How do cardiologists select patients for dual antiplatelet therapy continuation beyond 1 year after a myocardial infarction? Insights from the EYESHOT Post-MI Study

Background: Current guidelines suggest to consider dual antiplatelet therapy (DAPT) continuation for longer than 12 months in selected patients with myocardial infarction (MI). Hypothesis: We sought to assess the criteria used by cardiologists in daily practice to select patients with a history of MI eligible for DAPT continuation beyond 1 year. Methods: We analyzed data from the EYESHOT Post-MI, a prospective, observational, nationwide study aimed to evaluate the management of patients presenting to cardiologists 1 to 3 years from the last MI event. Results: Out of the 1633 post-MI patients enrolled in the study between March and December 2017, 557 (34.1%) were on DAPT at the time of enrolment, and 450 (27.6%) were prescribed DAPT after cardiologist assessment. At multivariate analyses, a percutaneous coronary intervention (PCI) with multiple stents and the presence of peripheral artery disease (PAD) resulted as independent predictors of DAPT continuation, while atrial fibrillation was the only independent predictor of DAPT interruption for patients both at the second and the third year from MI at enrolment and the time of discharge/end of the visit. Conclusions: Risk scores recommended by current guidelines for guiding decisions on DAPT duration are underused and misused in clinical practice. A PCI with multiple stents and a history of PAD resulted as the clinical variables more frequently associated with DAPT continuation beyond 1 year from the index MI

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

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

A remarkable synergistic effect at the transcriptomic level in peach fruits doubly infected by Prunus necrotic ringspot virus and Peach latent mosaic viroid

[EN] Background: Microarray profiling is a powerful technique to investigate expression changes of large amounts of genes in response to specific environmental conditions. The majority of the studies investigating gene expression changes in virus-infected plants are limited to interactions between a virus and a model host plant, which usually is Arabidopsis thaliana or Nicotiana benthamiana. In the present work, we performed microarray profiling to explore changes in the expression profile of field-grown Prunus persica (peach) originating from Chile upon single and double infection with Prunus necrotic ringspot virus (PNRSV) and Peach latent mosaic viroid (PLMVd), worldwide natural pathogens of peach trees. Results: Upon single PLMVd or PNRSV infection, the number of statistically significant gene expression changes was relatively low. By contrast, doubly-infected fruits presented a high number of differentially regulated genes. Among these, down-regulated genes were prevalent. Functional categorization of the gene expression changes upon double PLMVd and PNRSV infection revealed protein modification and degradation as the functional category with the highest percentage of repressed genes whereas induced genes encoded mainly proteins related to phosphate, C-compound and carbohydrate metabolism and also protein modification. Overrepresentation analysis upon double infection with PLMVd and PNRSV revealed specific functional categories over- and underrepresented among the repressed genes indicating active counter-defense mechanisms of the pathogens during infection. Conclusions: Our results identify a novel synergistic effect of PLMVd and PNRSV on the transcriptome of peach fruits. We demonstrate that mixed infections, which occur frequently in field conditions, result in a more complex transcriptional response than that observed in single infections. Thus, our data demonstrate for the first time that the simultaneous infection of a viroid and a plant