Método para la obtención de cultivares de tomate con frutos partenocárpicos (sin semillas) y mayor calidad organoléptica

Método para la obtención de cultivares de tomate con frutos partenocárpicos (sin semillas) y mayor calidad organoléptica. El método se basa en la transferencia y expresión del gen LFY de Arabidopsis thaliana en plantas transgénicas de tomate. Los frutos de las plantas transgénicas con el gen LFY mantienen el mismo tamaño y peso que los del cultivar original, pero carecen de semillas, tienen más carne, menos pulpa y una forma ligeramente apuntillada. El análisis de calidad refleja un incremento del 60% en el contenido en sólidos solubles (la media alcanza 6,12 ºBrix) y del 60% en ácidos valorables (la media llega al 0,72%), lo que indica una mejora de la calidad organoléptica de los frutos en comparación con los del cultivar original no transgénico. Además, los frutos de las plantas transgénicas tienen otros atributos que indican una mayor calidad, tales como un mayor contenido en azúcares (sobre todo glucosa y fructosa) y licopeno, una sustancia que tiene propiedades antioxidantes.Peer reviewedUniversidad Politécnica de Valencia, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Científicas (España), Universidad de AlmeríaB2 Patente con examen previ

Comparison of different vascular risk engines in the identification of type 2 diabetes patients with high cardiovascular risk

Background: Some authors consider that secondary prevention should be conducted for all DM2 patients, while others suggest that the drug preventive treatment should start or be increased depending on each patient''s individual CVR, estimated using cardiovascular or coronary risk functions to identify the patients with a higher CVR. The principal objective of this study was to assess three different cardiovascular risk prediction models in type 2 diabetes patients. Methods: Multicentre, cross-sectional descriptive study of 3, 041 patients with type 2 diabetes and no history of cardiovascular disease. The demographic, clinical, analytical, and cardiovascular risk factor variables associated with type 2 diabetes were analysed. The risk function and probability that a cardiovascular disease could occur were estimated using three risk engines: REGICOR, UKPDS and ADVANCE. A patient was considered to have a high cardiovascular risk when REGICOR = 10 % or UKPDS = 15 % in 10 years or when ADVANCE = 8 % in 4 years. Results: The ADVANCE and UKPDS risk engines identified a higher number of diabetic patients with a high cardiovascular risk (24.2 % and 22.7 %, respectively) compared to the REGICOR risk engine (10.2 %). The correlation using the REGICOR risk engine was low compared to UKPDS and ADVANCE (r = 0.288 and r = 0.153, respectively//p < 0.0001). The agreement values in the allocation of a particular patient to the high risk group was low between the REGICOR engine and the UKPDS and ADVANCE engines (k = 0.205 and k = 0.123, respectively//p < 0.0001) and acceptable between the ADVANCE and UKPDS risk engines (k = 0.608). Conclusions: There are discrepancies between the general population and the type 2 diabetic patient-specific risk engines. The results of this study indicate the need for a prospective study which validates specific equations for diabetic patients in the Spanish population, as well as research on new models for cardiovascular risk prediction in these patients

A Broad Genomic Survey Reveals Multiple Origins and Frequent Losses in the Evolution of Respiratory Hemerythrins and Hemocyanins

Abstract Hemerythrins and hemocyanins are respiratory proteins present in some of the most ecologically diverse animal lineages; however, the precise evolutionary history of their enzymatic domains (hemerythrin, hemocyanin M, and tyrosinase) is still not well understood. We survey a wide dataset of prokaryote and eukaryote genomes and RNAseq data to reconstruct the phylogenetic origins of these proteins. We identify new species with hemerythrin, hemocyanin M, and tyrosinase domains in their genomes, particularly within animals, and demonstrate that the current distribution of respiratory proteins is due to several events of lateral gene transfer and/or massive gene loss. We conclude that the last common metazoan ancestor had at least two hemerythrin domains, one hemocyanin M domain, and six tyrosinase domains. The patchy distribution of these proteins among animal lineages can be partially explained by physiological adaptations, making these genes good targets for investigations into the interplay between genomic evolution and physiological constraints

Comparison of different vascular risk engines in the identification of type 2 diabetes patients with high cardiovascular risk

