS", "[9].", "Cotinine", "may", "be", "taken", "from", "different", "tissues", "or", "fluids", "in", "the", "body", "[10].", "Among", "infants", "at", "age", "three", "or", "younger,", "urine", "sam-", "ples", "seem", "to", "be", "particularly", "feasible", "since", "blood", "samples", "are", "more", "invasive", "and", "hair", "samples", "may", "not", "be", "available", "or", "may", "not", "be", "tolerated", "by", "children", "or", "parents.", "Cotinine", "©", "2010", "Kehl", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Research", "Transcriptome", "Analysis", "in", "Peripheral", "Blood", "of", "Humans", "Exposed", "to", "Environmental", "Carcinogens:", "A", "Promising", "New", "Biomarker", "in", "Environmental", "Health", "Studies", "Danitsja", "M.", "van", "Leeuwen,1", "Ralph", "W.H.", "Gottschalk,1", "Greet", "Schoeters,2", "Nicolas", "A.", "van", "Larebeke,3", "Vera", "Nelen,4", "Willy", "F.", "Baeyens,5", "Jos", "C.S.", "Kleinjans,1", "and", "Joost", "H.M.", "van", "Delft1", "1Department", "of", "Health", "Risk", "Analysis", "and", "Toxicology,", "Maastricht", "University,", "Maastricht,", "the", "Netherlands,", "2Center", "of", "Expertise", "in", "Environmental", "Toxicology,", "Flemish", "Institute", "for", "Technological", "Research,", "Mol,", "Belgium;", "3Study", "Centre", "for", "Carcinogenesis", "and", "Primary", "Prevention", "of", "Cancer,", "Ghent", "University", "Hospital,", "Ghent,", "Belgium,", "4Provincial", "Institute", "of", "Hygiene,", "Antwerp,", "Belgium;", "5Laboratory", "of", "Analytical", "and", "Environmental", "Chemistry,", "Vrije", "Universiteit", "Brussel,", "Brussels,", "Belgium", "BACKGROUND:", "Human", "carcinogenesis", "is", "known", "to", "be", "initiated", "and/or", "promoted", "by", "exposure", "to", "chemicals", "that", "occur", "in", "the", "environment.", "Molecular", "cancer", "epidemiology", "is", "used", "to", "identify", "human", "environmental", "cancer", "risks", "by", "applying", "a", "range", "of", "effect", "biomarkers,", "which", "tend", "to", "be", "nonspecific", "and", "do", "not", "generate", "insights", "into", "underlying", "modes", "of", "action.", "Toxicogenomic", "technologies", "may", "improve", "on", "this", "by", "providing", "the", "opportunity", "to", "identify", "molecular", "biomarkers", "consisting", "of", "altered", "gene", "expression", "profiles.", "OBJECTIVES:", "The", "aim", "of", "the", "present", "study", "was", "to", "monitor", "the", "expression", "of", "selected", "genes", "in", "a", "random", "sample", "of", "adults", "in", "Flanders", "selected", "from", "specific", "regions", "with", "(presumably)", "different", "envi-", "ronmental", "burdens.", "Furthermore,", "associations", "of", "gene", "expression", "with", "blood", "and", "urinary", "measures", "of", "biomarkers", "of", "exposure,", "early", "phenotypic", "effects,", "and", "tumor", "markers", "were", "investigated.", "RESULTS:", "Individual", "gene", "expression", "of", "cytochrome", "p450", "1B1,", "activating", "transcription", "factor", "4,", "mitogen-activated", "protein", "kinase", "14,", "superoxide", "dismutase", "2", "(Mn),", "chemokine", "(C-X-C", "motif)", "lig-", "and", "1", "(melanoma", "growth", "stimulating", "activity,", "alpha),", "diacylglycerol", "O-acyltransferase", "homolog", "2", "(mouse),", "tigger", "transposable", "element", "derived", "3,", "and", "PTEN-induced", "putative", "kinase1", "were", "meas-", "ured", "by", "means", "of", "quantitative", "polymerase", "chain", "reaction", "in", "peripheral", "blood", "cells", "of", "398", "individu-", "als.", "After", "correction", "for", "the", "confounding", "effect", "of", "tobacco", "smoking,", "inhabitants", "of", "the", "Olen", "region", "showed", "the", "highest", "differences", "in", "gene", "expression", "levels", "compared", "with", "inhabitants", "from", "the", "Gent", "and", "fruit", "cultivation", "regions.", "Importantly,", "we", "observed", "multiple", "significant", "correlations", "of", "particu-", "lar", "gene", "expressions", "with", "blood", "and", "urinary", "measures", "of", "various", "environmental", "carcinogens.", "CONCLUSIONS:", "Considering", "the", "observed", "significant", "differences", "between", "gene", "expression", "levels", "in", "inhabitants", "of", "various", "regions", "in", "Flanders", "and", "the", "associations", "of", "gene", "expression", "with", "blood", "or", "uri-", "nary", "measures", "of", "environmental", "carcinogens,", "we", "conclude", "that", "gene", "expression", "profiling", "appears", "promising", "as", "a", "tool", "for", "biological", "monitoring", "in", "relation", "to", "environmental", "exposures", "in", "humans.", "KEY", "WORDS:", "biomarker,", "biomonitoring,", "environmental", "carcinogens,", "human", "blood,", "transcriptomics.", "Environ", "Health", "Perspect", "116:1519–1525", "(2008).", "doi:10.1289/ehp.11401", "available", "via", "http://dx.doi.org/", "[Online", "23", "June", "2008]", "Cancer", "is", "among", "the", "major", "causes", "of", "death", "in", "modern", "society", "(Boyle", "and", "Ferlay", "2005).", "Carcinogenesis", "is", "initiated", "and/or", "promoted", "by", "exposure", "to", "chemicals", "with", "carcinogenic", "properties", "that", "occur", "in", "the", "human", "environ-", "ment,", "for", "example,", "from", "ambient", "air,", "food,", "or", "lifestyle-related", "factors", "such", "as", "cigarette", "smoke", "(Czene", "et", "al.", "2002;", "Higginson", "1993;", "Le", "Marchand", "2005;", "Luch", "2005).", "Thus,", "in", "the-", "ory,", "a", "portion", "of", "cancer", "cases", "is", "preventable.", "Molecular", "epidemiology", "tools", "are", "used", "to", "iden-", "tify", "human", "cancer", "risks", "posed", "by", "exposure", "to", "environmental", "carcinogens,", "thereby", "contribut-", "ing", "to", "the", "scientific", "basis", "for", "environmental", "health", "policy", "measures.", "To", "this", "end,", "biomark-", "ers", "are", "investigated", "that", "enable", "human", "risk", "assessment", "long", "before", "traceable,", "diagnostic", "health", "effects", "appear.", "In", "monitoring", "environmental", "cancer", "risk", "among", "human", "populations,", "several", "markers", "of", "early", "biological", "effects", "[e.g.,", "DNA", "damage", "markers", "such", "as", "micronuclei", "(MN)", "and", "DNA", "strand", "breaks]", "have", "been", "developed", "and", "applied", "over", "the", "last", "decades", "(Bonassi", "et", "al.", "2005).", "However,", "these", "biomarkers", "tend", "to", "be", "nonspecific,", "raise", "questions", "about", "their", "sensitiv-", "ity,", "and", "do", "not", "generate", "insights", "in", "underlying", "modes", "of", "action.", "Genomic", "technologies", "such", "as", "microarrays", "and", "quantitative", "polymerase", "chain", "reaction", "(PCR)", "provide", "the", "opportunity", "to", "explore", "altered", "expression", "of", "large", "numbers", "of", "genes", "simultaneously", "(Afshari", "et", "al.", "1999;", "Gerhold", "et", "al.", "2001;", "Lobenhofer", "et", "al.", "2001;", "Lockhart", "and", "Winzeler", "2000)", "and", "therefore", "may", "provide", "the", "opportunity", "to", "identify", "molecular", "biomarkers", "consisting", "of", "altered", "gene", "expression", "profiles", "representing", "environmental", "health", "risks.", "Studies", "on", "carcinogen-induced", "dif-", "ferential", "gene", "expression", "have", "been", "conducted", "in", "our", "laboratory", "previously.", "Besides", "experi-", "mental", "in", "vitro", "studies", "that", "were", "directed", "toward", "obtaining", "gene", "expression", "profiles", "from", "model", "carcinogens", "in", "human", "blood", "mono-", "nuclear", "cells", "(van", "Leeuwen", "et", "al.", "2005),", "a", "con-", "cise", "human", "population", "of", "smoking-discordant", "monozygotic", "twin", "pairs", "has", "been", "investigated;", "genes", "were", "identified", "of", "which", "the", "expression", "significantly", "differed", "in", "smokers", "compared", "with", "their", "nonsmoking,", "genetically", "identical", "siblings", "(van", "Leeuwen", "et", "al.", "2007).", "Furthermore,", "in", "a", "Environmental", "Health", "Perspectives", "•", "VOLUME", "116", "|", "NUMBER", "11", "|", "November", "2008", "study", "of", "children", "from", "the", "Czech", "Republic,", "numerous", "gene", "expressions", "appeared", "relatively", "increased", "among", "children", "inhabiting", "a", "severely", "polluted", "area", "(van", "Leeuwen", "et", "al.", "2006).", "From", "these", "studies,", "eight", "genes", "have", "been", "identified", "as", "promising", "biomarkers", "for", "envi-", "ronmental", "carcinogenesis.", "They", "encompass", "genes", "of", "which", "the", "expression", "differed", "signifi-", "cantly", "between", "carcinogen-exposed", "and", "non-", "exposed", "individuals,", "in", "addition", "to", "genes", "that", "correlated", "significantly", "with", "an", "established", "biomarker", "of", "early", "biological", "effect", "(i.e.,", "MN", "frequencies)", "(van", "Leeuwen", "et", "al.", "2006,", "2007).", "The", "aim", "of", "the", "present", "study", "was", "to", "monitor", "the", "expression", "of", "this", "set", "of", "genes", "in", "humans", "inhabiting", "specific", "regions", "in", "Flanders", "and", "to", "associate", "these", "with", "blood", "and", "urinary", "meas-", "ures", "of", "established", "biomarkers", "of", "exposure", "and", "early", "biological", "effect.", "We", "measured", "the", "expression", "levels", "of", "these", "eight", "key", "genes—", "cytochrome", "P450", "1B1", "(CYP1B1),", "activating", "transcription", "factor", "4", "(ATF4),", "mitogen-", "activated", "protein", "kinase", "14", "(MAPK14),", "super-", "oxide", "dismutase", "2", "(Mn)", "(SOD2),", "chemokine", "(C-X-C", "motif)", "ligand", "1", "(melanoma", "growth", "stimulating", "activity,", "alpha)", "(CXCL1),", "diacyl-", "glycerol", "O-acyltransferase", "homolog", "2", "(mouse)", "(DGAT2),", "tigger", "transposable", "element", "derived", "3", "(TIGD3),", "and", "PTEN-induced", "putative", "kinase-1", "(PINK1)", "(van", "Leeuwen", "et", "al.", "2006,", "2007)", "(Table", "1)—in", "peripheral", "blood", "cells", "by", "means", "of", "quantitative", "PCR.", "Furthermore,", "we", "explored", "associations", "with", "blood", "and", "urinary", "measures", "of", "biomarkers", "of", "Address", "correspondence", "to", "D.M.", "van", "Leeuwen,", "Department", "of", "Health", "Risk", "Analysis", "and", "Toxicology,", "Maastricht", "University,", "P.O.", "Box", "616,", "6200", "MD", "Maastricht,", "the", "Netherlands.", "Telephone:", "31", "(0)433882127.", "Fax:", "31", "(0)433884146.", "E-mail:", "d.vanleeuwen@grat.unimaas.nl", "We", "thank", "the", "volunteers", "for", "participating", "and", "the", "nurses", "for", "the", "sample", "collections.", "This", "study", "was", "conducted", "as", "part", "of", "the", "Flemish", "Centre", "of", "Expertise", "of", "Environment", "and", "Health", "and", "was", "commissioned,", "financed,", "and", "steered", "by", "the", "Ministry", "of", "the", "Flemish", "Community", "(Department", "of", "Economics,", "Science", "and", "Innovation;", "Flemish", "Agency", "for", "Care", "and", "Health;", "and", "Department", "of", "Environment,", "Nature", "and", "Energy).", "The", "sponsor", "was", "not", "involved", "in", "analysis", "or", "interpretation", "of", "the", "data.", "The", "authors", "declare", "they", "have", "no", "competing", "financial", "interests.", "Received", "21", "February", "2008;", "accepted", "23", "June", "2008.", "1519" ]

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[ "BMC", "Psychiatry", "Research", "article", "Development", "of", "mental", "health", "first", "aid", "guidelines", "for", "suicidal", "ideation", "and", "behaviour:", "A", "Delphi", "study", "Claire", "M", "Kelly*†,", "Anthony", "F", "Jorm†,", "Betty", "A", "Kitchener", "and", "Robyn", "L", "Langlands", "BioMed", "Central", "Open", "Access", "Address:", "ORYGEN", "Research", "Centre,", "University", "of", "Melbourne,", "Australia", "Email:", "Claire", "M", "Kelly*", "-", "ckel@unimelb.edu.au;", "Anthony", "F", "Jorm", "-", "ajorm@unimelb.edu.au;", "Betty", "A", "Kitchener", "-", "bettyk@unimelb.edu.au;", "Robyn", "L", "Langlands", "-", "robyn.langlands@vuw.ac.nz", "*", "Corresponding", "author", "†Equal", "contributors", "Published:", "18", "March", "2008", "BMC", "Psychiatry", "2008,", "8:17", "doi:10.1186/1471-244X-8-17", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-244X/8/17", "Received:", "11", "September", "2007", "Accepted:", "18", "March", "2008", "©", "2008", "Kelly", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "Suicide", "is", "a", "statistically", "rare", "event,", "but", "devastating", "to", "those", "left", "behind", "and", "one", "of", "the", "worst", "possible", "outcomes", "associated", "with", "mental", "illness.", "Although", "a", "friend,", "family", "member", "or", "co-worker", "may", "be", "the", "first", "person", "to", "notice", "that", "a", "person", "is", "highly", "distressed,", "few", "have", "the", "knowledge", "and", "skills", "required", "to", "assist.", "Simple", "guidelines", "may", "help", "such", "a", "person", "to", "encourage", "a", "suicidal", "individual", "to", "seek", "professional", "help", "or", "decide", "against", "suicide.", "Methods:", "This", "research", "was", "conducted", "using", "the", "Delphi", "methodology,", "a", "method", "of", "reaching", "consensus", "in", "a", "panel", "of", "experts.", "Experts", "recruited", "to", "the", "panels", "included", "22", "professionals,", "10", "people", "who", "had", "been", "suicidal", "in", "the", "past", "and", "6", "carers", "of", "people", "who", "had", "been", "suicidal", "in", "the", "past.", "Statements", "about", "how", "to", "assist", "someone", "who", "is", "thinking", "about", "suicide", "were", "sourced", "through", "a", "systematic", "search", "of", "both", "professional", "and", "lay", "literature.", "The", "guidelines", "were", "written", "using", "the", "items", "most", "consistently", "endorsed", "by", "all", "three", "panels.", "Results:", "Of", "114", "statements", "presented", "to", "the", "panels,", "30", "were", "accepted.", "These", "statements", "were", "used", "to", "develop", "the", "guidelines", "appended", "to", "this", "paper.", "Conclusion:", "There", "are", "a", "number", "of", "actions", "which", "are", "considered", "to", "be", "useful", "for", "members", "of", "the", "public", "when", "they", "encounter", "someone", "who", "is", "experiencing", "suicidal", "thoughts", "or", "engaging", "in", "suicidal", "behaviour.", "These", "guidelines", "will", "be", "useful", "in", "revision", "of", "curricula", "of", "mental", "health", "first", "aid", "and", "suicide", "intervention", "training", "programs.", "They", "can", "also", "be", "used", "by", "members", "of", "the", "public", "who", "want", "immediate", "information", "about", "how", "to", "assist", "a", "suicidal", "person.", "Background", "Many", "different", "approaches", "have", "been", "tried", "to", "prevent", "sui-", "cide,", "but", "few", "have", "any", "strong", "supporting", "evidence.", "A", "sys-", "tematic", "review", "of", "suicide", "prevention", "strategies", "concluded", "that", "education", "of", "physicians", "and", "restriction", "of", "lethal", "means", "were", "effective,", "while", "methods", "such", "public", "educa-", "tion,", "screening", "programs", "and", "media", "education", "need", "fur-", "ther", "evaluation", "[1].", "Major", "reasons", "for", "the", "lack", "of", "evidence", "are", "the", "difficulty", "in", "researching", "the", "prevention", "of", "a", "statis-", "tically", "rare", "event", "like", "suicide", "and", "the", "ethical", "dilemma", "in", "withholding", "intervention", "in", "controlled", "trials.", "Despite", "these", "difficulties,", "there", "is", "much", "that", "can", "be", "done", "to", "improve", "the", "quality", "of", "interventions", "that", "are", "being", "tried.", "In", "this", "paper,", "we", "aim", "to", "improve", "one", "particular", "approach", "to", "public", "education", "–", "training", "of", "members", "of", "the", "public", "in", "Page", "1", "of", "10", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "SAGE-Hindawi", "Access", "to", "Research", "Stroke", "Research", "and", "Treatment", "Volume", "2011,", "Article", "ID", "534812,", "10", "pages", "doi:10.4061/2011/534812", "Review", "Article", "The", "Psychology", "of", "Stroke", "in", "Young", "Adults:", "The", "Roles", "of", "Service", "Provision", "and", "Return", "to", "Work", "Reg", "Morris", "School", "of", "Psychology,", "Cardiff", "University,", "and", "Cardiff", "and", "Vale", "University", "Local", "Health", "Board,", "Archway", "House,", "77", "TY", "Glas", "Avenue,", "Llanishen,", "Cardiff", "CF14", "5DX,", "UK", "Correspondence", "should", "be", "addressed", "to", "Reg", "Morris,", "reg.morris@wales.nhs.uk", "Received", "4", "September", "2010;", "Revised", "23", "December", "2010;", "Accepted", "9", "January", "2011", "Academic", "Editor:", "Halvor", "Naess", "Copyright", "©", "2011", "Reg", "Morris.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Literature", "about", "the", "psychological", "consequences", "of", "stroke", "in", "those", "under", "65", "is", "reviewed", "focussing", "on", "services", "and", "work.", "Despite", "similarities,", "young", "and", "old", "survivors", "have", "different", "experiences", "and", "needs.", "These", "are", "attributable", "to", "the", "effects", "of", "stroke", "on", "age-normative", "roles", "and", "activities,", "self-image,", "and", "the", "young", "person’s", "stage", "in", "the", "life-cycle,", "especially", "family", "and", "work.", "“Hidden”", "cognitive", "impairments,", "a", "disrupted", "sense", "of", "self,", "and", "the", "incongruity", "of", "suffering", "an", "“older", "person’s”", "disease", "are", "salient.", "Young", "survivors", "benefit", "from", "services,", "but", "experience", "lack", "of", "congruence", "between", "their", "needs", "and", "service", "philosophy,", "methods,", "and", "aims,", "and", "consequently", "have", "unmet", "needs.", "Employment", "is", "psychologically", "salient,", "and", "the", "evidence", "about", "return", "rates,", "factors", "that", "affect", "return,", "and", "the", "adequacy", "of", "employment-related", "service", "provision", "is", "reviewed.", "Specific", "and", "general", "recommendations", "are", "made", "for", "increasing", "congruence", "between", "young", "survivors’", "needs", "and", "service", "provision", "and", "also", "for", "facilitating", "their", "return", "to", "work.", "1.", "Definitions", "and", "Scope", "In", "this", "paper", "a", "“young”", "stroke", "survivor", "will", "be", "considered", "to", "be", "someone", "aged", "18", "to", "65", "years.", "The", "lower", "boundary", "ties", "in", "with", "the", "current", "dividing", "line", "between", "childhood", "and", "adulthood,", "and", "the", "upper", "boundary", "with", "the", "division", "between", "working", "age", "and", "old", "age", "health", "services", "in", "many", "countries.", "This", "paper", "is", "based", "upon", "literature", "searches", "of", "several", "data", "bases", "(ASSIA,", "AMED,", "British", "Nursing", "Index,", "Cochrane", "database", "of", "systematic", "reviews,", "MEDLINE,", "Psych-", "Info,", "SCOPUS,", "Zetoc,", "Google", "Scholar).", "Reference", "lists", "of", "relevant", "articles", "were", "scanned,", "and", "papers", "that", "cited", "articles", "were", "also", "examined", "to", "supplement", "these", "searches.", "Reviews", "and", "original", "articles", "that", "included", "material", "of", "psychological", "relevance", "were", "selected", "for", "further", "scrutiny", "and", "possible", "inclusion.", "The", "focus", "of", "the", "paper", "is", "upon", "factors", "that", "affect", "the", "psychological", "adjustment", "of", "stroke", "survivors,", "particularly", "service", "provision", "and", "employment.", "2.", "Introduction", "The", "risk", "of", "stroke", "increases", "with", "age,", "and", "the", "relationship", "with", "age", "is", "universally", "found", "across", "nations", "[1].", "The", "incidence", "of", "stroke", "in", "younger", "people", "is", "low,", "but", "the", "population", "demographics", "of", "age", "mean", "that", "a", "significant", "proportion", "of", "new", "strokes", "occur", "in", "the", "under", "65s.", "This", "proportion", "has", "been", "estimated", "as", "21%", "in", "the", "UK", "[2].", "As", "an", "example,", "a", "country", "of", "the", "size", "of", "England,", "with", "a", "population", "of", "about", "50", "million,", "and", "about", "29", "million", "under", "45,", "would", "expect", "around", "5,800", "new", "strokes", "in", "people", "under", "45", "each", "year.", "Since", "people", "who", "have", "a", "stroke", "when", "young", "are", "likely", "to", "live", "longer", "than", "their", "elderly", "counterparts,", "the", "prevalence", "rate", "for", "younger", "strokes", "is", "about", "25%", "[2,", "3].", "Younger", "people", "have", "proportionately", "more", "haemorrhagic", "strokes", "[4,", "5],", "and", "ethnic", "differences", "in", "the", "risk", "of", "stroke", "are", "accentuated", "in", "younger", "age", "groups", "[6].", "3.", "Stroke", "and", "Psychological", "Adjustment", "in", "the", "Young", "The", "psychological", "effects", "of", "stroke", "and", "the", "evidence", "for", "their", "occurrence", "are", "summarised", "in", "Table", "1.", "Quality", "of", "life", "after", "stroke", "for", "all", "age", "groups", "was", "impaired", "in", "comparison", "with", "comparable", "healthy", "adults", "[7,", "8],", "and", "studies", "comparing", "the", "quality", "of", "life", "of", "younger", "and", "older" ]

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[ "A", "Novel", "Flow", "Cytometric", "HTS", "Assay", "Reveals", "Functional", "Modulators", "of", "ATP", "Binding", "Cassette", "Transporter", "ABCB6", "Kishore", "Polireddy1.,", "Mohiuddin", "Md.", "Taimur", "Khan2,3,4.,", "Hemantkumar", "Chavan1,", "Susan", "Young", "2", ",", "Xiaochao", "Ma1,", "Anna", "Waller2,", "Matthew", "Garcia2,", "Dominique", "Perez2,", "Stephanie", "Chavez2,", "Jacob", "J.", "Strouse2,", "Mark", "K.", "Haynes2,", "Cristian", "G.", "Bologa2,3,", "Tudor", "I.", "Oprea2,3,", "George", "P.", "Tegos2,4,5,6*,", "Larry", "A.", "Sklar2,3,4*,", "Partha", "Krishnamurthy1*", "1", "Department", "of", "Pharmacology,", "Toxicology,", "and", "Therapeutics,", "The", "University", "of", "Kansas", "Medical", "Center,", "Kansas", "City,", "Kansas,", "United", "States", "of", "America,", "2", "Center", "for", "Molecular", "Discovery,", "University", "of", "New", "Mexico,", "Albuquerque,", "New", "Mexico,", "United", "States", "of", "America,", "3", "Division", "of", "Biocomputing,", "University", "of", "New", "Mexico", "Health", "Sciences", "Center,", "Albuquerque,", "New", "Mexico,", "United", "States", "of", "America,", "4", "Department", "of", "Pathology,", "University", "of", "New", "Mexico", "School", "of", "Medicine,", "Albuquerque,", "New", "Mexico,", "United", "States", "of", "America,", "5", "Wellman", "Center", "for", "Photomedicine,", "Massachusetts", "General", "Hospital,", "Boston,", "Massachusetts,", "United", "States", "of", "America,", "6", "Department", "of", "Dermatology,", "Harvard", "Medical", "School,", "Boston,", "Massachusetts,", "United", "States", "of", "America", "Abstract", "ABCB6", "is", "a", "member", "of", "the", "adenosine", "triphosphate", "(ATP)-binding", "cassette", "family", "of", "transporter", "proteins", "that", "is", "increasingly", "recognized", "as", "a", "relevant", "physiological", "and", "therapeutic", "target.", "Evaluation", "of", "modulators", "of", "ABCB6", "activity", "would", "pave", "the", "way", "toward", "a", "more", "complete", "understanding", "of", "the", "significance", "of", "this", "transport", "process", "in", "tumor", "cell", "growth,", "proliferation", "and", "therapy-related", "drug", "resistance.", "In", "addition,", "this", "effort", "would", "improve", "our", "understanding", "of", "the", "function", "of", "ABCB6", "in", "normal", "physiology", "with", "respect", "to", "heme", "biosynthesis,", "and", "cellular", "adaptation", "to", "metabolic", "demand", "and", "stress", "responses.", "To", "search", "for", "modulators", "of", "ABCB6,", "we", "developed", "a", "novel", "cell-based", "approach", "that,", "in", "combination", "with", "flow", "cytometric", "high-throughput", "screening", "(HTS),", "can", "be", "used", "to", "identify", "functional", "modulators", "of", "ABCB6.", "Accumulation", "of", "protoporphyrin,", "a", "fluorescent", "molecule,", "in", "wild-type", "ABCB6", "expressing", "K562", "cells,", "forms", "the", "basis", "of", "the", "HTS", "assay.", "Screening", "the", "Prestwick", "Chemical", "Library", "employing", "the", "HTS", "assay", "identified", "four", "compounds,", "benzethonium", "chloride,", "verteporfin,", "tomatine", "hydrochloride", "and", "piperlongumine,", "that", "reduced", "ABCB6", "mediated", "cellular", "porphyrin", "levels.", "Validation", "of", "the", "identified", "compounds", "employing", "the", "hemin-agarose", "affinity", "chromatography", "and", "mitochondrial", "transport", "assays", "demonstrated", "that", "three", "out", "of", "the", "four", "compounds", "were", "capable", "of", "inhibiting", "ABCB6", "mediated", "hemin", "transport", "into", "isolated", "mitochondria.", "However,", "only", "verteporfin", "and", "tomatine", "hydrochloride", "inhibited", "ABCB6’s", "ability", "to", "compete", "with", "hemin", "as", "an", "ABCB6", "substrate.", "This", "assay", "is", "therefore", "sensitive,", "robust,", "and", "suitable", "for", "automation", "in", "a", "high-throughput", "environment", "as", "demonstrated", "by", "our", "identification", "of", "selective", "functional", "modulators", "of", "ABCB6.", "Application", "of", "this", "assay", "to", "other", "libraries", "of", "synthetic", "compounds", "and", "natural", "products", "is", "expected", "to", "identify", "novel", "modulators", "of", "ABCB6", "activity.", "Citation:", "Polireddy", "K,", "Khan", "MMT,", "Chavan", "H,", "Young", "S,", "Ma", "X,", "et", "al.", "(2012)", "A", "Novel", "Flow", "Cytometric", "HTS", "Assay", "Reveals", "Functional", "Modulators", "of", "ATP", "Binding", "Cassette", "Transporter", "ABCB6.", "PLoS", "ONE", "7(7):", "e40005.", "doi:10.1371/journal.pone.0040005", "Editor:", "Irina", "V.", "Lebedeva,", "Enzo", "Life", "Sciences,", "Inc.,", "United", "States", "of", "America", "Received", "November", "29,", "2011;", "Accepted", "May", "30,", "2012;", "Published", "July", "10,", "2012", "Copyright:", "2012", "Polireddy", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "Funding", "for", "GPT", "and", "LAS", "was", "provided", "by", "the", "National", "Institutes", "of", "Health", "(NIH,", "5U54MH084690-02,", "Center", "Driven", "Initiative", "1)", "and", "PK", "by", "R03MH093193.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "No", "additional", "external", "funding", "received", "for", "this", "study.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "gtegos@salud.unm.edu", "(GPT);", "lsklar@salud.unm.edu", "(LAS);", "pkrishnamurthy@kumc.edu", "(PK)", ".", "These", "authors", "contributed", "equally", "to", "this", "work.", "Introduction", "Transporters", "perform", "essential", "roles", "in", "cellular", "metabolism", "and", "activity.", "They", "differ", "in", "membrane", "topology,", "energy", "coupling", "mechanisms,", "and", "most", "importantly", "in", "substrate", "specificities", "[1–4].", "Based", "on", "their", "sequence", "similarity", "and", "structural", "homology,", "transporters", "are", "classified", "into", "six", "super-families", "[1,3].", "The", "ATP", "binding", "cassette", "transporter", "superfamily", "is", "the", "largest,", "comprising", "seven", "subfamilies", "designated", "A", "to", "G", "[1,4].", "ABC", "transporters", "are", "increasingly", "recognized", "as", "playing", "important", "roles", "in", "normal", "biology", "and", "therapeutic", "responses", "to", "medications", "in", "mammalian", "cells.", "The", "highly", "conserved", "ABC", "domains", "of", "ABC", "transporters", "provide", "the", "nucleotide-dependent", "engine", "that", "drives", "transport", "[1,2].", "ABCB6", "belongs", "to", "the", "B", "sub-family", "of", "ABC", "transporters,", "which", "includes", "the", "well-characterized", "human", "transporter", "ABCB1", "that", "was", "the", "first", "ABC", "transporter", "implicated", "in", "multidrug", "resistance,", "the", "intracellular", "peptide", "transporters", "(TAP1", "and", "TAP2)", "that", "function", "in", "major", "histocompatibility", "complex", "class", "I", "antigen", "presentation", "and", "ABCB5", "which", "is", "essential", "for", "melanoma", "induction,", "as", "a", "doxorubicin", "efflux", "mediator", "in", "melanomas", "and", "xenotransplantation", "proliferation", "models", "[3,5].", "ABCB6", "is", "increas-", "ingly", "recognized", "as", "a", "relevant", "physiologic", "and", "therapeutic", "target.", "ABCB6", "expression", "is", "upregulated", "in", "many", "tumor", "cell", "lines", "and", "in", "liver", "tumors", "where", "it", "appears", "to", "promote", "cell", "survival", "and", "tumor", "growth", "and", "proliferation", "[5–7].", "ABCB6", "gene", "is", "amplified", "in", "tumor", "cells", "with", "acquired", "chemotherapeutic", "resistance", "[8–13].", "ABCB6", "expression", "is", "also", "induced", "under", "cell", "stress,", "where", "it", "promotes", "cell", "survival", "[8,14–16].", "Thus,", "ABCB6", "expression", "could", "promote", "PLoS", "ONE", "|", "www.plosone.org", "1", "July", "2012", "|", "Volume", "7", "|", "Issue", "7", "|", "e40005" ]

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[ "Cerqueira", "et", "al.", "BMC", "Microbiology", "2011,", "11:101", "http://www.biomedcentral.com/1471-2180/11/101", "M", "E", "T", "H", "O", "D", "O", "L", "O", "G", "Y", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "PNA-FISH", "as", "a", "new", "diagnostic", "method", "for", "the", "determination", "of", "clarithromycin", "resistance", "of", "Helicobacter", "pylori", "Laura", "Cerqueira1,", "Ricardo", "M", "Fernandes1,", "Rui", "M", "Ferreira2,3,", "Fátima", "Carneiro2,3,4,", "Mário", "Dinis-Ribeiro3,5,", "Céu", "Figueiredo2,3,", "Charles", "W", "Keevil6,", "Nuno", "F", "Azevedo1,7", "and", "Maria", "J", "Vieira1*", "Abstract", "Background:", "Triple", "therapy", "is", "the", "gold", "standard", "treatment", "for", "Helicobacter", "pylori", "eradication", "from", "the", "human", "stomach,", "but", "increased", "resistance", "to", "clarithromycin", "became", "the", "main", "factor", "of", "treatment", "failure.", "Until", "now,", "fastidious", "culturing", "methods", "are", "generally", "the", "method", "of", "choice", "to", "assess", "resistance", "status.", "In", "this", "study,", "a", "new", "genotypic", "method", "to", "detect", "clarithromycin", "resistance", "in", "clinical", "samples,", "based", "on", "fluorescent", "in", "situ", "hybridization", "(FISH)", "using", "a", "set", "of", "peptide", "nucleic", "acid", "probes", "(PNA),", "is", "proposed.", "Results:", "The", "set", "of", "probes", "targeting", "the", "point", "mutations", "responsible", "for", "clarithromycin", "resistance", "was", "applied", "to", "H.", "pylori", "suspensions", "and", "showed", "100%", "sensitivity", "and", "specificity", "(95%", "CI,", "79.9-100", "and", "95%", "CI,", "71.6-100", "respectively).", "This", "method", "can", "also", "be", "amenable", "for", "application", "to", "gastric", "biopsy", "samples,", "as", "resistance", "to", "clarithromycin", "was", "also", "detected", "when", "histological", "slides", "were", "tested.", "Conclusions:", "The", "optimized", "PNA-FISH", "based", "diagnostic", "method", "to", "detect", "H.", "pylori", "clarithromycin", "resistance", "shown", "to", "be", "a", "very", "sensitive", "and", "specific", "method", "for", "the", "detection", "of", "clarithromycin", "resistance", "in", "the", "H.", "pylori", "smears", "and", "also", "proved", "to", "be", "a", "reliable", "method", "for", "the", "diagnosis", "of", "this", "pathogen", "in", "clinical", "samples", "and", "an", "alternative", "to", "existing", "plating", "methods.", "Background", "Helicobacter", "pylori", "is", "well", "known", "for", "its", "ability", "to", "colo-", "nize", "human", "stomach", "and,", "while", "most", "human", "carriers", "are", "asymptomatic,", "colonization", "can", "lead", "to", "the", "develop-", "ment", "of", "several", "gastric", "diseases,", "such", "as", "peptic", "ulcer", "dis-", "ease,", "gastric", "mucosa-associated", "lymphoid", "tissue", "(MALT)", "lymphoma", "and", "gastric", "carcinoma.", "The", "over-usage", "of", "antimicrobial", "compounds", "has", "led", "to", "an", "increase", "of", "H.", "pylori", "resistance", "to", "antibiotics", "and", "consequent", "failure", "in", "treatment", "therapy", "[1,2].", "In", "accor-", "dance", "with", "the", "Maastricht", "Consensus", "in", "Europe,", "the", "recommended", "therapy", "for", "H.", "pylori", "eradication", "in", "the", "stomach", "mucosa", "is", "the", "use", "of", "a", "proton", "pump", "inhibitor", "associated", "with", "two", "antibiotics,", "such", "as", "metronidazole,", "amoxicillin", "or", "clarithromycin", "for", "a", "7-14", "days", "period", "[3].", "*", "Correspondence:", "mjv@deb.uminho.pt", "1IBB", "-", "Institute", "for", "Biotechnology", "and", "Bioengineering,", "Centre", "of", "Biological", "Engineering,", "Universidade", "do", "Minho,", "Campus", "de", "Gualtar", "4710-057,", "Braga,", "Portugal", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "This", "therapy,", "although", "highly", "effective,", "is", "unselectively", "proposed", "to", "all", "patients", "and", "can", "imply", "serious", "discom-", "fort", "to", "patients", "due", "to", "side", "effects", "of", "the", "antibiotics.", "Clarithromycin", "resistance", "is", "one", "of", "the", "most", "prevalent", "and", "can", "reach", "up", "to", "20%", "in", "Southern", "European", "coun-", "tries", "[1].", "The", "resistance", "is", "associated", "with", "point", "muta-", "tions", "in", "the", "peptidyltransferase", "region", "encoded", "in", "domain", "V", "of", "the", "H.", "pylori", "23S", "rRNA", "gene", "[2,4,5].", "The", "three", "most", "prevalent", "point", "mutations", "are", "the", "transitions", "A2142G", "and", "A2143G", "and", "the", "transversion", "A2142C", "[1,2,4].", "Until", "now,", "the", "antibiotic", "susceptibility", "has", "been", "detected", "in", "clinical", "laboratories", "by", "several", "phenotypical", "methods", "such", "as", "the", "agar", "dilution", "method,", "as", "recom-", "mended", "by", "the", "National", "Committee", "for", "Clinical", "Labora-", "tory", "Standards", "(NCCLS)", "[6],", "or", "the", "alternative", "E-test", "that", "is", "considered", "to", "be", "more", "simple", "[7-10].", "However,", "these", "methods", "are", "fastidious,", "time", "consuming", "[11],", "and", "fail", "to", "give", "any", "information", "about", "the", "point", "mutation", "within", "the", "sample", "[3].", "Therefore,", "molecular", "methods", "for", "the", "detection", "of", "clarithromycin", "resistance", "in", "H.", "pylori", "©", "2011", "Cerqueira", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", 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[ "Ann", "Hematol", "(2010)", "89", "(Suppl", "1):S5–S10", "DOI", "10.1007/s00277-010-0941-1", "MANAGEMENT", "ENDPOINTS", "Consensus", "Paper—ICIS", "Expert", "Meeting", "Basel", "2009", "treatment", "milestones", "in", "immune", "thrombocytopenia", "Hannah", "Tamary", "&", "Jelena", "Roganovic", "&", "Meera", "Chitlur", "&", "Diane", "J.", "Nugent", "Received:", "10", "December", "2009", "/", "Accepted:", "4", "March", "2010", "/", "Published", "online:", "1", "April", "2010", "#", "The", "Author(s)", "2010.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "The", "rarity", "of", "severe", "complications", "of", "this", "disease", "in", "children", "makes", "randomized", "clinical", "trials", "in", "immune", "throm-", "bocytopenia", "(ITP)", "unfeasible.", "Therefore,", "the", "current", "manage-", "ment", "recommendations", "for", "ITP", "are", "largely", "dependent", "on", "clinical", "expertise", "and", "observations.", "As", "part", "of", "its", "discussions", "during", "the", "Intercontinental", "Cooperative", "ITP", "Study", "Group", "Expert", "Meeting", "in", "Basel,", "the", "Management", "working", "group", "recommended", "that", "the", "decision", "to", "treat", "an", "ITP", "patient", "be", "individualized", "and", "based", "mainly", "on", "bleeding", "symptoms", "and", "not", "on", "the", "actual", "platelet", "count", "number", "and", "should", "be", "supported", "by", "bleeding", "scores", "using", "a", "validated", "assessment", "tool.", "The", "group", "stressed", "the", "need", "to", "develop", "a", "uniform", "validated", "bleeding", "score", "system", "and", "to", "explore", "new", "measures", "to", "evaluate", "bleeding", "risk", "in", "thrombocytopenic", "patients—the", "role", "of", "rituximab", "as", "a", "splenectomy-sparing", "agent", "in", "resistant", "disease", "was", "also", "discussed.", "Given", "the", "apparently", "high", "recurrence", "rate", "to", "rituximab", "therapy", "in", "H.", "Tamary", "Pediatric", "Hematology", "Oncology", "Center,", "Schneider", "Children’s", "Medical", "Center", "of", "Israel,", "Petach", "Tikva", "and", "Sackler", "Faculty", "of", "Medicine,", "Tel", "Aviv", "University,", "Tel", "Aviv,", "Israel", "J.", "Roganovic", "Division", "of", "Hematology", "and", "Oncology,", "University", "Children’s", "Hospital,", "Rijeka,", "Croatia", "M.", "Chitlur", "Department", "of", "Pediatric", "Hematology/Oncology,", "Children’s", "Hospital", "of", "Michigan", "Detroit,", "Detroit,", "MI,", "USA", "D.", "J.", "Nugent", "(*)", "Pediatric", "Hematology,", "CHOC", "Children’s", "Hospital", "and", "University", "of", "California,", "Irvine,", "CA,", "USA", "e-mail:", "tomdiane@cox.net", "children", "and", "the", "drug's", "possible", "toxicity,", "the", "group", "felt", "that", "until", "more", "data", "are", "available,", "a", "conservative", "approach", "may", "be", "considered,", "reserving", "rituximab", "for", "patients", "who", "failed", 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[ "W444–W450", "Nucleic", "Acids", "Research,", "2007,", "Vol.", "35,", "Web", "Server", "issue", "doi:10.1093/nar/gkm364", "ProtSweep,", "2Dsweep", "and", "DomainSweep:", "protein", "analysis", "suite", "at", "DKFZ", "C.", "del", "Val1,2,*,", "P.", "Ernst1,", "M.", "Falkenhahn", "1", ",", "C.", "Fladerer1,", "K.", "H.", "Glatting", "1", ",", "S.", "Suhai1", "and", "A.", "Hotz-Wagenblatt1", "1DKFZ,", "German", "Cancer", "Research", "Center,", "Division", "of", "Molecular", "Biophysics,", "Im", "Neuenheimer", "Feld", "580,", "D-69120", "Heidelberg,", "Germany", "and", "2Department", "of", "Computer", "Science", "and", "Artificial", "Intelligence,", "ETSII", "University", "of", "Granada,", "C/Daniel", "Saucedo", "Aranda", "s/n", "18071,", "Granada,", "Spain", "Received", "January", "31,", "2007;", "Revised", "April", "4,", "2007;", "Accepted", "April", "25,", "2007", "ABSTRACT", "The", "wealth", "of", "transcript", "information", "that", "has", "been", "made", "publicly", "available", "in", "recent", "years", "has", "led", "to", "large", "pools", "of", "individual", "web", "sites", "offering", "access", "to", "bioinformatics", "software.", "However,", "finding", "out", "which", "services", "exist,", "what", "they", "can", "or", "cannot", "do,", "how", "to", "use", "them", "and", "how", "to", "feed", "results", "from", "one", "service", "to", "the", "next", "one", "in", "the", "right", "format", "can", "be", "very", "time", "and", "resource", "consuming,", "especially", "for", "non-experts.", "Automating", "this", "task,", "we", "present", "a", "suite", "of", "protein", "annotation", "pipelines", "(tasks)", "developed", "at", "the", "German", "Cancer", "Research", "Centre", "(DKFZ)", "oriented", "to", "protein", "annotation", "by", "homology", "(ProtSweep),", "by", "domain", "analysis", "(DomainSweep),", "and", "by", "secondary", "structure", "elements", "(2Dsweep).", "The", "aim", "of", "these", "tasks", "is", "to", "perform", "an", "exhaustive", "structural", "and", "functional", "analysis", "employing", "a", "wide", "variety", "of", "methods", "in", "combination", "with", "the", "most", "updated", "public", "databases.", "The", "three", "servers", "are", "available", "for", "academic", "users", "at", "the", "HUSAR", "open", "server", "http://", "genius.embnet.dkfz-heidelberg.de/menu/biounit/", "open-husar/", "INTRODUCTION", "As", "more", "and", "more", "genomes", "are", "automatically", "sequenced,", "comprehensive", "protein", "annotation", "is", "a", "needed", "step", "after", "gene", "identification.", "Even", "in", "good", "annotated", "genomes", "(human,", "mouse)", "about", "30%", "of", "all", "proteins", "are", "not", "functionally", "identified", "(1–3),", "and", "thus", "often", "a", "similarity", "search", "will", "not", "be", "sufficient.", "Here,", "we", "present", "a", "suite", "of", "protein", "tasks,", "ProtSweep,", "DomainSweep", "and", "2Dsweep,", "which", "perform", "analysis", "from", "sequence", "similarity", "to", "small", "domains", "and", "structural", "elements.", "This", "includes", "similarity", "searches", "against", "protein", "sequence", "databases", "and", "special-", "ized", "motif", "collections,", "prediction", "of", "secondary", "structural", "elements,", "attributing", "each", "sequence", "to", "known", "super-", "families,", "protein", "localization", "prediction,", "physicochemical", "protein", "characteristics", "and", "domain", "functional", "assignation.", "Our", "strategy", "for", "assigning", "relevant", "functional", "roles", "is", "based", "on", "the", "joint", "use", "of", "both", "global", "(homology", "similarity)", "and", "local", "(domain", "and", "motif)", "sequence", "similarities", "(4).", "The", "three", "servers", "are", "available", "for", "academic", "users", "at", "the", "HUSAR", "open", "server", "http://genius.", "embnet.dkfz-heidelberg.de/menu/biounit/open-husar/", "WEB", "INTERFACE", "The", "input", "for", "all", "the", "three", "servers", "is", "a", "protein", "sequence.", "Several", "query", "sequences", "can", "be", "uploaded", "by", "the", "usual", "‘copy", "&", "paste’", "procedure", "into", "the", "input", "box", "using", "FASTA", "format.", "If", "more", "than", "one", "sequence", "is", "to", "be", "queried,", "a", "multiple", "FASTA", "file", "can", "be", "used.", "The", "query", "starts", "by", "clicking", "on", "the", "‘submit’", "button.", "Then", "the", "user", "will", "be", "redirected", "to", "an", "application", "page,", "and", "the", "run‘‘", "button", "can", "start", "the", "task.", "Additionally,", "there", "is", "a", "link", "to", "an", "online", "help,", "indicated", "with", "a", "‘?’,", "with", "the", "following", "topics:", "short", "description,", "programs", "employed,", "algorithm,", "output,", "additional", "options", "and", "acknowledgments.", "Results", "can", "be", "received", "by", "selecting", "the", "tab", "‘Go", "to", "results", "page’.", "The", "results", "are", "provided", "as", "HTML", "for", "visual", "inspection", "or", "can", "be", "downloaded", "as", "XML", "for", "storage", "in", "private", "databases.", "In", "case", "of", "error", "when", "clicking", "on", "the", "application", "name", "in", "the", "Results", "Manager", "page,", "a", "log-file", "is", "displayed", "where", "more", "human", "readable", "error", "messages", "can", "be", "found.", "Databases", "Standard", "protein", "databases", "used", "by", "the", "tasks", "like", "Uniprot/SwissProt,", "Uniprot/TREMBL", "and", "RefSeq", "are", "automatically", "updated", "whenever", "new", "versions", "become", "*To", "whom", "correspondence", "should", "be", "addressed.", "Tel:", "þ49-6221-422349;", "Fax:", "þ49-6221-439633;", "Email:", "c.delval@dkfz.de,", "delval@decsai.ugr.as", "Present", "address:", "M.", "Falkenhann,", "Sanofi-Aventis", "Deutschland", "GmbH,", "Germany", "C.", "Fladerer,", "Proteom", "Centrum", "Tu¨", "bingen,", "Germany", "2007", "The", "Author(s)", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/", "by-nc/2.0/uk/)", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Nutrients", "2010,", "2,", "230-240;", "doi:10.3390/nu2030240", "OPEN", "ACCESS", "nutrients", "ISSN", "2072-6643", "www.mdpi.com/journal/nutrients", "Article", "Continuous", "Feedings", "of", "Fortified", "Human", "Milk", "Lead", "to", "Nutrient", "Losses", "of", "Fat,", "Calcium", "and", "Phosphorous", "Stefanie", "P.", "Rogers", "1,", "Penni", "D.", "Hicks", "2,", "Maria", "Hamzo", "2,", "Lauren", "E.", "Veit", "3", "and", "Steven", "A.", "Abrams", "2,4,*", "1", "2", "3", "4", "Northwest", "Newborn", "Specialists", "501", "N,", "Graham", "Suite", "265,", "Portland,", "OR", "97227", "USA;", "E-Mail:", "stefanie@nwnewborn.com", "United", "States", "Department", "of", "Agriculture/Agricultural", "Research", "Service,", "Children's", "Nutrition", "Research", "Center,", "Department", "of", "Pediatrics,", "Baylor", "College", "of", "Medicine,", "1100", "Bates", "St.", "Houston,", "Texas", "77030", "USA;", "E-Mails:", "hamzom@stthom.edu", "(M.H.);", "pennih@bcm.edu", "(P.D.H.)", "Department", "of", "Biomedical", "Engineering,", "Rensselaer", "Polytechnic", "Institute,", "Troy,", "NY", "12180", "USA;", "E-Mail:", "Veitl@rpi.edu", "Section", "of", "Neonatology,", "Department", "of", "Pediatrics,", "Baylor", "College", "of", "Medicine", "and", "Texas", "Children’s", "Hospital,", "Houston,", "Texas", "77030", "USA", "*", "Author", "to", "whom", "correspondence", "should", "be", "addressed;", "E-Mail:", "sabrams@bcm.edu.", "Received:", "4", "February", "2010", "/", "Accepted:", "25", "February", "2010", "/", "Published:", "26", "February", "2010", "Abstract:", "Substantial", "losses", "of", "nutrients", "may", "occur", "during", "tube", "(gavage)", "feeding", "of", "fortified", "human", "milk.", "Our", "objective", "was", "to", "compare", "the", "losses", "of", "key", "macronutrients", "and", "minerals", "based", "on", "method", "of", "fortification", "and", "gavage", "feeding", "method.", "We", "used", "clinically", "available", "gavage", "feeding", "systems", "and", "measured", "pre-", "and", "post-feeding", "(end-point)", "nutrient", "content", "of", "calcium", "(Ca),", "phosphorus", "(Phos),", "protein,", "and", "fat.", "Comparisons", "were", "made", "between", "continuous,", "gravity", "bolus,", "and", "30-minute", "infusion", "pump", "feeding", "systems,", "as", "well", "as", "human", "milk", "fortified", "with", "donor", "human", "milk-based", "and", "bovine", "milk-based", "human", "milk", "fortifier", "using", "an", "in", "vitro", "model.", "Feeding", "method", "was", "significantly", "associated", "with", "fat", "and", "Ca", "losses,", "with", "increased", "losses", "in", "continuous", "feeds.", "Fat", "losses", "in", "continuous", "feeds", "were", "substantial,", "with", "40", "±", "3", "%", "of", "initial", "fat", "lost", "during", "the", "feeding", "process.", "After", "correction", "for", "feeding", "method,", "human", "milk", "fortified", "with", "donor", "milk-based", "fortifier", "was", "associated", "with", "significantly", "less", "loss", "of", "Ca", "(8", "±", "4%", "vs.", "28", "±", "4%,", "p<", "0.001),", "Phos", "(3", "±", "4%", "vs.", "24", "±", "4%,", "p", "<", "0.001),", "and", "fat", "(17", "±", "2%", "vs.", "25", "±", "2%,", "p", "=", "0.001)", "than", "human", "milk", "fortified", "with", "a", "bovine", "milk-based", "fortifier", "(Mean", "±", "SEM)." ]

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[ "Michard", "et", "al.", "Critical", "Care", "2011,", "15:445", "http://ccforum.com/content/15/5/445", "L", "E", "T", "T", "E", "R", "Perioperative", "hemodynamic", "therapy:", "quality", "improvement", "programs", "should", "help", "to", "resolve", "our", "uncertainty", "Frederic", "Michard*1,", "Maxime", "Cannesson2", "and", "Benoit", "Vallet3", "See", "related", "commentary", "by", "MacDonald", "and", "Pearse,", "http://ccforum.com/content/15/3/122", "We", "read", "with", "interest", "the", "commentary", "by", "MacDonald", "and", "Pearse", "[1]", "stating", "that", "only", "large", "randomized", "clinical", "trials", "(RCTs)", "can", "resolve", "our", "uncertainty", "regarding", "the", "value", "of", "perioperative", "hemodynamic", "therapy.", "Over", "the", "past", "20", "years,", "more", "than", "20", "small", "to", "medium", "size", "RCTs", "and", "several", "meta-analyses", "have", "shown", "that", "perioperative", "hemodynamic", "optimization", "improves", "post-operative", "outcome", "[2].", "Despite", "this", "level", "of", "evidence,", "we", "fully", "agree", "with", "MacDonald", "and", "Pearse", "that", "uncertainty", "remains", "for", "many", "anesthetists", "[3].", "This", "uncertainty", "is", "nicely", "illus-", "trated", "by", "a", "recent", "survey", "showing", "that", "the", "vast", "majority", "of", "anesthetists", "do", "not", "follow", "perioperative", "hemodynamic", "protocols", "during", "high-risk", "surgery", "[4].", "We", "are", "not", "convinced,", "however,", "that", "only", "large", "RCTs", "can", "resolve", "our", "uncertainty.", "First,", "a", "blind", "design", "is", "not", "applicable", "in", "this", "context.", "Second,", "manpower", "is", "rarely", "an", "issue", "when", "conducting", "a", "clinical", "trial", "with", "dedicated", "investigators", "while", "it", "may", "become", "a", "limitation", "when", "implementing", "a", "new", "treatment", "protocol", "in", "daily", "practice.", "Last", "but", "not", "least,", "the", "Hawthorne", "effect", "-", "a", "form", "of", "reactivity", "whereby", "caregivers", "improve", "or", "modify", "their", "behavior", "when", "participating", "in", "a", "study", "-", "may", "affect", "the", "outcome", "in", "both", "groups,", "rendering", "hazardous", "the", "extrapolation", "of", "RCT", "results", "to", "the", "real", "world.", "This", "is", "particularly", "true", "for", "perioperative", "hemodynamic", "therapy", "since", "the", "mere", "eyeballing", "of", "the", "arterial", "pressure", "waveform", "gives", "valuable", "information", "regarding", "fluid", "responsiveness.", "As", "a", "result,", "large", "and", "visible", "respiratory", "swings", "in", "arterial", "pressure", "will", "likely", "trigger", "fluid", "administration", "in", "patients", "who", "do", "not", "belong", "to", "the", "goal-", "directed", "therapy", "group.", "Quality", "improvement", "research", "programs", "have", "emerged", "over", "the", "past", "5", "years", "and", "allow", "the", "evaluation", "of", "new", "*Correspondence:", "michard.frederic@free.fr", "1Critical", "Care,", "Edwards", "Lifesciences,", "Irvine,", "CA", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "©", "2010", "BioMed", "Central", "Ltd", "©", "2011", "BioMed", "Central", "Ltd", "clinical", "strategies", "in", "real", "life", "conditions", "[5].", "These", "before-", "and-after", "evaluations", "could", "be", "applied", "to", "perioperative", "hemodynamic", "therapy", "and", "we", "believe", "they", "have", "strong", "potential", "to", "resolve", "our", "uncertainty.", "RCTs,", "definitely", "gold", "standards", "for", "double-blind", "drug", "trials,", "may", "not", "be", "the", "most", "appropriate", "method", "to", "assess", "the", "value", "of", "new", "monitoring", "strategies", "and", "treatment", "protocols", "in", "the", "real", "world.", "Abbreviations", "RCT,", "randomized", "clinical", "trial.", "Competing", "interests", "FM", "is", "a", "Vice-President,", "Global", "Medical", "Strategy,", "at", "Edwards", "Lifesciences.", "The", "above", "statements", "do", "not", "support", "the", "use", "of", "any", "specific", "medical", "device.", "The", "other", "authors", "declare", "that", "they", "have", "no", "competing", "interests.", "Author", "details", "1Critical", "Care,", "Edwards", "Lifesciences,", "Irvine,", "CA.", "2Department", "of", "Anesthesia", "and", "Perioperative", "Care,", "University", "of", "California", "Irvine,", "USA.", "3Department", "of", "Anesthesia,", "University", "Hospital", "of", "Lille,", "France.", "Published:", "10", "October", "2011", "References", "1.", "McDonald", "N,", "Pearse", "RM:", "Peri-operative", "hemodynamic", "therapy:", "only", "large", "clinical", "trials", "can", "resolve", "our", "uncertainty.", "Crit", "Care", "2011,", "15:122.", "2.", "Hamilton", "MA,", "Cecconi", "M,", "Rhodes", "A:", "A", "systematic", "review", "and", "meta-analysis", "on", "the", "use", "of", "preemptive", "hemodynamic", "intervention", "to", "improve", "postoperative", "outcomes", "in", "moderate", "and", "high-risk", "surgical", "patients.", "Anesth", "Analg", "2011,", "112:1392-1402.", "3.", "Miller", "TE,", "Roche", "AM,", "Gan", "TJ:", "Poor", "adoption", "of", "hemodynamic", "optimization", "during", "major", "surgery:", "are", "we", "practicing", "substandard", "care?", "Anesth", "Analg", "2011,", "112:1274-1276.", "4.", "Cannesson", "M,", "Pestel", "G,", "Ricks", "C,", "Hoeft", "A,", "Perel", "A:", "Hemodynamic", "monitoring", "and", "management", "in", "patients", "undergoing", "high", "risk", "surgery:", "a", "survey", "among", "American", "society", "of", "anesthesiologists", "and", "European", "society", "of", "anaesthesiology", "members.", "Crit", "Care", "2011,", "15:in", "press.", "5.", "Pronovost", "P,", "Needham", "D,", "Berenholtz", "S,", "Sinopoli", "D,", "Chu", "H,", "Cosgrove", "S,", "Sexton", "B,", "Hyzy", "R,", "Welsh", "R,", "Roth", "G,", "Bander", "J,", "Kepros", "J,", "Goeschel", "C:", "An", "intervention", "to", "decrease", "catheter-related", "bloodstream", "infections", "in", "the", "ICU.", "N", "Engl", "J", "Med", "2006,", "355:2725-2732.", "doi:10.1186/cc10336", "Cite", "this", "article", "as:", "Michard", "F,", "et", "al.:", "Perioperative", "hemodynamic", "therapy:", "quality", "improvement", "programs", "should", "help", "to", "resolve", "our", "uncertainty.", "Critical", "Care", "2011,", "15:445." ]

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[ "88", "The", "Open", "AIDS", "Journal,", "2010,", "4,", "88-95", "Socio-Demographic", "Determinants", "of", "Condom", "Use", "Among", "Sexually", "Active", "Young", "Adults", "in", "Rural", "KwaZulu-Natal,", "South", "Africa", "Natsayi", "Z.", "Chimbindi*,", "Nuala", "McGrath,", "Kobus", "Herbst,", "Khin", "San", "Tint", "and", "Marie-Louise", "Newell", "Africa", "Centre", "for", "Health", "and", "Population", "Studies,", "University", "of", "KwaZulu-Natal,", "South", "Africa", "Abstract:", "Aim:", "To", "investigate", "patterns,", "levels", "and", "socio-demographic", "determinants", "of", "condom", "use", "and", "consistency", "of", "use", "among", "young", "adults", "aged", "15-24", "years.", "Background:", "Condoms", "are", "known", "to", "prevent", "HIV", "infection.", "However,", "HIV", "prevalence", "and", "incidence", "remain", "high.", "Methods:", "This", "study", "was", "conducted", "in", "the", "Africa", "Centre", "Demographic", "Surveillance", "Area", "(ACDSA)", "in", "rural", "KwaZulu-", "Natal.", "Analysis", "focused", "on", "resident", "young", "adults", "aged", "15-24", "years", "in", "2005.", "In", "univariable", "and", "multivariable", "analyses,", "determinants", "of", "condom", "use", "and", "consistency", "of", "use", "among", "15-24", "year", "olds", "were", "estimated", "using", "data", "collected", "in", "2005.", "‘Ever’", "condom", "use", "was", "defined", "as", "the", "proportion", "who", "reported", "having", "used", "a", "condom;", "consistent", "use", "among", "those", "ever", "using", "as", "“always”", "using", "condoms", "with", "most", "recent", "partner", "in", "the", "last", "year.", "Results:", "3,914", "participants", "aged", "15-24", "years", "reported", "ever", "having", "sex,", "of", "whom", "52%", "reported", "condom", "use.", "Adjusting", "for", "age,", "sex,", "number", "of", "partners,", "residence", "of", "partner,", "partner", "age", "difference,", "type", "of", "partner", "and", "socio-economic", "status", "(SES),", "having", "an", "older", "partner", "decreased", "likelihood", "(aOR=0.69,", "p<0.01),", "while", "belonging", "to", "a", "household", "in", "a", "higher", "SES", "increased", "likelihood", "of", "ever", "using", "condoms", "(aOR=1.82,", "p<0.01).", "Being", "female", "(aOR=0.61", "p<0.01)", "and", "having", "a", "regular", "partner", "(aOR=0.65", "p<0.01)", "were", "independently", "associated", "with", "low", "consistent", "condom", "use.", "Conclusions:", "In", "this", "rural", "South", "African", "setting,", "condom", "use", "remains", "low,", "especially", "among", "females", "and", "with", "an", "older", "partner,", "situations", "commonly", "associated", "with", "increased", "HIV", "acquisition.", "Targeted", "supportive", "interventions", "to", "increase", "condom", "use", "need", "to", "be", "developed", "if", "HIV", "prevention", "programmes", "are", "to", "be", "successful.", "Keywords:", "AIDS,", "condom", "use,", "consistency,", "determinants,", "HIV,", "South", "Africa.", "Open", "Access", "BACKGROUND", "In", "2005,", "approximately", "40%", "of", "pregnant", "women", "in", "KwaZulu-Natal,", "South", "Africa,", "were", "living", "with", "HIV", "[1];", "in", "a", "general", "population", "of", "adult", "residents", "in", "rural", "KwaZulu", "Natal,", "the", "overall", "HIV", "prevalence", "was", "27%", "among", "15-50", "year", "old", "females", "and", "14%", "in", "15-54", "year", "old", "males", "[2],", "with", "incidence", "remaining", "high", "[3].", "Rates", "peaked", "in", "the", "young", "adult", "ages", "[4].", "Although", "health", "education", "information", "messaging", "regarding", "condom", "use", "is", "widespread", "and", "disseminated", "by", "health", "care", "providers,", "the", "media", "and", "other", "sources", "[5],", "the", "uptake", "of", "such", "messages", "is", "not", "usually", "evaluated.", "Condoms", "are", "known", "to", "be", "effective", "in", "preventing", "HIV", "infection", "if", "used", "consistently", "[6],", "and", "are", "currently", "one", "of", "the", "main", "prevention", "approaches.", "It", "is", "thus", "particularly", "important", "to", "identify", "factors", "associated", "with", "ever", "condom", "use", "[6-8]", "and", "to", "understand", "young", "adults’", "sexual", "behaviour", "and", "factors", "that", "influence", "their", "use", "of", "condoms", "[8-10].", "In", "South", "Africa,", "injectable", "hormonal", "contraception", "is", "popular,", "[11,", "12]", "which,", "although", "effective", "against", "pregnancy,", "does", "not", "prevent", "HIV", "acquisition.", "The", "South", "African", "Demographic", "Health", "Survey", "(SADHS)", "found", "that", "in", "2003", "[13],", "63%", "of", "sexually", "active", "women", "in", "rural", "areas", "aged", "15-49", "years", "were", "currently", "using", "a", "modern", "method", "of", "family", "*Address", "correspondence", "to", "this", "author", "at", "the", "Africa", "Centre", "for", "Health", "and", "Population", "Studies,", "University", "of", "KwaZulu-Natal,", "South", "Africa;", "Tel:", "+27", "35", "550", "7500;", "Fax:", "+27", "35", "550", "7503;", "E-mails:", "nchimbindi@africacentre.ac.za,", "nchimbindi@gmail.com", "planning,", "with", "injectables", "being", "the", "most", "popular", "contra-", "ceptive", "method,", "with", "38%", "of", "women", "reporting", "current", "use", "at", "the", "time", "of", "the", "survey.", "There", "continues", "to", "exist", "a", "risk", "of", "HIV", "acquisition", "in", "relations", "if", "either", "or", "both", "partners", "are", "not", "faithful", "or", "if", "HIV", "is", "brought", "into", "the", "start", "of", "a", "new", "relationship.", "This", "means", "that", "although", "non-barrier", "contra-", "ception", "use", "confers", "women", "protection", "against", "pregnancy,", "dual", "protection", "with", "condoms", "-", "against", "both", "pregnancy", "and", "HIV,", "is", "still", "required.", "Additional", "condom", "use", "is", "difficult", "to", "explain", "in", "settings", "of", "high", "hormonal", "contraceptive", "use.", "Knowledge", "about", "condoms", "and", "HIV", "prevention", "[14,", "15]", "are", "high", "among", "young", "adults", "but", "general", "perception", "of", "risk", "to", "infection", "and", "vulnerability", "is", "low", "despite", "high", "HIV", "rates.", "Several", "factors", "affect", "young", "adults’", "correct", "and", "consistent", "use", "of", "condoms.", "In", "Angola", "among", "15-24", "year", "olds,", "consistent", "condom", "use", "was", "positively", "associated", "with", "higher", "levels", "of", "education,", "with", "belief", "that", "condoms", "did", "not", "diminish", "sexual", "pleasure,", "believing", "that", "condoms", "were", "safe", "(among", "males)", "and", "having", "multiple", "partners", "(among", "males)", "and", "negatively", "associated", "with", "being", "married", "or", "being", "in", "a", "cohabiting", "relationship,", "and", "equating", "condom", "use", "with", "lack", "of", "trust", "(among", "females)", "[16].", "Other", "external", "factors", "that", "could", "influence", "condom", "use", "are", "accessibility", "to", "health", "facilities,", "reliable", "and", "correct", "reproductive", "health", "information,", "operating", "hours", "and", "issues", "of", "confidentiality", "[17]", "and", "availability", "of", "condoms.", "Type", "of", "sexual", "partner,", "whether", "casual", "or", "regular,", "and", "socio-economic", "status", "of", "the", "family", "to", "which", "the", "young", "adult", "belongs,", "have", "been", "found", "to", "1874-6136/10", "2010", "Bentham", "Open" ]

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[ "Original", "paper", "1Integrative", "Medicine", "Service,", "Memorial", "Sloan-Kettering", "Cancer", "Center,", "New", "York,", "USA", "2Department", "of", "Surgery,", "Memorial", "Sloan-Kettering", "Cancer", "Center,", "New", "York,", "USA", "3Breast", "Cancer", "Medicine", "Service,", "Memorial", "Sloan-", "Kettering", "Cancer", "Center,", "New", "York,", "USA", "4Integrative", "Medicine", "Service", "and", "Department", "of", "Epidemiology", "and", "Biostatistics,", "Memorial", "Sloan-Kettering", "Cancer", "Center,", "New", "York,", "USA", "Correspondence", "to", "Dr", "Barrie", "R", "Cassileth,", "Chief,", "Integrative", "Medicine", "Service,", "Memorial", "Sloan-Kettering", "Cancer", "Center,", "1429", "First", "Avenue,", "New", "York,", "NY", "10021,", "USA;", "Cassileth@mskcc.org", "Accepted", "14", "April", "2011", "Published", "Online", "First", "18", "June", "2011", "170", "A", "safety", "and", "efficacy", "pilot", "study", "of", "acupuncture", "for", "the", "treatment", "of", "chronic", "lymphoedema", "Barrie", "R", "Cassileth1,", "Kimberly", "J", "Van", "Zee2,", "Yi", "Chan1,", "Marci", "I", "Coleton1,", "Clifford", "A", "Hudis3,", "Sara", "Cohen3,", "James", "Lozada1,", "Andrew", "J", "Vickers4", "ABSTRACT", "Background", "Lymphoedema", "is", "a", "distressing", "problem", "affecting", "many", "women", "after", "breast", "cancer", "surgery.", "There", "is", "no", "cure", "and", "existing", "treatments", "are", "marginally", "beneficial,", "rarely", "reducing", "arm", "swelling", "in", "any", "meaningful", "way.", "Needling", "and", "even", "lifting", "of", "objects", "using", "the", "affected", "arm", "has", "been", "prohibited,", "but", "our", "clinical", "experience", "and", "that", "of", "others", "suggested", "that", "acupuncture", "was", "safe", "and", "that", "it", "might", "be", "a", "useful", "treatment", "for", "lymphoedema.", "Objective", "We", "sought", "to", "conduct", "a", "pilot", "study", "of", "the", "safety", "and", "effectiveness", "of", "acupuncture", "in", "women", "diagnosed", "with", "chronic", "lymphoedema", "for", "at", "least", "6", "months", "and", "less", "than", "5", "years.", "Methods", "Women", "with", "chronic", "lymphoedema", "(affected", "arm", "with", ">2", "cm", "circumference", "than", "unaffected", "arm)", "after", "breast", "cancer", "surgery", "received", "acupuncture", "twice", "a", "week", "for", "4", "weeks.", "Response", "was", "defined", "as", "at", "least", "a", "30%", "reduction", "in", "the", "difference", "in", "size", "between", "the", "affected", "and", "unaffected", "arms.", "Monthly", "follow-up", "calls", "for", "6", "months", "following", "treatment", "were", "made", "to", "obtain", "information", "about", "side", "effects.", "Results", "Study", "goals", "were", "met", "after", "nine", "subjects", "were", "treated:", "four", "women", "showed", "at", "least", "a", "30%", "reduction", "in", "the", "extent", "of", "lymphoedema", "at", "4", "weeks", "when", "compared", "with", "their", "respective", "baseline", "values.", "No", "serious", "adverse", "events", "occurred", "during", "or", "after", "73", "treatment", "sessions.", "Limitations", "This", "pilot", "study", "requires", "a", "larger,", "randomised", "follow-up", "investigation", "plus", "enquiries", "into", "possible", "mechanisms.", "Both", "are", "in", "development", "by", "our", "group.", "Conclusion", "Acupuncture", "appears", "safe", "and", "may", "reduce", "lymphoedema", "associated", "with", "breast", "cancer", "surgery.", "BACKGROUND", "A", "primary", "cause", "of", "lymphoedema,", "or", "swelling", "of", "a", "limb,", "is", "surgery", "or", "radiation", "treatment", "for", "breast", "cancer.", "The", "accumulation", "of", "fluid", "occurs", "when", "lymph", "nodes", "are", "removed.", "In", "a", "study", "of", "251", "women", "who", "had", "surgical", "treatment", "for", "breast", "cancer", "involving", "sampling,", "excision", "or", "biopsy", "of", "axillary", "nodes,", "39", "(20.7%)", "had", "devel-", "oped", "lymphoedema", "at", "3", "years", "postsurgery.", "Risk", "factors", "for", "development", "of", "lymphoedema", "in", "this", "study", "included", "mastectomy", "and", "body", "mass", "index", "≥26.1", "Lymphoedema", "is", "considered", "a", "chronic,", "life-long", "condition", "as", "there", "are", "no", "curative", "treatments.2", "While", "uncommon", "when", "axillary", "surgery", "is", "restricted", "to", "sentinel", "lymph", "node", "biopsy", "(6.9%", "of", "patients),3", "a", "study", "of", "109", "patients", "with", "mild", "lymphoedema", "found", "that", "the", "unpredictable", "rate", "of", "progression", "from", "mild", "to", "more", "severe", "lymphoedema", "was", "79%", "at", "1", "year,", "66%", "at", "3", "years", "and", "52%", "at", "5", "years.4", "Physical", "problems", "and", "emotional", "distress", "are", "commonly", "reported", "by", "breast", "cancer", "survi-", "vors", "with", "lymphoedema.", "Impaired", "quality", "of", "life,", "limitations", "to", "daily", "activities,", "the", "constant", "protection", "required", "to", "avoid", "activities", "feared", "to", "exacerbate", "or", "cause", "lymphoedema,", "and", "the", "body", "image", "issues", "associated", "with", "hav-", "ing", "one", "abnormally", "enlarged", "limb", "are", "reported", "in", "numerous", "publications.5–14", "A", "study", "of", "the", "economic", "burden", "of", "breast", "cancer-related", "lym-", "phoedema", "includes", "greater", "risk", "of", "infections", "and", "higher", "medical", "costs.15", "Little", "research", "has", "been", "published", "on", "acu-", "puncture", "for", "lymphoedema.", "In", "the", "USA,", "this", "is", "due", "in", "large", "part", "to", "the", "prohibition", "against", "needling", "and", "to", "other", "efforts", "to", "pro-", "tect", "the", "affected", "arm.", "However,", "studies", "from", "Japan", "and", "USA", "on", "acupuncture", "for", "lymphoe-", "dema", "found", "neither", "infection", "nor", "other", "side", "effects.16", "17", "Acupuncture", "is", "a", "safe", "treatment", "when", "performed", "by", "qualified", "practitioners.", "After", "760", "000", "treatments", "in", "97", "733", "patients", "receiving", "acupuncture", "in", "Germany,", "only", "six", "cases", "of", "serious", "adverse", "events", "(SAEs)", "were", "reported.18", "In", "another", "study", "from", "Germany,", "229", "230", "patients", "received", "over", "2.2", "million", "acu-", "puncture", "sessions.", "Adverse", "effects", "occurred", "in", "8.6%", "of", "the", "sampled", "patients,", "however,", "most", "were", "minor", "events", "such", "as", "bleeding", "and", "bruis-", "ing.", "Of", "all", "adverse", "effects,", "0.1%", "was", "indica-", "tive", "of", "negligence", "or", "malpractice", "(broken", "or", "forgotten", "needle,", "pneumothorax,", "burns", "after", "moxibustion).19", "This", "study", "sought", "to", "obtain", "preliminary", "evi-", "dence", "of", "the", "effects", "of", "acupuncture", "on", "chronic", "lymphoedema", "due", "to", "breast", "cancer", "treatment", "and", "to", "further", "evaluate", "the", "safety", "of", "acupunc-", "ture", "in", "this", "setting.", "METHODS", "After", "approval", "of", "the", "protocol", "by", "the", "institu-", "tional", "review", "board,", "patients", "were", "identified", "Acupunct", "Med", "2011;29:170–172.", "doi:10.1136/aim.2011.004069" ]

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[ "Hindawi", "Publishing", "Corporation", "Journal", "of", "Nutrition", "and", "Metabolism", "Volume", "2011,", "Article", "ID", "708183,", "11", "pages", "doi:10.1155/2011/708183", "Review", "Article", "Cancer", "Risk", "in", "Type", "2", "Diabetes", "Mellitus:", "Metabolic", "Links", "and", "Therapeutic", "Considerations", "Grace", "Sun", "and", "Sangeeta", "R.", "Kashyap", "Department", "of", "Endocrinology,", "Diabetes,", "and", "Metabolism,", "Cleveland", "Clinic,", "Cleveland,", "OH", "44195,", "USA", "Correspondence", "should", "be", "addressed", "to", "Sangeeta", "R.", "Kashyap,", "kashyas@ccf.org", "Received", "23", "November", "2010;", "Revised", "10", "February", "2011;", "Accepted", "24", "March", "2011", "Academic", "Editor:", "Maria", "Luz", "Fernandez", "Copyright", "©", "2011", "G.", "Sun", "and", "S.", "R.", "Kashyap.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Type", "2", "diabetes", "mellitus", "(DM2)", "is", "increasing", "in", "incidence,", "creating", "worldwide", "public", "health", "concerns", "and", "impacting", "morbidity", "and", "mortality", "rates.", "An", "increasing", "number", "of", "studies", "have", "demonstrated", "shared", "associations", "between", "DM2", "and", "malignancy,", "including", "key", "clinical,", "biochemical,", "and", "metabolic", "commonalities.", "This", "paper", "will", "attempt", "to", "explore", "the", "relationship", "between", "the", "various", "types", "of", "cancer", "and", "diabetes,", "the", "common", "metabolic", "pathways", "underlying", "cancer", "development,", "and", "the", "potential", "impact", "of", "various", "antidiabetes", "therapies", "on", "cancer", "risk.", "1.", "Introduction", "The", "association", "between", "diabetes", "and", "cancer", "was", "described", "long", "before", "the", "21st", "century,", "as", "far", "back", "as", "1885", "[1].", "DM2", "continues", "to", "increase", "in", "prevalence", "affecting", "17.9", "million", "Americans", "with", "5.7", "million", "undiagnosed,", "costing", "an", "esti-", "mated", "174", "billion", "healthcare", "dollars", "[2].", "Cancer,", "second", "only", "to", "heart", "disease", "in", "mortality,", "is", "also", "on", "the", "rise", "with", "estimated", "costs", "in", "the", "US", "of", "$263.8", "billion", "[3].", "These", "two", "high-impact", "diseases", "share", "factors", "which", "influence", "their", "development", "and", "progression,", "important", "in", "modifying", "each", "other’s", "outcome.", "1.1.", "Clinical", "Factors", "Underlying", "Cancer", "Risk.", "Common", "non-", "modifiable", "(age,", "sex,", "and", "race/ethnicity)", "and", "modifiable", "(weight,", "diet,", "physical", "activity,", "tobacco", "use,", "and", "alcohol", "use)", "risk", "factors", "underlie", "the", "development", "of", "cancer", "and", "DM2.", "Figure", "1(a)", "illustrates", "the", "general", "risk", "factors", "for", "cancer", "development", "in", "diabetes.", "It", "is", "known", "that", "both", "DM2", "and", "cancer", "increase", "with", "age;", "those", "≥55", "years", "comprise", "almost", "80%", "of", "newly", "diagnosed", "cancers", "and", "23.1%", "of", "patients", "≥", "60", "years", "develop", "DM2", "compared", "to", "10.7%", "of", "younger", "adults", "[4,", "5].", "Men", "have", "slightly", "more", "cancer", "and", "diabetes", "compared", "to", "women", "after", "adjusting", "for", "other", "risks", "[4–6].", "African-", "Americans", "as", "a", "subgroup", "appear", "hardest", "hit", "with", "regards", "to", "cancer-related", "deaths,", "DM2,", "and", "obesity", "compared", "to", "non-Hispanic", "white", "counterparts", "[4,", "5].", "Central", "obesity,", "a", "marker", "of", "insulin", "resistance", "and", "a", "key", "player", "in", "both", "DM2", "and", "the", "metabolic", "syndrome,", "has", "also", "been", "linked", "to", "breast,", "colorectal,", "liver,", "and", "endometrial,", "malignancies", "[5].", "Dietary", "choices", "high", "in", "glycemic", "load", "and", "saturated", "fat", "and", "low", "in", "fiber", "accompanied", "by", "reduced", "physical", "activity", "also", "increase", "the", "risk", "for", "DM2", "and", "malignancy,", "particularly", "for", "the", "colon,", "endometrium", "and", "breast", "[5,", "7].", "Moreover,", "studies", "show", "that", "tobacco", "and", "excess", "alcohol", "usage", "linked", "to", "cancer", "can", "also", "worsen", "diabetes", "complications", "[5].", "1.2.", "Types", "of", "Cancers", "Linked", "to", "DM2", "and", "Common", "Metabolic", "Pathways.", "Diabetes", "has", "been", "recognized", "as", "a", "key", "factor", "contributing", "to", "the", "development", "of", "solid", "organ", "malignancies", "including", "liver,", "pancreas,", "colorectal,", "breast,", "endometrial,", "uterine,", "and", "bladder", "[3,", "5,", "8–18].", "The", "two", "cancers", "showing", "the", "strongest", "association", "to", "DM2", "are", "those", "of", "the", "liver", "[1,", "5,", "9,", "18–20]", "and", "pancreas", "[1,", "5,", "18–20].", "Not", "only", "does", "there", "appear", "to", "be", "an", "association", "between", "DM2", "and", "cancer,", "but", "having", "both", "diagnoses", "may", "increase", "mortality,", "regardless", "of", "the", "type", "of", "cancer", "[9,", "21].", "Studies", "performed", "in", "Japan,", "Korea,", "and", "Hong", "Kong", "demonstrated", "increased", "cancer", "risk", "[19,", "20,", "22]", "and", "mortality", "[19,", "22]", "among", "participants", "with", "DM2,", "especially", "those", "with", "poorly", "controlled", "DM2", "based", "on", "HbA1c", "[22]", "and", "fasting", "serum", "glucose", "levels", "[19].", "A", "recent", "meta-analysis", "of", "23", "articles", "indicated", "a", "41%", "increase", "in", "can-", "cer", "mortality", "related", "to", "endometrial,", "breast,", "and", "colorectal", "cancer", "in", "patients", "with", "preexisting", "diabetes", "as", "compared", "to", "normoglycemic", "individuals", "[21].", "In", "the", "American", "Cancer" ]

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[ "International", "Scholarly", "Research", "Network", "ISRN", "Surgery", "Volume", "2012,", "Article", "ID", "389385,", "5", "pages", "doi:10.5402/2012/389385", "Clinical", "Study", "Factors", "Related", "to", "Long-Term", "Survival", "in", "Patients", "Affected", "by", "Well-Differentiated", "Endocrine", "Tumors", "of", "the", "Pancreas", "Riccardo", "Casadei,1", "Claudio", "Ricci,1", "Paola", "Tomassetti,2", "Davide", "Campana,2", "and", "Francesco", "Minni1", "1", "Department", "of", "Surgery,", "S.Orsola-Malpighi", "Hospital,", "Alma", "Mater", "Studiorum,", "University", "of", "Bologna,", "40138", "Bologna,", "Italy", "2", "Department", "of", "Internal", "Medicine,", "S.Orsola-Malpighi", "Hospital,", "Alma", "Mater", "Studiorum,", "University", "of", "Bologna,", "40138", "Bologna,", "Italy", "Correspondence", "should", "be", "addressed", "to", "Riccardo", "Casadei,", "riccardo.casadei@aosp.bo.it", "Received", "10", "April", "2012;", "Accepted", "15", "May", "2012", "Academic", "Editors:", "S.", "Germanos,", "K.-E.", "Kahnberg,", "and", "A.", "Petroianu", "Copyright", "©", "2012", "Riccardo", "Casadei", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Aim.", "To", "identify", "factors", "related", "to", "survival", "in", "patients", "affected", "by", "well-differentiated", "PETs", "(benign,", "uncertain", "behavior,", "and", "carcinoma)", "who", "underwent", "R0", "pancreatic", "resection.", "Methods.", "Retrospective", "study", "of", "74", "consecutive", "patients", "followed", "up", "from", "January", "1980", "to", "December", "2011.", "Prognostic", "factors", "were", "sex,", "age,", "type", "of", "tumor,", "presence", "of", "symptoms,", "type", "of", "surgical", "procedure,", "size", "of", "tumor,", "lymph", "nodes", "status,", "WHO", "classification,", "and", "TNM", "stage.", "Overall", "survival", "was", "evaluated", "using", "the", "Kaplan-Meier", "method.", "Cox", "regression", "analyses", "were", "used", "to", "identify", "the", "factors", "associated", "with", "prognosis", "in", "univariate", "and", "multivariate", "analysis.", "Results.", "The", "mean", "follow-up", "of", "all", "the", "patients", "was", "106", "±", "89", "months.", "The", "5–10-year", "long-term", "survival", "was", "90.9%", "and", "79.1%,", "respectively.", "At", "univariate", "analysis,", "patient", "age", "<55", "years", "was", "significantly", "related", "to", "a", "better", "long-term", "survival", "compared", "to", "patients", "age", "≥55", "years", "(307", "±", "15", "months", "versus", "192", "±", "25", "months;", "P", "=", "0.010).", "Multivariate", "analysis", "showed", "that", "female", "gender", "(P", "=", "0.006),", "patients", "without", "comorbidities", "(P", "=", "0.033),", "and", "patients", "affected", "by", "well-differentiated", "benign", "pancreatic", "endocrine", "tumors", "(P", "=", "0.008", "and", "P", "=", "0.002", "in", "relation", "to", "tumors", "with", "uncertain", "behavior", "and", "carcinomas,", "resp.)", "were", "factors", "significantly", "related", "to", "a", "better", "long-term", "survival.", "Conclusions.", "Patients", "factors", "were", "strongly", "related", "to", "a", "better", "long-term", "survival", "in", "patients", "observed.", "WHO", "classification", "is", "a", "very", "useful", "prognostic", "tool", "for", "well-differentiated", "PETs.", "1.", "Introduction", "Pancreatic", "endocrine", "tumors", "(PETs)", "are", "rare", "neoplasms", "with", "a", "poorly", "defined", "natural", "history", "that,", "in", "general,", "have", "a", "more", "indolent", "tumor", "biology", "with", "better", "long-term", "survival", "rates", "than", "tumors", "of", "the", "exocrine", "pancreas", "[1].", "Surgery", "is", "generally", "considered", "the", "treatment", "of", "choice", "and,", "for", "patients", "with", "localized", "disease,", "it", "can", "be", "curative.", "The", "biological", "behavior", "of", "PETs", "is", "variable,", "necessitating", "close", "long-term", "follow-up.", "The", "World", "Health", "Organization", "(WHO)", "[2,", "3]", "as", "well", "as", "tumor", "node", "metastasis", "(TNM)", "[4,", "5]", "classifications", "recognized", "different", "groups", "of", "PETs", "with", "different", "biologic", "behaviors.", "Moreover,", "several", "authors", "[6–11]", "reported", "factors", "predicting", "survival", "after", "the", "resection", "of", "PETs.", "To", "our", "knowledge,", "there", "are", "no", "studies", "in", "the", "literature", "that", "reported", "prognostics", "factors", "related", "to", "long-term", "survival", "in", "patients", "with", "well-differentiated", "PETs.", "Thus,", "the", "present", "study", "was", "carried", "out", "in", "order", "to", "identify", "the", "factors", "related", "to", "long-term", "survival", "in", "patients", "affected", "by", "well-differentiated", "PETs", "(benign,", "uncertain", "behavior,", "and", "carcinoma)", "who", "underwent", "R0", "pancreatic", "resection.", "2.", "Patients", "and", "Methods", "A", "retrospective", "study", "of", "a", "prospective", "database", "of", "74", "consecutive", "patients", "who", "underwent", "R0", "pancreatic", "resection", "for", "well-differentiated", "PETs", "(benign,", "uncertain", "behavior,", "and", "carcinoma)", "was", "conducted", "from", "January", "1980", "to", "December", "2011.", "All", "the", "patients", "were", "followed", "up,", "and", "for", "each", "patient", "long-term", "overall", "survival", "(OS)", "was", "calculated", "from", "the", "date", "of", "surgery", "to", "the", "date", "of", "the", "death", "or", "last", "follow-up.", "December", "2011", "was", "the", "end", "of", "the", "follow-up", "period", "for", "surviving", "patients.", "Prognostic", "factors", "considered", "for", "each" ]

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[ "Hypoxia-Induced", "Mitogenic", "Factor", "(HIMF/FIZZ1/RELMa)", "Recruits", "Bone", "Marrow-Derived", "Cells", "to", "the", "Murine", "Pulmonary", "Vasculature", "Daniel", "J.", "Angelini1,", "Qingning", "Su1,", "Irina", "A.", "Kolosova1,", "Chunling", "Fan1,", "John", "T.", "Skinner1,", "Kazuyo", "Yamaji-Kegan", "1", ",", "Michael", "Collector2,", "Saul", "J.", "Sharkis2,", "Roger", "A.", "Johns1,3*", "1", "Department", "of", "Anesthesiology", "and", "Critical", "Care", "Medicine,", "Johns", "Hopkins", "University", "School", "of", "Medicine,", "Baltimore,", "Maryland,", "United", "States", "of", "America,", "2", "Department", "of", "Oncology", "and", "Cancer", "Biology,", "Johns", "Hopkins", "University", "School", "of", "Medicine,", "Baltimore,", "Maryland,", "United", "States", "of", "America,", "3", "Division", "of", "Pulmonary", "and", "Critical", "Care", "Medicine,", "Department", "of", "Medicine,", "Johns", "Hopkins", "University", "School", "of", "Medicine,", "Baltimore,", "Maryland,", "United", "States", "of", "America", "Abstract", "Background:", "Pulmonary", "hypertension", "(PH)", "is", "a", "disease", "of", "multiple", "etiologies", "with", "several", "common", "pathological", "features,", "including", "inflammation", "and", "pulmonary", "vascular", "remodeling.", "Recent", "evidence", "has", "suggested", "a", "potential", "role", "for", "the", "recruitment", "of", "bone", "marrow-derived", "(BMD)", "progenitor", "cells", "to", "this", "remodeling", "process.", "We", "recently", "demonstrated", "that", "hypoxia-induced", "mitogenic", "factor", "(HIMF/FIZZ1/RELMa)", "is", "chemotactic", "to", "murine", "bone", "marrow", "cells", "in", "vitro", "and", "involved", "in", "pulmonary", "vascular", "remodeling", "in", "vivo.", "Methodology/Principal", "Findings:", "We", "used", "a", "mouse", "bone", "marrow", "transplant", "model", "in", "which", "lethally", "irradiated", "mice", "were", "rescued", "with", "bone", "marrow", "transplanted", "from", "green", "fluorescent", "protein", "(GFP)+", "transgenic", "mice", "to", "determine", "the", "role", "of", "HIMF", "in", "recruiting", "BMD", "cells", "to", "the", "lung", "vasculature", "during", "PH", "development.", "Exposure", "to", "chronic", "hypoxia", "and", "pulmonary", "gene", "transfer", "of", "HIMF", "were", "used", "to", "induce", "PH.", "Both", "models", "resulted", "in", "markedly", "increased", "numbers", "of", "BMD", "cells", "in", "and", "around", "the", "pulmonary", "vasculature;", "in", "several", "neomuscularized", "small", "(,20", "mm)", "capillary-like", "vessels,", "an", "entirely", "new", "medial", "wall", "was", "made", "up", "of", "these", "cells.", "We", "found", "these", "GFP+", "BMD", "cells", "to", "be", "positive", "for", "stem", "cell", "antigen-1", "and", "c-kit,", "but", "negative", "for", "CD31", "and", "CD34.", "Several", "of", "the", "GFP+", "cells", "that", "localized", "to", "the", "pulmonary", "vasculature", "were", "a-smooth", "muscle", "actin+", "and", "localized", "to", "the", "media", "layer", "of", "the", "vessels.", "This", "finding", "suggests", "that", "these", "cells", "are", "of", "mesenchymal", "origin", "and", "differentiate", "toward", "myofibroblast", "and", "vascular", "smooth", "muscle.", "Structural", "location", "in", "the", "media", "of", "small", "vessels", "suggests", "a", "functional", "role", "in", "the", "lung", "vasculature.", "To", "examine", "a", "potential", "mechanism", "for", "HIMF-dependent", "recruitment", "of", "mesenchymal", "stem", "cells", "to", "the", "pulmonary", "vasculature,", "we", "performed", "a", "cell", "migration", "assay", "using", "cultured", "human", "mesenchymal", "stem", "cells", "(HMSCs).", "The", "addition", "of", "recombinant", "HIMF", "induced", "migration", "of", "HMSCs", "in", "a", "phosphoinosotide-3-kinase-dependent", "manner.", "Conclusions/Significance:", "These", "results", "demonstrate", "HIMF-dependent", "recruitment", "of", "BMD", "mesenchymal-like", "cells", "to", "the", "remodeling", "pulmonary", "vasculature.", "Citation:", "Angelini", "DJ,", "Su", "Q,", "Kolosova", "IA,", "Fan", "C,", "Skinner", "JT,", "et", "al.", "(2010)", "Hypoxia-Induced", "Mitogenic", "Factor", "(HIMF/FIZZ1/RELMa)", "Recruits", "Bone", "Marrow-Derived", "Cells", "to", "the", "Murine", "Pulmonary", "Vasculature.", "PLoS", "ONE", "5(6):", "e11251.", "doi:10.1371/journal.pone.0011251", "Editor:", "Marcelo", "G.", "Bonini,", "University", "of", "Illinois", "at", "Chicago,", "United", "States", "of", "America", "Received", "February", "22,", "2010;", "Accepted", "May", "25,", "2010;", "Published", "June", "22,", "2010", "Copyright:", "2010", "Angelini", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "was", "supported", "by", "NIH", "SCCOR", "P50", "084946", "(RAJ),", "NIH", "NHLBI", "39706", "(RAJ),", "NIH", "fellowship", "T32", "GM075774-09", "(DJA),", "Maryland", "Stem", "Cell", "Fund", "Exploratory", "Grant", "(IAK),", "and", "NIH", "PO1", "CA070970", "(SJS,", "MC).", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "anaysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "rajohns@jhmi.edu", "Introduction", "Hypoxia-induced", "mitogenic", "factor", "(HIMF),", "also", "known", "as", "‘‘found", "in", "inflammatory", "zone", "1’’", "(FIZZ1)", "and", "resistin-like", "molecule", "alpha", "(RELMa),", "is", "a", "pleiotropic", "cytokine", "that", "is", "highly", "inducible", "in", "lung", "[1–3].", "We", "have", "shown", "it", "to", "have", "mitogenic,", "angiogenic,", "vasocon-", "strictive,", "and", "chemokine-like", "properties", "[3–6].", "We", "initially", "described", "HIMF", "in", "the", "remodeling", "vasculature", "of", "the", "chronic", "hypoxia", "model", "of", "pulmonary", "hypertension", "(PH)", "[3]", "and", "have", "recently", "determined", "that", "HIMF", "plays", "a", "critical", "role", "in", "this", "process", "[7].", "In", "rats,", "in", "vivo", "knockdown", "of", "HIMF", "specifically", "in", "the", "lung", "reduces", "the", "mean", "pulmonary", "artery", "pressure,", "pulmonary", "vascular", "resistance,", "and", "vascular", "remodeling", "associated", "with", "chronic", "hypoxia,", "whereas", "pulmonary", "gene", "transfer", "of", "HIMF", "initiates", "vascular", "remodeling", "and", "increases", "these", "physiological", "measurements", "[7].", "Liu", "et", "al.", "[8]", "has", "shown", "that", "HIMF", "plays", "a", "key", "role", "in", "the", "transition", "of", "fibroblasts", "to", "myofibroblasts,", "which", "is", "essential", "to", "bleomycin-induced", "fibrosis", "and", "may", "play", "a", "role", "in", "vascular", "remodeling", "associated", "with", "PH.", "Our", "lab", "and", "others", "have", "demonstrated", "that", "the", "addition", "of", "recombinant", "HIMF", "to", "cultured", "cells", "activates", "the", "phosphoinosotide-3-kinase", "(PI-", "3K)/Akt", "and", "extracellular", "signal-regulated", "kinase", "1/2", "(ERK1/2)", "mitogen-activated", "kinase", "(p42/44", "MAPK)", "pathways", "in", "several", "different", "cell", "types", "[3,9,10].", "Finally,", "we", "have", "demonstrated", "that", "HIMF", "is", "chemotactic", "for", "undifferentiated", "murine", "bone", "marrow-", "derived", "(BMD)", "cells", "and", "this", "action", "is", "mediated", "through", "Bruton’s", "tyrosine", "kinase", "(BTK)", "[5].", "Pulmonary", "vascular", "remodeling", "is", "a", "key", "component", "of", "the", "pathogenesis", "of", "PH.", "Recent", "evidence", "has", "suggested", "the", "possibility", "PLoS", "ONE", "|", "www.plosone.org", "1", "June", "2010", "|", "Volume", "5", "|", "Issue", "6", "|", "e11251" ]

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[ "Ben", "Jemaa", "et", "al.", "Journal", "of", "Experimental", "&", "Clinical", "Cancer", "Research", "2010,", "29:171", "http://www.jeccr.com/content/29/1/171", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "Co-expression", "and", "impact", "of", "prostate", "specific", "membrane", "antigen", "and", "prostate", "specific", "antigen", "in", "prostatic", "pathologies", "Awatef", "Ben", "Jemaa", "1,", "Yosra", "Bouraoui", "1,", "Sataa", "Sallami2,", "Ahmed", "Banasr3,", "Nawfel", "Ben", "Rais4,", "Latifa", "Ouertani5,", "Yassin", "Nouira2,", "Ali", "Horchani2,", "Ridha", "Oueslati1*", "Abstract", "Background:", "The", "present", "study", "was", "undertaken", "to", "relate", "the", "co-expression", "of", "prostate-associated", "antigens,", "PSMA", "and", "PSA,", "with", "the", "degree", "of", "vascularization", "in", "normal", "and", "pathologic", "(hyperplasia", "and", "cancer)", "prostate", "tissues", "to", "elucidate", "their", "possible", "role", "in", "tumor", "progression.", "Methods:", "The", "study", "was", "carried", "out", "in", "6", "normal,", "44", "benign", "prostatic", "hyperplastic", "and", "39", "cancerous", "human", "prostates.", "Immunohistochemical", "analysis", "were", "performed", "using", "the", "monoclonal", "antibody", "CD34", "to", "determine", "the", "angiogenic", "activity,", "and", "the", "monoclonal", "antibodies", "3E6", "and", "ER-PR8", "to", "assess", "PSMA", "and", "PSA", "expression,", "respectively.", "Results:", "In", "our", "study", "we", "found", "that", "in", "normal", "prostate", "tissue,", "PSMA", "and", "PSA", "were", "equally", "expressed", "(3.7", "±", "0.18", "and", "3.07", "±", "0.11).", "A", "significant", "difference", "in", "their", "expression", "was", "see", "in", "hyperplastic", "and", "neoplastic", "prostates", "tissues", "(16.14", "±", "0.17", "and", "30.72", "±", "0.85,", "respectively)", "for", "PSMA", "and", "(34.39", "±", "0.53", "and", "17.85", "±", "1.21,", "respectively)", "for", "PSA.", "Study", "of", "prostate", "tumor", "profiles", "showed", "that", "the", "profile", "(PSA+,", "PSMA-)", "expression", "levels", "decreased", "between", "normal", "prostate,", "benign", "prostatic", "tissue", "and", "primary", "prostate", "cancer.", "In", "the", "other", "hand,", "the", "profile", "(PSA-,", "PSMA+)", "expression", "levels", "increased", "from", "normal", "to", "prostate", "tumor", "tissues.", "PSMA", "overexpression", "was", "associated", "with", "high", "intratumoral", "angiogenesis", "activity.", "By", "contrast,", "high", "PSA", "expression", "was", "associated", "with", "low", "angiogenesis", "activity.", "Conclusion:", "These", "data", "suggest", "that", "these", "markers", "are", "regulated", "differentially", "and", "the", "difference", "in", "their", "expression", "showed", "a", "correlation", "with", "malignant", "transformation.", "With", "regard", "to", "the", "duality", "PSMA-PSA,", "this", "implies", "the", "significance", "of", "their", "investigation", "together", "in", "normal", "and", "pathologic", "prostate", "tissues.", "Introduction", "The", "prostate", "gland", "is", "the", "site", "of", "two", "most", "pathological", "processes", "among", "elderly", "men,", "benign", "prostatic", "hyperpla-", "sia", "(BPH)", "and", "prostate", "cancer", "(PC)", "[1].", "According", "to", "the", "zonal", "origin,", "prostate", "cancer", "arising", "mainly", "in", "the", "periph-", "eral", "zone", "(PZ),", "whereas", "the", "transition", "zone", "(TZ)", "is", "the", "exclusive", "location", "for", "the", "origin", "of", "BPH", "and", "PC", "develop-", "ing", "in", "this", "latter", "zone", "are", "frequently", "found", "incidentally.", "There", "are", "different", "biological", "features", "between", "PZ", "and", "TZ", "of", "prostate", "gland", "[2].", "Aberrant", "prostate", "growth", "arises", "as", "a", "consequence", "of", "changes", "in", "the", "balance", "between", "cell", "*", "Correspondence:", "oridha2003@yahoo.fr", "1Unit", "of", "Immunology", "and", "Microbiology", "Environmental", "and", "Carcinogenesis", "(IMEC),", "Faculty", "of", "Sciences", "of", "Bizerte,", "7021,", "Zarzouna,", "University", "of", "7-November", "at", "Carthage,", "Tunisia", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "proliferation", "and", "cell", "death", "[3].", "This", "deregulation", "may", "result", "in", "production", "of", "prostate", "specific", "markers", "such", "as", "the", "secreted", "protease", "prostate-specific", "antigen", "(PSA)", "and", "the", "cell", "surface", "prostate-specific", "membrane", "antigen", "(PSMA)", "[4].", "A", "transmembrane", "glycoprotein", "expressed", "in", "the", "human", "prostate", "parenchyma,", "from", "where", "it", "was", "first", "cloned", "and", "named", "prostate-specific", "membrane", "antigen", "(PSMA)", "[5]", "has", "gained", "increased", "attention", "in", "diagnosis,", "monitoring", "and", "treatment", "of", "PC", "[6].", "PSMA", "is", "a", "metallo-", "peptidase", "belonging", "to", "the", "peptidase", "family", "M28", "[7]", "and", "has", "apparent", "molecular", "masses", "of", "84-100", "kDa", "[8]", "with", "a", "unique", "three-part", "structure:", "a", "short", "cytoplasmic", "amino", "terminus", "that", "interacts", "with", "an", "actin", "filament,", "a", "single", "membrane-spanning", "domain", "and", "a", "large", "extracellular", "domain", "[9].", "Several", "alternative", "isoforms", "have", "been", "©", "2010", "Ben", "Jemaa", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Kastner", "et", "al.", "BMC", "Medical", "Informatics", "and", "Decision", "Making", "2010,", "10:40", "http://www.biomedcentral.com/1472-6947/10/40", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Development", "of", "a", "prototype", "clinical", "decision", "support", "tool", "for", "osteoporosis", "disease", "management:", "a", "qualitative", "study", "of", "focus", "groups", "Monika", "Kastner1*†,", "Jamy", "Li2†,", "Danielle", "Lottridge2†,", "Christine", "Marquez3†,", "David", "Newton3†,", "Sharon", "E", "Straus1,3†", "Abstract", "Background:", "Osteoporosis", "affects", "over", "200", "million", "people", "worldwide,", "and", "represents", "a", "significant", "cost", "burden.", "Although", "guidelines", "are", "available", "for", "best", "practice", "in", "osteoporosis,", "evidence", "indicates", "that", "patients", "are", "not", "receiving", "appropriate", "diagnostic", "testing", "or", "treatment", "according", "to", "guidelines.", "The", "use", "of", "clinical", "decision", "support", "systems", "(CDSSs)", "may", "be", "one", "solution", "because", "they", "can", "facilitate", "knowledge", "translation", "by", "providing", "high-quality", "evidence", "at", "the", "point", "of", "care.", "Findings", "from", "a", "systematic", "review", "of", "osteoporosis", "interventions", "and", "consultation", "with", "clinical", "and", "human", "factors", "engineering", "experts", "were", "used", "to", "develop", "a", "conceptual", "model", "of", "an", "osteoporosis", "tool.", "We", "conducted", "a", "qualitative", "study", "of", "focus", "groups", "to", "better", "understand", "physicians’", "perceptions", "of", "CDSSs", "and", "to", "transform", "the", "conceptual", "osteoporosis", "tool", "into", "a", "functional", "prototype", "that", "can", "support", "clinical", "decision", "making", "in", "osteoporosis", "disease", "management", "at", "the", "point", "of", "care.", "Methods:", "The", "conceptual", "design", "of", "the", "osteoporosis", "tool", "was", "tested", "in", "4", "progressive", "focus", "groups", "with", "family", "physicians", "and", "general", "internists.", "An", "iterative", "strategy", "was", "used", "to", "qualitatively", "explore", "the", "experiences", "of", "physicians", "with", "CDSSs;", "and", "to", "find", "out", "what", "features,", "functions,", "and", "evidence", "should", "be", "included", "in", "a", "working", "prototype.", "Focus", "groups", "were", "conducted", "using", "a", "semi-structured", "interview", "guide", "using", "an", "iterative", "process", "where", "results", "of", "the", "first", "focus", "group", "informed", "changes", "to", "the", "questions", "for", "subsequent", "focus", "groups", "and", "to", "the", "conceptual", "tool", "design.", "Transcripts", "were", "transcribed", "verbatim", "and", "analyzed", "using", "grounded", "theory", "methodology.", "Results:", "Of", "the", "3", "broad", "categories", "of", "themes", "that", "were", "identified,", "major", "barriers", "related", "to", "the", "accuracy", "and", "feasibility", "of", "extracting", "bone", "mineral", "density", "test", "results", "and", "medications", "from", "the", "risk", "assessment", "questionnaire;", "using", "an", "electronic", "input", "device", "such", "as", "a", "Tablet", "PC", "in", "the", "waiting", "room;", "and", "the", "importance", "of", "including", "well-", "balanced", "information", "in", "the", "patient", "education", "component", "of", "the", "osteoporosis", "tool.", "Suggestions", "for", "modifying", "the", "tool", "included", "the", "addition", "of", "a", "percentile", "graph", "showing", "patients’", "10-year", "risk", "for", "osteoporosis", "or", "fractures,", "and", "ensuring", "that", "the", "tool", "takes", "no", "more", "than", "5", "minutes", "to", "complete.", "Conclusions:", "Focus", "group", "data", "revealed", "the", "facilitators", "and", "barriers", "to", "using", "the", "osteoporosis", "tool", "at", "the", "point", "of", "care", "so", "that", "it", "can", "be", "optimized", "to", "aid", "physicians", "in", "their", "clinical", "decision", "making.", "Background", "Osteoporosis", "is", "a", "major", "public", "health", "concern,", "affecting", "over", "200", "million", "people", "worldwide", "[1],", "an", "estimated", "10", "million", "in", "the", "US", "[2],", "4", "million", "in", "the", "UK", "[3],", "and", "1.4", "million", "in", "Canada", "[4,5].", "Without", "effective", "osteoporo-", "sis", "prevention", "and", "treatment,", "the", "burden", "of", "treating", "*", "Correspondence:", "monika.kastner@utoronto.ca", "†", "Contributed", "equally", "1Department", "of", "Health", "Policy,", "Management", "and", "Evaluation,", "Faculty", "of", "Medicine,", "University", "of", "Toronto,", "Health", "Sciences", "Building,", "155", "College", "Street,", "Suite", "425,", "Toronto,", "ON,", "M5T", "3M6,", "Canada", "fractures", "in", "Canada", "is", "projected", "to", "reach", "$32.5", "billion", "by", "the", "year", "2018", "[5,6],", "and", "$25.3", "billion", "per", "year", "in", "the", "US", "by", "the", "year", "2025", "[4].", "This", "is", "further", "compounded", "by", "the", "increasing", "proportion", "of", "people", "aged", "65", "and", "older,", "which", "will", "likely", "lead", "to", "increased", "numbers", "of", "people", "who", "will", "suffer", "from", "osteoporosis", "[6-8].", "Fragility", "frac-", "tures", "are", "the", "clinical", "consequence", "of", "osteoporosis,", "and", "hip", "fractures", "have", "the", "most", "devastating", "prognosis", "[9,10],", "as", "they", "can", "significantly", "impair", "quality", "of", "life,", "physical", "function", "and", "social", "interaction,", "and", "can", "lead", "to", "admis-", "sion", "to", "long-term", "care", "[10,11].", "Although", "guidelines", "are", "©", "2010", "Kastner", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Pollock", "et", "al.", "Malaria", "Journal", "2011,", "10:97", "http://www.malariajournal.com/content/10/1/97", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "Daily", "Plasmodium", "yoelii", "infective", "mosquito", "bites", "do", "not", "generate", "protection", "or", "suppress", "previous", "immunity", "against", "the", "liver", "stage", "Tzvi", "Pollock1†,", "Ricardo", "Leitao1†,", "Cristina", "Galan-Rodriguez1,", "Kurt", "A", "Wong1,2", "and", "Ana", "Rodriguez1*", "Abstract", "Background:", "Human", "populations", "that", "are", "naturally", "subjected", "to", "Plasmodium", "infection", "do", "not", "acquire", "complete", "protection", "against", "the", "liver", "stage", "of", "this", "parasite", "despite", "prolonged", "and", "frequent", "exposure.", "However,", "sterile", "immunity", "against", "Plasmodium", "liver", "stage", "can", "be", "achieved", "after", "repeated", "exposure", "to", "radiation", "attenuated", "sporozoites.", "The", "reasons", "for", "this", "different", "response", "remain", "largely", "unknown,", "but", "a", "suppressive", "effect", "of", "blood", "stage", "Plasmodium", "infection", "has", "been", "proposed", "as", "a", "cause", "for", "the", "lack", "of", "liver", "stage", "protection.", "Methods:", "Using", "Plasmodium", "yoelii", "17XNL,", "the", "response", "generated", "in", "mice", "subjected", "to", "daily", "infective", "bites", "from", "normal", "or", "irradiated", "mosquitoes", "was", "compared.", "The", "effect", "of", "daily-infected", "mosquito", "bites", "on", "mice", "that", "were", "previously", "immunized", "against", "P.", "yoelii", "liver", "stage", "was", "also", "studied.", "Results:", "It", "was", "observed", "that", "while", "the", "bites", "of", "normal", "infected", "mosquitoes", "do", "not", "generate", "strong", "antibody", "responses", "and", "protection,", "the", "bites", "of", "irradiated", "mosquitoes", "result", "in", "high", "levels", "of", "anti-sporozoite", "antibodies", "and", "protection", "against", "liver", "stage", "Plasmodium", "infection.", "Exposure", "to", "daily", "infected", "mosquito", "bites", "did", "not", "eliminate", "the", "protection", "acquired", "previously", "with", "a", "experimental", "liver", "stage", "vaccine.", "Conclusions:", "Liver", "stage", "immunity", "generated", "by", "irradiated", "versus", "normal", "P.", "yoelii", "infected", "mosquitoes", "is", "essentially", "different,", "probably", "because", "of", "the", "blood", "stage", "infection", "that", "follows", "normal", "mosquito", "bites,", "but", "not", "irradiated.", "While", "infective", "mosquito", "bites", "do", "not", "induce", "a", "protective", "liver", "stage", "response,", "they", "also", "do", "not", "interfere", "with", "previously", "acquired", "liver", "stage", "protective", "responses,", "even", "if", "they", "induce", "a", "complete", "blood", "stage", "infection.", "Considering", "that", "the", "recently", "generated", "anti-malaria", "vaccines", "induce", "only", "partial", "protection", "against", "infection,", "it", "is", "encouraging", "that,", "at", "least", "in", "mouse", "models,", "immunity", "is", "not", "negatively", "affected", "by", "subsequent", "exposure", "and", "infection", "with", "the", "parasite.", "Background", "Malaria", "is", "a", "widespread", "mosquito-borne", "infectious", "dis-", "ease", "that", "kills", "almost", "one", "million", "persons", "per", "year,", "most", "of", "which", "are", "children.", "Growing", "scientific", "knowledge", "and", "the", "recent", "malaria", "research", "trend", "provide", "unparalleled", "opportunities", "to", "develop", "a", "malaria", "vaccine.", "Although", "the", "subunit", "vaccines", "are", "the", "most", "advanced", "in", "research", "pipelines", "and", "field", "clinical", "trials", "[1],", "an", "effective", "and", "focused", "effort", "prevails", "in", "order", "to", "develop", "an", "attenuated", "sporozoite-based", "vaccine", "[2,3],", "once", "the", "protective", "*", "Correspondence:", "Ana.Rodriguez@nyumc.org", "†", "Contributed", "equally", "1Department", "of", "Microbiology,", "Division", "of", "Medical", "Parasitology,", "New", "York", "University", "School", "of", "Medicine,", "New", "York,", "NY", "10010,", "USA", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "immunity", "produced", "by", "attenuated", "sporozoites", "is", "stron-", "ger", "and", "more", "unswerving", "than", "that", "induced", "by", "subunit", "vaccination", "[4].", "Immunization", "with", "irradiated", "Plasmo-", "dium", "sporozoites", "grants", "protection", "against", "inoculation", "with", "non-attenuated", "sporozoites", "in", "mice", "models", "and", "humans", "[5,6].", "However,", "individuals", "in", "malaria", "endemic", "regions", "do", "not", "develop", "fully", "protective", "immune", "responses", "against", "Plasmodium", "liver", "stage", "infections", "even", "if", "exposed", "to", "more", "than", "two", "infective", "mosquito", "bites", "daily", "[7,8],", "as", "is", "the", "case", "in", "high", "transmission", "areas", "[9].", "Using", "a", "mouse", "model,", "a", "previous", "study", "showed", "that", "the", "mode", "of", "irradiated", "sporozoite", "delivery:", "daily", "mos-", "quito", "bites", "(as", "in", "endemic", "areas)", "versus", "few", "large", "doses", "of", "sporozoites", "(as", "in", "immunization", "protocols)", "does", "not", "affect", "the", "generation", "of", "protective", "liver", "stage", "immunity", "©", "2011", "Pollock", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Dynein", "Intermediate", "Chain", "Mediated", "Dynein–Dynactin", "Interaction", "Is", "Required", "for", "Interphase", "Microtubule", "Organization", "and", "Centrosome", "Replication", "and", "Separation", "in", "Dictyostelium", "Shuo", "Ma,*", "Leda", "Triviños-Lagos,*", "Ralph", "Gräf,‡", "and", "Rex", "L.", "Chisholm*", "*Department", "of", "Cell", "and", "Molecular", "Biology,", "and", "Robert", "H.", "Lurie", "Comprehensive", "Cancer", "Center,", "Northwestern", "University", "Medical", "School,", "Chicago,", "Illinois", "60611;", "and", "‡Adolf-Butenandt-Institut/Zellbiologie,", "Universitaet", "Muenchen,", "D-80336", "Muenchen,", "Germany", "Abstract.", "Cytoplasmic", "dynein", "intermediate", "chain", "(IC)", "mediates", "dynein–dynactin", "interaction", "in", "vitro", "(Karki,", "S.,", "and", "E.L.", "Holzbaur.", "1995.", "J.", "Biol.", "Chem.", "270:28806–", "28811;", "Vaughan,", "K.T.,", "and", "R.B.", "Vallee.", "1995.", "J.", "Cell", "Biol.", "131:1507–1516).", "To", "investigate", "the", "physiological", "role", "of", "IC", "and", "dynein–dynactin", "interaction,", "we", "ex-", "pressed", "IC", "truncations", "in", "wild-type", "Dictyostelium", "cells.", "ICDC", "associated", "with", "dynactin", "but", "not", "with", "dynein", "heavy", "chain,", "whereas", "ICDN", "truncations", "bound", "to", "dy-", "nein", "but", "bound", "dynactin", "poorly.", "Both", "mutations", "re-", "sulted", "in", "abnormal", "localization", "to", "the", "Golgi", "complex,", "confirming", "dynein", "function", "was", "disrupted.", "Striking", "dis-", "organization", "of", "interphase", "microtubule", "(MT)", "networks", "was", "observed", "when", "mutant", "expression", "was", "induced.", "In", "a", "majority", "of", "cells,", "the", "MT", "networks", "collapsed", "into", "large", "bundles.", "We", "also", "observed", "cells", "with", "multiple", "cy-", "toplasmic", "asters", "and", "MTs", "lacking", "an", "organizing", "center.", "C", "YTOPLASMIC", "tubule", "(MT)1-based", "dynein,", "a", "motor,", "minus-end–directed,", "has", "been", "implicated", "micro-", "in", "a", "broad", "range", "of", "MT-dependent", "activities", "both", "in", "mitosis", "and", "interphase.", "Cytoplasmic", "dynein", "is", "important", "for", "spindle", "orientation", "in", "yeast", "(Eshel", "et", "al.,", "1993)", "and", "nu-", "clear", "migration", "in", "filamentous", "fungi", "(Plamann", "et", "al.,", "1994;", "Xiang", "et", "al.,", "1994).", "In", "Drosophila", "and", "mammalian", "cells,", "it", "is", "required", "for", "spindle", "formation", "and", "function", "(Vaisberg", "et", "al.,", "1993;", "Echeverri", "et", "al.,", "1996;", "Gepner", "et", "al.,", "1996).", "Dur-", "ing", "interphase,", "cytoplasmic", "dynein", "mediates", "the", "move-", "ment", "of", "membranous", "vesicles", "such", "as", "perinuclear", "position-", "ing", "of", "the", "Golgi", "apparatus", "(Corthesy-Theulaz", "et", "al.,", "1992;", "Burkhardt", "et", "al.,", "1997;", "Harada", "et", "al.,", "1998),", "ER-to-Golgi", "Address", "correspondence", "to", "Rex", "L.", "Chisholm,", "Department", "of", "Cell", "and", "Molecular", "Biology,", "Northwestern", "University", "Medical", "School,", "303", "East", "Chicago", "Ave.,", "Ward", "11-100,", "Chicago,", "IL", "60611-3072.", "Tel.:", "(312)", "503-4151.", "Fax:", "(312)", "503-5994.", "E-mail:", "r-chisholm@nwu.edu", "1.", "Abbreviations", "used", "in", "this", "paper:", "DAPI,", "4,6-diamidino-2-phenylindole;", "HC,", "heavy", "chain;", "IC,", "intermediate", "chain;", "IP,", "immunoprecipitation;", "MT,", "microtubule;", "MTOC,", "MT", "organizing", "center.", "These", "cells", "accumulated", "abnormal", "DNA", "content,", "sug-", "gesting", "a", "defect", "in", "mitosis.", "Striking", "defects", "in", "cen-", "trosome", "morphology", "were", "also", "observed", "in", "IC", "mutants,", "mostly", "larger", "than", "normal", "centrosomes.", "Ultrastructural", "analysis", "of", "centrosomes", "in", "IC", "mutants", "showed", "inter-", "phase", "accumulation", "of", "large", "centrosomes", "typical", "of", "prophase", "as", "well", "as", "unusually", "paired", "centrosomes,", "sug-", "gesting", "defects", "in", "centrosome", "replication", "and", "separa-", "tion.", "These", "results", "suggest", "that", "dynactin-mediated", "cytoplasmic", "dynein", "function", "is", "required", "for", "the", "proper", "organization", "of", "interphase", "MT", "network", "as", "well", "as", "cen-", "trosome", "replication", "and", "separation", "in", "Dictyostelium.", "Key", "words:", "dynein", "function", "•", "intermediate", "chain", "•", "dynein–dynactin", "interaction", "•", "microtubule", "organiza-", "tion", "•", "centrosome", "replication", "and", "separation", "transport", "(Presley", "et", "al.,", "1997),", "and", "retrograde", "axonal", "transport", "(Dillman", "et", "al.,", "1996;", "Waterman-Storer", "et", "al.,", "1997).", "Despite", "this", "we", "have", "a", "limited", "understanding", "of", "how", "dynein", "is", "targeted", "and", "regulated", "to", "accomplish", "these", "varied", "functions.", "The", "best", "candidate", "for", "targeting", "and", "regulating", "dynein", "activity", "is", "the", "dynactin", "complex.", "Dynactin,", "named", "for", "dy-", "nein", "activator,", "was", "initially", "isolated", "as", "a", "factor", "required", "to", "activate", "dynein-dependent", "vesicle", "transport", "in", "vitro", "(Gill", "et", "al.,", "1991;", "Schroer", "and", "Sheetz,", "1991).", "Dynactin", "is", "a", "large", "complex", "containing", "at", "least", "nine", "different", "subunits,", "includ-", "ing", "p150/Glued,", "p50", "(dynamitin),", "Arp1,", "actin,", "capping", "protein,", "p62,", "p24,", "and", "others", "(Schafer", "et", "al.,", "1994).", "Genetic", "analysis", "in", "several", "different", "organisms", "indicates", "that", "dy-", "nactin", "functions", "in", "the", "same", "genetic", "pathway", "as", "dynein", "(Clark", "and", "Meyer,", "1994;", "Muhua", "et", "al.,", "1994;", "Plamann", "et", "al.,", "1994;", "McGrail", "et", "al.,", "1995;", "Bruno", "et", "al.,", "1996;", "Tinsley", "et", "al.,", "1996).", "Overexpression", "of", "the", "p50/dynamitin", "subunits", "in", "mammalian", "cells", "disrupted", "dynactin", "and", "led", "to", "dynein", "re-", "distribution.", "These", "cells", "accumulated", "in", "prometaphase", "and", "had", "dispersed", "Golgi", "apparatus", "(Echeverri", "et", "al.,", "1996;", "ª", "The", "Rockefeller", "University", "Press,", "0021-9525/99/12/1261/13", "$5.00", "The", "Journal", "of", "Cell", "Biology,", "Volume", "147,", "Number", "6,", "December", "13,", "1999", "1261–1273", "http://www.jcb.org", "1261" ]

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"College,", "Valhalla,", "New", "York,", "NY", "10595,", "USA", "4", "Department", "of", "Statistics", "and", "Institute", "for", "Health,", "Health", "Care", "Policy", "and", "Aging", "Research,", "Rutgers", "University,", "110", "Frelinghuysen", "Road,", "Room", "473,", "Piscataway,", "NJ", "08854,", "USA", "Correspondence", "should", "be", "addressed", "to", "Di", "Shi,", "deandishi@yahoo.com", "Received", "4", "June", "2012;", "Accepted", "8", "August", "2012", "Academic", "Editor:", "Francesc", "Formiga", "Copyright", "©", "2012", "Di", "Shi", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Objectives.", "To", "examine", "associations", "between", "having", "bone", "density", "tests", "and", "level", "of", "education", "among", "white", "elderly", "women", "in", "managed", "Medicare.", "Method.", "Data", "from", "the", "ninth", "through", "twelfth", "cohort", "(2006–2009)", "of", "the", "Medicare", "Health", "Outcome", "Survey", "(HOS)", "of", "managed", "Medicare", "plans", "were", "analyzed;", "239331", "white", "elderly", "women", "were", "included.", "Respondents", "were", "grouped", "by", "education", "level", "and", "the", "percentages", "of", "respondents", "who", "had", "lifetime", "bone", "density", "testing", "done", "among", "each", "group", "were", "analyzed.", "Results.", "62.7%", "of", "respondents", "with", "less", "than", "a", "high", "school", "education", "reported", "previously", "taking", "a", "bone", "density", "test.", "This", "was", "lower", "than", "the", "73.8%", "for", "respondents", "who", "completed", "high", "school", "and", "the", "81.0%", "for", "respondents", "with", "more", "than", "a", "high", "school", "education.", "When", "potential", "confounding", "factors", "such", "as", "age,", "body", "mass", "index,", "marital", "status,", "smoking", "history,", "year", "of", "HOS", "survey,", "and", "region", "were", "factored", "in,", "the", "odds", "ratios", "of", "having", "a", "bone", "density", "test", "when", "compared", "to", "respondents", "with", "less", "than", "a", "high", "school", "education", "were", "1.61", "and", "2.39,", "respectively,", "for", "those", "with", "just", "a", "high", "school", "education", "and", "more", "than", "a", "high", "school", "education", "(P", "<", "0.001).", "Conclusion.", "Higher", "education", "was", "independently", "associated", "with", "greater", "use", "of", "bone", "density", "test", "in", "these", "elderly", "white", "women.", "1.", "Introduction", "In", "recent", "years,", "many", "studies", "have", "found", "a", "link", "between", "education", "level", "and", "the", "overall", "health", "of", "a", "person.", "Lower", "edu-", "cation", "was", "found", "worldwide", "to", "be", "correlated", "with", "increases", "in", "many", "areas", "of", "health", "risk", "including", "cardiac", "dysfunction", "[1],", "preterm", "birth", "[2],", "mortality", "[3],", "and", "others", "diseases", "[4,", "5].", "Furthermore,", "these", "effects", "of", "education", "disparity", "on", "greater", "disease", "prevalence", "[4]", "and", "lower", "life", "expectancy", "may", "be", "growing", "[6].", "When", "treating", "patients", "with", "lower", "education", "levels,", "physicians", "spend", "less", "time", "discussing", "health", "related", "issues", "[7]", "which", "may", "lead", "to", "gaps", "in", "health", "awareness", "including", "the", "use", "of", "preventive", "services.", "For", "example,", "lower", "levels", "of", "education", "have", "been", "linked", "to", "lower", "use", "of", "public", "health", "services", "in", "Brazil", "[8]", "and", "lower", "use", "of", "HIV", "testing", "in", "Portugal’s", "immigrant", "population", "[9].", "The", "goal", "of", "this", "paper", "is", "to", "see", "if", "lower", "education", "also", "effects", "use", "of", "bone", "mineral", "density", "test", "among", "a", "group", "that", "would", "benefit", "most", "from", "testing,", "elderly", "white", "women", "in", "the", "United", "States.", "Bone", "fractures", "can", "have", "devastating", "consequences", "including", "pain,", "loss", "of", "mobility", "function,", "and", "death.", "Among", "elderly,", "particularly", "postmenopausal", "women,", "deterioration", "in", "bone", "mass", "progressively", "increases", "the", "risk", "of", "fragility", "fractures", "compared", "to", "people", "with", "healthy", "bone", "[10].", "While", "all", "elderly", "women", "in", "America", "are", "at", "higher", "risk", "for", "fractures,", "Caucasians", "are", "at", "higher", "risk", "than", "others", "in", "particular", "African", "Americans.", "Among", "50-year-old", "white", "women,", "the", "risk", "for", "suffering", "a", "hip", "fracture", "at", "some", "future", "point", "in", "their", "life", "is", "16%", "while", "the", "risks", "for", "suffering", "a", "forearm", "or", "thoracic/lumbar", "spine", "fracture", "are", "15%", "and", "32%," ]

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[ "International", "Archives", "of", "Medicine", "Original", "research", "Pain", "management", "among", "medical", "in-patients", "in", "Blantyre,", "Malawi", "Adamson", "S", "Muula*", "and", "Humphreys", "E", "Misiri", "BioMed", "Central", "Open", "Access", "Address:", "Department", "of", "Public", "Health,", "Division", "of", "Community", "Health,", "College", "of", "Medicine,", "University", "of", "Malawi,", "Blantyre,", "Malawi", "Email:", "Adamson", "S", "Muula*", "-", "muula@email.unc.edu;", "Humphreys", "E", "Misiri", "-", "hemisri@medcol.mw", "*", "Corresponding", "author", "Published:", "26", "March", "2009", "International", "Archives", "of", "Medicine", "2009,", "2:6", "doi:10.1186/1755-7682-2-6", "This", "article", "is", "available", "from:", "http://www.intarchmed.com/content/2/1/6", "Received:", "17", "November", "2008", "Accepted:", "26", "March", "2009", "©", "2009", "Muula", "and", "Misiri;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "Pain", "is", "a", "leading", "symptom", "which", "influences", "patients", "to", "seek", "medical", "attention.", "The", "management", "of", "pain", "among", "patients", "attending", "in-patient", "care", "in", "southern", "African", "countries", "has", "been", "little", "described.", "Information", "regarding", "the", "prevalence", "of", "pain", "and", "the", "quality", "of", "its", "management", "may", "be", "useful", "in", "guiding", "clinical", "decisions,", "training", "of", "health", "workers", "and", "health", "care", "quality", "improvements.", "Methods:", "A", "hospital-based", "audit", "was", "conducted", "to", "estimate", "the", "prevalence", "of", "pain", "and", "examine", "the", "quality", "of", "its", "management", "among", "patients", "admitted", "to", "adult", "medical", "wards", "at", "Queen", "Elizabeth", "Central", "Hospital", "(QECH),", "Blantyre,", "Malawi", "in", "2004.", "Data", "were", "abstracted", "from", "ward", "charts", "of", "consecutive", "patients'", "who", "had", "been", "either", "been", "discharged", "or", "had", "died", "within", "a", "specified", "period.", "Characteristics", "of", "interest", "included;", "socio-demographic", "data,", "presence", "or", "absence", "of", "pain", "at", "admission,", "characterization", "or", "description", "of", "pain", "when", "present,", "and", "drug", "treatment", "given.", "Data", "were", "analyzed", "to", "obtain", "frequencies", "and", "proportions", "of", "the", "characteristics", "and", "assess", "the", "prevalence", "of", "pain", "and", "quality", "of", "care.", "Results:", "A", "total", "of", "121", "patients'", "case", "notes", "were", "reviewed", "and", "the", "prevalence", "of", "pain", "was", "recorded", "for", "91", "(75.2%)", "of", "the", "patients.", "Clinicians", "had", "recorded", "pertinent", "information", "regarding", "pain", "management", "with", "the", "following", "frequency:", "pain", "severity", "or", "intensity", "5/91", "(5.5%),", "alleviating", "factors", "5", "(5.5%),", "pain", "radiation", "7", "(7.7%),", "exacerbating", "factors", "in", "9", "(9.9%)", "and", "periodicity", "in", "43", "(47.3%)", "of", "the", "cases.", "Males", "with", "pain", "were", "more", "than", "3", "times", "more", "likely", "to", "receive", "analgesic", "as", "compared", "to", "females,", "p", "<", "0.01.", "Paracetamol", "was", "the", "commonest", "analgesic", "prescribed.", "Conclusion:", "Inadequate", "management", "of", "pain", "among", "patients", "attending", "medical", "wards", "at", "QECH", "was", "found.", "There", "is", "need", "for", "prospective", "studies", "to", "further", "characterize", "pain", "management", "and", "identify", "pain", "management", "gaps", "in", "Malawi.", "Interviews", "of", "clinicians", "and", "documentation", "of", "observations", "within", "clinical", "practice", "are", "likely", "to", "be", "of", "value.", "Background", "Pain", "is", "a", "common", "medical", "symptom", "prompting", "patients", "to", "seek", "care.", "However", "adequate", "management", "of", "pain", "remains", "a", "global", "challenge.", "In", "1982,", "the", "World", "Health", "Organization", "(WHO)", "recognized", "inadequate", "manage-", "ment", "of", "(cancer)", "pain", "as", "an", "international", "health", "problem", "[1].", "While", "cancer", "pain", "management", "has", "certainly", "received", "some", "attention", "however,", "pain", "experienced", "during", "child-", "birth,", "that", "arising", "from", "infectious", "diseases,", "in", "post-surgi-", "cal", "care", "and", "in", "other", "clinical", "situations", "remains", "under-", "appreciated", "among", "researchers", "in", "southern", "Africa.", "In", "addition,", "while", "there", "is", "deserved", "interest", "in", "the", "clinical", "Page", "1", "of", "5", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Tsigkas", "et", "al.", "Journal", "of", "Cardiothoracic", "Surgery", "2011,", "6:101", "http://www.cardiothoracicsurgery.org/content/6/1/101", "C", "A", "S", "E", "R", "E", "P", "O", "R", "T", "Open", "Access", "A", "successfully", "thrombolysed", "acute", "inferior", "myocardial", "infarction", "due", "to", "type", "A", "aortic", "dissection", "with", "lethal", "consequences:", "the", "importance", "of", "early", "cardiac", "echocardiography", "Grigorios", "Tsigkas1,", "Georgios", "Kasimis1*,", "Konstantinos", "Theodoropoulos1,", "Konstantinos", "Chouchoulis1,", "Nikolaos", "G", "Baikoussis2,", "Efstratios", "Apostolakis2,", "Eleni", "Bousoula1,", "Athanasios", "Moulias1", "and", "Dimitrios", "Alexopoulos1", "Abstract", "Thrombolysis,", "a", "standard", "therapy", "for", "ST", "elevation", "myocardial", "infarction", "(STEMI)", "in", "non-PCI-capable", "hospitals,", "may", "be", "catastrophic", "for", "patients", "with", "aortic", "dissection", "leading", "to", "further", "expansion,", "rupture", "and", "uncontrolled", "bleeding.", "Stanford", "type", "A", "aortic", "dissection,", "rarely", "may", "mimic", "myocardial", "infarction.", "We", "report", "a", "case", "of", "a", "patient", "with", "an", "inferior", "STEMI", "thrombolysed", "with", "tenecteplase", "and", "followed", "by", "clinical", "and", "electrocardiographic", "evidence", "of", "successful", "reperfusion,", "which", "was", "found", "later", "to", "be", "a", "lethal", "acute", "aortic", "dissection.", "Prognostic", "implications", "of", "early", "diagnosis", "applying", "transthoracic", "echocardiography", "(TTE)", "are", "described.", "Background", "Acute", "myocardial", "infarction", "(AMI)", "usually", "results", "from", "an", "occlusive", "coronary", "thrombus", "at", "the", "site", "of", "a", "ruptured", "atherosclerotic", "plaque", "[1].", "Reperfusion", "therapies", "such", "as", "primary", "percutaneous", "coronary", "intervention", "(PPCI)", "and", "thrombolysis", "are", "mandatory", "steps", "for", "reducing", "mortality", "and", "limiting", "the", "infarct", "size", "in", "patients", "with", "ST", "segment", "elevation", "myocardial", "infarction", "(STEMI).", "The", "greatest", "benefit", "occurs,", "if", "reperfusion", "therapy", "is", "initiated", "within", "the", "first", "hours", "from", "the", "onset", "of", "symptoms", "and", "there", "is", "no", "preference", "for", "either", "strategy,", "if", "these", "symptoms", "are", "present", "for", "less", "than", "3", "hours", "[2].", "Clinically", "speaking,", "many", "conditions,", "such", "as", "acute", "aortic", "dissection,", "peri-", "carditis,", "pulmonary", "embolism", "and", "myocarditis", "may", "mimic", "acute", "myocardial", "infarction.", "Thrombolysis", "in", "most", "of", "these", "situations", "is", "absolutely", "contraindicated", "due", "to", "its", "potentially", "lethal", "complications.", "Clinicians", "should", "always", "bear", "in", "mind", "the", "possibility", "that", "a", "type", "A", "aortic", "dissection", "(AAD)", "may", "mimic", "an", "AMI,", "which", "requires", "an", "urgent", "surgical", "repair", "without", "any", "delay.", "*", "Correspondence:", "gksup@yahoo.gr", "1Department", "of", "Cardiology,", "Patras", "University", "School", "of", "Medicine,", "Patras,", "Greece", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "Case", "presentation", "A", "57-year-old", "woman,", "with", "a", "history", "of", "hypertension,", "was", "admitted", "to", "the", "emergency", "department", "of", "a", "rural", "non-PCI-capable", "Hospital", "due", "to", "an", "atypical,", "non-com-", "pressing,", "non-excruciating", "chest", "pain", "of", "recent", "origin", "(30", "minutes)", "with", "radiation", "to", "the", "back.", "The", "patient", "was", "hemodynamically", "stable,", "with", "no", "peripheral", "pulse", "deficit.", "Auscultation", "of", "the", "heart", "revealed", "a", "2/6", "systolic", "murmur", "at", "the", "right", "base", "and", "apex", "and", "an", "early", "diastolic", "mur-", "mur", "at", "the", "right", "base", "without", "pericardial", "friction.", "The", "electrocardiogram", "(ECG)", "(Figure", "1)", "was", "compatible", "with", "the", "diagnosis", "of", "a", "STEMI", "of", "the", "inferior", "wall.", "The", "doc-", "tor", "in", "charge", "decided", "to", "administer", "thrombolytic", "treat-", "ment", "with", "tenecteplase", "(TNK)", "(Metalyse®)", "without", "further", "delay.", "The", "patient’s", "symptoms", "were", "partially", "relieved,", "while", "the", "pre-existing", "ST", "elevation", "did", "not", "seem", "to", "be", "completely", "normalized", "in", "the", "following", "60", "minutes.", "For", "this", "reason,", "she", "was", "referred", "to", "our", "hospi-", "tal", "for", "rescue", "angioplasty", "[3].", "When", "the", "patient", "arrived", "had", "a", "remission", "both", "of", "the", "initial", "thoracic", "pain", "and", "of", "ST-elevation", "in", "the", "ECG", "(Figure", "2),", "remaining", "hemody-", "namically", "stable", "without", "obvious", "perceivable", "peripheral", "artery", "pulse", "deficit,", "but", "was", "clearly", "uncomfortable", "and", "she", "was", "complaining", "for", "a", "diffuse", "abdominal", "pain", "with-", "out", "any", "sign", "of", "peritoneal", "irritation.", "In", "addition,", "she", "was", "©", "2011", "Tsigkas", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Iranian", "Red", "Crescent", "Medical", "Journal", "ORIGINAL", "ARTICLE", "Effect", "of", "Metformin", "on", "Serum", "Ferritin", "Level", "in", "Women", "with", "Polycystic", "Ovary", "Syndrome", "S", "Behradmanesh", "1", ",", "GhH", "Ranjbar", "Omrani2,", "F", "Ghazanfarpour3,", "A", "Baradaran", "4", "*", "1Department", "of", "Internal", "Medicine", "and", "Endocrinology,", "Shahr-e-Kord", "University", "of", "Medical", "Sciences,", "Shahr-e-Kord,", "Iran", "2Department", "of", "Internal", "Medicine", "and", "Endocrinology,", "Endocrine", "and", "Metabolic", "Re-", "search", "Center,", "Nemazee", "Hospital,", "Shiraz", "University", "of", "Medical", "Sciences,", "Shiraz,", "Iran", "3Skin", "Diseases", "and", "Leishmaniasis", "Research", "Center,", "Isfahan", "University", "of", "Medical", "Sciences,", "Isfahan,", "Iran", "4Department", "of", "Pa-", "thology,", "Isfahan", "University", "of", "Medical", "Sciences,", "Isfahan,", "Iran", "Abstract", "Background:", "Polycystic", "ovary", "syndrome", "(PCOS)", "is", "one", "of", "the", "most", "common", "diseases", "among", "women", "associat-", "ed", "with", "various", "inflammatory", "reactants", "such", "as", "C-reactive", "protein", "(CRP)", "and", "ferritin.", "This", "study", "aimed", "to", "investi-", "gate", "the", "effect", "of", "metformin", "on", "probable", "reduction", "of", "serum", "ferritin", "in", "patients", "with", "PCOS.", "Methods:", "This", "study", "was", "conducted", "on", "45", "patients", "with", "PCOS", "who", "had", "not", "other", "systemic", "diseases", "and", "did", "not", "take", "any", "medications.", "Weight,", "waist", "and", "hip", "circumstances", "(WHR),", "body", "mass", "index", "(BMI),", "metabolic", "indexes,", "CRP,", "ferritin", "and", "“Homeostasis", "Model", "Assessment", "of", "Insulin", "Resistance", "(HOMA-IR)", "˝", "were", "measured", "before", "the", "study.", "Metformin", "(500", "mg/tid)", "tablets", "were", "prescribed", "for", "three", "months", "and", "then", "same", "above", "parameters", "were", "re-measured.", "Results:", "Of", "45", "patients,", "19", "(42.2%)", "were", "overweight", "and", "14", "(31.1%)", "were", "obese.", "After", "drug", "therapy,", "there", "was", "a", "significant", "reduction", "in", "waist", "circumstance", "and", "serum", "ferritin.", "This", "reduction", "was", "significant", "only", "in", "the", "lean", "and", "overweight", "groups", "but", "not", "in", "the", "obese", "group.", "There", "was", "not", "significant", "association", "between", "serum", "ferritin", "and", "CRP,", "HOMA-IR,", "BMI", "and", "WHR.", "There", "was", "not", "significant", "correlation", "between", "CRP", "and", "HOMA-IR", "and", "also", "BMI.", "Conclusion:", "The", "effect", "of", "metformin", "on", "reduction", "of", "serum", "ferritin", "was", "not", "significant", "just", "in", "obese", "group", "and", "was", "not", "associated", "with", "metabolic", "and", "anthropometric", "indexes.", "Keywords:", "Ferritin;", "Polycystic", "Ovary", "Syndrome;", "Metformin", "Introduction", "Polycystic", "ovary", "syndrome", "(PCOS)", "is", "one", "of", "the", "most", "common", "diseases", "with", "prevalence", "of", "6-7%", "among", "women", "in", "their", "reproductive", "age.1-4", "Obesity,", "hyper-", "androgenism,", "ovarian", "dysfunction", "and", "insulin", "re-", "sistance", "are", "features", "of", "this", "disease.5", "In", "addition,", "other", "diseases", "such", "as", "type", "2", "diabetes", "mellitus", "(T2DM),", "metabolic", "syndrome", "(MetS)", "and", "cardiovascular", "dis-", "eases", "(CVD)", "are", "related", "to", "this", "syndrome.6-9", "It", "has", "been", "recently", "found", "that", "acute", "phase", "reactants", "of", "in-", "*Correspondence:", "Azar", "Baradaran,", "MD,", "Associate", "Professor", "of", "Pathology,", "Al-Zahra", "Medical", "Center,", "Isfahan", "University", "of", "Medical", "Sciences,", "Isfahan,", "Iran.", "Tel:", "+98-913-3278027,", "e-mail:", "azarbaradaran@yahoo.com", "Received:", "October", "15,", "2010;", "Accepted:", "February", "12,", "2011", "flammation", "including", "C-reactive", "protein", "(CRP)", "are", "higher", "than", "normal", "in", "T2DM,", "hyperinsulinemia10", "and", "PCOS.11", "Serum", "level", "of", "CRP", "has", "a", "higher", "value", "in", "obese", "PCOS", "subjects", "than", "those", "non-obese", "with", "PCOS.", "A", "treatment", "with", "metformin", "for", "six", "months", "lowers", "CRP", "serum", "level", "in", "all", "subjects", "as", "well", "as", "obese", "and", "non–obese.12", "Another", "acute", "phase", "reactants", "of", "inflammation", "is", "ferritin", "which", "is", "higher", "than", "nor-", "mal", "in", "patients", "with", "metabolic", "syndrome,", "T2DM", "pa-", "tients", "and", "PCOS.13-15", "Serum", "ferritin", "levels", "in", "over-", "weight", "and", "obese", "women", "with", "PCOS", "are", "significantly", "higher", "compared", "to", "overweight", "and", "obese", "women", "without", "this", "disorder.15-18", "Metformin", "causes", "improvement", "of", "insulin", "re-", "sistance", "in", "patients", "with", "PCOS.19,20", "Regarding", "the", "prevalence", "of", "PCOS", "among", "women", "at", "reproductive", "age4", "and", "accompany", "of", "acute", "phase", "reactants", "of", "in-", "Iran", "Red", "Crescent", "Med", "J", "2011;", "13(7):487-492", "©Iranian", "Red", "Crescent", "Medical", "Journal" ]

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[ "CLINICS", "2011;66(4):717-718", "CASE", "REPORT", "DOI:10.1590/S1807-59322011000400031", "Acute", "treatment", "of", "uncompensated", "heart", "failure", "with", "10%", "hypertonic", "saline", "and", "its", "subsequent", "effect", "on", "respiratory", "patterns", "Fernando", "Godinho", "Zampieri,I,II", "Pedro", "CarusoI,III", "I", "Unidade", "de", "Terapia", "Intensiva,", "Hospital", "AC", "Camargo,", "Fundac¸a˜", "o", "Antoˆ", "nio", "Prudente,", "S", "a˜o", "Paulo,", "Brasil.", "II", "Disciplina", "de", "Emergeˆ", "ncia", "Cl´ınica,", "Hospital", "das", "Cl´ınicas,", "Faculdade", "de", "Medicina", "da", "Universidade", "de", "S", "a˜o", "Paulo,", "S", "a˜o", "Paulo,", "Brasil.", "III", "UTI", "Respirat", "o´ria,", "Disciplina", "de", "Pneumologia,", "Faculdade", "de", "Medicina", "da", "Universidade,", "Sa˜", "o", "Paulo,", "Brasil.", "Email:", "fgzampa@uol.com.br", "Tel.:", "55", "11", "96008428", "INTRODUCTION", "Uncompensated", "heart", "failure", "(UHF)", "is", "a", "leading", "cause", "of", "hospitalization.", "The", "available", "drugs", "to", "treat", "acute", "UHF", "include", "inotropes,", "diuretics", "and", "vasodilators.", "In", "recent", "years,", "hypertonic", "saline", "(HTS)", "has", "emerged", "as", "a", "new", "potential", "therapy", "for", "refractory", "heart", "failure,", "usually", "in", "association", "with", "high", "doses", "of", "diuretics.", "However,", "there", "have", "been", "no", "reports", "describing", "the", "use", "of", "HTS", "as", "a", "first-line", "treatment", "for", "UHF.", "Here,", "we", "report", "a", "case", "in", "which", "a", "10%", "NaCl", "solution", "was", "used", "as", "the", "primary", "therapy", "for", "a", "patient", "with", "UHF.", "Almost", "immediately,", "hypertonic", "saline", "was", "able", "to", "restore", "the", "patient’s", "hemodynamic", "profile", "and", "to", "eliminate", "Cheyne-Stokes", "respiration", "(CSR),", "which", "is", "asso-", "ciated", "with", "a", "low", "cardiac", "output", "state.", "CASE", "DESCRIPTION", "A", "90-year-old", "man", "was", "admitted", "to", "the", "intensive", "care", "unit", "(ICU)", "because", "of", "dyspnea", "and", "lethargy.", "The", "patient", "had", "been", "diagnosed", "with", "prostatic", "cancer", "ten", "years", "before", "but", "had", "not", "received", "chemotherapy", "in", "the", "last", "two", "years.", "He", "also", "had", "chronic", "congestive", "heart", "failure", "with", "atrial", "fibrillation,", "probably", "related", "to", "arterial", "hypertension.", "His", "current", "prescriptions", "included", "furosemide", "(40", "mg", "once", "a", "day)", "and", "captopril", "(25", "mg", "twice", "daily).", "He", "had", "been", "institutionalized", "in", "a", "hospice", "for", "the", "previous", "six", "months", "and", "had", "symptoms", "of", "dyspnea", "after", "performing", "light", "to", "moderate", "activities.", "Upon", "admission,", "the", "patient", "was", "somnolent", "(hypoactive", "delirium)", "and", "exhibited", "no", "focal", "neurologic", "signs.", "He", "complained", "of", "shortness", "of", "breath", "and", "lower", "back", "pain.", "His", "extremities", "were", "cold", "and", "had", "delayed", "capillary", "refill", "(about", "4", "seconds).", "The", "patient’s", "blood", "pressure", "was", "74/", "46", "mmHg,", "and", "his", "heart", "rate", "was", "120", "beats", "per", "minute", "(atrial", "fibrillation).", "His", "central", "venous", "pressure", "was", "clini-", "cally", "estimated", "to", "be", "17", "cm", "of", "water.", "His", "breathing", "pattern", "was", "periodic", "and", "presented", "as", "apnea", "interspersed", "with", "faster", "and", "deeper", "breaths,", "which", "we", "determined", "to", "be", "Cheyne-Stokes", "respiration", "(CSR).", "He", "received", "supplemen-", "tary", "oxygen", "through", "a", "nasal", "catheter", "at", "two", "liters", "per", "minute", "Copyright", "2011", "CLINICS", "–", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://", "creativecommons.org/licenses/by-nc/3.0/)", "which", "permits", "unrestricted", "non-", "commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "717", "with", "a", "peripheral", "arterial", "O2", "saturation", "of", "99%.", "Rales", "were", "detected", "throughout", "the", "length", "of", "the", "patient’s", "hemi-", "thoraces.", "Laboratory", "exams", "showed", "a", "moderate", "level", "of", "metabolic", "acidosis,", "with", "a", "pH", "of", "7.20,", "a", "low", "bicarbonate", "level", "of", "17.8", "mEq/L", "and", "a", "standard", "base", "excess", "of", "-10", "mmol/L.", "His", "carbon", "dioxide", "level", "was", "slightly", "elevated", "at", "46.3", "mmHg,", "his", "lactate", "level", "was", "2", "mmol/L,", "and", "there", "were", "no", "electrolyte", "disorders", "detected.", "Initial", "troponin", "and", "creatine", "kinase-MB", "were", "both", "within", "normal", "ranges.", "Echocardiography", "was", "not", "available", "at", "the", "time.", "A", "diagnosis", "of", "cardiogenic", "shock", "was", "established.", "After", "meeting", "with", "the", "patient’s", "family,", "it", "was", "decided", "to", "treat", "the", "patient", "without", "invasive", "mechanical", "ventilation,", "dialysis,", "central", "venous", "puncture", "or", "vasoactive", "amines.", "The", "patient", "also", "refused", "noninvasive", "mechanical", "ventilation.", "Because", "the", "patient", "had", "already", "received", "1L", "of", "0.9%", "NaCl", "before", "ICU", "admission,", "only", "a", "small", "fluid", "challenge", "of", "250", "mL", "of", "lactated", "Ringer’s", "solution", "was", "administered.", "However,", "no", "improve-", "ment", "in", "the", "patients", "parameters", "was", "observed.", "A", "low", "dose", "of", "dobutamine", "was", "administered,", "but", "the", "patient", "developed", "several", "episodes", "of", "non-sustained", "ventricular", "tachycardia", "and", "hypotension,", "so", "dobutamine", "administration", "was", "stopped.", "Additionally,", "nitrates", "were", "not", "administered", "due", "to", "the", "patient’s", "low", "arterial", "blood", "pressure.", "Nesiritide", "was", "not", "available", "at", "the", "time.", "Therefore,", "we", "decided", "to", "try", "hypertonic", "saline", "infusion", "as", "a", "final,", "non-invasive", "approach", "to", "improve", "myocardial", "contractility.", "We", "infused", "100", "mL", "of", "10%", "NaCl", "over", "a", "period", "of", "10", "minutes.", "Less", "than", "three", "minutes", "after", "the", "infusion,", "the", "patient’s", "breathing", "pattern", "improved,", "with", "the", "progressive", "reduction", "in", "the", "time", "of", "peak", "ventilation,", "cycle", "length,", "apnea", "length", "and", "ventilation", "length.", "Finally,", "the", "patient’s", "breathing", "pattern", "returned", "to", "normal", "(figure", "1).", "The", "patient’s", "blood", "pressure", "increased", "to", "110/70", "mmHg,", "and", "his", "heart", "rate", "decreased", "to", "106", "beats", "per", "minute.", "His", "capillary", "refill", "time", "also", "improved.", "One", "hour", "later,", "intravenous", "infusion", "of", "a", "low", "dose", "of", "nitroprusside", "was", "performed,", "which", "was", "well", "tolerated", "by", "the", "patient.", "The", "patient", "was", "discharged", "from", "the", "ICU", "after", "being", "treated", "with", "oral", "vasodilators", "for", "an", "additional", "few", "days.", "DISCUSSION", "Recently,", "the", "use", "of", "hypertonic", "saline", "was", "proposed", "as", "a", "treatment", "for", "refractory", "heart", "failure", "associated", "with" ]

