Variabilidad dentro del Registro Nacional multicéntrico en Vigilancia Activa; cuestionario a urólogos

Introducción: Nuestro objetivo principal es describir la utilización actual en España de la vigilancia activa (VA) identificando áreas de potencial mejora. Métodos: Un cuestionario generado en AEU/PIEM/2014/0001 (NCT02865330) fue remitido a todos los investigadores asociados (IA) durante los meses de enero-marzo del 2016. Incluía 7 dominios diferentes cubriendo diferentes aspectos en VA. Resultados: Treinta y tres de cuarenta y un IA respondieron el cuestionario. La VA es principalmente controlada por los Servicios de Urología (87,9%). Hubo una gran heterogeneidad en las clásicas variables clínico-patológicas como criterios de selección. La densidad de antígeno prostático específico (PSAd) solo se usaba en el 36,4% IA. La RMmp era claramente infrautilizada como estadificación inicial (6%). Solo el 27,3% reconocía un alto nivel de experiencia en RMmp de sus colegas radiólogos. Con relación a la biopsia de confirmación, la mayoría de los centros utilizaban la vía transrectal y solo 2/33 la vía transperineal/software de fusión. La mitad de los IA entrevistados pasaron a tratamiento activo ante progresión patológica a Gleason 7 (3 + 4). No existió consenso en cuanto a cuándo pasar a estrategia de observación. Conclusiones: El estudio demostró la infrautilización del consentimiento informado y de los cuestionarios de calidad de vida. El PSAd no se incluía como elemento decisor en la estrategia inicial en la mayoría. Se plasmó una desconfianza en la experiencia de los urólogos con la RMmp y una infrautilización de la vía transperineal, así como la no existencia de consenso en los protocolos de seguimiento y en los criterios de tratamiento activo., confirmando la necesidad de estudios prospectivos analizando el papel de la RMmp y los biomarcadores. Background: Our main objective was to report the current use of active surveillance in Spain and to identify areas for potential improvement. Methods: A questionnaire generated by the Platform for Multicentre Studies of the Spanish Urology Association (AEU/PIEM/2014/0001, NCT02865330) was sent to all associate researchers from January to March 2016. The questionnaire included 7 domains covering various aspects of active surveillance. Results: Thirty-three of the 41 associate researchers responded to the questionnaire. Active surveillance is mainly controlled by the urology departments (87.9%). There was considerable heterogeneity in the classical clinical-pathological variables as selection criteria. Only 36.4% of the associate researchers used prostate-specific antigen density (PSAd). Multiparametric magnetic resonance imaging (mpMRI) was clearly underused as initial staging (6%). Only 27.3% of the researchers stated that their radiology colleagues had a high level of experience in mpMRI. In terms of the confirmation biopsy, most of the centres used the transrectal pathway, and only 2 out of 33 used the transperineal pathway or fusion software. Half of the researchers interviewed applied active treatment when faced with disease progression to Gleason 7 (3+4). There was no consensus on when to transition to an observation strategy. Conclusions: The study showed the underutilisation of informed consent and quality-of-life questionnaires. PSAd was not included as a decisive element in the initial strategy for most researchers. There was a lack of confidence in the urologists’ mpMRI experience and an underutilisation of the transperineal pathway. There was also no consensus on the follow-up protocols and active treatment criteria, confirming the need for prospective studies to analyse the role of mpMRI and biomarkers

Optimizing the clinical utility of PCA3 to diagnose prostate cancer in initial prostate biopsy