Background: Some authors consider that secondary prevention should be conducted for all DM2 patients, while others suggest that the drug preventive treatment should start or be increased depending on each patient's individual CVR, estimated using cardiovascular or coronary risk functions to identify the patients with a higher CVR. The principal objective of this study was to assess three different cardiovascular risk prediction models in type 2 diabetes patients. Methods: Multicentre, cross-sectional descriptive study of 3,041 patients with type 2 diabetes and no history of cardiovascular disease. The demographic, clinical, analytical, and cardiovascular risk factor variables associated with type 2 diabetes were analysed. The risk function and probability that a cardiovascular disease could occur were estimated using three risk engines: REGICOR, UKPDS and ADVANCE. A patient was considered to have a high cardiovascular risk when REGICOR ≥ 10 % or UKPDS ≥ 15 % in 10 years or when ADVANCE ≥ 8 % in 4 years. Results: The ADVANCE and UKPDS risk engines identified a higher number of diabetic patients with a high cardiovascular risk (24.2 % and 22.7 %, respectively) compared to the REGICOR risk engine (10.2 %). The correlation using the REGICOR risk engine was low compared to UKPDS and ADVANCE (r = 0.288 and r = 0.153, respectively; p < 0.0001). The agreement values in the allocation of a particular patient to the high risk group was low between the REGICOR engine and the UKPDS and ADVANCE engines (k = 0.205 and k = 0.123, respectively; p < 0.0001) and acceptable between the ADVANCE and UKPDS risk engines (k = 0.608). Conclusions: There are discrepancies between the general population and the type 2 diabetic patient-specific risk engines. The results of this study indicate the need for a prospective study which validates specific equations for diabetic patients in the Spanish population, as well as research on new models for cardiovascular risk prediction in these patients. Keywords: Type 2 diabetes, Cardiovascular risk prediction, Cardiovascular disease, Risk prediction models, Primary predictio

Relationship between Symptoms and Gene Expression Induced by the Infection of Three Strains of Rice dwarf virus

BACKGROUND: Rice dwarf virus (RDV) is the causal agent of rice dwarf disease, which often results in severe yield losses of rice in East Asian countries. The disease symptoms are stunted growth, chlorotic specks on leaves, and delayed and incomplete panicle exsertion. Three RDV strains, O, D84, and S, were reported. RDV-S causes the most severe symptoms, whereas RDV-O causes the mildest. Twenty amino acid substitutions were found in 10 of 12 virus proteins among three RDV strains. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the gene expression of rice in response to infection with the three RDV strains using a 60-mer oligonucleotide microarray to examine the relationship between symptom severity and gene responses. The number of differentially expressed genes (DEGs) upon the infection of RDV-O, -D84, and -S was 1985, 3782, and 6726, respectively, showing a correlation between the number of DEGs and symptom severity. Many DEGs were related to defense, stress response, and development and morphogenesis processes. For defense and stress response processes, gene silencing-related genes were activated by RDV infection and the degree of activation was similar among plants infected with the three RDV strains. Genes for hormone-regulated defense systems were also activated by RDV infection, and the degree of activation seemed to be correlated with the concentration of RDV in plants. Some development and morphogenesis processes were suppressed by RDV infection, but the degree of suppression was not correlated well with the RDV concentration. CONCLUSIONS/SIGNIFICANCE: Gene responses to RDV infection were regulated differently depending on the gene groups regulated and the strains infecting. It seems that symptom severity is associated with the degree of gene response in defense-related and development- and morphogenesis-related processes. The titer levels of RDV in plants and the amino acid substitutions in RDV proteins could be involved in regulating such gene responses

A multi-stakeholder multicriteria decision analysis for the reimbursement of orphan drugs (FinMHU-MCDA study)