virus synergistically affect the host transcriptome in infected peach fruits. These field studies can help to fully understand plant-pathogen interactions and to develop appropriate crop protection strategies.We thank Drs M.A. Perez-Amador y J. Gadea for helping in the result analysis. This work was supported by grant BIO2011-25018 from the Spanish granting agency Direccion General de Investigacion Cientifica for the transcriptomic analyses and from the grant 2009CL0020 from the bilateral project INIA-Chile/CSIC-Spain for the phytosanitary evaluation. MC Herranz was the recipient of a contract from the Juan de la Cierva program of the Ministerio de Educacion y Ciencia of Spain.Herranz Gordo, MDC.; Niehl, A.; Rosales, M.; Fiore, N.; Zamorano, A.; Granell Richart, A.; Pallás Benet, V. (2013). A remarkable synergistic effect at the transcriptomic level in peach fruits doubly infected by Prunus necrotic ringspot virus and Peach latent mosaic viroid. Virology Journal. 10:11-15. https://doi.org/10.1186/1743-422X-10-164S111510Pallas V, Garcia JA: How do plant viruses induce disease? Interactions and interference with host components. J Gen Virol 2011, 92: 2691-2705.Whitham SA, Yang C, Goodin MM: Global impact: elucidating plant responses to viral infection. Mol Plant Microbe Interact 2006, 19: 1207-1215.Havelda Z, Varallyay E, Valoczi A, Burgyan J: Plant virus infection-induced persistent host gene downregulation in systemically infected leaves. Plant J 2008, 55: 278-288.Aranda M, Maule A: Virus-induced host gene shutoff in animals and plants. Virology 1998, 243: 261-267.Whitham SA, Quan S, Chang HS, Cooper B, Estes B, Zhu T, Wang X, Hou YM: Diverse RNA viruses elicit the expression of common sets of genes in susceptible Arabidopsis thaliana plants. Plant J 2003, 33: 271-283.Liu Y, Ren D, Pike S, Pallardy S, Gassmann W, Zhang S: Chloroplast-generated reactive oxygen species are involved in hypersensitive response-like cell death mediated by a mitogen-activated protein kinase cascade. Plant J 2007, 51: 941-954.Hadidi A, Barba M: Economic impact of pome and stone fruit viruses and viroids. In Virus and Virus Like Diseases of Pome and Stone Fruits. Edited by: Hadidi A, Barba M, Candresse T, Jelkmann W. St Paul, MN: American Phytopathological Society; 2011:1-8.Flores R, Delgado S, Rodio ME, Ambros S, Hernandez C, Serio FD: Peach latent mosaic viroid: not so latent. Mol Plant Pathol 2006, 7: 209-221.Pallas V, Aparicio F, Herranz MC, Amari K, Sanchez-Pina MA, Myrta A, Sanchez-Navarro JA: Ilarviruses of Prunus spp.: A continued concern for fruit trees. Phytopathology 2012,102(12):1108-1120.Rowland O, Jones JD: Unraveling regulatory networks in plant defense using microarrays. Genome Biol 2001,2(1):1001.1-1001.3.Trinks D, Rajeswaran R, Shivaprasad PV, Akbergenov R, Oakeley EJ, Veluthambi K, Hohn T, Pooggin MM: Suppression of RNA silencing by a geminivirus nuclear protein, AC2, correlates with transactivation of host genes. J Virol 2005, 79: 2517-2527.Senthil G, Liu H, Puram VG, Clark A, Stromberg A, Goodin MM: Specific and common changes in Nicotiana benthamiana gene expression in response to infection by enveloped viruses. J Gen Virol 2005, 86: 2615-2625.Marathe R, Guan Z, Anandalakshmi R, Zhao H, Dinesh-Kumar SP: Study of Arabidopsis thaliana resistome in response to cucumber mosaic virus infection using whole genome microarray. Plant Mol Biol 2004, 55: 501-520.Agudelo-Romero P, Carbonell P, de la Iglesia F, Carrera J, Rodrigo G, Jaramillo A, Perez-Amador MA, Elena SF: Changes in the gene expression profile of Arabidopsis thaliana after infection with Tobacco etch virus. Virol J 2008, 5: 92.Itaya A, Matsuda Y, Gonzales RA, Nelson RS, Ding B: Potato spindle tuber viroid strains of different pathogenicity induces and suppresses expression of common and unique genes in infected tomato. Mol Plant Microbe Interact 2002, 15: 990-999.Huang Z, Yeakley