Background: PCA3 has been included in a nomogram outperforming previous clinical models for the prediction of any prostate cancer (PCa) and high grade PCa (HGPCa) at the initial prostate biopsy (IBx). Our objective is to validate such IBx-specific PCA3-based nomogram. We also aim to optimize the use of this nomogram in clinical practice through the definition of risk groups. Methods: Independent external validation. Clinical and biopsy data from a contemporary cohort of 401 men with the same inclusion criteria to those used to build up the reference’s nomogram in IBx. The predictive value of the nomogram was assessed by means of calibration curves and discrimination ability through the area under the curve (AUC). Clinical utility of the nomogram was analyzed by choosing thresholds points that minimize the overlapping between probability density functions (PDF) in PCa and no PCa and HGPCa and no HGPCa groups, and net benefit was assessed by decision curves. Results: We detect 28 % of PCa and 11 % of HGPCa in IBx, contrasting to the 46 and 20 % at the reference series. Due to this, there is an overestimation of the nomogram probabilities shown in the calibration curve for PCa. The AUC values are 0.736 for PCa (C.I.95 %:0.68–0.79) and 0.786 for HGPCa (C.I.95 %:0.71–0.87) showing an adequate discrimination ability. PDF show differences in the distributions of nomogram probabilities in PCa and not PCa patient groups. A minimization of the overlapping between these curves confirms the threshold probability of harboring PCa >30 % proposed by Hansen is useful to indicate a IBx, but a cut-off > 40 % could be better in series of opportunistic screening like ours. Similar results appear in HGPCa analysis. The decision curve also shows a net benefit of 6.31 % for the threshold probability of 40 %. Conclusions: PCA3 is an useful tool to select patients for IBx. Patients with a calculated probability of having PCa over 40 % should be counseled to undergo an IBx if opportunistic screening is required

Role of the 4Kscore test as a predictor of reclassification in prostate cancer active surveillance

Background: Management of active surveillance (AS) in low-risk prostate cancer (PCa) patients could be improved with new biomarkers, such as the 4Kscore test. We analyze its ability to predict tumor reclassification by upgrading at the confirmatory biopsy at 6 months. Methods: Observational, prospective, blinded, and non-randomized study, within the Spanish National Registry on AS (AEU/PIEM/2014/0001; NCT02865330) with 181 patients included after initial Bx and inclusion criteria: PSA =10 ng/mL, cT1c-T2a, Grade group 1, =2 cores, and =5 mm/50% length core involved. Central pathological review of initial and confirmatory Bx was performed on all biopsy specimens. Plasma was collected 6 months after initial Bx and just before confirmatory Bx to determine 4Kscore result. In order to predict reclassification defined as Grade group =2, we analyzed 4Kscore, percent free to total (%f/t) PSA ratio, prostate volume, PSA density, family history, body mass index, initial Bx, total cores, initial Bx positive cores, initial Bx % of positive cores, initial Bx maximum cancer core length and initial Bx cancer % involvement. Wilcoxon rank-sum test, non-parametric trend test or Fisher’s exact test, as appropriate established differences between groups of reclassification. Results: A total of 137 patients met inclusion criteria. Eighteen patients (13.1%) were reclassified at confirmatory Bx. The %f/t PSA ratio and 4Kscore showed differences between the groups of reclassification (Yes/No). Using 7.5% as cutoff for the 4Kscore, we found a sensitivity of 89% and a specificity of 29%, with no reclassifications to Grade group 3 for patients with 4Kscore below 7.5% and 2 (6%) missed Grade group 2 reclassified patients. Using this threshold value there is a biopsy reduction of 27%. Additionally, 4Kscore was also associated with changes in tumor volume. Conclusions: Our preliminary findings suggest that the 4Kscore may be a useful tool in the decision-making process to perform a confirmatory Bx in active surveillance management

The Genome Sequence Of Leishmania (leishmania) Amazonensis: Functional Annotation And Extended Analysis Of Gene Models

We present the sequencing and annotation of the Leishmania (Leishmania) amazonensis genome, an etiological agent of human cutaneous leishmaniasis in the Amazon region of Brazil. L. (L.) amazonensis shares features with Leishmania (L.) mexicana but also exhibits unique characteristics regarding geographical distribution and clinical manifestations of cutaneous lesions (e.g. borderline disseminated cutaneous leishmaniasis). Predicted genes were scored for orthologous gene families and conserved domains in comparison with other human pathogenic Leishmania spp. Carboxypeptidase, aminotransferase, and 3′-nucleotidase genes and ATPase, thioredoxin, and chaperone-related domains were represented more abundantly in L. (L.) amazonensis and L. (L.) mexicana species. Phylogenetic analysis revealed that these two species share groups of amastin surface proteins unique to the genus that could be related to specific features of disease outcomes and host cell interactions. Additionally, we describe a hypothetical hybrid interactome of potentially secreted L. (L.) amazonensis proteins and host proteins under the assumption that parasite factors mimic their mammalian counterparts. The model predicts an interaction between an L. (L.) amazonensis heat-shock protein and mammalian Toll-like receptor 9, which is implicated in important immune responses such as cytokine and nitric oxide production. The analysis presented here represents valuable information for future studies of leishmaniasis pathogenicity and treatment. © The Author 2013.206567581(2010) Control of the Leishmaniasis WHOTechnical Report Series, , WHO. WHO Press: GenevaLainson, R., Shaw, J.J., (1987) The leishmaniases in biology and medicine. Evolution, classification and geographical distributionBates, P.A., Transmission of Leishmania metacyclic promastigotes by phlebotomine sand flies (2007) Int. J. Parasitol., 37, pp. 1097-1106Dedet, J.P., Pratlong, F., Lanotte, G., Ravel, C., Cutaneous leishmaniasis The parasite (1999) Clin. Dermatol., 17, pp. 261-268Murray, H.W., Berman, J.D., Davies, C.R., Saravia, N.G., Advances in leishmaniasis (2005) Lancet, 366, pp. 1561-1577Camara Coelho, L.I., Paes, M., Guerra, J.A., Characterization of Leishmania spp causing cutaneous leishmaniasis in Manaus, Amazonas, Brazil (2011) Parasitol. Res., 108, pp. 671-677Silveira, F.T., Lainson, R., Corbett, C.E., Further observations on clinical, histopathological, and immunological features of borderline disseminated cutaneous leishmaniasis caused by Leishmania (Leishmania) amazonensis (2005) Mem Inst Oswaldo Cruz, 100, pp. 525-534Real, F., Mortara, R.A., The diverse and dynamic nature of Leishmania parasitophorous vacuoles studied by multidimensional imaging (2012) PLoS Negl. Trop. Dis., 6, pp. e1518Real, F., Pouchelet, M., Rabinovitch, M., Leishmania (L) amazonensis: Fusion between parasitophorous vacuoles in infected bone-marrow derived mousemacrophages (2008) Exp Parasitol., 119, pp. 15-23Alpuche-Aranda, C.M., Racoosin, E.L., Swanson, J.A., Miller, S.I., Salmonella stimulate macrophage macropinocytosis and persist within spacious phagosomes (1994) J. Exp. Med., 179, pp. 601-608Real, F., Mortara, R.A., Rabinovitch, M., Fusion between Leishmania amazonensis and Leishmania major parasitophorous vacuoles: Live imaging of coinfected macrophages (2010) PLoS Negl. Trop. Dis., 4, pp. e905Ndjamen, B., Kang, B.H., Hatsuzawa, K., Kima, P.E., Leishmania parasitophorous vacuoles interact continuously with the host cell's endoplasmic reticulumparasitophorous vacuoles are hybrid compartments (2010) Cell Microbiol., 12, pp. 1480-1494Clayton, C., Shapira, M., Post-Transcriptional regulation of gene expression in trypanosomes and leishmanias (2007) Mol. Biochem. Parasitol., 156, pp. 93-101Martinez-Calvillo, S., Yan, S., Nguyen, D., Fox, M., Stuart, K., Myler, P.J., Transcription of Leishmania major Friedlin chromosome 1 initiates in both directions within a single region (2003) Mol. Cell, 11, pp. 1291-1299Haile, S., Papadopoulou, B., Developmental regulation of gene expression in trypanosomatid parasitic protozoa (2007) Curr. Opin. Microbiol., 10, pp. 569-577Martinez-Calvillo, S., Vizuet-de-Rueda, J.C., Florencio- Martinez, L.E., Manning-Cela, R.G., Figueroa-Angulo, E.E., Gene