Background: Patient access to orphan medicinal products (OMPs) is limited and varies between countries, reimbursement decisions on OMPs are complex, and there is a need for more transparent processes to know which criteria should be considered to inform these decisions. This study aimed to determine the most relevant criteria for the reimbursement of OMPs in Spain, from a multi-stakeholder perspective, and using multicriteria decision analysis (MCDA). Methods: An MCDA was developed in 3 phases and included 28 stakeholders closely related to the field of rare diseases (6 physicians, 5 hospital pharmacists, 7 health economists, 4 patient representatives and 6 members from national and regional health authorities). Initially [phase A], a bibliographic review was conducted to identify the potential reimbursement criteria. Then, a reduced advisory board (8 members) proposed, selected, and defined the final list of criteria that could be relevant for reimbursement. A discrete choice experiment (DCE) [phase B] was developed to determine the relevance and relative importance weight of such criteria according to the stakeholders’ preferences by choosing between pairs of hypothetical financing scenarios. A multinomial logit model was fitted to analyze the DCE responses. Finally [phase C], the advisory board review the results using a deliberative process. Results: Thirteen criteria were selected, related to 4 dimensions: patient population, disease, treatment, and economic evaluation. Nine criteria were deemed relevant for decision-making and associated with a higher relative importance: Health-related quality of life (HRQL) (23.53%), treatment efficacy (14.64%), availability of treatment alternatives (13.51%), disease severity (12.62%), avoided costs (11.21%), age of target population (7.75%), safety (seriousness of adverse events) (4.72%), quality of evidence (3.82%) and size of target population (3.12%). The remaining criteria had a < 3% relative importance: economic burden of disease (2.50%), cost of treatment (1.73%), cost-effectiveness (0.83%) and safety (frequency of adverse events) (0.03%). Conclusion: The reimbursement of OMPs in Spain should be determined by its effect on patient’s HRQL, the extent of its therapeutic benefit from efficacy and the availability of other therapeutic options. Furthermore, the severity of the rare disease should also influence the decision along with the potential of the treatment to avoid associated costs

Expression of two barley proteinase inhibitors in tomato promotes endogenous defensive response and enhances resistance to Tuta absoluta

[EN] Background: For as long as 350 million years, plants and insects have coexisted and developed a set of relationships which affect both organisms at different levels. Plants have evolved various morphological and biochemical adaptations to cope with herbivores attacks. However, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) has become the major pest threatening tomato crops worldwide and without the appropriated management it can cause production losses between 80 to 100%. Results: The aim of this study was to investigate the in vivo effect of a serine proteinase inhibitor (BTI-CMe) and a cysteine proteinase inhibitor (Hv-CPI2) from barley on this insect and to examine the effect their expression has on tomato defensive response. We found that larvae fed on the double transgenic plants showed a notable reduction in weight. Moreover, only 56% of the larvae reached the adult stage. The emerged adults showed wings deformities and reduced fertility. We also investigated the effect of proteinase inhibitors ingestion on the insect digestive enzymes. Our results showed a decrease in larval trypsin activity. Transgenes expression had no harmful effect on Nesidiocoris tenuis (Reuter) (Heteroptera: Miridae), a predator of Tuta absoluta, despite transgenic tomato plants attracted the mirid. We also found that barley cystatin expression promoted plant defense by inducing the expression of the tomato endogenous wound inducible Proteinase inhibitor 2 (Pin2) gene, increasing the production of glandular trichomes and altering the emission of volatile organic compounds. Conclusion: Our results demonstrate the usefulness of the co-expression of different proteinase inhibitors for the enhancement of plant resistance to Tuta absoluta.This work was partly supported by grants BIO2013-40747-R and AGL2014-55616-C3 from the Spanish Ministry of Economy and Competitiveness (MINECO)Hamza, R.; Pérez-Hedo, M.; Urbaneja, A.; Rambla Nebot, JL.; Granell Richart, A.; Gaddour, K.; Beltran Porter, JP.... (2018). Expression of two barley proteinase inhibitors in tomato promotes endogenous defensive response and enhances resistance to Tuta absoluta. BMC Plant Biology. 18. https://doi.org/10.1186/s12870-018-1240-6S18Oerke EC. Crop losses to pests. J Agric Sci. 2005;144(01):31.Jouanin L, Bonadé-Bottino M, Girard C, Morrot G, Giband M. Transgenic plants for insect resistance. Plant Sci. 1998;131(1):1–11.Markwick NP, Docherty LC, Phung MM, Lester MT, Murray C, Yao JL, Mitra DS, Cohen D, Beuning LL, Kutty-Amma S, et al. 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Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe