149 research outputs found

    Respuesta humoral a dos inmunógenos contra la Peste Porcina Clásica en condiciones de campo

    Get PDF
    La Peste Porcina Clásica (PPC) es una enfermedad altamente contagiosa, presente en Cuba de forma endémica, por lo que está sujeta a un programa de control que incluye la vacunación con la vacuna viva atenuada de la cepa China lapinizada (LABIOFAM, S.A.), de probada seguridad y efectividad. Por las bondades que brinda el uso de una vacuna marcadora en fases avanzadas del control, fue aplicado en condiciones de campo un candidato vacunal de subunidad, basado en la glicoproteína E2 (CVE2) del virus de la peste porcina clásica. Se comparó la respuesta serológica inducida por el nuevo candidato vacunal con la inducida por la vacuna cepa China (VCC) en un mismo escenario epidemiológico, una granja porcina con antecedentes de manifestación clínica de la enfermedad y sujeta a vacunación sistemática con la VCC. Se evaluó la respuesta inmune humoral de animales vacunados con ambos productos mediante el ensayo de neutralización ligado a la peroxidasa (NPLA). Para ello se investigaron muestras de sangre obtenidas en diferentes fases del ciclo tecnológico. Se encontró en los sueros evaluados de animales vacunados con el CVE2 que estos mantuvieron altos títulos (³ 1:100) hasta el final de la ceba, a diferencia de los vacunados con la VCC. También se comprobó que animales vacunados con la VCC tuvieron un riesgo relativo 12,2 veces mayor de tener títulos de anticuerpos <1:50 que los vacunados con el CVE2

    The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis

    Get PDF
    Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P = 1.34×10<sup>−8</sup>, OR = 1.22, CI 95% = 1.14–1.30; rs2004640: P = 4.60×10<sup>−7</sup>, OR = 0.84, CI 95% = 0.78–0.90; rs10488631: P = 7.53×10<sup>−20</sup>, OR = 1.63, CI 95% = 1.47–1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P = 9.04×10<sup>−22</sup>, OR = 1.75, CI 95% = 1.56–1.97) better explained the observed association (likelihood P-value = 1.48×10<sup>−4</sup>), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific

    The state of the Martian climate

    Get PDF
    60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

    First RNA-seq approach to study fruit set and parthenocarpy in zucchini (Cucurbita pepo L.)