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[ "RESEARCH", "Antimicrobial", "Resistance", "Incidence", "and", "Risk", "Factors", "among", "Helicobacter", "pylori–Infected", "Persons,", "United", "States", "William", "M.", "Duck,*", "Jeremy", "Sobel,*", "Janet", "M.", "Pruckler,*", "Qunsheng", "Song,*", "David", "Swerdlow,*", "Cindy", "Friedman,*", "Alana", "Sulka,*", "Balasubra", "Swaminathan,*", "Tom", "Taylor,*", "Mike", "Hoekstra,*", "Patricia", "Griffin,*", "Duane", "Smoot,†", "Rick", "Peek,‡", "DavidC.", "Metz,§", "Peter", "B.", "Bloom,¶", "Steven", "Goldschmid,¶", "Julie", "Parsonnet,#", "George", "Triadafilopoulos,#", "Guillermo", "I.", "Perez-Perez,**", "Nimish", "Vakil,††", "Peter", "Ernst,‡‡", "Steve", "Czinn,§§", "Donald", "Dunne,¶¶", "and", "Ben", "D.", "Gold*", "Helicobacter", "pylori", "is", "the", "primary", "cause", "of", "peptic", "ulcer", "disease", "and", "an", "etiologic", "agent", "in", "the", "development", "of", "gas-", "tric", "cancer.", "H.", "pylori", "infection", "is", "curable", "with", "regimens", "of", "multiple", "antimicrobial", "agents,", "and", "antimicrobial", "resistance", "is", "a", "leading", "cause", "of", "treatment", "failure.", "The", "Helicobacter", "pylori", "Antimicrobial", "Resistance", "Monitoring", "Program", "(HARP)", "is", "a", "prospective,", "multicenter", "U.S.", "network", "that", "tracks", "national", "incidence", "rates", "of", "H.", "pylori", "antimicrobial", "resistance.", "Of", "347", "clinical", "H.", "pylori", "isolates", "collected", "from", "December", "1998", "through", "2002,", "101", "(29.1%)", "were", "resistant", "to", "one", "antimicrobial", "agent,", "and", "17", "(5%)", "were", "resistant", "to", "two", "or", "more", "antimicrobial", "agents.", "Eighty-seven", "(25.1%)", "isolates", "were", "resistant", "to", "metronidazole,", "45", "(12.9%)", "to", "clar-", "ithromycin,", "and", "3", "(0.9%)", "to", "amoxicillin.", "On", "multivariate", "analysis,", "black", "race", "was", "the", "only", "significant", "risk", "factor", "(p", "<", "0.01,", "hazard", "ratio", "2.04)", "for", "infection", "with", "a", "resistant", "H.", "pylori", "strain.", "Formulating", "pretreatment", "screening", "strategies", "or", "providing", "alternative", "therapeutic", "regimens", "for", "high-risk", "populations", "may", "be", "important", "for", "future", "clinical", "practice.", "Twide", "is", "approximately", "50%", "(1),", "as", "high", "as", "80%–90%", "he", "prevalence", "of", "Helicobacter", "pylori", "infection", "world-", "in", "developing", "countries,", "and", "≈35%–40%", "in", "the", "United", "*Centers", "for", "Disease", "Control", "and", "Prevention,", "Atlanta,", "Georgia,", "USA;", "†Howard", "University", "Medical", "Center,", "Washington,", "DC,", "USA;", "‡Vanderbilt", "University", "Medical", "Center,", "Nashville,", "Tennessee,", "USA;", "§University", "of", "Pennsylvania", "Medical", "Center,", "Philadelphia,", "Pennsylvania,", "USA;", "¶Atlanta", "Veterans", "Affairs", "Medical", "Center,", "Atlanta,", "Georgia,", "USA;", "#Stanford", "University", "Medical", "Center,", "Palo", "Alto,", "California,", "USA;", "**New", "York", "University", "School", "of", "Medicine,", "New", "York,", "New", "York,", "USA;", "††Sinai", "Samaritan", "Medical", "Center,", "Milwaukee,", "Wisconsin,", "USA;", "‡‡University", "of", "Virginia,", "Charlottesville,", "Virginia,", "USA;", "§§University", "Hospitals", "of", "Cleveland,", "Cleveland,", "Ohio,", "USA;", "and", "¶¶Indiana", "University", "Medical", "Center,", "Indianapolis,", "Indiana,", "USA", "States", "(1).", "Approximately", "20%", "of", "persons", "infected", "with", "H.", "pylori", "develop", "related", "gastroduodenal", "disorders", "during", "their", "lifetime", "(1).", "H.", "pylori", "is", "an", "etiologic", "agent", "of", "peptic", "ulcer", "disease,", "primary", "gastritis,", "gastric", "mucosa-associated", "lymphoid-tissue", "lymphoma,", "and", "gastric", "adenocarcinoma", "(2).", "The", "annual", "incidence", "of", "H.", "pylori", "infection", "is", "≈4%–15%", "in", "developing", "countries,", "compared", "with", "approximately", "0.5%", "in", "industrialized", "countries", "(3).", "Documented", "risk", "factors", "include", "low", "socioeconomic", "sta-", "tus,", "overcrowding,", "poor", "sanitation", "or", "hygiene,", "and", "living", "in", "a", "developing", "country", "(2).", "Eradication", "therapy", "of", "symptomatic", "H.", "pylori", "infection", "substantially", "reduces", "the", "recurrence", "of", "associated", "gastro-", "duodenal", "diseases.", "Therapy", "entails", "complicated", "regimens", "of", "several", "antimicrobial", "agents", "for", "at", "least", "2", "weeks.", "In", "gen-", "eral,", "triple", "therapy", "regimens", "usually", "entail", "two", "of", "the", "fol-", "lowing", "antimicrobial", "agents:", "metronidazole,", "amoxicillin,", "tetracycline,", "or", "clarithromycin", "in", "combination", "with", "a", "pro-", "ton", "pump", "inhibitor", "or", "bismuth", "(4).", "The", "most", "common", "causes", "of", "treatment", "failure", "are", "patient", "noncompliance", "and", "antimicrobial", "resistance", "of", "the", "infecting", "H.", "pylori", "strain", "(5).", "Quadruple", "regimens", "are", "used", "as", "a", "salvage", "therapy", "when", "triple", "therapy", "regimens", "have", "failed", "(4).", "Pretreatment", "resistance", "of", "H.", "pylori", "has", "been", "reported", "to", "compromise", "the", "efficacy", "of", "treatment.", "For", "example,", "therapy", "regimens", "containing", "metronidazole", "and", "clarithromycin", "fail", "in", "as", "many", "as", "38%", "and", "55%", "of", "cases,", "respectively,", "when", "used", "to", "treat", "infection", "with", "an", "organism", "resistant", "to", "one", "of", "these", "antimicrobial", "agents", "(6).", "In", "addition,", "published", "data", "are", "lacking", "that", "describe", "the", "effect", "conferred", "by", "polymicrobial", "resistance", "on", "eradication", "success.", "The", "Helicobacter", "pylori", "Antimicrobial", "Resistance", "Monitoring", "Project", "(HARP)", "is", "a", "prospective,", "longitudinal", "1088", "Emerging", "Infectious", "Diseases", "•", "www.cdc.gov/eid", "•", "Vol.", "10,", "No.", "6,", "June", "2004" ]

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[ "Research", "Genetic", "Effects", "on", "Toxic", "and", "Essential", "Elements", "in", "Humans:", "Arsenic,", "Cadmium,", "Copper,", "Lead,", "Mercury,", "Selenium,", "and", "Zinc", "in", "Erythrocytes", "Nicholas", "G.", "Martin1", "John", "B.", "Whitfield,1", "Veronica", "Dy,2", "Robert", "McQuilty,2", "Gu", "Zhu,1", "Andrew", "C.", "Heath,3", "Grant", "W.", "Montgomery,1", "and", "1Genetic", "Epidemiology", "Unit,", "Queensland", "Institute", "of", "Medical", "Research,", "Brisbane,", "Australia;", "2Biochemistry", "Department,", "Royal", "Prince", "Alfred", "Hospital,", "Sydney,", "Australia;", "3Midwest", "Alcoholism", "Research", "Center,", "Washington", "University,", "St.", "Louis,", "Missouri,", "USA", "Background", "and", "o", "Bjectivs", ":", "An", "excess", "of", "toxic", "trace", "elements", "or", "a", "deficiency", "of", "essential", "ones", "has", "been", "implicated", "in", "many", "common", "diseases", "or", "public", "health", "problems,", "but", "little", "is", "known", "about", "causes", "of", "variation", "between", "people", "living", "within", "similar", "environments.", "We", "estimated", "effects", "of", "per-", "sonal", "and", "socioeconomic", "characteristics", "on", "concentrations", "of", "arsenic", "(As),", "cadmium", "(Cd),", "copper", "(Cu),", "mercury", "(Hg),", "lead", "(Pb),", "selenium", "(Se),", "and", "zinc", "(Zn)", "in", "erythrocytes", "and", "tested", "for", "genetic", "effects", "using", "data", "from", "twin", "pairs.", "Methods", ":", "We", "used", "blood", "samples", "from", "2,926", "adult", "twins", "living", "in", "Australia", "(1,925", "women", "and", "1,001", "men;", "30–92", "years", "of", "age)", "and", "determined", "element", "concentrations", "in", "erythrocytes", "by", "induc-", "tively", "coupled", "plasma-mass", "spectrometry.", "We", "assessed", "associations", "between", "element", "concentrations", "and", "personal", "and", "socioeconomic", "characteristics,", "as", "well", "as", "the", "sources", "of", "genetic", "and", "environmental", "variation", "and", "covariation", "in", "element", "concentrations.", "We", "evaluated", "the", "chromosomal", "locations", "of", "genes", "affecting", "these", "characteristics", "by", "linkage", "analysis", "in", "501", "dizygotic", "twin", "pairs.", "r", "esult", ":", "Concentrations", "of", "Cu,", "Se,", "and", "Zn,", "and", "of", "As", "and", "Hg", "showed", "substantial", "correlations,", "concentrations", "of", "As", "and", "Hg", "due", "mainly", "to", "common", "genetic", "effects.", "Genetic", "linkage", "analysis", "showed", "significant", "linkage", "for", "Pb", "[chromosome", "3,", "near", "SLC4A7", "(solute", "carrier", "family", "4,", "sodium", "bicarbonate", "cotransporter,", "member", "7)]", "and", "suggestive", "linkage", "for", "Cd", "(chromosomes", "2,", "18,", "20,", "and", "X),", "Hg", "(chromosome", "5),", "Se", "(chromosomes", "4", "and", "8),", "and", "Zn", "{chromosome", "2,", "near", "SLC11A1", "[solute", "carrier", "family", "11", "(proton-coupled", "divalent", "metal", "ion", "transporters)]}.", "c", "onclusi", ":", "Although", "environmental", "exposure", "is", "a", "precondition", "for", "accumulation", "of", "toxic", "ele-", "ments,", "individual", "characteristics", "and", "genetic", "factors", "are", "also", "important.", "Identification", "of", "the", "con-", "tributory", "genetic", "polymorphisms", "will", "improve", "our", "understanding", "of", "trace", "and", "toxic", "element", "uptake", "and", "distribution", "mechanisms.", "k", "ey", "words", ":", "arsenic,", "cadmium,", "copper,", "erythrocytes,", "genetics,", "lead,", "mercury,", "selenium,", "twins,", "zinc.", "Environ", "Health", "Perspect", "118:776–782", "(2010).", "doi:10.1289/ehp.0901541", "[Online", "5", "January", "2010]", "Many", "investigators", "have", "considered", "the", "toxic", "effects", "of", "exposure", "to", "metals", "such", "as", "arsenic", "(As),", "cadmium", "(Cd),", "lead", "(Pb),", "and", "mercury", "(Hg),", "and", "there", "has", "been", "substantial", "expendi-", "ture", "on", "measures", "to", "reduce", "human", "exposure.", "Although", "toxic", "effects", "are", "clearly", "established", "for", "occupationally", "exposed", "people", "and", "for", "peo-", "ple", "in", "locations", "where", "particularly", "high", "levels", "are", "present,", "demonstration", "of", "harmful", "effects", "population-wide", "has", "been", "more", "difficult.", "One", "possible", "reason", "is", "that", "at", "comparatively", "low", "levels", "of", "exposure,", "only", "some", "people", "are", "at", "risk,", "and", "this", "makes", "an", "association", "more", "difficult", "to", "find", "(Bellinger", "2008).", "Study", "of", "the", "causes", "of", "individual", "variation", "could", "improve", "the", "power", "of", "epidemiological", "studies", "to", "detect", "harm", "to", "susceptible", "people.", "Chronic", "exposure", "to", "As", "has", "been", "associ-", "ated", "with", "diabetes", "(Coronado-Gonzalez", "et", "al.", "2007;", "Navas-Acien", "et", "al.", "2006),", "cardiovascular", "disease", "(Wang", "et", "al.", "2007),", "intellectual", "impair-", "ment", "in", "children", "(von", "Ehrenstein", "et", "al.", "2007;", "Wasserman", "et", "al.", "2007),", "and", "lung", "and", "bladder", "cancers", "(Navarro", "Silvera", "and", "Rohan", "2007).", "Cd", "primarily", "affects", "the", "kidneys,", "with", "tubu-", "lar", "proteinuria", "providing", "a", "useful", "marker", "of", "the", "renal", "damage.", "Studies", "in", "Cd-polluted", "areas", "have", "reported", "an", "excess", "mortality", "risk", "among", "people", "showing", "tubular", "or", "glomerular", "776", "proteinuria,", "but", "the", "causes", "of", "this", "excess", "mortality", "are", "unclear", "(Satarug", "et", "al.", "2003).", "Other", "claimed", "adverse", "effects", "of", "Cd", "include", "low", "bone-mineral", "density", "and", "osteoporosis", "(Alfven", "et", "al.", "2000,", "2004)", "and", "lung", "cancer", "(Navarro", "Silvera", "and", "Rohan", "2007).", "Hg", "has", "been", "implicated", "in", "severe", "but", "localized", "poison-", "ings", "(Ekino", "et", "al.", "2007).", "Widely", "publicized", "concerns", "about", "effects", "of", "Hg", "from", "vaccine", "pre-", "servatives", "have", "been", "refuted", "(Thompson", "et", "al.", "2007),", "but", "effects", "on", "intellectual", "functioning", "or", "behavior", "have", "been", "reported", "or", "suggested", "(Axelrad", "et", "al.", "2007;", "Davidson", "et", "al.", "2004).", "Cardiovascular", "(Virtanen", "et", "al.", "2007)", "and", "renal", "(Hodgson", "et", "al.", "2007)", "disease", "have", "been", "associated", "with", "low-level", "Hg", "exposure.", "For", "Pb,", "the", "main", "concerns", "have", "been", "about", "impaired", "intellectual", "development", "in", "infancy", "and", "child-", "hood", "(Canfield", "et", "al.", "2003;", "Needleman", "2004;", "Pocock", "et", "al.", "1994;", "Schwartz", "1994),", "but", "adult", "cognitive", "function", "may", "also", "be", "affected", "(Schwartz", "and", "Hu", "2007;", "Shih", "et", "al.", "2007).", "There", "is", "also", "evidence", "that", "higher", "Pb", "values", "are", "associated", "with", "hypertension", "(Navas-Acien", "et", "al.", "2007),", "peripheral", "vascular", "disease", "(Navas-", "Acien", "et", "al.", "2004),", "increased", "adult", "mortality", "(Lustberg", "and", "Silbergeld", "2002;", "Schober", "et", "al.", "2006),", "and", "cognitive", "decline", "in", "older", "people", "(Weisskopf", "et", "al.", "2004).", "Studies", "on", "overall", "and", "cause-specific", "mortality", "suggest", "a", "40–60%", "increase", "in", "adjusted", "mortality", "with", "increas-", "ing", "Pb", "concentration", "in", "the", "U.S.", "population", "(Jemal", "et", "al.", "2002;", "Lustberg", "and", "Silbergeld", "2002;", "Menke", "et", "al.", "2006;", "Schober", "et", "al.", "2006).", "Exposure", "is", "a", "precondition", "for", "accumu-", "lation", "of", "these", "elements.", "There", "is", "undoubt-", "edly", "individual", "variation", "in", "exposure,", "but", "this", "may", "be", "only", "one", "of", "several", "factors", "influencing", "toxic", "element", "accumulation", "and", "body", "burden.", "Identification", "of", "“host", "factors”", "has", "the", "potential", "to", "clarify", "the", "relationships", "between", "exposure", "and", "harm.", "These", "may", "act", "through", "variation", "in", "absorption", "or", "distribution", "within", "the", "body,", "brought", "about", "by", "differences", "in", "behavior", "(such", "as", "smoking", "and", "alcohol", "consumption),", "or", "by", "genetic", "differences", "in", "metabolic", "or", "biotransfor-", "mation", "processes.", "Furthermore,", "even", "at", "a", "uni-", "form", "level", "of", "cell", "or", "tissue", "exposure", "there", "may", "be", "differences", "in", "response", "because", "of", "variation", "in", "repair", "mechanisms,", "antioxidant", "status,", "avail-", "ability", "of", "protective", "elements,", "or", "other", "so", "far", "unrecognized", "factors.", "Several", "attempts", "have", "been", "made", "to", "test", "for", "effects", "of", "genetic", "polymorphisms", "on", "toxic", "element", "accumulation,", "particu-", "larly", "using", "blood", "or", "bone", "Pb", "values.", "So", "far", "there", "are", "mixed", "results,", "with", "allelic", "associa-", "tions", "both", "reported", "and", "denied", "for", "the", "ALAD", "(δ-aminolevulinic", "acid", "dehydratase)", "and", "VDR", "[vitamin", "D", "(1,25-dihydroxyvitamin", "D3)", "receptor]", "genes.", "More", "generally,", "only", "a", "few", "studies", "(Bjorkman", "et", "al.", "2000;", "Hopper", "et", "al.", "Address", "correspondence", "to", "J.B.", "Whitfield,", "Genetic", "Epidemiology", "Unit,", "Queensland", "Institute", "of", "Medical", "Research,", "P.O.", "Royal", "Brisbane", "Hospital,", "Queensland", "4029,", "Australia.", "Telephone:", "(61)", "7", "3362", "0229.", "Fax:", "(61)", "7", "3362", "0101.", "E-mail:", "john.whitfield@qimr.edu.au", "Supplemental", "Material", "is", "available", "online", "(doi:10.1289/ehp.0901541", "via", "http://dx.doi.org/).", "We", "thank", "the", "twins", "for", "their", "participation.", "In", "addi-", "tion,", "we", "thank", "the", "staff", "of", "the", "Genetic", "Epidemiology", "Unit,", "Queensland", "Institute", "of", "Medical", "Research,", "for", "project", "management,", "subject", "recruitment", "and", "interviews,", "sample", "collection,", "and", "sample", "processing.", "Trace", "element", "measurements", "were", "made", "using", "the", "facilities", "of", "the", "Department", "of", "Clinical", "Biochemistry,", "Royal", "Prince", "Alfred", "Hospital,", "Sydney,", "Australia.", "Sample", "collection", "and", "the", "recruitment", "and", "interview-", "ing", "of", "participants", "was", "funded", "by", "grant", "AA007535", "from", "the", "National", "Institute", "on", "Alcohol", "Abuse", "and", "Alcoholism.", "J.B.W.", "owns", "shares", "in", "BHP", "Billiton,", "a", "company", "engaged", "in", "mining", "and", "minerals", "processing.", "The", "remaining", "authors", "declare", "they", "have", "no", "actual", "or", "potential", "competing", "financial", "interests.", "Received", "5", "October", "2009;", "accepted", "5", "January", "2010.", "ovlume", "118", "|", "number", "6", "|", "June", "2010", "•", "Environmental", "Health", "Perspectives" ]

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[ "JCB", "Article", "Activation", "of", "ARF6", "by", "ARNO", "stimulates", "epithelial", "cell", "migration", "through", "downstream", "activation", "of", "both", "Rac1", "and", "phospholipase", "D", "Lorraine", "C.", "Santy", "and", "James", "E.", "Casanova", "Department", "of", "Cell", "Biology,", "University", "of", "Virginia", "Health", "Sciences", "Center,", "Charlottesville,", "VA", "22908", "Mmorphogenesis,", "wound", "healing,", "and", "metastasis", "of", "igration", "of", "epithelial", "cells", "is", "essential", "for", "tissue", "epithelial", "tumors.", "Here", "we", "show", "that", "ARNO,", "a", "guanine", "nucleotide", "exchange", "factor", "for", "ADP-ribosylation", "factor", "(ARF)", "GTPases,", "induces", "Madin-Darby", "canine", "kidney", "epithelial", "cells", "to", "develop", "broad", "lamellipodia,", "to", "separate", "from", "neighboring", "cells,", "and", "to", "exhibit", "a", "dramatic", "increase", "in", "migratory", "behavior.", "This", "transition", "requires", "ARNO", "cata-", "lytic", "activity,", "which", "we", "show", "leads", "to", "enhanced", "activation", "of", "endogenous", "ARF6,", "but", "not", "ARF1,", "using", "a", "novel", "pull-", "down", "assay.", "We", "further", "demonstrate", "that", "expression", "of", "Introduction", "Columnar", "epithelia", "grow", "as", "sheets", "of", "cells", "in", "which", "neighbor-", "ing", "cells", "are", "attached", "to", "each", "other", "by", "junctional", "complexes,", "including", "tight", "junctions", "and", "adherens", "junctions.", "In", "tissues,", "epithelial", "cells", "are", "normally", "stationary", "and", "nonmigratory,", "however,", "during", "embryonic", "development,", "wound", "healing,", "or", "metastasis", "of", "tumors", "they", "may", "become", "migratory", "(Gumbiner,", "1996;", "Schmitz", "et", "al.,", "2000).", "The", "adoption", "of", "a", "motile", "pheno-", "type", "requires", "regulated", "changes", "in", "the", "actin", "cytoskeleton", "and", "in", "the", "attachment", "of", "cells", "to", "the", "substratum.", "Small", "GTPases", "of", "the", "Rho", "family", "are", "intimately", "involved", "in", "regulating", "these", "processes", "(for", "review", "see", "Schmitz", "et", "al.,", "2000).", "Recent", "work", "has", "demonstrated", "that", "members", "of", "the", "ADP-ribosylation", "fac-", "tor", "(ARF)*", "family", "of", "small", "GTPases", "can", "also", "regulate", "assembly", "of", "the", "actin", "cytoskeleton", "(Radhakrishna", "et", "al.,", "1996;", "D’Souza-", "Schorey", "et", "al.,", "1997;", "Norman", "et", "al.,", "1998;", "Radhakrishna", "et", "al.,", "1999;", "Zhang", "et", "al.,", "1999;", "Boshans", "et", "al.,", "2000).", "The", "online", "version", "of", "this", "article", "contains", "supplementary", "material.", "Address", "correspondence", "to", "James", "Casanova,", "Department", "of", "Cell", "Biology,", "University", "of", "Virginia", "Health", "Sciences", "Center,", "Charlottesville,", "VA", "22908.", "Tel.:", "(804)", "243-4821.", "Fax:", "(804)", "982-3912.", "E-mail:", "jec9e@virginia.edu", "*Abbreviations", "used", "in", "this", "paper:", "ARF,", "ADP-ribosylation", "factor;", "GAP,", "GTPase", "activating", "protein;", "GEF,", "guanine", "nucleotide", "exchange", "factor;", "GST,", "glutathione", "S-transferase;", "PA,", "phosphatidic", "acid;", "PLD,", "phospholi-", "pase", "D.", "Key", "words:", "ARF;", "Rac;", "ARNO;", "migration;", "phospholipase", "D", "", "The", "Rockefeller", "University", "Press,", "0021-9525/2001/08/599/12", "$5.00", "The", "Journal", "of", "Cell", "Biology,", "Volume", "154,", "Number", "3,", "August", "6,", "2001", "599–610", "http://www.jcb.org/cgi/doi/10.1083/jcb.200104019", "ARNO", "leads", "to", "increased", "activation", "of", "endogenous", "Rac1,", "and", "that", "Rac", "activation", "is", "required", "for", "ARNO-induced", "cell", "motility.", "Finally,", "ARNO-induced", "activation", "of", "ARF6", "also", "re-", "sults", "in", "increased", "activation", "of", "phospholipase", "D", "(PLD),", "and", "inhibition", "of", "PLD", "activity", "also", "inhibits", "motility.", "However,", "in-", "hibition", "of", "PLD", "does", "not", "prevent", "activation", "of", "Rac.", "Together,", "these", "data", "suggest", "that", "ARF6", "activation", "stimulates", "two", "dis-", "tinct", "signaling", "pathways,", "one", "leading", "to", "Rac", "activation,", "the", "other", "to", "changes", "in", "membrane", "phospholipid", "composition,", "and", "that", "both", "pathways", "are", "required", "for", "cell", "motility.", "Like", "Rho", "GTPases,", "ARFs", "are", "members", "of", "the", "Ras", "super-", "family", "and", "have", "been", "well", "characterized", "as", "regulators", "of", "vesic-", "ular", "transport.", "The", "six", "known", "ARF", "isoforms", "can", "be", "divided", "into", "three", "classes.", "Class", "1", "ARFs", "(ARFs", "1–3)", "regulate", "traffick-", "ing", "in", "the", "secretory", "pathway", "and", "in", "endosomes.", "Very", "little", "is", "known", "about", "the", "role", "of", "class", "II", "ARFs", "(ARFs", "4", "and", "5).", "The", "sole", "class", "III", "ARF,", "ARF6,", "functions", "in", "the", "endosomal", "plasma", "membrane", "system,", "and", "has", "been", "shown", "to", "regulate", "traffick-", "ing", "between", "these", "compartments", "(for", "review", "see", "Chavrier", "and", "Goud,", "1999).", "It", "is", "becoming", "increasingly", "clear", "that", "modulation", "of", "actin", "assembly", "is", "an", "important", "function", "of", "ARF", "proteins.", "For", "ex-", "ample,", "ARF1", "has", "recently", "been", "shown", "to", "regulate", "the", "re-", "cruitment", "of", "paxillin", "into", "focal", "adhesions", "(Norman", "et", "al.,", "1998).", "Activation", "of", "ARF6", "also", "results", "in", "reorganization", "of", "the", "cortical", "actin", "cytoskeleton", "(Radhakrishna", "et", "al.,", "1996;", "D’Souza-Schorey", "et", "al.,", "1997).", "Several", "studies", "have", "sug-", "gested", "an", "intimate", "connection", "between", "ARF6", "and", "the", "Rho", "family", "of", "small", "GTPases;", "however,", "the", "precise", "relationship", "is", "poorly", "understood", "(D’Souza-Schorey", "et", "al.,", "1997;", "Rad-", "hakrishna", "et", "al.,", "1999;", "Zhang", "et", "al.,", "1999;", "Boshans", "et", "al.,", "2000).", "Like", "all", "GTPases,", "ARFs", "are", "switches", "that", "are", "active", "when", "bound", "to", "GTP", "and", "inactive", "when", "bound", "to", "GDP.", "Intercon-", "version", "of", "the", "two", "states", "requires", "the", "activity", "of", "several", "acces-", "599" ]

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[ "Ardalan", "et", "al.", "Journal", "of", "Medical", "Case", "Reports", "2011,", "5:191", "http://www.jmedicalcasereports.com/content/5/1/191", "C", "A", "S", "E", "R", "E", "P", "O", "R", "T", "JOURNAL", "OF", "MEDICAL", "CASE", "REPORTS", "Open", "Access", "Concomitant", "pulmonary", "tuberculosis", "and", "tuberculous", "appendicitis", "in", "a", "recipient", "of", "a", "renal", "transplant:", "a", "case", "report", "Mohammad", "R", "Ardalan1,", "Mohammadali", "M", "Shoja2", "and", "Kamyar", "Ghabili2*", "Abstract", "Introduction:", "Tuberculosis", "is", "still", "a", "serious", "infection", "among", "recipients", "of", "renal", "transplants.", "Although", "the", "ileocecal", "region", "is", "the", "most", "affected", "part", "in", "intestinal", "tuberculosis,", "acute", "tuberculous", "appendicitis", "is", "quite", "a", "rare", "entity.", "We", "report", "a", "case", "of", "concomitant", "pulmonary", "tuberculosis", "and", "tuberculous", "appendicitis", "in", "a", "recipient", "of", "a", "renal", "transplant.", "Case", "presentation:", "A", "27-year-old", "Iranian", "woman,", "who", "had", "been", "the", "recipient", "of", "a", "renal", "transplant", "five", "years", "earlier,", "presented", "with", "a", "two-week", "history", "of", "coughing,", "fever", "and", "weight", "loss.", "The", "cause", "of", "her", "end-stage", "renal", "disease", "was", "chronic", "pyelonephritis.", "There", "were", "fine", "crackles", "noted", "during", "a", "chest", "examination,", "and", "a", "plain", "chest", "radiography", "showed", "fine", "miliary", "nodules", "throughout", "her", "entire", "lung", "fields.", "Sputum", "and", "bronchial", "aspirate", "examination", "was", "positive", "for", "acid-fast", "bacilli,", "suggestive", "of", "Mycobacterium", "tuberculosis", "infection.", "A", "chest", "computed", "tomography", "scan", "revealed", "widespread", "miliary", "nodules,", "compatible", "with", "miliary", "tuberculosis.", "She", "developed", "severe", "abdominal", "pain", "and", "abdominal", "surgery", "disclosed", "a", "perforated", "appendicitis.", "Histopathological", "examination", "of", "the", "resected", "appendix", "revealed", "widespread", "caseating", "epithelioid", "granulomas,", "suggestive", "of", "tuberculosis.", "Conclusion:", "Our", "case", "report", "highlights", "a", "rare", "presentation", "of", "tuberculosis", "in", "a", "patient", "who", "has", "undergone", "renal", "transplant.", "Such", "unusual", "presentation", "of", "tuberculosis,", "particularly", "among", "patients", "receiving", "potent", "immunosuppressive", "protocols,", "should", "be", "considered", "by", "clinicians.", "Introduction", "Tuberculosis", "(TB)", "remains", "a", "major", "health", "hazard", "parti-", "cularly", "in", "developing", "countries", "[1].", "Renal", "transplant", "recipients", "are", "at", "high", "risk", "of", "a", "number", "of", "infections", "including", "mycobacterial", "diseases", "[2,3].", "The", "cumulative", "incidence", "of", "post-transplant", "TB", "in", "developing", "countries", "is", "as", "high", "as", "13.3%", "with", "a", "relatively", "high", "rate", "of", "extra-", "pulmonary", "TB.", "Although", "the", "ileocecal", "region", "is", "the", "most", "affected", "part", "in", "gastrointestinal", "TB,", "acute", "tubercu-", "lous", "appendicitis", "is", "quite", "a", "rare", "entity", "[4].", "Here,", "the", "authors", "report", "a", "renal", "transplant", "recipient", "who", "devel-", "oped", "concomitant", "pulmonary", "TB", "and", "tuberculosis", "appendicitis.", "*", "Correspondence:", "kghabili@gmail.com", "2Tuberculosis", "and", "Lung", "Disease", "Research", "Center,", "Tabriz", "University", "of", "Medical", "Sciences,", "Tabriz,", "Iran", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "Case", "report", "A", "27-year-old", "Iranian", "woman,", "recipient", "of", "a", "living,", "unrelated", "renal", "transplant", "five", "years", "earlier,", "presented", "with", "a", "productive", "cough,", "weight", "loss", "and", "fever.", "The", "cause", "of", "her", "end-stage", "renal", "disease", "was", "chronic", "pyelo-", "nephritis.", "Six", "weeks", "prior", "to", "her", "admission,", "her", "immu-", "nosuppressant", "regimen", "was", "switched", "from", "oral", "cyclosporine", "(100", "mg,", "twice", "daily)", "to", "oral", "sirolimus", "(1", "mg,", "twice", "daily)", "with", "a", "diagnosis", "of", "chronic", "allograft", "nephropathy", "(serum", "creatinine", "level", "of", "2", "mg/dL).", "Her", "mycophenolate", "mofetil", "dose", "was", "decreased", "from", "2000", "to", "1000", "mg/day", "and", "prednisolone", "was", "continued", "with", "the", "previous", "dose", "(5", "mg,", "daily).", "Four", "weeks", "later,", "she", "devel-", "oped", "a", "mild", "cough,", "weakness", "and", "anorexia.", "Her", "condi-", "tion", "progressed", "to", "a", "more", "constant", "cough", "and", "weight", "loss", "until", "she", "was", "hospitalized.", "Physical", "examination", "revealed", "her", "blood", "pressure", "to", "be", "110/60", "mm/Hg,", "respiratory", "rate", "20/min,", "pulse", "rate", "92/min", "and", "body", "temperature", "38°C.", "A", "chest", "©", "2011", "Ardalan", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "The", "GTPase", "Rho", "Controls", "a", "p53-dependent", "Survival", "Checkpoint", "during", "Thymopoiesis", "By", "Patrick", "S.", "Costello,", "Steve", "C.", "Cleverley,", "Ricciarda", "Galandrini,", "Stefan", "W.", "Henning,", "and", "Doreen", "A.", "Cantrell", "From", "the", "Lymphocyte", "Activation", "Laboratory,", "Imperial", "Cancer", "Research", "Fund,", "London", "WC2A", "3PX,", "United", "Kingdom", "Abstract", "During", "the", "early", "stages", "of", "thymopoiesis,", "cell", "survival", "is", "controlled", "by", "cytokines", "that", "regulate", "the", "expression", "of", "antiapoptotic", "proteins", "such", "as", "Bcl-2.", "At", "the", "pre-T", "cell", "stage,", "a", "critical", "checkpoint", "for", "b", "chain", "selection", "is", "monitored", "by", "the", "tumor", "suppressor", "p53:", "pre-T", "cells", "can", "survive", "and", "dif-", "ferentiate", "when", "p53", "is", "removed", "genetically", "or", "when", "its", "proapoptotic", "function", "is", "inactivated", "physiologically", "as", "a", "consequence", "of", "signaling", "through", "the", "pre-T", "cell", "receptor", "complex.", "Previ-", "ous", "work", "has", "shown", "that", "the", "guanine", "nucleotide", "binding", "protein", "Rho", "controls", "cell", "survival", "in", "T", "cell", "progenitors.", "Here", "we", "define", "the", "survival", "pathways", "controlled", "by", "Rho", "in", "pre-T", "cells", "and", "show", "that", "this", "GTPase", "is", "a", "pivotal", "regulator", "of", "the", "p53-mediated", "checkpoint", "operating", "at", "the", "time", "of", "b", "selection:", "loss", "of", "Rho", "function", "results", "in", "apoptosis", "in", "pre-T", "cells,", "but", "this", "cell", "death", "is", "prevented", "by", "loss", "of", "p53.", "The", "prevention", "of", "cell", "death", "by", "loss", "of", "p53", "restored", "numbers", "of", "early", "T", "cell", "progenitors", "but", "did", "not", "fully", "restore", "thymic", "cellularity.", "Further", "analysis", "revealed", "that", "loss", "of", "Rho", "function", "caused", "survival", "defects", "in", "CD4/8", "double-positive", "thymocytes", "that", "is", "indepen-", "dent", "of", "p53", "but", "can", "be", "prevented", "by", "ectopic", "expression", "of", "Bcl-2.", "These", "studies", "highlight", "that", "the", "GTPase", "Rho", "is", "a", "crucial", "component", "of", "survival", "signaling", "pathways", "in", "at", "least", "two", "different", "thymocyte", "subpopulations:", "Rho", "controls", "the", "p53", "survival", "checkpoint", "in", "pre-T", "cells", "and", "is", "also", "crucial", "for", "a", "p53", "independent", "survival", "signaling", "pathway", "in", "CD4/8", "double", "positives.", "Key", "words:", "pre-T", "cell", "•", "signaling", "•", "development", "•", "apoptosis", "•", "thymus", "Introduction", "The", "development", "and", "maturation", "of", "T", "lymphocytes", "in", "the", "thymus", "is", "an", "essential", "process", "for", "the", "formation", "of", "the", "pe-", "ripheral", "immune", "system.", "The", "progression", "of", "T", "cells", "through", "the", "early", "stages", "of", "intrathymic", "differentiation", "may", "be", "defined", "by", "the", "sequential", "pattern", "of", "expression", "of", "a", "number", "of", "surface", "markers,", "including", "CD44", "and", "CD25", "(for", "review", "see", "references", "1–3).", "Initially,", "cells", "are", "CD441", "CD252", "(termed", "DN1);", "they", "then", "go", "on", "to", "acquire", "CD25", "(DN2),", "when", "they", "become", "committed", "to", "the", "T", "cell", "lineage", "and", "begin", "to", "rearrange", "TCR", "b", "loci.", "The", "cells", "then", "lose", "P.S.", "Costello", "and", "S.C.", "Cleverley", "contributed", "equally", "to", "this", "work.", "R.", "Galandrini’s", "present", "address", "is", "Dept.", "of", "Experimental", "Medicine", "and", "Pathology,", "University", "of", "Rome", "La", "Sapienza,", "V.le", "R.", "Elena,", "324", "Rome,", "Italy.", "S.W.", "Henning’s", "present", "address", "is", "Dept.", "of", "Molecular", "and", "Cell", "Biol-", "ogy,", "University", "of", "California,", "415", "Life", "Science", "Addition,", "Berkeley,", "CA", "94720.", "Address", "correspondence", "to", "Doreen", "A.", "Cantrell,", "Lymphocyte", "Activa-", "tion", "Laboratory,", "Rm.", "105,", "Imperial", "Cancer", "Research", "Fund,", "44", "Lincolns", "Inn", "Fields,", "London", "WC2A", "3PX,", "UK.", "Phone:", "44-020-7269-3231;", "Fax:", "44-020-7269-2831;", "E-mail:", "d.cantrell@icrf.icnet.uk", "CD44", "expression", "and", "continue", "b", "chain", "rearrangements", "to", "completion", "(DN3).", "At", "the", "DN3", "pre-T", "cell", "stage,", "cells", "that", "successfully", "rearrange", "their", "TCR", "b", "locus", "and", "express", "a", "functional", "receptor", "complex", "known", "as", "the", "pre-TCR", "com-", "plex", "proliferate", "rapidly,", "downregulate", "CD25,", "and", "differen-", "tiate", "into", "DN4", "cells", "(3–5).", "At", "the", "next", "developmental", "stage,", "cells", "coexpress", "the", "receptors", "for", "MHCs,", "CD4", "and", "CD8,", "and", "within", "the", "CD4/8", "double-positive", "(DP)1", "com-", "partment", "undergo", "TCR", "a", "chain", "rearrangements.", "Upon", "expression", "of", "a", "functional", "pre-TCR", "complex,", "cells", "are", "sub-", "jected", "to", "the", "processes", "of", "positive", "and", "negative", "selection", "(for", "review", "see", "references", "6", "and", "7)", "that", "ensure", "the", "genera-", "tion", "of", "mature", "CD4", "or", "CD8", "single-positive", "(SP)", "T", "lym-", "phocytes", "that", "exit", "to", "the", "peripheral", "lymphatic", "organs.", "In", "the", "thymus,", "the", "ordered", "acquisition", "of", "antigen", "receptors", "and", "cytokine", "receptors", "allows", "T", "cells", "to", "survive", "and", "progress", "to", "the", "next", "developmental", "stage.", "Any", "genetic", "ma-", "nipulation", "that", "interferes", "with", "thymocyte", "survival", "mecha-", "1Abbreviations", "used", "in", "this", "paper:", "DP,", "double-positive;", "RAG,", "recombinase-", "activating", "gene;", "SP,", "single-positive.", "77", "J.", "Exp.", "Med.", "The", "Rockefeller", "University", "Press", "•", "0022-1007/2000/07/77/09", "$5.00", "Volume", "192,", "Number", "1,", "July", "3,", "2000", "77–85", "http://www.jem.org/cgi/current/full/192/1/77" ]

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[ "Nutrition", "Research", "and", "Practice", "(Nutr", "Res", "Pract)", "2011;5(4):322-328", "http://dx.doi.org/10.4162/nrp.2011.5.4.322", "Evaluation", "of", "dietary", "quality", "of", "adolescents", "using", "Healthy", "Eating", "Index", "Nilufer", "Acar", "Tek§,", "Hilal", "Yildiran,", "Gamze", "Akbulut,", "Saniye", "Bilici,", "Eda", "Koksal,", "Makbule", "Gezmen", "Karadag", "and", "Nevin", "Sanlıer", "Department", "of", "Nutrition", "and", "Dietetics", "Besevler,", "Gazi", "University", "Faculty", "of", "Health", "Sciences,", "Ankara,", "Turkey", "Abstract", "The", "aim", "of", "this", "study", "was", "to", "use", "the", "Healthy", "Eating", "Index-2005", "(HEI-2005)", "to", "assess", "diet", "quality", "and", "determine", "the", "relationship", "between", "the", "HEI-2005", "and", "the", "energy", "and", "nutrient", "intakes", "of", "adolescents.", "A", "cross-sectional", "study", "was", "conducted", "on", "1,104", "healthy", "adolescents,", "mean", "age", "of", "15.8", "±", "1.24", "years.", "Dietary", "intake", "was", "measured", "with", "the", "24-hour", "dietary", "recall", "method,", "and", "dietary", "quality", "was", "assessed", "by", "means", "of", "the", "HEI-2005.", "Diet", "quality", "scores", "ranged", "from", "23.7", "to", "77.5.", "The", "mean", "score", "was", "found", "to", "be", "51.5", "±", "9.07", "according", "to", "the", "HEI-2005.", "There", "were", "no", "differences", "according", "to", "gender;", "42.8%", "had", "a", "poor", "diet", "and", "57.2%", "had", "a", "diet", "that", "needs", "improvement.", "No", "subjects", "had", "a", "“good", "diet”.", "Lower", "mean", "subgroup", "scores", "were", "found", "for", "whole", "grains,", "total", "vegetables,", "total", "fruits,", "dairy", "products,", "and", "meat", "and", "beans.", "Fruits", "and", "vegetables", "scores", "were", "significantly", "high", "in", "girls,", "whereas", "sodium,", "oil,", "and", "meat", "and", "beans", "scores", "were", "significantly", "high", "in", "boys.", "Total", "HEI-2005", "scores", "were", "increasingly", "associated", "with", "parental", "education", "level", "when", "age", "and", "gender", "were", "adjusted.", "There", "was", "a", "negative", "correlation", "between", "HEI-2005", "scores", "and", "age,", "total", "energy", "intake,", "and", "fat", "intake.", "Positive", "correlation", "was", "only", "observed", "in", "the", "HEI-2005", "scores", "for", "protein", "and", "dietary", "fibre", "intakes.", "Consequently,", "the", "overall", "diet", "quality", "and", "nutritional", "habits", "of", "Turkish", "adolescents", "need", "modification", "and", "improvement.", "In", "the", "family,", "measures", "should", "be", "initiated", "by", "the", "government,", "including", "advertisements", "and", "campaigns.", "Key", "Words:", "Adolescent,", "diet", "quality,", "healthy", "eating", "index,", "nutrition", "Introduction7)", "A", "number", "of", "studies", "have", "assessed", "the", "diets", "of", "individuals", "and", "populations", "in", "terms", "of", "single", "foods,", "food", "groups,", "nutrients,", "or", "other", "individual", "dietary", "components.", "An", "alternative", "approach", "is", "to", "examine", "overall", "diet", "quality", "in", "order", "to", "reflect", "the", "complexity", "of", "food", "intake", "patterns", "and", "dietary", "exposure", "[1].", "The", "assessment", "of", "diet", "quality", "in", "a", "population", "is", "important", "in", "policy-making,", "monitoring", "service", "outcomes,", "and", "designing", "research", "interventions", "[2].", "The", "Healthy", "Eating", "Index", "(HEI)", "was", "developed", "by", "the", "US", "Department", "of", "Agriculture", "(USDA)", "“to", "provide", "a", "single", "summary", "of", "diet", "quality", "based", "on", "different", "aspects", "of", "a", "healthy", "diet”", "[3].", "The", "HEI-2005", "is", "a", "valid", "measure", "of", "diet", "quality", "and", "has", "various", "potential", "purposes.", "It", "is", "used", "for", "epidemiological", "research", "to", "monitor", "a", "population’s", "diet", "and", "evaluate", "nutrition", "interventions.", "The", "HEI-2005", "assesses", "dietary", "intakes", "on", "a", "per", "calorie", "basis", "rather", "than", "on", "the", "basis", "of", "absolute", "amounts", "of", "foods", "consumed;", "thus,", "the", "HEI-2005", "assesses", "the", "quality", "of", "the", "relative", "proportions", "of", "foods", "consumed", "rather", "than", "the", "quantity", "of", "foods", "consumed", "[4].", "In", "recent", "years,", "epidemiological", "studies", "on", "diet", "and", "chronic", "diseases", "have", "tended", "to", "focus", "on", "the", "relationship", "between", "diet", "quality", "and", "disease", "risk", "in", "different", "age", "groups,", "including", "children,", "adolescents,", "adults,", "and", "elderly", "people", "[2,5-7].", "Most", "of", "these", "studies", "performed", "on", "adolescents", "determined", "diet", "quality", "and", "the", "relationship", "between", "diet", "quality", "and", "health", "outcomes", "[8-10].", "The", "HEI", "is", "a", "useful", "index", "in", "assessing", "diet", "quality,", "and", "it", "has", "been", "used", "to", "successfully", "monitor", "the", "diet", "in", "adolescents", "[8,10].", "Adolescence,", "the", "transition", "from", "childhood", "to", "adulthood,", "is", "one", "of", "the", "most", "dynamic", "periods", "of", "human", "development", "[11].", "Physiological", "and", "social", "conditions", "affect", "adolescents’", "dietary", "patterns.", "Physiologically,", "energy", "and", "nutrient", "requirements", "rise", "due", "to", "increasing", "body", "size", "and", "sexual", "maturation,", "including", "menarche", "in", "girls.", "Socially,", "adolescence", "affords", "an", "opportunity", "for", "food", "selection", "independent", "of", "parental", "guidance.", "Consequently,", "adolescents", "may", "tend", "to", "acquire", "unhealthy", "eating", "behaviours", "such", "as", "skipping", "meals,", "under-eating,", "or", "over-eating,", "all", "of", "which", "decrease", "diet", "quality", "[12].", "However,", "according", "to", "our", "knowledge,", "no", "study", "has", "been", "specifically", "performed", "to", "determine", "the", "diet", "quality", "in", "Turkish", "adolescents.", "The", "aim", "of", "this", "study", "was", "to", "use", "the", "HEI-2005", "to", "assess", "diet", "quality", "and", "determine", "the", "relationship", "between", "the", "HEI-2005", "and", "energy", "and", "nutrient", "intakes", "of", "adolescents.", "Subjects", "and", "Methods", "Participants", "and", "study", "area", "§", "Corresponding", "Author:", "Nilufer", "Acar", "Tek,", "Tel.", "90-312-216-26-34,", "Fax.", "90-312-216-26-36,", "Email.", "ntek@gazi.edu.tr", "Received:", "January", "13,", "2011,", "Revised:", "April", "13,", "2011,", "Accepted:", "April", "13,", "2011", "ⓒ2011", "The", "Korean", "Nutrition", "Society", "and", "the", "Korean", "Society", "of", "Community", "Nutrition", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/by-nc/3.0/)", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Nam", "et", "al.", "BMC", "Medical", "Genomics", "2012,", "5:18", "http://www.biomedcentral.com/1755-8794/5/18", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "+", "MicroRNA", "profiling", "of", "a", "CD133", "spheroid-forming", "subpopulation", "of", "the", "OVCAR3", "human", "ovarian", "cancer", "cell", "line", "Eun", "Ji", "Nam,", "Maria", "Lee†,", "Ga", "Won", "Yim†,", "Jae", "Hoon", "Kim†,", "Sunghoon", "Kim†,", "Sang", "Wun", "Kim†", "and", "Young", "Tae", "Kim*", "Abstract", "Background:", "Cancer", "stem", "cells", "(CSCs)", "are", "thought", "to", "be", "a", "source", "of", "tumor", "recurrence", "due", "to", "their", "stem", "cell-like", "properties.", "MicroRNAs", "(miRNAs)", "regulate", "both", "normal", "stem", "cells", "and", "CSCs,", "and", "dysregulation", "of", "miRNAs", "has", "an", "important", "role", "in", "tumorigenesis.", "Cluster", "of", "differentiation", "(CD)", "133+", "and", "spheroid", "formation", "have", "been", "reported", "to", "be", "one", "of", "the", "main", "features", "of", "ovarian", "CSCs.", "Therefore,", "we", "determined", "the", "miRNA", "expression", "profile", "of", "a", "CD133+", "spheroid-forming", "subpopulation", "of", "the", "OVCAR3", "human", "ovarian", "cancer", "cell", "line.", "Methods:", "Initially,", "we", "confirmed", "the", "enrichment", "of", "the", "OVCAR3", "CD133", "subpopulation", "by", "evaluating", "in", "vitro", "anchorage-independent", "growth.", "After", "obtaining", "a", "subpopulation", "of", "CD133+", "OVCAR3", "cells", "with", ">", "98%", "purity", "via", "cell", "sorting,", "miRNA", "microarray", "and", "real-time", "reverse", "transcription-polymerase", "chain", "reaction", "(RT-PCR)", "were", "performed", "to", "evaluate", "its", "miRNA", "profile.", "Results:", "We", "found", "37", "differentially", "expressed", "miRNAs", "in", "the", "CD133+", "spheroid-forming", "subpopulation", "of", "OVCAR3", "cells,", "34", "of", "which", "were", "significantly", "up-regulated,", "including", "miR-205,", "miR-146a,", "miR-200a,", "miR-200b,", "and", "miR-3,", "and", "3", "of", "which", "were", "significantly", "down-regulated,", "including", "miR-1202", "and", "miR-1181.", "Conclusions:", "Our", "results", "indicate", "that", "dysregulation", "of", "miRNA", "may", "play", "a", "role", "in", "the", "stem", "cell-like", "properties", "of", "ovarian", "CSCs.", "Keywords:", "MicroRNA,", "Cancer", "stem", "cell,", "Ovarian", "cancer,", "CD133,", "OVCAR3,", "Chemoresistance", "Background", "Epithelial", "ovarian", "cancer", "(EOC)", "is", "the", "most", "lethal", "of", "all", "gynecologic", "malignancies.", "Although", "an", "initial", "treatment", "method", "offers", "a", "response", "rate", "of", "70%,", "most", "patients", "eventually", "relapse", "with", "chemo-resistant", "disease", "[1].", "Thus,", "identification", "of", "new", "molecular", "markers", "that", "tar-", "get", "chemo-resistant", "disease", "is", "needed", "for", "therapeutic", "approaches", "to", "ovarian", "cancer.", "Cancer", "stem", "cells", "(CSCs)", "have", "recently", "been", "deter-", "mined", "to", "comprise", "a", "small", "proportion", "of", "highly", "malignant", "cancer", "cells", "possessing", "stem", "cell", "properties", "[2].", "It", "is", "generally", "accepted", "that", "stem", "cells", "are", "more", "resistant", "*", "Correspondence:", "ytkchoi@yuhs.ac", "†Equal", "contributors", "Institute", "of", "Women's", "Life", "Medical", "Science,", "Women's", "Cancer", "Clinic,", "Department", "of", "Obstetrics", "and", "Gynecology,", "Yonsei", "University", "College", "of", "Medicine,", "Seongsan-no", "250,", "Seodaemun-gu,", "Seoul,", "South", "Korea", "120-752", "to", "apoptosis", "and", "DNA", "damage", "and", "are", "therefore", "more", "likely", "to", "be", "resistant", "to", "chemotherapy", "[3].", "As", "such,", "if", "CSCs", "are", "refractory", "to", "therapy,", "they", "are", "unlikely", "to", "be", "curative", "and", "relapse", "would", "be", "expected.", "Previous", "studies", "of", "acute", "myelogenous", "leukemia", "(AML)", "provided", "compelling", "evi-", "dence", "of", "the", "existence", "of", "CSCs", "[4].", "Thereafter,", "several", "stu-", "dies", "characterized", "CSCs", "in", "other", "types", "of", "tumors", "including", "those", "of", "the", "brain,", "breast,", "colon,", "pancreas,", "pros-", "tate,", "and", "ovaries.", "Self-renewal", "and", "lineage", "capacity", "are", "the", "hallmarks", "of", "any", "stem", "cell", "[2].", "Therefore,", "a", "few", "methods", "have", "been", "developed", "to", "use", "these", "characteristics", "in", "order", "to", "assay", "cancer", "stem", "cells.", "The", "ability", "of", "cells", "to", "form", "tumor", "spheres", "is", "one", "such", "method,", "evaluating", "the", "capacity", "of", "cancer", "cells", "to", "grow", "as", "multi-cellular", "spheroids", "under", "non-differentiating", "and", "non-adherent", "conditions", "[5].", "Using", "this", "method,", "ovarian", "CSCs", "from", "patients", "with", "©", "2012", "Nam", "et", "al.;", "licensee", "BioMed", "Central", "Ltd;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Alcaraz", "et", "al.", "BMC", "Genomics", "2010,", "11:332", "http://www.biomedcentral.com/1471-2164/11/332", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Understanding", "the", "evolutionary", "relationships", "and", "major", "traits", "of", "Bacillus", "through", "comparative", "genomics", "Luis", "David", "Alcaraz1,", "Gabriel", "Moreno-Hagelsieb2,", "Luis", "E", "Eguiarte3,", "Valeria", "Souza3,", "Luis", "Herrera-Estrella1,4,", "Gabriela", "Olmedo1*", "Abstract", "Background:", "The", "presence", "of", "Bacillus", "in", "very", "diverse", "environments", "reflects", "the", "versatile", "metabolic", "capabilities", "of", "a", "widely", "distributed", "genus.", "Traditional", "phylogenetic", "analysis", "based", "on", "limited", "gene", "sampling", "is", "not", "adequate", "for", "resolving", "the", "genus", "evolutionary", "relationships.", "By", "distinguishing", "between", "core", "and", "pan-genome,", "we", "determined", "the", "evolutionary", "and", "functional", "relationships", "of", "known", "Bacillus.", "Results:", "Our", "analysis", "is", "based", "upon", "twenty", "complete", "and", "draft", "Bacillus", "genomes,", "including", "a", "newly", "sequenced", "Bacillus", "isolate", "from", "an", "aquatic", "environment", "that", "we", "report", "for", "the", "first", "time", "here.", "Using", "a", "core", "genome,", "we", "were", "able", "to", "determine", "the", "phylogeny", "of", "known", "Bacilli,", "including", "aquatic", "strains", "whose", "position", "in", "the", "phylogenetic", "tree", "could", "not", "be", "unambiguously", "determined", "in", "the", "past.", "Using", "the", "pan-genome", "from", "the", "sequenced", "Bacillus,", "we", "identified", "functional", "differences,", "such", "as", "carbohydrate", "utilization", "and", "genes", "involved", "in", "signal", "transduction,", "which", "distinguished", "the", "taxonomic", "groups.", "We", "also", "assessed", "the", "genetic", "architecture", "of", "the", "defining", "traits", "of", "Bacillus,", "such", "as", "sporulation", "and", "competence,", "and", "showed", "that", "less", "than", "one", "third", "of", "the", "B.", "subtilis", "genes", "are", "conserved", "across", "other", "Bacilli.", "Most", "variation", "was", "shown", "to", "occur", "in", "genes", "that", "are", "needed", "to", "respond", "to", "environmental", "cues,", "suggesting", "that", "Bacilli", "have", "genetically", "specialized", "to", "allow", "for", "the", "occupation", "of", "diverse", "habitats", "and", "niches.", "Conclusions:", "The", "aquatic", "Bacilli", "are", "defined", "here", "for", "the", "first", "time", "as", "a", "group", "through", "the", "phylogenetic", "analysis", "of", "814", "genes", "that", "comprise", "the", "core", "genome.", "Our", "data", "distinguished", "between", "genomic", "components,", "especially", "core", "vs.", "pan-genome", "to", "provide", "insight", "into", "phylogeny", "and", "function", "that", "would", "otherwise", "be", "difficult", "to", "achieve.", "A", "phylogeny", "may", "mask", "the", "diversity", "of", "functions,", "which", "we", "tried", "to", "uncover", "in", "our", "approach.", "The", "diversity", "of", "sporulation", "and", "competence", "genes", "across", "the", "Bacilli", "was", "unexpected", "based", "on", "previous", "studies", "of", "the", "B.", "subtilis", "model", "alone.", "The", "challenge", "of", "uncovering", "the", "novelties", "and", "variations", "among", "genes", "of", "the", "non-subtilis", "groups", "still", "remains.", "This", "task", "will", "be", "best", "accomplished", "by", "directing", "efforts", "toward", "understanding", "phylogenetic", "groups", "with", "similar", "ecological", "niches.", "Background", "Bacillus", "is", "one", "of", "the", "best", "characterized", "bacterial", "genera.", "Since", "the", "late", "19th", "century,", "the", "long", "history", "of", "Bacilli", "research", "has", "included", "classical", "microbiology,", "biochemis-", "try,", "and", "more", "modern", "genomic", "and", "proteomic", "approaches.", "Bacillus", "is", "defined", "as", "a", "Gram-positive,", "rod-", "shaped", "bacterium", "that", "can", "be", "aerobic", "or", "facultative", "anaerobic", "[1]", "and", "produces", "highly", "resistant", "dormant", "*", "Correspondence:", "golmedo@ira.cinvestav.mx", "1Departamento", "de", "Ingeniería", "Genética,", "Centro", "de", "Investigación", "y", "de", "Estudios", "Avanzados", "del", "I.P.N.", "Campus", "Guanajuato,", "AP", "629", "Irapuato,", "Guanajuato", "36500,", "México", "endospores", "in", "response", "to", "nutritional", "or", "environmental", "stresses", "[2].", "Bacilli", "are", "ubiquitous", "bacteria", "that", "exploit", "a", "wide", "variety", "of", "organic", "and", "inorganic", "substrates", "as", "nutrient", "sources", "[1].", "However,", "spore", "dispersal", "by", "air", "and", "water", "[3]", "may", "lead", "to", "false", "conclusions", "about", "the", "ecological", "significance", "of", "recovered", "bacillus", "isolates,", "since", "it", "is", "not", "clear", "if", "the", "robust", "presence", "of", "the", "bacteria", "is", "due", "to", "the", "resistant", "nature", "of", "the", "dispersed", "spores", "or", "due", "rather", "to", "a", "large", "adaptive", "capacity", "that", "would", "allow", "the", "bacteria", "to", "be", "found", "in", "an", "active,", "vegetative", "state", "in", "diverse", "environments", "[2].", "This", "study", "of", "the", "Bacillus", "©", "2010", "Alcaraz", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "PSYCHIATRY", "ORIGINAL", "RESEARCH", "ARTICLE", "published:", "22", "August", "2011", "doi:", "10.3389/fpsyt.2011.00051", "Impaired", "neural", "synchrony", "in", "the", "theta", "frequency", "range", "in", "adolescents", "at", "familial", "risk", "for", "schizophrenia", "Franc", "C.", "L.", "Donkers*,", "Shane", "R.", "Schwikert", ",", "Anna", "M.", "Evans,", "Katherine", "M.", "Cleary", ",", "Diana", "O.", "Perkins", "and", "Aysenil", "Belger", "Department", "of", "Psychiatry,", "University", "of", "North", "Carolina", "at", "Chapel", "Hill,", "Chapel", "Hill,", "NC,", "USA", "Edited", "by:", "Josephine", "Johns,", "University", "of", "North", "Carolina", "at", "Chapel", "Hill,", "USA", "Reviewed", "by:", "Juliana", "Yordanova,", "Bulgarian", "Academy", "of", "Sciences,", "Bulgaria", "Linda", "Mayes,", "Yale", "University,", "USA", "*Correspondence:", "Franc", "C.", "L.", "Donkers,", "Department", "of", "Psychiatry,", "University", "of", "North", "Carolina", "at", "Chapel", "Hill,", "Campus", "Box", "7160,", "367", "Medical", "School", "Wing", "C,", "Chapel", "Hill,", "NC", "27599,", "USA.", "e-mail:", "franc_donkers@med.unc.edu", "Puberty", "is", "a", "critical", "period", "for", "the", "maturation", "of", "the", "fronto-limbic", "and", "fronto-striate", "brain", "circuits", "responsible", "for", "executive", "function", "and", "affective", "processing.", "Puberty", "also", "coin-", "cides", "with", "the", "emergence", "of", "the", "prodromal", "signs", "of", "schizophrenia,", "which", "may", "indicate", "an", "association", "between", "these", "two", "processes.", "Time-domain", "analysis", "and", "wavelet", "based", "time–", "frequency", "analysis", "was", "performed", "on", "electroencephalographic", "(EEG)", "data", "of", "30", "healthy", "control", "(HC)", "subjects", "and", "24", "individuals", "at", "familial", "risk", "(FR)", "for", "schizophrenia.", "All", "participants", "were", "between", "the", "ages", "of", "13", "and", "18", "years", "and", "were", "carefully", "matched", "for", "age,", "gender,", "ethnicity,", "education,", "and", "Tanner", "Stage.", "Electrophysiological", "recordings", "were", "obtained", "from", "32", "EEG", "channels", "while", "participants", "performed", "a", "visual", "oddball", "task,", "where", "they", "identified", "rare", "visual", "targets", "among", "standard", "“scrambled”", "images", "and", "rare", "aversive", "and", "neutral", "dis-", "tracter", "pictures.", "The", "time-domain", "analysis", "showed", "that", "during", "target", "processing", "the", "FR", "group", "showed", "smaller", "event-related", "potentials", "in", "the", "P2", "and", "P3", "range", "as", "compared", "to", "the", "HC", "group.", "In", "addition,", "EEG", "activity", "in", "the", "theta", "(4–8", "Hz)", "frequency", "range", "was", "significantly", "reduced", "during", "target", "processing", "in", "the", "FR", "group.", "Inefficient", "cortical", "information", "process-", "ing", "during", "puberty", "may", "be", "an", "early", "indicator", "of", "altered", "brain", "function", "in", "adolescents", "at", "FR", "for", "schizophrenia", "and", "may", "represent", "a", "vulnerability", "marker", "for", "illness", "onset.", "Longitudinal", "assessments", "will", "have", "to", "determine", "their", "predictive", "value", "for", "illness", "onset", "in", "populations", "at", "FR", "for", "psychotic", "illness.", "Keywords:", "schizophrenia,", "familial", "risk,", "P300,", "ERP,", "wavelet", "analysis,", "time–frequency", "decomposition,", "theta", "frequency,", "phase-locking", "factor", "INTRODUCTION", "Little", "is", "known", "about", "how", "or", "why", "psychotic", "disorders", "like", "schizophrenia", "develop.", "Although", "structural", "brain", "abnormalities", "occurring", "early", "in", "life", "may", "be", "necessary", "for", "the", "future", "emergence", "of", "psychotic", "symptoms,", "the", "notion", "that", "psychotic", "symptoms", "do", "not", "typically", "manifest", "until", "after", "puberty", "has", "led", "researchers", "to", "believe", "that", "neurodevelopmental", "processes", "active", "during", "this", "period", "may", "also", "play", "a", "role", "in", "the", "pathogenesis", "of", "schizophrenia", "(Feinberg,", "1982;", "Weinberger,", "1987).", "Adolescence", "represents", "a", "period", "of", "active", "brain", "development,", "during", "which", "increases", "in", "neuronal", "efficiency", "are", "accompanied", "by", "a", "reduction", "(i.e.,", "pruning)", "of", "excess", "synapses", "and", "by", "myelination", "of", "axonal", "connections", "in", "regions", "critical", "for", "higher", "order", "cognition,", "particularly", "the", "prefrontal", "cortex", "(Hut-", "tenlocher,", "1979;", "Keshavan", "et", "al.,", "1994;", "Woods,", "1998).", "The", "behav-", "ioral", "expression", "of", "schizophrenia-related", "neural", "disturbances", "also", "seems", "to", "vary", "with", "maturation,", "and", "becomes", "more", "“psychosis-", "like”", "the", "closer", "to", "the", "onset", "of", "a", "psychotic", "episode", "(Cannon,", "2005).", "The", "fact", "that", "schizophrenia", "is", "increasingly", "viewed", "as", "a", "neurodevelopmental", "disorder", "suggests", "that", "potential", "precursors", "to", "psychotic", "illness", "may", "be", "detectable", "in", "individuals", "at", "famil-", "ial", "risk", "(FR)", "for", "developing", "schizophrenia.", "Although,", "the", "idea", "of", "examining", "individuals", "at", "FR", "for", "developing", "schizophrenia", "is", "not", "new", "(e.g.,", "Fish", "et", "al.,", "1992;", "Marcus", "et", "al.,", "1993;", "McNeil", "et", "al.,", "1993)", "to", "date", "there", "has", "been", "relatively", "little", "study", "into", "the", "neurodevelopmental", "changes", "occurring", "around", "puberty,", "and", "comparing", "those", "to", "the", "changes", "occurring", "in", "subjects", "at", "FR", "for", "developing", "schizophrenia.", "Focusing", "attention", "on", "young", "at-risk", "individuals", "provides", "a", "unique", "window", "on", "the", "unfolding", "patho-", "physiology", "of", "the", "illness,", "and", "does", "not", "suffer", "from", "the", "clouding", "effects", "of", "disease", "chronicity", "or", "long-term", "treatment", "that", "plague", "studies", "of", "patients", "with", "established", "illness.", "Longitudinal", "assess-", "ments", "of", "young", "at-risk", "relatives", "also", "provides", "an", "opportunity", "to", "determine", "whether", "biological", "or", "biobehavioral", "differences", "are", "present", "prior", "to", "typical", "onset", "of", "schizophrenia", "in", "those", "individuals", "who", "progress.", "These", "differences", "hold", "the", "potential", "to", "serve", "as", "vul-", "nerability", "markers", "or", "predictors", "of", "illness,", "and", "may", "inform", "targets", "for", "prevention.", "Electroencephalography", "(EEG)", "has", "long", "been", "used", "in", "search", "for", "biomarkers", "of", "schizophrenia", "through", "the", "analysis", "of", "event-", "related", "potentials", "(ERPs).", "ERPs", "can", "provide", "detailed", "information", "about", "neuronal", "events", "underlying", "sensory,", "cognitive,", "or", "motor", "functions.", "One", "of", "the", "most", "reliably", "demonstrated", "ERP", "abnor-", "malities", "in", "schizophrenia", "is", "the", "amplitude", "reduction", "of", "the", "P3", "(e.g.,", "Ford,", "1999;", "Jeon", "and", "Polich,", "2003).", "The", "P3", "is", "a", "late", "scalp-", "positive", "ERP", "component", "usually", "recorded", "in", "an", "auditory", "or", "visual", "“oddball”", "experimental", "paradigm", "in", "which", "a", "subject", "detects", "an", "infrequent", "deviant", "or", "task-relevant", "“target”", "stimulus", "randomly", "presented", "within", "a", "series", "of", "frequent", "non-target", "or", "“standard”", "www.frontiersin.org", "August", "2011", "|", "Volume", "2", "|", "Article", "51", "|", "1" ]

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[ "BMC", "Public", "Health", "Research", "article", "Reliability", "and", "validity", "of", "a", "short", "form", "household", "food", "security", "scale", "in", "a", "Caribbean", "community", "Martin", "C", "Gulliford*1,", "Deepak", "Mahabir2", "and", "Brian", "Rocke2", "BioMed", "Central", "Open", "Access", "Address:", "1Department", "of", "Public", "Health", "Sciences", "King's", "College", "London", "and", "2Nutrition", "and", "Metabolism", "Division", "Ministry", "of", "Health", "Laventille", "Trinidad", "and", "Tobago", "Email:", "Martin", "C", "Gulliford*", "-", "martin.gulliford@kcl.ac.uk;", "Deepak", "Mahabir", "-", "martin.gulliford@kcl.ac.uk;", "Brian", "Rocke", "-", "martin.gulliford@kcl.ac.uk", "*", "Corresponding", "author", "Published:", "16", "June", "2004", "BMC", "Public", "Health", "2004,", "4:22", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2458/4/22", "Received:", "23", "October", "2003", "Accepted:", "16", "June", "2004", "©", "2004", "Gulliford", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article:", "verbatim", "copying", "and", "redistribution", "of", "this", "article", "are", "permitted", "in", "all", "media", "for", "any", "purpose,", "provided", "this", "notice", "is", "preserved", "along", "with", "the", "article's", "original", "URL.", "food", "securityfood", "insecurityreliabilityvalidityquestionnairesWest", "IndiesTrinidad", "and", "Tobago", "Abstract", "Background:", "We", "evaluated", "the", "reliability", "and", "validity", "of", "the", "short", "form", "household", "food", "security", "scale", "in", "a", "different", "setting", "from", "the", "one", "in", "which", "it", "was", "developed.", "Methods:", "The", "scale", "was", "interview", "administered", "to", "531", "subjects", "from", "286", "households", "in", "north", "central", "Trinidad", "in", "Trinidad", "and", "Tobago,", "West", "Indies.", "We", "evaluated", "the", "six", "items", "by", "fitting", "item", "response", "theory", "models", "to", "estimate", "item", "thresholds,", "estimating", "agreement", "among", "respondents", "in", "the", "same", "households", "and", "estimating", "the", "slope", "index", "of", "income-related", "inequality", "(SII)", "after", "adjusting", "for", "age,", "sex", "and", "ethnicity.", "Results:", "Item-score", "correlations", "ranged", "from", "0.52", "to", "0.79", "and", "Cronbach's", "alpha", "was", "0.87.", "Item", "responses", "gave", "within-household", "correlation", "coefficients", "ranging", "from", "0.70", "to", "0.78.", "Estimated", "item", "thresholds", "(standard", "errors)", "from", "the", "Rasch", "model", "ranged", "from", "-2.027", "(0.063)", "for", "the", "'balanced", "meal'", "item", "to", "2.251", "(0.116)", "for", "the", "'hungry'", "item.", "The", "'balanced", "meal'", "item", "had", "the", "lowest", "threshold", "in", "each", "ethnic", "group", "even", "though", "there", "was", "evidence", "of", "differential", "functioning", "for", "this", "item", "by", "ethnicity.", "Relative", "thresholds", "of", "other", "items", "were", "generally", "consistent", "with", "US", "data.", "Estimation", "of", "the", "SII,", "comparing", "those", "at", "the", "bottom", "with", "those", "at", "the", "top", "of", "the", "income", "scale,", "gave", "relative", "odds", "for", "an", "affirmative", "response", "of", "3.77", "(95%", "confidence", "interval", "1.40", "to", "10.2)", "for", "the", "lowest", "severity", "item,", "and", "20.8", "(2.67", "to", "162.5)", "for", "highest", "severity", "item.", "Food", "insecurity", "was", "associated", "with", "reduced", "consumption", "of", "green", "vegetables", "after", "additionally", "adjusting", "for", "income", "and", "education", "(0.52,", "0.28", "to", "0.96).", "Conclusions:", "The", "household", "food", "security", "scale", "gives", "reliable", "and", "valid", "responses", "in", "this", "setting.", "Differing", "relative", "item", "thresholds", "compared", "with", "US", "data", "do", "not", "require", "alteration", "to", "the", "cut-", "points", "for", "classification", "of", "'food", "insecurity", "without", "hunger'", "or", "'food", "insecurity", "with", "hunger'.", "The", "data", "provide", "further", "evidence", "that", "re-evaluation", "of", "the", "'balanced", "meal'", "item", "is", "required.", "Background", "Food", "insecurity", "has", "been", "defined", "as", "the", "'limited", "or", "uncer-", "tain", "availability", "of", "nutritionally", "adequate", "and", "safe", "foods,", "or", "limited", "or", "uncertain", "ability", "to", "acquire", "food", "in", "socially", "Page", "1", "of", "9", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Hindawi", "Publishing", "Corporation", "Case", "Reports", "in", "Medicine", "Volume", "2011,", "Article", "ID", "606920,", "4", "pages", "doi:10.1155/2011/606920", "Case", "Report", "Evidence", "of", "Acute", "Mycoplasma", "Infection", "in", "a", "Patient", "with", "Incomplete", "and", "Atypical", "Kawasaki", "Disease:", "A", "Case", "Report", "M.", "Ebrahim,1", "M.", "Gabay,1,", "2,", "3", "and", "R.", "F.", "Rivas-Chacon3", "1", "Miami", "Children’s", "Hospital,", "Miami,", "FL", "33155,", "USA", "2", "Department", "of", "Pediatrics,", "Nova", "Southeastern", "University,", "Fort", "Lauderdale-Davie,", "FL", "33314-7796,", "USA", "3", "Department", "of", "Rheumatology,", "University", "of", "Miami,", "Miami,", "FL", "33136,", "USA", "Correspondence", "should", "be", "addressed", "to", "M.", "Ebrahim,", "mohdi84@gmail.com", "Received", "30", "August", "2011;", "Revised", "31", "October", "2011;", "Accepted", "1", "November", "2011", "Academic", "Editor:", "C.", "G.", "M.", "Kallenberg", "Copyright", "©", "2011", "M.", "Ebrahim", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "The", "etiology", "of", "Kawasaki", "disease", "remains", "unknown", "despite", "extensive", "studies.", "Some", "researchers", "suggest", "that", "it", "is", "caused", "by", "an", "infectious", "agent.", "This", "is", "a", "case", "report", "where", "a", "patient", "with", "incomplete", "Kawasaki", "disease", "was", "found", "to", "have", "evidence", "compatible", "with", "acute", "Mycoplasma", "pneumoniae", "infection.", "This", "is", "one", "of", "the", "several", "case", "reports", "linking", "Mycoplasma", "pneumoniae", "to", "Kawasaki", "disease", "as", "a", "possible", "trigger.", "This", "is", "perhaps", "due", "to", "a", "superantigen", "or", "is", "mediated", "by", "some", "other", "mechanism.", "Accurate", "and", "timely", "testing", "for", "Mycoplasma", "infections", "is", "difficult", "and", "has", "its", "limitations.", "Despite", "this,", "Mycoplasma", "pneumoniae", "should", "be", "considered", "in", "the", "differential", "and", "workup", "for", "Kawasaki", "disease.", "1.", "Case", "A", "previously", "healthy,", "fully", "vaccinated", "12-year-old", "Hispanic", "male", "presented", "with", "a", "6-day", "history", "of", "high-grade", "and", "inter-", "mittent", "daily", "fever", "(up", "to", "105◦F)", "upon", "admission.", "His", "initial", "symptoms", "were", "sore", "throat,", "nausea,", "and", "vomiting", "in", "addition", "to", "fever.", "Three", "days", "prior", "to", "admission,", "the", "patient", "was", "seen", "in", "a", "pediatric", "emergency", "department", "and", "discharged", "with", "a", "diagnosis", "of", "viral", "illness.", "The", "fever", "persisted,", "and", "he", "became", "more", "ill", "appearing", "with", "complaints", "of", "weakness,", "malaise,", "and", "myalgias,", "and", "a", "faint", "generalized,", "nonpruritic", "rash", "began", "to", "appear.", "There", "was", "no", "history", "of", "joint", "involvement,", "sick", "con-", "tacts,", "recent", "travel,", "or", "exposures", "other", "than", "a", "family", "dog.", "Physical", "examination", "at", "the", "time", "of", "admission", "revealed", "a", "tachycardic", "(heart", "rate", "of", "118", "beats/min),", "tachypneic", "(respi-", "ratory", "rate", "of", "20/min),", "febrile", "(101.5◦F),", "ill-appearing", "patient", "with", "normal", "blood", "pressure", "(121/75).", "An", "erythematous", "mac-", "ular", "rash", "was", "present", "on", "the", "face,", "abdomen,", "and", "extremities.", "He", "had", "conjunctival", "injection", "and", "pharyngeal", "erythema", "without", "observed", "oral", "ulcers.", "Small", "bilateral", "cervical", "lym-", "phadenopathy", "were", "palpated", "and", "measured", "to", "be", "less", "than", "1.5", "cm", "in", "size.", "There", "was", "no", "associated", "edema,", "erythema,", "or", "desquamation", "of", "the", "hands", "or", "feet.", "Laboratory", "workup", "was", "initiated", "for", "suspected", "infecti-", "ous", "or", "rheumatologic", "causes.", "Abnormal", "laboratory", "find-", "ings", "included", "a", "leukocytosis", "(17", "×", "103/mm3)", "with", "predom-", "inant", "neutrophils", "and", "a", "normocytic,", "normochromic", "ane-", "mia", "(12.2", "mg/dL).", "Complete", "blood", "count", "showed", "an", "initial", "thrombocytopenia", "(143", "×", "103/mm3)", "that", "was", "later", "followed", "by", "thrombocytosis", "(398", "×", "103/mm3).", "In", "addition,", "analysis", "revealed", "an", "elevated", "CRP", "(14.2", "mg/L),", "ESR", "(64", "mm/h),", "and", "hypoalbuminemia", "(2.5", "g/dL).", "Mycoplasma", "pneumoniae", "IgM", "serology", "was", "positive", "(Mycoplasma", "IgM", "titer", "≥1.10).", "Chest", "X-ray", "showed", "faint", "bilateral", "interstitial", "markings", "without", "lung", "consolidation", "or", "collapse.", "Comprehensive", "viral", "studies", "and", "cultures", "from", "the", "throat,", "urine,", "and", "blood", "were", "negative.", "The", "remainder", "of", "the", "initial", "workup,", "which", "included", "elec-", "trolytes,", "urinalysis,", "renal", "function", "test,", "and", "lupus", "analyzer,", "was", "within", "normal", "range.", "A", "diagnosis", "of", "viral", "syndrome", "was", "initially", "suspected,", "although", "a", "course", "of", "azithromycin", "(10", "mg/kg/day)", "was", "start-", "ed.", "Acute", "Mycoplasma", "pneumoniae", "infection", "was", "made", "after", "the", "Mycoplasma", "IgM", "serology", "came", "back", "positive.", "Subse-", "quently,", "the", "possibility", "of", "Incomplete", "Kawasaki", "disease", "was", "entertained", "given", "the", "patient’s", "presentation.", "This", "was", "later", "confirmed", "on", "day", "1", "of", "hospitalization", "by", "an", "echocardiogram" ]

