Ultrasound evaluation of interstitial lung disease in rheumatoid arthritis and autoimmune diseases

Lung ultrasound; Rheumatoid arthritis; Autoimmune diseasesEcografia pulmonar; Artritis reumatoide; Malalties autoimmunesEcografía pulmonar; Artritis reumatoide; Enfermedades autoinmunesThe interpretation of lung ultrasound (US) is the result of the analysis of artifacts, rather than exact representations of anatomical structures, which appear when changes in the physical properties of the lung occur. Its application to the study of interstitial lung disease (ILD) associated with autoimmune diseases has aroused great interest in the last 10 years, as evidenced by a growing number of publications studying its usefulness in the diagnostic process, as a prognostic marker, and as an aid in monitoring of patients. The main elements in lung US interpretation in ILD are the B lines and the changes in the pleural line. B lines are vertical artifacts that are generated when there is a partial decrease in the air content of the lung parenchyma and/or the volume of the interstitial area expands. Pleural line alterations that can be seen are irregularities, thickening, fragmentation, or subpleural nodules. Both the B lines and the changes in the pleural line have shown a significant positive correlation with the evidence on chest computed tomography (high-resolution computed tomography [HRCT]) of ILD associated with autoimmune diseases, with sensitivity and negative predictive values of up to 100%. These results, together with the safety, accessibility, and low cost of lung US, support this imaging technique as a promising screening method for optimizing the indication for HRCT. The role of lung US regarding sensitivity to change needs further investigation with multicenter prospective studie

Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents

Background: the DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) inhibits the killing of tumor cells by alkylating agents. MGMT activity is controlled by a promoter; methylation of the promoter silences the gene in cancer, and the cells no longer produce MGMT. We examined gliomas to determine whether methylation of the MGMT promoter is related to the responsiveness of the tumor to alkylating agents. Methods: we analyzed the MGMT promoter in tumor DNA by a methylation-specific polymerase-chain-reaction assay. The gliomas were obtained from patients who had been treated with carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea, or BCNU). The molecular data were correlated with the clinical outcome. Results: the MGMT promoter was methylated in gliomas from 19 of 47 patients (40 percent). This finding was associated with regression of the tumor and prolonged overall and disease-free survival. It was an independent and stronger prognostic factor than age, stage, tumor grade, or performance status. Conclusions: methylation of the MGMT promoter in gliomas is a useful predictor of the responsiveness of the tumors to alkylating agents

Pharmacological Interactions of Nintedanib and Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis in Times of COVID-19 Pandemic

The discovery of antifibrotic agents have resulted in advances in the therapeutic management of idiopathic pulmonary fibrosis (IPF). Currently, nintedanib and pirfenidone have become the basis of IPF therapy based on the results of large randomized clinical trials showing their safety and efficacy in reducing disease advancement. However, the goal of completely halting disease progress has not been reached yet. Administering nintedanib with add-on pirfenidone is supposed to enhance the therapeutic benefit by simultaneously acting on two different pathogenic pathways. All this becomes more important in the context of the ongoing global pandemic of coronavirus disease 2019 (COVID-19) because of the fibrotic consequences following SARS-CoV-2 infection in some patients. However, little information is available about their drug-drug interaction, which is important mainly in polymedicated patients. The aim of this review is to describe the current management of progressive fibrosing interstitial lung diseases (PF-ILDs) in general and of IPF in particular, focusing on the pharmacokinetic drug-drug interactions between these two drugs and their relationship with other medications in patients with IPF

Unmet needs in the management of cardiovascular risk in inflammatory joint diseases

Introduction: Increased cardiovascular (CV) morbidity and mortality is observed in inflammatory joint diseases (IJDs) such as rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. However, the management of CV disease in these conditions is far from being well established.Areas covered: This review summarizes the main epidemiologic, pathophysiological, and clinical risk factors of CV disease associated with IJDs. Less common aspects on early diagnosis and risk stratification of the CV disease in these conditions are also discussed. In Europe, the most commonly used risk algorithm in patients with IJDs is the modified SCORE index based on the revised recommendations proposed by the EULAR task force in 2017.Expert opinion: Early identification of IJD patients at high risk of CV disease is essential. It should include the use of complementary noninvasive imaging techniques. A multidisciplinary approach aimed to improve heart-healthy habits, including strict control of classic CV risk factors is crucial. Adequate management of the underlying IJD is also of main importance since the reduction of disease activity decreases the risk of CV events. Non-steroidal anti-inflammatory drugs may have a lesser harmful effect in IJD than in the general population, due to their anti-inflammatory effects along with other potential beneficial effects.MA González-Gay’s research has been supported by grants from “Fondo de Investigaciones Sanitarias” PI06/0024, PS09/00748, PI12/00060, PI15/00525,PI18/00043, and RD12/0009/0013 and RD16/0012 (RIER) from “Instituto de Salud Carlos III” (ISCIII) (Spain), co-funded by FEDER funds

Treatment of polymyalgia rheumatica

Polymyalgia rheumatica (PMR) is an inflammatory disease characterized by bilateral pain involving predominantly the shoulders and proximal aspects of the arms and less commonly the neck and the pelvic girdle. This review discusses briefly the main epidemiological data and clinical features of this condition. Especial attention is paid in the management of the disease. For this reason, both the classic management and the impact of new therapies are discussed in depth. In general, patients with PMR experience a rapid response to 12.5-25?mg/prednisone/day in less than a week. Patients with poor response to glucocorticoids or with relapsing disease require other therapies aimed mainly to spare glucocorticoids. Among them, methotrexate is the most commonly used. Nevertheless, different studies indicate that this agent yields only a modest effect. Biologic therapies against the main cytokines involved in the pathogenesis of the disease have been used in refractory patients. However, randomized controlled trials do not support the use of anti-tumor necrosis factor agents in PMR. In contrast, several case series and retrospective studies highlight the efficacy of the anti-interleukin-6 receptor tocilizumab in PMR. Nonetheless, controlled trials are needed to fully establish the beneficial effect of this agent. The potential favorable effect of the Janus-kinase inhibitors and new anti-interleukin-6 antagonists remains to be determined

High-throughput molecular technologies for unraveling the mystery of soil microbial community: challenges and future prospects

Soil microbial communities play a crucial role in soil fertility, sustainability, and plant health. However, intensive agriculture with increasing chemical inputs and changing environments have influenced native soil microbial communities. Approaches have been developed to study the structure, diversity, and activity of soil microbes to better understand the biology and plant-microbe interactions in soils. Unfortunately, a good understanding of soil microbial community remains a challenge due to the complexity of community composition, interactions of the soil environment, and limitations of technologies, especially related to the functionality of some taxa rarely detected using conventional techniques. Culture-based methods have been shown unable and sometimes are biased for assessing soil microbial communities. To gain further knowledge, culture-independent methods relying on direct analysis of nucleic acids, proteins, and lipids are worth exploring. In recent years, metagenomics, metaproteomics, metatranscriptomics, and proteogenomics have been increasingly used in studying microbial ecology. In this review, we examined the importance of microbial community to soil quality, the mystery of rhizosphere and plant-microbe interactions, and the biodiversity and multi-trophic interactions that influence the soil structure and functionality. The impact of the cropping system and climate change on the soil microbial community was also explored. Importantly, progresses in molecular biology, especially in the development of high-throughput biotechnological tools, were extensively assessed for potential uses to decipher the diversity and dynamics of soil microbial communities, with the highlighted advantages/limitations

Tomato floral induction and flower development are orchestrated by the interplay between gibberellin and two unrelated microRNA-controlled modules

[EN] Age-regulated microRNA156 (miR156) and targets similarly control the competence to flower in diverse species. By contrast, the diterpene hormone gibberellin (GA) and the microRNA319-regulated TEOSINTE BRANCHED/CYCLOIDEA/PCF (TCP) transcription factors promote flowering in the facultative long-day Arabidopsis thaliana, but suppress it in the day-neutral tomato (Solanum lycopersicum). We combined genetic and molecular studies and described a new interplay between GA and two unrelated miRNA-associated pathways that modulates tomato transition to flowering. Tomato PROCERA/DELLA activity is required to promote flowering along with the miR156-targeted SQUAMOSA PROMOTER BINDING-LIKE (SPL/SBP) transcription factors by activating SINGLE FLOWER TRUSS (SFT) in the leaves and the MADS-Boxgene APETALA1(AP1)/MC at the shoot apex. Conversely, miR319-targeted LANCEOLATE represses floral transition by increasing GA concentrations and inactivating SFT in the leaves and AP1/MC at the shoot apex. Importantly, the combination of high GA concentrations/responses with the loss of SPL/SPB function impaired canonical meristem maturation and flower initiation in tomato. Our results reveal a cooperative regulation of tomato floral induction and flower development, integrating age cues (miR156 module) with GA responses and miR319-controlled pathways. Importantly, this study contributes to elucidate the mechanisms underlying the effects of GA in controlling flowering time in a day-neutral species.We thank Dr C. Schommer for kindly providing tcp4-soj8/+ seeds, and Carlos Rojas for Arabidopsis flowering time analyses. This work was supported by FAPESP (grant no. 15/17892-7 and fellowships nos 15/23826-7 and 13/16949-0). The authors declare no conflict of interest.Silva, G.; Silva, E.; Correa, J.; Vicente, M.; Jiang, N.; Notini, M.; Junior, A.... (2018). Tomato floral induction and flower development are orchestrated by the interplay between gibberellin and two unrelated microRNA-controlled modules. New Phytologist. 221(3):1328-1344. https://doi.org/10.1111/nph.15492S132813442213Andrés, F., & Coupland, G. (2012). The genetic basis of flowering responses to seasonal cues. Nature Reviews Genetics, 13(9), 627-639. doi:10.1038/nrg3291Bassel, G. W., Mullen, R. T., & Bewley, J. D. (2008). procerais a putative DELLA mutant in tomato (Solanum lycopersicum): effects on the seed and vegetative plant. Journal of Experimental Botany, 59(3), 585-593. doi:10.1093/jxb/erm354Ben‐Naim, O., Eshed, R., Parnis, A., Teper‐Bamnolker, P., Shalit, A., Coupland, G., … Lifschitz, E. (2006). The CCAAT binding factor can mediate interactions between CONSTANS‐like proteins and DNA. The Plant Journal, 46(3), 462-476. doi:10.1111/j.1365-313x.2006.02706.xBoss, P. K., & Thomas, M. R. (2002). Association of dwarfism and floral induction with a grape ‘green revolution’ mutation. Nature, 416(6883), 847-850. doi:10.1038/416847aBurko, Y., Shleizer-Burko, S., Yanai, O., Shwartz, I., Zelnik, I. D., Jacob-Hirsch, J., … Ori, N. (2013). A Role for APETALA1/FRUITFULL Transcription Factors in Tomato Leaf Development. The Plant Cell, 25(6), 2070-2083. doi:10.1105/tpc.113.113035Cardon, G., Höhmann, S., Klein, J., Nettesheim, K., Saedler, H., & Huijser, P. (1999). Molecular characterisation of the Arabidopsis SBP-box genes. Gene, 237(1), 91-104. doi:10.1016/s0378-1119(99)00308-xCarrera, E., Ruiz-Rivero, O., Peres, L. E. P., Atares, A., & Garcia-Martinez, J. L. (2012). Characterization of the procera Tomato Mutant Shows Novel Functions of the SlDELLA Protein in the Control of Flower Morphology, Cell Division and Expansion, and the Auxin-Signaling Pathway during Fruit-Set and Development. Plant Physiology, 160(3), 1581-1596. doi:10.1104/pp.112.204552Carvalho, R. F., Campos, M. L., Pino, L. E., Crestana, S. L., Zsögön, A., Lima, J. E., … Peres, L. E. (2011). Convergence of developmental mutants into a single tomato model system: «Micro-Tom» as an effective toolkit for plant development research. Plant Methods, 7(1), 18. doi:10.1186/1746-4811-7-18Cubas, P., Lauter, N., Doebley, J., & Coen, E. (1999). The TCP domain: a motif found in proteins regulating plant growth and development. The Plant Journal, 18(2), 215-222. doi:10.1046/j.1365-313x.1999.00444.xDavière, J.