expression in trypanosomatid parasites (2010) J. Biomed. Biotechnol., 2010, p. 525241Wincker, P., Ravel, C., Blaineau, C., The Leishmania genome comprises 36 chromosomes conserved across widely divergent human pathogenic species (1996) Nucleic Acids Res., 24, pp. 1688-1694Britto, C., Ravel, C., Bastien, P., Conserved linkage groups associated with large-scale chromosomal rearrangements between Old World and New World Leishmania genomes (1998) Gene, 222, pp. 107-117Peacock, C.S., Seeger, K., Harris, D., Comparative genomic analysis of three Leishmania species that cause diverse human disease (2007) Nat. Genet., 39, pp. 839-847Raymond, F., Boisvert, S., Roy, G., Genome sequencing of the lizard parasite Leishmania tarentolae reveals loss of genes associated to the intracellular stage of human pathogenic species (2012) Nucleic Acids Res., 40, pp. 1131-1147Rovai, L., Tripp, C., Stuart, K., Simpson, L., Recurrent polymorphisms in small chromosomes of Leishmania tarentolae after nutrient stress or subcloning (1992) Mol. Biochem. Parasitol., 50, pp. 115-125Ivens, A.C., Peacock, C.S., Worthey, E.A., The genome of the kinetoplastid parasite Leishmania major (2005) Science, 309, pp. 436-442Downing, T., Imamura, H., Decuypere, S., Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance (2011) Genome Res., 21, pp. 2143-2156Rogers, M.B., Hilley, J.D., Dickens, N.J., Chromosome and gene copy number variation allow major structural change between species and strains of Leishmania (2011) Genome Res., 21, pp. 2129-2142Smith, D.F., Peacock, C.S., Cruz, A.K., Comparative genomics: Fromgenotype to disease phenotype in the leishmaniases (2007) Int. J. Parasitol., 37, pp. 1173-1186Lye, L.F., Owens, K., Shi, H., Retention and loss of RNA interference pathways in trypanosomatid protozoans (2010) PLoS Pathog., 6, pp. e1001161Messing, J., Crea, R., Seeburg, P.H., A system for shotgun DNA sequencing (1981) Nucleic Acids Res., 9, pp. 309-321Zerbino, D.R., Birney, E., Velvet: Algorithms for de novo short read assembly using de Bruijn graphs (2008) Genome Res., 18, pp. 821-829Quinn, N.L., Levenkova, N., Chow, W., Assessing the feasibility of GS FLX Pyrosequencing for sequencing the Atlantic salmon genome (2008) BMC Genomics, 9, p. 404Sommer, D.D., Delcher, A.L., Salzberg, S.L., Pop, M., Minimus: A fast, lightweight genome assembler BMC Bioinformatics, 8, p. 64Pop, M., Kosack, D.S., Salzberg, S.L., Hierarchical scaffolding with Bambus (2004) Genome Res., 14, pp. 149-159Slater, G.S., Birney, E., Automated generation of heuristics for biological sequence comparison (2005) BMC Bioinformatics, 6, p. 31Salzberg, S.L., Delcher, A.L., Kasif, S., White, O., Microbial gene identification using interpolated Markov models (1998) Nucleic Acids Res., 26, pp. 544-548Lomsadze, A., Ter-Hovhannisyan, V., Chernoff, Y.O., Borodovsky, M., Gene identification in novel eukaryotic genomes by self-Training algorithm (2005) Nucleic Acids Res., 33, pp. 6494-6506Haas, B.J., Salzberg, S.L., Zhu, W., Automated eukaryotic gene structure annotation using EVidence Modeler and the program to assemble spliced alignments (2008) Genome Biol., 9, pp. R7Koski, L.B., Gray, M.W., Lang, B.F., Burger, G., AutoFACT: An automatic functional annotation and classification tool (2005) BMC Bioinformatics, 6, p. 151Suzek, B.E., Huang, H., McGarvey, P., Mazumder, R., Wu, C.H., UniRef: Comprehensive and non-redundant UniProt reference clusters (2007) Bioinformatics, 23, pp. 1282-1288Marchler-Bauer, A., Bryant, S.H., CD-Search: Protein domain annotations on the fly (2004) Nucleic Acids Res., 32, pp. W327-W331Bateman, A., Birney, E., Cerruti, L., The Pfam protein families database (2002) Nucleic Acids Res., 30, pp. 276-280Kanehisa, M., Goto, S., KEGG: Kyoto encyclopedia of genes and genomes (2000) Nucleic Acids Res., 28, pp. 27-30Chen, F., Mackey, A.J., Stoeckert, C.J., Jrand Roos, D.S., OrthoMCL-DB: Querying a comprehensive multi-species collection of ortholog groups (2006) Nucleic Acids Res., 34, pp. D363-D368Chen, F., Mackey, A.J., Vermunt, J.K., Roos, D.S., Assessing performance of orthology detection strategies applied to eukaryotic genomes (2007) PLoS One, 2, pp. e383Quinlan, A.R., Hall, I.M., BEDTools: A flexible suite of utilities for comparing genomic features (2010) Bioinformatics, 26, pp. 841-842Sharp, P.M., Li, W.H., The codon adaptation index - A measure of directional synonymous codon usage bias, and its potential applications (1987) Nucleic Acids Res., 15, pp. 1281-1295Sharp, P.M., Tuohy, T.M., Mosurski, K.R., Codon usage in yeast: Cluster analysis clearly differentiates highly and lowly expressed genes (1986) Nucleic Acids Res., 14, pp. 5125-5143Comeron, J.M., Aguade, M., An evaluation of measures of synonymous codon usage bias (1998) J. Mol. Evol., 47, pp. 268-274Aslett, M., Aurrecoechea, C., Berriman, M., TriTrypDB: A functional genomic resource for the Trypanosomatidae (2010) Nucleic Acids Res., 38, pp. D457-D462Drummond, A.J., Ashton, B., Buxton, S., (2011) Geneious v5.6.3., , http://www.geneious.com/, (June 2012, date last accessed)Edgar, R.C., MUSCLE: Multiple sequence alignment with high accuracy and high throughput (2004) Nucleic Acids Res., 32, pp. 1792-1797Ronquist, F., Huelsenbeck, J.P., MrBayes 3: Bayesian phylogenetic inference under mixed models (2003) Bioinformatics, 19, pp. 1572-1574Whelan, S., Goldman, N., A general empirical model of protein evolution derived from multiple protein families using a maximum-likelihood approach (2001) Mol. Biol. Evol., 18, pp. 691-699Emanuelsson, O., Brunak, S., Von Heijne, G., Nielsen, H., Locating proteins in the cell using TargetP SignalP and related tools Nat. Protoc., 2, pp. 953-971Bendtsen, J.D., Jensen, L.J., Blom, N., Von Heijne, G., Brunak, S., Feature-based prediction of nonclassical and leaderless protein secretion (2004) Protein Eng Des Sel: PEDS, 17, pp. 349-356Paape, D., Barrios-Llerena, M.E., Le Bihan, T., Mackay, L., Aebischer, T., Gel free analysis of the proteome of intracellular Leishmania mexicana (2010) Mol. Biochem. Parasitol., 169, pp. 108-114Lowe, T.M., Eddy, S.R., TRNAscan-SE: A program for improved detection of transfer RNA genes in genomic sequence (1997) Nucleic Acids Res., 25, pp. 955-964Castillo-Ramirez, S., Vazquez-Castellanos, J.F., Gonzalez, V., Cevallos, M.A., Horizontal gene transfer and diverse functional constrains within a common replication- partitioning system in Alphaproteobacteria: The repABC operon (2009) BMC Genomics, 10, p. 536Bastien, P., Blaineau, C., Pages, M., Leishmania: Sex, lies and karyotype (1992) Parasitol. Today, 8, pp. 174-177Mannaert, A., Downing, T., Imamura, H., Dujardin, J.C., Adaptivemechanisms in pathogens: Universal aneuploidy in Leishmania (2012) Trends Parasitol., 28, pp. 370-376Sterkers, Y., Lachaud, L., Bourgeois, N., Crobu, L., Bastien, P., Pages, M., Novel insights intogenomeplasticity in Eukaryotes: Mosaic aneuploidy in Leishmania (2012) Mol. Microbiol., 86, pp. 15-23Ning, Z., Cox, A.J., Mullikin, J.C., SSAHA: A fast search method for large DNA databases (2001) Genome Res., 11, pp. 1725-1729Gentil, L.G., Lasakosvitsch, F., Silveira, J.F., Santos, M.R., Barbieri, C.L., Analysis and chromosomal mapping of Leishmania (Leishmania) amazonensis amastigote expressed sequence tags (2007) Mem Inst Oswaldo Cruz, 102, pp. 707-711Hutson, S., Structure and function of branched chain aminotransferases (2001) Prog Nucleic Acid Res. Mol. Biol., 70, pp. 175-206Ginger, M.L., Chance, M.L., Goad, L.J., Elucidation of carbon sources used for the biosynthesis of fatty acids and sterols in the trypanosomatid Leishmania mexicana (1999) Biochem. J., 342, pp. 397-405Arruda, D.C., D'Alexandri, F.L., Katzin, A.M., Uliana, S.R., Leishmania amazonensis: Biosynthesis of polyprenols of 9 isoprene units by amastigotes Exp. Parasitol., 118, pp. 624-628Neubert, T.A., Gottlieb, M., An inducible 30- nucleotidase/nuclease from the trypanosomatid Crithidia luciliae Purification and characterization (1990) J. Biol. Chem., 265, pp. 7236-7242Paletta-Silva, R., Vieira, D.P., Vieira-Bernardo, R., Leishmania amazonensis: Characterization of an ecto-30-nucleotidase activity and its possible role in virulence (2011) Exp Parasitol., 129, pp. 277-283Holmgren, A., Lu., J., Thioredoxin and thioredoxin reductase: Current research with special reference to human disease, Biochem (2010) Biophys. Res. Commun., 396, pp. 120-124Scott, P., Sher, A., A spectrum in the susceptibility of leishmanial strains to intracellular killing by