    Full text link
    [EN] Background: Zucchini fruit set can be limited due to unfavourable environmental conditions in off-seasons crops that caused ineffective pollination/fertilization. Parthenocarpy, the natural or artificial fruit development without fertilization, has been recognized as an important trait to avoid this problem, and is related to auxin signalling. Nevertheless, differences found in transcriptome analysis during early fruit development of zucchini suggest that other complementary pathways could regulate fruit formation in parthenocarpic cultivars of this species. The development of next-generation sequencing technologies (NGS) as RNA-sequencing (RNA-seq) opens a new horizon for mapping and quantifying transcriptome to understand the molecular basis of pathways that could regulate parthenocarpy in this species. The aim of the current study was to analyze fruit transcriptome of two cultivars of zucchini, a non-parthenocarpic cultivar and a parthenocarpic cultivar, in an attempt to identify key genes involved in parthenocarpy. Results: RNA-seq analysis of six libraries (unpollinated, pollinated and auxin treated fruit in a non-parthenocarpic and parthenocarpic cultivar) was performed mapping to a new version of C. pepo transcriptome, with a mean of 92% success rate of mapping. In the non-parthenocarpic cultivar, 6479 and 2186 genes were differentially expressed (DEGs) in pollinated fruit and auxin treated fruit, respectively. In the parthenocarpic cultivar, 10,497 in pollinated fruit and 5718 in auxin treated fruit. A comparison between transcriptome of the unpollinated fruit for each cultivar has been performed determining that 6120 genes were differentially expressed. Annotation analysis of these DEGs revealed that cell cycle, regulation of transcription, carbohydrate metabolism and coordination between auxin, ethylene and gibberellin were enriched biological processes during pollinated and parthenocarpic fruit set. Conclusion: This analysis revealed the important role of hormones during fruit set, establishing the activating role of auxins and gibberellins against the inhibitory role of ethylene and different candidate genes that could be useful as markers for parthenocarpic selection in the current breeding programs of zucchini.Research worked is supported by the project RTA2014-00078 from the Spanish Institute of Agronomy Research INIA (Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria) and also PP.AVA.AVA201601.7, FEDER y FSE (Programa Operativo FSE de Andalucia 2007-2013 "Andalucia se mueve con Europa"). TPV is supported by a FPI scholarship from RTA2011-00044-C02-01/02 project of INIA. The funding agencies were not involved in the design of the study, collection, analysis, and interpretation of data and in writing the manuscript.Pomares-Viciana, T.; Del Rio-Celestino, M.; Roman, B.; Die, J.; Picó Sirvent, MB.; Gómez, P. (2019). First RNA-seq approach to study fruit set and parthenocarpy in zucchini (Cucurbita pepo L.). BMC Plant Biology. 19:1-20. https://doi.org/10.1186/s12870-019-1632-2S12019Varga A, Bruinsma J. Tomato. In: Monselise SP, editor. CRC Handbook of Fruit Set and Development. Boca Raton: CRC Press; 1986. p. 461–80.Nepi M, Cresti L, Guarnieri M, Pacini E. Effect of relative humidity on water content, viability and carbohydrate profile of Petunia hybrid and Cucurbita pepo pollen. Plant Syst Evol. 2010;284:57–64.Gustafson FG. Parthenocarpy: natural and artificial. Bot Rev. 1942;8:599–654.Robinson RW, Reiners S. Parthenocarpy in summer squash. Hortscience. 1999;34:715–7.Pomares-Viciana T, Die J, Del Río-Celestino M, Román B, Gómez P. Auxin signalling regulation during induced and parthenocarpic fruit set in zucchini. Mol Breeding. 2017;37:56.Ozga JA, Reinecke DM. Hormonal interactions in fruit development. J Plant Growth Regul. 2003;22:73–81.Kim IS, Okubo H, Fujieda K. Endogenous levels of IAA in relation to parthenocarpy in cucumber (Cucumis sativus L). Sci Hortic. 1992;52:1–8.Olimpieri I, Siligato F, Caccia R, Mariotti L, Ceccarelli N, Soressi GP, et al. Tomato fruit set driven by pollination or by the parthenocarpic fruit allele are mediated by transcriptionally regulated gibberellin biosynthesis. Planta. 2007;226:877–88.Cui L, Zhang T, Li J, Lou Q, Chen J. Cloning and expression analysis of Cs-TIR1/AFB2: the fruit development-related genes of cucumber (Cucumis sativus L.). Acta Physiol Plant. 