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[ "Reichert", "et", "al.", "BMC", "Infectious", "Diseases", "2010,", "10:5", "http://www.biomedcentral.com/1471-2334/10/5", "D", "E", "B", "A", "T", "E", "Open", "Access", "Does", "Glycosylation", "as", "a", "modifier", "of", "Original", "Antigenic", "Sin", "explain", "the", "case", "age", "distribution", "and", "unusual", "toxicity", "in", "pandemic", "novel", "H1N1", "influenza?", "Tom", "Reichert1*,", "Gerardo", "Chowell2,3,", "Hiroshi", "Nishiura4,5,", "Ronald", "A", "Christensen1,", "Jonathan", "A", "McCullers6", "Abstract", "Background:", "A", "pandemic", "novel", "H1N1", "swine-origin", "influenza", "virus", "has", "emerged.", "Most", "recently", "the", "World", "Health", "Organization", "has", "announced", "that", "in", "a", "country-dependent", "fashion,", "up", "to", "15%", "of", "cases", "may", "require", "hospitalization,", "often", "including", "respiratory", "support.", "It", "is", "now", "clear", "that", "healthy", "children", "and", "young", "adults", "are", "disproportionately", "affected,", "most", "unusually", "among", "those", "with", "severe", "respiratory", "disease", "without", "underlying", "conditions.", "One", "possible", "explanation", "for", "this", "case", "age", "distribution", "is", "the", "doctrine", "of", "Original", "Antigenic", "Sin,", "i.e.,", "novel", "H1N1", "may", "be", "antigenically", "similar", "to", "H1N1", "viruses", "that", "circulated", "at", "an", "earlier", "time.", "Persons", "whose", "first", "exposure", "to", "influenza", "viruses", "was", "to", "such", "similar", "viruses", "would", "be", "relatively", "immune.", "However,", "this", "principle", "is", "not", "sufficient", "to", "explain", "the", "graded", "susceptibility", "between", "ages", "20", "and", "60,", "the", "reduced", "susceptibility", "in", "children", "below", "age", "10,", "and", "the", "unusual", "toxicity", "observed.", "Methods:", "We", "collected", "case", "data", "from", "11", "countries,", "about", "60%", "of", "all", "cases", "reported", "through", "mid-July", "2009.", "We", "compared", "sequence", "data", "for", "the", "hemagglutinin", "of", "novel", "H1N1", "with", "sequences", "of", "H1N1", "viruses", "from", "1918", "to", "the", "present.", "We", "searched", "for", "sequence", "differences", "that", "imply", "loss", "of", "antigenicity", "either", "directly", "through", "amino", "acid", "substitution", "or", "by", "the", "appearance", "of", "sites", "for", "potential", "glycosylation", "proximal", "to", "sites", "known", "to", "be", "antigenic", "in", "humans.", "We", "also", "considered", "T-cell", "epitopes.", "Results:", "In", "our", "composite,", "over", "75%", "of", "confirmed", "cases", "of", "novel", "H1N1", "occurred", "in", "persons", "≤", "30", "years", "old,", "with", "peak", "incidence", "in", "the", "age", "range", "10-19", "years.", "Less", "than", "3%", "of", "cases", "occurred", "in", "persons", "over", "65,", "with", "a", "gradation", "in", "incidence", "between", "ages", "20", "and", "60", "years.", "The", "sequence", "data", "indicates", "that", "novel", "H1N1", "is", "most", "similar", "to", "H1N1", "viruses", "that", "circulated", "before", "1943.", "Novel", "H1N1", "lacks", "glycosylation", "sites", "on", "the", "globular", "head", "of", "hemagglutinin", "(HA1)", "near", "antigenic", "regions,", "a", "pattern", "shared", "with", "the", "1918", "pandemic", "strain", "and", "H1N1", "viruses", "that", "circulated", "until", "the", "early", "1940s.", "Later", "H1N1", "viruses", "progressively", "added", "new", "glycosylation", "sites", "likely", "to", "shield", "antigenic", "epitopes,", "while", "T-cell", "epitopes", "were", "relatively", "unchanged.", "Conclusions:", "In", "this", "evolutionary", "context,", "Original", "Antigenic", "Sin", "exposure", "should", "produce", "an", "immune", "response", "increasingly", "mismatched", "to", "novel", "H1N1", "in", "progressively", "younger", "persons.", "We", "suggest", "that", "it", "is", "this", "mismatch", "that", "produces", "both", "the", "gradation", "in", "susceptibility", "and", "the", "unusual", "toxicity.", "Several", "murine", "studies", "suggest", "specific", "cell", "types", "as", "a", "likely", "basis", "of", "the", "unusual", "toxicity.", "These", "studies", "also", "point", "to", "widely", "available", "pharmaceutical", "agents", "as", "plausible", "candidates", "for", "mitigating", "the", "toxic", "effects.", "The", "principle", "of", "Original", "Antigenic", "Sin", "modified", "by", "glycosylation", "appears", "to", "explain", "both", "the", "case", "age", "distribution", "and", "the", "unusual", "toxicity", "pattern", "of", "the", "novel", "H1N1", "pandemic.", "In", "addition,", "it", "suggests", "pharmaceutical", "agents", "for", "immediate", "investigation", "for", "mitigation", "potential,", "and", "provides", "strategic", "guidance", "for", "the", "distribution", "of", "pandemic", "mitigation", "resources", "of", "all", "types.", "*", "Correspondence:", "treichert@entropylimited.com", "1Entropy", "Research", "Institute,", "345", "S.", "Great", "Road,", "Lincoln,", "01773,", "Massachusetts,", "USA", "©", "2010", "Reichert", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Acta", "Crystallographica", "Section", "F", "Structural", "Biology", "and", "Crystallization", "Communications", "ISSN", "1744-3091", "Hsiu-Ju", "Chiu,a,b", "Constantina", "Bakolitsa,a,c", "Arne", "Skerra,d", "Andrei", "Lomize,e", "Dennis", "Carlton,a,f", "Mitchell", "D.", "Miller,a,c", "S.", "Sri", "Krishna,a,b,g", "Polat", "Abdubek,a,h", "Tamara", "Astakhova,a,g", "Herbert", "L.", "Axelrod,a,c", "Thomas", "Clayton,a,f", "Marc", "C.", "Deller,a,f", "Lian", "Duan,a,g", "Julie", "Feuerhelm,a,h", "Joanna", "C.", "Grant,a,h", "Slawomir", "K.", "Grzechnik,a,g", "Gye", "Won", "Han,a,f", "Lukasz", "Jaroszewski,a,b,g", "Kevin", "K.", "Jin,a,c", "Heath", "E.", "Klock,a,h", "Mark", "W.", "Knuth,a,h", "Piotr", "Kozbial,a,b", "Abhinav", "Kumar,a,c", "David", "Marciano,a,f", "Daniel", "McMullan,a,h", "Andrew", "T.", "Morse,a,g", "Edward", "Nigoghossian,a,h", "Linda", "Okach,a,h", "Jessica", "Paulsen,a,h", "Ron", "Reyes,a,c", "Christopher", "L.", "Rife,a,c", "Henry", "van", "den", "Bedem,a,c", "Dana", "Weekes,a,b", "Qingping", "Xu,a,c", "Keith", "O.", "Hodgson,a,i", "John", "Wooley,a,g", "Marc-Andre´", "Elsliger,a,f", "Ashley", "M.", "Deacon,a,c", "Adam", "Godzik,a,b,g", "Scott", "A.", "Lesleya,f,h", "and", "Ian", "A.", "Wilsona,f*", "aJoint", "Center", "for", "Structural", "Genomics,", "http://", "www.jcsg.org,", "USA,", "bStanford", "Synchrotron", "Radiation", "Lightsource,", "SLAC", "National", "Accelerator", "Laboratory,", "Menlo", "Park,", "CA,", "USA,", "cProgram", "on", "Bioinformatics", "and", "Systems", "Biology,", "Burnham", "Institute", "for", "Medical", "Research,", "La", "Jolla,", "CA,", "USA,", "dLehrstuhl", "fu¨", "r", "Biologische", "Chemie,", "Technische", "Universita¨t", "Mu¨", "nchen,", "85350", "Freizing-Weihenstephan,", "Germany,", "eDepartment", "of", "Medicinal", "Chemistry,", "College", "of", "Pharmacy,", "University", "of", "Michigan,", "Ann", "Arbor,", "MI", "48109-1065,", "USA,", "fDepartment", "of", "Molecular", "Biology,", "The", "Scripps", "Research", "Institute,", "La", "Jolla,", "CA,", "USA,", "gCenter", "for", "Research", "in", "Biological", "Systems,", "University", "of", "California,", "San", "Diego,", "La", "Jolla,", "CA,", "USA,", "hProtein", "Sciences", "Department,", "Genomics", "Institute", "of", "the", "Novartis", "Research", "Foundation,", "San", "Diego,", "CA,", "USA,", "and", "iPhoton", "Science,", "SLAC", "National", "Accelerator", "Laboratory,", "Menlo", "Park,", "CA,", "USA", "Correspondence", "e-mail:", "wilson@scripps.edu", "Received", "12", "June", "2009", "Accepted", "17", "September", "2009", "PDB", "Reference:", "NE1406", "from", "N.", "europaea,", "2ich,", "r2ichsf.", "Acta", "Cryst.", "(2010).", "F66,", "1153–1159", "structural", "communications", "Structure", "of", "the", "first", "representative", "of", "Pfam", "family", "PF09410", "(DUF2006)", "reveals", "a", "structural", "signature", "of", "the", "calycin", "superfamily", "that", "suggests", "a", "role", "in", "lipid", "metabolism", "The", "first", "structural", "representative", "of", "the", "domain", "of", "unknown", "function", "DUF2006", "family,", "also", "known", "as", "Pfam", "family", "PF09410,", "comprises", "a", "lipocalin-like", "fold", "with", "domain", "duplication.", "The", "finding", "of", "the", "calycin", "signature", "in", "the", "N-terminal", "domain,", "combined", "with", "remote", "sequence", "similarity", "to", "two", "other", "protein", "families", "(PF07143", "and", "PF08622)", "implicated", "in", "isoprenoid", "metabolism", "and", "the", "oxidative", "stress", "response,", "support", "an", "involvement", "in", "lipid", "metabolism.", "Clusters", "of", "conserved", "residues", "that", "interact", "with", "ligand", "mimetics", "suggest", "that", "the", "binding", "and", "regulation", "sites", "map", "to", "the", "N-terminal", "domain", "and", "to", "the", "inter-", "domain", "interface,", "respectively.", "1.", "Introduction", "In", "an", "effort", "to", "extend", "the", "structural", "coverage", "of", "proteins", "for", "which", "the", "biological", "function", "is", "unknown", "and", "cannot", "be", "deduced", "by", "homology", "(domains", "of", "unknown", "function;", "DUFs),", "targets", "were", "selected", "from", "Pfam", "protein", "family", "PF09410", "(DUF2006).", "Here,", "we", "report", "the", "crystal", "structure", "of", "NE1406,", "the", "first", "structural", "repre-", "sentation", "of", "this", "family,", "which", "was", "determined", "using", "the", "semi-", "automated", "high-throughput", "pipeline", "of", "the", "Joint", "Center", "for", "Structural", "Genomics", "(JCSG;", "Lesley", "et", "al.,", "2002)", "as", "part", "of", "the", "NIGMS", "Protein", "Structure", "Initiative", "(PSI).", "The", "NE1406", "gene", "of", "Nitrosomonas", "europaea,", "an", "obligate", "chemolithoautotroph,", "encodes", "a", "protein", "with", "a", "molecular", "weight", "of", "40.1", "kDa", "(residues", "1–356)", "and", "a", "calculated", "isoelectric", "point", "of", "5.0.", "2.", "Materials", "and", "methods", "2.1.", "Protein", "production", "and", "crystallization", "Clones", "were", "generated", "using", "the", "polymerase", "incomplete", "primer", "extension", "(PIPE)", "cloning", "method", "(Klock", "et", "al.,", "2008).", "The", "gene", "encoding", "NE1406", "(GenBank", "NP_841447,", "gi|30249377,", "Swiss-Prot", "Q82US3)", "was", "amplified", "by", "polymerase", "chain", "reaction", "(PCR)", "from", "N.", "europaea", "strain", "ATCC", "19718", "genomic", "DNA", "using", "PfuTurbo", "DNA", "polymerase", "(Stratagene)", "and", "I-PIPE", "(Insert)", "primers", "(forward", "primer", "50-ctgtacttccagggcATGCGTTACTTATGGATACTGTTG-30,", "reverse", "primer", "50-aattaagtcgcgttaCATCGATAACGGACGTACG-30;", "target", "sequence", "in", "upper", "case)", "that", "included", "sequences", "for", "the", "predicted", "50", "and", "30", "ends.", "The", "expression", "vector", "pSpeedET,", "which", "encodes", "an", "amino-terminal", "tobacco", "etch", "virus", "(TEV)", "protease-", "cleavable", "expression", "and", "purification", "tag", "(MGSDKIHHHHHHEN-", "LYFQ/G),", "was", "PCR-amplified", "with", "V-PIPE", "(Vector)", "primers.", "V-PIPE", "and", "I-PIPE", "PCR", "products", "were", "mixed", "to", "anneal", "the", "amplified", "DNA", "fragments", "together.", "Escherichia", "coli", "GeneHogs", "(Invitrogen)", "com-", "petent", "cells", "were", "transformed", "with", "the", "V-PIPE/I-PIPE", "mixture", "and", "dispensed", "onto", "selective", "LB-agar", "plates.", "The", "cloning", "junctions", "were", "confirmed", "by", "DNA", "sequencing.", "Using", "the", "PIPE", "method,", "the", "part", "of", "the", "gene", "encoding", "residues", "Met1–Pro22", "was", "deleted.", "Expression", "was", "performed", "in", "a", "selenomethionine-containing", "medium", "with", "suppres-", "sion", "of", "normal", "methionine", "synthesis.", "At", "the", "end", "of", "fermentation,", "lysozyme", "was", "added", "to", "the", "culture", "to", "a", "final", "concentration", "of", "250", "mg", "ml", "1", "and", "the", "cells", "were", "harvested", "and", "frozen.", "After", "one", "freeze–thaw", "cycle,", "the", "cells", "were", "sonicated", "in", "lysis", "buffer", "[50", "mM", "HEPES", "pH", "8.0,", "50", "mM", "NaCl,", "10", "mM", "imidazole,", "1", "mM", "tris(2-car-", "doi:10.1107/S1744309109037749", "1153" ]

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[ "접수번호:", "2008-103", "Korean", "Journal", "of", "Ophthalm", "ology", "2009;23:210-214", "ISSN", ":", "1011-8942", "DOI", ":", "10.3341/kjo.2009.23.3.210", "A", "Case", "of", "Primary", "Intraocular", "Lymphoma", "Treated", "by", "Intravitreal", "Methotrexate", "Eunah", "Kim,", "MD1,", "Changhyun", "Kim,", "MD1,", "Jiwoong", "Lee,", "MD2,", "Youngwook", "Cho,", "MD1", "1Department", "of", "Ophthalmology,", "Daegu", "Fatima", "Hospital,", "Daegu,", "Korea", "2Department", "of", "Ophthalmology,", "School", "of", "Medicine,", "Pusan", "National", "University,", "Busan,", "Korea", "A", "40-year-old", "female", "visited", "our", "clinic", "for", "visual", "disturbance", "of", "the", "right", "eye,", "in", "which", "a", "few", "creamy-yellow", "retinal", "lesions", "and", "visual", "field", "constrictions", "were", "noted.", "She", "had", "been", "treated", "for", "primary", "CNS", "lymphoma", "and", "was", "in", "complete", "remission.", "After", "failure", "to", "follow-up", "for", "three", "months,", "she", "lost", "vision", "in", "the", "right", "eye,", "at", "which", "time", "active", "panuveitis", "was", "seen.", "Decreased", "vision", "and", "field", "constriction", "was", "observed", "in", "the", "left", "eye.", "Her", "left", "eye", "showed", "a", "granular", "pattern", "and", "dye", "leakage", "from", "the", "vessels", "and", "disc", "on", "fluorescein", "angiography", "and", "small", "RPE", "humps", "were", "seen", "in", "optical", "coherence", "tomography", "(OCT).", "Diffuse", "large", "malignant", "B-cells", "with", "strong", "immunoreactivities", "with", "CD20", "immunostaining", "were", "seen", "in", "the", "epiretinal", "membrane", "biopsy", "specimen.", "Intravitreal", "injections", "of", "metho-", "trexate", "(MTX)", "(800", "μg/0.1", "ml", "in", "the", "right", "eye,", "400", "μg/0.05", "ml", "in", "the", "left", "eye)", "were", "performed", "twice", "weekly", "for", "one", "month,", "once", "weekly", "for", "the", "following", "month,", "once", "every", "two", "weeks", "for", "the", "next", "month,", "followed", "by", "nine", "monthly", "injections.", "Both", "eyes", "were", "free", "from", "malignant", "cells", "on", "vitreous", "biopsy", "six", "months", "later.", "There", "was", "no", "leakage", "seen", "by", "angiography,", "but", "the", "granular", "pattern", "persisted.", "Visual", "field", "constriction", "was", "slightly", "improved,", "and", "the", "small", "RPE", "humpsdetachments", "seen", "in", "OCT", "disappeared.", "EOG", "Arden", "ratio", "was", "decreased", "in", "both", "eyes,", "and", "b", "wave", "amplitude", "of", "scotopic", "ERG", "was", "decreased", "in", "the", "left", "eye.", "She", "was", "free", "from", "recurrence", "until", "six", "months", "later.", "No", "ocular", "complications", "except", "minimal", "opacity", "of", "the", "crystalline", "lenses", "were", "noted", "in", "both", "eyes.", "Korean", "J", "Ophthalmol", "2009;23:210-214", "ⓒ", "2009", "by", "the", "Korean", "Ophthalmological", "Society.", "Key", "Words:", "Intravitreal", "injection,", "Masquerade", "syndrome,", "Methotrexate,", "Primary", "intraocular", "lymphoma,", "Uveitis", "Primary", "intraocular", "lymphoma", "(PIOL)", "is", "considered", "to", "be", "a", "subset", "of", "primary", "CNS", "lymphoma", "(PCNSL).1", "One-fifth", "of", "patients", "with", "PCNSL", "may", "demonstrate", "ocular", "involvement", "at", "the", "time", "of", "diagnosis,", "and", "the", "eye", "can", "be", "involved", "prior", "of", "the", "onset", "of", "CNS", "disease.2,3", "The", "exact", "incidence", "of", "PIOL", "is", "un-", "known,", "but", "it", "is", "reported", "to", "be", "in", "the", "range", "of", "30", "to", "50", "cases", "per", "10", "million", "people", "in", "the", "United", "States.4,5", "Only", "one", "case", "has", "been", "reported", "in", "Korea.6", "So", "far,", "there", "are", "three", "main", "treatment", "options", "for", "PIOL;", "sys-", "temic", "high-dose", "MTX", "injection,", "orbital", "irradiation,", "and", "intra-", "vitreal", "chemotherapy", "with", "MTX", "injections.", "These", "may", "be", "com-", "bined", "or", "used", "separately.7,8", "Initial", "approaches", "for", "the", "treatment", "of", "PIOL/PCNSL", "centered", "on", "radiotherapy,", "but", "it", "had", "a", "minimal", "effect", "on", "survival", "and", "may", "have", "been", "associated", "with", "radiation", "retinopathy.9", "Isolated", "radiation", "therapy", "is", "currently", "less", "com-", "monly", "used,10", "and", "treatment", "can", "be", "limited", "to", "the", "eye", "in", "pa-", "tients", "with", "PIOL", "limited", "to", "the", "eye.11", "There", "are", "some", "reports", "of", "PIOL", "effectively", "treated", "with", "intravitreal", "chemotherapy,", "and", "Received:", "October", "13,", "2008", "Accepted:", "August", "7,", "2009", "Reprint", "requests", "to", "Youngwook", "Cho,", "MD.", "Department", "of", "Ophthalmology,", "Fatima", "Hospital,", "#576-31", "Sinam-dong,", "Dong-gu,", "Daegu", "701-600,", "Korea.", "Tel:", "82-53-940-7143,", "Fax:", "82-53-954-7417,", "E-mail:", "vitreo-retina@hanmail.net", "*", "This", "study", "was", "presented", "as", "a", "poster", "at", "the", "99th", "annual", "meeting", "of", "the", "Korean", "Ophthalmological", "Society", "in", "April,", "2008.", "210", "it", "has", "been", "often", "recommended", "as", "a", "first-line", "therapy", "for", "initial", "and", "recurrent", "PIOL.11-13", "To", "our", "knowledge,", "this", "is", "the", "first", "report", "of", "PIOL", "treated", "by", "intravitreal", "chemotherapy,", "and", "the", "first", "to", "describe", "fluorescein", "angiographic", "findings,", "visual", "field", "exams,", "OCT", "findings", "and", "the", "electrophysiological", "characteristics", "of", "PIOL", "in", "Koreas.", "Case", "Repo", "rt", "A", "40-year-old", "female", "visited", "our", "clinic", "for", "agradual", "visual", "disturbance", "in", "her", "right", "eye", "in", "January", "2007.", "Her", "best-corrected", "visual", "acuity", "(BCVA)", "was", "20/160", "OD", "and", "20/20", "OS.", "A", "few", "barely", "detectable", "creamy-yellow", "retinal", "lesions", "were", "seen", "in", "the", "right", "eye.", "Eighteen", "months", "prior,", "she", "had", "been", "diagnosed", "with", "PCNSL", "in", "the", "right", "temporo-parietal", "lobe", "which", "had", "been", "pathologically", "confirmed", "as", "malignant", "large", "B-cells.", "Systemic", "chemotherapy", "with", "MTX", "was", "used", "initially,", "but", "it", "failed.", "Com-", "plete", "remission", "was", "achieved", "by", "whole", "brain", "irradiation.", "A", "gra-", "nular", "pattern", "of", "mixed", "hyperfluorescent", "and", "hypofluorescent", "spots,", "along", "with", "leakage", "from", "the", "retinal", "vessels", "and", "the", "optic", "disc,", "were", "observed", "in", "fluorescein", "angiography", "of", "the", "right", "eye.", "Her", "visual", "field", "was", "considerably", "constricted", "and", "OCT", "(STRA-", "TUS", "OCT", "model", "3000,", "Zeiss", "Instruments", "INC.", "San", "Leandro,", "CA)", "showed", "small", "irregular", "RPE", "detachments", "in", "the", "right", "eye", "(Fig.", "1).", "P1", "amplitude", "and", "latency", "of", "the", "right", "eye", "were", "mar-", "kedly", "decreased", "compared", "with", "those", "of", "the", "left", "eye,", "as", "deter-" ]

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[ "Gut", "and", "Liver,", "Vol.", "5,", "No.", "3,", "September", "2011,", "pp.", "315-320", "ORiginal", "Article", "Relationship", "between", "the", "Extent", "of", "DNA", "Damage", "and", "Gastritis", "in", "Normal", "and", "Helicobacter", "pylori", "-Infected", "Patients", "Mohammed", "Ali", "M.", "Marie*", "and", "Isam", "Elshaikh", "Altahir†", "*Clinical", "Laboratory", "Department,", "King", "Saud", "University,", "College", "of", "Applied", "Medical", "Sciences,", "and", "Clinical", "Laboratory", "Department,", "King", "Saud", "University", "Riyadh,", "College", "of", "Health", "Sciences,", "Riyadh,", "Saudi", "Arabia", "Background/Aims:", "The", "role", "of", "Helicobacter", "pylori", "in", "gastric", "carcinogenesis", "is", "unclear,", "but", "H.", "pylori", "infection", "is", "thought", "to", "predispose", "carriers", "to", "gastric", "cancer.", "The", "aim", "of", "this", "study", "was", "to", "investigate", "the", "relationship", "between", "the", "extent", "of", "DNA", "damage", "in", "normal", "gastric", "epithelial", "cells", "and", "H.", "pylori-", "positive", "and", "-negative", "gastritis", "according", "to", "histological", "diag-", "nosis.", "We", "also", "compared", "the", "percentage", "of", "cometed", "cells", "on", "the", "surface", "of", "the", "gastric", "epithelial", "cells", "to", "the", "percentage", "beneath", "the", "gastric", "mucosal", "cells", "using", "serial", "incubations", "times.", "Methods:", "The", "comet", "assay", "is", "a", "rapid,", "efficient", "and", "re-", "producible", "measure", "of", "DNA", "damage", "in", "single", "cell", "and", "it", "was", "used", "in", "this", "study.", "DNA", "damage", "was", "evaluated", "in", "52", "cases", "using", "alkaline", "single", "cell", "gel", "electrophoresis", "(comet", "assay).", "Comparisons", "were", "made", "between", "19", "normal", "individuals,", "19", "patients", "with", "H.", "pylori-positive", "and", "-negative", "gastritis", "and", "14", "mixed", "cases", "with", "different", "histology", "gradings", "to", "determine", "if", "there", "was", "a", "relationship", "between", "histological", "diagnosis", "and", "DNA", "damage", "(comet", "percentage).", "Results:", "The", "comet", "percentages", "in", "specimens", "from", "cases", "with", "normal", "histol-", "ogy", "were", "significantly", "higher", "than", "the", "comet", "percentages", "in", "specimens", "from", "cases", "with", "H.", "pylori-positive", "gastritis.", "In", "ad-", "dition,", "there", "was", "a", "significant", "increase", "in", "the", "percentage", "of", "cometed", "cells", "on", "the", "surface", "of", "gastric", "epithelial", "cells", "in", "both", "normal", "and", "H.", "pylori-infected", "cells", "compared", "to", "the", "subse-", "quent", "gastric", "cell", "layers", "of", "the", "same", "specimen.", "Conclusions:", "A", "relationship", "between", "the", "comet", "percentage", "and", "the", "histo-", "logical", "diagnosis", "was", "observed.", "(Gut", "Liver", "2011;5:315-320)", "Key", "Words:", "Comet", "assay;", "Helicobacter", "pylori;", "Gastric", "cancer", "INTRODUCTION", "Gastric", "cancer", "is", "the", "second", "most", "common", "malignancy", "in", "the", "world,", "accounting", "for", "9.9%", "of", "all", "cancer", "incidence", "and", "12.1%", "of", "all", "cancer", "death.1", "Carcinogenesis", "is", "a", "multistep", "process", "and", "steps", "involved", "on", "it", "relate", "to", "initiation-promotion", "sequences.", "Initiation", "cause", "permanent", "DNA", "damage", "(mutation).", "It", "is", "there-", "fore", "potentially", "leads", "to", "cancer", "development.", "Promoters", "can", "induce", "tumours", "in", "initiated", "cells,", "but", "they", "are", "non-tumourgenic", "by", "themselves.2", "Gastritis", "and", "Helicobacter", "pylori", "are", "considered", "to", "be", "risk", "factors", "for", "gastric", "carcinoma.3", "There", "is", "growing", "evi-", "dence", "supporting", "an", "association", "between", "H.", "pylori", "and", "gastric", "cancer.", "H.", "pylori", "infection", "induces", "chronic", "inflammation", "that", "can", "progress", "to", "gastric", "atrophy,", "intestinal", "metaplasia", "and", "gastric", "adenocarcinoma.4", "The", "objective", "of", "this", "study", "is", "to", "investigate", "the", "relationship", "between", "the", "extent", "of", "DNA", "damage", "and", "the", "histological", "grad-", "ing", "of", "the", "gastric", "epithelium", "from", "which", "the", "biopsy", "was", "taken.", "Secondly", "for", "the", "comparison", "of", "percentages", "of", "gastric", "epithelia", "cells", "of", "H.", "pylori-positive", "and", "-negative", "gastritis", "with", "the", "nor-", "mal", "gastric", "cells.", "Finally", "the", "study", "compared", "the", "percentages", "of", "DNA", "damaged", "on", "the", "surface", "of", "gastric", "epithelial", "cells", "with", "the", "cells", "underneath", "in", "both", "normal", "individuals", "and", "patients", "with", "H.", "pylori-positive", "and", "-negative", "gastritis", "patients.", "MATERIALS", "AND", "METHODS", "The", "study", "population", "consisted", "of", "52", "unselected", "patients", "at-", "tending", "endoscopy", "clinic", "suffering", "from", "dyspepsia", "at", "Al", "Iman", "General", "Hospital,", "Riyadh,", "Saudi", "Arabia.", "At", "endoscopy", "unit,", "biop-", "sies", "were", "taken", "from", "the", "gastric", "antrum", "for", "histopathology", "and", "for", "H.", "pylori", "urease", "testing.", "After", "the", "comet", "and", "histopathology", "were", "performed,", "we", "selected", "and", "compared", "the", "results", "showing", "the", "per-", "centages", "of", "DNA", "damage", "of", "gastric", "cells", "of", "19", "normal", "individuals", "with", "19", "patients", "with", "positive", "and", "negative", "H.", "pylori", "gastritis", "and", "14", "cases", "of", "different", "histological", "diagnosis", "were", "tested.", "Correspondence", "to:", "Mohammed", "Ali", "M.", "Marie", "Clinical", "Laboratory", "Department,", "King", "Saud", "University", "College", "of", "Applied", "Medical", "Sciences,", "P.O.", "Box", "10219,", "Riyadh", "11433,", "Saudi", "Arabia", "Tel:", "+96614696022,", "Fax:", "+96614693738,", "E-mail:", "mmarie@ksu.edu.sa", "Received", "on", "November", "9,", "2010.", "Accepted", "on", "March", "13,", "2011.", "pISSN", "1976-2283", "eISSN", "2005-1212", "http://dx.doi.org/10.5009/gnl.2011.5.3.315", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/by-nc/3.0)", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Hindawi", "Publishing", "Corporation", "Prostate", "Cancer", "Volume", "2011,", "Article", "ID", "565230,", "10", "pages", "doi:10.1155/2011/565230", "Research", "Article", "Prostate", "Cancer", "Incidence", "and", "Mortality", "in", "Barbados,", "West", "Indies", "Anselm", "J.", "M.", "Hennis,1,", "2,", "3,", "4", "Ian", "R.", "Hambleton,1", "Suh-Yuh", "Wu,2", "Desiree", "H.-A.", "Skeete,4", "Barbara", "Nemesure,2", "and", "M.", "Cristina", "Leske2", "1", "Chronic", "Disease", "Research", "Centre,", "The", "University", "of", "the", "West", "Indies,", "Jemmott’s", "Lane,", "St.", "Michael,", "Barbados", "2", "Department", "of", "Preventive", "Medicine,", "Stony", "Brook", "University", "Medical", "Center,", "Stony", "Brook,", "NY", "11794-8036,", "USA", "3", "Ministry", "of", "Health,", "Jemmott’s", "Lane,", "Bridgetown,", "Barbados", "4", "Faculty", "of", "Medical", "Sciences,", "The", "University", "of", "the", "West", "Indies,", "St.", "Michael,", "Barbados", "Correspondence", "should", "be", "addressed", "to", "Anselm", "J.", "M.", "Hennis,", "anselm.hennis@cavehill.uwi.edu", "Received", "20", "December", "2010;", "Accepted", "27", "January", "2011", "Academic", "Editor:", "Cathryn", "Bock", "Copyright", "©", "2011", "Anselm", "J.", "M.", "Hennis", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "We", "describe", "prostate", "cancer", "incidence", "and", "mortality", "in", "Barbados,", "West", "Indies.", "We", "ascertained", "all", "histologically", "confirmed", "cases", "of", "prostate", "cancer", "during", "the", "period", "July", "2002", "to", "December", "2008", "and", "reviewed", "each", "death", "registration", "citing", "prostate", "cancer", "over", "a", "14-year", "period", "commencing", "January", "1995.", "There", "were", "1101", "new", "cases", "for", "an", "incidence", "rate", "of", "160.4", "(95%", "Confidence", "Interval:", "151.0–170.2)", "per", "100,000", "standardized", "to", "the", "US", "population.", "Comparable", "rates", "in", "African-American", "and", "White", "American", "men", "were", "248.2", "(95%", "CI:", "246.0–250.5)", "and", "158.0", "(95%", "CI:", "157.5–158.6)", "per", "100,000,", "respectively.", "Prostate", "cancer", "mortality", "rates", "in", "Barbados", "ranged", "from", "63.2", "to", "101.6", "per", "100,000,", "compared", "to", "51.1", "to", "78.8", "per", "100,000", "among", "African", "Americans.", "Prostate", "cancer", "risks", "are", "lower", "in", "Caribbean-origin", "populations", "than", "previously", "believed,", "while", "mortality", "rates", "appeared", "to", "be", "higher", "than", "reported", "in", "African-American", "men.", "Studies", "in", "Caribbean", "populations", "may", "assist", "understanding", "of", "disparities", "among", "African-", "origin", "populations", "with", "shared", "heredity.", "1.", "Introduction", "Prostate", "cancer", "rates", "are", "higher", "in", "westernized", "African-", "origin", "populations", "when", "compared", "to", "other", "ethnic", "and", "racial", "groups", "[1,", "2].", "In", "the", "United", "States,", "prostate", "can-", "cer", "remains", "the", "principal", "malignancy", "in", "African-American", "men", "and", "the", "leading", "cause", "of", "cancer-related", "death", "in", "this", "group", "[3,", "4].", "Similar", "findings", "have", "been", "reported", "from", "the", "English-speaking", "Caribbean", "[5],", "where", "the", "majority", "of", "the", "population", "shares", "a", "common", "heredity", "with", "African", "Americans,", "as", "a", "result", "of", "the", "West", "African", "diaspora", "[6].", "Despite", "the", "importance", "of", "prostate", "cancer", "as", "a", "cause", "of", "ill", "health", "and", "mortality", "in", "the", "Caribbean,", "there", "remains", "limited", "information", "about", "disease", "rates,", "risk", "factors,", "and", "the", "clinical", "and", "public", "health", "implications", "for", "the", "region", "[7–10].", "The", "Barbados", "National", "Cancer", "Study", "(BNCS),", "funded", "by", "the", "National", "Institutes", "of", "Health,", "was", "established", "in", "2002", "to", "document", "the", "incidence", "and", "risk", "factors", "for", "prostate", "and", "breast", "cancer,", "among", "the", "country’s", "men", "and", "women,", "respectively.", "Such", "malignancies", "are", "known", "to", "be", "the", "most", "frequent", "among", "the", "island’s", "residents", "[11].", "The", "African-", "descent", "Barbados", "population", "shares", "a", "common", "heredity", "with", "African", "Americans", "(but", "with", "lower", "admixture)", "[12],", "as", "well", "as", "high", "rates", "of", "lifestyle-related", "noncommunicable", "disease", "[13–16].", "While", "investigation", "of", "conditions", "relevant", "to", "African", "Americans", "in", "the", "US", "may", "be", "confounded", "by", "associations", "with", "socioeconomic", "factors,", "the", "public", "care", "system", "in", "Barbados", "provides", "easy", "access", "to", "comprehensive", "healthcare", "at", "no", "cost,", "thus", "minimizing", "such", "concerns.", "As", "demonstrated", "in", "our", "previous", "work,", "findings", "from", "the", "Bar-", "badian", "population", "may", "therefore", "have", "direct", "relevance", "to", "the", "health", "of", "African-American", "populations", "[17].", "In", "addition", "to", "collecting", "data", "on", "prostate", "cancer", "inci-", "dence,", "a", "key", "outcome", "of", "the", "BNCS,", "we", "also", "utilized", "the", "es-", "tablished", "research", "infrastructure", "to", "collect", "additional", "infor-", "mation", "on", "prostate", "cancer-related", "mortality.", "The", "purpose", "of", "this", "paper", "is", "to", "present", "the", "first", "comprehensive", "data", "about", "prostate", "cancer", "incidence", "and", "mortality", "in", "Barbados,", "West", "Indies,", "and", "provide", "comparisons", "with", "African", "Americans.", "Although", "African", "Americans", "are", "consistently", "reported", "to" ]

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[ "BMC", "Bioinformatics", "Research", "article", "Reannotation", "of", "the", "CELO", "genome", "characterizes", "a", "set", "of", "previously", "unassigned", "open", "reading", "frames", "and", "points", "to", "novel", "modes", "of", "host", "interaction", "in", "avian", "adenoviruses", "Stefan", "Washietl1,2", "and", "Frank", "Eisenhaber*1", "BioMed", "Central", "Open", "Access", "Address:", "1Research", "Institute", "of", "Molecular", "Pathology,", "Dr.", "Bohrgasse", "7,", "A-1030", "Vienna,", "Austria", "and", "2Current", "address:", "Institute", "for", "Theoretical", "Chemistry", "and", "Structural", "Biology,", "University", "of", "Vienna,", "Waehringerstrasse", "17,", "A-1090", "Vienna,", "Austria", "Email:", "Stefan", "Washietl", "-", "wash@tbi.univie.ac.at;", "Frank", "Eisenhaber*", "-", "Frank.Eisenhaber@imp.univie.ac.at", "*", "Corresponding", "author", "Published:", "07", "November", "2003", "BMC", "Bioinformatics", "2003,", "4:55", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2105/4/55", "Received:", "02", "September", "2003", "Accepted:", "07", "November", "2003", "©", "2003", "Washietl", "and", "Eisenhaber;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article:", "verbatim", "copying", "and", "redistribution", "of", "this", "article", "are", "per-", "mitted", "in", "all", "media", "for", "any", "purpose,", "provided", "this", "notice", "is", "preserved", "along", "with", "the", "article's", "original", "URL.", "Abstract", "Background:", "The", "genome", "of", "the", "avian", "adenovirus", "Chicken", "Embryo", "Lethal", "Orphan", "(CELO)", "has", "two", "terminal", "regions", "without", "detectable", "homology", "in", "mammalian", "adenoviruses", "that", "are", "left", "without", "annotation", "in", "the", "initial", "analysis.", "Since", "adenoviruses", "have", "been", "a", "rich", "source", "of", "new", "insights", "into", "molecular", "cell", "biology", "and", "practical", "applications", "of", "CELO", "as", "gene", "a", "delivery", "vector", "are", "being", "considered,", "this", "genome", "appeared", "worth", "revisiting.", "We", "conducted", "a", "systematic", "reannotation", "and", "in-depth", "sequence", "analysis", "of", "the", "CELO", "genome.", "Results:", "We", "describe", "a", "strongly", "diverged", "paralogous", "cluster", "including", "ORF-2,", "ORF-12,", "ORF-13,", "and", "ORF-14", "with", "an", "ATPase/helicase", "domain", "most", "likely", "acquired", "from", "adeno-associated", "parvoviruses.", "None", "of", "these", "ORFs", "appear", "to", "have", "retained", "ATPase/helicase", "function", "and", "alternative", "functions", "(e.g.", "modulation", "of", "gene", "expression", "during", "the", "early", "life-cycle)", "must", "be", "considered", "in", "an", "adenoviral", "context.", "Further,", "we", "identified", "a", "cluster", "of", "three", "putative", "type-1-", "transmembrane", "glycoproteins", "with", "IG-like", "domains", "(ORF-9,", "ORF-10,", "ORF-11)", "which", "are", "good", "candidates", "to", "substitute", "for", "the", "missing", "immunomodulatory", "functions", "of", "mammalian", "adenoviruses.", "ORF-16", "(located", "directly", "adjacent)", "displays", "distant", "homology", "to", "vertebrate", "mono-ADP-", "ribosyltransferases.", "Members", "of", "this", "family", "are", "known", "to", "be", "involved", "in", "immuno-regulation", "and", "similiar", "functions", "during", "CELO", "life", "cycle", "can", "be", "considered", "for", "this", "ORF.", "Finally,", "we", "describe", "a", "putative", "triglyceride", "lipase", "(merged", "ORF-18/19)", "with", "additional", "domains,", "which", "can", "be", "expected", "to", "have", "specific", "roles", "during", "the", "infection", "of", "birds,", "since", "they", "are", "unique", "to", "avian", "adenoviruses", "and", "Marek's", "disease-like", "viruses,", "a", "group", "of", "pathogenic", "avian", "herpesviruses.", "Conclusions:", "We", "could", "characterize", "most", "of", "the", "previously", "unassigned", "ORFs", "pointing", "to", "functions", "in", "host-virus", "interaction.", "The", "results", "provide", "new", "directives", "for", "rationally", "designed", "experiments.", "Background", "Chicken", "embryo", "lethal", "orphan", "virus", "(CELO)", "is", "an", "adeno-", "virus", "infecting", "avian", "species", "[1,2].", "It", "is", "a", "member", "of", "the", "genus", "Aviadenovirus", "and", "also", "referred", "to", "as", "Fowl", "Adenovi-", "rus", "1", "(FAdV-1).", "Compared", "to", "mammalian", "and,", "in", "partic-", "ular,", "human", "adenoviruses", "of", "the", "genus", "Mastadenovirus,", "which", "have", "been", "studied", "extensively", "over", "the", "years", "(reviewed", "in", "[3]),", "relatively", "little", "information", "is", "available", "Page", "1", "of", "17", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Case", "Report", "Korean", "J", "Anesthesiol", "2011", "December", "61(6):", "528-532", "http://dx.doi.org/10.4097/kjae.2011.61.6.528", "Anesthetic", "experiences", "of", "myxoma", "removal", "surgery", "in", "two", "patients", "with", "Carney", "complex", "-A", "report", "of", "two", "cases-", "Young", "Mi", "Kang,", "and", "Yoon", "Hee", "Kim", "Department", "of", "Anesthesiology", "and", "Pain", "Medicine,", "College", "of", "Medicine,", "Chungnam", "National", "University,", "Daejeon,", "Korea", "Carney", "complex", "is", "an", "autosomal", "dominant", "disorder", "that", "occurs", "due", "to", "a", "mutation", "in", "PRKAR1A,", "which", "encodes", "protein", "kinase", "A.", "The", "clinical", "features", "are", "multiple", "endocrine", "gland", "neoplasms,", "skin", "tumors,", "pigmented", "skin", "lesions,", "myxomas,", "and", "schwannomas.", "In", "Carney", "complex,", "the", "cardiac", "myxoma", "is", "a", "common", "co-morbidity.", "It", "occurs", "in", "multiples,", "during", "young", "age,", "regardless", "of", "gender", "and", "cardiac", "chamber", "and", "is", "known", "to", "recur", "frequently.", "Therefore", "there", "are", "high", "risks", "of", "adhesion", "and", "massive", "bleeding", "due", "to", "repeated", "surgeries.", "Such", "surgical", "risks", "account", "for", "over", "50%", "of", "disease-specific", "mortality", "of", "Carney", "complex", "patients.", "Here,", "we", "present", "anesthetic", "experiences", "of", "myxoma", "removal", "surgery", "in", "two", "patients", "with", "Carney", "complex.", "(Korean", "J", "Anesthesiol", "2011;", "61:", "528-532)", "Key", "Words:", "Anesthesia,", "Carney", "complex,", "Myxoma.", "Carney", "complex", "is", "an", "autosomal", "dominant", "disorder", "that", "occurs", "due", "to", "a", "mutation", "in", "the", "gene", "subunit", "PRKAR1A,", "which", "encodes", "protein", "kinase", "A.", "Clinical", "features", "are", "multiple", "endo-", "crine", "tumor,", "skin", "tumor,", "pigmented", "skin", "lesions,", "myxomas,", "and", "schwannomas", "[1,2].", "Carney", "complex", "can", "cause", "multiple", "endocrine", "dysfunctions", "in", "the", "pituitary", "gland,", "thyroid", "gland,", "adrenal", "gland,", "and", "testicular", "gland", "and", "induce", "difficult", "airway", "from", "acromegaly", "[3,4]", "and", "hemodynamic", "instability", "from", "adrenal", "gland", "dysfunction", "[1,5,6].", "Cardiac", "myxomas", "are", "also", "commonly", "accompanied", "[1,7,8].", "There", "are", "increasing", "risks", "of", "cardiac", "blood", "flow", "obstruction,", "arrhythmia,", "embolization,", "and", "sudden", "death", "depending", "on", "the", "size", "and", "location", "of", "the", "myxoma", "[7-9].", "Compared", "to", "general", "myxomas,", "this", "differs", "by", "having", "no", "link", "to", "sex", "or", "cardiac", "chambers,", "usually", "appearing", "during", "younger", "age", "and", "in", "multiple,", "with", "frequent", "relapses", "and", "a", "tendency", "to", "increase", "rapidly", "in", "size", "[7,8].", "Thus", "most", "cases", "require", "immediate", "surgical", "treatment", "after", "diagnosis,", "which", "has", "led", "to", "high", "risks", "of", "adhesion", "and", "massive", "bleeding", "due", "to", "repeated", "surgeries,", "and", "such", "surgical", "risks", "account", "for", "over", "50%", "of", "disease-specific", "mortality", "of", "Carney", "complex", "patients", "[1,2].", "The", "authors", "present", "the", "anesthetic", "experiences", "of", "cardiac", "myxoma", "removal", "of", "two", "Carney", "complex", "patients", "with", "multiple", "endocrine", "tumors", "and", "multiple", "cardiac", "myxomas.", "Received:", "April", "28,", "2011.", "Revised:", "1st,", "July", "8,", "2011;", "2nd,", "July", "19,", "2011.", "Accepted:", "July", "19,", "2011.", "Corresponding", "author:", "Yoon", "Hee", "Kim,", "M.D.,", "Department", "of", "Anesthesiology", "and", "Pain", "Medicine,", "College", "of", "Medicine,", "Chungnam", "National", "University,", "33,", "Munhwaro,", "Jung-gu,", "Daejeon", "301-721,", "Korea.", "Tel:", "82-42-280-7840,", "Fax:", "82-42-280-7968,", "E-mail:", "yhkim0404@cnu.ac.kr", "CC", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://", "creativecommons.org/licenses/by-nc/3.0/),", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Copyright", "ⓒ", "the", "Korean", "Society", "of", "Anesthesiologists,", "2011", "www.ekja.org" ]

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[ "International", "Journal", "for", "Equity", "in", "Health", "Research", "Exploring", "the", "equity", "of", "GP", "practice", "prescribing", "rates", "for", "selected", "coronary", "heart", "disease", "drugs:", "a", "multiple", "regression", "analysis", "with", "proxies", "of", "healthcare", "need", "Paul", "R", "Ward*1,", "Peter", "R", "Noyce2", "and", "Antony", "S", "St", "Leger3", "BioMed", "Central", "Open", "Access", "Address:", "1Section", "of", "Public", "Health,", "School", "of", "Health", "and", "Related", "Research", "(ScHARR),", "University", "of", "Sheffield,", "Sheffield,", "UK,", "2School", "of", "Pharmacy", "and", "Pharmaceutical", "Sciences,", "University", "of", "Manchester,", "Manchester,", "UK", "and", "3Evidence", "for", "Population", "Health", "Unit,", "School", "of", "Epidemiology", "and", "Health", "Sciences,", "University", "of", "Manchester,", "Manchester,", "UK", "Email:", "Paul", "R", "Ward*", "-", "p.r.ward@sheffield.ac.uk;", "Peter", "R", "Noyce", "-", "peter.noyce@man.ac.uk;", "Antony", "S", "St", "Leger", "-", "selwyn.st.leger@man.ac.uk", "*", "Corresponding", "author", "Published:", "08", "February", "2005", "International", "Journal", "for", "Equity", "in", "Health", "2005,", "4:3", "doi:10.1186/1475-9276-4-3", "This", "article", "is", "available", "from:", "http://www.equityhealthj.com/content/4/1/3", "Received:", "13", "July", "2004", "Accepted:", "08", "February", "2005", "©", "2005", "Ward", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "There", "is", "a", "small,", "but", "growing", "body", "of", "literature", "highlighting", "inequities", "in", "GP", "practice", "prescribing", "rates", "for", "many", "drug", "therapies.", "The", "aim", "of", "this", "paper", "is", "to", "further", "explore", "the", "equity", "of", "prescribing", "for", "five", "major", "CHD", "drug", "groups", "and", "to", "explain", "the", "amount", "of", "variation", "in", "GP", "practice", "prescribing", "rates", "that", "can", "be", "explained", "by", "a", "range", "of", "healthcare", "needs", "indicators", "(HCNIs).", "Methods:", "The", "study", "involved", "a", "cross-sectional", "secondary", "analysis", "in", "four", "primary", "care", "trusts", "(PCTs", "1–4)", "in", "the", "North", "West", "of", "England,", "including", "132", "GP", "practices.", "Prescribing", "rates", "(average", "daily", "quantities", "per", "registered", "patient", "aged", "over", "35", "years)", "and", "HCNIs", "were", "developed", "for", "all", "GP", "practices.", "Analysis", "was", "undertaken", "using", "multiple", "linear", "regression.", "Results:", "Between", "22–25%", "of", "the", "variation", "in", "prescribing", "rates", "for", "statins,", "beta-blockers", "and", "bendrofluazide", "was", "explained", "in", "the", "multiple", "regression", "models.", "Slightly", "more", "variation", "was", "explained", "for", "ACE", "inhibitors", "(31.6%)", "and", "considerably", "more", "for", "aspirin", "(51.2%).", "Prescribing", "rates", "were", "positively", "associated", "with", "CHD", "hospital", "diagnoses", "and", "procedures", "for", "all", "drug", "groups", "other", "than", "ACE", "inhibitors.", "The", "proportion", "of", "patients", "aged", "55–74", "years", "was", "positively", "related", "to", "all", "prescribing", "rates", "other", "than", "aspirin,", "where", "they", "were", "positively", "related", "to", "the", "proportion", "of", "patients", "aged", ">75", "years.", "However,", "prescribing", "rates", "for", "statins", "and", "ACE", "inhibitors", "were", "negatively", "associated", "with", "the", "proportion", "of", "patients", "aged", ">75", "years", "in", "addition", "to", "the", "proportion", "of", "patients", "from", "minority", "ethnic", "groups.", "Prescribing", "rates", "for", "aspirin,", "bendrofluazide", "and", "all", "CHD", "drugs", "combined", "were", "negatively", "associated", "with", "deprivation.", "Conclusion:", "Although", "around", "25–50%", "of", "the", "variation", "in", "prescribing", "rates", "was", "explained", "by", "HCNIs,", "this", "varied", "markedly", "between", "PCTs", "and", "drug", "groups.", "Prescribing", "rates", "were", "generally", "characterised", "by", "both", "positive", "and", "negative", "associations", "with", "HCNIs,", "suggesting", "possible", "inequities", "in", "prescribing", "rates", "on", "the", "basis", "of", "ethnicity,", "deprivation", "and", "the", "proportion", "of", "patients", "aged", "over", "75", "years", "(for", "statins", "and", "ACE", "inhibitors,", "but", "not", "for", "aspirin).", "Page", "1", "of", "11", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Tonini", "et", "al.", "Journal", "of", "Occupational", "Medicine", "and", "Toxicology", "2011,", "6:29", "http://www.occup-med.com/content/6/1/29", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "Work-related", "stress", "and", "bullying:", "gender", "differences", "and", "forensic", "medicine", "issues", "in", "the", "diagnostic", "procedure", "Stefano", "Tonini1,2*,", "Andrea", "Lanfranco1,2,", "Antonio", "Dellabianca1,", "Diego", "Lumelli1,2,", "Ines", "Giorgi3,", "Fulvio", "Mazzacane4,", "Camilla", "Fusi5,", "Fabrizio", "Scafa1,2", "and", "Stefano", "M", "Candura1,2", "Abstract", "Background:", "The", "attention", "of", "international", "agencies", "and", "scientific", "community", "on", "bullying", "and", "work-related", "stress", "is", "increasing.", "This", "study", "describes", "the", "gender", "differences", "found", "in", "victims", "of", "bullying", "and", "work-related", "stress", "in", "an", "Italian", "case", "series", "and", "analyzes", "the", "critical", "issues", "in", "the", "diagnostic", "workup.", "Methods:", "Between", "2001", "and", "2009", "we", "examined", "345", "outpatients", "(148", "males,", "197", "females;", "mean", "age:", "41", "±", "10.49)", "for", "suspected", "psychopathological", "work-related", "problems.", "Diagnosis", "of", "bullying", "was", "established", "using", "international", "criteria", "(ICD-10", "and", "DSM-IV).", "Results:", "After", "interdisciplinary", "diagnostic", "evaluation", "(Occupational", "Medicine", "Unit,", "Psychology", "and", "Psychiatry", "Service),", "the", "diagnosis", "of", "bullying", "was", "formulated", "in", "35", "subjects,", "12", "males", "and", "23", "females", "(2", "cases", "of", "Post-", "Traumatic", "Stress", "Disorder", "and", "33", "of", "Adjustment", "Disorder).", "Fifty-four", "(20", "males,", "34", "females)", "suffered", "from", "work-", "related", "anxiety,", "while", "work-unrelated", "Adjustment", "Disorder", "and", "other", "psychiatric", "disorders", "were", "diagnosed", "in", "7", "and", "112", "subjects,", "respectively.", "Women", "between", "34", "and", "45", "years", "showed", "a", "high", "prevalence", "(65%)", "of", "“mobbing", "syndrome”", "or", "other", "work-related", "stress", "disorders.", "Conclusions:", "At", "work,", "women", "are", "more", "subject", "to", "harassment", "(for", "personal", "aspects", "related", "to", "emotional", "and", "relational", "factors)", "than", "men.", "The", "knowledge", "of", "the", "phenomenon", "is", "an", "essential", "requisite", "to", "contrast", "bullying;", "prevention", "can", "be", "carried", "out", "only", "through", "effective", "information", "and", "training", "of", "workers", "and", "employers,", "who", "have", "the", "legal", "obligation", "to", "preserve", "the", "integrity", "of", "the", "mental", "and", "physical", "status", "of", "their", "employees", "during", "work.", "Keywords:", "psychosocial", "risk,", "mobbing,", "women’s", "work,", "risk", "evaluation", "Background", "Few", "studies", "about", "gender", "differences", "in", "bullying", "have", "been", "carried", "out,", "despite", "the", "increasing", "attention", "of", "Institutions", "and", "the", "international", "scientific", "community.", "This", "study", "describes", "gender", "differences", "in", "the", "victims", "of", "bullying", "and", "work-related", "stress", "examined", "in", "the", "Occu-", "pational", "Medicine", "Unit", "of", "our", "Institute,", "and", "analyzes,", "from", "a", "forensic", "point", "of", "view,", "the", "critical", "issues", "still", "pre-", "sent", "in", "the", "diagnostic", "workup.", "So", "far,", "the", "“mobbing", "syndrome”", "does", "not", "have", "a", "clear", "nosological", "definition.", "The", "ICD-10", "(International", "*", "Correspondence:", "stefano.tonini23@libero.it", "1Department", "of", "Public", "Health", "and", "Neuroscience,", "University", "of", "Pavia,", "Pavia,", "Italy", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "Classification", "of", "Disease)", "and", "DSM-IV", "(Diagnostical", "and", "Statistical", "Manual", "of", "Mental", "Disorders)", "indicate", "two", "conditions,", "not", "necessarily", "work-related,", "that", "are", "directly", "related", "to", "stress:", "1)", "the", "Post-Traumatic", "Stress", "Disorder", "(PTSD),", "characterized", "by", "behaviors", "aimed", "at", "avoiding", "any", "situation", "that", "reminds", "a", "certain", "problem,", "obsessive", "thinking", "about", "work", "issues,", "alertness", "and", "anxiety;", "and", "2)", "the", "Adjustment", "Disorder", "(AD),", "with", "risk", "factors", "and", "clinical", "features", "similar", "to", "PTSD,", "but", "of", "less", "intensity", "and", "severity.", "These", "are", "also", "the", "only", "recognized", "nosolo-", "gical", "entities", "by", "the", "Italian", "workers", "compensation", "system.", "Recently,", "attention", "to", "gender", "differences", "in", "employ-", "ment", "is", "gradually", "increasing", "from", "a", "sectorial", "knowledge,", "©", "2011", "Tonini", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Hindawi", "Publishing", "Corporation", "Case", "Reports", "in", "Dentistry", "Volume", "2012,", "Article", "ID", "327812,", "4", "pages", "doi:10.1155/2012/327812", "Case", "Report", "An", "Innovative", "Approach", "for", "Management", "of", "Vertical", "Coronal", "Fracture", "in", "Molar:", "Case", "Report", "Ambica", "Kathuria,1", "M.", "Kavitha,2", "and", "P.", "Ravishankar3", "1", "Maulana", "Azad", "Institute", "of", "Dental", "Sciences,", "MAMC", "Complex,", "Bahadur", "Shah", "Zafar", "Marg,", "New", "Delhi", "110002,", "India", "2", "Tamilnadu", "Goverment", "Dental", "College", "and", "Hospital,", "Near", "Chennai", "Fort,", "Chennai", "600003,", "India", "3", "Thai", "Mooghambigai", "Dental", "College,", "Chennai,", "Tamilnadu,", "India", "Correspondence", "should", "be", "addressed", "to", "Ambica", "Kathuria,", "dr", "ambics@yahoo.com", "Received", "24", "October", "2011;", "Accepted", "17", "November", "2011", "Academic", "Editors:", "L.", "Junquera", "and", "K.", "Yamazaki", "Copyright", "©", "2012", "Ambica", "Kathuria", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Unlike", "anterior", "teeth,", "acute", "exogenous", "trauma", "is", "an", "infrequent", "cause", "of", "posterior", "coronal", "vertical", "tooth", "fractures.", "Endodontic", "and", "restorative", "management", "of", "such", "fractures", "is", "a", "great", "challenge", "for", "the", "clinician.", "Newer", "advancements", "in", "adhesive", "techniques", "can", "provide", "successful", "intracoronal", "splinting", "of", "such", "teeth", "to", "reinforce", "the", "remaining", "tooth", "structure.", "This", "paper", "describes", "the", "diagnosis", "and", "management", "of", "a", "case", "of", "complicated", "vertical", "coronal", "fracture", "in", "mandibular", "first", "molar", "induced", "by", "a", "traffic", "accident.", "1.", "Introduction", "Coronal", "fractures", "of", "posterior", "teeth", "usually", "occur", "due", "to", "chronic", "masticatory", "trauma", "presence", "of", "large", "restorations", "or", "unrestored", "endodontically", "treated", "teeth", "[1,", "2]", "and", "rarely", "due", "to", "acute", "trauma.", "If", "a", "visible", "separation", "occurs", "at", "the", "interface", "of", "segments", "along", "the", "line", "of", "fracture,", "such", "fractures", "are", "termed", "as", "“complete”", "as", "coined", "by", "Luebke", "[3].", "The", "fracture", "commences", "in", "the", "crown", "and", "generally", "terminates", "near", "the", "cementoenamel", "junction", "or", "may", "extend", "apically", "into", "the", "root.", "Coronal", "fractures", "often", "involve", "a", "marginal", "ridge", "with", "the", "fracture", "extending", "in", "a", "mesiodistal", "direction.", "There", "is", "relatively", "scarce", "research", "on", "vertical", "tooth", "frac-", "tures,", "and", "several", "doubts", "still", "persist", "regarding", "their", "diagnosis", "and", "treatment.", "Management", "of", "such", "teeth", "should", "involve", "recognition", "of", "signs", "and", "symptoms", "and", "the", "provision", "of", "adequate", "restorations", "that", "protect", "the", "remaining", "tooth", "struc-", "ture", "[4].", "This", "paper", "attempts", "to", "highlight", "an", "innovative", "approach", "for", "the", "management", "of", "fractured", "fragments", "and", "preservation", "of", "remaining", "tooth", "structure", "in", "a", "case", "of", "posterior", "vertical", "coronal", "tooth", "fracture.", "Orthodontic", "wires", "and", "fiber-rein-", "forced", "composites", "have", "been", "suggested", "as", "means", "for", "addi-", "tional", "splinting", "of", "fractured", "segments.", "2.", "Case", "history", "A", "35-year-old", "male", "patient", "presented", "with", "the", "complaint", "of", "pain", "in", "the", "lower", "right", "posterior", "tooth", "region", "for", "three", "days,", "after", "he", "met", "with", "a", "traffic", "accident.", "Examination", "re-", "vealed", "a", "vertical", "fracture", "in", "crown", "of", "right", "mandibular", "first", "molar", "with", "pulpal", "exposure", "(Figure", "1).", "The", "fracture", "line", "was", "seen", "to", "extend", "mesiodistally", "more", "towards", "the", "mesiolingual", "aspect.", "Although", "the", "fragments", "were", "intact", "and", "undisplaced,", "wedging", "with", "a", "probe", "resulted", "in", "slight", "movement", "of", "the", "lingual", "segment", "indicating", "a", "complete", "fracture.", "All", "the", "tooth", "surfaces", "were", "carefully", "checked", "in", "dry", "field", "for", "presence", "of", "other", "cracks", "or", "craze", "lines.", "Gingiva", "around", "the", "tooth", "was", "palpated", "to", "check", "for", "possible", "evidence", "of", "an", "underlying", "dehiscence", "or", "fenestration", "to", "rule", "out", "vertical", "root", "fracture.", "Radiographs", "were", "taken", "at", "different", "horizontal", "angula-", "tions.", "Fractured", "fragments", "were", "seen", "to", "be", "separated", "by", "a", "narrow", "radiolucent", "line", "extending", "to", "the", "CEJ", "(Figure", "1).", "Hence", "the", "case", "was", "diagnosed", "as", "a", "vertical", "coronal", "fracture", "running", "mesiodistally", "into", "the", "dentin", "and", "pulp", "but", "confined", "to", "the", "crown", "of", "the", "tooth.", "The", "tooth", "was", "immediately", "adjusted", "out", "of", "occlusion.", "A", "preformed", "orthodontic", "stainless", "steel", "molar", "band", "(Ortho", "organizers,", "CA,", "USA)", "was", "cemented", "around", "the", "tooth", "to" ]

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[ "Rizzo", "et", "al.", "Nutrition", "Journal", "2012,", "11:82", "http://www.nutritionj.com/content/11/1/82", "R", "E", "S", "E", "A", "R", "C", "H", "Comparison", "between", "the", "AA/EPA", "ratio", "in", "depressed", "and", "non", "depressed", "elderly", "females:", "omega-3", "fatty", "acid", "supplementation", "correlates", "with", "improved", "symptoms", "but", "does", "not", "change", "immunological", "parameters", "Angela", "Maria", "Rizzo1*,", "Paola", "Antonia", "Corsetto1,", "Gigliola", "Montorfano1,", "Annalisa", "Opizzi2,", "Milena", "Faliva2,", "Attilio", "Giacosa3,", "Giovanni", "Ricevuti4,", "Claudio", "Pelucchi5,", "Bruno", "Berra1", "and", "Mariangela", "Rondanelli2", "Abstract", "Background:", "Depression", "is", "one", "of", "the", "most", "frequently", "missed", "diagnoses", "in", "elderly", "people,", "with", "obvious", "negative", "effects", "on", "quality", "of", "life.", "Various", "studies", "have", "shown", "that", "long", "chain", "omega-3", "polyunsaturated", "fatty", "acids", "(n-3", "PUFA)", "may", "be", "useful", "in", "its", "management.", "Our", "objective", "was", "to", "evaluate", "whether", "a", "supplement", "containing", "n-3", "PUFA", "improves", "depressive", "symptoms", "in", "depressed", "elderly", "patients,", "and", "whether", "the", "blood", "fatty", "acid", "pattern", "is", "correlated", "with", "these", "changes.", "Methods:", "The", "severity", "of", "depressive", "symptoms", "according", "to", "the", "Geriatric", "Depression", "Scale", "(GDS),", "blood", "fatty", "acid", "composition", "and", "erythrocyte", "phospholipids", "were", "analyzed", "in", "46", "depressed", "females", "aged", "66-95y,", "diagnosed", "with", "depression", "according", "to", "DSMIV,", "within", "the", "context", "of", "a", "randomized,", "double-blind,", "placebo-controlled", "trial.", "22", "depressed", "females", "were", "included", "in", "the", "intervention", "group", "(2.5", "g/day", "of", "n-3", "PUFA", "for", "8", "weeks),", "and", "24", "in", "the", "placebo", "group.", "We", "also", "measured", "immunological", "parameters", "(CD2,", "CD3,", "CD4,", "CD8,", "CD16,", "CD19", "and", "cytokines", "(IL-5,", "IL-15).", "Results:", "The", "mean", "GDS", "score", "and", "AA/EPA", "ratio,", "in", "whole", "blood", "and", "RBC", "membrane", "phospholipids,", "were", "significantly", "lower", "after", "2", "months", "supplementation", "with", "n-3", "PUFA.", "A", "significant", "correlation", "between", "the", "amelioration", "of", "GDS", "and", "the", "AA/EPA", "ratio", "with", "some", "immunological", "parameters,", "such", "as", "CD2,", "CD19,", "CD4,", "CD16", "and", "the", "ratio", "CD4/CD8,", "was", "also", "found.", "Nevertheless,", "omega-3", "supplementation", "did", "not", "significantly", "improve", "the", "studied", "immunological", "functions.", "Conclusions:", "n-3", "PUFA", "supplementation", "ameliorates", "symptoms", "in", "elderly", "depression.", "The", "n-3", "PUFA", "status", "may", "be", "monitored", "by", "means", "of", "the", "determination", "of", "whole", "blood", "AA/EPA", "ratio.", "Keywords:", "Omega-3", "long", "chain", "polyunsaturated", "fatty", "acids,", "Depressed", "mood,", "Elderly,", "AA/EPA,", "Cell", "membrane,", "Phospholipids,", "EPA,", "DHA", "Open", "Access", "*", "Correspondence:", "angelamaria.rizzo@unimi.it", "1Dipartimento", "di", "Scienze", "Farmacologiche", "e", "Biomolecolari,", "Università", "degli", "Studi", "di", "Milano,", "Via", "D.", "Trentacoste", "2,", "Milan", "20134,", "Italy", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "©", "2012", "Rizzo", "et", "al.;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "J", "Orthopaed", "Traumatol", "(2011)", "12:131–136", "DOI", "10.1007/s10195-011-0142-2", "O", "R", "I", "G", "I", "N", "A", "L", "A", "R", "T", "I", "C", "L", "E", "Cemented", "fixed-bearing", "PFC", "total", "knee", "arthroplasty:", "survival", "and", "failure", "analysis", "at", "12–17", "years", "A.", "Bistolfi", "•", "G.", "Massazza", "•", "F.", "Rosso", "•", "D.", "Deledda", "•", "V.", "Gaito", "•", "F.", "Lagalla", "•", "C.", "Olivero", "•", "M.", "Crova", "Received:", "7", "March", "2011", "/", "Accepted:", "25", "May", "2011", "/", "Published", "online:", "23", "June", "2011", "The", "Author(s)", "2011.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "Background", "Total", "knee", "arthroplasty", "(TKA)", "is", "the", "appropriate", "treatment", "for", "degenerative", "pathology", "of", "the", "knee.", "Implant", "surveillance", "is", "mandatory", "to", "improve", "clinical", "results.", "We", "present", "the", "long-term", "results", "of", "a", "series", "of", "consecutive", "TKA", "Press", "Fit", "Condylar", "(J&J),", "cemented", "fixed", "bearing", "with", "selective", "patellar", "resurfacing", "in", "nonselected", "patients.", "Materials", "and", "methods", "In", "this", "prospective", "case", "series,", "223", "TKA", "were", "clinically", "and", "radiographically", "evaluated", "using", "the", "Hospital", "for", "Special", "Surgery", "(HSS)", "knee", "score", "and", "the", "Knee", "Society", "Roentgenographic", "Evaluation", "and", "Scoring", "System.", "Results", "There", "were", "197", "patients,", "with", "an", "average", "age", "of", "68.4", "years", "[95%", "confidence", "interval", "(CI)", "52.7–84.1", "years];", "49", "arthroplasties", "were", "implanted", "in", "men", "(21.1%)", "and", "184", "(78.9%)", "in", "women.", "The", "average", "follow-up", "was", "approxi-", "mately", "13.5", "years", "(162.1", "months;", "95%", "CI", "132.3–191.9),", "and", "it", "was", "possible", "to", "evaluate", "179", "implants", "(76.8%", "of", "the", "implanted", "prosthesis)", "in", "176", "patients.", "The", "average", "HSS", "score", "increased", "from", "61.5", "(95%", "CI", "60.4–62.7)", "to", "89.4", "(95%", "CI", "87.7–.93.5)", "points.", "The", "cumulative", "average", "sur-", "vival", "rate", "at", "15", "years", "(the", "endpoint", "being", "failure", "with", "A.", "Bistolfi", "G.", "Massazza", "F.", "Lagalla", "C.", "Olivero", "M.", "Crova", "Department", "of", "Orthopedics", "and", "Traumatology,", "CTO/M.", "Adelaide", "Hospital,", "Turin,", "Italy", "A.", "Bistolfi", "G.", "Massazza", "F.", "Rosso", "D.", "Deledda", "V.", "Gaito", "M.", "Crova", "Department", "of", "Orthopedics", "and", "Traumatology,", "University", "of", "the", "Studies", "of", "Turin,", "Turin,", "Italy", "A.", "Bistolfi", "(&)", "c/o", "AO", "CTO/M.", "Adelaide,", "Via", "Zuretti", "29,", "10126", "Turin,", "Italy", "e-mail:", "alessandro.bistolfi@cto.to.it", "revision)", "was", "90.6%", "±", "2%", "standard", "deviation.", "Resurfac-", "ing", "the", "patella", "did", "not", "make", "a", "difference", "in", "terms", "of", "implant", "survival.", "Progressive", "radiolucent", "lines", "were", "observed", "around", "20", "implants", "(14.3%);", "all", "were", "revised.", "Conclusions", "The", "PFC", "system", "is", "an", "excellent", "prosthetic", "solution.", "Early", "clinical", "complications,", "mechanical", "axis", "and", "patellar", "resurfacing", "do", "not", "correlate", "with", "implant", "failure,", "whereas", "progressive", "radiolucent", "lines", "do.", "Keywords", "Total", "knee", "arthroplasty", "Failure", "analysis", "Long-term", "survival", "Introduction", "Total", "knee", "arthroplasty", "(TKA)", "is", "the", "appropriate", "treatment", "for", "degenerative", "pathology", "of", "the", "knee.", "Among", "many", "existing", "implants,", "the", "Press", "Fit", "Condylar", "(PFC)", "total", "knee", "prosthesis", "(Johnson", "&", "Johnson,", "Raynham,", "MA,", "USA)", "was", "introduced", "in", "the", "1980s", "to", "obtain", "a", "long-term,", "strong", "interface", "between", "prosthesis", "and", "bone.", "Despite", "the", "sub-", "sequent", "introduction", "of", "rotating", "and", "uncemented", "implants", "[1–3],", "the", "cemented", "models", "with", "a", "fixed", "bearing", "still", "rep-", "resent", "the", "gold", "standard,", "with", "good", "results", "and", "survival", "reported", "beyond", "10", "years", "[4,", "5].", "Nevertheless,", "the", "primary", "reason", "for", "TKA", "failure", "is", "still", "not", "clear,", "and", "several", "problems", "such", "as", "malalignment,", "wear,", "loosening,", "infec-", "tions,", "unexplainable", "persistent", "pain,", "etc.", "have", "been", "observed.", "In", "addition,", "it", "is", "still", "a", "subject", "of", "debate", "whether", "or", "not", "patella", "resurfacing", "should", "be", "performed.", "Therefore,", "long-term", "prospective", "surveillance", "of", "the", "implants", "and", "analysis", "of", "the", "causes", "of", "failure", "are", "still", "of", "interest", "to", "knee", "surgeons.", "In", "this", "study,", "we", "analysed", "a", "series", "of", "cemented", "TKA,", "with", "a", "fixed", "bearing", "and", "selective", "patellar", "resurfac-", "ing,", "in", "nonselected", "patients", "operated", "randomly", "by", "different", "123" ]