JM, Garcia EW, Holdridge JD, Fan JB, Whitham SA: Salicylic acid-dependent expression of host genes in compatible Arabidopsis-virus interactions. Plant Physiol 2005, 137: 1147-1159.Rizza S, Conesa A, Juarez J, Catara A, Navarro L, Duran-Vila N, Ancillo G: Microarray analysis of Etrog citron (Citrus medica L.) reveals changes in chloroplast, cell wall, peroxidase and symporter activities in response to viroid infection. Mol Plant Pathol 2012,13(8):852-864.Golem S, Culver JN: Tobacco mosaic virus induced alterations in the gene expression profile of Arabidopsis thaliana. Mol Plant Microbe Interact 2003, 16: 681-688.Dardick C: Comparative expression profiling of Nicotiana benthamiana leaves systemically infected with three fruit tree viruses. Mol Plant Microbe Interact 2007, 20: 1004-1017.Hull R: In Matthews’ Plant Virology. London: Edited by Academic Press; 2002.Gonzalez-Jara P, Tenllado F, Martinez-Garcia B, Atencio FA, Barajas D, Vargas M, Diaz-Ruiz J, Diaz-Ruiz JR: Host-dependent differences during synergistic infection by Potyviruses with potato virus X. Mol Plant Pathol 2004, 5: 29-35.Gonzalez-Jara P, Atencio FA, Martinez-Garcia B, Barajas D, Tenllado F, Diaz-Ruiz JR: A Single Amino Acid Mutation in the Plum pox virus Helper Component-Proteinase Gene Abolishes Both Synergistic and RNA Silencing Suppression Activities. Phytopathology 2005, 95: 894-901.Vance VB: Replication of potato virus X RNA is altered in coinfections with potato virus Y. Virology 1991, 182: 486-494.Garcia-Marcos A, Pacheco R, Martianez J, Gonzalez-Jara P, Diaz-Ruiz JR, Tenllado F: Transcriptional changes and oxidative stress associated with the synergistic interaction between Potato virus X and Potato virus Y and their relationship with symptom expression. Mol Plant Microbe Interact 2009, 22: 1431-1444.Postnikova OA, Nemchinov LG: Comparative analysis of microarray data in Arabidopsis transcriptome during compatible interactions with plant viruses. Virol J 2012, 9: 101.Zanchin A, Bonghi C, Casadoro G, Ramina A, Rascio N: Cell enlargement and cell separation during peach fruit development. International Journal of Plant Science 1994, 155: 49-56.Herranz MC, Sanchez-Navarro JA, Aparicio F, Pallas V: Simultaneous detection of six stone fruit viruses by non-isotopic molecular hybridization using a unique riboprobe or ‘polyprobe’. J Virol Methods 2005, 124: 49-55.Pallas V, Mas P, Sanchez-Navarro JA: Detection of plant RNA viruses by nonisotopic dot-blot hybridization. Methods Mol Biol 1998, 81: 461-468.Lilly ST, Drummond RS, Pearson MN, MacDiarmid RM: Identification and validation of reference genes for normalization of transcripts from virus-infected Arabidopsis thaliana. Mol Plant Microbe Interact 2011, 24: 294-304.Cosgrove JD: Expansive growth of plant cell walls. Plant Physiol Biochem 2000,38(1–2):109-124.Tessitori M, Maria G, Capasso C, Catara G, Rizza S, De Luca V, Catara A, Capasso A, Carginale V: Differential display analysis of gene expression in Etrog citron leaves infected by Citrus viroid III. Biochim Biophys Acta 2007, 1769: 228-235.Rizza S, Capasso C, Catara A, Capasso A, Conte E, Catara A Proceedings of the 17th Conference of the International Organization of Citrus Virologists-IOCV, pp. XVII. In Transcriptional response of Troyer citrange, sour orange and alemow rootstocks to Citrus viroid IIIb (CVd-IIIb) infection. Adana, Turkey: Conference of the International Organization of Citrus Virologists; 2010:142-149. http://www.ivia.es/iocv/Owens RA, Tech KB, Shao JY, Sano T, Baker CJ: Global analysis of tomato gene expression during Potato spindle tuber viroid infection reveals a complex array of changes affecting hormone signaling. Mol Plant Microbe Interact 2012, 25: 582-598.Ogundiwin EA, Marti C, Forment J, Pons C, Granell A, Gradziel TM, Peace CP, Crisosto CH: Development of ChillPeach genomic tools and identification of cold-responsive genes in peach