2014;36:139–49.De Jong M, Wolters-Arts J, Feron R, Mariani C, Vriezen WH. The Solanum lycopersicum auxin response factor 7 (SlARF7) regulates auxin signalling during tomato fruit set and development. Plant J. 2009;57:160–70.Wang H, Jones B, Li Z, Frasse P, Delalande C, Regad F, Chaabouni S, Latché A, Pech JC, Bouzayen M. The tomato aux/IAA transcription factor IAA9 is involved in fruit development and leaf morphogenesis. Plant Cell. 2005;17(10):2676–92.Goetz M, Vivian-Smith A, Johnson SD, Koltunow AM. AUXIN RESPONSE FACTOR 8 is a negative regulator of fruit initiation in Arabidopsis. Plant Cell. 2006;18(8):1873–86.Mazzucato A, Cellini F, Bouzayen M, Zouine M, Mila I, Minoia S et al. A TILLING allele of the tomato aux/IAA9 gene offers new insights into fruit set mechanisms and perspectives for breeding seedless tomatoes. Mol Breeding. 2015; 35(22):1-15.Blanca J, Cañizares J, Roig C, Ziarsolo P, Nuez F, Picó B. Transcriptome characterization and high throughput SSRs and SNPs discovery in Cucurbita pepo (Cucurbitaceae). BMC Genomics. 2011;12:104.Wang Z, Gerstein M, Snyder M. RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet. 2009;10(1):57–63.Da Fonseca RR, Albrechtsen A, Themudo GE, Ramos-Madrigal J, Sibbesen JA, Maretty L, et al. Next-generation biology: sequencing and data analysis approaches for non-model organisms. Mar Genomics. 2016;30:3–13.Conesa A, Madrigal P, Tarazona S, Gomez-Cabrero D, Cervera A, McPherson A, et al. A survey of best practices for RNA-seq data analysis. Genome Biol. 2016;17:13.Li J, Cui ZWJ, Zhang T, Guo Q, Xu J, Li J, et al. Transcriptome comparison of global distinctive features between pollination and parthenocarpic fruit set reveals transcriptional phytohormone cross-talk in cucumber (Cucumis sativus L). Plant Cell Physiol. 2014;55(7):1325–42.Fu L, Niu B, Zhu Z, Wu S, Li W. CD-HIT: accelerated for clustering the next-generation sequencing data. Bioinformatics. 2012;28(23):3150–2.Montero-Pau J, Blanca J, Bombarely A, Ziarsolo P, Esteras C, Martí-Gómez C, et al. De novo assembly of the zucchini genome reveals a whole genome duplication associated with the origin of the Cucurbita genus. Plant Biotechnol J. 2017. https://doi.org/10.1111/pbi.12860 .Vriezen WH, Feron R, Maretto F, Keijman J, Mariani C. Changes in tomato ovary transcriptome demonstrate complex hormonal regulation of fruit set. New Phytol. 2008;177:60–76.Tang N, Deng W, Hu G, Hu N, Li Z. Transcriptome profiling reveals the regulatory mechanism underlying pollination dependent and parthenocarpic fruit set mainly mediated by auxin and gibberellin. PLoS One. 2015;10(4):e0125355.Li J, Yan S, Yang W, Li Y, Xia M, Chen Z, et al. Transcriptomic analysis reveals the roles of microtubule-related genes and transcription factors in fruit length regulation in cucumber (Cucumis sativus L.). Sci Rep. 2015;26(5):8031.Mironov V, De Veylder L, Van Montagu M, Inze D. Cyclin-dependent kinases and cell division in plants- the nexus. Plant Cell. 1999;11(4):509–22.Perrot-Rechenmann C. Cellular responses to auxin: division versus expansion. Cold Spring Harb Perspect Biol. 2010;2(5):a001446.De Veylder L, Beeckman T, Beemster GT, Krols L, Terras F, Landrieu I, et al. Functional analysis of cyclin-dependent kinase inhibitors of Arabidopsis. Plant Cell. 2001;13:1653–68.Nieuwland J, Menges M, Murray JAH. The plant cyclins. In: Inze D, editor. Cell cycle control and plant development, vol. 2007. Oxford: Wiley-Blackwell Publishing; 2007. p. 33–61.Menges M, Samland AK, Planchais S, Murray JA. The D-type cyclin CYCD3;1 is limiting for the G1-to-S-phasetransition in Arabidopsis. Plant Cell. 2006;18:893–906.Boruc J, Mylle E, Duda M, De Clercq R, Rombauts S, Geelen D, et al. Systematic localization of the Arabidopsis core cell cycle proteins reveals novel cell division complexes. Plant Physiol. 2010;152(2):553–65.Sampedro J, Cosgrove DJ. The expansin superfamily. Genome Biol. 2005;6:242.Esmon CA, Tinsley AG, Ljung K, Sandberg G, Hearne LB, Liscum E. A gradient of auxin and auxin-dependent transcription precedes tropic growth responses. Proc Natl Acad Sci. 2006;103:236–41.De Folter S, Busscher J, Colombo L, Losa A, Angenent GC. Transcript profiling of transcription factors genes during siliques development in Arabidopsis. Plant Mol Bio. 2004;56:351–3662004.Son O, Cho HY, Kim MR, Lee H, Lee MS, Song E, et al. Induction of a homeodomain-leucine zipper gene by auxin is inhibited by cytokinin in Arabidopsis roots. Biochem Biophys Res Commun. 2005;326(1):203–9.Olsson ASB, Engstroem P, Seoderman E. The homeobox genes ATHB12 and ATHB7 encode potential regulators of growth in response to water deficit in Arabidopsis. Plant Mol Biol. 2004;55:663–77.Merrow SB, Hopp RJ. Storage effects on winter squashes. Associations between the sugar and starch content of and the degree of preference for winter squashes. J Agric Food Chem. 1961;9:321–6.Berg JM, Tymoczko JL, Stryer L. Carbohydrates. In: Freeman WH, editor. Biochemistry. 