murine macrophages (1986) J. Immunol., 136, pp. 1461-1466Krauth-Siegel, R.L., Comini, M.A., Redox control in trypanosomatids, parasitic protozoa with trypanothione- based thiol metabolism (2008) Biochim Biophys. Acta, 1780, pp. 1236-1248De Souza Carmo, E.V., Katz, S., Barbieri, C.L., Neutrophils reduce the parasite burden in Leishmania (Leishmania) amazonensis-infected macrophages (2010) PLoS One, 5, pp. e13815Asato, Y., Oshiro, M., Myint, C.K., Phylogenic analysis of the genus Leishmania by cytochrome b gene sequencing (2009) Exp. Parasitol., 121, pp. 352-361Fraga, J., Montalvo, A.M., DeDoncker, S., Dujardin, J.C., Van Der Auwera, G., Phylogeny of Leishmania species based on the heat-shock protein 70 gene (2010) Infect Genet. Evol., 10, pp. 238-245Rochette, A., McNicoll, F., Girard, J., Characterization and developmental gene regulation of a large gene family encoding amastin surface proteins in Leishmania spp (2005) Mol. Biochem. Parasitol., 140, pp. 205-220Jackson, A.P., The evolution of amastin surface glycoproteins in trypanosomatid parasites (2010) Mol. Biol. Evol., 27, pp. 33-45Cruz, M.C., Souza-Melo, N., Da Silva, C.V., Trypanosomacruzi: Role of delta-Amastinonextracellular amastigote cell invasion and differentiation (2012) PLoS One, 7, pp. e51804Stober, C.B., Lange, U.G., Roberts, M.T., From genome to vaccines for leishmaniasis: Screening 100 novel vaccine candidates against murine Leishmania major infection (2006) Vaccine, 24, pp. 2602-2616Rafati, S., Hassani, N., Taslimi, Y., Movassagh, H., Rochette, A., Papadopoulou, B., Amastin peptide-binding antibodies as biomarkers of active human visceral leishmaniasis (2006) Clin. Vaccine Immunol., 13, pp. 1104-1110Salotra, P., Duncan, R.C., Singh, R., Subba Raju, B.V., Sreenivas, G., Nakhasi, H.L., Upregulation of surface proteins in Leishmania donovani isolated from patients of post kala-Azar dermal leishmaniasis (2006) Microbes Infect., 8, pp. 637-644Rochette, A., Raymond, F., Ubeda, J.M., Genome-wide gene expression profiling analysis of Leishmania major and Leishmania infantum developmental stages reveals substantial differences between the two species (2008) BMC Genomics, 9, p. 255Azizi, H., Hassani, K., Taslimi, Y., Najafabadi, H.S., Papadopoulou, B., Rafati, S., Searching for virulence factors in the non-pathogenic parasite to humans Leishmania tarentolae (2009) Parasitology, 136, pp. 723-735Naderer, T., McConville, M.J., The Leishmaniamacrophage interaction: A metabolic perspective (2008) Cell Microbiol., 10, pp. 301-308De Souza Leao, S., Lang, T., Prina, E., Hellio, R., Antoine, J.C., Intracellular Leishmania amazonensis amastigotes internalize and degrade MHC class II molecules of their host cells (1995) J. Cell Sci., 108, pp. 3219-3231Silverman, J.M., Chan, S.K., Robinson, D.P., Proteomic analysis of the secretome of Leishmania donovani (2008) Genome Biol., 9, pp. R35Mouchess, M.L., Arpaia, N., Souza, G., Transmembrane mutations in Toll-like receptor 9 bypass the requirement for ectodomain proteolysis and induce fatal inflammation (2011) Immunity, 35, pp. 721-732Tuon, F.F., Fernandes, E.R., Pagliari, C., Duarte, M.I., Amato, V.S., The expression of TLR9 in human cutaneous leishmaniasis is associated with granuloma (2010) Parasite Immunol., 32, pp. 769-772Abou Fakher, F.H., Rachinel, N., Klimczak, M., Louis, J., Doyen, N., TLR9-dependent activation of dendritic cells byDNA fromLeishmania major favors Th1 cell development and the resolution of lesions (2009) J. Immunol., 182, pp. 1386-1396Carvalho, L.P., Petritus, P.M., Trochtenberg, A.L., Lymph node hypertrophy following Leishmania major infection is dependent on TLR9 (2012) J. Immunol., 188, pp. 1394-1401Favali, C., Tavares, N., Clarencio, J., Barral, A., Barral- Netto, M., Brodskyn, C., Leishmania amazonensis infection impairs differentiation and function of human dendritic cells (2007) J. Leukoc. Biol., 82, pp. 1401-1406Lezama-Davila, C.M., Isaac-Marquez, A.P., Systemic cytokine response in humans with chiclero's ulcers (2006) Parasitol Res., 99, pp. 546-553Linares, E., Augusto, O., Barao, S.C., Giorgio, S., Leishmania amazonensis infection does not inhibit systemic nitric oxide levels elicited by lipopolysaccharide in vivo (2000) J. Parasitol., 86, pp. 78-8