fruit. Plant Mol Biol 2008, 68: 379-397.Sánchez-Navarro JA FA, Rowhani A, Pallás V: Comparative analysis of ELISA, nonradioactive molecular hybridization and PCR for the detection of Prunus necrotic ringspot virus in herbaceous and prunus host. Plant Pathol 1998, 47: 780-786.Astruc N, Marcos JF, Macquaire G, Candresse T, Pallas V: Studies on the diagnosis of hop stunt viroid in fruit trees: Identification of new hosts and application of a nucleic acid extraction procedure based on non-organic solvents. Eur J Plant Pathol 1996, 102: 837-846.Myrta A, Di Terlizzi B, Pallas V, Savino V: Viruses and viroids of apricot in the Mediterranean: incidence and biodiversity. Acta Horticulturae 2006, 701: 409-417.Bouzayen M, Latché A, Nath P, Pech JC: Mechanism of fruit ripening. In Plant Developmental Biology- Biotechnological Perspectives: Volume I Edited by: Pua EC, Darvey MR. 2010, 319-339. Chapter 16Trainotti L, Bonghi C, Ziliotto F, Zanin D, Rasori A, Casadoro G, Ramina A, T P: The use of microarray mPEACH 1.0 to investigate transcriptome changes during transition from pre-climateric to climacteric phase in peach fruit. Plant Sci 2006, 170: 606-613.Lombardo VA, Osorio S, Borsani J, Lauxmann MA, Bustamante CA, Budde CO, Andreo CS, Lara MV, Fernie AR MFD: Metabolic profiling during peach fruit development and ripening reveals the metabolic networks that underpin each developmental stage. Plant Physiol 2011,157(4):1696-1710.Manganaris GA RA, Bassi D, Geuna F, Ramina A, Tonutti P, Bonghi C: Comparative transcript profiling of apricot (Prunus armeniaca L.) fruit development and on-tree ripening. Tree Genet Genomes 2011, 7: 609-616.Uyemoto JK, Scott SW: Important diseases of Prunus caused by viruses and other graft-transmissible pathogens in California and South Carolina. Plant Dis 1992, 76: 5-11.Li J, Yang H, Peer WA, Richter G, Blakeslee J, Bandyopadhyay A, Titapiwantakun B, Undurraga S, Khodakovskaya M, Richards EL, et al.: Arabidopsis H+-PPase AVP1 regulates auxin-mediated organ development. Science 2005, 310: 121-125.Paponov IA, Paponov M, Teale W, Menges M, Chakrabortee S, Murray JA, Palme K: Comprehensive transcriptome analysis of auxin responses in Arabidopsis. Mol Plant 2008, 1: 321-337.Padmanabhan MS, Goregaoker SP, Golem S, Shiferaw H, Culver JN: Interaction of the tobacco mosaic virus replicase protein with the Aux/IAA protein PAP1/IAA26 is associated with disease development. J Virol 2005, 79: 2549-2558.Padmanabhan MS, Shiferaw H, Culver JN: The Tobacco mosaic virus replicase protein disrupts the localization and function of interacting Aux/IAA proteins. Mol Plant Microbe Interact 2006, 19: 864-873.Padmanabhan MS, Kramer SR, Wang X, Culver JN: Tobacco mosaic virus replicase-auxin/indole acetic acid protein interactions: reprogramming the auxin response pathway to enhance virus infection. J Virol 2008, 82: 2477-2485.Kuhn JM, Boisson-Dernier A, Dizon MB, Maktabi MH, Schroeder JI: The protein phosphatase AtPP2CA negatively regulates abscisic acid signal transduction in Arabidopsis, and effects of abh1 on AtPP2CA mRNA. Plant Physiol 2006, 140: 127-139.Whenham RJ, Fraser RSS, Brown LP, Payne JA: Tobacco-mosaic-virus-induced increase in abscisic-acid concentration in tobacco leaves: Intracellular location in light and dark-green areas, and relationship to symptom development. Planta 1986, 168: 592-598.Bari R, Jones JD: Role of plant hormones in plant defence responses. Plant Mol Biol 2009, 69: 473-488.Kotchoni SO, Kuhns C, Ditzer A, Kirch HH, Bartels D: Over-expression of different aldehyde dehydrogenase genes in Arabidopsis thaliana confers tolerance to abiotic stress and protects plants against lipid peroxidation and oxidative stress. Plant Cell Environ 2006, 29: 1033-1048.Mowla SB, Cuypers A, Driscoll SP, Kiddle G, Thomson J, Foyer CH, Theodoulou FL: Yeast complementation reveals a role for an Arabidopsis thaliana late embryogenesis