5th ed. New York: W H Freeman; 2002.Prabhakar V, Löttgert T, Gigolashvili T, Bell K, Flügge UI, Häusler RE. Molecular and functional characterization of the plastid-localized phosphoenolpyruvate enolase (ENO1) from Arabidopsis thaliana. FEBS Lett. 2009;583(6):983–91.Rius SP, Casati P, Iglesias AA, Gomez-Casati DF. Characterization of Arabidopsis lines deficient in GAPC-1, a cytosolic NAD-dependent glyceraldehyde-3-phosphate dehydrogenase. Plant Physiol. 2008;148(3):1655–67.Van der Linde K, Gutsche N, Leffers HM, Lindermayr C, Müller B, Holtgrefe S, et al. Regulation of plant cytosolic aldolase functions by redox-modifications. Plant Physiol Biochem. 2011;49(9):946–57.Lim H, Cho MH, Jeon JS, Bhoo SH, Kwon YK, Hahn TR. Altered expression of pyrophosphate: fructose-6-phosphate 1-phosphotransferase affects the growth of transgenic Arabidopsis plants. Mol Cells. 2009;27(6):641–9.Baud S, Wuillème S, Dubreucq B, De Almeida A, Vuagnat C, Lepiniec L, et al. Function of plastidial pyruvate kinases in seeds of Arabidopsis thaliana. Plant J. 2007;52:405–19.De Jong M, Mariani C, Vriezen WH. The role of auxin and gibberellin in tomato fruit set. J Exp Bot. 2009;60(5):1523–32.Martínez C, Manzano S, Megías Z, Garrido D, Picó B, Jamilena M. Involvement of ethylene biosynthesis and signalling in fruit set and early fruit development in zucchini squash (Cucurbita pepo L.). BMC Plant Biol. 2013;13:139.Serrani JC, Fos M, Atarés A, Garcia-martinez JL. Effect of gibberellin and auxin on parthenocarpic fruit growth induction in the cv. micro-tom of tomato. J Plant Growth Regul. 2007;26:211–21.Mapelli S. Changes in cytokinin in the fruits of parthenocarpic and normal tomatoes. Plant Sci Lett. 1981;22:227–33.Ulmasov T, Hagen G, Guilfoyle TJ. Activation and repression of transcription by auxin-response factors. Proc Natl Acad Sci U S A. 1999;96:5844–9.Ulmasov T, Hagen G, Guilfoyle TJ. Dimerization and DNA binding of auxin response factors. Plant J. 1999;19:309–19.Tiwari SB, Hagen G, Guilfoyle TJ. Aux/IAA proteins contain a potent transcriptional repression domain. Plant Cell. 2004;16:533–43.Switzenberg JA, Beaudry RM, Grumet R. Effect of CRC:: etr1-1 transgene expression on ethylene production, sex expression, fruit set and fruit ripening in transgenic melon (Cucumis melo L.). Transgenic Res. 2015;24(3):497-507.Nitsch LM, Oplaat C, Feron R, Ma Q, Wolters-Arts M, Hedden P, et al. Abscisic acid levels in tomato ovaries are regulated by LeNCED1 and SlCYP707A1. Planta. 2009;229(6):1335–46.Mortazavi A, Williams BA, McCue K, Schaeffer L, Wold B. Mapping and quantifying mammalian transcriptomes by RNA-seq. Nat Methods. 2008;5(7):621–8.Robinson MD, McCarthy DJ, Smyth GK. Edger: a bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2008;26(1):139–40.Raza K, Mishra A. A novel anticlustering filtering algorithm for the prediction of genes as a drug target. Am J Bio Engi. 2012;2(5):206–11.Van Iterson M, Boer JM, Menezes RX. Filtering, FDR and power. BMCBioinformatics. 2010;11:450.Conesa A, Götz S, Garcia-Gomez JM, Terol J, Talon M, Robles M. Blast2GO: a universal tool for annotation, visualization and analysis in functional genomics research. Bioinformatics. 2005;21:3674–6.Berardini TZ, Reiser L, Li D, Mezheritsky Y, Muller R, Strait E, Huala E. The Arabidopsis information resource: making and mining the “gold standard” annotated reference plant genome. Genesis. 2015. https://doi.org/10.1002/dvg.22877 .Bairoch A, Apweiler R. The SWISS-PROT protein sequence database and its supplement TrEMBL. Nucleic Acids Res. 2000;28(1):45–8.Johnson M, Zaretskaya I, Raytselis Y, Merezhuk Y, McGinnis S, Madden TL. NCBI BLAST: a better web interface. Nucleic Acids Res. 2008;36:W5–9.Wyatt LE, Strickler SR, Mueller LA, Mazourek M. An acorn squash (Cucurbita pepo ssp. ovifera) fruit and seed transcriptome as a resource for the study of fruit traits in Cucurbita. Hortic Res. 2015;2:14070. https://doi.org/10.1038/hortres.2014.70 .Zhang A, Ren GA, Sun YA, Guo H, Zhang SA, Zhang FA, et al. A high-density genetic map for anchoring genome sequences and identifying QTLs associated with dwarf vine in pumpkin (Cucurbita maxima Duch.). BMC Genomics. 2015;16:1101.Finn RD, Attwood TK, Babbit AB, Bork P, Bridge AJ, Chang HY. InterPro in 2017-beyond protein family and domain annotations. Nucleic Acids Res. https://doi.org/10.1093/nar/gkw1107 .Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Sherlock G. Gene ontology: tool for the unification of biology. Nat Genet. 2000;25(1):25–9.Kanehisa M, Araki M, Goto S, et al. KEGG for linking genomes to life and the environment. Nucleic Acids Res. 2008;36:480–4