Global data on earthworm abundance, biomass, diversity and corresponding environmental properties

14 p.Earthworms are an important soil taxon as ecosystem engineers, providing a variety of crucial ecosystem functions and services. Little is known about their diversity and distribution at large spatial scales, despite the availability of considerable amounts of local-scale data. Earthworm diversity data, obtained from the primary literature or provided directly by authors, were collated with information on site locations, including coordinates, habitat cover, and soil properties. Datasets were required, at a minimum, to include abundance or biomass of earthworms at a site. Where possible, site-level species lists were included, as well as the abundance and biomass of individual species and ecological groups. This global dataset contains 10,840 sites, with 184 species, from 60 countries and all continents except Antarctica. The data were obtained from 182 published articles, published between 1973 and 2017, and 17 unpublished datasets. Amalgamating data into a single global database will assist researchers in investigating and answering a wide variety of pressing questions, for example, jointly assessing aboveground and belowground biodiversity distributions and drivers of biodiversity change

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Genetic diversity and insecticide. resistance of Myzus persicae (Hemiptera : Aphididae) populations from tobacco in Chile: evidence for the existence of a single predominant clone

Fuentes-Contreras, E. and Reyes, M. Departmento de Producción, Agrícola, Facultad de Ciencias Agrarias, Universidad de Talca, Casilla 747, Talca, Chile.The tobacco-feeding race of Myzus persicae (Sulzer), formerly known as M. nicotianae Blackman, was introduced into Chile during the last decade. In order to evaluate the genetic diversity and insecticide resistance status of Chilean tobacco aphid populations, a field survey was conducted in 35 tobacco fields covering a 300 km latitudinal survey. The populations sampled were characterized using microsatellite markers and morphometric multivariate analysis. Insecticide resistance levels were assessed through a microplate esterase assay and the mutation status of the kdr gene. All samples collected corresponded to the same anholocyclic aphid genotype, and showed morphological variation within the range expected for the tobacco-feeding race of M. persicae. Esterase activity showed the level and variability expected for an R1 clone lacking mutations in the sodium channels (susceptible kdr), thus corresponding to a type slightly resistant to organophosphate and carbamate, and susceptible to pyrethroid insecticide

Urología y recursos predictivos en la Web

Current medicine pursues a professional specialization and therapeutic individualization under the concept of individualized medicine, which is a personalized genomic medicine. However, our clinical practice is far from able to have an individualized genomic analysis of each patient and with enough evidence to provide personalized therapeutic advice. Overcoming the current limitations to this personalized medicine with a genetic basis is an important goal of this century. However, indirectly, we do have resources that can offer individualized medical advice to our patients. These resources come from the statistical and mathematical analyses of a large series of patients, their characteristics, evolution, and objectified results. We are referring to the complex multivariate analyses using more or less conventional techniques, such as logistic regression or Cox proportional hazards regression, or more advanced techniques, models based on artificial intelligence

Genetic diversity and insecticide resistance during the growing season in the green peach aphid (Hemiptera: Aphididae) on primary and secondary hosts: a farm-scale study in Central Chile

The seasonal dynamics of neutral genetic diversity and the insecticide resistance mechanisms of insect pests at the farm scale are still poorly documented. Here this was addressed in the green peach aphid Myzus persicae (Sulzer) (Hemiptera: Aphididae) in Central Chile. Samples were collected from an insecticide sprayed peach (Prunus persica L.) orchard (primary host), and a sweet-pepper (Capsicum annum var. grossum L.) field (secondary host). In addition, aphids from weeds (secondary hosts) growing among these crops were also sampled. Many unique multi-locus genotypes were found on peach trees, while secondary hosts were colonized mostly by the six most common genotypes, which were predominantly sensitive to insecticides. In both fields, a small but significant genetic differentiation was found between aphids on the crops vs. their weeds. Within-season comparisons showed genetic differentiation between early and late season samples from peach, as well as for weeds in the peach orchard. The knock-down resistance (kdr) mutation was detected mostly in the heterozygote state, often associated with modified acetylcholinesterase throughout the season for both crops. This mutation was found in high frequency, mainly in the peach orchard. The super-kdr mutation was found in very low frequencies in both crops. This study provides farm-scale evidence that the aphid M. persicae can be composed of slightly different genetic groups between contiguous populations of primary and secondary hosts exhibiting different dynamics of insecticide resistance through the growing season

Genetic structure and clonal diversity of an introduced pest in Chile, the cereal aphid Sitobion avenae

International audienceIn Chile, the aphid Sitobion avenae is of recent introduction, lives on cultivated and wild Poaceae, and is thought to reproduce by permanent parthenogenesis. In order to study the genetic variability and population structure of this species, five microsatellite loci were typed from individual aphids collected from different cultivated and wild host plants, from different geographical zones, and years. Chilean populations showed a high degree of heterozygosity and a low genetic variability across regions and years, with four predominant genotypes representing nearly 90% of the sample. This pattern of low clonal diversity and high heterozygosity was interpreted as the result of recent founder events from a few asexually reproducing genotypes. Most geographical and temporal variation observed in the genetic composition resulted from fluctuations of a few predominant clones. In addition, comparisons of the genotypes found in Chile with those described in earlier surveys of S. a! venae populations in Western Europe led us to identify 'superclones' with large geographical distribution and high ecological success, and to make a preliminary exploration of the putative origin(s) of S. avenae individuals introduced to Chile