abundant (LEA)-like protein in oxidative stress tolerance. Plant J 2006, 48: 743-756.Amari K, Diaz-Vivancos P, Pallas V, Sanchez-Pina MA, Hernandez JA: Oxidative stress induction by Prunus necrotic ringspot virus infection in apricot seeds. Physiol Plant 2007, 131: 302-310.Gilroy EM, Hein I, van der Hoorn R, Boevink PC, Venter E, McLellan H, Kaffarnik F, Hrubikova K, Shaw J, Holeva M, et al.: Involvement of cathepsin B in the plant disease resistance hypersensitive response. Plant J 2007, 52: 1-13.Kruger J, Thomas CM, Golstein C, Dixon MS, Smoker M, Tang S, Mulder L, Jones JD: A tomato cysteine protease required for Cf-2-dependent disease resistance and suppression of autonecrosis. Science 2002, 296: 744-747.Bernoux M, Timmers T, Jauneau A, Briere C, De Wit PJ, Marco Y, Deslandes L: RD19, an Arabidopsis cysteine protease required for RRS1-R-mediated resistance, is relocalized to the nucleus by the Ralstonia solanacearum PopP2 effector. Plant Cell 2008, 20: 2252-2264.Shabab M, Shindo T, Gu C, Kaschani F, Pansuriya T, Chintha R, Harzen A, Colby T, Kamoun S, van der Hoorn RA: Fungal effector protein AVR2 targets diversifying defense-related cys proteases of tomato. Plant Cell 2008, 20: 1169-1183.Van Esse HP, Van’t Klooster JW, Bolton MD, Yadeta KA, Van Baarlen P, Boeren S, Vervoort J, De Wit PJ, Thomma BP: The Cladosporium fulvum virulence protein Avr2 inhibits host proteases required for basal defense. Plant Cell 2008, 20: 1948-1963.Song J, Win J, Tian M, Schornack S, Kaschani F, Ilyas M, van der Hoorn RA, Kamoun S: Apoplastic effectors secreted by two unrelated eukaryotic plant pathogens target the tomato defense protease Rcr3. Proc Natl Acad Sci U S A 2009, 106: 1654-1659.Tian M, Win J, Song J, van der Hoorn R, van der Knaap E, Kamoun S: A Phytophthora infestans cystatin-like protein targets a novel tomato papain-like apoplastic protease. Plant Physiol 2007, 143: 364-377.Rooney H, Van’t Klooster J, Van der Hoorn R, Joosten M, Jones J: Cladosporium Avr2 inhibits tomato Rcr3 protease required for Cf-2-dependent disease resistance. Science 2005, 308: 1783-1786.Auger AJ: Tomato ringspot virus associated with brownline disease on prune trees in Chile. Acta Horticulturae 1989, 235: 197-204.Herrera G: Enfermedades causadas por virus en frutales en Chile. Santiago, Chile: Instituto de Investigación Agropecuaria; 2001. Boletín INIA N°52. 65pFiore N, Abou Ghanem-Sabanadzovic N, Infante R, Myrta A, Pallás V: Detection of Peach latent mosaic viroid in stone fruits from Chile. In Option Méditerranéennes, Sér. B/n°45 –Virus ad virus-like disease of stone fruits, with particular reference to the Mediterranean region Edited by: Myrta A, Di Terlizzi B, Savino V. 2003, 143-145.Torres H, Gómez G, Pallás V, Stamo B, Shalaby A, Aouane B, Gavriel I, Kominek P, Caglayan K, Sipahioglu M, et al.: Detection by tissue printing of stone fruit viroids, from europe, the mediterranean and north and south America. Acta Horticulturae 2004, 657: 379-383.Peiró A, Pallás V, Sánchez-Navarro JA: Simultaneous detection of eight viruses and two viroids affecting stone fruit trees by using a unique polyprobe. Eur J Plant Pathol 2012,132(4):469-475.Meisel L, Fonseca B, Gonzalez S, Baeza-Yates R, Cambiazo V, Campos R, Gonzalez M, Orellana A, Retamales J, Silva H: A rapid and efficient method for purifying high quality total RNA from peaches (Prunus persica) for functional genomics analyses. Biol Res 2005, 38: 83-88.Van Gelder RN, Von Zastrow ME, Yool A, Dement WC, Barchas JD JHE: Amplified RNA synthesized from limited quantities of heterogeneous cDNA. Proc Natl Acad Sci U S A 1990,87(5):1663-1667.Tusher VG, Tibshirani R, Chu G: Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A 2001, 98: 5116-5121.Sanchez-Navarro JA, Canizares MC, Cano EA, Pallas V: Simultaneous detection of five carnation viruses by non-isotopic molecular hybridization. J Virol Methods 1999, 82: 167-175