    Next-generation care pathways for allergic rhinitis and asthma multimorbidity: A model for multimorbid non-communicable diseases—Meeting Report (Part 2)

    Get PDF

    Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology

    Get PDF
    Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.Peer reviewe

    Correlation between work impairment, scores of rhinitis severity and asthma using the MASK-air (R) App

    Get PDF
    Background In allergic rhinitis, a relevant outcome providing information on the effectiveness of interventions is needed. In MASK-air (Mobile Airways Sentinel Network), a visual analogue scale (VAS) for work is used as a relevant outcome. This study aimed to assess the performance of the work VAS work by comparing VAS work with other VAS measurements and symptom-medication scores obtained concurrently. Methods All consecutive MASK-air users in 23 countries from 1 June 2016 to 31 October 2018 were included (14 189 users; 205 904 days). Geolocalized users self-assessed daily symptom control using the touchscreen functionality on their smart phone to click on VAS scores (ranging from 0 to 100) for overall symptoms (global), nose, eyes, asthma and work. Two symptom-medication scores were used: the modified EAACI CSMS score and the MASK control score for rhinitis. To assess data quality, the intra-individual response variability (IRV) index was calculated. Results A strong correlation was observed between VAS work and other VAS. The highest levels for correlation with VAS work and variance explained in VAS work were found with VAS global, followed by VAS nose, eye and asthma. In comparison with VAS global, the mCSMS and MASK control score showed a lower correlation with VAS work. Results are unlikely to be explained by a low quality of data arising from repeated VAS measures. Conclusions VAS work correlates with other outcomes (VAS global, nose, eye and asthma) but less well with a symptom-medication score. VAS work should be considered as a potentially useful AR outcome in intervention studies.Peer reviewe

    ARIA 2016 : Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

    Get PDF
    The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.Peer reviewe

    Study of the production of charged pions, kaons, and protons in pPb collisions at √SNN=5.02 TeV

    Get PDF
    Peer reviewe

    Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

    Get PDF
    BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events
    corecore