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[ "Sensors", "2012,", "12,", "5966-5977;", "doi:10.3390/s120505966", "OPEN", "ACCESS", "sensors", "ISSN", "1424-8220", "www.mdpi.com/journal/sensors", "Article", "Fusion-Triggered", "Switching", "of", "Enzymatic", "Activity", "on", "an", "Artificial", "Cell", "Membrane", "Masaru", "Mukai", "1,2,", "Yoshihiro", "Sasaki", "3,4", "and", "Jun-ichi", "Kikuchi", "1,*", "1", "Graduate", "School", "of", "Materials", "Science,", "Nara", "Institute", "of", "Science", "and", "Technology,", "8916-5", "Takayama,", "Ikoma,", "Nara", "630-0192,", "Japan", "2", "Nanotube", "Research", "Center,", "National", "Institute", "of", "Advanced", "Industrial", "Science", "and", "Technology,", "Tsukuba", "Central", "5,", "1-1-1", "Higashi,", "Tsukuba,", "Ibaraki", "305-8565,", "Japan;", "E-Mail:", "mukai-m@aist.go.jp", "3", "Institute", "of", "Biomaterials", "and", "Bioengineering,", "Tokyo", "Medical", "and", "Dental", "University,", "2-3-10", "Kanda-Surugadai,", "Chiyoda,", "Tokyo", "101-0062,", "Japan;", "E-Mail:", "ysasaki.org@tmd.ac.jp", "4", "PRESTO,", "Japan", "Science", "and", "Technology", "Agency,", "4-1-8", "Honcho", "Kawaguchi,", "Saitama", "332-0012,", "Japan", "*", "Author", "to", "whom", "correspondence", "should", "be", "addressed;", "E-Mail:", "jkikuchi@ms.naist.jp;", "Tel.:", "+81-743-726-090;", "Fax:", "+81-743-726-099.", "Received:", "14", "March", "2012;", "in", "revised", "form:", "13", "April", "2012", "/", "Accepted:", "3", "May", "2012", "/", "Published:", "9", "May", "2012", "Abstract:", "A", "nanosensory", "membrane", "device", "was", "constructed", "for", "detecting", "liposome", "fusion", "through", "changes", "in", "an", "enzymatic", "activity.", "Inspired", "by", "a", "biological", "signal", "transduction", "system,", "the", "device", "design", "involved", "functionalized", "liposomal", "membranes", "prepared", "by", "self-assembly", "of", "the", "following", "molecular", "components:", "a", "synthetic", "peptide", "lipid", "and", "a", "phospholipid", "as", "matrix", "membrane", "components,", "a", "Schiff’s", "base", "of", "pyridoxal", "5’-phosphate", "with", "phosphatidylethanolamine", "as", "a", "thermo-responsive", "artificial", "receptor,", "NADH-dependent", "L-lactate", "dehydrogenase", "as", "a", "signal", "amplifier,", "and", "Cu2+", "ion", "as", "a", "signal", "mediator", "between", "the", "receptor", "and", "enzyme.", "The", "enzymatic", "activity", "of", "the", "membrane", "device", "was", "adjustable", "by", "changing", "the", "matrix", "lipid", "composition,", "reflecting", "the", "thermotropic", "phase", "transition", "behavior", "of", "the", "lipid", "membranes,", "which", "in", "turn", "controlled", "receptor", "binding", "affinity", "toward", "the", "enzyme-inhibiting", "mediator", "species.", "When", "an", "effective", "fusogen", "anionic", "polymer", "was", "added", "to", "these", "cationic", "liposomes,", "membrane", "fusion", "occurred,", "and", "the", "functionalized", "liposomal", "membranes", "responded", "with", "changes", "in", "enzymatic", "activity,", "thus", "serving", "as", "an", "effective", "nanosensory", "device", "for", "liposome", "fusion", "detection." ]

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[ "R", "E", "V", "I", "E", "W", "Cardiometabolic", "aspects", "of", "polycystic", "ovarian", "syndrome", "Li", "Wei", "Cho1", "Harpal", "S", "Randeva2", "Stephen", "L", "Atkin1", "1Department", "of", "Medicine,", "University", "of", "Hull;", "2Metabolic", "Unit,", "University", "Hospitals", "Coventry", "&", "Warwickshire", "NHS", "Trust,", "UK", "Correspondence:", "Li", "Wei", "Cho", "Michael", "White", "Centre", "for", "Diabetes", "and", "Endocrinology,", "Hull", "Royal", "Infirmary,", "220-", "236", "Anlaby", "Road,", "Hull,", "HU3", "2RW,", "UK", "Tel", "+44", "1482", "675371", "Fax", "+44", "1482", "675395", "Email", "l.cho@hull.ac.uk", "Abstract:", "It", "is", "estimated", "that", "6%–7%", "of", "women", "of", "reproductive", "age", "have", "polycystic", "ovarian", "syndrome", "(PCOS).", "Women", "with", "this", "condition", "exhibit", "an", "adverse", "cardiovascular", "risk", "profile,", "characteristic", "of", "the", "cardiometabolic", "syndrome", "and", "given", "the", "high", "prevalence", "of", "PCOS", "in", "the", "female", "population,", "this", "condition", "may", "contribute", "towards", "the", "acceleration", "of", "cardiovascular", "disease", "among", "young", "women.", "This", "article", "summarizes", "the", "recent", "development", "and", "findings", "in", "the", "cardiometabolic", "abnormalities", "in", "patients", "with", "PCOS.", "Patients", "with", "PCOS", "have", "the", "clinical", "features", "of", "oligomenorrhoea,", "hirsutism", "and", "infertility;", "however,", "they", "also", "exhibit", "hyperinsu-", "linemia,", "obesity,", "hypertension,", "dyslipidemia,", "and", "an", "increased", "pro-thrombotic", "state.", "They", "have", "an", "increased", "risk", "of", "type", "2", "diabetes", "and", "impaired", "glucose", "tolerance,", "and", "sleep", "apnea", "is", "also", "found", "more", "commonly", "in", "this", "population.", "However,", "despite", "the", "presence", "of", "cardiovascular", "risk", "factors", "and", "increased", "surrogate", "markers", "of", "cardiovascular", "disease", "it", "is", "unclear", "if", "they", "have", "accelerated", "atherosclerosis.", "End", "point", "studies", "are", "currently", "lacking", "and", "the", "available", "evidence", "are", "conflicting.", "Adipose", "tissue", "has", "emerged", "as", "an", "important", "endocrine", "organ", "over", "the", "last", "decade", "and", "gained", "recognition", "in", "having", "an", "important", "role", "in", "the", "cardiometabolic", "syndrome.", "Adiponectin", "that", "is", "secreted", "exclusively", "by", "adipocytes", "has", "recently", "been", "recognized", "as", "an", "important", "marker", "of", "cardiometabolic", "syndrome,", "obesity,", "type", "2", "diabetes,", "and", "coronary", "artery", "disease.", "Other", "adipo-", "cytokines", "like", "leptin", "and", "resistin", "have", "also", "recently", "been", "recognized.", "This", "article", "will", "address", "the", "current", "evidence", "for", "the", "adverse", "cardiovascular", "risk", "in", "PCOS", "and", "the", "other", "factors", "that", "may", "be", "implicated.", "Finally", "the", "therapeutic", "options", "for", "treatment", "will", "be", "discussed.", "Keywords:", "cardiometabolic", "syndrome,", "polycystic", "ovarian", "syndrome,", "cardiovascular", "disease", "Introduction", "Polycystic", "ovarian", "syndrome", "(PCOS)", "is", "a", "common", "endocrine", "disorder", "affecting", "6%–7%", "of", "the", "population", "(Knochenhauer", "et", "al", "1998;", "Diamanti-Kandarakis", "et", "al", "1999;", "Asuncion", "et", "al", "2000;", "Azziz", "et", "al", "2004).", "It", "is", "characterized", "by", "chronic", "anovulation", "and", "hyperandrogenism", "with", "the", "clinical", "manifestation", "of", "oligomenorrhoea,", "hirsut-", "ism,", "and", "acne", "(Franks", "1995).", "In", "January", "2004,", "the", "European", "Society", "for", "Human", "Reproduction", "and", "Embryology", "(ESHRE)", "and", "the", "American", "Society", "for", "Reproductive", "Medicine", "(ASRM)", "co-sponsored", "the", "Rotterdam", "polycystic", "ovary", "syndrome", "consensus", "workshop", "that", "published", "diagnostic", "guidelines,", "building", "on", "the", "consensus", "statement", "of", "the", "National", "Institutes", "of", "Health", "1990", "(ESHRE/ASRM-Sponsored_PCOS_Con-", "sensus_Workshop_Group", "2004).", "The", "Rotterdam", "criteria", "for", "the", "diagnosis", "of", "PCOS", "states", "2", "of", "the", "3", "features", "needs", "to", "be", "present", "to", "make", "the", "diagnosis", "and", "with", "the", "exclu-", "sion", "of", "other", "etiologies", "(congenital", "adrenal", "hyperplasia,", "androgen-secreting", "tumors,", "Cushing’s", "syndrome).", "These", "features", "includes", "(1)", "Oligo-", "or", "anovulation", "(2)", "Clinical", "and/or", "biochemical", "signs", "of", "hyperandrogenism", "and", "(3)", "Polycystic", "ovaries", "(either", "12", "or", "more", "follicles", "measuring", "2–9", "mm", "in", "diameter,", "or", "an", "ovarian", "volume", "of", ">10", "cm3)", "(Balen", "et", "al", "2003).", "Vascular", "Health", "and", "Risk", "Management", "2007:3(1)", "55–63", "©", "2007", "Dove", "Medical", "Press", "Limited.", "All", "rights", "reserved", "55" ]

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"responsible", "for", "Alzheimer’s", "disease", "(AD).", "The", "bio-", "genesis", "and", "trafficking", "of", "this", "important", "enzyme", "in", "relation", "to", "aberrant", "Aβ", "processing", "is", "not", "well", "defined.", "Using", "a", "cell-", "free", "reaction", "to", "monitor", "the", "exit", "of", "cargo", "proteins", "from", "the", "endoplasmic", "reticulum", "(ER),", "we", "have", "isolated", "a", "transient", "intermediate", "of", "γ-secretase.", "Here,", "we", "provide", "direct", "evi-", "dence", "that", "the", "γ-secretase", "complex", "is", "formed", "in", "an", "in-", "active", "complex", "at", "or", "before", "the", "assembly", "of", "an", "ER", "transport", "vesicle", "dependent", "on", "the", "COPII", "sorting", "subunit,", "Sec24A.", "Maturation", "of", "the", "holoenzyme", "is", "achieved", "in", "a", "subsequent", "compartment.", "Two", "familial", "AD", "(FAD)–linked", "PS1", "variants", "are", "inefficiently", "packaged", "into", "transport", "vesicles", "generated", "from", "the", "ER.", "Our", "results", "suggest", "that", "aberrant", "trafficking", "of", "PS1", "may", "contribute", "to", "disease", "pathology.", "Introduction", "Alzheimer’s", "disease", "(AD)", "is", "a", "neurodegenerative", "disorder", "char-", "acterized", "by", "the", "presence", "of", "amyloid", "plaques", "and", "neurofibril-", "lary", "tangles", "in", "hippocampal", "regions", "of", "the", "brain.", "A", "major", "constituent", "of", "the", "amyloid", "plaque", "is", "a", "small", "Aβ", "peptide", "frag-", "ment", "derived", "from", "the", "β-amyloid", "precursor", "protein", "(APP).", "APP", "is", "cleaved", "along", "the", "secretory", "pathway", "by", "several", "proteases,", "two", "of", "which,", "the", "β-", "and", "γ-secretases,", "normally", "generate", "a", "40-amino", "acid", "long", "Aβ40", "peptide.", "Abnormal", "cleavage", "by", "γ-secretase", "yields", "an", "aggregation-prone", "42-amino", "acid", "long", "Aβ42", "peptide", "that", "builds", "up", "over", "time", "to", "form", "neuritic", "plaques.", "Mutations", "in", "APP", "and", "presenilin", "1", "and", "2", "(PS1", "and", "PS2)", "account", "for", "most", "of", "the", "familial", "forms", "of", "AD", "(FAD),", "which", "lead", "to", "early", "onset", "of", "the", "disease.", "These", "mutations", "either", "enhance", "the", "ratio", "of", "Aβ42/Aβ40", "or", "increase", "the", "level", "of", "both", "Aβ42", "and", "Aβ40", "without", "changing", "the", "ratio", "(for", "review", "see", "Walsh", "and", "Selkoe,", "2004).", "Presenilin", "(PS)", "is", "believed", "to", "be", "the", "catalytic", "subunit", "of", "γ-secretase.", "γ-Secretase", "is", "a", "multi-subunit", "protein", "complex", "whose", "minimal", "components", "are", "nicastrin", "(NCT),", "anterior", "pharynx-1", "(APH-1),", "presenilin", "enhancer-2", "(PEN-2),", "and", "PS", "(Yu", "et", "al.,", "2000;", "Correspondence", "to", "Randy", "W.", "Schekman:", "schekman@berkeley.edu", "J.", "Kim’s", "present", "address", "is", "Section", "of", "Genetics,", "Department", "of", "Pediatrics,", "M.I.N.D.", "Institute,", "University", "of", "California-Davis", "Medical", "Center,", "Sacramento,", "CA", "95817.", "Abbreviations", "used", "in", "this", "paper:", "APP,", "amyloid", "precursor", "protein;", "COPII,", "coat", "protein", "complex", "II;", "CTF,", "C-terminal", "fragment;", "ERGIC,", "ER-to-Golgi", "intermediate", "compartments;", "FAD,", "familial", "Alzheimer’s", "disease;", "FL,", "full", "length;", "NTF,", "N-terminal", "fragment;", "PS,", "presenilin;", "SIC,", "semi-intact", "cell;", "WT,", "wild", "type.", "The", "online", "version", "of", "this", "paper", "contains", "supplemental", "material.", "©", "The", "Rockefeller", "University", "Press", "$30.00", "The", "Journal", "of", "Cell", "Biology,", "Vol.", "179,", "No.", "5,", "December", "3,", "2007", "951–963", "http://www.jcb.org/cgi/doi/10.1083/jcb.200709012", "Francis", "et", "al.,", "2002;", "Goutte", "et", "al.,", "2002;", "LaVoie", "et", "al.,", "2003;", "Luo", "et", "al.,", "2003;", "Takasugi", "et", "al.,", "2003).", "Other", "possible", "regulatory", "components", "of", "γ-secretase,", "such", "as", "CD147", "and", "TMP21,", "have", "been", "reported", "(Zhou", "et", "al.,", "2005;", "Chen", "et", "al.,", "2006).", "Although", "not", "essential,", "these", "regulator", "proteins", "affect", "Aβ", "production.", "There-", "fore,", "the", "assembly", "and", "activation", "of", "γ-secretase", "may", "be", "linked", "to", "processing", "and", "misprocessing", "of", "APP.", "Early", "secretory", "compartments", "such", "as", "endoplasmic", "retic-", "ulum", "(ER),", "ER-Golgi", "intermediate", "compartment", "(ERGIC),", "and", "cis-Golgi", "play", "a", "critical", "role", "in", "the", "synthesis,", "assembly,", "and", "quality", "control", "inspection", "of", "multi-subunit", "membrane", "protein", "com-", "plexes", "(Ellgaard", "et", "al.,", "1999).", "In", "the", "case", "of", "γ-secretase,", "retrieval", "of", "unassembled", "Pen-2", "and", "NCT,", "subunits", "of", "γ-secretase,", "is", "regula-", "ted", "by", "Rer1", "at", "the", "cis-Golgi", "(Kaether", "et", "al.,", "2007;", "Spasic", "et", "al.,", "2007).", "Down-regulation", "of", "Rer1", "causes", "an", "increase", "of", "γ-secretase", "at", "cell", "surface.", "Thus,", "abnormal", "assembly", "and", "traffic", "of", "γ-secretase", "in", "the", "early", "secretory", "pathway", "may", "impact", "γ-secretase", "function", "in", "later", "compartments.", "Proteins", "traverse", "the", "secretory", "pathway", "in", "defined", "trans-", "port", "carriers,", "the", "first", "of", "which,", "COPII", "vesicles,", "conveys", "newly", "synthesized", "and", "assembled", "proteins", "from", "the", "ER", "to", "the", "ERGIC", "(Schekman", "and", "Orci,", "1996).", "However,", "because", "these", "COPII", "vesicles", "are", "transient,", "it", "is", "difficult", "to", "analyze", "the", "molecular", "characteristics", "of", "protein", "intermediates", "in", "cells.", "Such", "intermedi-", "ates", "may", "be", "evaluated", "by", "generating", "transport", "vesicles", "in", "vitro.", "We", "exploited", "a", "biochemical", "assay", "to", "monitor", "the", "export", "of", "γ-secretase", "components", "from", "the", "ER", "(Kim", "et", "al.,", "2005).", "JCB", "951" ]

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[ "BMC", "Microbiology", "Research", "article", "Blockade", "of", "catecholamine-induced", "growth", "by", "adrenergic", "and", "dopaminergic", "receptor", "antagonists", "in", "Escherichia", "coli", "O157:H7,", "Salmonella", "enterica", "and", "Yersinia", "enterocolitica", "Primrose", "PE", "Freestone1,", "Richard", "D", "Haigh1", "and", "Mark", "Lyte*2", "BioMed", "Central", "Open", "Access", "Address:", "1Department", "of", "Infection,", "Immunity", "and", "Inflammation,", "University", "of", "Leicester", "School", "of", "Medicine,", "Leicester,", "UK", "and", "2Department", "of", "Pharmacy", "Practice,", "School", "of", "Pharmacy,", "Texas", "Tech", "University", "Health", "Sciences", "Center,", "Lubbock,", "TX", "79430,", "USA", "Email:", "Primrose", "PE", "Freestone", "-", "ppef1@le.ac.uk;", "Richard", "D", "Haigh", "-", "rxh@le.ac.uk;", "Mark", "Lyte*", "-", "mark.lyte@ttuhsc.edu", "*", "Corresponding", "author", "Published:", "30", "January", "2007", "BMC", "Microbiology", "2007,", "7:8", "doi:10.1186/1471-2180-7-8", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2180/7/8", "Received:", "11", "October", "2006", "Accepted:", "30", "January", "2007", "©", "2007", "Freestone", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "The", "ability", "of", "catecholamines", "to", "stimulate", "bacterial", "growth", "was", "first", "demonstrated", "just", "over", "a", "decade", "ago.", "Little", "is", "still", "known", "however,", "concerning", "the", "nature", "of", "the", "putative", "bacterial", "adrenergic", "and/or", "dopaminergic", "receptor(s)", "to", "which", "catecholamines", "(norepinephrine,", "epinephrine", "and", "dopamine)", "may", "bind", "and", "exert", "their", "effects,", "or", "even", "whether", "the", "binding", "properties", "of", "such", "a", "receptor", "are", "similar", "between", "different", "species.", "Results:", "Use", "of", "specific", "catecholamine", "receptor", "antagonists", "revealed", "that", "only", "α,", "and", "not", "β,", "adrenergic", "antagonists", "were", "capable", "of", "blocking", "norepinephrine", "and", "epinephrine-induced", "growth,", "while", "antagonism", "of", "dopamine-mediated", "growth", "was", "achieved", "with", "the", "use", "of", "a", "dopaminergic", "antagonist.", "Both", "adrenergic", "and", "dopaminergic", "antagonists", "were", "highly", "specific", "in", "their", "mechanism", "of", "action,", "which", "did", "not", "involve", "blockade", "of", "catecholamine-facilitated", "iron-acquisition.", "Use", "of", "radiolabeled", "norepinephrine", "suggested", "that", "the", "adrenergic", "antagonists", "could", "be", "acting", "by", "inhibiting", "catecholamine", "uptake.", "Conclusion:", "The", "present", "data", "demonstrates", "that", "the", "ability", "of", "a", "specific", "pathogen", "to", "respond", "to", "a", "particular", "hormone", "is", "dependent", "upon", "the", "host", "anatomical", "region", "in", "which", "the", "pathogen", "causes", "disease", "as", "well", "as", "the", "neuroanatomical", "specificity", "to", "which", "production", "of", "the", "particular", "hormone", "is", "restricted;", "and", "that", "both", "are", "anatomically", "coincidental", "to", "each", "other.", "As", "such,", "the", "present", "report", "suggests", "that", "pathogens", "with", "a", "high", "degree", "of", "exclusivity", "to", "the", "gastrointestinal", "tract", "have", "evolved", "response", "systems", "to", "neuroendocrine", "hormones", "such", "as", "norepinephrine", "and", "dopamine,", "but", "not", "epinephrine,", "which", "are", "found", "with", "the", "enteric", "nervous", "system.", "Background", "During", "the", "past", "decade,", "there", "has", "been", "increasing", "recogni-", "tion", "that", "microorganisms", "can", "actively", "respond", "to", "the", "host's", "neurophysiological", "hormonal", "output", "through", "the", "utilization", "of", "neuroendocrine", "hormones", "as", "environmen-", "tal", "cues", "to", "initiate", "growth", "and", "pathogenic", "processes", "[1,2].", "The", "study", "of", "such", "microbial-neuroendocrine", "hormone", "interaction", "has", "been", "termed", "microbial", "endocrinology", "[1,2].", "To", "date,", "the", "most", "studied", "neuroendocrine", "hormo-", "nal", "family", "from", "a", "microbial", "endocrinology", "perspective", "has", "been", "the", "catecholamines", "due", "to", "their", "central", "role", "in", "stress-mediated", "phenomena", "such", "as", "traumatic", "injury", "Page", "1", "of", "13", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Meningococcal", "Outer", "Membrane", "Protein", "NhhA", "Triggers", "Apoptosis", "in", "Macrophages", "Mikael", "Sjo¨", "linder1,", "Georg", "Altenbacher1,", "Matthias", "Hagner1,", "Wei", "Sun2,", "Sophia", "Schedin-Weiss2¤,", "Hong", "Sjo¨", "linder1*", "1", "Department", "of", "Genetics,", "Microbiology", "and", "Toxicology,", "Stockholm", "University,", "Stockholm,", "Sweden,", "2", "Department", "of", "Medical", "Biochemistry", "and", "Microbiology,", "Uppsala", "Biomedical", "Centre,", "Uppsala", "University,", "Uppsala,", "Sweden", "Abstract", "Phagocytotic", "cells", "play", "a", "fundamental", "role", "in", "the", "defense", "against", "bacterial", "pathogens.", "One", "mechanism", "whereby", "bacteria", "evade", "phagocytosis", "is", "to", "produce", "factors", "that", "trigger", "apoptosis.", "Here", "we", "identify", "for", "the", "first", "time", "a", "meningococcal", "protein", "capable", "of", "inducing", "macrophage", "apoptosis.", "The", "conserved", "meningococcal", "outer", "membrane", "protein", "NhhA", "(Neisseria", "hia/hsf", "homologue", "A,", "also", "known", "as", "Hsf)", "mediates", "bacterial", "adhesion", "and", "interacts", "with", "extracellular", "matrix", "components", "heparan", "sulphate", "and", "laminin.", "Meningococci", "lacking", "NhhA", "fail", "to", "colonise", "nasal", "mucosa", "in", "a", "mouse", "model", "of", "meningococcal", "disease.", "We", "found", "that", "exposure", "of", "macrophages", "to", "NhhA", "resulted", "in", "a", "highly", "increased", "rate", "of", "apoptosis", "that", "proceeded", "through", "caspase", "activation.", "Exposure", "of", "macrophages", "to", "NhhA", "also", "led", "to", "iNOS", "induction", "and", "nitric", "oxide", "production.", "However,", "neither", "nitric", "oxide", "production", "nor", "TNF-a", "signaling", "was", "found", "to", "be", "a", "prerequisite", "for", "NhhA-induced", "apoptosis.", "Macrophages", "exposed", "to", "wildtype", "NhhA-expressing", "meningococci", "were", "also", "found", "to", "undergo", "apoptosis", "whereas", "NhhA-", "deficient", "meningococci", "had", "a", "markedly", "decreased", "capacity", "to", "induce", "macrophage", "apoptosis.", "These", "data", "provide", "new", "insights", "on", "the", "role", "of", "NhhA", "in", "meningococcal", "disease.", "NhhA-induced", "macrophage", "apoptosis", "could", "be", "a", "mechanism", "whereby", "meningococci", "evade", "immunoregulatory", "and", "phagocytotic", "actions", "of", "macrophages.", "Citation:", "Sjo¨", "linder", "M,", "Altenbacher", "G,", "Hagner", "M,", "Sun", "W,", "Schedin-Weiss", "S,", "et", "al.", "(2012)", "Meningococcal", "Outer", "Membrane", "Protein", "NhhA", "Triggers", "Apoptosis", "in", "Macrophages.", "PLoS", "ONE", "7(1):", "e29586.", "doi:10.1371/journal.pone.0029586", "Editor:", "Ray", "Borrow,", "Health", "Protection", "Agency,", "United", "Kingdom", "Received", "July", "1,", "2011;", "Accepted", "December", "1,", "2011;", "Published", "January", "4,", "2012", "Copyright:", "2012", "Sjo¨", "linder", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "was", "supported", "by", "the", "Swedish", "Research", "Council", "(Grant", "no.", "2008-2572,", "2008-3367,", "www.vr.se),", "the", "Swedish", "Society", "of", "Medicine", "(www.sls.se),", "the", "Magnus", "Bergvalls", "Foundation", "(http://www.magnbergvallsstiftelse.nu),", "the", "Harald", "Jeanssons", "Foundation", "(http://www.jeanssonsstiftelser.se),", "the", "Tore", "Nilsons", "Foundation", "(http://www.torenilsonsstiftelse.nu),", "and", "the", "A˚ke", "Wiberg", "Foundation", "(http://www.ake-wiberg.com).", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "hong.sjolinder@gmt.su.se", "¤", "Current", "address:", "Department", "of", "Neurobiology,", "Care", "Sciences", "and", "Society,", "Karolinska", "Institute,", "Novum,", "Huddinge,", "Sweden", "Introduction", "The", "pathogenic", "bacterium", "Neisseria", "meningitidis", "is", "a", "leading", "cause", "of", "bacterial", "meningitis", "and", "septicemia.", "During", "asymptomatic", "carriage", "meningococci", "colonise", "the", "nasopharynx", "but", "under", "certain", "conditions", "bacteria", "spread", "to", "the", "bloodstream", "and", "meninges.", "Disease", "progression", "is", "rapid", "and", "associated", "with", "high", "mortality.", "Neisseria", "hia/hsf", "homologue", "(NhhA)", "is", "an", "outer", "membrane", "protein", "homologous", "to", "the", "Hia", "and", "Hsf", "adhesins", "of", "Haemophilus", "influenzae", "[1].", "A", "strain", "survey", "showed", "that", "the", "NhhA", "gene", "was", "present", "in", "all", "(85)", "strains", "tested", "and", "immuno-electron", "microscopy", "demonstrated", "the", "presence", "of", "NhhA", "on", "the", "outer", "membrane", "[1].", "In", "a", "screen", "for", "vaccine", "candidates", "against", "serogroup", "B", "meningococci,", "NhhA", "was", "identified", "as", "a", "surface-exposed", "antigen", "that", "could", "be", "used", "to", "produce", "an", "antibactericidal", "antibody", "response", "in", "mice", "[2–3].", "The", "C-terminal", "domain", "of", "NhhA", "is", "able", "to", "trimerize", "and", "form", "a", "translocator", "domain", "that", "allows", "localization", "of", "the", "protein", "to", "the", "bacterial", "surface", "[4].", "In", "agreement,", "a", "C-terminal", "point", "mutation", "was", "shown", "to", "block", "trimerisation", "of", "NhhA", "[5].", "E.", "coli", "expressing", "recombinant", "Nhha", "can", "bind", "to", "epithelial", "cells", "and", "furthermore", "direct", "interaction", "between", "purified", "NhhA", "and", "laminin", "as", "well", "as", "heparan", "sulphate", "was", "observed", "[4].", "Meningococci", "lacking", "NhhA", "are", "more", "sensitive", "to", "complement-mediated", "bacterial", "killing", "in", "human", "serum", "and", "can", "be", "more", "easily", "phagocytosed", "by", "macrophages.", "In", "addition,", "NhhA", "promotes", "the", "interaction", "between", "capsulated,", "wildtype", "meningococci", "and", "macrophages", "[6].", "Using", "a", "mouse", "model", "of", "meningococcal", "disease,", "Nhha", "was", "found", "to", "be", "of", "importance", "for", "colonization", "of", "nasal", "mucosa.", "Bacterial", "survival", "upon", "intranasal", "administration", "could", "only", "be", "observed", "when", "using", "wildtype", "meningococci", "and", "not", "with", "meningococci", "lacking", "NhhA", "[6].", "Programmed", "cell", "death", "of", "host", "cells", "can", "be", "triggered", "by", "the", "release", "of", "proapoptotic", "factors", "from", "pathogenic", "bacteria", "or", "exposure", "of", "proapoptotic", "factors", "on", "the", "bacterial", "surface.", "Several", "species", "of", "bacteria", "can", "induce", "apoptosis", "such", "as", "Pseudomonas", "aeruginosa", "[7]", "and", "enteropathogenic", "E.", "coli", "[8].", "Apoptosis", "can", "play", "an", "important", "role", "during", "bacterial", "infections", "and", "be", "either", "induced", "or", "inhibited", "by", "bacterial", "factors", "under", "different", "pathological", "conditions.", "In", "N.", "meningitidis,", "the", "ability", "of", "highly", "pathogenic", "strains", "and", "isolates", "to", "cause", "invasive", "disease", "and", "tissue", "damage", "was", "found", "to", "be", "closely", "linked", "to", "pro-apoptotic", "activity", "[9].", "In", "contrast,", "strains", "associated", "with", "asymptomatic", "carriage", "did", "not", "induce", "apoptosis", "[9].", "The", "bacterial", "membrane", "component", "lipopolysaccharide", "(LPS)", "and", "related", "compounds", "such", "as", "lipooligosaccharide", "(LOS)", "of", "N.", "meningitidis", "are", "important", "apoptosis-inducing", "factors", "[10].", "Howev-", "er,", "meningococci", "lacking", "LOS", "can", "also", "provoke", "proinflammatory", "responses", "[11]", "and", "induce", "apoptosis", "[9].", "The", "N.", "meningitidis", "porin", "PLoS", "ONE", "|", "www.plosone.org", "1", "January", "2012", "|", "Volume", "7", "|", "Issue", "1", "|", "e29586" ]

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[ "Hsieh", "et", "al.", "Journal", "of", "Neuroinflammation", "2012,", "9:110", "http://www.jneuroinflammation.com/content/9/1/110", "R", "E", "S", "E", "A", "R", "C", "H", "JOURNAL", "OF", "NEUROINFLAMMATION", "Open", "Access", "NADPH", "oxidase-mediated", "redox", "signal", "contributes", "to", "lipoteichoic", "acid-induced", "MMP-9", "upregulation", "in", "brain", "astrocytes", "Hsi-Lung", "Hsieh1†,", "Chih-Chung", "Lin2†,", "Ruey-Horng", "Shih3,", "Li-Der", "Hsiao3", "and", "Chuen-Mao", "Yang3,4*", "Abstract", "Background:", "Lipoteichoic", "acid", "(LTA)", "is", "a", "component", "of", "gram-positive", "bacterial", "cell", "walls", "and", "may", "be", "elevated", "in", "the", "cerebrospinal", "fluid", "of", "patients", "suffering", "from", "meningitis.", "Among", "matrix", "metalloproteinases", "(MMPs),", "MMP-9", "has", "been", "observed", "in", "patients", "with", "brain", "inflammatory", "diseases", "and", "may", "contribute", "to", "the", "pathology", "of", "brain", "diseases.", "Moreover,", "several", "studies", "have", "suggested", "that", "increased", "oxidative", "stress", "is", "implicated", "in", "the", "pathogenesis", "of", "brain", "inflammation", "and", "injury.", "However,", "the", "molecular", "mechanisms", "underlying", "LTA-induced", "redox", "signal", "and", "MMP-9", "expression", "in", "brain", "astrocytes", "remain", "unclear.", "Objective:", "Herein", "we", "explored", "whether", "LTA-induced", "MMP-9", "expression", "was", "mediated", "through", "redox", "signals", "in", "rat", "brain", "astrocytes", "(RBA-1", "cells).", "Methods:", "Upregulation", "of", "MMP-9", "by", "LTA", "was", "evaluated", "by", "zymographic", "and", "RT-PCR", "analyses.", "Next,", "the", "MMP-9", "regulatory", "pathways", "were", "investigated", "by", "pretreatment", "with", "pharmacological", "inhibitors", "or", "transfection", "with", "small", "interfering", "RNAs", "(siRNAs),", "Western", "blotting,", "and", "chromatin", "immunoprecipitation", "(ChIP)-PCR", "and", "promoter", "activity", "reporter", "assays.", "Moreover,", "we", "determined", "the", "cell", "functional", "changes", "by", "migration", "assay.", "Results:", "These", "results", "showed", "that", "LTA", "induced", "MMP-9", "expression", "via", "a", "PKC(α)-dependent", "pathway.", "We", "further", "demonstrated", "that", "PKCα", "stimulated", "p47phox/NADPH", "oxidase", "2", "(Nox2)-dependent", "reactive", "oxygen", "species", "(ROS)", "generation", "and", "then", "activated", "the", "ATF2/AP-1", "signals.", "The", "activated-ATF2", "bound", "to", "the", "AP-1-binding", "site", "of", "MMP-9", "promoter,", "and", "thereby", "turned", "on", "MMP-9", "gene", "transcription.", "Additionally,", "the", "co-activator", "p300", "also", "contributed", "to", "these", "responses.", "Functionally,", "LTA-induced", "MMP-9", "expression", "enhanced", "astrocytic", "migration.", "Conclusion:", "These", "results", "demonstrated", "that", "in", "RBA-1", "cells,", "activation", "of", "ATF2/AP-1", "by", "the", "PKC(α)-mediated", "Nox", "(2)/ROS", "signals", "is", "essential", "for", "upregulation", "of", "MMP-9", "and", "cell", "migration", "enhanced", "by", "LTA.", "Background", "Matrix", "metalloproteinases", "(MMPs)", "comprise", "a", "family", "of", "calcium-", "and", "zinc-dependent", "proteinases,", "and", "are", "in-", "volved", "in", "normal", "development", "and", "wound", "healing", "as", "well", "as", "in", "pathological", "conditions", "such", "as", "atherosclerosis", "and", "metastasis.", "In", "brain,", "MMP-9", "has", "been", "shown", "to", "be", "upregulated", "during", "various", "CNS", "diseases", "[1,2].", "Previous", "*", "Correspondence:", "chuenmao@mail.cgu.edu.tw", "†Equal", "contributors", "3Department", "of", "Pharmacology", "and", "Health", "Aging", "Research", "Center,", "College", "of", "Medicine,", "Chang", "Gung", "University,", "Tao-Yuan,", "Taiwan", "4Department", "of", "Pharmacology,", "College", "of", "Medicine,", "Chang", "Gung", "University,", "259", "Wen-Hwa", "1st", "Road,", "Kwei-San,", "Tao-Yuan,", "Taiwan", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "reports", "have", "indicated", "that", "a", "series", "of", "functional", "elem-", "ent-binding", "sites", "have", "been", "identified,", "including", "NF-κB,", "Ets", "and", "AP-1", "within", "the", "MMP-9", "promoter", "[3],", "which", "can", "be", "regulated", "by", "diverse", "stimuli.", "Moreover,", "proin-", "flammatory", "factors", "including", "cytokines,", "endotoxins", "and", "oxidative", "stress", "have", "been", "reported", "to", "upregulate", "MMP-", "9", "in", "astrocytes", "in", "vitro", "[4-6],", "implying", "that", "MMP-9", "ac-", "tivity", "may", "be", "regulated", "by", "diverse", "factors", "in", "the", "CNS", "during", "neuroinflammation.", "It", "is", "worth", "noting", "that", "bacterial", "infections", "have", "been", "found", "to", "trigger", "brain", "inflammatory", "diseases", "[7].", "Gram-", "positive", "bacterial", "infections", "of", "the", "CNS", "occur", "in", "bacterial", "meningitis", "and", "brain", "abscess,", "being", "localized", "to", "the", "mem-", "branes", "surrounding", "the", "brain", "or", "in", "its", "parenchyma,", "©", "2012", "Hsieh", "et", "al.;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Liu", "et", "al.", "Lipids", "in", "Health", "and", "Disease", "2010,", "9:110", "http://www.lipidworld.com/content/9/1/110", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "Association", "of", "the", "LIPG", "584C", ">", "T", "polymorphism", "and", "serum", "lipid", "levels", "in", "the", "Guangxi", "Bai", "Ku", "Yao", "and", "Han", "populations", "Wang-Ying", "Liu1,", "Rui-Xing", "Yin1*,", "Lin", "Zhang1,", "Xiao-Li", "Cao1,", "Lin", "Miao1,", "Dong-Feng", "Wu1,", "Lynn", "Htet", "Htet", "Aung1,", "Xi-Jiang", "Hu1,", "Wei-Xiong", "Lin2,", "De-Zhai", "Yang2", "Abstract", "Background:", "Endothelial", "lipase", "(EL)", "is", "a", "major", "determinant", "of", "high-density", "lipoprotein-cholesterol", "(HDL-C)", "metabolism,", "but", "the", "association", "of", "endothelial", "lipase", "gene", "(LIPG)", "polymorphism", "and", "serum", "HDL-C", "levels", "is", "scarce", "and", "conflicting", "in", "diverse", "populations.", "Bai", "Ku", "Yao", "is", "an", "isolated", "subgroup", "of", "the", "Yao", "minority", "in", "China.", "This", "study", "was", "designed", "to", "detect", "the", "association", "of", "LIPG", "584C", ">", "T", "(rs2000813)", "polymorphism", "and", "several", "environmental", "factors", "with", "serum", "lipid", "levels", "in", "the", "Guangxi", "Bai", "Ku", "Yao", "and", "Han", "populations.", "Methods:", "A", "total", "of", "645", "subjects", "of", "Bai", "Ku", "Yao", "and", "638", "participants", "of", "Han", "Chinese", "were", "randomly", "selected", "from", "our", "previous", "stratified", "randomized", "cluster", "samples.", "Genotyping", "of", "the", "LIPG", "584C", ">", "T", "was", "performed", "by", "polymerase", "chain", "reaction", "and", "restriction", "fragment", "length", "polymorphism", "combined", "with", "gel", "electrophoresis,", "and", "then", "confirmed", "by", "direct", "sequencing.", "Results:", "The", "levels", "of", "serum", "total", "cholesterol", "(TC),", "HDL-C,", "low-density", "lipoprotein", "cholesterol", "(LDL-C)", "and", "apolipoprotein", "(Apo)", "AI", "and", "ApoB", "were", "lower", "in", "Bai", "Ku", "Yao", "than", "in", "Han", "(P", "<", "0.05", "-", "0.001).", "The", "frequency", "of", "C", "and", "T", "alleles", "was", "73.5%", "and", "26.5%", "in", "Bai", "Ku", "Yao,", "and", "67.9%", "and", "32.1%", "in", "Han", "(P", "<", "0.01);", "respectively.", "The", "frequency", "of", "CC,", "CT", "and", "TT", "genotypes", "was", "50.4%,", "46.2%", "and", "3.4%", "in", "Bai", "Ku", "Yao,", "and", "41.4%,", "53.1%", "and", "5.5%", "in", "Han", "(P", "<", "0.01);", "respectively.", "Serum", "HDL-C", "levels", "in", "both", "ethnic", "groups", "were", "different", "among", "the", "three", "genotypes", "(P", "<", "0.05", "for", "each).", "Serum", "TC", "levels", "in", "both", "ethnic", "groups", "were", "also", "different", "between", "the", "CC", "and", "CT/TT", "genotypes", "(P", "<", "0.05", "for", "each).", "The", "T", "allele", "carriers", "had", "higher", "serum", "HDL-C", "and", "TC", "levels", "than", "the", "T", "allele", "noncarriers.", "Multivariate", "logistic", "regression", "analysis", "showed", "that", "the", "levels", "of", "HDL-C", "and", "ApoB", "were", "correlated", "with", "genotypes", "in", "Bai", "Ku", "Yao", "(P", "<", "0.05", "for", "each),", "whereas", "the", "levels", "of", "TC", "and", "HDL-C", "were", "associated", "with", "genotypes", "in", "Han", "Chinese", "(P", "<", "0.05", "and", "P", "<", "0.01).", "Serum", "lipid", "parameters", "were", "also", "correlated", "with", "several", "environmental", "factors", "in", "the", "both", "ethnic", "groups.", "Conclusions:", "The", "frequency", "of", "LIPG", "584T", "allele", "is", "lower", "in", "Bai", "Ku", "Yao", "than", "in", "Han", "Chinese.", "The", "LIPG", "584T", "allele", "is", "associated", "with", "increased", "serum", "HDL-C,", "TC", "and", "ApoB", "levels.", "The", "differences", "in", "serum", "HDL-C,", "TC", "and", "ApoB", "levels", "between", "the", "two", "ethnic", "groups", "might", "partly", "result", "from", "different", "genotypic", "and", "allelic", "frequencies", "of", "LIPG", "584C", ">", "T", "or", "different", "LIPG-enviromental", "interactions.", "*", "Correspondence:", "yinruixing@yahoo.com.cn", "1Department", "of", "Cardiology,", "Institute", "of", "Cardiovascular", "Diseases,", "the", "First", "Affiliated", "Hospital,", "Guangxi", "Medical", "University,", "22", "Shuangyong", "Road,", "Nanning", "530021,", "Guangxi,", "People’s", "Republic", "of", "China", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "©", "2010", "Wanying", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Molecular", "Vision", "2009;", "15:2841-2847", "<http://www.molvis.org/molvis/v15/a300>", "Received", "27", "July", "2009", "|", "Accepted", "9", "December", "2009", "|", "Published", "20", "December", "2009", "©", "2009", "Molecular", "Vision", "Outcome", "of", "ABCA4", "microarray", "screening", "in", "routine", "clinical", "practice", "Paul", "J.G.", "Ernest,1,2", "Camiel", "J.F.", "Boon,3", "B.", "Jeroen", "Klevering,3", "Lies", "H.", "Hoefsloot,4", "Carel", "B.", "Hoyng3", "1Department", "of", "Ophthalmology,", "University", "Hospital", "Maastricht,", "Maastricht,", "The", "Netherlands;", "2Department", "of", "Epidemiology,", "Maastricht", "University,", "Maastricht,", "The", "Netherlands;", "3Department", "of", "Ophthalmology,", "Radboud", "University", "Nijmegen", "Medical", "Centre,", "Nijmegen,", "The", "Netherlands;", "4Department", "of", "Human", "Genetics,", "Radboud", "University", "Nijmegen", "Medical", "Centre,", "Nijmegen,", "The", "Netherlands", "Purpose:", "To", "retrospectively", "analyze", "the", "clinical", "characteristics", "of", "patients", "who", "were", "screened", "for", "mutations", "with", "the", "ATP-binding", "cassette", "transporter", "gene", "ABCA4", "(ABCA4)", "microarray", "in", "a", "routine", "clinical", "DNA", "diagnostics", "setting.", "Methods:", "We", "performed", "a", "retrospective", "analysis", "of", "the", "medical", "charts", "of", "65", "patients", "who", "underwent", "an", "ABCA4", "microarray", "screening", "between", "the", "years", "2002", "and", "2006.", "An", "additional", "denaturing", "gradient", "gel", "electrophoresis", "(DGGE)", "was", "performed", "in", "these", "patients", "if", "less", "than", "two", "mutations", "were", "found", "with", "the", "microarray.", "We", "included", "all", "patients", "who", "were", "suspected", "of", "autosomal", "recessive", "Stargardt", "disease", "(STGD1),", "autosomal", "recessive", "cone–rod", "dystrophy", "(arCRD),", "or", "autosomal", "recessive", "retinitis", "pigmentosa", "at", "the", "time", "of", "microarray", "request.", "After", "a", "retrospective", "analysis", "of", "the", "clinical", "characteristics,", "the", "patients", "who", "were", "suspected", "of", "STGD1", "were", "categorized", "as", "having", "either", "a", "typical", "or", "atypical", "form", "of", "STGD1,", "according", "to", "the", "age", "at", "onset,", "fundus", "appearance,", "fluorescein", "angiography,", "and", "electroretinography.", "The", "occurrence", "of", "typical", "clinical", "features", "for", "STGD1", "was", "compared", "between", "patients", "with", "different", "numbers", "of", "discovered", "mutations.", "Results:", "Of", "the", "44", "patients", "who", "were", "suspected", "of", "STGD1,", "26", "patients", "(59%)", "had", "sufficient", "data", "available", "for", "a", "classification", "in", "either", "typical", "(six", "patients;", "23%)", "or", "atypical", "(20", "patients;", "77%)", "STGD1.", "In", "the", "suspected", "STGD1", "group,", "59%", "of", "all", "expected", "pathogenic", "alleles", "were", "found", "with", "the", "ABCA4", "microarray.", "DGGE", "led", "to", "the", "finding", "of", "12", "more", "mutations,", "resulting", "in", "an", "overall", "detection", "rate", "of", "73%.", "Thirty-one", "percent", "of", "patients", "with", "two", "or", "three", "discovered", "ABCA4", "mutations", "met", "all", "typical", "STGD1", "criteria.", "An", "age", "at", "onset", "younger", "than", "25", "years", "and", "a", "dark", "choroid", "on", "fluorescein", "angiography", "were", "the", "most", "predictive", "clinical", "features", "to", "find", "ABCA4", "mutations", "in", "patients", "suspected", "of", "STGD1.", "In", "18", "patients", "suspected", "of", "arCRD,", "microarray", "screening", "detected", "22%", "of", "the", "possible", "pathogenic", "alleles.", "Conclusions:", "In", "addition", "to", "confirmation", "of", "the", "diagnosis", "in", "typical", "STGD1,", "ABCA4", "microarray", "screening", "is", "usually", "requested", "in", "daily", "clinical", "practice", "to", "strengthen", "the", "diagnosis", "when", "the", "disease", "is", "atypical.", "This", "study", "supports", "the", "view", "that", "the", "efficiency", "and", "accuracy", "of", "ABCA4", "microarray", "screening", "are", "directly", "dependent", "upon", "the", "clinical", "features", "of", "the", "patients", "who", "are", "screened.", "The", "autosomal", "recessive", "form", "of", "Stargardt", "disease", "(STGD1)", "is", "caused", "by", "variations", "in", "the", "ATP-binding", "cassette", "transporter", "gene", "ABCA4", "(ABCA4)", "[1].", "The", "gene", "product", "of", "ABCA4", "is", "localized", "to", "the", "rim", "of", "the", "rod", "and", "cone", "outer", "segment", "disc", "membranes", "[2,3].", "Pathological", "mutations", "in", "ABCA4", "result", "in", "an", "accumulation", "of", "all-trans", "retinal", "in", "the", "membrane", "of", "the", "photoreceptor", "disc.", "Following", "phagocytosis", "of", "the", "photoreceptor", "outer", "segments,", "toxic", "derivatives", "of", "all-", "trans", "retinal", "accumulate", "in", "the", "retinal", "pigment", "epithelium", "(RPE)", "and", "may", "ultimately", "lead", "to", "RPE", "cell", "death", "and", "atrophy", "of", "the", "overlying", "photoreceptor", "layer", "[4].", "Besides", "STGD1,", "ABCA4", "mutations", "may", "also", "be", "found", "in", "a", "significant", "percentage", "(65%)", "of", "patients", "with", "autosomal", "recessive", "cone–", "rod", "dystrophy", "(arCRD)", "[5].", "In", "addition,", "mutations", "in", "this", "gene", "have", "been", "described", "in", "atypical", "autosomal", "recessive", "retinitis", "Correspondence", "to:", "Paul", "J.G.", "Ernest,", "Department", "of", "Ophthalmology,", "University", "Hospital", "Maastricht,", "P.O.", "Box", "5800,", "6202", "AZ", "Maastricht,", "The", "Netherlands;", "Phone:", "+31-43-3882242;", "FAX:", "+31-43-3875343;", "email:", "p.j.g.ernest@gmail.com", "pigmentosa", "(arRP)", "and", "may", "play", "a", "role", "in", "age-related", "macular", "degeneration", "[6,7].", "STGD1", "appears", "to", "be", "monogenic;", "no", "sibships", "have", "been", "found", "in", "which", "ABCA4", "alleles", "do", "not", "co-segregate", "with", "the", "disease.", "However,", "intrafamilial", "variability", "of", "the", "phenotype", "has", "been", "reported", "[8].", "Differences", "between", "siblings", "may", "indicate", "the", "influence", "of", "environmental", "factors", "as", "well", "as", "other", "genes", "that", "modify", "the", "expression", "of", "a", "given", "ABCA4", "genotype.", "Moreover,", "ABCA4", "has", "a", "large", "allelic", "diversity.", "The", "nucleotide", "diversity", "of", "the", "ABCA4", "coding", "region", "was", "found", "to", "be", "9–400", "times", "greater", "than", "that", "of", "two", "other", "macular", "disease", "genes", "that", "were", "examined", "in", "a", "similar", "fashion", "(bestrophin", "1", "and", "EGF-", "containing", "fibulin-like", "extracellular", "matrix", "protein", "1)", "[9].", "Allelic", "heterogeneity", "and", "the", "size", "of", "the", "gene", "have", "substantially", "complicated", "genetic", "analysis", "of", "ABCA4-", "associated", "retinal", "disease.", "All", "mutation", "detection", "techniques", "that", "remain", "exclusively", "PCR-based", "are", "relatively", "inefficient,", "expensive,", "and", "labor", "intensive.", "Therefore,", "the", "ABCA4", "genotyping", "microarray", "was", "developed", "[10].", "The", "ABCR400", "microarray", "contains", "all", "disease-associated", "genetic", "variants", "2841" ]

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[ "Original", "Article", "http://dx.doi.org/10.3349/ymj.2012.53.6.1081", "pISSN:", "0513-5796,", "eISSN:", "1976-2437", "Yonsei", "Med", "J", "53(6):1081-1084,", "2012", "The", "Effects", "of", "Thoracic", "Sympathotomy", "on", "Heart", "Rate", "Variability", "in", "Patients", "with", "Palmar", "Hyperhidrosis", "Tong-yuan", "Zhang,", "Long", "Wang,", "and", "Jin-jin", "Xu", "Department", "of", "Anesthesiology,", "Renmin", "Hospital", "of", "Wuhan", "University,", "Wuhan,", "Hubei,", "China.", "Received:", "April", "4,", "2012", "Revised:", "May", "16,", "2012", "Accepted:", "June", "11,", "2012", "Corresponding", "author:", "Dr.", "Long", "Wang,", "Department", "of", "Anesthesiology,", "Renmin", "Hospital", "of", "Wuhan", "University,", "Jie", "Fang", "Road", "238#,", "WuHan,", "HuBei,", "China.", "Tel:", "0086-2788041911-81026,", "Fax:", "0086-2788042922", "E-mail:", "wanglongwhu@163.com", "∙", "The", "authors", "have", "no", "financial", "conflicts", "of", "interest.", "Purpose:", "To", "observe", "the", "evolution", "of", "heart", "rate", "variability", "(HRV)", "in", "patients", "with", "palmar", "hyperhidrosis", "before", "and", "after", "endoscopic", "thoracic", "sympathotomy", "and", "to", "evaluate", "the", "effects", "of", "the", "surgery", "on", "the", "autonomic", "nervous", "system.", "Materials", "and", "Methods:", "Endoscopic", "thoracic", "sympathotomy", "was", "performed", "on", "20", "patients", "with", "palmar", "hyperhidrosis.", "The", "thoracic", "sympathetic", "chain", "at", "the", "level", "of", "the", "third", "to", "fourth", "rib", "(R3-R4)", "was", "transected,", "but", "the", "ganglia", "were", "left", "in", "position", "without", "removal.", "A", "slightly", "larger", "ramus,", "in", "comparison", "to", "the", "other", "rami,", "that", "arose", "later-", "ally", "from", "the", "sympathetic", "chain", "was", "interrupted", "to", "achieve", "adequate", "sympathetic", "denervation", "of", "the", "upper", "extremity.", "Before", "and", "on", "the", "day", "after", "the", "surgery,", "24-", "hour", "Holter", "Electrocardiograph", "was", "performed,", "obtaining", "time", "domain", "and", "fre-", "quency", "domain", "parameters.", "Results:", "Compared", "with", "preoperative", "variables,", "there", "was", "a", "significant", "increase", "in", "the", "number", "of", "adjacent", "normal", "R", "wave", "to", "R", "wave", "(R-", "R)", "intervals", "that", "differed", "by", "more", "than", "50", "ms,", "as", "percent", "of", "the", "total", "number", "of", "normal", "RR", "intervals", "(pNN50);", "root", "mean", "square", "difference,", "the", "square", "root", "of", "the", "mean", "of", "the", "sum", "of", "squared", "differences", "between", "adjacent", "normal", "RR", "intervals", "over", "the", "entire", "24-hour", "recording;", "standard", "deviation", "of", "the", "average", "normal", "RR", "in-", "terval", "for", "all", "5-minute", "segments", "of", "a", "24-hour", "recording", "(SDANN)", "after", "thoracic", "sympathotomy.", "Low", "frequencies", "(LF,", "0.04", "to", "0.15", "Hz)", "decreased", "significantly.", "There", "was", "no", "statistical", "difference", "in", "high", "frequencies", "(HF,", "0.15", "to", "0.40", "Hz),", "LF/", "HF", "ratio", "(LF/HF),", "or", "standard", "deviation", "for", "all", "normal", "RR", "intervals", "for", "the", "entire", "24-h", "recording", "(SDNN)", "before", "and", "after", "thoracic", "sympathotomy.", "Conclusion:", "There", "was", "a", "significant", "improvement", "in", "HRV", "in", "patients", "with", "palmar", "hyperhidro-", "sis", "after", "thoracic", "sympathotomy.", "This", "may", "be", "attributable", "to", "an", "improvement", "auto-", "nomic", "nervous", "system", "balance", "and", "parasympathetic", "predominance", "in", "the", "early", "postoperative", "stage.", "Key", "Words:", "Sympathotomy,", "hyperhidrosis,", "heart", "rate,", "autonomic", "nervous", "system", "©", "Copyright:", "Yonsei", "University", "College", "of", "Medicine", "2012", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-", "Commercial", "License", "(http://creativecommons.org/", "licenses/by-nc/3.0)", "which", "permits", "unrestricted", "non-", "commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "INTRODUCTION", "Palmar", "hyperhidrosis,", "a", "type", "of", "primary", "hyperhidrosis", "without", "a", "known", "etiology,", "is", "characterized", "by", "excessive", "sweating", "of", "the", "palms", "and", "often", "the", "armpits.", "It", "has", "been", "associated", "with", "dysfunction", "of", "the", "sympathetic", "nervous", "system.1", "Ablation", "of", "Yonsei", "Med", "J", "http://www.eymj.org", "Volume", "53", "Number", "6", "November", "2012", "1081" ]

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[ "A", "Phosphorylation", "Site", "Regulates", "Sorting", "of", "the", "Vesicular", "Acetylcholine", "Transporter", "to", "Dense", "Core", "Vesicles", "David", "E.", "Krantz,‡§", "Clarissa", "Waites,*", "Viola", "Oorschot,¶", "Yongjian", "Liu,‡", "Rachel", "I.", "Wilson,i", "Philip", "K.", "Tan,‡", "Judith", "Klumperman,¶", "and", "Robert", "H.", "Edwards*‡i", "*Graduate", "Programs", "in", "Neuroscience,", "Cell", "Biology,", "and", "Biomedical", "Sciences,", "and", "‡Department", "of", "Neurology,", "§Department", "of", "Psychiatry,", "and", "iDepartment", "of", "Physiology,", "University", "of", "California", "at", "San", "Francisco", "School", "of", "Medicine,", "San", "Francisco,", "California", "94143-0435;", "and", "¶Department", "of", "Cell", "Biology,", "University", "Medical", "Center", "and", "Institute", "of", "Biomembranes,", "Utrecht", "University,", "3584", "CX", "Utrecht,", "The", "Netherlands", "Abstract.", "Vesicular", "transport", "proteins", "package", "classical", "neurotransmitters", "for", "regulated", "exocytotic", "release,", "and", "localize", "to", "at", "least", "two", "distinct", "types", "of", "secretory", "vesi-", "cles.", "In", "PC12", "cells,", "the", "vesicular", "acetylcholine", "trans-", "porter", "(VAChT)", "localizes", "preferentially", "to", "synaptic-like", "microvesicles", "(SLMVs),", "whereas", "the", "closely", "related", "ve-", "sicular", "monoamine", "transporters", "(VMATs)", "localize", "preferentially", "to", "large", "dense", "core", "vesicles", "(LDCVs).", "VAChT", "and", "the", "VMATs", "contain", "COOH-terminal,", "cy-", "toplasmic", "dileucine", "motifs", "required", "for", "internalization", "from", "the", "plasma", "membrane.", "We", "now", "show", "that", "VAChT", "undergoes", "regulated", "phosphorylation", "by", "protein", "kinase", "C", "on", "a", "serine", "(Ser-480)", "five", "residues", "upstream", "of", "the", "dileucine", "motif.", "Replacement", "of", "Ser-480", "by", "glutamate,", "Introduction", "At", "least", "two", "distinct", "populations", "of", "secretory", "vesicles", "me-", "diate", "the", "regulated", "exocytotic", "release", "of", "neurotransmit-", "ters.", "Synaptic", "vesicles", "(SVs)1", "appear", "almost", "exclusively", "in", "nerve", "terminals", "where", "they", "cluster", "at", "the", "synaptic", "cleft", "(Calakos", "and", "Scheller,", "1996).", "In", "contrast,", "large", "dense", "core", "vesicles", "(LDCVs)", "appear", "throughout", "the", "cell,", "and", "release", "transmitter", "more", "slowly", "and", "in", "response", "to", "different", "stim-", "uli", "than", "SVs", "(De", "Camilli", "and", "Jahn,", "1990;", "Martin,", "1994).", "Although", "SVs", "are", "generally", "considered", "to", "contain", "classical", "transmitters,", "whereas", "LDCVs", "store", "neural", "peptides,", "both", "types", "of", "regulated", "secretory", "vesicles", "contain", "monoamines,", "Address", "correspondence", "to", "R.H.", "Edwards,", "UCSF", "School", "of", "Medicine,", "513", "Parnassus", "Avenue,", "San", "Francisco,", "CA", "94143-0435.", "Tel.:", "(415)", "502-5687.", "Fax:", "(415)", "502-5687.", "E-mail:", "edwards@itsa.ucsf.edu", "1Abbreviations", "used", "in", "this", "paper:", "ACh,", "acetylcholine;", "BIS,", "bisindolyl-", "maleimide", "I;", "GABA,", "g-aminobutyric", "acid;", "GST,", "glutathione", "S-trans-", "ferase;", "HA,", "hemagglutinin;", "LDCVs,", "large", "dense", "core", "vesicles;", "PKC,", "pro-", "tein", "kinase", "C;", "PNS,", "postnuclear", "supernatant;", "SGII,", "secretogranin", "II;", "SLMVs,", "synaptic-like", "microvesicles;", "SVs,", "synaptic", "vesicles;", "syn1,", "synapto-", "physin", "positive;", "TMD,", "transmembrane", "domain;", "VAChT,", "vesicular", "acetyl-", "choline", "transporter;", "VMATs,", "vesicular", "monoamine", "transporters.", "to", "mimic", "the", "phosphorylation", "event,", "increases", "the", "local-", "ization", "of", "VAChT", "to", "LDCVs.", "Conversely,", "the", "VMATs", "contain", "two", "glutamates", "upstream", "of", "their", "dileucine-like", "motif,", "and", "replacement", "of", "these", "residues", "by", "alanine", "conversely", "reduces", "sorting", "to", "LDCVs.", "The", "results", "pro-", "vide", "some", "of", "the", "first", "information", "about", "sequences", "in-", "volved", "in", "sorting", "to", "LDCVs.", "Since", "the", "location", "of", "the", "transporters", "determines", "which", "vesicles", "store", "classical", "neurotransmitters,", "a", "change", "in", "VAChT", "trafficking", "due", "to", "phosphorylation", "may", "also", "influence", "the", "mode", "of", "transmitter", "release.", "Key", "words:", "neurotransmitter", "•", "kinase", "•", "trafficking", "•", "exocytosis", "•", "monoamine", "indicating", "the", "potential", "for", "release", "of", "a", "single", "transmitter", "through", "two", "distinct", "mechanisms", "(Thureson-Klein,", "1983;", "Bruns", "and", "Jahn,", "1995).", "Since", "classical", "transmitters,", "includ-", "ing", "monoamines,", "are", "synthesized", "in", "the", "cytoplasm,", "the", "subcellular", "location", "of", "the", "transporters", "required", "for", "pack-", "aging", "them", "into", "secretory", "vesicles", "determines", "the", "site", "of", "vesicular", "storage,", "and", "hence,", "the", "mode", "of", "exocytotic", "re-", "lease.", "Secretory", "vesicles", "exhibit", "four", "distinct", "neurotransmitter", "transport", "activities,", "including", "one", "for", "monoamines,", "a", "sec-", "ond", "for", "acetylcholine", "(ACh),", "a", "third", "for", "g-aminobutyric", "acid", "(GABA),", "and", "a", "fourth", "for", "glutamate", "(Liu", "and", "Ed-", "wards,", "1997b).", "All", "of", "these", "activities", "depend", "on", "the", "H1", "electrochemical", "gradient", "across", "the", "vesicle", "membrane,", "and", "exchange", "lumenal", "protons", "for", "cytoplasmic", "transmitter", "(Schuldiner", "et", "al.,", "1995).", "Pharmacologic", "manipulation", "of", "vesicular", "transport", "indicates", "the", "importance", "of", "these", "activ-", "ities", "for", "behavior.", "The", "antihypertensive", "drug", "reserpine", "in-", "hibits", "vesicular", "monoamine", "transport", "and", "induces", "a", "syn-", "drome", "resembling", "depression", "(Frize,", "1954).", "In", "addition,", "amphetamines", "induce", "efflux", "from", "vesicular", "monoamine", "stores", "(Sulzer", "et", "al.,", "1995)", "and", "can", "cause", "psychosis.", "Thus,", "ª", "The", "Rockefeller", "University", "Press,", "0021-9525/2000/04/379/17", "$5.00", "The", "Journal", "of", "Cell", "Biology,", "Volume", "149,", "Number", "2,", "April", "17,", "2000", "379–395", "http://www.jcb.org", "379" ]

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[ "Diabetologia", "(2011)", "54:2965–2967", "DOI", "10.1007/s00125-011-2306-2", "LETTER", "High", "serum", "potassium", "levels", "after", "losartan", "can", "reflect", "more", "severe", "renal", "disease.", "Reply", "to", "Gonçalves", "AR,", "El", "Nahas", "AM", "[letter]", "S.", "S.", "Roscioni", "&", "Y.", "Miao", "&", "D.", "de", "Zeeuw", "&", "H.", "J.", "Lambers", "Heerspink", "Received:", "23", "June", "2011", "/", "Accepted:", "12", "August", "2011", "/", "Published", "online:", "17", "September", "2011", "#", "The", "Author(s)", "2011.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Keywords", "Diabetic", "nephropathy", ".", "End-stage", "renal", "disease", ".", "Hyperkalaemia,", "Losartan", ".", "Serum", "potassium", "Abbreviations", "ACEI", "Angiotensin-converting", "enzyme", "inhibitor", "ARB", "Angiotensin", "receptor", "blocker", "RAAS", "Renin–angiotensin–aldosterone", "system", "RENAAL", "Reduction", "of", "Endpoints", "in", "NIDDM", "with", "the", "Angiotensin", "II", "Antagonist", "Losartan", "To", "the", "Editor:", "Gonçalves", "and", "El", "Nahas", "[1]", "raise", "interesting", "comments", "on", "our", "publication", "describing", "how", "blockade", "of", "the", "angiotensin", "I", "receptor", "with", "losartan", "increases", "serum", "potassium", "which", "is,", "in", "turn,", "associated", "with", "an", "increased", "risk", "of", "renal", "outcomes", "in", "patients", "with", "diabetes", "and", "nephropathy", "[2].", "In", "their", "letter,", "Gonçalves", "and", "El", "Nahas", "suggest", "that", "those", "patients", "who", "developed", "hyperkalaemia", "were", "more", "likely", "to", "have", "pre-existing", "glomerular", "or", "tubulointerstitial", "damage,", "which", "could", "have", "accounted", "for", "the", "faster", "progression", "of", "renal", "disease.", "Although", "this", "could,", "S.", "S.", "Roscioni", ":", "Y.", "Miao", ":", "D.", "de", "Zeeuw", ":", "H.", "J.", "Lambers", "Heerspink", "(*)", "Department", "of", "Clinical", "Pharmacology,", "University", "Medical", "Centre", "Groningen,", "Antonius", "Deusinglaan", "1,", "9713", "AV", "Groningen,", "the", "Netherlands", "e-mail:", "h.j.lambers.heerspink@umcg.nl", "to", "a", "certain", "extent,", "hold", "true,", "we", "believe", "that", "such", "a", "theory", "does", "not", "explain", "our", "findings.", "We", "performed", "various", "analyses", "to", "ensure", "that", "the", "relationship", "between", "increased", "serum", "potassium", "and", "renal", "outcome", "was", "independent", "of", "the", "severity", "of", "the", "underlying", "renal", "disease.", "First,", "we", "corrected", "for", "various", "renal", "risk", "markers,", "most", "notably", "the", "baseline", "and", "change", "in", "estimated", "glomerular", "filtration", "rate.", "Second,", "we", "conducted", "a", "pair-", "matched", "analysis", "selecting", "patients", "with", "similar", "character-", "istics", "who", "did", "and", "did", "not", "develop", "hyperkalaemia.", "Both", "analyses", "consistently", "showed", "that", "participants", "in", "whom", "serum", "potassium", "levels", "rose", "had", "a", "higher", "risk", "of", "renal", "disease.", "We", "therefore", "consider", "it", "unlikely", "that", "the", "greater", "degree", "of", "pre-existing", "renal", "injury", "in", "individuals", "who", "developed", "high", "serum", "potassium", "levels", "is", "the", "main", "factor", "responsible", "for", "their", "higher", "renal", "risk.", "Nevertheless,", "since", "neither", "glomerular", "nor", "tubulointerstitial", "damage", "was", "measured", "in", "the", "Reduction", "of", "Endpoints", "in", "NIDDM", "with", "the", "Angiotensin", "II", "Antagonist", "Losartan", "(RENAAL)", "trial,", "we", "cannot", "completely", "rule", "out", "the", "possibility", "that", "individuals", "who", "developed", "hyperkalaemia", "also", "had", "pre-", "existing", "renal", "damage.", "Further", "indirect", "evidence", "to", "support", "our", "hypothesis", "that", "the", "increase", "in", "serum", "potassium", "is", "associated", "with", "renal", "outcome", "stems", "from", "an", "additional", "analysis", "showing", "that", "adjustment", "of", "the", "losartan", "treatment", "effect", "for", "the", "residual", "potassium", "level", "(the", "serum", "potassium", "level", "during", "treat-", "ment)", "improves", "the", "overall", "renoprotective", "response", "to", "losartan.", "These", "data", "suggest", "that", "the", "increase", "in", "serum", "potassium", "during", "losartan", "therapy", "attenuates", "its", "long-term" ]

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[ "Review", "A", "Framework", "for", "Examining", "Social", "Stress", "and", "Susceptibility", "to", "Air", "Pollution", "in", "Respiratory", "Health", "Jane", "E.", "Clougherty1", "and", "Laura", "D.", "Kubzansky", "2", "1Department", "of", "Environmental", "Health,", "and", "2Department", "of", "Society,", "Human", "Development,", "and", "Health,", "Harvard", "School", "of", "Public", "Health,", "Boston,", "Massachusetts,", "USA", "Objectiv", ":", "hTere", "is", "growing", "interest", "in", "disentangling", "the", "health", "effects", "of", "spatially", "clustered", "social", "and", "physical", "environmental", "exposures", "and", "in", "exploring", "potential", "synergies", "among", "them,", "with", "particular", "attention", "directed", "to", "the", "combined", "effects", "of", "psychosocial", "stress", "and", "air", "pollution.", "Both", "exposures", "may", "be", "elevated", "in", "lower-income", "urban", "communities,", "and", "it", "has", "been", "hypothesized", "that", "stress,", "which", "can", "influence", "immune", "function", "and", "susceptibility,", "may", "potentiate", "the", "effects", "of", "air", "pol-", "lution", "in", "respiratory", "disease", "onset", "and", "exacerbation.", "In", "this", "paper,", "we", "attempt", "to", "synthesize", "the", "rele-", "vant", "research", "from", "social", "and", "environmental", "epidemiology,", "toxicology,", "immunology,", "and", "exposure", "assessment", "to", "provide", "a", "useful", "framework", "for", "environmental", "health", "researchers", "aiming", "to", "investigate", "the", "health", "effects", "of", "environmental", "pollution", "in", "combination", "with", "social", "or", "psychological", "factors.", "Dat", "syntheis", ":", "We", "review", "the", "existing", "epidemiologic", "and", "toxicologic", "evidence", "on", "synergistic", "effects", "of", "stress", "and", "pollution,", "and", "then", "describe", "the", "physiologic", "effects", "of", "stress", "and", "key", "issues", "related", "to", "measuring", "and", "evaluating", "stress", "as", "it", "relates", "to", "physical", "environmental", "exposures", "and", "sus-", "ceptibility.", "Finally,", "we", "identify", "some", "of", "the", "major", "methodologic", "challenges", "ahead", "as", "we", "work", "toward", "disentangling", "the", "health", "effects", "of", "clustered", "social", "and", "physical", "exposures", "and", "accurately", "describing", "the", "interplay", "among", "these", "exposures.", "c", "Onclusi", "Ons", ":", "There", "is", "still", "tremendous", "work", "to", "be", "done", "toward", "understanding", "the", "combined", "and", "potentially", "synergistic", "health", "effects", "of", "stress", "and", "pollution.", "As", "this", "research", "proceeds,", "we", "recommend", "careful", "attention", "to", "the", "relative", "temporalities", "of", "stress", "and", "pollution", "exposures,", "to", "non-", "linearities", "in", "their", "independent", "and", "combined", "effects,", "to", "physiologic", "pathways", "not", "elucidated", "by", "epidemiologic", "methods,", "and", "to", "the", "relative", "spatial", "distributions", "of", "social", "and", "physical", "exposures", "at", "multiple", "geographic", "scales.", "Key", "w", "Or", "Ds", ":", "air", "pollution,", "social", "stress,", "spatial", "analysis,", "synergistic", "effects,", "urban", "community", "health.", "Environ", "Health", "Perspect", "117:1351–1358", "(2009).", "doi:10.1289/ehp.0900612", "available", "via", "http://", "dx.doi.org/", "[Online", "12", "May", "2009]", "There", "is", "growing", "interest", "within", "environ-", "mental", "health", "in", "disentangling", "effects", "of", "clus-", "tered", "social", "and", "environmental", "exposures", "and", "exploring", "potential", "synergies", "among", "these", "exposures", "(Gee", "and", "Payne-Sturges", "2004;", "Morello-Frosch", "and", "Shenassa", "2006;", "O’Neill", "et", "al.", "2003,", "2007a,", "2007b;", "Weiss", "and", "Bellinger", "2006).", "This", "interest", "stems", "from", "the", "observation", "that", "social", "stressors", "(i.e.,", "violence,", "poverty)", "and", "environmental", "exposures", "(i.e.,", "traffic-related", "and", "industrial", "air", "pollution)", "are", "often", "spatially", "correlated", "and", "may", "cluster", "in", "lower-income", "communities,", "often", "in", "locations", "with", "lower", "property", "values", "along", "highways", "and", "industrial", "corridors", "(Bullard", "1990;", "Graves", "1988).", "Traffic-", "related", "air", "pollution", "is", "a", "complex", "chemical", "mix", "(Schauer", "et", "al.", "2006),", "often", "spatially", "associ-", "ated", "with", "noise,", "poverty,", "and", "other", "stressors", "(Wheeler", "and", "Ben-Shlomo", "2005).", "Social", "stres-", "sors", "may", "lead", "to", "poor", "health", "outcomes", "directly", "or", "may", "increase", "susceptibility", "to", "physical", "expo-", "sures,", "such", "as", "air", "pollution,", "through", "alterations", "in", "immune", "function", "and", "biological", "systems", "(McEwen", "and", "Seeman", "1999).", "Thus,", "the", "most", "pollution-exposed", "communities", "may", "also", "be", "more", "susceptible", "because", "of", "higher", "prevalence", "of", "social", "stressors", "(Lipfert", "2004).", "This", "poten-", "tial", "for", "spatial", "confounding", "and", "effect", "modifi-", "cation", "by", "social", "stressors", "presents", "a", "challenge", "to", "air", "pollution", "epidemiology.", "Disentangling", "social", "and", "physical", "environmental", "risks", "(U.S.", "Environmental", "Protection", "Agency", "2008),", "understanding", "synergies", "among", "these", "expo-", "sures,", "and", "identifying", "modifiable", "exposures", "are", "particularly", "important", "for", "understanding", "how", "best", "to", "protect", "susceptible", "populations", "and", "improve", "overall", "population", "health.", "There", "is", "significant", "evidence", "linking", "traffic-", "related", "pollution", "exposure", "to", "respiratory", "ill-", "ness.", "Chronic", "exposure", "to", "traffic-related", "and", "particulate", "air", "pollution", "among", "adults", "has", "been", "linked", "to", "upper", "respiratory", "tract", "inflammation", "(Hiltermann", "et", "al.", "1997),", "chronic", "obstructive", "pulmonary", "disease", "(COPD)", "(Schikowski", "et", "al.", "2005),", "lung", "cancer", "(Vineis", "et", "al.", "2007),", "and", "premature", "mortality", "(Dockery", "1993;", "Pope", "et", "al.", "1995).", "In", "children,", "traffic-related", "pollution", "exposures,", "often", "indicated", "by", "residential", "prox-", "imity", "to", "major", "roads,", "has", "been", "associated", "with", "airway", "hyperresponsiveness", "(Jang", "et", "al.", "2003),", "wheeze", "(Ryan", "et", "al.", "2007),", "asthma", "(McConnell", "et", "al.", "2006),", "reduced", "lung", "function", "(Pekkanen", "et", "al.", "1997),", "and", "asthma-related", "hospitalizations", "(Lin", "et", "al.", "2002;", "Moore", "et", "al.", "2008).", "There", "is", "now", "increased", "interest", "in", "understanding", "car-", "diovascular", "effects", "(Peters", "2005;", "Rückerl", "et", "al.", "2006),", "identifying", "causal", "constituents", "(Lanki", "et", "al.", "2006),", "and", "characterizing", "susceptible", "sub-", "populations", "(O’Neill", "et", "al.", "2007b).", "Psychological", "stress", "results", "when", "exter-", "nal", "demands", "exceed", "an", "individual’s", "perceived", "abilities", "and", "resources", "to", "meet", "those", "demands", "Environmental", "Health", "Perspectives", "•", "volume", "117", "|", "number", "9", "|", "September", "2009", "(Cohen", "et", "al.", "1995)", "and", "has", "been", "linked", "to", "respiratory", "disease", "and", "other", "illness.", "Limited", "but", "growing", "epidemiologic", "evidence", "indi-", "cates", "that", "psychological", "stress", "may", "also", "alter", "susceptibility", "to", "physical", "exposures,", "such", "as", "air", "pollution.", "This", "work", "examined", "social–", "environmental", "interactions", "in", "respiratory", "and", "cardiovascular", "disease,", "such", "as", "stress-related", "modification", "of", "traffic-related", "air", "pollution", "effects", "on", "asthma", "etiology", "(Clougherty", "et", "al.", "2007)", "or", "exacerbation", "(Chen", "et", "al.", "2008).", "There", "is", "also", "evidence", "of", "stress-related", "modi-", "fication", "in", "the", "relationship", "between", "bone", "lead", "level", "and", "hypertension", "among", "older", "men", "(Peters", "et", "al.", "2007).", "In", "the", "same", "data", "set,", "we", "recently", "identified", "modification", "by", "stress", "in", "the", "relation", "between", "bone", "lead", "and", "heart", "rate", "variability", "(Clougherty", "JE,", "Peters", "JL,", "Schwartz", "J,", "Kubzansky", "L,", "unpublished", "data).", "One", "possible", "pathway", "for", "these", "differential", "susceptibilities", "is", "allostatic", "load", "(McEwen", "and", "Seeman", "1999).", "Allostasis", "(literally,", "“achiev-", "ing", "stability", "through", "change”)", "refers", "to", "the", "body’s", "ability", "to", "adapt", "to", "transient", "stressors", "and", "exposures.", "Over", "time,", "chronic", "psycho-", "logical", "stress", "and", "maladaptive", "behaviors", "(e.g.,", "poor", "diet,", "sleep", "deprivation)", "(McEwen", "2006)", "may", "impair", "the", "body’s", "ability", "to", "maintain", "allostasis,", "producing", "wear", "and", "tear", "on", "bodily", "systems,", "compromised", "immune", "function,", "and", "enhanced", "general", "susceptibility", "(McEwen", "2006;", "McEwen", "and", "Seeman", "1999),", "and", "enhancing", "responsivity", "to", "environmental", "toxi-", "cants", "including", "air", "pollution.", "For", "example,", "some", "toxicologic", "evidence", "suggests", "perma-", "nent", "alteration", "in", "hypothalamic–pituitary–", "adrenal", "(HPA)", "function", "associated", "with", "chronic", "stress", "and", "lead", "exposures", "(Virgolini", "et", "al.", "2005,", "2006).", "However,", "some", "biological", "systems", "involved", "in", "maintaining", "allostasis", "may", "also", "be", "worn", "down", "by", "repeated", "exposure", "to", "physical", "toxicants,", "as", "particle", "exposures", "may", "influence", "HPA", "function", "(Sirivelu", "et", "al.", "2006).", "Finally,", "some", "air", "pollutants", "and", "psycho-", "social", "stress", "may", "independently", "affect", "com-", "mon", "physiologic", "processes", "such", "as", "oxidative", "Address", "correspondence", "to", "J.E.", "Clougherty,", "Harvard", "School", "of", "Public", "Health,", "Landmark", "Building,", "4th", "Floor", "West,", "Boston,", "MA", "02215", "USA.", "Telephone:", "(617)", "816-7717.", "Fax:", "(617)", "384-8859.", "E-mail:", "jcloughe@hsph.harvard.edu", "We", "are", "very", "grateful", "to", "B.", "McEwen", "for", "his", "helpful", "suggestions", "on", "this", "manuscript.", "The", "authors", "declare", "they", "have", "no", "competing", "financial", "interests.", "Received", "23", "January", "2009;", "accepted", "12", "May", "2009.", "1351" ]

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[ "pISSN:", "1011-8942", "eISSN:", "2092-9382", "Calcinosis", "Cutis", "at", "the", "Tarsus", "of", "the", "Upper", "Eyelid", "Ikhyun", "Jun1,", "Sung", "Eun", "Kim", "1", ",", "Sang", "Yeul", "Lee1,", "Gi", "Jeong", "Kim2,", "Jin", "Sook", "Yoon1", "1Institute", "of", "Vision", "Research,", "Department", "of", "Ophthalmology,", "Yonsei", "University", "College", "of", "Medicine,", "Seoul,", "Korea", "2Department", "of", "Pathology,", "Yonsei", "University", "College", "of", "Medicine,", "Seoul,", "Korea", "Calcinosis", "cutis", "involves", "the", "inappropriate", "deposition", "of", "calcium", "within", "the", "dermis", "layer", "of", "the", "skin,", "and", "is", "often", "as-", "sociated", "with", "rheumatoid", "disease.", "A", "42-year-old", "woman", "presented", "for", "evaluation", "of", "a", "hard", "palpable", "mass", "on", "the", "left", "upper", "eyelid.", "After", "everting", "the", "eyelid,", "a", "large", "papillomatous", "mass", "with", "a", "broad", "base", "was", "identified", "on", "the", "superi-", "or", "area", "of", "the", "tarsus.", "The", "lesion", "was", "partially", "excised", "posteriorly", "under", "local", "anesthesia,", "and", "pathologists", "identified", "the", "mass", "as", "calcinosis", "cutis.", "The", "patient", "had", "no", "systemic", "or", "trauma", "history,", "and", "the", "serum", "levels", "of", "calcium", "and", "phosphorous", "were", "normal.", "Idiopathic", "calcinosis", "cutis", "should", "be", "included", "in", "the", "differential", "diagnosis", "for", "a", "protruding", "papillomatous", "mass", "of", "the", "tarsal", "plate,", "and", "surgical", "debulking", "could", "be", "a", "viable", "option", "for", "large", "protruding", "lesions,", "although", "more", "follow-up", "is", "necessary", "to", "monitor", "regrowth.", "Key", "Words:", "Calcinosis", "cutis,", "Idiopathic,", "Papillomatous", "mass,", "Tarsus", "Korean", "J", "Ophthalmol", "2011;25(6):440-442", "http://dx.doi.org/10.3341/kjo.2011.25.6.440", "Case", "Report", "Calcinosis", "cutis", "is", "a", "recognizable", "disorder", "characterized", "by", "the", "deposition", "of", "amorphous", "calcium", "and", "phosphate", "salts", "under", "the", "epidermal", "layer", "[1,2].", "This", "condition", "is", "frequently", "associated", "with", "rheumatoid", "disease,", "and", "can", "lead", "to", "pain", "and", "disability", "in", "these", "patients", "[3].", "Calcinosis", "cutis", "can", "be", "div-", "ided", "into", "four", "types:", "dystrophic,", "metastatic,", "iatrogenic,", "and", "idiopathic.", "The", "dystrophic", "type", "is", "observed", "in", "damaged", "or", "devitalized", "tissues,", "while", "the", "metastatic", "type", "is", "associated", "with", "high", "serum", "levels", "of", "calcium", "or", "phosphate,", "as", "can", "be", "seen", "with", "various", "systemic", "diseases.", "The", "iatrogenic", "type", "of", "calcinosis", "cutis", "is", "generally", "associated", "with", "calcium-containing", "medical", "devices", "or", "medications", "[2],", "and", "the", "idiopathic", "type", "occurs", "in", "the", "absence", "of", "tissue", "injury", "or", "detectable", "disease", "in", "otherwise", "healthy", "individuals.", "Several", "cases", "of", "idiopathic", "calcinosis", "cutis", "involving", "the", "scrotum,", "penis,", "vulva,", "breast,", "or", "extremities", "have", "been", "de-", "scribed", "[1,3,4].", "A", "subepidermal", "calcified", "nodule,", "which", "is", "a", "form", "of", "calcinosis", "cutis,", "on", "the", "eyelid", "beneath", "the", "skin", "has", "al-", "so", "been", "reported", "[5].", "There", "is", "a", "case", "of", "ossification", "of", "the", "eyelid", "and", "orbit", "in", "a", "patient", "with", "pseudo-pseudohypopar-", "athyroidism", "[6].", "However,", "there", "has", "been", "no", "report", "of", "idio-", "pathic", "calcinosis", "cutis", "protruding", "from", "the", "tarsus.", "This", "is", "the", "Received:", "October", "26,", "2010", "Accepted:", "December", "16,", "2010", "Corresponding", "Author:", "Jin", "Sook", "Yoon,", "MD.", "Department", "of", "Ophthalmology,", "Yonsei", "University", "College", "of", "Medicine,", "#250", "Seongsan-ro,", "Seodaemun-gu,", "Seoul", "120-752,", "Korea.", "Tel:", "82-2-2228-3570,", "Fax:", "82-2-3463-1049,", "E-mail:", "yoonjs@yuhs.ac", "first", "case", "report", "of", "idiopathic", "calcinosis", "cutis", "occurring", "at", "the", "upper", "tarsus", "in", "a", "healthy", "woman.", "Case", "Report", "A", "42-year-old", "woman", "presented", "for", "evaluation", "of", "a", "slow-", "growing,", "painless,", "palpable", "mass", "on", "the", "left", "upper", "eyelid,", "which", "initially", "developed", "several", "years", "earlier.", "She", "was", "a", "hepatitis", "B", "virus", "carrier,", "but", "otherwise", "in", "a", "healthy", "condition.", "No", "history", "of", "orbital", "trauma", "or", "filler", "injection", "was", "reported.", "At", "the", "time", "of", "her", "first", "visit,", "her", "uncorrected", "vision", "was", "1.0", "for", "both", "eyes.", "Under", "slit-lamp", "examination,", "slight", "conjunctival", "Fig.", "1.", "Papillomatous", "mass", "involving", "the", "tarsus", "is", "shown", "in", "the", "left", "eye.", "ⓒ", "2011", "The", "Korean", "Ophthalmological", "Society", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses", "/by-nc/3.0/)", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "440" ]

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[ "SAGE-Hindawi", "Access", "to", "Research", "Genetics", "Research", "International", "Volume", "2011,", "Article", "ID", "497148,", "13", "pages", "doi:10.4061/2011/497148", "Review", "Article", "Cytogenetics", "and", "Molecular", "Genetics", "of", "Myxoid", "Soft-Tissue", "Sarcomas", "Jun", "Nishio,1", "Hiroshi", "Iwasaki,2", "Kazuki", "Nabeshima,2", "and", "Masatoshi", "Naito1", "1", "Department", "of", "Orthopaedic", "Surgery,", "Faculty", "of", "Medicine,", "Fukuoka", "University,", "7-45-1", "Nanakuma,", "Jonan-ku,", "Fukuoka", "814-0180,", "Japan", "2", "Department", "of", "Pathology,", "Faculty", "of", "Medicine,", "Fukuoka", "University,", "Fukuoka", "814-0180,", "Japan", "Correspondence", "should", "be", "addressed", "to", "Jun", "Nishio,", "jnishio@cis.fukuoka-u.ac.jp", "Received", "21", "March", "2011;", "Accepted", "6", "June", "2011", "Academic", "Editor:", "Jose´", "Mar´ıa", "Sayague´s", "Copyright", "©", "2011", "Jun", "Nishio", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Myxoid", "soft-tissue", "sarcomas", "represent", "a", "heterogeneous", "group", "of", "mesenchymal", "tumors", "characterized", "by", "a", "predominantly", "myxoid", "matrix,", "including", "myxoid", "liposarcoma", "(MLS),", "low-grade", "fibromyxoid", "sarcoma", "(LGFMS),", "extraskeletal", "myxoid", "chondrosarcoma", "(EMC),", "myxofibrosarcoma,", "myxoinflammatory", "fibroblastic", "sarcoma", "(MIFS),", "and", "myxoid", "dermatofibrosarcoma", "protuberans", "(DFSP).", "Cytogenetic", "and", "molecular", "genetic", "analyses", "have", "shown", "that", "many", "of", "these", "sarcomas", "are", "characterized", "by", "recurrent", "chromosomal", "translocations", "resulting", "in", "highly", "specific", "fusion", "genes", "(e.g.,", "FUS-DDIT3", "in", "MLS,", "FUS-CREB3L2", "in", "LGFMS,", "EWSR1-NR4A3", "in", "EMC,", "and", "COL1A1-PDGFB", "in", "myxoid", "DFSP).", "Moreover,", "recent", "molecular", "analysis", "has", "demonstrated", "a", "translocation", "t(1;", "10)(p22;", "q24)", "resulting", "in", "transcriptional", "upregulation", "of", "FGF8", "and", "NPM3", "in", "MIFS.", "Most", "recently,", "the", "presence", "of", "TGFBR3", "and", "MGEA5", "rearrangements", "has", "been", "identified", "in", "a", "subset", "of", "MIFS.", "These", "genetic", "alterations", "can", "be", "utilized", "as", "an", "adjunct", "in", "diagnostically", "challenging", "cases.", "In", "contrast,", "most", "myxofibrosarcomas", "have", "complex", "karyotypes", "lacking", "specific", "genetic", "alterations.", "This", "paper", "focuses", "on", "the", "cytogenetic", "and", "molecular", "genetic", "findings", "of", "myxoid", "soft-tissue", "sarcomas", "as", "well", "as", "their", "clinicopathological", "characteristics.", "1.", "Introduction", "Myxoid", "soft-tissue", "sarcomas", "encompass", "a", "heterogeneous", "group", "of", "rare", "tumors", "characterized", "by", "a", "marked", "abundance", "of", "mucoid/myxoid", "extracellular", "matrix.", "The", "main", "clinico-", "pathological", "entities", "in", "this", "group", "are", "myxoid", "liposarcoma,", "low-grade", "fibromyxoid", "sarcoma,", "extraskeletal", "myxoid", "chon-", "drosarcoma,", "myxofibrosarcoma,", "myxoinflammatory", "fibrob-", "lastic", "sarcoma,", "and", "myxoid", "dermatofibrosarcoma", "protuber-", "ans", "[1–4].", "The", "correct", "classification", "of", "these", "sarcomas", "is", "important", "because", "of", "their", "distinct", "biological", "behaviors", "and", "potentially", "different", "treatments.", "However,", "it", "is", "often", "difficult", "to", "set", "apart", "many", "of", "these", "sarcomas", "due", "to", "overlapping", "histo-", "logical", "features", "and", "lack", "of", "a", "distinct", "immunohistochemical", "profile.", "Moreover,", "the", "use", "of", "core", "needle", "biopsies", "to", "diagnose", "these", "sarcomas", "has", "become", "increasingly", "common,", "and", "this", "shift", "has", "created", "additional", "challenges.", "Cytogenetic", "and", "molecular", "genetic", "assays", "are", "routinely", "used", "for", "diagnostic", "and", "prognostic", "purposes", "in", "molec-", "ular", "pathology", "laboratories", "[5].", "Many", "of", "myxoid", "soft-", "tissue", "sarcomas", "are", "characterized", "by", "recurrent", "chromosomal", "translocations", "resulting", "in", "highly", "specific", "fusion", "genes", "[6,", "7].", "Advances", "in", "knowledge", "of", "the", "genetics", "of", "these", "sarcomas", "are", "leading", "to", "more", "accurate", "diagnosis.", "This", "paper", "reviews", "the", "cytogenetic", "and", "molecular", "genetic", "findings", "in", "these", "sarcoma", "types", "and", "their", "relationship", "with", "clinicopathological", "features.", "The", "consistent", "genetic", "alterations", "are", "summarized", "in", "Table", "1.", "2.", "Approaches", "to", "the", "Genetics", "of", "Soft-Tissue", "Sarcomas", "Conventional", "karyotyping", "is", "the", "most", "comprehensive", "method", "for", "spotting", "the", "various", "translocations", "and", "other", "structural", "or", "numerical", "aberrations.", "It", "is", "dependent", "on", "the", "availability", "of", "fresh,", "sterile", "tumor", "tissue,", "the", "success", "of", "tumor", "cell", "growth", "in", "culture,", "and", "quality", "of", "metaphase", "cell", "prepara-", "tions.", "When", "dividing", "cells", "are", "not", "available", "for", "cytogenetic", "studies,", "molecular", "approaches", "such", "as", "fluorescence", "in", "situ", "hybridization", "(FISH),", "comparative", "genomic", "hybridization", "(CGH),", "reverse", "transcriptase-polymerase", "chain", "reaction", "(RT-PCR),", "or", "gene", "expression", "microarray", "can", "be", "used", "to", "evaluate", "genetic", "alterations." ]

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[ "Original", "Article", "DOI", "10.3349/ymj.2010.51.1.82", "pISSN:", "0513-5796,", "eISSN:", "1976-2437", "Yonsei", "Med", "J", "51(1):", "82-87,", "2010", "Effect", "of", "Sildenafil", "on", "Neuropathic", "Pain", "and", "Hemodynamics", "in", "Rats", "Lan", "Ji", "Huang,2", "Myung", "Ha", "Yoon,1,2", "Jeong", "Il", "Choi,1", "Woong", "Mo", "Kim,1", "Hyung", "Gon", "Lee,1", "and", "Yeo", "Ok", "Kim1", "1Department", "of", "Anesthesiology", "and", "Pain", "Medicine,", "Chonnam", "National", "University", "Medical", "School,", "Gwangju;", "2The", "Brain", "Korea", "21", "Project,", "Center", "for", "Biomedical", "Human", "Resources", "at", "Chonnam", "National", "University,", "Gwangju,", "Korea.", "Purpose:", "The", "inhibition", "of", "phosphodiesterase", "5", "produces", "an", "antinociception", "through", "the", "increase", "of", "cyclic", "guanosine", "monophosphate", "(cGMP),", "and", "increasing", "cGMP", "levels", "enhance", "the", "release", "of", "γ", "-aminobutyric", "acid", "(GABA).", "Furthermore,", "this", "phosphodiesterase", "5", "plays", "a", "pivotal", "role", "in", "the", "regulation", "of", "the", "vasodilatation", "associated", "to", "cGMP.", "In", "this", "work,", "we", "examined", "the", "contribution", "of", "GABA", "receptors", "to", "the", "effect", "of", "sildenafil,", "a", "phosphodiesterase", "5", "inhibitor,", "in", "a", "neuropathic", "pain", "rat,", "and", "assessed", "the", "hemodynamic", "effect", "of", "sildenafil", "in", "normal", "rats.", "Materials", "and", "Methods:", "Neuropathic", "pain", "was", "induced", "by", "ligation", "of", "L5/6", "spinal", "nerves", "in", "Sprague-", "Dawley", "male", "rats.", "After", "observing", "the", "effect", "of", "intravenous", "sildenafil", "on", "neuropathic", "pain,", "GABAA", "receptor", "antagonist", "(bicuculline)", "and", "GABAB", "receptor", "antagonist", "(saclofen)", "were", "administered", "prior", "to", "delivery", "of", "sildenafil", "to", "determine", "the", "role", "of", "GABA", "receptors", "in", "the", "activity", "of", "sildenafil.", "For", "hemodynamic", "measurements,", "catheters", "were", "inserted", "into", "the", "tail", "artery.", "Mean", "arterial", "pressure", "(MAP)", "and", "heart", "rate", "(HR)", "were", "measured", "over", "60", "min", "following", "administration", "of", "sildenafil.", "Results:", "Intravenous", "sildenafil", "dose-dependently", "increased", "the", "withdrawal", "threshold", "to", "the", "von", "Frey", "filament", "application", "in", "the", "ligated", "paw.", "Intravenous", "bicuculline", "and", "saclofen", "reversed", "the", "antinociception", "of", "sildenafil.", "Intravenous", "sildenafil", "increased", "the", "magnitude", "of", "MAP", "reduction", "at", "the", "maximal", "dosage,", "but", "it", "did", "not", "affect", "HR", "response.", "Conclusion:", "These", "results", "suggest", "that", "sildenafil", "is", "active", "in", "causing", "neuropathic", "pain.", "Both", "GABAA", "and", "GABAB", "receptors", "are", "involved", "in", "the", "antinociceptive", "effect", "of", "sildenafil.", "Additionally,", "intravenous", "sildenafil", "reduces", "MAP", "without", "affecting", "HR.", "Key", "Words:", "Antinociception,", "GABA", "receptor,", "hemodynamics,", "neuropathic", "pain,", "sildenafil,", "Sprague-Dawley", "rat", "Received:", "February", "18,", "2009", "Revised:", "April", "13,", "2009", "Accepted:", "May", "9,", "2009", "Corresponding", "author:", "Dr.", "Myung", "Ha", "Yoon,", "Department", "of", "Anesthesiology", "and", "Pain", "Medicine,", "Chonnam", "National", "University", "Medical", "School,", "8", "Hak-dong,", "Dong-gu,", "Gwangju", "501-757,", "Korea.", "Tel:", "82-62-220-6893,", "Fax:", "82-62-232-6294", "E-mail:", "mhyoon@chonnam.ac.kr", "∙The", "authors", "have", "no", "financial", "conflicts", "of", "interest.", "©", "Copyright:", "Yonsei", "University", "College", "of", "Medicine", "2010", "INTRODUCTION", "Neuropathic", "pain", "refers", "to", "pain", "due", "to", "injury", "or", "diseases", "of", "the", "peripheral", "or", "central", "nervous", "system.1-3", "It", "is", "associated", "with", "severe,", "chronic", "sensory", "disturbances", "characterized", "by", "spontaneous", "pain,", "increased", "responsiveness", "to", "painful", "stimuli", "(hyperalgesia),", "and", "pain", "perceived", "in", "response", "to", "normally", "innocuous", "stimuli", "(allodynia).4,5", "Prevalent", "symptoms", "in", "human", "patients", "include", "cold", "hyperalgesia,", "mechanical", "allodynia,", "and,", "less", "commonly,", "heat", "hyperalgesia.", "Chronic", "neuro-", "pathic", "pain", "remains", "a", "significant", "clinical", "problem", "and", "is", "often", "resistant", "to", "conven-", "tional", "analgesics,", "therefore,", "multimodal", "therapeutic", "options", "have", "been", "proposed.1-3", "Guanylyl", "cyclase", "catalyzes", "the", "formation", "of", "cyclic", "guanosine", "monophosphate", "(cGMP)", "from", "GTP,", "leading", "to", "the", "synthesis", "of", "cGMP,", "whereas", "cGMP-specific", "phosphodiesterase", "catalyzes", "the", "hydrolysis", "of", "cGMP", "to", "GMP.2", "Accordingly,", "intra-", "cellular", "cGMP", "concentrations", "are", "regulated", "by", "the", "action", "of", "guanylyl", "cyclase", "and", "the", "rate", "of", "degradation", "by", "cGMP-specific", "phosphodiesterase.6,7", "82", "Yonsei", "Med", "J", "http://www.eymj.org", "Volume", "51", "Number", "1", "January", "2010" ]

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[ "Cases", "Journal", "Case", "Report", "A", "baby", "presenting", "with", "failure", "to", "thrive", "in", "primary", "care:", "a", "case", "report", "Karen", "J", "Hoare", "BioMed", "Central", "Open", "Access", "Address:", "General", "Practice", "and", "Primary", "Health", "Care,", "School", "of", "Population", "Health", "and", "School", "of", "Nursing,", "The", "University", "of", "Auckland,", "Private", "bag", "92019,", "Auckland,", "New", "Zealand", "Email:", "Karen", "J", "Hoare", "-", "k.hoare@auckland.ac.nz", "Published:", "11", "February", "2009", "Cases", "Journal", "2009,", "2:137", "doi:10.1186/1757-1626-2-137", "This", "article", "is", "available", "from:", "http://www.casesjournal.com/content/2/1/137", "Received:", "8", "January", "2009", "Accepted:", "11", "February", "2009", "©", "2009", "Hoare;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "A", "nine", "month", "old", "baby", "(A)", "presented", "to", "primary", "care", "with", "an", "episode", "of", "diarrhoea.", "Initially", "treated", "at", "home,", "he", "subsequently", "required", "admission", "to", "hospital", "for", "management", "of", "dehydration.", "During", "and", "following", "a", "24", "hour", "period", "of", "hospitalisation,", "his", "mother", "became", "severely", "depressed.", "Case", "presentation:", "A", "was", "examined", "in", "primary", "care", "at", "aged", "11", "months,", "after", "a", "referral", "was", "received", "from", "the", "well", "child", "nurse.", "A's", "weight", "had", "traversed", "downwards", "across", "four", "percentile", "lines", "and", "his", "development", "had", "regressed", "to", "the", "age", "of", "a", "5", "–", "6", "month", "old.", "Conclusion:", "Incomplete", "communication", "between", "health", "professionals", "and", "lack", "of", "follow-up", "and", "overall", "responsibility", "for", "A's", "family", "resulted", "in", "a", "serious", "insult", "to", "A's", "physical", "growth", "and", "development.", "New", "Zealand", "needs", "to", "adopt", "a", "system", "where", "one", "health", "professional", "case", "manages", "infants", "and", "young", "children", "in", "primary", "care.", "Background", "The", "case", "of", "baby", "A", "highlights", "the", "health", "risk", "to", "infants", "of", "having", "a", "mother", "with", "post", "natal", "depression", "(PND).", "PND", "has", "an", "estimated", "prevalence", "of", "13", "percent", "[1].", "Meta", "anal-", "yses", "conducted", "over", "the", "past", "decade", "suggest", "five", "factors", "contributing", "to", "an", "increased", "risk", "of", "PND,", "these", "include;", "a", "history", "of", "depression,", "depression", "or", "anxiety", "during", "preg-", "nancy,", "a", "history", "of", "other", "psychiatric", "conditions,", "recent", "stressful", "life", "events", "and", "poor", "social", "support,", "particularly", "the", "absence", "of", "a", "partner[1].", "Baby", "A's", "mother", "had", "four", "of", "these", "risk", "factors.", "Infant", "mother", "bonding", "is", "crucial", "in", "early", "development,", "interruptions", "may", "be", "detrimental", "to", "the", "moulding", "of", "the", "hypothalamic", "pituitary", "adrenal", "axis", "and", "subsequent", "brain", "development[2].", "Children", "of", "post-", "nataly", "depressed", "mothers", "are", "at", "increased", "risk", "of", "behav-", "ioural", "difficulties,", "with", "poor", "school", "adjustment", "and", "asso-", "ciated", "social", "disaffection.", "Significant", "links", "between", "antenatal", "anxiety", "and", "emotional", "problems", "in", "children,", "aged", "four", "years,", "were", "found", "in", "the", "British", "Avon", "longitudi-", "nal", "study", "of", "parents", "and", "children[3].", "The", "South", "London", "Child", "Development", "study,", "highlighted", "that", "pregnant", "depressed", "women", "were", "seven", "times", "more", "likely", "to", "have", "children", "diagnosed", "with", "conduct", "disorder", "at", "age", "11", "than", "those", "not", "depressed", "[4].", "Case", "presentation", "Baby", "A", "was", "a", "nine", "month", "old", "baby", "of", "mixed", "New", "Zealand", "European", "and", "Mâori", "ethnicity", "living", "with", "his", "solo", "mother", "and", "5", "year", "old", "brother.", "The", "family", "received", "state", "financial", "support.", "He", "was", "a", "normal", "delivery", "at", "term", "with", "a", "birth", "weight", "of", "3.5", "Kgs", "(50", "percentile).", "He", "had", "no", "medical", "his-", "tory", "of", "note.", "At", "9", "months", "old", "he", "attended", "primary", "care", "with", "a", "history", "of", "diarrhoea", "and", "reduced", "feeding", "for", "the", "previous", "two", "days.", "He", "had", "a", "temperature", "of", "37", "degrees,", "Page", "1", "of", "2", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Journal", "of", "Autoimmune", "Diseases", "Review", "Localization", "of", "the", "immunodominant", "region", "on", "human", "thyroid", "peroxidase", "in", "autoimmune", "thyroid", "diseases:", "an", "update", "Damien", "Bresson1,2,", "Sandra", "A", "Rebuffat1", "and", "Sylvie", "Péraldi-Roux*1", "BioMed", "Central", "Open", "Access", "Address:", "1CNRS", "UMR", "5160,", "Centre", "de", "Pharmacologie", "et", "Biotechnologie", "pour", "la", "Santé,", "Faculté", "de", "Pharmacie,", "15", "avenue", "Charles", "Flahault,", "BP", "14491,", "34093", "Montpellier", "Cedex", "5,", "France", "and", "2La", "Jolla", "Institute", "for", "Allergy", "and", "Immunology,", "Department", "of", "Developmental", "Immunology-3,", "10355", "Science", "Center", "Drive,", "San", "Diego,", "CA", "92121,", "USA", "Email:", "Damien", "Bresson", "-", "damienbresson@yahoo.fr;", "Sandra", "A", "Rebuffat", "-", "sandra.rebuffat@ibph.pharma.univ-montp1.fr;", "Sylvie", "Péraldi-", "Roux*", "-", "sylvie.roux@ibph.pharma.univ-montp1.fr", "*", "Corresponding", "author", "Published:", "15", "March", "2005", "Journal", "of", "Autoimmune", "Diseases", "2005,", "2:2", "doi:10.1186/1740-2557-2-2", "This", "article", "is", "available", "from:", "http://www.jautoimdis.com/content/2/1/2", "Received:", "14", "January", "2005", "Accepted:", "15", "March", "2005", "©", "2005", "Bresson", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "AutoimmunityThyroid", "Peroxidase", "(TPO)Autoantibody", "(aAb)Immunodominant", "region", "(IDR)Autoimmune", "Thyroid", "Diseases", "(AITD).", "Abstract", "Recent", "studies", "in", "the", "field", "of", "autoimmune", "thyroid", "diseases", "have", "largely", "focused", "on", "the", "delineation", "of", "B-cell", "auto-epitopes", "recognized", "by", "the", "main", "autoantigens", "to", "improve", "our", "understanding", "of", "how", "these", "molecules", "are", "seen", "by", "the", "immune", "system.", "Among", "these", "autoantigens", "which", "are", "targeted", "by", "autoantibodies", "during", "the", "development", "of", "autoimmune", "thyroid", "diseases,", "thyroid", "peroxidase", "is", "a", "major", "player.", "Indeed,", "high", "amounts", "of", "anti-thyroid", "peroxidase", "autoantibodies", "are", "found", "in", "the", "sera", "of", "patients", "suffering", "from", "Graves'", "disease", "and", "Hashimoto's", "thyroiditis,", "respectively", "hyper", "and", "hypothyroidism.", "Since", "anti-thyroid", "peroxidase", "autoantibodies", "from", "patients'sera", "mainly", "recognize", "a", "discontinuous", "immunodominant", "region", "on", "thyroid", "peroxidase", "and", "due", "to", "the", "complexity", "of", "the", "three", "dimensional", "structure", "of", "human", "thyroid", "peroxidase,", "numerous", "investigations", "have", "been", "necessary", "to", "closely", "localize", "this", "immunodominant", "region.", "The", "aim", "of", "the", "present", "review", "is", "to", "summarize", "the", "current", "knowledge", "regarding", "the", "localization", "of", "the", "immunodominant", "region", "recognized", "by", "human", "thyroid", "peroxidase-specific", "autoantibodies", "generated", "during", "the", "development", "of", "autoimmune", "thyroid", "diseases.", "1.", "Introduction", "Autoimmune", "Thyroid", "Diseases", "(AITD)", "are", "one", "of", "the", "most", "frequent", "organ-specific", "autoimmune", "diseases", "affect-", "ing", "more", "than", "3%", "of", "the", "total", "population", "worldwide.", "The", "clinical", "spectrum", "can", "be", "divided", "into", "two", "major", "subtypes,", "(i)", "glandular", "hyperfunction", "characterized", "by", "Graves'", "dis-", "ease,", "and", "(ii)", "glandular", "hypofunction", "as", "Hashimoto's", "thy-", "roiditis.", "In", "both", "diseases,", "there", "is", "a", "breakdown", "in", "tolerance", "and", "the", "generation", "of", "an", "immunoglobulin", "G", "response", "directed", "against", "thyrotropin", "receptor", "(predomi-", "nantly", "in", "Graves'", "disease", "[1,2]),", "thyroglobulin,", "and", "thy-", "roid", "peroxidase", "(TPO).", "Autoantibodies", "(aAbs)", "against", "TPO,", "a", "common", "denominator", "of", "AITD,", "are", "present", "in", "90%", "of", "Hashimoto's", "thyroiditis", "and", "75%", "of", "Graves'", "dis-", "ease", "patients'", "sera", "[3].", "Since", "anti-TPO", "aAbs", "are", "present", "at", "high", "concentration", "in", "patients'", "sera", "[4,5],", "they", "are", "invalu-", "able", "makers", "of", "the", "thyroid", "autoimmune", "response", "and", "thus", "extensively", "used", "to", "diagnose", "such", "pathologies.", "In", "vitro", "and", "in", "vivo", "cytotoxic", "effector", "functions", "have", "also", "been", "described", "such", "as", "C3", "complement", "activation", "[6-8]", "and", "antibody-dependent", "cell", "cytotoxicity", "[9-12]", "leading", "to", "the", "maintenance", "and", "amplification", "of", "thyroid", "cell", "destruction", "Page", "1", "of", "8", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Interaction", "between", "CXCR4", "and", "CCL20", "Pathways", "Regulates", "Tumor", "Growth", "Katia", "Beider1,", "Michal", "Abraham1,", "Michal", "Begin1,", "Hanna", "Wald1,", "Ido", "D.", "Weiss1,", "Ori", "Wald1,", "Eli", "Pikarsky2,", "Rinat", "Abramovitch1,3,", "Evelyne", "Zeira1,", "Eithan", "Galun", "1", ",", "Arnon", "Nagler4*,", "Amnon", "Peled", "1", "*", "1", "Goldyne", "Savad", "Institute", "of", "Gene", "Therapy,", "Hadassah", "Hebrew", "University", "Hospital,", "Jerusalem,", "Israel,", "2", "Department", "of", "Pathology,", "Hadassah", "Hebrew", "University", "Hospital,", "Jerusalem,", "Israel,", "3", "MRI", "Lab,", "HBRC,", "Hadassah", "Hebrew", "University", "Hospital,", "Jerusalem,", "Israel,", "4", "Bone", "Marrow", "Transplantation", "Department,", "Chaim", "Sheba", "Medical", "Center,", "Tel-", "Hashomer,", "Israel", "Abstract", "The", "chemokine", "receptor", "CXCR4", "and", "its", "ligand", "CXCL12", "is", "overexpressed", "in", "the", "majority", "of", "tumors", "and", "is", "critically", "involved", "in", "the", "development", "and", "metastasis", "of", "these", "tumors.", "CXCR4", "is", "expressed", "in", "malignant", "tumor", "cells", "whereas", "its", "ligand", "SDF-1", "(CXCL12)", "is", "expressed", "mainly", "by", "cancer", "associated", "fibroblasts", "(CAF).", "Similarly", "to", "CXCR4,", "the", "chemokine", "CCL20", "is", "overexpressed", "in", "variety", "of", "tumors;", "however", "its", "role", "and", "regulation", "in", "tumors", "is", "not", "fully", "clear.", "Here,", "we", "show", "that", "the", "chemokine", "receptor", "CXCR4", "stimulates", "the", "production", "of", "the", "chemokine", "CCL20", "and", "that", "CCL20", "stimulates", "the", "proliferation", "and", "adhesion", "to", "collagen", "of", "various", "tumor", "cells.", "Furthermore,", "overexpression", "of", "CCL20", "in", "tumor", "cells", "promotes", "growth", "and", "adhesion", "in", "vitro", "and", "increased", "tumor", "growth", "and", "invasiveness", "in", "vivo.", "Moreover,", "neutralizing", "antibodies", "to", "CCL20", "inhibit", "the", "in", "vivo", "growth", "of", "tumors", "that", "either", "overexpress", "CXCR4", "or", "CCL20", "or", "naturally", "express", "CCL20.", "These", "results", "reveal", "a", "role", "for", "CCL20", "in", "CXCR4-dependent", "and", "-independent", "tumor", "growth", "and", "suggest", "a", "therapeutic", "potential", "for", "CCL20", "and", "CCR6", "antagonists", "in", "the", "treatment", "of", "CXCR4-", "and", "CCL20-dependent", "malignancies.", "Citation:", "Beider", "K,", "Abraham", "M,", "Begin", "M,", "Wald", "H,", "Weiss", "ID,", "et", "al.", "(2009)", "Interaction", "between", "CXCR4", "and", "CCL20", "Pathways", "Regulates", "Tumor", "Growth.", "PLoS", "ONE", "4(4):", "e5125.", "doi:10.1371/journal.pone.0005125", "Editor:", "Neil", "Hotchin,", "University", "of", "Birmingham,", "United", "Kingdom", "Received", "October", "20,", "2008;", "Accepted", "March", "2,", "2009;", "Published", "April", "2,", "2009", "Copyright:", "2009", "Beider", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "was", "supported", "by", "the", "Prostate", "Cancer", "Fund", "(PCF),", "USA,", "and", "the", "Israeli", "Science", "Foundation", "(ISF).", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "arnon.nagler@sheba.health.gov.il", "(AN);", "peled@hadassah.org.il", "(AP)", "Introduction", "Chemokines,", "a", "family", "of", "small", "(5–20", "kDa)", "pro-inflammatory", "cytokines,", "are", "primarily", "responsible", "for", "the", "directional", "migration,", "or", "chemotaxis,", "of", "lymphocytes", "to", "specific", "lymphoid", "tissues,", "and", "the", "recruitment", "of", "leukocytes", "to", "the", "sites", "of", "infection", "or", "tissue", "damage.", "However,", "chemokines", "are", "also", "implicated", "in", "other", "biological", "events", "including", "angiogenesis,", "angiostasis,", "embryogenesis,", "hema-", "topoiesis,", "lymphopoiesis,", "and", "HIV", "pathogenesis", "[1].", "More", "recently,", "it", "has", "been", "established", "that", "cancer", "cells", "exploit", "signaling", "through", "chemokine", "receptors", "via", "several", "key", "steps", "involved", "in", "initiation", "and", "progression", "of", "primary", "and", "metastatic", "cancer.", "Different", "types", "of", "cancers", "express", "different", "chemokine", "receptors", "[2,3],", "however,", "only", "the", "chemokine", "receptor", "CXCR4", "appears", "to", "be", "expressed", "by", "the", "majority", "of", "cancer", "types.", "Tumor", "cells", "from", "at", "least", "23", "different", "types", "of", "cancers", "of", "epithelial,", "mesenchymal", "and", "haematopoietic", "origin", "express", "CXCR4", "[4].", "Moreover,", "CXCR4", "expression", "was", "found", "to", "be", "increased", "in", "several", "malignancies", "including", "gliomas,", "breast", "tumors,", "certain", "leukemia", "cell", "lines,", "uterine", "cancer,", "Burkitt’s", "lymphoma,", "neuroblastomas,", "and", "pancre-", "atic", "cancer", "[5,6,7,8,9,10].", "CXCR4", "was", "also", "found", "to", "play", "a", "critical", "role", "in", "the", "progression", "and", "development", "of", "various", "tumors", "including", "breast,", "prostate", "and", "clear", "cell", "renal", "carcinoma", "[6,11,12,13].", "The", "importance", "of", "the", "CXCR4/CXCL12", "pathway", "in", "tumor", "development", "was", "further", "demonstrated", "by", "neutralizing", "the", "interaction", "between", "CXCL12", "and", "CXCR4.", "[6,14,15,16].", "The", "mechanisms", "by", "which", "CXCR4", "regulate", "tumor", "progression", "are", "yet", "not", "clear.", "Our", "recent", "results", "provide", "a", "novel", "mechanism", "for", "CXCR4-mediated", "tumor", "growth", "and", "metastasis", "and", "establish", "a", "functional", "link", "between", "CXCR4/CXCL12", "and", "CCR6/CCL20", "pathways", "in", "tumor", "development.", "Results", "CXCR4", "up-regulates", "CCL20", "mRNA", "and", "protein", "expression", "in", "prostate", "cancer", "cells", "In", "our", "previous", "work,", "we", "provided", "the", "evidence", "that", "the", "CXCR4", "receptor", "promotes", "prostate", "tumor", "growth,", "invasion", "and", "vascularization", "[17].", "In", "this", "study,", "we", "generated", "single-cell", "clones", "of", "CXCR4-transduced", "PC3", "cells", "with", "high", "and", "stable", "levels", "of", "CXCR4", "expression", "(Fig.", "1A).", "CXCR4-transduced", "PC3", "cells", "with", "high", "and", "stable", "levels", "of", "CXCR4", "expression", "demonstrated", "a", "high", "proliferation", "rate", "in", "vitro", "in", "response", "to", "stimulation", "with", "CXCL12,", "and", "increased", "sensitivity", "to", "low", "concentrations", "of", "CXCL12,", "compared", "to", "wild-type", "PC3", "cells", "(Fig.", "1A).", "Moreover,", "mice", "injected", "subcutaneously", "with", "these", "cells", "developed", "bigger", "tumors", "compared", "to", "mice", "injected", "with", "wild-type", "PC3", "cells,", "similarly", "to", "our", "previous", "results", "(Fig.", "1B,C).", "In", "order", "to", "identify", "genes", "that", "are", "regulated", "by", "CXCR4", "and", "contribute", "to", "the", "aggressive", "phenotype", "of", "CXCR4-expressing", "prostate", "cancer,", "we", "compared", "the", "expression", "pattern", "of", "various", "chemokines", "between", "CXCL12-stimulated", "and", "non-stimulated", "PC3-CXCR4.5", "cells.", "We", "found", "an", "increase", "in", "expression", "of", "the", "chemokine", "CCL20", "following", "stimulation", "with", "CXCL12.", "To", "PLoS", "ONE", "|", "www.plosone.org", "1", "April", "2009", "|", "Volume", "4", "|", "Issue", "4", "|", "e5125" ]

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[ "Molecular", "Vision", "2012;", "18:1572-1582", "<http://www.molvis.org/molvis/v18/a162>", "Received", "23", "March", "2012", "|", "Accepted", "11", "June", "2012", "|", "Published", "14", "June", "2012", "©", "2012", "Molecular", "Vision", "Evaluation", "of", "inter-day", "and", "inter-individual", "variability", "of", "tear", "peptide/protein", "profiles", "by", "MALDI-TOF", "MS", "analyses", "Nerea", "González,1", "Ibon", "Iloro,2", "Juan", "A.", "Durán,3,4", "Félix", "Elortza,2", "Tatiana", "Suárez1", "(The", "first", "two", "authors", "contributed", "equally", "to", "the", "work)", "1Bioftalmik,", "Parque", "Tecnológico", "de", "Vizcaya,", "Derio,", "Spain;", "2Proteomics", "Platform,", "CIC", "bioGUNE,", "CIBERehd,", "ProteoRed-ISCIII,", "Parque", "Tecnológico", "de", "Vizcaya,", "Derio,", "Spain;", "3Instituto", "Clínico", "Quirúrgico", "de", "Oftalmología", "(ICQO),", "Bilbao,", "Spain;", "4Department", "of", "Ophthalmology,", "School", "of", "Medicine,", "University", "of", "Basque", "Country,", "Spain", "Purpose:", "To", "characterize", "the", "tear", "film", "peptidome", "and", "low", "molecular", "weight", "protein", "profiles", "of", "healthy", "control", "individuals,", "and", "to", "evaluate", "changes", "due", "to", "day-to-day", "and", "individual", "variation", "and", "tear", "collection", "methods,", "by", "using", "solid", "phase", "extraction", "coupled", "to", "matrix-assisted", "laser", "desorption/ionization", "time-of-flight", "mass", "spectrometry", "(MALDI-TOF", "MS)", "profiling.", "Methods:", "The", "tear", "protein", "profiles", "of", "six", "healthy", "volunteers", "were", "analyzed", "over", "seven", "days", "and", "inter-day", "and", "inter-", "individual", "variability", "was", "evaluated.", "The", "bilaterality", "of", "tear", "film", "and", "the", "effect", "of", "tear", "collection", "methods", "on", "protein", "profiles", "were", "also", "analyzed", "in", "some", "of", "these", "patients.", "MALDI-TOF", "MS", "analyses", "were", "performed", "on", "tear", "samples", "purified", "by", "using", "a", "solid", "phase", "extraction", "(SPE)", "method", "based", "on", "C18", "functionalized", "magnetic", "beads", "for", "peptide", "and", "low", "molecular", "weight", "protein", "enrichment,", "focusing", "spectra", "acquisition", "on", "the", "1", "to", "20", "kDa", "range.", "Spectra", "were", "analyzed", "using", "principal", "component", "analysis", "(PCA)", "with", "MultiExperiment", "Viewer", "(TMeV)", "software.", "Volunteers", "were", "examined", "in", "terms", "of", "tear", "production", "status", "(Schirmer", "I", "test),", "clinical", "assessment", "of", "palpebral", "lids", "and", "meibomian", "glands,", "and", "a", "subjective", "OSD", "questionnaire", "before", "tear", "collection", "by", "a", "glass", "micro-capillary.", "Results:", "Analysis", "of", "peptides", "and", "proteins", "in", "the", "1–20", "kDa", "range", "showed", "no", "significant", "inter-day", "differences", "in", "tear", "samples", "collected", "from", "six", "healthy", "individuals", "during", "seven", "days", "of", "monitoring,", "but", "revealed", "subtle", "intrinsic", "inter-", "individual", "differences.", "Profile", "analyses", "of", "tears", "collected", "from", "the", "right", "and", "left", "eyes", "confirmed", "tear", "bilaterality", "in", "four", "healthy", "patients.", "The", "addition", "of", "physiologic", "serum", "for", "tear", "sample", "collection", "did", "not", "affect", "the", "peptide", "and", "small", "protein", "profiles", "with", "respect", "to", "the", "number", "of", "resolved", "peaks,", "but", "it", "did", "reduce", "the", "signal", "intensity", "of", "the", "peaks,", "and", "increased", "variability.", "Magnetic", "beads", "were", "found", "to", "be", "a", "suitable", "method", "for", "tear", "film", "purification", "for", "the", "profiling", "study.", "Conclusions:", "No", "significant", "variability", "in", "tear", "peptide", "and", "protein", "profiles", "below", "20", "kDa", "was", "found", "in", "healthy", "controls", "over", "a", "seven", "day", "period,", "nor", "in", "right", "versus", "left", "eye", "profiles", "from", "the", "same", "individual.", "Subtle", "inter-individual", "differences", "can", "be", "observed", "upon", "tear", "profiling", "analysis", "and", "confirm", "intrinsic", "variability", "between", "control", "subjects.", "Addition", "of", "physiologic", "serum", "for", "tear", "collection", "affects", "the", "proteome", "and", "peptidome", "in", "terms", "of", "peak", "intensities,", "but", "not", "in", "the", "composition", "of", "the", "profiles", "themselves.", "This", "work", "shows", "that", "MALDI-TOF", "MS", "coupled", "with", "C18", "magnetic", "beads", "is", "an", "effective", "and", "reproducible", "methodology", "for", "tear", "profiling", "studies", "in", "the", "clinical", "monitoring", "of", "patients.", "Tear", "film", "is", "a", "complex", "gel", "mixture", "with", "a", "thickness", "of", "between", "6", "µm", "and", "20", "µm.", "It", "is", "distributed", "on", "the", "ocular", "surface", "and", "contains", "proteins,", "lipids,", "electrolytes,", "some", "small", "organic", "molecules", "and", "metabolites", "secreted", "by", "the", "main", "lacrimal", "gland", "and", "the", "palpebral", "accessory", "glands", "[1-3].", "The", "normal", "tear", "volume", "is", "around", "6", "µl,", "with", "a", "mean", "secretion", "rate", "about", "1.2", "µl", "per", "min,", "and", "a", "turnover", "rate", "of", "approximately", "16%", "per", "min", "[4].", "In", "spite", "of", "being", "similar", "to", "other", "body", "fluids", "in", "terms", "of", "protein", "composition,", "tear", "film", "has", "a", "characteristically", "high", "concentration", "of", "proteins", "(8", "μg/μl", "approximately),", "ions", "and", "antioxidant", "compounds", "[1,5],", "which", "makes", "it", "particularly", "Correspondence", "to:", "Tatiana", "Suárez,", "Bioftalmik,", "Parque", "Tecnológico", "de", "Vizcaya,", "Ed.", "800,", "2nd", "Floor,", "E-", "48160", "Derio,", "Vizcaya,", "Spain;", "Phone:", "+34-944-069-659;", "FAX:", "+34-946-562-379;", "email:", "tatiana.suarez@bioftalmik.com", "suitable", "for", "proteomic", "analysis,", "despite", "the", "small", "volume", "of", "the", "tear.", "In", "the", "past,", "tear", "film", "proteins", "have", "been", "studied", "by", "using", "gel", "electrophoresis", "and", "other", "techniques", "such", "as", "Edman", "degradation.", "These", "studies", "have", "revealed", "that", "the", "major", "tear", "proteins", "include", "lysozyme,", "lactoferrin,", "lipocalin,", "tear", "specific", "prealbumin,", "serum", "albumin,", "secretory", "IgA,", "and", "lipophilin", "[6-10].", "More", "recently,", "almost", "500", "different", "proteins", "have", "been", "identified", "in", "the", "human", "tear", "film", "[5],", "although", "it", "has", "been", "estimated", "that", "70%–85%", "of", "total", "secretory", "protein", "can", "be", "accounted", "for", "by", "lipocalin,", "lysozyme,", "lactoferrin", "and", "secretory", "immunoglobulin", "A", "[6,11].", "The", "concentration", "of", "these", "major", "tear", "film", "proteins", "can", "oscillate", "between", "1.5", "to", "2.07", "mg/ml.", "However,", "the", "concentration", "of", "other", "low", "abundance", "tear", "film", "proteins", "is", "below", "0.1", "mg/ml", "[11].", "1572" ]

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[ "Line-Tension", "Controlled", "Mechanism", "for", "Influenza", "Fusion", "Herre", "Jelger", "Risselada1*,", "Giovanni", "Marelli2.,", "Marc", "Fuhrmans2.,", "Yuliya", "G.", "Smirnova2,", "Helmut", "Grubmu¨", "ller1,", "Siewert", "Jan", "Marrink3,", "Marcus", "Mu¨", "ller2", "1", "Theoretical", "Molecular", "Biophysics", "Group,", "Max-Planck-Institute", "for", "Biophysical", "Chemistry,", "Go¨", "ttingen,", "Germany,", "2", "Institut", "fu¨", "r", "Theoretische", "Physik,", "Georg-August-", "Universita¨t,", "Go¨", "ttingen,", "Germany,", "3", "Groningen", "Biomolecular", "Sciences", "and", "Biotechnology", "Institute,", "Nijenborgh,", "AG", "Groningen,", "The", "Netherlands", "Abstract", "Our", "molecular", "simulations", "reveal", "that", "wild-type", "influenza", "fusion", "peptides", "are", "able", "to", "stabilize", "a", "highly", "fusogenic", "pre-fusion", "structure,", "i.e.", "a", "peptide", "bundle", "formed", "by", "four", "or", "more", "trans-membrane", "arranged", "fusion", "peptides.", "We", "rationalize", "that", "the", "lipid", "rim", "around", "such", "bundle", "has", "a", "non-vanishing", "rim", "energy", "(line-tension),", "which", "is", "essential", "to", "(i)", "stabilize", "the", "initial", "contact", "point", "between", "the", "fusing", "bilayers,", "i.e.", "the", "stalk,", "and", "(ii)", "drive", "its", "subsequent", "evolution.", "Such", "line-tension", "controlled", "fusion", "event", "does", "not", "proceed", "along", "the", "hypothesized", "standard", "stalk-hemifusion", "pathway.", "In", "modeled", "influenza", "fusion,", "single", "point", "mutations", "in", "the", "influenza", "fusion", "peptide", "either", "completely", "inhibit", "fusion", "(mutants", "G1V", "and", "W14A)", "or,", "intriguingly,", "specifically", "arrest", "fusion", "at", "a", "hemifusion", "state", "(mutant", "G1S).", "Our", "simulations", "demonstrate", "that,", "within", "a", "line-", "tension", "controlled", "fusion", "mechanism,", "these", "known", "point", "mutations", "either", "completely", "inhibit", "fusion", "by", "impairing", "the", "peptide’s", "ability", "to", "stabilize", "the", "required", "peptide", "bundle", "(G1V", "and", "W14A)", "or", "stabilize", "a", "persistent", "bundle", "that", "leads", "to", "a", "kinetically", "trapped", "hemifusion", "state", "(G1S).", "In", "addition,", "our", "results", "further", "suggest", "that", "the", "recently", "discovered", "leaky", "fusion", "mutant", "G13A,", "which", "is", "known", "to", "facilitate", "a", "pronounced", "leakage", "of", "the", "target", "membrane", "prior", "to", "lipid", "mixing,", "reduces", "the", "membrane", "integrity", "by", "forming", "a", "‘super’", "bundle.", "Our", "simulations", "offer", "a", "new", "interpretation", "for", "a", "number", "of", "experimentally", "observed", "features", "of", "the", "fusion", "reaction", "mediated", "by", "the", "prototypical", "fusion", "protein,", "influenza", "hemagglutinin,", "and", "might", "bring", "new", "insights", "into", "mechanisms", "of", "other", "viral", "fusion", "reactions.", "Citation:", "Risselada", "HJ,", "Marelli", "G,", "Fuhrmans", "M,", "Smirnova", "YG,", "Grubmu¨", "ller", "H,", "et", "al.", "(2012)", "Line-Tension", "Controlled", "Mechanism", "for", "Influenza", "Fusion.", "PLoS", "ONE", "7(6):", "e38302.", "doi:10.1371/journal.pone.0038302", "Editor:", "Stefan", "Poehlmann,", "German", "Primate", "Center,", "Germany", "Received", "January", "31,", "2012;", "Accepted", "May", "3,", "2012;", "Published", "June", "28,", "2012", "Copyright:", "2012", "Risselada", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "These", "authors", "have", "no", "support", "or", "funding", "to", "report.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "hrissel@gwdg.de", ".", "These", "authors", "contributed", "equally", "to", "this", "work.", "Introduction", "Membrane", "fusion", "is", "a", "fundamental", "process", "in", "biological", "cells,", "being", "involved", "in", "viral", "infection,", "endo-", "and", "exocytosis,", "and", "fertilization.", "The", "understanding", "of", "its", "molecular", "mechanism", "will", "open", "avenues", "for", "controlling", "a", "variety", "of", "collective", "biophysical", "processes", "that", "alter", "membrane", "topology.", "It", "is", "widely", "accepted", "that", "influenza", "hemagglutinin", "mediates", "a", "fusion", "mechanism", "that", "progresses", "through", "hemifusion", "[1,2].", "In", "the", "standard", "stalk-", "hemifusion", "pathway", "[3–5],", "illustrated", "in", "Fig.", "1,", "the", "initial", "contact", "point", "between", "the", "apposing", "cis-leaflets,", "i.e.", "the", "stalk,", "progresses", "via", "an", "axially", "symmetric", "radial", "expansion", "(stalk", "widening),", "which", "thins", "the", "stalk", "such", "that", "the", "two", "distal", "trans-leaflets", "eventually", "meet", "and", "form", "a", "single-bilayer-thick", "H-shaped", "diaphragm", "(H-HD).", "After", "rupture", "of", "the", "H-HD,", "the", "fusion", "is", "completed.", "Conductance", "measurements", "and", "fluorescence", "spectroscopy", "studies", "of", "fusion", "between", "the", "influenza", "envelope", "(host", "membrane)", "and", "lipid", "model", "membranes", "(target", "membrane)", "have", "reported", "that", "lipid", "mixing", "is", "preceded", "by", "the", "formation", "of", "an", "essential", "pre-fusion", "structure", "in", "the", "target", "membrane", "[6–11].", "Formation", "of", "such", "a", "pre-", "fusion", "structure", "is", "believed", "to", "involve", "perforation", "of", "the", "target", "membrane", "[6,7],", "because", "leakage", "through", "the", "target", "membrane", "is", "detected", "prior", "to", "lipid", "mixing", "[6–8,11,12].", "Intriguingly,", "the", "formation", "of", "a", "small", "(&5", "nm", "wide)", "stable", "p-", "shaped", "HD", "(p-HD),", "illustrated", "in", "Fig.", "2,", "which", "appears", "to", "be", "generated", "by", "a", "stalk", "that", "has", "partially", "encircled", "a", "formed", "membrane", "pore,", "has", "recently", "been", "observed", "by", "electron", "cryo-", "tomography", "of", "influenza", "fusion", "between", "a", "viral", "envelope", "and", "a", "pure", "DOPC", "vesicle", "[7].", "It", "was", "reported", "that", "a", "leaky", "funnel-like", "structure", "was", "formed", "in", "the", "target", "membrane", "prior", "to", "lipid", "mixing.", "Moreover,", "in", "this", "example,", "the", "trans-leaflet", "of", "the", "viral", "membrane", "is", "completely", "covered", "by", "a", "rigid,", "shape-stabilizing", "protein", "matrix", "[7],", "that", "impedes", "bending", "of", "the", "trans-leaflets,", "which", "is", "required", "for", "the", "stalk", "to", "expand", "into", "an", "HD", "(Fig.", "1", "II)", "[4,13].", "Such", "limitation", "should", "have", "substantially", "increased", "the", "already", "large", "barrier", "to", "form", "an", "H-HD", "within", "the", "standard", "hemi-fusion", "mechanism,", "ranging", "from", "15–63", "kBT", "in", "free", "membranes", "without", "protein", "matrix", "[4].", "In", "model", "influenza", "fusion,", "single", "point", "mutations", "of", "the", "fusion", "peptide", "have", "been", "shown", "to", "either", "completely", "inhibit", "fusion,", "specifically", "arrest", "fusion", "at", "a", "hemifusion", "stage,", "or", "induce", "pronounced", "leakage", "of", "the", "target", "membrane", "prior", "to", "lipid", "mixing", "[11,14,15].", "It", "is", "still", "puzzling", "why", "the", "fusion", "mechanism", "is", "so", "sensitive", "to", "minor", "changes", "in", "the", "fusion", "peptide.", "The", "important", "philosophy", "behind", "point", "mutations", "is", "that", "they", "alter", "specific", "and", "essential", "peptide-membrane", "interactions", "and", "thereby", "modify", "the", "ability", "to", "overcome", "free-energy", "barriers", "in", "the", "underlying", "fusion", "mechanism", "of", "the", "wild-type", "peptide.", "Point", "mutation", "studies", "therefore", "play", "a", "key", "role", "in", "unraveling", "the", "mechanism", "of", "influenza", "fusion.", "It", "is", "reasonable", "to", "assume", "that,", "to", "stabilize", "the", "initial", "stalk,", "fusion", "peptides", "should", "stabilize", "the", "negatively", "curved", "stalk", "structure", "[3,4,13,16–20].", "Experiments,", "PLoS", "ONE", "|", "www.plosone.org", "1", "June", "2012", "|", "Volume", "7", "|", "Issue", "6", "|", "e38302" ]

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[ "Published", "online", "11", "July", "2012", "SURVEY", "AND", "SUMMARY", "Nucleic", "Acids", "Research,", "2012,", "Vol.", "40,", "No.", "18", "8783–8792", "doi:10.1093/nar/gks586", "A", "fractal", "model", "for", "nuclear", "organization:", "current", "evidence", "and", "biological", "implications", "Aure´", "lien", "Bancaud1,2,*,", "Christophe", "Lavelle3,", "Se´", "bastien", "Huet4,5", "and", "Jan", "Ellenberg6,*", "1CNRS,", "LAAS,", "7", "avenue", "du", "colonel", "Roche,", "2Universite´", "de", "Toulouse,", "UPS,", "INSA,", "INP,", "ISAE,", "UT1,", "UTM,", "LAAS,", "Toulouse", "F-31077,", "3Genome", "Dynamics", "and", "Regulation,", "Muse´", "um", "National", "d’Histoire", "Naturelle,", "CNRS", "UMR", "7196/INSERM", "U565,", "Paris", "F-75005,", "4CNRS,", "UMR", "6061,", "Institut", "Ge´", "ne´", "tique", "et", "De´", "veloppement", "de", "Rennes,", "5Universite´", "Rennes", "1,", "UEB,UMR", "6290,", "Faculte´", "de", "Me´", "decine,", "Rennes", "F-35043,", "France", "and", "6Cell", "Biology", "and", "Biophysics", "Unit,", "European", "Molecular", "Biology", "Laboratory", "(EMBL),", "Meyerhofstr.", "1,", "Heidelberg", "69117,", "Germany", "Received", "April", "16,", "2012;", "Revised", "and", "Accepted", "May", "24,", "2012", "ABSTRACT", "Chromatin", "is", "a", "multiscale", "structure", "on", "which", "tran-", "scription,", "replication,", "recombination", "and", "repair", "of", "the", "genome", "occur.", "To", "fully", "understand", "any", "of", "these", "processes", "at", "the", "molecular", "level", "under", "physiological", "conditions,", "a", "clear", "picture", "of", "the", "poly-", "morphic", "and", "dynamic", "organization", "of", "chromatin", "in", "the", "eukaryotic", "nucleus", "is", "required.", "Recent", "studies", "indicate", "that", "a", "fractal", "model", "of", "chromatin", "architec-", "ture", "is", "consistent", "with", "both", "the", "reaction-diffusion", "properties", "of", "chromatin", "interacting", "proteins", "and", "with", "structural", "data", "on", "chromatin", "interminglement.", "In", "this", "study,", "we", "provide", "a", "critical", "overview", "of", "the", "experimental", "evidence", "that", "support", "a", "fractal", "organ-", "ization", "of", "chromatin.", "On", "this", "basis,", "we", "discuss", "the", "functional", "implications", "of", "a", "fractal", "chromatin", "model", "for", "biological", "processes", "and", "propose", "future", "experi-", "ments", "to", "probe", "chromatin", "organization", "further", "that", "should", "allow", "to", "strongly", "support", "or", "invalidate", "the", "fractal", "hypothesis.", "INTRODUCTION", "The", "structure", "of", "chromatin", "in", "vivo", "remains", "one", "of", "the", "major", "unsolved", "problems", "in", "biology,", "despite", "its", "eminent", "importance", "as", "template", "onto", "which", "transcription,", "replica-", "tion,", "recombination", "and", "repair", "occur.", "Chromatin", "is", "a", "hier-", "archical", "structure,", "and", "the", "nucleosome,", "which", "consists", "of", "150", "bp", "of", "deoxyribonucleic", "acid", "(DNA)", "wrapped", "around", "an", "octamer", "of", "histone", "proteins,", "is", "its", "constitutive", "basic", "element.", "The", "nucleosome", "structure", "has", "been", "resolved", "with", "atomic", "precision", "by", "X-ray", "diffraction", "(1,2),", "and", "its", "biological", "function", "has", "been", "extensively", "studied", "by", "mo-", "lecular", "biology", "and", "biophysics", "techniques", "over", "the", "past", "three", "decades.", "Beyond", "the", "nucleosome", "level,", "chromatin", "structure", "is", "far", "less", "characterized.", "Condensed", "nucleosome", "arrays", "that", "fold", "into", "a", "‘30", "nm", "fiber’", "have", "been", "described", "long", "ago", "using", "electron", "microscopy", "of", "chromatin", "spread", "at", "moderate", "ionic", "strength", "(3),", "yet", "their", "exact", "structure", "still", "remains", "strongly", "debated", "(4),", "and", "30", "nm", "fibers", "were", "not", "convincingly", "detected", "in", "vivo", "using", "high-resolution", "electron", "microscopy", "of", "thin", "nuclear", "sections,", "which", "rather", "pointed", "to", "the", "existence", "of", "fibers", "with", "a", "variety", "of", "diameters,", "none", "particularly", "resonant", "with", "a", "hierarchical", "organization", "built", "on", "a", "30", "nm", "structural", "element", "(5).", "At", "larger", "scales,", "chromatin", "is", "arranged", "in", "three", "dimensions", "(6),", "allowing", "for", "crosstalk", "between", "distant", "chromatin", "loci", "in", "cis", "and", "in", "trans", "that", "participate", "in", "large-scale", "expression", "regulation", "(7).", "Although", "this", "architectural", "level", "seems", "to", "be", "crucial", "for", "genomic", "transactions,", "as", "is", "its", "conservation", "through", "cell", "cycle", "(8),", "the", "multiscale", "structure", "of", "chroma-", "tin", "is", "still", "hotly", "debated", "(9),", "and", "the", "topological", "param-", "eters", "characterizing", "this", "organization", "remain", "unknown.", "Recent", "studies", "indicated", "that", "a", "fractal", "model", "of", "chro-", "matin", "architecture", "is", "consistent", "with", "structural", "data", "on", "chromatin", "interminglement", "(10)", "and", "with", "the", "diffusion", "and", "binding", "properties", "of", "chromatin", "interacting", "proteins", "(11).", "Fractal", "structures", "are", "self-similar,", "meaning", "that", "they", "consist", "of", "characteristic", "patterns", "that", "can", "be", "repeatedly", "observed", "after", "zooming", "in", "on", "any", "part", "of", "it", "at", "any", "mag-", "nification.", "The", "fractal", "formalism", "has", "been", "successfully", "used", "to", "describe", "numerous", "natural", "shapes", "[Figure", "1a,", "(12–14)],", "and", "several", "studies", "have", "invoked", "this", "model", "in", "the", "nuclear", "context.", "For", "instance,", "the", "analysis", "of", "genomic", "DNA", "sequences", "by", "statistical", "methods", "showed", "long-range", "*To", "whom", "correspondence", "should", "be", "addressed.", "Tel:", "+49", "6221", "3878391;", "Fax:", "+49", "6221", "3878512;", "Email:", "jan.ellenberg@embl.de", "Correspondence", "may", "also", "be", "addressed", "to", "Aur", "e´lien", "Bancaud.", "Tel:", "+33", "5", "6133", "6246;", "Fax:", "+33", "5", "6133", "6208;", "Email:", "abancaud@laas.fr", "The", "Author(s)", "2012.", "Published", "by", "Oxford", "University", "Press.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/", "by-nc/3.0),", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Original", "Article", "Karyotypic", "and", "fluorescent", "in", "situ", "hybridization", "study", "of", "the", "centromere", "of", "chromosome", "7", "in", "secondary", "myeloid", "neoplasms", "Roberta", "Sandra", "da", "Silva", "Tanizawa1", "Cristina", "Aiko", "Kumeda1", "Raymundo", "Soares", "de", "Azevedo", "Neto2", "Aline", "de", "Medeiros", "Leal1", "Patrícia", "de", "Barros", "Ferreira1", "Elvira", "Deolinda", "Rodrigues", "Pereira", "Velloso1", "1Cytogenetics", "Laboratory,", "Serviço", "de", "Hematologia", "do", "Hospital", "das", "Clínicas,", "Faculdade", "de", "Medicina,", "Universidade", "de", "São", "Paulo", "–", "USP,", "São", "Paulo,", "SP,", "Brazil", "2Pathology", "Service,", "Faculdade", "de", "Medicina,", "Universidade", "de", "São", "Paulo", "–", "USP,", "São", "Paulo,", "SP,", "Brazil", "Conflict-of-interest", "disclosure:", "The", "authors", "declare", "no", "competing", "financial", "interest", "Submitted:", "3/13/2011", "Accepted:", "9/5/2011", "Corresponding", "author:", "Roberta", "Sandra", "da", "Silva", "Tanizawa", "Laboratório", "de", "Citogenética", "Av.", "Dr.", "Enéas", "de", "Carvalho", "Aguiar,", "155", "1º", "andar,", "sala", "30", "–", "Cerqueira", "César", "05403-000", "–", "São", "Paulo,", "SP,", "Brazil", "Phone:", "55", "11", "3061-5544", "R-312", "robertatani@uol.com.br", "www.rbhh.org", "or", "www.scielo.br/rbhh", "DOI:", "10.5581/1516-8484.20110117", "Background:", "Secondary", "myeloid", "neoplasms", "comprise", "a", "group", "of", "secondary", "diseases", "following", "exposure", "to", "myelotoxic", "agents", "or", "due", "to", "congenital", "diseases.", "The", "improvement", "of", "anticancer", "agents", "and", "immunosuppressive", "drugs", "seem", "to", "be", "associated", "with", "an", "increased", "incidence", "of", "secondary", "myeloid", "neoplasms.", "Karyotyping", "of", "bone", "marrow", "is", "essential", "for", "diagnosis", "and", "prognosis.", "Previous", "use", "of", "alkylating", "agents", "and", "radiation", "are", "associated", "with", "clonal", "abnormalities", "such", "as", "recurrent", "unbalanced", "-5/5q-,", "-7/7q-", "and", "complex", "karyotypes,", "whereas", "topoisomerase-II", "inhibitors", "lead", "to", "changes", "such", "as", "the", "balanced", "11q23", "rearrangement,", "t(8;21),", "t(15;17)", "and", "inv(16).", "Objective:", "To", "study", "the", "clinical", "and", "cytogenetic", "data", "of", "patients", "with", "secondary", "myeloid", "neoplasms", "who", "took", "antineoplastic", "and/or", "immunosuppressive", "drugs", "or", "progressed", "from", "aplastic", "anemia.", "Methods:", "The", "clinical", "and", "cytogenetic", "characteristics", "of", "42", "patients", "diagnosed", "with", "secondary", "myeloid", "neoplasms", "in", "one", "institution", "were", "retrospectively", "evaluated.", "Of", "these,", "25,", "11", "and", "6", "patients", "had", "had", "oncological", "diseases,", "aplastic", "anemia", "and", "other", "diseases,", "respectively.", "Conventional", "cytogenetic", "and", "FISH", "analyses", "were", "performed", "for", "monosomy", "7.", "Results:", "The", "cytogenetic", "study", "was", "conclusive", "in", "32", "cases", "with", "84.4%", "of", "clonal", "abnormalities.", "Monosomy", "7", "and", "complex", "karyotypes", "were", "present", "in", "44.4%", "and", "37%,", "respectively.", "A", "high", "prevalence", "of", "unbalanced", "abnormalities", "(96.3%)", "was", "observed.", "Monosomy", "7", "was", "more", "prevalent", "in", "patients", "with", "myelodysplastic", "syndromes/myeloid", "neoplasms", "after", "aplastic", "anemia", "(66.6%).", "The", "median", "survival", "after", "diagnosis", "of", "myeloid", "neoplasms", "was", "only", "5.7", "months.", "Normal", "cytogenetics", "was", "associated", "to", "better", "survival", "(p-value", "=", "0.03).", "There", "was", "a", "slightly", "worse", "trend", "of", "survival", "for", "patients", "with", "complex", "karyotypes", "(p-value", "=", "0.057).", "Abnormal", "karyotype", "was", "an", "independent", "risk", "factor", "for", "poor", "survival", "(p-value", "=", "0.012).", "Conclusion:", "This", "study", "enhances", "the", "importance", "of", "cytogenetic", "analysis", "of", "patients", "at", "the", "time", "of", "diagnosis", "of", "secondary", "myeloid", "neoplasms.", "Keywords:", "Cytogenetic", "analysis;", "Myelodysplastic", "syndromes;", "Leukemia,", "myeloid", "Introduction", "The", "myelodysplastic", "syndromes", "(MDS),", "acute", "myeloid", "leukemias", "(AML)", "and", "secondary", "myeloproliferative", "syndromes", "(MPS)", "constitute", "a", "group", "of", "myeloid", "neoplasias", "(MNs)", "which", "result", "from", "exposure", "to", "risk", "factors", "such", "as", "chemotherapy", "and", "radiotherapy,", "acquired", "aplastic", "anemia", "associated", "with", "immunosuppression", "and", "congenital", "diseases.(1-5)", "A", "cytogenetic", "study", "of", "the", "bone", "marrow,", "fundamental", "for", "the", "characterization", "of", "the", "secondary", "MNs,", "provides", "essential", "information", "for", "the", "diagnosis", "and", "prognosis", "of", "the", "disease.", "Between", "80", "and", "95%", "of", "patients", "with", "MDS/MN", "present", "abnormal", "and", "frequently", "complex", "karyotypes", "(an", "average", "of", "5.3", "abnormalities", "per", "case).", "Chromosome", "7", "monosomy", "is", "the", "commonest", "alteration", "in", "patients", "with", "secondary", "MN", "after", "aplastic", "anemia", "(AA).(6)", "It", "is", "estimated", "that", "10-20%", "of", "myeloid", "neoplasia", "cases", "are", "secondary", "to", "the", "use", "of", "chemotherapeutic", "agents", "and/or", "radiotherapy.(5)", "The", "progress", "of", "therapeutic", "regimens", "used", "to", "treat", "primary", "neoplasias,", "as", "well", "as", "the", "new", "conditions", "of", "autologous", "hematopoietic", "stem", "cell", "transplantations", "(HSCT),", "have", "led", "to", "an", "increase", "in", "the", "rate", "of", "therapy-related", "myeloid", "neoplasia", "(MN-t)", "cases.(7)", "Some", "patterns", "of", "chromosomal", "abnormalities", "are", "recurrent", "after", "exposure", "to", "cytotoxic", "agents.", "The", "previous", "use", "of", "alkylating", "agents/radiation", "can", "favor", "the", "development", "of", "MN-t,", "which", "is", "usually", "associated", "with", "cytopenia", "and", "dysplasia", "and", "often", "involves", "unbalanced", "clonal", "genetic", "alterations", "including", "monosomies", "or", "deletions", "of", "chromosomes", "5", "and/or", "7,", "and", "complex", "karyotypes", "with", "numerous", "marker", "chromosomes", "that", "may", "progress", "to", "point", "alterations", "in", "the", "P53", "and", "AML1", "genes.", "Previous", "use", "of", "topoisomerase", "II", "inhibitors", "(etoposide,", "anthracyclines)", "is", "usually", "associated", "with", "the", "development", "of", "AML,", "frequently", "with", "Rev", "Bras", "Hematol", "Hemoter.", "2011;33(6):425-31", "425" ]

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[ "Tiago", "et", "al.", "Acta", "Veterinaria", "Scandinavica", "2012,", "54:20", "http://www.actavetscand.com/content/54/1/20", "C", "A", "S", "E", "R", "E", "P", "O", "R", "T", "Open", "Access", "Conception", "rate,", "uterine", "infection", "and", "embryo", "quality", "after", "artificial", "insemination", "and", "natural", "breeding", "with", "a", "stallion", "carrier", "of", "Pseudomonas", "aeruginosa:", "a", "case", "report", "Guimarães", "Tiago1,2,", "Carvalheira", "Júlio1,3", "and", "Rocha", "António1,2*", "Abstract", "Background:", "Pseudomonas", "aeruginosa", "may", "cause", "venereal", "disease", "and", "infertility", "in", "horses.", "A", "Pseudomonas", "aeruginosa", "-", "carrier", "stallion,", "often", "unresponsive", "to", "artificial", "vagina", "collection,", "was", "used", "to", "naturally", "breed", "mares.", "Semen", "collected", "from", "the", "same", "stallion", "was", "also", "used", "to", "perform", "artificial", "inseminations.", "Pregnancy", "rates,", "embryo", "quality", "and", "incidence", "of", "uterine", "infection", "were", "compared", "between", "inseminated", "or", "naturally-bred", "mares.", "Methods:", "P.", "aeruginosa", "was", "isolated", "from", "swabbing", "of", "the", "penis,", "prepuce", "and", "distal", "urethra", "of", "the", "stallion.", "Before", "being", "bred", "or", "inseminated,", "clitoral/vestibular", "samples", "were", "collected", "from", "all", "mares,", "and", "cultured", "for", "isolation", "of", "P.", "aeruginosa.", "At", "the", "first", "observed", "estrus,", "endometrial", "swabs", "were", "also", "collected.", "All", "mares", "subjected", "to", "natural", "mating", "(NS)", "were", "re-evaluated", "for", "P.aeruginosa", "by", "culture", "of", "clitoral", "and", "endometrial", "swabs.", "Artificial", "inseminations", "(AI)", "were", "performed", "either", "with", "fresh-extended", "semen", "(11", "AI/7", "mares)", "or", "frozen", "semen", "(10", "AI/7", "mares).", "The", "stallion", "was", "also", "used", "to", "breed", "3", "mares", "(4", "services).", "For", "embryo", "collection,", "2", "mares", "were", "inseminated", "with", "fresh-", "extended", "semen", "(1", "AI/mare),", "and", "2", "additional", "mares", "were", "inseminated", "with", "frozen", "semen", "(2", "AI/mare).", "Two", "mares", "were", "naturally-bred", "with", "a", "total", "of", "9", "services,", "for", "embryo", "collection.", "All", "mares", "were", "examined", "after", "AI", "or", "natural", "service", "(NS),", "for", "uterine", "pathologies.", "Embryo", "recoveries", "were", "attempted", "passing", "a", "catheter", "with", "inflatable", "cuff", "connected", "to", "a", "sterile", "flexible", "2-way", "flushing", "catheter,", "through", "the", "cervix.", "Flushed", "media", "was", "recovered", "into", "an", "Em-Con", "filter,", "and", "embryos", "searched", "using", "a", "stereoscope.", "Embryos", "were", "graded", "from", "1", "(excellent)", "to", "4", "(degenerated/dead).", "Results:", "Pregnancy", "rates", "obtained", "after", "NS", "was", "50%", "per", "cycle.", "However,", "more", "than", "half", "of", "the", "NS", "resulted", "in", "uterine", "disease,", "while", "uterine", "pathology", "was", "seen", "only", "in", "22%", "of", "the", "time", "following", "AI.", "Half", "of", "the", "mares", "bred", "by", "NS", "got", "positive", "to", "P.", "aeruginosa.", "Percentage", "of", "embryo", "recovery", "rates", "was", "identical", "after", "AI", "or", "NS", "(66.7%).", "The", "4", "embryos", "recovered", "after", "AI", "were", "classified", "as", "Grade", "1,", "while", "after", "NS", "only", "2", "out", "of", "the", "6", "recovered", "embryos", "were", "Grade", "1.", "Conclusion:", "a)", "there", "was", "no", "evidence", "of", "reduced", "fertilization", "after", "AI", "or", "NS,", "b)", "a", "numerically", "higher", "incidence", "of", "uterine", "disease", "was", "noticed", "after", "NS,", "c)", "venereal", "transmission", "of", "P.", "aeruginosa", "after", "NS", "was", "confirmed,", "d)", "a", "lower", "percentage", "of", "G1", "embryos", "may", "be", "obtained", "after", "NS.", "Overall,", "the", "data", "supports", "the", "indication", "for", "P.", "aeruginosa-", "carrier", "stallions", "to", "be", "bred", "by", "AI", "rather", "than", "by", "NS,", "and", "raises", "the", "possibility", "that", "P.", "aeruginosa", "may", "affect", "embryo", "quality.", "Keywords:", "Stallion,", "Pseudomonas", "aeruginosa,", "Venereal", "diseases,", "Artificial", "insemination,", "Embryo", "quality", "*", "Correspondence:", "arocha@mail.icav.up.pt", "1ICBAS", "-", "Abel", "Salazar", "Biomedical", "Institute,", "ICBAS,", "University", "of", "Porto,", "Campus", "Agrário", "de", "Vairão,", "Rua", "Padre", "Armando", "Quintas", "7,", "Vairão", "4485-661,", "Portugal", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "©", "2012", "Tiago", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Pimentel", "et", "al.", "Nutrition", "&", "Metabolism", "2011,", "8:11", "http://www.nutritionandmetabolism.com/content/8/1/11", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "b-Hydroxy-b-methylbutyrate", "(HMb)", "supplementation", "stimulates", "skeletal", "muscle", "hypertrophy", "in", "rats", "via", "the", "mTOR", "pathway", "Gustavo", "D", "Pimentel1,2*,", "José", "C", "Rosa1,", "Fábio", "S", "Lira1,", "Nelo", "E", "Zanchi3,", "Eduardo", "R", "Ropelle2,4,", "Lila", "M", "Oyama1,", "Cláudia", "M", "Oller", "do", "Nascimento1,", "Marco", "Túlio", "de", "Mello5,", "Sergio", "Tufik5,", "Ronaldo", "VT", "Santos6", "Abstract", "b-Hydroxy-b-methylbutyrate", "(HMb)", "supplementation", "is", "used", "to", "treat", "cancer,", "sepsis", "and", "exercise-induced", "muscle", "damage.", "However,", "its", "effects", "on", "animal", "and", "human", "health", "and", "the", "consequences", "of", "this", "treatment", "in", "other", "tissues", "(e.g.,", "fat", "and", "liver)", "have", "not", "been", "examined.", "The", "purpose", "of", "this", "study", "was", "to", "evaluate", "the", "effects", "of", "HMb", "supplementation", "on", "skeletal", "muscle", "hypertrophy", "and", "the", "expression", "of", "proteins", "involved", "in", "insulin", "signalling.", "Rats", "were", "treated", "with", "HMb", "(320", "mg/kg", "body", "weight)", "or", "saline", "for", "one", "month.", "The", "skeletal", "muscle", "hypertrophy", "and", "insulin", "signalling", "were", "evaluated", "by", "western", "blotting,", "and", "hormonal", "concentrations", "were", "evaluated", "using", "ELISAs.", "HMb", "supplementation", "induced", "muscle", "hypertrophy", "in", "the", "extensor", "digitorum", "longus", "(EDL)", "and", "soleus", "muscles", "and", "increased", "serum", "insulin", "levels,", "the", "expression", "of", "the", "mammalian", "target", "of", "rapamycin", "(mTOR)", "and", "phosphorylation", "of", "p70S6K", "in", "the", "EDL", "muscle.", "Expression", "of", "the", "insulin", "receptor", "was", "increased", "only", "in", "liver.", "Thus,", "our", "results", "suggest", "that", "HMb", "supplementation", "can", "be", "used", "to", "increase", "muscle", "mass", "without", "adverse", "health", "effects.", "Introduction", "The", "amino", "acid", "leucine", "has", "been", "shown", "to", "stimulate", "skeletal", "muscle", "protein", "synthesis", "and", "attenuate", "muscle", "proteolysis.", "Some", "of", "these", "benefits", "have", "been", "attributed", "to", "the", "conversion", "of", "leucine", "to", "its", "metabolite", "b-hydroxy-", "b-methylbutyrate", "(HMb)", "[1-4],", "which", "has", "been", "shown", "to", "be", "anti-catabolic", "and", "effective", "at", "attenuating", "muscle", "atrophy", "during", "exercise", "stress", "[2,5,6]", "and", "in", "models", "of", "cancer", "[4,7],", "congestive", "heart", "failure,", "sepsis,", "and", "HIV", "[8,9].", "According", "to", "a", "review", "published", "by", "Nelo", "et", "al.", "[10],", "the", "dose", "of", "HMb", "supplementation", "used", "in", "the", "majority", "of", "the", "previous", "studies", "to", "achieve", "these", "effects", "was", "3", "g/day", "of", "HMb;", "use", "of", "this", "dose", "is", "based", "on", "evi-", "dence", "that", "it", "produces", "better", "results", "than", "1.5", "g/day.", "HMb", "is", "produced", "by", "the", "transamination", "of", "a-ketoisocaproate", "(KIC),", "which", "is", "metabolised", "to", "isova-", "leryl-CoA", "by", "the", "enzyme", "KIC", "dioxygenase.", "The", "cytosolic", "dioxygenase", "enzyme", "differs", "from", "the", "mitochondrial", "KIC", "dehydrogenase", "enzyme", "in", "several", "ways.", "KIC", "dioxygenase", "*", "Correspondence:", "gupimentel@yahoo.com.br", "1Department", "of", "Physiology", "of", "Nutrition,", "Federal", "University", "of", "São", "Paulo", "(UNIFESP),", "São", "Paulo,", "SP", "-", "Brazil", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "produces", "free", "HMb", "in", "the", "cytosol,", "whereas", "the", "dehydro-", "genase", "enzyme", "produces", "the", "CoA", "derivative", "of", "isovaleric", "acid", "in", "the", "mitochondria", "[11,12].", "Quantitatively,", "it", "is", "estimated", "that", "approximately", "5%", "of", "all", "L-leucine", "oxi-", "dised", "in", "the", "human", "body", "is", "converted", "to", "HMb.", "There-", "fore,", "a", "subject", "weighing", "70", "kg", "produces", "approximately", "0.2", "-", "0.4", "g", "HMb/day,", "depending", "on", "the", "content", "of", "leu-", "cine", "in", "the", "diet.", "Because", "leucine,", "like", "all", "essential", "amino", "acids,", "is", "not", "synthesised", "in", "the", "human", "body,", "HMb", "is", "produced", "from", "dietary", "protein", "[13].", "The", "results", "of", "trials", "evaluating", "the", "effect", "of", "HMb", "sup-", "plementation", "on", "reversing", "cachexia", "associated", "with", "rheumatoid", "arthritis", "[14],", "HIV", "[8],", "and", "muscle", "damage", "[15,16]", "are", "performed", "merely", "with", "biochemical", "markers.", "Additionally,", "most", "of", "the", "available", "studies", "concerning", "the", "effects", "of", "HMb", "are", "related", "to", "effects", "on", "skeletal", "muscle,", "with", "an", "absence", "of", "relevant", "information", "con-", "cerning", "consequences", "in", "other", "peripheral", "tissues", "(e.g.,", "adipose", "tissue", "and", "liver).", "Recently,", "Holecek", "et", "al.", "[17]", "demonstrated", "increases", "in", "protein", "synthesis", "in", "the", "liver", "upon", "HMb", "supplementation.", "However,", "the", "authors", "did", "not", "describe", "the", "mechanisms", "involved", "in", "this", "increase.", "Moreover,", "descriptions", "of", "the", "©", "2011", "Pimentel", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Original", "Article", "Knee", "Surg", "Relat", "Res", "2012;24(1):14-18", "http://dx.doi.org/10.5792/ksrr.2012.24.1.14", "pISSN", "2234-0726", "·", "eISSN", "2234-2451", "Knee", "Surgery", "&", "Related", "Research", "The", "Efficacy", "and", "Safety", "of", "Postoperative", "Autologous", "Transfusion", "of", "Filtered", "Shed", "Blood", "and", "Anticoagulant", "Prophylaxis", "in", "Total", "Knee", "Arthroplasty", "Patients", "Kwon-Hee", "Park,", "MD,", "Sung-Rak", "Lee,", "MD,", "Jong-Mun", "Jin,", "MD", "and", "Myung-Sang", "Moon,", "MD", "Department", "of", "Orthopaedic", "Surgery,", "Cheju", "Halla", "General", "Hospital,", "Jeju,", "Korea", "Purpose:", "To", "assess", "the", "efficacy", "and", "safety", "of", "autologous", "transfusion", "of", "filtered", "shed", "blood", "in", "total", "knee", "arthroplasty", "(TKA).", "Materials", "and", "Methods:", "A", "total", "of", "42", "patients", "with", "TKA", "(group", "A;", "without", "autologous", "transfusion", "in", "15", "patients,", "group", "B;", "with", "autologous", "transfusion", "in", "27", "patients)", "were", "evaluated", "retrospectively.", "The", "influence", "of", "autologous", "reinfusion", "of", "filtered", "blood,", "bleeding", "tendency,", "amount", "of", "blood", "drainage,", "rate", "of", "allogenic", "transfusion,", "and", "the", "postoperative", "changes", "of", "hemoglobin", "were", "analyzed.", "Results:", "Allogenic", "transfusion", "was", "needed", "in", "26.7%", "(4/15)", "of", "group", "A", "and", "none", "of", "group", "B", "till", "postoperative", "48", "hours.", "Till", "postoperative", "14", "days,", "46.7%", "(7/15)", "of", "group", "A", "needed", "allogenic", "transfusion", "while", "7.4%", "(2/27)", "in", "group", "B.", "The", "average", "drained", "blood", "volume", "was", "1,197±400", "mL", "in", "group", "A", "and", "975±422", "mL", "in", "group", "B.", "The", "average", "decrease", "of", "hemoglobin", "at", "postoperative", "1,", "7,", "and", "14", "days", "was", "2.9±1.5,", "2.9±1.6,", "and", "2.3±1.5", "g/dL", "respectively", "in", "group", "A", "and", "2.7±0.8,", "4.0±1.0,", "and", "2.9±1.3", "g/dL", "respectively", "in", "group", "B.", "Conclusions:", "An", "autotransfusion", "system", "lowered", "the", "allogenic", "transfusion", "rate,", "while", "anticoagulants", "did", "not", "increase", "the", "amount", "of", "drained", "blood.", "An", "autotransfusion", "system", "with", "anticoagulants", "was", "effective", "and", "safe", "to", "save", "the", "shed", "blood", "in", "TKA.", "Key", "words:", "Total", "knee", "arthroplasty,", "Autotransfusion,", "Anticoagulants.", "Introduction", "deep", "vein", "thrombosis", "(DVT)", "can", "cause", "fatal", "pulmonary", "embolism", "(PE)2)", "and", "prophylactic", "anticoagulants", "have", "been", "Suction", "drainage", "in", "total", "knee", "arthroplasty", "(TKA)", "has", "been", "used", "commonly", "used", "to", "prevent", "DVT.", "In", "this", "study,", "we", "assessed", "the", "primarily", "to", "prevent", "hemoarthrosis,", "hematomas", "and", "infections,", "efficacy", "of", "autologous", "transfusion", "of", "filtered", "shed", "blood", "on", "and", "secondly", "to", "promote", "wound", "healing", "and", "rehabilitation1).", "In", "bleeding", "tendency", "and", "vital", "signs", "and", "safety", "of", "anticoagulation", "general,", "a", "large", "amount", "of", "blood", "is", "lost", "during", "and", "after", "surgery,", "prophylaxis.", "which", "requires", "allogenic", "transfusion", "to", "stabilize", "the", "patient’s", "vital", "signs.", "To", "reduce", "the", "amount", "of", "allogenic", "transfusion,", "various", "autotransfusion", "systems", "have", "been", "introduced.", "TKA-associated", "Received", "June", "13,", "2011;", "Revised", "(1st)", "July", "4,", "2011;", "(2nd)", "September", "7,", "2011;", "Accepted", "October", "4,", "2011.", "Correspondence", "to:", "Sung-Rak", "Lee,", "MD.", "Department", "of", "Orthopaedic", "Surgery,", "Cheju", "Halla", "General", "Hospital,", "65", "Doryeong-ro,", "Jeju", "690-170,", "Korea.", "Tel:", "+82-64-740-5030,", "Fax:", "+82-64-743-3110", "Email:", "drthatka@yahoo.co.kr", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/by-nc/3.0/)", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Copyright", "©", "2012.", "THE", "KOREAN", "KNEE", "SOCIETY", "www.jksrr.org", "14", "Materials", "and", "Methods", "1.", "Materials", "Between", "January", "2006", "and", "May", "2010,", "42", "female", "patients", "with", "unilateral", "TKA", "by", "a", "single", "surgeon", "were", "enrolled", "in", "the", "present", "study.", "Patients", "with", "a", "history", "of", "bleeding", "tendency", "were", "excluded.", "Fifteen", "TKA", "patients", "(group", "A)", "had", "a", "suction", "drain", "(Baro-Vac,", "Sewoon", "Medical,", "Cheonan,", "Korea)", "only", "without", "anticoagulant,", "while", "27", "TKA", "patients", "(group", "B)", "received", "autotransfusion", "(Consta-Vac,", "Stryker,", "Michigan,", "MI,", "USA)", "and", "anticoagulant", "therapy", "using", "Fondaparinux", "(Arixtra,", "Glaxo", "Smith", "Kline,", "London,", "England).", "The", "maximum", "negative", "pressure", "of", "Baro-Vac", "was", "90", "mm", "Hg", "and", "we", "used", "half", "pressure.", "The", "negative", "pressure", "of", "Consta-Vac", "was", "50", "mm", "Hg.", "The", "mean", "age", "of", "group", "A", "and", "B", "patients", "was", "72.9", "(range,", "54" ]

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"that", "are", "predictive", "of", "aMCI", "through", "informant-based", "information", "may", "provide", "some", "clinical", "utility", "in", "accurately", "identifying", "individuals", "who", "are", "at", "risk", "for", "developing", "Alzheimer’s", "disease", "(AD).", "Methods:", "The", "current", "study", "utilized", "a", "case-control", "design", "using", "data", "from", "an", "ongoing", "validation", "study", "of", "the", "Alzheimer’s", "Questionnaire", "(AQ),", "an", "informant-based", "dementia", "assessment.", "Data", "from", "51", "cognitively", "normal", "(CN)", "individuals", "participating", "in", "a", "brain", "donation", "program", "and", "47", "aMCI", "individuals", "seen", "in", "a", "neurology", "practice", "at", "the", "same", "institute", "were", "analyzed", "to", "determine", "which", "AQ", "items", "differentiated", "aMCI", "from", "CN", "individuals.", "Results:", "Forward", "stepwise", "multiple", "logistic", "regression", "analysis", "which", "controlled", "for", "age", "and", "education", "showed", "that", "4", "AQ", "items", "were", "strong", "indicators", "of", "aMCI", "which", "included:", "repetition", "of", "statements", "and/or", "questions", "[OR", "13.20", "(3.02,", "57.66)];", "trouble", "knowing", "the", "day,", "date,", "month,", "year,", "and", "time", "[OR", "17.97", "(2.63,", "122.77)];", "difficulty", "managing", "finances", "[OR", "11.60", "(2.10,", "63.99)];", "and", "decreased", "sense", "of", "direction", "[OR", "5.84", "(1.09,", "31.30)].", "Conclusions:", "Overall,", "these", "data", "indicate", "that", "certain", "informant-reported", "cognitive", "symptoms", "may", "help", "clinicians", "differentiate", "individuals", "with", "aMCI", "from", "those", "with", "normal", "cognition.", "Items", "pertaining", "to", "repetition", "of", "statements,", "orientation,", "ability", "to", "manage", "finances,", "and", "visuospatial", "disorientation", "had", "high", "discriminatory", "power.", "Background", "The", "process", "of", "differentiating", "age-associated", "memory", "decline", "from", "those", "who", "might", "have", "a", "clinically", "signifi-", "cant", "disorder", "of", "memory", "and", "cognition", "is", "difficult.", "In", "particular,", "distinguishing", "individuals", "with", "amnestic", "mild", "cognitive", "impairment", "(aMCI)", "from", "those", "who", "are", "cogni-", "tively", "normal", "(CN)", "is", "challenging,", "as", "memory", "and", "cogni-", "tive", "complaints", "are", "often", "reported", "in", "both", "groups", "from", "both", "the", "patient", "and", "informants", "[1].", "Given", "that", "the", "cur-", "rent", "diagnostic", "criteria", "for", "aMCI", "include", "subjective", "(patient", "and/or", "family", "report", "of", "decline)", "and", "objective", "(neuropsychological", "testing)", "evidence", "of", "memory", "decline,", "a", "clinician’s", "initial", "impression", "from", "a", "relatively", "short", "office", "visit", "may", "not", "allow", "for", "an", "accurate", "assess-", "ment", "[2].", "*", "Correspondence:", "michael.ahmadi@bannerhealth.com", "The", "Cleo", "Roberts", "Center", "for", "Clinical", "Research,", "Banner", "Sun", "Health", "Research", "Institute,", "Sun", "City,", "AZ,", "85351,", "USA", "Amnestic", "MCI", "was", "first", "characterized", "as", "a", "syndrome", "consisting", "of", "memory", "performance", "at", "or", "below", "1.5", "stan-", "dard", "deviations", "(SD)", "on", "age-", "and", "education-adjusted", "normative", "values", "on", "a", "verbal", "memory", "test", "along", "with", "subjective", "memory", "complaints,", "preserved", "global", "cogni-", "tion,", "and", "preserved", "activities", "of", "daily", "living", "[3].", "The", "diagnostic", "criteria", "for", "MCI", "have", "since", "been", "refined", "to", "differentiate", "between", "amnestic", "and", "non-amnestic", "forms,", "with", "the", "latter", "showing", "performance", "at", "or", "below", "1.5", "SD", "on", "a", "test", "or", "test(s)", "in", "one", "or", "more", "domains", "other", "than", "memory.", "Both", "amnestic", "and", "non-amnestic", "MCI", "can", "be", "further", "classified", "as", "single", "or", "multiple", "domain", "MCI", "depending", "upon", "the", "number", "of", "cognitive", "domains", "that", "show", "test", "performance(s)", "at", "or", "below", "1.5", "SD", "[4].", "Several", "studies", "have", "investigated", "the", "clinical", "course", "and", "presentation", "of", "individuals", "who", "have", "self-", "and", "infor-", "mant-reported", "memory", "complaints", "[5-8].", "Some", "evidence", "suggests", "that", "individuals", "who", "are", "cognitively", "normal", "and", "have", "subjective", "memory", "complaints", "demonstrate", "MRI", "©", "2012", "Malek-Ahmadi", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "NEURAL", "CIRCUITS", "Connectivity", "from", "OR37", "expressing", "olfactory", "sensory", "neurons", "to", "distinct", "cell", "types", "in", "the", "hypothalamus", "Andrea", "Bader", ",", "Bettina", "Klein", ",", "Heinz", "Breer", "and", "Jörg", "Strotmann", "*", "Institute", "of", "Physiology,", "University", "of", "Hohenheim,", "Stuttgart,", "Germany", "ORIGINAL", "RESEARCH", "ARTICLE", "published:", "16", "November", "2012", "doi:", "10.3389/fncir.2012.00084", "Edited", "by:", "Charles", "F.", "Stevens,", "The", "Salk", "Institute", "for", "Biological", "Studies,", "USA", "Reviewed", "by:", "Hartwig", "Spors,", "Max", "Planck", "Institute", "of", "Biophysics,", "Germany", "Bill", "S.", "Hansson,", "Max", "Planck", "Institute", "for", "Chemical", "Ecology,", "Germany", "*Correspondence:", "Jörg", "Strotmann,", "Institute", "of", "Physiology,", "University", "of", "Hohenheim,", "Garbenstrasse", "30,", "70593", "Stuttgart,", "Germany.", "e-mail:", "strotman@uni-hohenheim.de", "Olfactory", "sensory", "neurons", "(OSNs)", "which", "express", "a", "member", "from", "the", "OR37", "subfamily", "of", "odorant", "receptor", "(OR)", "genes", "are", "wired", "to", "the", "main", "olfactory", "bulb", "(MOB)", "in", "a", "unique", "monoglomerular", "fashion;", "from", "these", "glomeruli", "an", "untypical", "connectivity", "into", "higher", "brain", "centers", "exists.", "In", "the", "present", "study", "we", "have", "investigated", "by", "DiI", "and", "transsynaptic", "tracing", "approaches", "how", "the", "connection", "pattern", "from", "these", "glomeruli", "into", "distinct", "hypothalamic", "nuclei", "is", "organized.", "The", "application", "of", "DiI", "onto", "the", "ventral", "domain", "of", "the", "bulb", "which", "harbors", "the", "OR37", "glomeruli", "resulted", "in", "the", "labeling", "of", "fibers", "within", "the", "paraventricular", "nucleus", "(PVN)", "and", "supraoptic", "nucleus", "(SO)", "of", "the", "hypothalamus;", "some", "of", "these", "fibers", "were", "covered", "with", "varicose-like", "structures.", "No", "DiI-labeled", "cell", "somata", "were", "detectable", "in", "these", "nuclei.", "The", "data", "indicate", "that", "projection", "neurons", "which", "originate", "in", "the", "OR37", "region", "of", "the", "MOB", "form", "direct", "connections", "into", "these", "nuclei.", "The", "cells", "that", "were", "labeled", "by", "the", "transsynaptic", "tracer", "WGA", "in", "these", "nuclei", "were", "further", "characterized.", "Their", "distribution", "pattern", "in", "the", "paraventricular", "nucleus", "was", "reminiscent", "of", "cells", "which", "produce", "distinct", "neuropeptides.", "Double", "labeling", "experiments", "confirmed", "that", "they", "contained", "vasopressin,", "but", "not", "the", "related", "neuropeptide", "oxytocin.", "Morphological", "analysis", "revealed", "that", "they", "comprise", "of", "magno-", "and", "parvocellular", "cells.", "A", "comparative", "investigation", "of", "the", "WGA-", "positive", "cells", "in", "the", "SO", "demonstrated", "that", "these", "were", "vasopressin-positive,", "as", "well,", "whereas", "oxytocin-producing", "cells", "of", "this", "nucleus", "also", "contained", "no", "transsynaptic", "tracer.", "Together,", "the", "data", "demonstrates", "a", "connectivity", "from", "OR37", "expressing", "sensory", "neurons", "to", "distinct", "hypothalamic", "neurons", "with", "the", "same", "neuropeptide", "content.", "Keywords:", "olfaction,", "OR37,", "paraventricular", "nucleus,", "supraoptic", "nucleus,", "vasopressin,", "wiring", "INTRODUCTION", "Numerous", "vital", "behaviors", "such", "as", "the", "finding", "of", "food", "sources,", "avoiding", "predators,", "and", "recognizing", "conspecifics", "are", "triggered", "by", "olfactory", "cues.", "In", "mammalian", "species,", "the", "relevant", "odorous", "molecules", "are", "detected", "by", "specialized", "olfactory", "sensory", "neurons", "(OSNs)", "which", "are", "organized", "in", "structurally", "and", "functionally", "dis-", "tinct", "chemosensory", "subsystems", "[for", "reviews", "see", "(Breer", "et", "al.,", "2006;", "Ma,", "2007;", "Munger", "et", "al.,", "2009)].", "One", "special", "subsystem", "is", "located", "within", "the", "main", "olfactory", "system", "(MOS)", "and", "is", "formed", "by", "the", "so-", "called", "OR37", "subfamily", "of", "odorant", "receptors", "(ORs)", "(Strotmann", "et", "al.,", "1992).", "This", "type", "of", "OR", "is", "structurally", "unique", "due", "to", "an", "insertion", "of", "six", "amino", "acids", "in", "its", "third", "extracellular", "loop", "(Kubick", "et", "al.,", "1997);", "furthermore,", "it", "exists", "exclusively", "in", "mammalian", "species", "(Hoppe", "et", "al.,", "2006),", "and", "against", "the", "general", "trend", "for", "ORs,", "the", "various", "OR37", "subtypes", "are", "highly", "conserved", "among", "each", "other", "and", "across", "species", "borders", "from", "opossum", "to", "human", "(Hoppe", "et", "al.,", "2006).", "These", "features", "have", "led", "to", "the", "speculation", "that", "the", "OR37", "subsystem", "may", "be", "tuned", "to", "detect", "special", "chemical", "com-", "pounds,", "which", "might", "be", "particularly", "relevant", "for", "mammals.", "In", "fact,", "we", "have", "recently", "demonstrated", "that", "the", "OR37", "receptors", "are", "specifically", "activated", "by", "long-chain", "fatty", "aldehydes", "(Bautze", "et", "al.,", "2012);", "these", "compounds", "are", "extremely", "hydrophobic", "and", "were", "never", "described", "as", "active", "ligands", "for", "any", "other", "ORs", "in", "previous", "studies.", "These", "aspects", "raise", "the", "question", "whether", "the", "information", "received", "via", "the", "OR37", "sensory", "cells", "may", "also", "be", "processed", "in", "the", "brain", "in", "a", "way", "that", "differs", "from", "that", "of", "general", "OSNs.", "Indeed,", "the", "visualization", "of", "axonal", "projections", "from", "OSNs", "expressing", "defined", "OR37", "receptors", "into", "the", "main", "olfactory", "bulb", "(MOB)", "has", "revealed", "that", "they", "target", "only", "a", "single", "glomerulus", "(Strotmann", "et", "al.,", "2000),", "a", "pattern", "which", "is", "clearly", "different", "from", "that", "of", "most", "other", "OSN", "populations", "which", "typically", "send", "their", "axons", "to", "two", "glomeruli", "[for", "recent", "reviews", "see", "(Imai", "et", "al.,", "2010;", "Sakano,", "2010;", "Mori", "and", "Sakano,", "2011;", "Murthy,", "2011)].", "Interestingly,", "the", "glomeruli", "for", "the", "different", "OR37", "subtypes", "were", "found", "to", "be", "grouped", "together", "in", "the", "ventral", "domain", "of", "the", "MOB,", "a", "region", "which", "is", "believed", "to", "play", "a", "role", "in", "the", "processing", "of", "socially", "relevant", "olfactory", "cues", "(Schaefer", "et", "al.,", "2001,", "2002;", "Lin", "et", "al.,", "2007).", 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"Neural", "Circuits", "www.frontiersin.org", "November", "2012", "|", "Volume", "6", "|", "Article", "84", "|", "1" ]

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[ "Int.", "J.", "Mol.", "Sci.", "2012,", "13,", "9642-9648;", "doi:10.3390/ijms13089642", "OPEN", "ACCESS", "International", "Journal", "of", "Molecular", "Sciences", "ISSN", "1422-0067", "www.mdpi.com/journal/ijms", "Communication", "Neuroprotective", "Effects", "of", "Triterpene", "Glycosides", "from", "Glycine", "max", "against", "Glutamate", "Induced", "Toxicity", "in", "Primary", "Cultured", "Rat", "Cortical", "Cells", "Hyung-In", "Moon", "*", "and", "Jai-Heon", "Lee", "Department", "of", "Medicinal", "Biotechnology,", "College", "of", "Natural", "Resources", "and", "Life", "Science,", "Dong-A", "University,", "Busan", "604-714,", "Korea;", "E-Mail:", "hoffmannu@nate.com", "*", "Author", "to", "whom", "correspondence", "should", "be", "addressed;", "E-Mail:", "himun68@dau.ac.kr;", "Tel.:", "+82-51-200-7562;", "Fax:", "+82-51-200-6195.", "Received:", "7", "June", "2012;", "in", "revised", "form:", "16", "July", "2012", "/", "Accepted:", "23", "July", "2012", "/", "Published:", "2", "August", "2012", "Abstract:", "To", "examine", "the", "neuroprotective", "effects", "of", "Glycine", "max,", "we", "tested", "its", "protection", "against", "the", "glutamate-induced", "toxicity", "in", "primary", "cortical", "cultured", "neurons.", "In", "order", "to", "clarify", "the", "neuroprotective", "mechanism(s)", "of", "this", "observed", "effect,", "isolation", "was", "performed", "to", "seek", "and", "identify", "active", "fractions", "and", "components.", "From", "such", "fractionation,", "two", "triterpene", "glycosides,", "3-O-[α-L-rhamnopyranosyl(1-2)-β-D-glucopyranosyl(1-2)-β-D-", "glucuronopyranosyl]olean-12-en-3β,22β,24-triol", "(1)", "and", "3-O-[β-D-glucopyranosyl(1-2)-β-", "D-galactopyranosyl(1-2)-β-D-glucuronopyranosyl]olean-12-en-3β,22β,24-triol", "(2)", "were", "isolated", "with", "the", "methanol", "extracts", "with", "of", "air-dried", "Glycine", "max.", "Among", "these", "compounds,", "compound", "2", "exhibited", "significant", "neuroprotective", "activities", "against", "glutamate-induced", "toxicity,", "exhibiting", "cell", "viability", "of", "about", "50%", "at", "concentrations", "ranging", "from", "0.1", "μM", "to", "10", "μM.", "Therefore,", "the", "neuroprotective", "effect", "of", "Glycine", "max", "might", "be", "due", "to", "the", "inhibition", "of", "glutamate-induced", "toxicity", "by", "triterpene", "glycosides.", "Keywords:", "Glycine", "max;", "glutamate-induced", "toxicity;", "neuroprotective;", "triterpene", "glycosides", "1.", "Introduction", "Phytochemical", "compounds", "from", "grains", "are", "abundant", "in", "the", "human", "diet,", "particularly", "in", "fruit,", "vegetables", "and", "legumes,", "which", "have", "been", "consistently", "associated", "with", "a", "decreased", "risk", "of", "nutritional", "disease.", "They", "constitute", "one", "of", "the", "most", "abundant", "groups", "of", "natural", "metabolites", "and", "are", "now" ]

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[ "MiR-128", "Inhibits", "Tumor", "Growth", "and", "Angiogenesis", "by", "Targeting", "p70S6K1", "Zhu-mei", "Shi1.,", "Jing", "Wang2.,", "Zhiping", "Yan2,", "Yong-ping", "You", "1", ",", "Chong-yong", "Li2,", "Xu", "Qian2,", "Yu", "Yin2,", "Peng", "Zhao1,", "Ying-ying", "Wang", "1", ",", "Xie-feng", "Wang", "1", ",", "Ming-na", "Li3,", "Ling-Zhi", "Liu4,", "Ning", "Liu1,", "Bing-Hua", "Jiang1,2,4*", "1", "Department", "of", "Neurosurgery,", "The", "First", "Affiliated", "Hospital", "of", "Nanjing", "Medical", "University,", "Nanjing,", "China,", "2", "Department", "of", "Pathology,", "Cancer", "Center,", "Nanjing", "Medical", "University,", "Nanjing,", "China,", "3", "Department", "of", "Pathology,", "The", "First", "Affiliated", "Hospital", "of", "Nanjing", "Medical", "University,", "Nanjing,", "China,", "4", "Department", "of", "Pathology,", "Anatomy", "and", "Cell", "Biology,", "Kimmel", "Cancer", "Center,", "Thomas", "Jefferson", "University,", "Philadelphia,", "Pennsylvania,", "United", "States", "of", "America", "Abstract", "MicroRNAs", "are", "a", "class", "of", "small", "noncoding", "RNAs", "that", "function", "as", "critical", "gene", "regulators", "through", "targeting", "mRNAs", "for", "translational", "repression", "or", "degradation.", "In", "this", "study,", "we", "showed", "that", "miR-128", "expression", "levels", "were", "decreased", "in", "glioma,", "and", "identified", "p70S6K1", "as", "a", "novel", "direct", "target", "of", "miR-128.", "Overexpression", "of", "miR-128", "suppressed", "p70S6K1", "and", "its", "downstream", "signaling", "molecules", "such", "as", "HIF-1", "and", "VEGF", "expression,", "and", "attenuated", "cell", "proliferation,", "tumor", "growth", "and", "angiogenesis.", "Forced", "expression", "of", "p70S6K1", "can", "partly", "rescue", "the", "inhibitory", "effect", "of", "miR-128", "in", "the", "cells.", "Taken", "together,", "these", "findings", "will", "shed", "light", "to", "the", "role", "and", "mechanism", "of", "miR-128", "in", "regulating", "glioma", "tumor", "angiogenesis", "via", "miR-128/", "p70S6K1", "axis,", "and", "miR-128", "may", "serve", "as", "a", "potential", "therapeutic", "target", "in", "glioma", "in", "the", "future.", "Citation:", "Shi", "Z-m,", "Wang", "J,", "Yan", "Z,", "You", "Y-p,", "Li", "C-y,", "et", "al.", "(2012)", "MiR-128", "Inhibits", "Tumor", "Growth", "and", "Angiogenesis", "by", "Targeting", "p70S6K1.", "PLoS", "ONE", "7(3):", "e32709.", "doi:10.1371/journal.pone.0032709", "Editor:", "Jin", "Q.", "Cheng,", "H.Lee", "Moffitt", "Cancer", "Center", "&", "Research", "Institute,", "United", "States", "of", "America", "Received", "October", "26,", "2011;", "Accepted", "January", "30,", "2012;", "Published", "March", "19,", "2012", "Copyright:", "2012", "Shi", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "was", "supported", "in", "part", "by", "National", "Natural", "Science", "Foundation", "of", "China", "(81071642", "and", "81172389),", "by", "the", "National", "Key", "Basic", "Research", "Program", "of", "China", "(2011CB504003),", "Key", "Basic", "Research", "Program", "of", "the", "Jiangsu", "Higher", "Education", "Institutions", "of", "China", "(09KJA310001)", "and", "by", "National", "Cancer", "Institute,", "National", "Institutes", "of", "Health", "(R01CA109460).", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "binghjiang@yahoo.com", ".", "These", "authors", "contributed", "equally", "to", "this", "work.", "Introduction", "MicroRNAs", "(miRNAs)", "are", "a", "class", "of", "endogenously", "expressed", "small", "noncoding", "RNAs", "that", "are", "usually", "18,23", "nucleotides", "long,", "and", "regulate", "gene", "expression", "posttranscriptionally", "by", "targeting", "the", "untranslated", "regions", "[1].", "MiRNAs", "have", "been", "shown", "to", "participate", "in", "a", "variety", "of", "cellular", "functions", "including", "cell", "apoptosis,", "cell", "proliferation,", "neural", "development,", "and", "stem", "cell", "differentiation", "[1–", "3].", "They", "have", "been", "identified", "as", "a", "new", "kind", "of", "gene", "expression", "regulators", "through", "targeting", "mRNAs", "for", "translational", "repression", "or", "degradation", "[4].", "Gliomas", "are", "the", "most", "common", "type", "of", "primary", "brain", "tumors", "in", "adults.", "Among", "gliomas,", "astrocytomas", "have", "the", "highest", "incidence", "[5].", "According", "to", "World", "Health", "Organization’s", "classification,", "astrocytomas", "are", "divided", "into", "four", "grades:", "pilocytic", "astrocytoma,", "diffuse", "astrocytoma,", "anaplastic", "astrocytoma,", "and", "glioblastoma", "multiforme", "(GBM).", "Anaplastic", "astrocytoma", "and", "glioblastoma", "multiforme", "are", "considered", "malignant", "glioma.", "Recently,", "many", "miRNAs", "are", "found", "to", "play", "important", "roles", "in", "glioma.", "MiR-7", "was", "down-regulated", "in", "glioblastoma", "which", "inhibited", "invasiveness", "of", "primary", "glioblastoma", "lines", "[6],", "while", "miR-26", "promotes", "glioblastoma", "cell", "proliferation", "in", "vitro", "and", "tumor", "growth", "in", "vivo", "by", "targeting", "several", "tumor", "suppressor", "genes", "such", "as", "PTEN", "and", "RB1", "[7].", "MiR-128", "is", "a", "brain-enriched", "miRNA", "[8].", "Most", "of", "the", "studies", "of", "miR-128", "in", "carcinogenesis", "are", "focusing", "on", "glioma.", "For", "example,", "miR-128", "has", "been", "shown", "to", "be", "down-", "regulated", "in", "glioma", "[8–10].", "Overexpression", "of", "miR-128", "inhibits", "cell", "proliferation", "by", "targeting", "E2F3a", "and", "Bmi-1,", "and", "reduces", "neuroblastoma", "cell", "motility", "and", "invasiveness", "through", "inhibiting", "Reelin", "and", "DCX", "[8,10,11].", "However,", "further", "investigation", "needs", "to", "be", "performed", "to", "elucidate", "the", "role", "of", "miR-128", "in", "carcinogenesis", "and", "tumor", "development", "of", "glioma.", "P70S6K1", "is", "one", "of", "the", "key", "downstream", "targets", "of", "mammalian", "target", "of", "rapamycin", "(mTOR),", "which", "plays", "important", "roles", "in", "cancerous", "characteristics", "such", "as", "cell", "cycle,", "cell", "apoptosis,", "cell", "growth", "and", "proliferation", "[12,13].", "Growing", "evidence", "indicates", "that", "p70S6K1", "pathway", "is", "involved", "in", "carcinogenesis,", "metastasis", "and", "chemotherapeutic", "drug", "resistance", "[12–14].", "Our", "previous", "studies", "have", "demonstrated", "that", "mTOR/p70S6K1", "is", "involved", "in", "regulat-", "ing", "tumor", "angiogenesis", "and", "tumorigenesis", "[15–17].", "Tumor", "angiogenesis", "is", "required", "for", "tumor", "development", "and", "growth.", "Vascular", "endothelial", "growth", "factor", "(VEGF)", "is", "considered", "to", "be", "the", "most", "important", "growth", "factor", "among", "the", "angiogenic", "factors", "[18,19].", "Hypoxia-inducible", "factor", "1", "(HIF-1)", "is", "one", "of", "the", "major", "regulator", "of", "VEGF", "[20].", "High", "levels", "of", "HIF-1", "expression", "are", "observed", "in", "many", "human", "cancers,", "and", "correlated", "with", "tumori-", "genesis", "[21].", "P70S6K1", "is", "implicated", "in", "regulating", "HIF-1a", "expression", "[15,16,22,23].", "However,", "it", "is", "unclear", "what", "miRNAs", "directly", "regulate", "p70S6K1", "in", "glioma.", "In", "the", "present", "study,", "we", "found", "that", "miR-128", "was", "down-", "regulated", "in", "human", "glioma", "and", "acted", "as", "a", "tumor", "suppressor", "by", "directly", "targeting", "p70S6K1.", "Forced", "expression", "of", "miR-128", "inhibited", "p70S6K1,", "HIF-1a,", "and", "VEGF", "expression.", "Overexpres-", "sion", "of", "p70S6K1", "restored", "miR-128-inhibited", "HIF-1a", "and", "VEGF", "expression,", "confirming", "that", "p70S6K1", "is", "the", "downstream", "target", "of", "PLoS", "ONE", "|", "www.plosone.org", "1", "March", "2012", "|", "Volume", "7", "|", "Issue", "3", "|", "e32709" ]

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[ "Acta", "Crystallographica", "Section", "E", "Structure", "Reports", "Online", "ISSN", "1600-5368", "Dicarbonyl(hexamethylene-1,3,5,7-tetra-", "1", "5", "mine-jN", ")(g", "-pentamethylcyclopenta-", "dienyl)iron(II)", "tetrafluoridoborate", "Cyprian", "M.", "M’thiruaine,a*", "Holger", "B.", "Friedrich,a", "Evans", "O.", "Changamub", "and", "Manuel", "A.", "Fernandesc", "aSchool", "of", "Chemistry,", "University", "of", "KwaZulu-Natal,", "Private", "Bag", "X54001,", "Durban", "4000,", "South", "Africa,", "bChemistry", "Department,", "Kenyatta", "University,", "PO", "Box", "43844,", "Nairobi,", "Kenya,", "and", "cMolecular", "Sciences", "Institute,", "School", "of", "Chemistry,", "University", "of", "the", "Witwatersrand,", "PO", "Wits,", "2050", "Johannesburg,", "South", "Africa", "Correspondence", "e-mail:", "208529737@stu.ukzn.ac.za", "Received", "24", "May", "2012;", "accepted", "11", "June", "2012", "Key", "indicators:", "single-crystal", "X-ray", "study;", "T", "=", "173", "K;", "mean", "(C–C)", "=", "0.003", "A˚;", "R", "factor", "=", "0.033;", "wR", "factor", "=", "0.094;", "data-to-parameter", "ratio", "=", "17.5.", "In", "the", "title", "compound,", "[Fe(C10H15)(C6H12N4)(CO)2]BF4,", "the", "arrangement", "around", "the", "FeII", "atom", "corresponds", "to", "a", "three-", "legged", "piano", "stool.", "The", "pentamethylcyclopentadienyl", "(Cp*)", "ligand", "occupies", "three", "coordination", "sites,", "while", "two", "CO", "ligands", "and", "one", "N", "atom", "of", "the", "hexamethylenetetramine", "ligand", "occupy", "the", "remaining", "coordination", "sites,", "completing", "a", "pseudo-", "octahedral", "geometry.", "Both", "the", "complex", "cation", "and", "the", "BF4", "anion", "reside", "on", "crystallographic", "mirror", "planes.", "The", "Fe—N", "bond", "length", "is", "2.069", "(2)", "and", "the", "Fe—Cp*(centroid)", "distance", "is", "1.7452", "(3)", "A˚", ".", "Related", "literature", "For", "the", "synthesis", "of", "the", "title", "compound", "and", "structure", "of", "the", "dinuclear", "compound", "[Fe2(", "5-C5H5)2{N4(CH2)6}(CO)4](BF4)2", "see:", "M’thiruaine", "et", "al.", "(2012a).", "For", "other", "related", "compounds,", "see:", "Allan", "et", "al.", "(1970);", "Darensbourg", "et", "al.", "(2003);", "Lu", "et", "al.", "(2004);", "Matos", "&", "Verkade", "(2003);", "M’thiruaine", "et", "al.", "(2012b);", "Shafiq", "et", "al.", "(2000).", "For", "molecular", "structures", "of", "other", "metal", "complexes", "of", "hexamethylenetetramine,", "see:", "Zheng", "et", "al.", "(2008);", "Xue", "et", "al.", "(2009).", "For", "applications", "of", "hexamethylene-", "tetramine,", "see:", "Greenwood", "(1981);", "Strom", "&", "Jun", "(1986);", "Garcia", "et", "al.", "(2010).", "metal-organic", "compounds", "Experimental", "Crystal", "data", "[Fe(C10H15)(C6H12N4)(CO)2]BF4", "Mr", "=", "474.10", "Orthorhombic,", "Pnma", "a", "=", "13.8388", "(6)", "A˚", "b", "=", "9.1771", "(4)", "A˚", "c", "=", "16.4365", "(8)", "A˚", "Data", "collection", "Bruker", "APEXII", "CCD", "diffractometer", "Absorption", "correction:", "integration", "(SADABS;", "Bruker,", "2005)", "Tmin", "=", "0.746,", "Tmax", "=", "0.746", "Refinement", "R[F", "2", ">", "2", "(F", "2)]", "=", "0.033", "wR(F", "2)", "=", "0.094", "S", "=", "1.04", "2671", "reflections", "V", "=", "2087.44", "(16)", "A˚3", "Z", "=", "4", "Mo", "K", "radiation", "=", "0.78", "mm", "1", "T", "=", "173", "K", "0.40", "0.40", "0.40", "mm", "16663", "measured", "reflections", "2671", "independent", "reflections", "2065", "reflections", "with", "I", ">", "2", "(I)", "Rint", "=", "0.050", "153", "parameters", "H-atom", "parameters", "constrained", "max", "=", "0.56", "e", "A˚", "3", "min", "=", "0.55", "e", "A˚", "3", "Data", "collection:", "APEX2", "(Bruker,", "2005);", "cell", "refinement:", "SAINT-", "Plus", "(Bruker,", "2005);", "data", "reduction:", "SAINT-Plus", "and", "XPREP", "(Bruker,", "2005);", "program(s)", "used", "to", "solve", "structure:", "SHELXS97", "(Sheldrick,", "2008);", "program(s)", "used", "to", "refine", "structure:", "SHELXL97", "(Sheldrick,", "2008);", "molecular", "graphics:", "ORTEP-3", "Farrugia", "(1997);", "software", "used", "to", "prepare", "material", "for", "publication:", "SHELXL97", "and", "PLATON", "(Spek,", "2009).", "Our", "acknowledgement", "goes", "to", "the", "University", "of", "KwaZulu-", "Natal", "for", "resources", "and", "financial", "support.", "Supplementary", "data", "and", "figures", "for", "this", "paper", "are", "available", "from", "the", "IUCr", "electronic", "archives", "(Reference:", "FJ2565).", "References", "Allan,", "J.", "R.,", "Brown,", "D.", "H.", "&", "Lappin,", "M.", "(1970).", "J.", "Inorg.", "Nucl.", "Chem.", "32,", "2287–", "2292.", "Bruker", "(2005).", "APEX2,", "SAINT-Plus,", "XPREP", "and", "SADABS.", "Bruker", "AXS", "Inc.,", "Madison,", "Wisconsin,", "USA.", "Darensbourg,", "D.", "J.,", "Phelps,", "A.", "L.,", "Adams,", "M.", "J.", "&", "Yarbrough,", "J.", "C.", 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"Chim.", "Acta,", "382,", "27–34.", "Shafiq,", "F.,", "Szalda,", "D.", "J.,", "Creutz,", "C.", "&", "Bullock,", "R.", "M.", "(2000).", "Organometallics,", "19,", "824–833.", "Sheldrick,", "G.", "M.", "(2008).", "Acta", "Cryst.", "A64,", "112–122.", "Spek,", "A.", "L.", "(2009).", "Acta", "Cryst.", "D65,", "148–155.", "Strom,", "J.", "G.", "J.", "&", "Jun,", "H.", "W.", "(1986).", "J.", "Pharm.", "Sci.", "75,", "416–420.", "Xue,", "M.,", "Zhu,", "G.,", "Ding,", "H.,", "Wu,", "L.,", "Zhao,", "X.,", "Jin,", "Z.", "&", "Qiu,", "S.", "(2009).", "Cryst.", "Growth", "Des.", "9,", "1481–1488.", "Zheng,", "G.,", "Zhang,", "H.,", "Song,", "S.,", "Li,", "Y.", "&", "Guo,", "H.", "(2008).", "Eur.", "J.", "Inorg.", "Chem.", "pp.", "1756–1759.", "Acta", "Cryst.", "(2012).", "E68,", "m931", "doi:10.1107/S1600536812026360", "M’thiruaine", "et", "al.", "m931" ]

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[ "e", "n", "i", "c", "i", "d", "e", "M", "l", "a", "t", "n", "e", "m", "i", "r", "e", "p", "x", "E", "f", "o", "l", "a", "n", "r", "u", "o", "J", "e", "h", "T", "CORRESPONDENCE", "John", "M.", "Routes:", "routesj@njc.org", "JEM", "©", "The", "Rockefeller", "University", "Press", "$8.00", "Vol.", "202,", "No.", "4,", "August", "15,", "2005", "479–484", "www.jem.org/cgi/doi/10.1084/jem.20050381", "B", "R", "I", "E", "F", "D", "E", "F", "I", "N", "I", "T", "I", "V", "E", "R", "E", "P", "O", "R", "T", "Possible", "role", "of", "human", "her", "pesvirus", "8", "in", "the", "lymphoproliferative", "disorders", "in", "common", "var", "iable", "immunodeficiency", "William", "H.", "Wheat,1", "Carlyne", "D.", "Cool,2,7", "Yoshikazu", "Morimoto,7", "Pradeep", "R.", "Rai,2", "Charles", "H.", "Kirkpatrick,3", "Barbara", "A.", "Lindenbaum,7", "Christopher", "A.", "Bates,7", "Misoo", "C.", "Ellison,4,5,7", "Amanda", "E.", "Serls,2", "Kevin", "K.", "Brown,3,7", "and", "John", "M.", "Routes1,3,6,7", "1Integrated", "Department", "of", "Immunology,", "National", "Jewish", "Medical", "and", "Research", "Center", "and", "University", "of", "Colorado", "Health", "Sciences", "Center,", "2Department", "of", "Pathology,", "3Department", "of", "Medicine,", "4Department", "of", "Preventive", "Medicine,", "5Department", "of", "Biometrics,", "and", "6Cancer", "Center,", "University", "of", "Colorado", "Health", "Sciences", "Center,", "Denver,", "CO", "80262", "7Department", "of", "Medicine,", "National", "Jewish", "Medical", "and", "Research", "Center,", "Denver,", "CO", "80206", "Patients", "who", "have", "common", "variable", "immunodeficiency", "(CVID)", "and", "granulomatous/", "lymphocytic", "interstitial", "lung", "disease", "(GLILD)", "are", "at", "high", "risk", "for", "early", "mortality", "and", "B", "cell", "lymphomas.", "Infection", "with", "human", "herpes", "virus", "type", "8", "(HHV8),", "a", "B", "cell", "lymphotrophic", "virus,", "is", "linked", "to", "lymphoproliferative", "disorders", "in", "people", "who", "have", "secondary", "immunodeficiencies.", "Therefore,", "we", "determined", "the", "prevalence", "of", "HHV8", "infection", "in", "CVID", "patients", "with", "GLILD.", "Genomic", "DNA", "isolated", "from", "peripheral", "blood", "mononuclear", "cells", "was", "screened", "by", "nested-", "and", "real", "time-quantitative", "PCR", "(QRT-PCR)", "for", "the", "presence", "of", "HHV8", "genome.", "It", "was", "positive", "in", "6/9", "CVID", "patients", "with", "GLILD", "(CVID-GLILD),", "1/21", "CVID", "patients", "without", "GLILD", "(CVID-control),", "and", "no", "patients", "receiving", "intravenous", "gamma", "globulin", "(n", "13)", "or", "normal", "blood", "donors", "(n", "20).", "Immunohistochemistry", "(IHC)", "demonstrated", "expression", "of", "the", "latency-associated", "nuclear", "antigen-1", "(LANA-1)", "in", "the", "biopsies", "of", "the", "lung,", "liver,", "and", "bone", "marrow", "of", "four", "patients", "with", "CVID-GLILD.", "One", "CVID-GLILD", "patient", "developed", "a", "B", "cell", "lymphoma", "during", "the", "course", "of", "the", "study.", "QRT-PCR", "demonstrated", "high", "copy", "number", "of", "HHV8", "genome", "and", "IHC", "showed", "diffuse", "staining", "for", "LANA-1", "in", "the", "malignant", "lymph", "node.", "HHV8", "infection", "may", "be", "an", "important", "factor", "in", "the", "pathogenesis", "of", "the", "interstitial", "lung", "disease", "and", "lymphoproliferative", "disorders", "in", "patients", "with", "CVID.", "Common", "variable", "immunodeficiency", "(CVID)", "is", "a", "primary", "immunodeficiency", "of", "unknown", "etiol-", "ogy", "that", "is", "characterized", "by", "a", "low", "serum", "IgG", "and", "the", "inability", "to", "make", "specific", "antibodies", "in", "re-", "sponse", "to", "immunization", "or", "infection", "(1).", "Defects", "in", "cellular", "immunity,", "which", "occur", "in", "approxi-", "mately", "one", "third", "of", "patients,", "likely", "contribute", "to", "their", "susceptibility", "to", "conventional", "and", "opportu-", "nistic", "pathogens.", "We", "analyzed", "the", "prevalence,", "clinical", "findings,", "and", "natural", "history", "of", "diffuse", "parenchymal", "lung", "disease", "in", "69", "patients", "with", "CVID", "(2).", "Granulomatous", "or", "lymphocytic", "inter-", "stitial", "lung", "disease", "(GLILD)", "was", "present", "in", "20%", "of", "patients", "who", "had", "CVID;", "its", "presence", "por-", "tended", "a", "poor", "prognosis", "(2).", "Patients", "who", "had", "CVID", "and", "GLILD", "exhibited", "T", "cell", "lymphope-", "W.H.", "Wheat’s", "present", "address", "is", "Department", "of", "Microbiol-", "ogy,", "Immunology,", "and", "Pathology,", "Colorado", "State", "University,", "Fort", "Collins,", "CO", "80523.", "The", "online", "version", "of", "this", "article", "contains", "supplemental", "material.", "nia,", "splenomegaly,", "and", "were", "at", "high", "risk", "for", "B", "cell", "lymphoproliferative", "diseases", "(e.g.,", "non-", "Hodgkin’s", "lymphoma", "[NHL]),", "which", "occurred", "in", "nearly", "30%", "of", "these", "patients.", "This", "constellation", "of", "clinical", "findings", "in", "this", "cohort", "of", "patients", "raised", "the", "question", "of", "whether", "GLILD", "was", "a", "unique", "disease", "entity", "with", "a", "common", "etiologic", "basis.", "Human", "herpesvirus", "type", "8", "(HHV8)", "is", "a", "-herpes", "virus", "that", "also", "is", "known", "as", "Kaposi’s", "sar-", "coma", "(KS)–associated", "virus", "(3).", "In", "the", "context", "of", "secondary", "immunodeficiencies,", "such", "as", "HIV-1", "infection", "or", "organ", "transplantation,", "HHV8", "is", "an", "opportunistic", "pathogen", "that", "is", "linked", "to", "the", "de-", "velopment", "of", "lymphoproliferative", "diseases", "(e.g.,", "primary", "effusion", "lymphoma", "and", "multicentric", "Castleman’s", "disease;", "reference", "4).", "The", "proclivity", "of", "HHV8", "to", "cause", "lymphoproliferative", "disor-", "ders", "in", "the", "setting", "of", "immunodeficiency,", "together", "with", "our", "observations", "that", "CVID-GLILD", "pa-", "tients", "were", "highly", "susceptible", "to", "lymphoprolif-", "479" ]

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[ "Del", "Bufalo1*", "Abstract", "Bcl-2", "Regulates", "HIF-1a", "Protein", "Stabilization", "in", "Hypoxic", "Melanoma", "Cells", "via", "the", "Molecular", "Chaperone", "HSP90", "Daniela", "Trisciuoglio1,", "Chiara", "Gabellini1,2,", "Marianna", "Desideri1,", "Elio", "Ziparo2,", "Gabriella", "Zupi1,", "Donatella", "1", "Experimental", "Chemotherapy", "Laboratory,", "Regina", "Elena", "Cancer", "Institute,", "Rome,", "Italy,", "2", "Department", "of", "Histology", "and", "Medical", "Embryology,", "Sapienza", "University,", "Rome,", "Italy", "Background:", "Hypoxia-Inducible", "Factor", "1", "(HIF-1)", "is", "a", "transcription", "factor", "that", "is", "a", "critical", "mediator", "of", "the", "cellular", "response", "to", "hypoxia.", "Enhanced", "levels", "of", "HIF-1a,", "the", "oxygen-regulated", "subunit", "of", "HIF-1,", "is", "often", "associated", "with", "increased", "tumour", "angiogenesis,", "metastasis,", "therapeutic", "resistance", "and", "poor", "prognosis.", "It", "is", "in", "this", "context", "that", "we", "previously", "demonstrated", "that", "under", "hypoxia,", "bcl-2", "protein", "promotes", "HIF-1/Vascular", "Endothelial", "Growth", "Factor", "(VEGF)-mediated", "tumour", "angiogenesis.", "Methodology/Principal", "Findings:", "By", "using", "human", "melanoma", "cell", "lines", "and", "their", "stable", "or", "transient", "derivative", "bcl-2", "overexpressing", "cells,", "the", "current", "study", "identified", "HIF-1a", "protein", "stabilization", "as", "a", "key", "regulator", "for", "the", "induction", "of", "HIF-1", "by", "bcl-2", "under", "hypoxia.", "We", "also", "demonstrated", "that", "bcl-2-induced", "accumulation", "of", "HIF-1a", "protein", "during", "hypoxia", "was", "not", "due", "to", "an", "increased", "gene", "transcription", "or", "protein", "synthesis.", "In", "fact,", "it", "was", "related", "to", "a", "modulation", "of", "HIF-1a", "protein", "expression", "at", "a", "post-translational", "level,", "indeed", "its", "degradation", "rate", "was", "faster", "in", "the", "control", "lines", "than", "in", "bcl-2", "transfectants.", "The", "bcl-2-", "induced", "HIF-1a", "stabilization", "in", "response", "to", "low", "oxygen", "tension", "conditions", "was", "achieved", "through", "the", "impairment", "of", "ubiquitin-dependent", "HIF-1a", "degradation", "involving", "the", "molecular", "chaperone", "HSP90,", "but", "it", "was", "not", "dependent", "on", "the", "prolyl", "hydroxylation", "of", "HIF-1a", "protein.", "We", "also", "showed", "that", "bcl-2,", "HIF-1a", "and", "HSP90", "proteins", "form", "a", "tri-complex", "that", "may", "contribute", "to", "enhancing", "the", "stability", "of", "the", "HIF-1a", "protein", "in", "bcl-2", "overexpressing", "clones", "under", "hypoxic", "conditions.", "Finally,", "by", "using", "genetic", "and", "pharmacological", "approaches", "we", "proved", "that", "HSP90", "is", "involved", "in", "bcl-2-dependent", "stabilization", "of", "HIF-", "1a", "protein", "during", "hypoxia,", "and", "in", "particular", "the", "isoform", "HSP90b", "is", "the", "main", "player", "in", "this", "phenomenon.", "Conclusions/Significance:", "We", "identified", "the", "stabilization", "of", "HIF-1a", "protein", "as", "a", "mechanism", "through", "which", "bcl-2", "induces", "the", "activation", "of", "HIF-1", "in", "hypoxic", "tumour", "cells", "involving", "the", "b", "isoform", "of", "molecular", "chaperone", "HSP90.", "Citation:", "Trisciuoglio", "D,", "Gabellini", "C,", "Desideri", "M,", "Ziparo", "E,", "Zupi", "G,", "et", "al.", "(2010)", "Bcl-2", "Regulates", "HIF-1a", "Protein", "Stabilization", "in", "Hypoxic", "Melanoma", "Cells", "via", "the", "Molecular", "Chaperone", "HSP90.", "PLoS", "ONE", "5(7):", "e11772.", "doi:10.1371/journal.pone.0011772", "Editor:", "Marc", "Vooijs,", "UMC", "Utrecht,", "Netherlands", "Received", "February", "9,", "2010;", "Accepted", "June", "29,", "2010;", "Published", "July", "27,", "2010", "Copyright:", "2010", "Trisciuoglio", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "was", "supported", "by", "grants", "from", "the", "Italian", "Association", "for", "Cancer", "Research,", "grant", "number", "08/30/c/91", "(D.D.B.)", "and", "the", "Italian", "Ministry", "of", "Health,", "grant", "number", "08/01/c/48", "(D.D.B.)", "and", "08/01/c/1", "(G.Z.).", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "delbufalo@ifo.it", "Introduction", "The", "transcription", "factor", "Hypoxia-Inducible", "Factor", "1", "(HIF-1)", "regulates", "the", "expression", "of", "more", "than", "70", "genes", "involved", "in", "tumour", "angiogenesis,", "metabolic", "switch", "to", "anaerobic", "glycolysis,", "pro-", "survival,", "proliferative", "and", "apoptotic", "mechanisms", "[1].", "Overall,", "the", "expression", "of", "HIF-1", "target", "genes", "helps", "cells", "to", "adapt", "to,", "and", "thereby", "survive", "in,", "a", "stressful", "microenvironment.", "The", "activity", "of", "HIF-1", "dimer,", "which", "is", "composed", "of", "a", "and", "b", "subunits,", "is", "modulated", "by", "the", "availability", "of", "the", "extremely", "labile", "oxygen-sensitive", "HIF-1a", "protein", "subunit.", "HIF-1", "activity", "depends", "on", "the", "inhibition", "of", "the", "post-transcriptional", "hydroxylation", "of", "the", "subunit", "a", "by", "prolyl", "hydroxylases", "PHD1-3", "and", "Factor", "Inhibiting", "HIF-1", "(FIH-1).", "PHDs-mediated", "hydroxylation", "targets", "HIF-1a", "for", "proteasomal", "degradation", "via", "the", "ubiquitination-dependent", "Von", "Hippel-Lindau", "(VHL)", "complex,", "while", "FIH-1-mediated", "hydroxylation", "leads", "to", "the", "inhibition", "of", "HIF-1", "transactivation.", "The", "activity", "of", "PHD1-3", "enzymes", "is", "dependent", "on", "substrates", "oxygen", "and", "2-oxoglutarate,", "a", "Krebs", "cycle", "intermediate,", "and", "cofactor", "Fe2+;", "thus,", "under", "hypoxic", "conditions,", "PHDs", "are", "less", "active", "due", "to", "the", "substrate-limiting", "conditions.", "The", "regulation", "of", "HIF-1a", "stability", "by", "an", "oxygen-", "independent", "degradation", "pathway", "was", "also", "reported:", "the", "molec-", "ular", "chaperone", "Heat", "Shock", "Protein", "90", "(HSP90)", "binds", "and", "stabilizes", "HIF-1a,", "competing", "with", "Receptor", "of", "Activated", "protein", "Kinase", "C", "(RACK1),", "which", "mediates", "prolyl", "hydroxylase/VHL-", "independent", "ubiquitination", "and", "proteasomal", "degradation", "of", "HIF-", "1a", "[2].", "Other", "post-translational", "modifications", "of", "HIF-1a,", "such", "as", "acetylation,", "phosphorylation", "and", "nitrosylation,", "were", "also", "reported,", "despite", "contradictory", "results", "with", "regard", "to", "their", "effect", "on", "HIF-1a", "protein", "stability", "and", "transcriptional", "activity", "[3–6].", "Adding", "to", "the", "complexity", "of", "HIF-1a", "regulation,", "it", "has", "recently", "been", "shown", "that", "the", "SUMOylation", "of", "HIF-1a", "enables", "the", "hydroxylation-indepen-", "dent", "binding", "and", "subsequent", "degradation", "of", "HIF-1a", "by", "the", "VHL-", "E3", "ligase", "complex", "[7].", "Although", "hypoxia", "is", "considered", "the", "main", "stimulus", "that", "drives", "HIF-1", "function,", "a", "number", "of", "non-hypoxic", "stimuli", "allows", "the", "formation", "of", "an", "active", "HIF-1", "complex", "in", "many", "types", "of", "human", "cancers.", "Effectors", "implicated", "in", "stimulating", "or", "suppressing", "an", "PLoS", "ONE", "|", "www.plosone.org", "1", "July", "2010", "|", "Volume", "5", "|", "Issue", "7", "|", "e11772" ]

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"article", "is", "available", "from:", "http://www.jmolecularsignaling.com/content/3/1/18", "Received:", "22", "August", "2008", "Accepted:", "1", "December", "2008", "©", "2008", "Zhuang", "and", "Miskimins;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "The", "antihyperglycemic", "drug", "metformin", "may", "have", "beneficial", "effects", "on", "the", "prevention", "and", "treatment", "of", "cancer.", "Metformin", "is", "known", "to", "activate", "AMP-activated", "protein", "kinase", "(AMPK).", "It", "has", "also", "been", "shown", "to", "inhibit", "cyclin", "D1", "expression", "and", "proliferation", "of", "some", "cultured", "cancer", "cells.", "However,", "the", "mechanisms", "of", "action", "by", "which", "metformin", "mediates", "cell", "cycle", "arrest", "are", "not", "completely", "understood.", "Results:", "In", "this", "study,", "metformin", "was", "found", "to", "inhibit", "proliferation", "of", "most", "cultured", "breast", "cancer", "cell", "lines.", "This", "was", "independent", "of", "estrogen", "receptor,", "HER2,", "or", "p53", "status.", "Inhibition", "of", "cell", "proliferation", "was", "associated", "with", "arrest", "within", "G0/G1", "phase", "of", "the", "cell", "cycle.", "As", "in", "previous", "studies,", "metformin", "treatment", "led", "to", "activation", "of", "(AMPK)", "and", "downregulation", "of", "cyclin", "D1.", "However,", "these", "events", "were", "not", "sufficient", "for", "cell", "cycle", "arrest", "because", "they", "were", "also", "observed", "in", "the", "MDA-MB-", "231", "cell", "line,", "which", "is", "not", "sensitive", "to", "growth", "arrest", "by", "metformin.", "In", "sensitive", "breast", "cancer", "lines,", "the", "reduction", "in", "cyclin", "D1", "led", "to", "release", "of", "sequestered", "CDK", "inhibitors,", "p27Kip1", "and", "p21Cip1,", "and", "association", "of", "these", "inhibitors", "with", "cyclin", "E/CDK2", "complexes.", "The", "metformin-resistant", "cell", "line", "MDA-MB-231", "expresses", "significantly", "lower", "levels", "of", "p27Kip1", "and", "p21Cip1", "than", "the", "metformin-", "sensitive", "cell", "line,", "MCF7.", "When", "p27Kip1", "or", "p21Cip1", "were", "overexpressed", "in", "MDA-MB-231,", "the", "cells", "became", "sensitive", "to", "cell", "cycle", "arrest", "in", "response", "to", "metformin.", "Conclusion:", "Cell", "cycle", "arrest", "in", "response", "to", "metformin", "requires", "CDK", "inhibitors", "in", "addition", "to", "AMPK", "activation", "and", "cyclin", "D1", "downregulation.", "This", "is", "of", "interest", "because", "many", "cancers", "are", "associated", "with", "loss", "or", "downregulation", "of", "CDK", "inhibitors", "and", "the", "results", "may", "be", "relevant", "to", "the", "development", "of", "anti-tumor", "reagents", "that", "target", "the", "AMPK", "pathway.", "Background", "Metformin", "hydrochloride", "(N,", "N-dimethylimidodicarbon-", "imidic", "diamide", "hydrochloride)", "is", "a", "commonly", "prescribed", "oral", "antihyperglycemic", "drug", "used", "in", "the", "management", "of", "Type", "2", "diabetes.", "Recent", "evidence", "indicates", "that", "metformin", "has", "significant", "effects", "on", "tumorigenesis", "and", "cancer", "cell", "growth.", "It", "was", "reported", "that", "patients", "with", "Type", "2", "diabetes", "who", "are", "prescribed", "metformin", "have", "a", "lower", "risk", "of", "cancer", "compared", "to", "patients", "that", "do", "not", "take", "metformin", "[1,2].", "In", "a", "mouse", "xenograft", "model,", "metformin", "suppressed", "tumor", "Page", "1", "of", "11", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Frontiers", "in", "Zoology", "Research", "Sponge", "budding", "is", "a", "spatiotemporal", "morphological", "patterning", "process:", "Insights", "from", "synchrotron", "radiation-based", "x-ray", "microtomography", "into", "the", "asexual", "reproduction", "of", "Tethya", "wilhelma", "Jörg", "U", "Hammel1,", "Julia", "Herzen2,", "Felix", "Beckmann2", "and", "Michael", "Nickel*1", "BioMed", "Central", "Open", "Access", "Address:", "1Institut", "für", "Spezielle", "Zoologie", "und", "Evolutionsbiologie,", "Friedrich-Schiller-Universität", "Jena,", "Erbertstr.", "1,", "07743", "Jena,", "Germany", "and", "2GKSS", "Research", "Center,", "Max-Planck-Str.", "1,", "21502", "Geesthacht,", "Germany", "Email:", "Jörg", "U", "Hammel", "-", "joerg.hammel@uni-jena.de;", "Julia", "Herzen", "-", "julia.herzen@gkss.de;", "Felix", "Beckmann", "-", "felix.beckmann@gkss.de;", "Michael", "Nickel*", "-", "m.nickel@uni-jena.de", "*", "Corresponding", "author", "Published:", "8", "September", "2009", "Frontiers", "in", "Zoology", "2009,", "6:19", "doi:10.1186/1742-9994-6-19", "This", "article", "is", "available", "from:", "http://www.frontiersinzoology.com/content/6/1/19", "Received:", "26", "June", "2009", "Accepted:", "8", "September", "2009", "©", "2009", "Hammel", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "Primary", "agametic-asexual", "reproduction", "mechanisms", "such", "as", "budding", "and", "fission", "are", "present", "in", "all", "non-bilaterian", "and", "many", "bilaterian", "animal", "taxa", "and", "are", "likely", "to", "be", "metazoan", "ground", "pattern", "characters.", "Cnidarians", "display", "highly", "organized", "and", "regulated", "budding", "processes.", "In", "contrast,", "budding", "in", "poriferans", "was", "thought", "to", "be", "less", "specific", "and", "related", "to", "the", "general", "ability", "of", "this", "group", "to", "reorganize", "their", "tissues.", "Here", "we", "test", "the", "hypothesis", "of", "morphological", "pattern", "formation", "during", "sponge", "budding.", "Results:", "We", "investigated", "the", "budding", "process", "in", "Tethya", "wilhelma", "(Demospongiae)", "by", "applying", "3D", "morphometrics", "to", "high", "resolution", "synchrotron", "radiation-based", "x-ray", "microtomography", "(SR-μCT)", "image", "data.", "We", "followed", "the", "morphogenesis", "of", "characteristic", "body", "structures", "and", "identified", "distinct", "morphological", "states", "which", "indeed", "reveal", "characteristic", "spatiotemporal", "morphological", "patterns", "in", "sponge", "bud", "development.", "We", "discovered", "the", "distribution", "of", "skeletal", "elements,", "canal", "system", "and", "sponge", "tissue", "to", "be", "based", "on", "a", "sequential", "series", "of", "distinct", "morphological", "states.", "Based", "on", "morphometric", "data", "we", "defined", "four", "typical", "bud", "stages.", "Once", "they", "have", "reached", "the", "final", "stage", "buds", "are", "released", "as", "fully", "functional", "juvenile", "sponges", "which", "are", "morphologically", "and", "functionally", "equivalent", "to", "adult", "specimens.", "Conclusion:", "Our", "results", "demonstrate", "that", "budding", "in", "demosponges", "is", "considerably", "more", "highly", "organized", "and", "regulated", "than", "previously", "assumed.", "Morphological", "pattern", "formation", "in", "asexual", "reproduction", "with", "underlying", "genetic", "regulation", "seems", "to", "have", "evolved", "early", "in", "metazoans", "and", "was", "likely", "part", "of", "the", "developmental", "program", "of", "the", "last", "common", "ancestor", "of", "all", "Metazoa", "(LCAM).", "Background", "Sponges", "(Porifera)", "display", "a", "wide", "range", "of", "reproduction", "strategies,", "both", "sexual", "and", "asexual.", "Asexual", "reproduction", "in", "sponges", "occurs", "as", "a", "variety", "of", "mechanisms,", "including", "budding,", "fragmentation", "and", "gemmulation", "[1].", "In", "general,", "asexual", "reproduction", "seems", "to", "be", "part", "of", "the", "ground", "pat-", "tern", "of", "all", "Metazoa", "[2].", "However,", "primary", "agametic-asex-", "ual", "reproduction", "mechanisms", "such", "as", "fission", "or", "budding", "should", "be", "clearly", "distinguished", "from", "secondary", "asexual", "reproduction", "mechanisms", "such", "as", "parthenogenesis.", "Apart", "Page", "1", "of", "14", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "BMC", "Medical", "Informatics", "and", "Decision", "Making", "Software", "The", "tissue", "microarray", "data", "exchange", "specification:", "A", "document", "type", "definition", "to", "validate", "and", "enhance", "XML", "data", "David", "G", "Nohle*", "and", "Leona", "W", "Ayers", "BioMed", "Central", "Open", "Access", "Address:", "The", "Mid-Region", "AIDS", "and", "Cancer", "Specimen", "Resource", "(ACSR),", "Department", "of", "Pathology,", "The", "Ohio", "State", "University,", "Columbus,", "OH", "USA", "Email:", "David", "G", "Nohle*", "-", "nohle-1@medctr.osu.edu;", "Leona", "W", "Ayers", "-", "ayers.1@osu.edu", "*", "Corresponding", "author", "Published:", "04", "May", "2005", "BMC", "Medical", "Informatics", "and", "Decision", "Making", "2005,", "5:12", "doi:10.1186/1472-", "6947-5-12", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1472-6947/5/12", "Received:", "22", "February", "2005", "Accepted:", "04", "May", "2005", "©", "2005", "Nohle", "and", "Ayers;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "The", "Association", "for", "Pathology", "Informatics", "(API)", "Extensible", "Mark-up", "Language", "(XML)", "TMA", "Data", "Exchange", "Specification", "(TMA", "DES)", "proposed", "in", "April", "2003", "provides", "a", "community-based,", "open", "source", "tool", "for", "sharing", "tissue", "microarray", "(TMA)", "data", "in", "a", "common", "format.", "Each", "tissue", "core", "within", "an", "array", "has", "separate", "data", "including", "digital", "images;", "therefore", "an", "organized,", "common", "approach", "to", "produce,", "navigate", "and", "publish", "such", "data", "facilitates", "viewing,", "sharing", "and", "merging", "TMA", "data", "from", "different", "laboratories.", "The", "AIDS", "and", "Cancer", "Specimen", "Resource", "(ACSR)", "is", "a", "HIV/AIDS", "tissue", "bank", "consortium", "sponsored", "by", "the", "National", "Cancer", "Institute", "(NCI)", "Division", "of", "Cancer", "Treatment", "and", "Diagnosis", "(DCTD).", "The", "ACSR", "offers", "HIV-related", "malignancies", "and", "uninfected", "control", "tissues", "in", "microarrays", "(TMA)", "accompanied", "by", "de-identified", "clinical", "data", "to", "approved", "researchers.", "Exporting", "our", "TMA", "data", "into", "the", "proposed", "API", "specified", "format", "offers", "an", "opportunity", "to", "evaluate", "the", "API", "specification", "in", "an", "applied", "setting", "and", "to", "explore", "its", "usefulness.", "Results:", "A", "document", "type", "definition", "(DTD)", "that", "governs", "the", "allowed", "common", "data", "elements", "(CDE)", "in", "TMA", "DES", "export", "XML", "files", "was", "written,", "tested", "and", "evolved", "and", "is", "in", "routine", "use", "by", "the", "ACSR.", "This", "DTD", "defines", "TMA", "DES", "CDEs", "which", "are", "implemented", "in", "an", "external", "file", "that", "can", "be", "supplemented", "by", "internal", "DTD", "extensions", "for", "locally", "defined", "TMA", "data", "elements", "(LDE).", "Conclusion:", "ACSR", "implementation", "of", "the", "TMA", "DES", "demonstrated", "the", "utility", "of", "the", "specification", "and", "allowed", "application", "of", "a", "DTD", "to", "validate", "the", "language", "of", "the", "API", "specified", "XML", "elements", "and", "to", "identify", "possible", "enhancements", "within", "our", "TMA", "data", "management", "application.", "Improvements", "to", "the", "specification", "have", "additionally", "been", "suggested", "by", "our", "experience", "in", "importing", "other", "institution's", "exported", "TMA", "data.", "Enhancements", "to", "TMA", "DES", "to", "remove", "ambiguous", "situations", "and", "clarify", "the", "data", "should", "be", "considered.", "Better", "specified", "identifiers", "and", "hierarchical", "relationships", "will", "make", "automatic", "use", "of", "the", "data", "possible.", "Our", "tool", "can", "be", "used", "to", "reorder", "data", "and", "add", "identifiers;", "upgrading", "data", "for", "changes", "in", "the", "specification", "can", "be", "automatically", "accomplished.", "Using", "a", "DTD", "(optionally", "reflecting", "our", "proposed", "enhancements)", "can", "provide", "stronger", "validation", "of", "exported", "TMA", "data.", "Page", "1", "of", "9", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Hindawi", "Publishing", "Corporation", "Journal", "of", "Oncology", "Volume", "2010,", "Article", "ID", "932371,", "13", "pages", "doi:10.1155/2010/932371", "Review", "Article", "Ovarian", "Cancer", "Pathogenesis:", "A", "Model", "in", "Evolution", "Alison", "M.", "Karst1", "and", "Ronny", "Drapkin1,", "2", "1", "Department", "of", "Medical", "Oncology,", "Center", "for", "Molecular", "Oncologic", "Pathology,", "Dana-Farber", "Cancer", "Institute,", "44", "Binney", "Street,", "Boston,", "MA", "02115,", "USA", "2", "Department", "of", "Pathology,", "Brigham", "and", "Women’s", "Hospital,", "75", "Francis", "Street,", "Boston,", "MA", "02115,", "USA", "Correspondence", "should", "be", "addressed", "to", "Ronny", "Drapkin,", "ronny", "drapkin@dfci.harvard.edu", "Received", "1", "June", "2009;", "Accepted", "23", "June", "2009", "Academic", "Editor:", "Tian-Li", "Wang", "Copyright", "©", "2010", "A.", "M.", "Karst", "and", "R.", "Drapkin.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Ovarian", "cancer", "is", "a", "deadly", "disease", "for", "which", "there", "is", "no", "effective", "means", "of", "early", "detection.", "Ovarian", "carcinomas", "comprise", "a", "diverse", "group", "of", "neoplasms,", "exhibiting", "a", "wide", "range", "of", "morphological", "characteristics,", "clinical", "manifestations,", "genetic", "alterations,", "and", "tumor", "behaviors.", "This", "high", "degree", "of", "heterogeneity", "presents", "a", "major", "clinical", "challenge", "in", "both", "diagnosing", "and", "treating", "ovarian", "cancer.", "Furthermore,", "the", "early", "events", "leading", "to", "ovarian", "carcinoma", "development", "are", "poorly", "understood,", "thus", "complicating", "efforts", "to", "develop", "screening", "modalities", "for", "this", "disease.", "Here,", "we", "provide", "an", "overview", "of", "the", "current", "models", "of", "ovarian", "cancer", "pathogenesis,", "highlighting", "recent", "findings", "implicating", "the", "fallopian", "tube", "fimbria", "as", "a", "possible", "site", "of", "origin", "of", "ovarian", "carcinomas.", "The", "ovarian", "cancer", "model", "will", "continue", "to", "evolve", "as", "we", "learn", "more", "about", "the", "genetics", "and", "etiology", "of", "this", "disease.", "1.", "Introduction", "Ovarian", "cancer", "afflicts", "∼204", "000", "women", "worldwide", "each", "year,", "including", "∼21", "650", "Americans", "[1,", "2].", "Despite", "its", "rela-", "tively", "low", "incidence", "rate,", "ovarian", "cancer", "is", "an", "extremely", "lethal", "disease.", "Globally,", "it", "claims", "125", "000", "lives", "per", "year,", "making", "it", "the", "seventh", "leading", "cause", "of", "cancer-related", "deaths", "among", "women", "[2].", "In", "the", "United", "States,", "ovarian", "cancer", "mortality", "is", "even", "higher;", "it", "ranks", "as", "the", "fifth", "deadliest", "malignancy", "among", "women,", "with", "an", "estimated", "15", "520", "deaths", "per", "year", "[1].", "In", "fact,", "of", "the", "top", "ten", "cancer", "types", "afflicting", "American", "women", "in", "2008,", "ovarian", "cancer", "had", "the", "highest", "death-to-", "incidence", "ratio,", "exceeding", "even", "that", "of", "lung", "cancer", "[1].", "Its", "high", "mortality", "is", "primarily", "due", "to", "difficulties", "in", "diagnosing", "early", "stage", "disease.", "Although", "the", "5", "years", "survival", "rate", "for", "stage", "I", "ovarian", "cancer", "is", ">90%,", "stage", "I", "diagnoses", "are", "more", "often", "the", "exception", "than", "the", "rule.", "Most", "patients", "(∼75%)", "present", "with", "advanced", "stage", "(III/IV)", "tumors,", "for", "which", "the", "5", "years", "survival", "rate", "is", "a", "dismal", "30%", "[1].", "This", "is", "not", "surprising", "when", "one", "considers", "the", "anatomical", "problem—the", "ovaries", "are", "a", "pair", "of", "tiny", "organs,", "only", "∼2–4", "cm", "in", "diameter,", "suspended", "on", "either", "side", "of", "the", "uterus", "and", "not", "readily", "accessible", "by", "pelvic", "examination", "unless", "significantly", "enlarged.", "By", "definition,", "a", "stage", "I", "tumor", "is", "confined", "to", "the", "ovary", "[3]", "and", "is", "therefore", "unlikely", "to", "be", "noticed", "without", "the", "aid", "of", "a", "sensitive", "screening", "test.", "Unfortunately,", "there", "are", "currently", "no", "effective", "screening", "modalities", "for", "detecting", "ovarian", "cancer", "in", "asymptomatic", "individuals.", "Furthermore,", "there", "are", "no", "tell-tale", "physical", "signs", "of", "the", "disease.", "Typical", "symptoms—which", "include", "abdominal", "discomfort,", "bloating,", "gas,", "nausea,", "and", "urinary", "urgency—are", "vague", "and", "often", "mistaken", "for", "gastrointestinal", "problems", "[4,", "5].", "In", "many", "cases,", "symptoms", "may", "not", "even", "present", "until", "the", "tumor", "has", "reached", "an", "advanced", "stage.", "Consequently,", "ovarian", "cancer", "is", "frequently", "nicknamed", "the", "“silent", "killer”", "[5–7].", "2.", "Early", "Detection", "The", "best", "tools", "currently", "available", "for", "detecting", "early-stage", "ovarian", "cancer", "are", "transvaginal", "sonography", "(TVS)", "and", "serum", "biomarker", "testing.", "TVS", "is", "a", "noninvasive", "technique", "that", "provides", "detailed", "images", "of", "ovary", "size", "and", "shape,", "facilitating", "the", "detection", "of", "ovarian", "masses.", "Large-scale", "studies", "evaluating", "its", "ability", "to", "identify", "early-stage", "tumors", "have", "reported", "mixed", "results", "[8–13].", "Overall,", "TVS", "has", "not", "demonstrated", "adequate", "sensitivity", "to", "warrant", "its", "use", "in", "screening", "general", "populations.", "Furthermore,", "even", "in", "the", "most", "optimistic", "reports,", "it", "is", "clear", "that", "TVS", "can", "only", "detect", "tumors", "that", "cause", "a", "significant", "increase", "in", "ovarian" ]

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[ "BMC", "Medical", "Research", "Methodology", "Research", "article", "Meta-analytic", "methods", "for", "pooling", "rates", "when", "follow-up", "duration", "varies:", "a", "case", "study", "James", "P", "Guevara*1,", "Jesse", "A", "Berlin2", "and", "Fredric", "M", "Wolf3", "BioMed", "Central", "Open", "Access", "Address:", "1Department", "of", "Pediatrics,", "The", "Children's", "Hospital", "of", "Philadelphia", "and", "the", "University", "of", "Pennsylvania", "School", "of", "Medicine,", "3535", "Market", "St,", "Room", "1531,", "Philadelphia,", "PA", "19104,", "USA,", "2Department", "of", "Biostatistics", "and", "Epidemiology,", "Center", "for", "Clinical", "Epidemiology", "and", "Biostatistics,", "Center", "for", "Education", "and", "Research", "on", "Therapeutics,", "University", "of", "Pennsylvania", "School", "of", "Medicine,", "Blockley", "Hall,", "Room", "611,", "Philadelphia,", "PA", "19104,", "USA", "and", "3Department", "of", "Medical", "Education", "and", "Biomedical", "Informatics,", "University", "of", "Washington", "School", "of", "Medicine,", "1959", "NE", "Pacific", "St,", "Room", "E-312,", "Seattle,", "WA", "98195,", "USA", "Email:", "James", "P", "Guevara*", "-", "guevara@email.chop.edu;", "Jesse", "A", "Berlin", "-", "jberlin@cceb.upenn.edu;", "Fredric", "M", "Wolf", "-", "wolf@u.washington.edu", "*", "Corresponding", "author", "Published:", "12", "July", "2004", "BMC", "Medical", "Research", "Methodology", "2004,", "4:17", "doi:10.1186/1471-2288-4-17", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2288/4/17", "Received:", "19", "March", "2004", "Accepted:", "12", "July", "2004", "©", "2004", "Guevara", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article:", "verbatim", "copying", "and", "redistribution", "of", "this", "article", "are", "permitted", "in", "all", "media", "for", "any", "purpose,", "provided", "this", "notice", "is", "preserved", "along", "with", "the", "article's", "original", "URL.", "Abstract", "Background:", "Meta-analysis", "can", "be", "used", "to", "pool", "rate", "measures", "across", "studies,", "but", "challenges", "arise", "when", "follow-up", "duration", "varies.", "Our", "objective", "was", "to", "compare", "different", "statistical", "approaches", "for", "pooling", "count", "data", "of", "varying", "follow-up", "times", "in", "terms", "of", "estimates", "of", "effect,", "precision,", "and", "clinical", "interpretability.", "Methods:", "We", "examined", "data", "from", "a", "published", "Cochrane", "Review", "of", "asthma", "self-management", "education", "in", "children.", "We", "selected", "two", "rate", "measures", "with", "the", "largest", "number", "of", "contributing", "studies:", "school", "absences", "and", "emergency", "room", "(ER)", "visits.", "We", "estimated", "fixed-", "and", "random-effects", "standardized", "weighted", "mean", "differences", "(SMD),", "stratified", "incidence", "rate", "differences", "(IRD),", "and", "stratified", "incidence", "rate", "ratios", "(IRR).", "We", "also", "fit", "Poisson", "regression", "models,", "which", "allowed", "for", "further", "adjustment", "for", "clustering", "by", "study.", "Results:", "For", "both", "outcomes,", "all", "methods", "gave", "qualitatively", "similar", "estimates", "of", "effect", "in", "favor", "of", "the", "intervention.", "For", "school", "absences,", "SMD", "showed", "modest", "results", "in", "favor", "of", "the", "intervention", "(SMD", "-0.14,", "95%", "CI", "-0.23", "to", "-0.04).", "IRD", "implied", "that", "the", "intervention", "reduced", "school", "absences", "by", "1.8", "days", "per", "year", "(IRD", "-0.15", "days/child-month,", "95%", "CI", "-0.19", "to", "-0.11),", "while", "IRR", "suggested", "a", "14%", "reduction", "in", "absences", "(IRR", "0.86,", "95%", "CI", "0.83", "to", "0.90).", "For", "ER", "visits,", "SMD", "showed", "a", "modest", "benefit", "in", "favor", "of", "the", "intervention", "(SMD", "-0.27,", "95%", "CI:", "-0.45", "to", "-0.09).", "IRD", "implied", "that", "the", "intervention", "reduced", "ER", "visits", "by", "1", "visit", "every", "2", "years", "(IRD", "-0.04", "visits/child-month,", "95%", "CI:", "-0.05", "to", "-0.03),", "while", "IRR", "suggested", "a", "34%", "reduction", "in", "ER", "visits", "(IRR", "0.66,", "95%", "CI", "0.59", "to", "0.74).", "In", "Poisson", "models,", "adjustment", "for", "clustering", "lowered", "the", "precision", "of", "the", "estimates", "relative", "to", "stratified", "IRR", "results.", "For", "ER", "visits", "but", "not", "school", "absences,", "failure", "to", "incorporate", "study", "indicators", "resulted", "in", "a", "different", "estimate", "of", "effect", "(unadjusted", "IRR", "0.77,", "95%", "CI", "0.59", "to", "0.99).", "Conclusions:", "Choice", "of", "method", "among", "the", "ones", "presented", "had", "little", "effect", "on", "inference", "but", "affected", "the", "clinical", "interpretability", "of", "the", "findings.", "Incidence", "rate", "methods", "gave", "more", "clinically", "interpretable", "results", "than", "SMD.", "Poisson", "regression", "allowed", "for", "further", "adjustment", "for", "heterogeneity", "across", "studies.", "These", "data", "suggest", "that", "analysts", "who", "want", "to", "improve", "the", "clinical", "interpretability", "of", "their", "findings", "should", "consider", "incidence", "rate", "methods.", "Page", "1", "of", "7", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Halogenase", "Genes", "in", "Nonribosomal", "Peptide", "Synthetase", "Gene", "Clusters", "of", "Microcystis", "(Cyanobacteria):", "Sporadic", "Distribution", "and", "Evolution", "Sabrina", "Cadel-Six,*", "Catherine", "Dauga,", "Anne", "Marie", "Castets,*", "Rosmarie", "Rippka,*", "Christiane", "Bouchier,", "Nicole", "Tandeau", "de", "Marsac,*", "and", "Martin", "Welker*§1", "*Institut", "Pasteur,", "Unite´", "des", "Cyanobacte´ries;", "Centre", "National", "de", "la", "Recherche", "Scientifique,", "Unite´", "de", "Recherche", "Associe´e", "2172,", "Paris,", "France;", "Institut", "Pasteur,", "Genopole", "Ile", "de", "France—Plateforme", "4,", "Paris,", "France;", "Institut", "Pasteur,", "Genopole", "Ile", "de", "France—Plateforme", "1,", "Paris,", "France;", "and", "§Technische", "Universita¨t", "Berlin,", "Institut", "Chemie,", "AG", "Biochemie", "&", "Molekulare", "Biologie,", "Berlin,", "Germany", "Cyanobacteria", "of", "the", "genus", "Microcystis", "are", "known", "to", "produce", "secondary", "metabolites", "of", "large", "structural", "diversity", "by", "nonribosomal", "peptide", "synthetase", "(NRPS)", "pathways.", "For", "a", "number", "of", "such", "compounds,", "halogenated", "congeners", "have", "been", "reported", "along", "with", "nonhalogenated", "ones.", "In", "the", "present", "study,", "chlorinated", "cyanopeptolin-", "and/or", "aeruginosin-type", "peptides", "were", "detected", "by", "mass", "spectrometry", "in", "17", "out", "of", "28", "axenic", "strains", "of", "Microcystis.", "In", "these", "strains,", "a", "halogenase", "gene", "was", "identified", "between", "2", "genes", "coding", "for", "NRPS", "modules", "in", "respective", "gene", "clusters,", "whereas", "it", "was", "consistently", "absent", "when", "the", "strains", "produced", "only", "nonchlorinated", "corresponding", "congeners.", "Nucleotide", "sequences", "were", "obtained", "for", "12", "complete", "halogenase", "genes", "and", "14", "intermodule", "regions", "of", "gene", "clusters", "lacking", "a", "halogenase", "gene", "or", "containing", "only", "fragments", "of", "it.", "When", "a", "halogenase", "gene", "was", "found", "absent,", "a", "specific,", "identical", "excision", "pattern", "was", "observed", "for", "both", "synthetase", "gene", "clusters", "in", "most", "strains.", "A", "phylogenetic", "analysis", "including", "other", "bacterial", "halogenases", "showed", "that", "the", "NRPS-related", "halogenases", "of", "Microcystis", "form", "a", "monophyletic", "group", "divided", "into", "2", "subgroups,", "corresponding", "to", "either", "the", "cyanopeptolin", "or", "the", "aeruginosin", "peptide", "synthetases.", "The", "distribution", "of", "these", "peptide", "synthetase", "gene", "clusters,", "among", "the", "tested", "Microcystis", "strains,", "was", "found", "in", "relative", "agreement", "with", "their", "phylogeny", "reconstructed", "from", "16S–23S", "rDNA", "intergenic", "spacer", "sequences,", "whereas", "the", "distribution", "of", "the", "associated", "halogenase", "genes", "appears", "to", "be", "sporadic.", "The", "presented", "data", "suggest", "that", "in", "cyanobacteria", "these", "prevalent", "halogenase", "genes", "originated", "from", "an", "ancient", "horizontal", "gene", "transfer", "followed", "by", "duplication", "in", "the", "cyanobacterial", "lineage.", "We", "propose", "an", "evolutionary", "scenario", "implying", "repeated", "gene", "losses", "to", "explain", "the", "distribution", "of", "halogenase", "genes", "in", "2", "NRPS", "gene", "clusters", "that", "subsequently", "defines", "the", "seemingly", "erratic", "production", "of", "halogenated", "and", "nonhalogenated", "aeruginosins", "and", "cyanopeptolins", "among", "Microcystis", "strains.", "Introduction", "Cyanobacteria", "are", "a", "rich", "source", "of", "structurally", "diverse", "oligopeptides", "that", "are", "predominantly", "synthesized", "by", "nonri-", "bosomal", "peptide", "synthetases", "(NRPS).", "In", "Microcystis,", "a", "common", "genus", "in", "eutrophic", "freshwaters,", "numerous", "bio-", "active", "peptides", "have", "been", "identified", "that", "can", "be", "mostly", "classified", "as", "aeruginosins,", "microginins,", "microcystins,", "cya-", "nopeptolins,", "and", "anabaenopeptins", "(Welker", "and", "von", "D", "o¨hren", "2006).", "One", "intriguing", "property", "of", "these", "peptides", "is", "their", "structural", "diversity,", "achieved", "either", "by", "variability", "of", "amino", "acid", "moieties", "in", "particular", "positions", "or", "by", "modifications", "like", "glycosylation,", "sulfatation,", "methylation,", "or", "halogenation", "(Ishida", "et", "al.", "1999,", "2007;", "Rouhiainen", "et", "al.", "2000;", "von", "Elert", "et", "al.", "2005)", "giving", "rise", "to", "virtually", "hundreds", "of", "congeners", "in", "each", "peptide", "class.", "The", "potential", "of", "Microcystis", "to", "produce", "a", "multitude", "of", "chlorinated", "peptides", "has", "been", "recognized", "in", "chemotyping", "studies", "of", "natural", "populations", "(Welker", "et", "al.", "2006).", "Halogenated", "congeners", "have", "mainly", "been", "found", "among", "aeruginosin-,", "cyanopeptolin-", "(fig.", "1),", "and", "microginin-type", "peptides,", "so", "far.", "It", "has", "to", "be", "noted", "that", "the", "names", "‘‘aerugino-", "sin’’", "and", "‘‘cyanopeptolin’’", "refer", "to", "peptide", "types", "with", "unique", "features", "(see", "fig.", "1)", "regardless", "whether", "individual", "peptide", "structures", "have", "been", "named", "differently.", "Cyanopeptolin-type", "peptides,", "for", "example,", "have", "been", "named", "cyanopeptolins,", "1", "Present", "address:", "Anagnostec", "GmbH,", "Am", "Mu¨hlenberg", "11,", "Potsdam,", "Germany.", "Key", "words:", "halogenase,", "cyanopeptolin,", "aeruginosin,", "DNA", "rearrange-", "ment,", "secondary", "peptide", "metabolite,", "chlorination,", "internal", "transcribed", "spacer,", "phylogeny.", "E-mail:", "ntmarsac@pasteur.fr.", "Mol.", "Biol.", "Evol.", "25(9):2031–2041.", "2008", "doi:10.1093/molbev/msn150", "Advance", "Access", "publication", "July", "8,", "2008", "anabaenopeptilides,", "microcystilide,", "aeruginopeptins,", "or", "os-", "cillapeptins", "in", "the", "original", "publications", "(for", "a", "review,", "see", "Welker", "and", "von", "D", "o¨hren", "2006).", "Cyanopeptolin-type", "pepti-", "des", "have", "been", "reported", "from", "distant", "cyanobacterial", "taxa", "be-", "longing", "to", "the", "Orders", "Chroococcales,", "Oscillatoriales,", "and", "Nostocales", "(Welker", "and", "von", "D", "o¨hren", "2006).", "Most", "structural", "variants", "inhibit", "serine", "proteases", "(trypsin,", "chymotrypsin,", "or", "elastase)", "by", "preventing", "the", "hydrolytic", "attack", "on", "substrates", "by", "covering", "the", "active", "center", "with", "the", "rigid", "ring", "structure", "(Matern", "et", "al.", "2003).", "Many", "structural", "variants", "of", "aerugino-", "sins", "have", "been", "reported", "from", "Microcystis", "(Chroococcales)", "and", "Planktothrix", "(Oscillatoriales).", "Aeruginosins", "have", "also", "been", "shown", "to", "inhibit", "serine", "proteases,", "especially", "thrombin", "(Ishida", "et", "al.", "1999).", "Despite", "the", "ubiquitous", "presence", "of", "these", "peptides", "(and", "others)", "in", "natural", "cyanobacterial", "consortia,", "a", "consistent", "hypothesis", "explaining", "their", "function", "in", "produc-", "ing", "cells", "has", "not", "yet", "been", "proposed.", "In", "microginins,", "linear", "tetra-", "or", "pentapeptides,", "chlorina-", "tion", "occurs", "at", "an", "N-terminal", "aliphatic", "moiety", "(a", "modified", "decanoic", "acid)", "(Ishida", "et", "al.", "1998),", "whereas", "in", "aeruginosins", "and", "cyanopeptolins,", "chlorination", "occurs", "at", "aromatic", "moie-", "ties.", "Expectedly,", "halogenating", "enzymes", "differ", "for", "these", "2", "types", "of", "chlorination.", "Aliphatic", "halogenation", "has", "been", "re-", "ported", "for", "the", "barbamide", "biosynthesis", "pathway", "of", "Lyngbya", "majuscula", "(Sitachitta", "et", "al.", "2000),", "where", "a", "chlorine", "is", "transferred", "to", "a", "native", "leucine", "during", "biosynthesis", "by", "a", "nonheme", "FeII", "halogenase", "(Galonic", "et", "al.", "2006).", "A", "sim-", "ilar", "enzyme", "has", "been", "reported", "for", "the", "syringomycin", "bio-", "synthesis", "in", "Pseudomonas", "syringae", "(Vaillancourt", "et", "al.", "2005).", "Halogenation", "on", "aromatic", "moieties", "is", "thought", "to", "be", "catalyzed", "primarily", "by", "FADH2-dependent", "halogenases", "(Vaillancourt", "et", "al.", "2006;", "van", "Pe´", "e", "and", "Patallo", "2006).", "In", "Microcystis,", "mono-", "or", "dichlorination", "of", "aeruginosins", "2008", "The", "Authors", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/by-nc/2.0/", "uk/)", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Journal", "of", "Medical", "Case", "Reports", "Case", "report", "Gigantic", "retroperitoneal", "hematoma", "as", "a", "complication", "of", "anticoagulation", "therapy", "with", "heparin", "in", "therapeutic", "doses:", "a", "case", "report", "Stavros", "I", "Daliakopoulos*1,", "Andreas", "Bairaktaris1,", "Dimitrios", "Papadimitriou2", "and", "Perikles", "Pappas2", "BioMed", "Central", "Open", "Access", "Address:", "1Herz-", "und", "Diabeteszentrum", "Nordrhein,", "Westfalen,", "Georgstrasse,", "Bad", "Oeynhausen,", "Universitätsklinikum", "der", "Ruhr-Universität", "Bochum,", "Germany", "and", "2Department", "of", "Vascular", "and", "Endovascular", "Surgery,", "424", "Military", "Hospital,", "Thessaloniki,", "Greece", "Email:", "Stavros", "I", "Daliakopoulos*", "-", "sdaliak@otenet.gr;", "Andreas", "Bairaktaris", "-", "abairaktaris@hdz-nrw.de;", "Dimitrios", "Papadimitriou", "-", "dimitriospapa@yahoo.gr;", "Perikles", "Pappas", "-", "vasilaki@med.auth.gr", "*", "Corresponding", "author", "Published:", "17", "May", "2008", "Journal", "of", "Medical", "Case", "Reports", "2008,", "2:162", "doi:10.1186/1752-1947-2-162", "This", "article", "is", "available", "from:", "http://www.jmedicalcasereports.com/content/2/1/162", "Received:", "6", "November", "2007", "Accepted:", "17", "May", "2008", "©", "2008", "Daliakopoulos", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Introduction:", "Spontaneous", "retroperitoneal", "hemorrhage", "is", "a", "distinct", "clinical", "entity", "that", "can", "present", "as", "a", "rare", "life-threatening", "event", "characterized", "by", "sudden", "onset", "of", "bleeding", "into", "the", "retroperitoneal", "space,", "occurring", "in", "association", "with", "bleeding", "disorders,", "intratumoral", "bleeding,", "or", "ruptures", "of", "any", "retroperitoneal", "organ", "or", "aneurysm.", "The", "spontaneous", "form", "is", "the", "most", "infrequent", "retroperitoneal", "hemorrhage,", "causing", "significant", "morbidity", "and", "representing", "a", "diagnostic", "challenge.", "Case", "presentation:", "We", "report", "the", "case", "of", "a", "patient", "with", "coronary", "artery", "disease", "who", "presented", "with", "transient", "ischemic", "attack,", "in", "whom", "anticoagulant", "therapy", "with", "heparin", "precipitated", "a", "massive", "spontaneous", "atraumatic", "retroperitoneal", "hemorrhage", "(with", "international", "normalized", "ratio", "2.4),", "which", "was", "treated", "conservatively.", "Conclusion:", "Delay", "in", "diagnosis", "is", "potentially", "fatal", "and", "high", "clinical", "suspicion", "remains", "crucial.", "Finally,", "it", "is", "a", "matter", "of", "controversy", "whether", "retroperitoneal", "hematomas", "should", "be", "surgically", "evacuated", "or", "conservatively", "treated", "and", "the", "final", "decision", "should", "be", "made", "after", "taking", "into", "consideration", "patient's", "general", "condition", "and", "the", "possibility", "of", "permanent", "femoral", "or", "sciatic", "neuropathy", "due", "to", "compression", "syndrome.", "Introduction", "Hemorrhage", "is", "the", "most", "important", "complication", "of", "unfractionated", "heparin", "in", "patients", "with", "atrial", "fibrillation", "(AF)", "treated", "with", "oral", "vitamin", "K", "antagonist", "(VKA)", "during", "hospitalization", "or", "among", "those", "receiving", "anticoagulants", "in", "terms", "of", "emergency", "or", "elective", "cardiac", "surgery", "[1,2]", "or", "in", "the", "initial", "treatment", "of", "deep", "venous", "thrombosis", "[3,4].", "Analysis", "of", "the", "data", "presented", "by", "the", "European", "AF", "Trial", "Study", "Group", "[5]", "shows", "that", "as", "the", "international", "normal-", "ized", "ratio", "(INR)", "increased,", "there", "was", "an", "increase", "in", "the", "risk", "of", "major", "bleeding,", "such", "that", "at", "INR", "≥", "5.0,", "the", "risk", "of", "bleed-", "ing", "increased", "3.6-fold", "relative", "to", "INR", "≤", "2.", "The", "optimal", "intensity", "of", "anticoagulation", "that", "achieved", "maximum", "ther-", "apeutic", "effect", "with", "minimum", "risk", "was", "determined", "to", "be", "at", "Page", "1", "of", "5", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "F-Spondin/spon1b", "Expression", "Patterns", "in", "Developing", "and", "Adult", "Zebrafish", "1", "1", "1", "1", "2", "Veronica", "Akle", ",", "Emmanuel", "Guelin", ",", "Lili", "Yu", ",", "Helena", "Brassard-Giordano", ",", "Barbara", "E.", "Slack", ",", "1", "Irina", "V.", "Zhdanova", "*", "1", "Department", "of", "Anatomy", "&", "Neurobiology,", "Boston", "University", "School", "of", "Medicine,", "Boston,", "Massachusetts,", "United", "States", "of", "America,", "2", "Department", "of", "Pathology", "and", "Laboratory", "Medicine,", "Boston", "University", "School", "of", "Medicine,", "Boston,", "Massachusetts,", "United", "States", "of", "America", "Abstract", "F-spondin,", "an", "extracellular", "matrix", "protein,", "is", "an", "important", "player", "in", "embryonic", "morphogenesis", "and", "CNS", "development,", "but", "its", "presence", "and", "role", "later", "in", "life", "remains", "largely", "unknown.", "We", "generated", "a", "transgenic", "zebrafish", "in", "which", "GFP", "is", "expressed", "under", "the", "control", "of", "the", "F-spondin", "(spon1b)", "promoter,", "and", "used", "it", "in", "combination", "with", "complementary", "techniques", "to", "undertake", "a", "detailed", "characterization", "of", "the", "expression", "patterns", "of", "F-spondin", "in", "developing", "and", "adult", "brain", "and", "periphery.", "We", "found", "that", "F-spondin", "is", "often", "associated", "with", "structures", "forming", "long", "neuronal", "tracts,", "including", "retinal", "ganglion", "cells,", "the", "olfactory", "bulb,", "the", "habenula,", "and", "the", "nucleus", "of", "the", "medial", "longitudinal", "fasciculus", "(nMLF).", "F-spondin", "expression", "coincides", "with", "zones", "of", "adult", "neurogenesis", "and", "is", "abundant", "in", "CSF-contacting", "secretory", "neurons,", "especially", "those", "in", "the", "hypothalamus.", "Use", "of", "this", "new", "transgenic", "model", "also", "revealed", "F-spondin", "expression", "patterns", "in", "the", "peripheral", "CNS,", "notably", "in", "enteric", "neurons,", "and", "in", "peripheral", "tissues", "involved", "in", "active", "patterning", "or", "proliferation", "in", "adults,", "including", "the", "endoskeleton", "of", "zebrafish", "fins", "and", "the", "continuously", "regenerating", "pharyngeal", "teeth.", "Moreover,", "patterning", "of", "the", "regenerating", "caudal", "fin", "following", "fin", "amputation", "in", "adult", "zebrafish", "was", "associated", "with", "F-spondin", "expression", "in", "the", "blastema,", "a", "proliferative", "region", "critical", "for", "tissue", "reconstitution.", "Together,", "these", "findings", "suggest", "major", "roles", "for", "F-spondin", "in", "the", "CNS", "and", "periphery", "of", "the", "developing", "and", "adult", "vertebrate.", "Citation:", "Akle", "V,", "Guelin", "E,", "Yu", "L,", "Brassard-Giordano", "H,", "Slack", "BE,", "et", "al.", "(2012)", "F-Spondin/spon1b", "Expression", "Patterns", "in", "Developing", "and", "Adult", "Zebrafish.", "PLoS", "ONE", "7(6):", "e37593.", "doi:10.1371/journal.pone.0037593", "Editor:", "Filippo", "Del", "Bene,", "Institut", "Curie,", "France", "Received", "February", "17,", "2012;", "Accepted", "April", "26,", "2012;", "Published", "June", "29,", "2012", "Copyright:", "2012", "Akle", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "The", "work", "was", "supported", "by", "a", "grant", "from", "the", "Chaikin-Wile", "Foundation.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "Abbreviations:", "A,", "Anterior", "hypothalamic", "nucleus;", "APP,", "Amyloid", "precursor", "protein;", "BNSM,", "Bed", "nucleus", "of", "stria", "medullaris;", "BrdU,", "5-Bromo-2-deoxyuridine;", "DAB-1,", "Disabled-1;", "Cans,", "Ansulate", "commissure;", "Cant,", "Anterior", "commissure;", "CC,", "Cerebellar", "crest;", "CCe,", "Cerebellar", "corpus;", "Cgus,", "Gustatory", "commissure;", "cHb,", "Caudal", "habenula;", "Chor,", "Horizontal", "commissure;", "CM,", "Mammillary", "corpus;", "Cp,", "Central", "posterior", "thalamic", "nucleus;", "Cpost,", "Posterior", "commissure;", "Ctec,", "Tectal", "commissure;", "D,", "Dorsal", "pallium;", "Dd,", "Dorsal", "nucleus", "of", "dorsal", "telencephalon;", "dHb,", "Dorsal", "habenula;", "Dl,", "Lateral", "nucleus", "of", "dorsal", "telencephalon;", "dlHb,", "Dorsolateral", "habenula;", "Dm,", "Medial", "nucleus", "of", "dorsal", "telencephalon;", "dmHb,", "Dorsomedial", "habenula;", "dmHbi,", "Inferior", "nucleus", "of", "dorsomedial", "habenula;", "DOT,", "Dorsal", "optic", "tract;", "DON,", "Descending", "octaval", "nucleus;", "Dp,", "Posterior", "zone", "of", "dorsal", "telencephalic", "area;", "ECM,", "Extracellular", "matrix;", "EG,", "Granular", "eminence;", "fp,", "Floor", "plate;", "FR,", "Fasciculus", "retroflexus;", "Fv,", "Ventral", "funiculus;", "GL,", "Glomerular", "layer", "of", "olfactory", "bulbs;", "H,", "Hypothalamus;", "Hb,", "Habenula;", "Hc,", "Caudal", "hypothalamus;", "Hd,", "Dorsal", "hypothalamus;", "Hv,", "Ventral", "zone", "of", "periventricular", "hypothalamus;", "IAF,", "Internal", "arcuate", "fibers;", "ICL,", "Inner", "cell", "layer", "of", "olfactory", "bulbs;", "LLF,", "Lateral", "longitudinal", "fasciculus;", "LOT,", "Lateral", "olfactory", "tract;", "LX,", "Vagal", "lobe;", "Me,", "Medula", "oblongata;", "MLF,", "Medial", "longitudinal", "fasciculus;", "mn,", "Motor", "neuron;", "MOT,", "Medial", "olfactory", "tract;", "NI,", "Nucleus", "isthmi;", "Nin,", "Interpeduncular", "nucleus;", "nMLF,", "Nucleus", "of", "medial", "longitudinal", "fasciculus;", "no,", "Notochord;", "NPR,", "Nucleus", "of", "the", "posterior", "recess;", "NXm,", "Motor", "nucleus", "of", "vagus;", "OB,", "Olfactory", "bulb;", "on,", "Optic", "nerve;", "PGm,", "Medial", "preglomerular", "nucleus;", "PGl,", "Lateral", "preglomerular", "nucleus;", "PGZ,", "Periventricular", "grey", "zone;", "PNT,", "Posterior", "tuberal", "nucleus;", "Ppa,", "Parvocellular", "preoptic", "area,", "anterior;", "Ppp,", "Posterior", "preoptic", "area;", "PVO,", "Paraventricular", "organ;", "PM,", "Magnocellular", "preoptic", "nucleus;", "PTN,", "Posterior", "tuberal", "nucleus;", "PPd,", "Periventricular", "pretectal", "nucleus,", "dorsal", "part;", "PPv,", "Periventricular", "pretectal", "nucleus,", "ventral", "part;", "Pur,", "Purkinje", "cell", "layer;", "PVO,", "Paraventricular", "nucleus;", "SAC,", "Stratum", "album", "centrale;", "SCO,", "Subcommissural", "organ;", "SFGS,", "Stratum", "fiibrosum", "et", "griseum", "superficiale;", "SGC,", "Stratum", "griseum", "centrale;", "SGN,", "Secondary", "gustatory", "nucleus;", "sm", "Stria", "medullaris,", ";", "SM,", "Stratum", "marginale;", "SO,", "Stratum", "opticum;", "SPV,", "Stratum", "periventriculare;", "SR,", "Superior", "raphe;", "RGC,", "Retinal", "ganglion", "cells;", "RF,", "Reticular", "formation;", "RV,", "Rhomboencephalic", "ventricle;", "Tel,", "Telencephalon;", "TeO,", "Optic", "tectum;", "TPp,", "Posterior", "tuberculum;", "TL,", "Torus", "longitudinalis;", "TTB,", "Tectobulbar", "tract;", "URL,", "Upper", "rhombic", "lip;", "Val,", "Valvula", "cerebellis;", "Vl,", "Ventrolateral", "nucleus", "of", "the", "thalamus;", "VOT,", "Ventrolateral", "optic", "tract;", "Vv,", "Ventral", "nucleus", "of", "ventral", "telencephalic", "area;", "vHb,", "Ventral", "nucleus", "of", "habenula;", "vNIn,", "Ventral", "interpeduncular", "nucleus;", "Te,", "Telencephalon", "*", "E-mail:", "zhdanova@bu.edu", "Introduction", "The", "extracellular", "matrix", "(ECM)", "is", "an", "essential", "component", "of", "many", "tissues,", "providing", "for", "structural", "support", "and", "guidance,", "and", "affecting", "signaling", "and", "homeostasis", "[1].", "A", "small", "family", "of", "ECM", "proteins,", "called", "spondins,", "is", "evolutionarily", "well", "conserved", "and", "includes", "f-spondin,", "mindin", "and", "subcommissural", "organ", "(SCO)-", "spondin", "[2].", "F-spondin", "was", "found", "to", "be", "an", "important", "player", "in", "embryonic", "morphogenesis", "in", "such", "diverse", "species", "as", "C.", "elegans", "and", "rat", "[3,4].", "It", "is", "also", "expressed", "in", "adult", "tissues", "and", "might", "play", "diverse", "roles", "in", "the", "central", "nervous", "system", "(CNS)", "and", "the", "periphery", "[2,5–8].", "The", "F-spondin", "molecule", "consists", "of", "about", "800", "amino", "acids,", "and", "contains", "an", "N-terminal", "domain", "homologous", "to", "the", "amino", "terminus", "of", "reelin,", "a", "spondin", "domain", "and", "six", "C-terminal", "thrombospondin", "repeats", "[4].", "This", "structure", "allows", "F-spondin", "to", "affect", "different", "processes", "through", "binding", "to", "the", "ECM", "or", "membrane", "receptors.", "For", "example,", "during", "development,", "the", "two", "proteolytic", "fragments", "of", "F-spondin", "were", "found", "to", "play", "opposing", "though", "complementary", "roles", "in", "guiding", "the", "growth", "of", "commissural", "neurons", "between", "the", "floor", "plate", "cells", "and", "the", "basement", "membrane", "[9].", "Thus,", "whereas", "the", "C-terminal", "fragment", "binds", "to", "the", "ECM,", "promoting", "neuronal", "outgrowth", "along", "the", "basement", "membrane", "PLoS", "ONE", "|", "www.plosone.org", "1", "June", "2012", "|", "Volume", "7", "|", "Issue", "6", "|", "e37593" ]

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[ "Kadow", "et", "al.", "AMB", "Express", "2011,", "1:13", "http://www.amb-express.com/content/1/1/13", "O", "R", "I", "G", "I", "N", "A", "L", "Open", "Access", "Recombinant", "expression", "and", "purification", "of", "the", "2,5-diketocamphane", "1,2-monooxygenase", "from", "the", "camphor", "metabolizing", "Pseudomonas", "putida", "strain", "NCIMB", "10007", "Maria", "Kadow,", "Stefan", "Saß,", "Marlen", "Schmidt", "and", "Uwe", "T", "Bornscheuer*", "Abstract", "Three", "different", "Baeyer-Villiger", "monooxygenases", "(BVMOs)", "were", "reported", "to", "be", "involved", "in", "the", "camphor", "metabolism", "by", "Pseudomonas", "putida", "NCIMB", "10007.", "During", "(+)-camphor", "degradation,", "2,5-diketocamphane", "is", "formed", "serving", "as", "substrate", "for", "the", "2,5-diketocamphane", "1,2-monooxygenase.", "This", "enzyme", "is", "encoded", "on", "the", "CAM", "plasmid", "and", "depends", "on", "the", "cofactors", "FMN", "and", "NADH", "and", "hence", "belongs", "to", "the", "group", "of", "type", "II", "BVMOs.", "We", "have", "cloned", "and", "recombinantly", "expressed", "the", "oxygenating", "subunit", "of", "the", "2,5-diketocamphane", "1,2-monooxygenase", "(2,5-DKCMO)", "in", "E.", "coli", "followed", "by", "His-tag-based", "affinity", "purification.", "A", "range", "of", "compounds", "representing", "different", "BVMO", "substrate", "classes", "were", "then", "investigated,", "but", "only", "bicyclic", "ketones", "were", "converted", "by", "2,5-DKCMO", "used", "as", "crude", "cell", "extract", "or", "after", "purification.", "Interestingly,", "also", "(-)-camphor", "was", "oxidized,", "but", "conversion", "was", "about", "3-fold", "lower", "compared", "to", "(+)-camphor.", "Moreover,", "activity", "of", "purified", "2,5-DKCMO", "was", "observed", "in", "the", "absence", "of", "an", "NADH-", "dehydrogenase", "subunit.", "Keywords:", "Baeyer-Villiger", "monooxygenases,", "camphor,", "Pseudomonas", "putida", "NCIMB", "10007,", "2,5-diketocamphane", "1,2-", "monooxygenase,", "bicyclic", "ketones", "Introduction", "The", "discovery", "of", "the", "enzymatic", "Baeyer-Villiger", "reaction", "is", "closely", "connected", "to", "the", "exploration", "of", "the", "biodegra-", "dation", "of", "camphor", "(1)", "in", "Pseudomonads", "(Figure", "1).", "Initial", "studies", "on", "the", "microbial", "decomposition", "of", "(+)-1", "by", "Pseudomonas", "putida", "NCIMB", "10007", "isolated", "from", "sewage", "sludge", "were", "already", "carried", "out", "in", "1959", "(Bradshaw", "et", "al.", "1959)", "and", "the", "involved", "enzymes", "were", "separated", "and", "characterized", "during", "the", "following", "decade.", "In", "studies", "of", "the", "enzymatic", "lactonization", "of", "the", "inter-", "mediate", "2,5-diketocamphane", "(3)", "from", "the", "(+)-camphor-", "grown", "organism", "it", "was", "shown", "that", "two", "enzyme", "fractions", "were", "responsible", "for", "the", "Baeyer-Villiger-monooxygenase", "(BVMO)", "catalyzed", "reaction", "step", "(Conrad", "et", "al.", "1961,).", "The", "first", "enzyme", "turned", "out", "to", "be", "a", "FMN-coupled", "NADH-dehydrogenase", "[EC", "1.6.8.1],", "while", "the", "second", "*", "Correspondence:", "uwe.bornscheuer@uni-greifswald.de", "Department", "of", "Biotechnology", "and", "Enzyme", "Catalysis,", "Institute", "of", "Biochemistry,", "Greifswald", "University,", "Felix-Hausdorff-Str.", "4,", "D-17487", "Greifswald,", "Germany", "subunit", "was", "claimed", "to", "be", "a", "ketolactonase.", "Since", "mechanistic", "similarities", "to", "the", "chemical", "Baeyer-Villiger", "oxidation", "of", "bicyclic", "ketones", "(Meinwald", "and", "Frauenglass", "1960)", "were", "detected,", "the", "nomenclature", "of", "the", "ketolacto-", "nase", "was", "changed", "to", "a", "BVMO.", "In", "1965", "a", "second", "lacto-", "nizing", "system", "for", "the", "degradation", "of", "(-)-1", "was", "found", "(Conrad", "et", "al.", "1965a).", "Thus", "it", "was", "claimed", "that", "(+)-1", "and", "its", "derivatives", "were", "only", "converted", "by", "the", "(+)-camphor", "induced", "2,5-diketocamphane", "1,2-monooxy-", "genase", "(2,5-DKCMO),", "while", "(-)-1", "is", "converted", "by", "the", "(-)-camphor", "induced", "3,6-diketocamphane", "1,6-monooxy-", "genase", "(Jones", "et", "al.", "1993)", "(Figure", "1).", "Later", "it", "was", "claimed,", "that", "whichever", "enantiomer", "of", "camphor", "is", "given", "to", "the", "growth", "medium,", "both", "diketocamphane", "monooxy-", "genases", "are", "induced", "(Gagnon", "et", "al.", "1994).", "The", "ability", "to", "decompose", "camphor", "turned", "out", "to", "be", "inducible", "in", "several", "fluorescent", "Pseudomonads,", "where", "most", "of", "the", "involved", "enzymes,", "including", "both", "type", "II", "monooxy-", "genases,", "are", "located", "on", "a", "230", "kb", "(165", "MDa)", "plasmid", "(CAM", "plasmid,", "Figure", "2)", "(Chakrabarty", "1976).", "©", "2011", "Kadow", "et", "al;", "licensee", "Springer.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "COMPUTATIONAL", "NEUROSCIENCE", "The", "stomatogastric", "nervous", "system", "as", "a", "model", "for", "studying", "sensorimotor", "interactions", "in", "real-time", "closed-loop", "conditions", "Nelly", "Daur", "1†,", "Florian", "Diehl", "1,", "Wolfgang", "Mader", "1", "and", "Wolfgang", "Stein2*", "1", "Institute", "of", "Neurobiology,", "Ulm", "University,", "Ulm,", "Germany", "2", "School", "of", "Biological", "Sciences,", "Illinois", "State", "University,", "Normal,", "IL,", "USA", "METHODS", "ARTICLE", "published:", "14", "March", "2012", "doi:", "10.3389/fncom.2012.00013", "Edited", "by:", "Misha", "Tsodyks,", "Weizmann", "Institute", "of", "Science,", "Israel", "Reviewed", "by:", "Andre", "Longtin,", "University", "of", "Ottawa,", "Canada", "Jordan", "Chambers,", "University", "of", "Melbourne,", "Australia", "Evan", "Thomas,", "Florey", "Neuroscience", "Institutes,", "Australia", "*Correspondence:", "Wolfgang", "Stein,", "School", "of", "Biological", "Sciences,", "Illinois", "State", "University,", "Normal,", "IL", "61790,", "USA.", "e-mail:", "wstein@neurobiologie.de", "†Present", "address:", "Nelly", "Daur,", "Whitney", "Laboratory", "for", "Marine", "Bioscience,", "University", "of", "Florida,", "St.", "Augustine,", "FL", "32080,", "USA.", "The", "perception", "of", "proprioceptive", "signals", "that", "report", "the", "internal", "state", "of", "the", "body", "is", "one", "of", "the", "essential", "tasks", "of", "the", "nervous", "system", "and", "helps", "to", "continuously", "adapt", "body", "move-", "ments", "to", "changing", "circumstances.", "Despite", "the", "impact", "of", "proprioceptive", "feedback", "on", "motor", "activity", "it", "has", "rarely", "been", "studied", "in", "conditions", "in", "which", "motor", "output", "and", "sensory", "activity", "interact", "as", "they", "do", "in", "behaving", "animals,", "i.e.,", "in", "closed-loop", "conditions.", "The", "interaction", "of", "motor", "and", "sensory", "activities,", "however,", "can", "create", "emergent", "properties", "that", "may", "govern", "the", "functional", "characteristics", "of", "the", "system.", "We", "here", "demonstrate", "a", "method", "to", "use", "a", "well-", "characterized", "model", "system", "for", "central", "pattern", "generation,", "the", "stomatogastric", "nervous", "system,", "for", "studying", "these", "properties", "in", "vitro.", "We", "created", "a", "real-time", "computer", "model", "of", "a", "single-cell", "muscle", "tendon", "organ", "in", "the", "gastric", "mill", "of", "the", "crab", "foregut", "that", "uses", "intracellular", "current", "injections", "to", "control", "the", "activity", "of", "the", "biological", "proprioceptor.", "The", "resulting", "motor", "output", "of", "a", "gastric", "mill", "motor", "neuron", "is", "then", "recorded", "intracellularly", "and", "fed", "into", "a", "sim-", "ple", "muscle", "model", "consisting", "of", "a", "series", "of", "low-pass", "filters.", "The", "muscle", "output", "is", "used", "to", "activate", "a", "one-dimensional", "Hodgkin–Huxley", "type", "model", "of", "the", "muscle", "tendon", "organ", "in", "real-", "time,", "allowing", "closed-loop", "conditions.", "Model", "properties", "were", "either", "hand", "tuned", "to", "achieve", "the", "best", "match", "with", "data", "from", "semi-intact", "muscle", "preparations,", "or", "an", "exhaustive", "search", "was", "performed", "to", "determine", "the", "best", "set", "of", "parameters.", "We", "report", "the", "real-time", "capabilities", "of", "our", "models,", "its", "performance", "and", "its", "interaction", "with", "the", "biological", "motor", "system.", "Keywords:", "central", "pattern", "generation,", "sensorimotor,", "proprioception,", "spike", "frequency", "adaptation,", "emergent", "properties", "INTRODUCTION", "The", "perception", "of", "proprioceptive", "signals", "that", "report", "the", "inter-", "nal", "state", "of", "the", "body", "is", "one", "of", "the", "essential", "tasks", "of", "the", "nervous", "system,", "because", "it", "adapts", "ongoing", "motor", "activity", "to", "changes", "in", "the", "environment", "or", "the", "body", "(review", "in", "Pearson,", "1986;", "Grill-", "ner,", "2003;", "Pearson,", "2004).", "In", "fact,", "phasic", "proprioceptive", "feed-", "back", "contributes", "significantly", "to", "the", "motor", "output", "in", "many", "rhythmic", "motor", "systems", "(Rossignol", "et", "al.,", "2006;", "Ausborn", "et", "al.,", "2007).", "It", "is", "thus", "often", "regarded", "as", "an", "integral", "part", "of", "the", "rhythm", "generating", "machinery", "(Pearson,", "2004),", "even", "if", "the", "basic", "motor", "pattern", "can", "still", "be", "expressed", "after", "removing", "all", "sensory", "input.", "The", "effects", "of", "sensory", "organs", "on", "motor", "circuits", "have", "been", "demonstrated", "in", "many", "systems,", "typically", "using", "open-loop", "con-", "ditions,", "i.e.,", "with", "emphasis", "on", "how", "sensory", "signals", "alter", "motor", "output,", "or", "information", "flows", "toward", "that", "output.", "Sensory", "activ-", "ity", "itself,", "however,", "remains", "unaffected", "by", "motor", "output", "in", "these", "conditions", "despite", "the", "fact", "that", "the", "nervous", "system", "always", "acts", "in", "closed-loop", "conditions", "in", "behaving", "animals.", "The", "dynamical", "components", "determined", "by", "the", "interaction", "of", "motor", "and", "sensory", "activities", "can", "create", "emergent", "properties", "that", "govern", "the", "func-", "tional", "characteristics", "of", "the", "system", "(Lehmann", "and", "Dickinson,", "2000;", "Büschges,", "2005).", "While", "already", "a", "standard", "for", "investigating", "movement", "or", "behavior", "in", "general", "(e.g.,", "fly", "and", "bee", "flight:", "Dickinson,", "2005;", "Fry", "et", "al.,", "2008;", "Mronz", "and", "Lehmann,", "2008;", "Sareen", "et", "al.,", "2011;", "Srinivasan,", "2011;", "monkey", "motor", "control", "and", "vision:", "Nicolelis,", "2003;", "robotics:", "Novellino", "et", "al.,", "2007),", "the", "idio-", "syncratic", "dynamics", "created", "by", "the", "sensorimotor", "interaction", "have", "only", "rarely", "been", "elucidated", "on", "the", "levels", "of", "networks", "and", "single", "neurons.", "In", "the", "few", "instances", "in", "which", "they", "have", "been", "studied", "(Bässler", "and", "Nothof,", "1994;", "Ausborn", "et", "al.,", "2007,", "2009;", "Smaran-", "dache", "et", "al.,", "2008),", "it", "is", "obvious", "that", "they", "play", "an", "important", "role", "in", "shaping", "the", "motor", "output.", "On", "the", "other", "hand,", "the", "functional", "and", "circuit", "properties", "as", "well", "as", "the", "cellular", "characteristics", "of", "many", "pattern", "generating", "networks", "are", "known", "in", "great", "detail.", "This", "is", "particularly", "true", "for", "central", "pat-", "tern", "generators,", "which", "often", "govern", "basic,", "but", "essential", "behaviors", "such", "as", "breathing,", "heartbeat,", "or", "chewing", "(Briggman", "and", "Kris-", "tan,", "2008)", "and", "can", "be", "studied", "in", "isolation", "from", "the", "body.", "They", "allow", "access", "to", "the", "cellular", "level", "for", "investigations,", "but", "sensory", "feedback", "(in", "contrast", "to", "sensory", "input", ")", "is", "not", "available", "due", "to", "missing", "sensory", "structures.", "One", "way", "to", "circumvent", "this", "problem", "is", "to", "provide", "artificial", "sensory", "feedback", "in", "real-time", "which", "is", "altered", "according", "to", "the", "motor", "activity.", "In", "most", "systems", "this", "is", "not", "fea-", "sible", "since", "either", "the", "sense", "organs", "or", "the", "sensory", "activity", "are", "too", "complex", "to", "be", "understood", "sufficiently", "to", "serve", "as", "foundation", "for", "Frontiers", "in", "Computational", "Neuroscience", "www.frontiersin.org", "March", "2012", "|", "Volume", "6", "|", "Article", "13", "|", "1" ]

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[ "Ahmad", "et", "al.", "Trials", "2010,", "11:20", "http://www.trialsjournal.com/content/11/1/20", "R", "E", "S", "E", "A", "R", "C", "H", "TRIALS", "Open", "Access", "Applicability", "and", "generalisability", "of", "the", "results", "of", "systematic", "reviews", "to", "public", "health", "practice", "and", "policy:", "a", "systematic", "review", "Nizar", "Ahmad1,2,3*,", "Isabelle", "Boutron1,2,3,", "Agnès", "Dechartres1,2,3,", "Pierre", "Durieux4,5,", "Philippe", "Ravaud1,2,3,4", "Abstract", "Background:", "The", "purpose", "of", "the", "study", "was", "to", "evaluate", "systematic", "reviews", "of", "research", "into", "two", "public", "health", "priorities,", "tobacco", "consumption", "and", "HIV", "infection,", "in", "terms", "of", "the", "reporting", "of", "data", "related", "to", "the", "applicability", "of", "trial", "results", "(i.e.,", "whether", "the", "results", "of", "a", "trial", "can", "be", "reasonably", "applied", "or", "generalized", "to", "a", "definable", "group", "of", "patients", "in", "a", "particular", "setting", "in", "routine", "practice,", "also", "called", "external", "validity", "or", "generalisability).", "Methods:", "All", "systematic", "reviews", "of", "interventions", "aimed", "at", "reducing", "or", "stopping", "tobacco", "use", "and", "treating", "or", "preventing", "HIV", "infection", "published", "in", "the", "Cochrane", "database", "of", "systematic", "reviews", "and", "in", "journals", "indexed", "in", "MEDLINE", "between", "January", "1997", "and", "December", "2007", "were", "selected.", "We", "used", "a", "standardized", "data", "abstraction", "form", "to", "extract", "data", "related", "to", "applicability", "in", "terms", "of", "the", "context", "of", "the", "trial,", "(country,", "centres,", "settings),", "participants", "(recruitment,", "inclusion", "and", "exclusion", "criteria,", "baseline", "characteristics", "of", "participants", "such", "as", "age,", "sex,", "ethnicity,", "coexisting", "diseases", "or", "co-morbidities,", "and", "socioeconomic", "status),", "treatment", "(duration,", "intensity/dose", "of", "treatment,", "timing", "and", "delivery", "format),", "and", "the", "outcomes", "assessment", "from", "selected", "reviews.", "Results:", "A", "total", "of", "98", "systematic", "reviews", "were", "selected", "(57", "Cochrane", "reviews", "and", "41", "non-Cochrane", "reviews);", "49", "evaluated", "interventions", "aimed", "at", "reducing", "or", "stopping", "tobacco", "use", "and", "49", "treating", "or", "preventing", "HIV", "infection.", "The", "setting", "of", "the", "individual", "studies", "was", "reported", "in", "45", "(46%)", "of", "the", "systematic", "reviews,", "the", "number", "of", "centres", "in", "21", "(21%),", "and", "the", "country", "where", "the", "trial", "took", "place", "in", "62", "(63%).", "Inclusion", "and", "exclusion", "criteria", "of", "the", "included", "studies", "were", "reported", "in", "16", "(16%)", "and", "13", "(13%)", "of", "the", "reviews,", "respectively.", "Baseline", "characteristics", "of", "participants", "in", "the", "included", "studies", "were", "described", "in", "59", "(60%)", "of", "the", "reviews.", "These", "characteristics", "concerned", "age", "in", "about", "half", "of", "the", "reviews,", "sex", "in", "46", "(47%),", "and", "ethnicity", "in", "9", "(9%).", "Applicability", "of", "results", "was", "discussed", "in", "13", "(13%)", "of", "the", "systematic", "reviews.", "The", "reporting", "was", "better", "in", "systematic", "reviews", "by", "the", "Cochrane", "Collaboration", "than", "by", "non-Cochrane", "groups.", "Conclusions:", "Our", "study", "highlighted", "the", "lack", "of", "consideration", "of", "applicability", "of", "results", "in", "systematic", "reviews", "of", "research", "into", "2", "public", "health", "priorities:", "tobacco", "consumption", "and", "HIV", "infection.", "Background", "Systematic", "reviews", "are", "an", "important", "source", "of", "valid", "evi-", "dence", "[1]", "because", "they", "identify,", "appraise", "and", "synthesize", "all", "the", "available", "evidence", "on", "a", "particular", "topic", "[1-3].", "Theoretically,", "systematic", "reviews", "should", "evaluate", "and", "take", "into", "account", "the", "internal", "validity", "(i.e.,", "the", "extent", "to", "which", "systematic", "errors", "or", "bias", "are", "avoided)", "of", "each", "trial", "included", "but", "also", "the", "applicability", "and", "generalizability", "or", "*", "Correspondence:", "nizar.ahmad@htd.aphp.fr", "1Centre", "d’épidémiologie", "Clinique,", "Hôpital", "Hôtel", "Dieu,", "AP-HP", "(Assistance", "Publique", "des", "Hôpitaux", "de", "Paris),", "1", "place", "du", "Parvis", "Notre-Dame,", "Paris", "75181,", "France", "external", "validity", "(i.e.,", "whether", "the", "results", "of", "a", "trial", "can", "be", "reasonably", "applied", "to", "a", "definable", "group", "of", "patients", "in", "a", "particular", "setting", "in", "routine", "practice)[4].", "Several", "meth-", "odological", "works", "have", "been", "published", "to", "allow", "for", "ade-", "quately", "understanding", "and", "assessing", "internal", "validity", "[5-10].", "Recently,", "the", "Cochrane", "Collaboration", "developed", "a", "specific", "tool", "to", "appraise", "the", "internal", "validity", "of", "trial", "results", "included", "in", "systematic", "reviews,", "the", "Risk", "of", "Bias", "tool", "[11]", "and", "research", "is", "still", "being", "conducted", "in", "this", "field[12].", "In", "contrast,", "methodological", "research", "on", "the", "applicability", "of", "trial", "results", "is", "still", "at", "its", "beginning", "[13-15].", "Some", "authors", "have", "highlighted", "that", "external", "©", "2010", "Ahmad", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Interplay", "between", "Telecommunications", "and", "Face-to-", "Face", "Interactions:", "A", "Study", "Using", "Mobile", "Phone", "Data", "Francesco", "Calabrese1,2*,", "Zbigniew", "Smoreda3,", "Vincent", "D.", "Blondel4,5,", "Carlo", "Ratti2", "1", "IBM", "Research,", "Dublin,", "Ireland,", "2", "Senseable", "City", "Laboratory,", "Massachusetts", "Institute", "of", "Technology,", "Cambridge,", "Massachusetts,", "United", "States", "of", "America,", "3", "Sociology", "and", "Economics", "of", "Networks", "and", "Services", "Department,", "Orange", "Labs,", "Issy-les-Moulineaux,", "France,", "4", "LIDS,", "Massachusetts", "Institute", "of", "Technology,", "Cambridge,", "Massachusetts,", "United", "States", "of", "America,", "5", "Department", "of", "Mathematical", "Engineering,", "Universite´", "Catholique", "de", "Louvain,", "Louvain-la-Neuve,", "Belgium", "Abstract", "In", "this", "study", "we", "analyze", "one", "year", "of", "anonymized", "telecommunications", "data", "for", "over", "one", "million", "customers", "from", "a", "large", "European", "cellphone", "operator,", "and", "we", "investigate", "the", "relationship", "between", "people’s", "calls", "and", "their", "physical", "location.", "We", "discover", "that", "more", "than", "90%", "of", "users", "who", "have", "called", "each", "other", "have", "also", "shared", "the", "same", "space", "(cell", "tower),", "even", "if", "they", "live", "far", "apart.", "Moreover,", "we", "find", "that", "close", "to", "70%", "of", "users", "who", "call", "each", "other", "frequently", "(at", "least", "once", "per", "month", "on", "average)", "have", "shared", "the", "same", "space", "at", "the", "same", "time", "-", "an", "instance", "that", "we", "call", "co-location.", "Co-locations", "appear", "indicative", "of", "coordination", "calls,", "which", "occur", "just", "before", "face-to-face", "meetings.", "Their", "number", "is", "highly", "predictable", "based", "on", "the", "amount", "of", "calls", "between", "two", "users", "and", "the", "distance", "between", "their", "home", "locations", "-", "suggesting", "a", "new", "way", "to", "quantify", "the", "interplay", "between", "telecommunications", "and", "face-to-face", "interactions.", "Citation:", "Calabrese", "F,", "Smoreda", "Z,", "Blondel", "VD,", "Ratti", "C", "(2011)", "Interplay", "between", "Telecommunications", "and", "Face-to-Face", "Interactions:", "A", "Study", "Using", "Mobile", "Phone", "Data.", "PLoS", "ONE", "6(7):", "e20814.", "doi:10.1371/journal.pone.0020814", "Editor:", "Enrico", "Scalas,", "Universita’", "del", "Piemonte", "Orientale,", "Italy", "Received", "January", "18,", "2011;", "Accepted", "May", "11,", "2011;", "Published", "July", "13,", "2011", "Copyright:", "2011", "Calabrese", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "The", "authors", "were", "partially", "funded", "by", "the", "AT&T", "Foundation,", "the", "National", "Science", "Foundation", "(grant", "number", "0735956),", "the", "MIT", "SMART", "program,", "GE,", "Audi", "Volkswagen,", "SNCF", "and", "ENEL.", "Francesco", "Calabrese", "was", "partially", "funded", "by", "IBM", "Research,", "which", "had", "no", "role", "in", "study", "design,", "data", "collection,", "data", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Zbigniew", "Smoreda", "was", "funded", "by", "Orange", "Labs,", "which", "contributed", "to", "data", "collection", "and", "had", "no", "role", "in", "study", "design,", "data", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "The", "other", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "Francesco", "Calabrese", "is", "employed", "by", "IBM", "Research.", "Zbigniew", "Smoreda", "is", "employed", "by", "Orange", "Labs.", "These", "affiliations", "do", "not", "alter", "the", "authors’", "adherence", "to", "all", "PLoS", "ONE", "policies", "on", "the", "sharing", "of", "data", "and", "materials.", "*", "E-mail:", "fcalabre@ie.ibm.com", "Introduction", "The", "interplay", "between", "telecommunications,", "travel", "and", "face-to-", "face", "meetings", "is", "an", "unresolved", "puzzle.", "In", "some", "cases", "it", "has", "been", "suggested", "that", "telecommunications", "may", "be", "a", "substitute", "for", "physical", "interaction", "[1]", "-", "an", "idea", "that", "gained", "traction", "during", "the", "nineties", "and", "the", "rapid", "expansion", "of", "the", "Internet", "[2,3].", "In", "other", "cases", "conflicting", "hypotheses", "have", "been", "made,", "including", "those", "of", "a", "complementary", "[4,5],", "neutral", "[6]", "or", "reinforcing", "[7]", "effect.", "Recently,", "social", "networks", "have", "been", "identified", "as", "possible", "predictors", "of", "travel", "behavior,", "as", "well", "as", "the", "possible", "decision", "to", "telecommute", "[8,9].", "Social", "interaction", "has", "thus", "been", "integrated", "in", "activity-travel", "models", "[10],", "in", "addition", "to", "the", "existing", "categories", "of", "travel", "such", "as", "commuting,", "leisure", "and", "business.", "Furthermore,", "researchers", "such", "as", "Urry", "and", "others", "[11–13]", "have", "argued", "that", "flows", "and", "meetings", "of", "people", "produce", "small", "worlds,", "which", "require", "connections", "and", "meeting", "places", "-", "a", "phenomenon", "which", "is", "also", "known", "as", "the", "new", "mobilities", "paradigm.", "This", "study", "aims", "to", "provide", "a", "new", "perspective", "into", "the", "relationship", "between", "telecommunicating", "people", "and", "their", "physical", "locations", "through", "an", "assesment", "of", "anonymized", "Call", "Detail", "Records", "(CDRs).", "CDRs", "show", "great", "promise", "for", "academic", "research:", "they", "have", "recently", "been", "used", "to", "explore", "human", "communications", "[14,15],", "the", "geography", "of", "social", "networks", "[16,17],", "urban", "dynamics", "[18],", "and", "human", "mobility", "patterns", "[19–22].", "In", "this", "paper", "we", "use", "them", "for", "the", "first", "time", "to", "study", "the", "relationship", "between", "the", "telecommunications", "patterns", "of", "any", "two", "people", "and", "their", "physical", "locations.", "Results", "We", "use", "a", "large", "anonymized", "dataset", "of", "billing", "records", "for", "over", "one", "million", "mobile", "phone", "users,", "which", "was", "gathered", "in", "Portugal", "over", "a", "twelve", "month", "period", "between", "2006", "and", "2007", "(see", "Methods).", "We", "look", "at", "all", "communications", "between", "pairs", "of", "users,", "together", "with", "their", "locations", "at", "call", "time.", "As", "we", "are", "interested", "in", "comparing", "people", "locations,", "we", "discard", "users", "for", "which", "we", "do", "not", "have", "enough", "samples.", "We", "use", "two", "subsets:", "D1,", "which", "contains", "all", "reciprocal", "communications", "between", "the", "top", "100,000", "callers;", "and", "D2,", "which", "contains", "10,000", "pairs", "from", "D1,", "sampled", "at", "different", "home", "distances", "to", "ensure", "the", "same", "home", "distances", "distribution", "found", "in", "D1", "(see", "Text", "S2).", "In", "the", "sequel,", "we", "use", "D2", "in", "cases", "where", "computational", "complexity", "limits", "the", "use", "of", "a", "larger", "set.", "We", "discover", "that", "at", "least", "93%", "of", "users", "in", "D1", "who", "reciprocally", "call", "each", "other,", "have", "at", "least", "once", "shared", "the", "same", "cell", "tower", "area", "in", "one", "year.", "The", "percentage", "decreases", "slightly", "as", "the", "distances", "between", "their", "homes", "decreases,", "but", "the", "value", "is", "still", "above", "90%", "for", "users", "living", "100", "km", "apart", "(see", "Figure", "1).", "It", "appears", "that", "almost", "all", "remote", "communications", "are", "associated", "with", "being", "physically", "sharing", "space.", "It", "may", "also", "be", "noted", "that", "we", "are", "underestimating", "the", "percentage", "as", "our", "data", "is", "only", "based", "on", "locations", "at", "call", "time,", "so", "users", "might", "have", "also", "shared", "space", "without", "this", "being", "recorded", "in", "our", "data.", "Results", "are", "consistent", "with", "what", "was", "recently", "found", "analyzing", "spatio-temporal", "coincidences", "in", "a", "geo-tagged", "pictures", 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