-M., Wild, M., Regnault, T., Baumberger, N., Eisler, H., Genschik, P., & Achard, P. (2014). Class I TCP-DELLA Interactions in Inflorescence Shoot Apex Determine Plant Height. Current Biology, 24(16), 1923-1928. doi:10.1016/j.cub.2014.07.012Silva, G. F. F. e, Silva, E. M., da Silva Azevedo, M., Guivin, M. A. C., Ramiro, D. A., Figueiredo, C. R., … Nogueira, F. T. S. (2014). microRNA156-targeted SPL/SBP box transcription factors regulate tomato ovary and fruit development. The Plant Journal, 78(4), 604-618. doi:10.1111/tpj.12493Gallego-Bartolome, J., Minguet, E. G., Marin, J. A., Prat, S., Blazquez, M. A., & Alabadi, D. (2010). Transcriptional Diversification and Functional Conservation between DELLA Proteins in Arabidopsis. Molecular Biology and Evolution, 27(6), 1247-1256. doi:10.1093/molbev/msq012Gallego-Giraldo, L., García-Martínez, J. L., Moritz, T., & López-Díaz, I. (2007). Flowering in Tobacco Needs Gibberellins but is not Promoted by the Levels of Active GA1 and GA4 in the Apical Shoot. Plant and Cell Physiology, 48(4), 615-625. doi:10.1093/pcp/pcm034Galvao, V. C., Horrer, D., Kuttner, F., & Schmid, M. (2012). Spatial control of flowering by DELLA proteins in Arabidopsis thaliana. Development, 139(21), 4072-4082. doi:10.1242/dev.080879García-Hurtado, N., Carrera, E., Ruiz-Rivero, O., López-Gresa, M. P., Hedden, P., Gong, F., & García-Martínez, J. L. (2012). The characterization of transgenic tomato overexpressing gibberellin 20-oxidase reveals induction of parthenocarpic fruit growth, higher yield, and alteration of the gibberellin biosynthetic pathway. Journal of Experimental Botany, 63(16), 5803-5813. doi:10.1093/jxb/ers229Gargul, J. M., Mibus, H., & Serek, M. (2013). Constitutive overexpression of Nicotiana GA 2 ox leads to compact phenotypes and delayed flowering in Kalanchoë blossfeldiana and Petunia hybrida. Plant Cell, Tissue and Organ Culture (PCTOC), 115(3), 407-418. doi:10.1007/s11240-013-0372-5Goldberg-Moeller, R., Shalom, L., Shlizerman, L., Samuels, S., Zur, N., Ophir, R., … Sadka, A. (2013). Effects of gibberellin treatment during flowering induction period on global gene expression and the transcription of flowering-control genes in Citrus buds. Plant Science, 198, 46-57. doi:10.1016/j.plantsci.2012.09.012Hauvermale, A. L., Ariizumi, T., & Steber, C. M. (2012). Gibberellin Signaling: A Theme and Variations on DELLA Repression. Plant Physiology, 160(1), 83-92. doi:10.1104/pp.112.200956Hyun, Y., Richter, R., Vincent, C., Martinez-Gallegos, R., Porri, A., & Coupland, G. (2016). Multi-layered Regulation of SPL15 and Cooperation with SOC1 Integrate Endogenous Flowering Pathways at the Arabidopsis Shoot Meristem. Developmental Cell, 37(3), 254-266. doi:10.1016/j.devcel.2016.04.001Itoh, H., Ueguchi-Tanaka, M., Sato, Y., Ashikari, M., & Matsuoka, M. (2002). The Gibberellin Signaling Pathway Is Regulated by the Appearance and Disappearance of SLENDER RICE1 in Nuclei. The Plant Cell, 14(1), 57-70. doi:10.1105/tpc.010319Jung, J.-H., Ju, Y., Seo, P. J., Lee, J.-H., & Park, C.-M. (2011). The SOC1-SPL module integrates photoperiod and gibberellic acid signals to control flowering time in Arabidopsis. The Plant Journal, 69(4), 577-588. doi:10.1111/j.1365-313x.2011.04813.xKing, R. W., & Ben-Tal, Y. (2001). A Florigenic Effect of Sucrose in Fuchsia hybrida Is Blocked by Gibberellin-Induced Assimilate Competition. Plant Physiology, 125(1), 488-496. doi:10.1104/pp.125.1.488Kubota, A., Ito, S., Shim, J. S., Johnson, R. S., Song, Y. H., Breton, G., … Imaizumi, T. (2017). TCP4-dependent induction of CONSTANS transcription requires GIGANTEA in photoperiodic flowering in Arabidopsis. PLOS Genetics, 13(6), e1006856. doi:10.1371/journal.pgen.1006856Kudla, J., & Bock, R. (2016). Lighting the Way to Protein-Protein Interactions: Recommendations on Best Practices for Bimolecular Fluorescence Complementation Analyses. The Plant Cell, 28(5), 1002-1008. doi:10.1105/tpc.16.00043Lifschitz, E., Eviatar, T., Rozman, A., Shalit, A., Goldshmidt, A., Amsellem, Z., … Eshed, Y. (2006). The tomato FT ortholog triggers systemic signals that regulate growth and flowering and substitute for diverse environmental stimuli. Proceedings of the National Academy of Sciences, 103(16), 6398-6403. doi:10.1073/pnas.0601620103Liu, J., Cheng, X., Liu, P., Li, D., Chen, T., Gu, X., & Sun, J. (2017). MicroRNA319-regulated TCPs interact with FBHs and PFT1 to activate CO transcription and control flowering time in Arabidopsis. PLOS Genetics, 13(5), e1006833. doi:10.1371/journal.pgen.1006833Livak, K. J., & Schmittgen, T. D. (2001). Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method. Methods, 25(4), 402-408. doi:10.1006/meth.2001.1262Livne, S., Lor, V. S., Nir, I., Eliaz, N., Aharoni, A., Olszewski, N. E., … Weiss, D. (2015). Uncovering DELLA-Independent Gibberellin Responses by Characterizing New Tomato procera Mutants. The Plant Cell, 27(6), 1579-1594. doi:10.1105/tpc.114.132795Lombardi-Crestana, S., da Silva Azevedo, M., e Silva, G. F. F., Pino, L. E., Appezzato-da-Glória, B., Figueira, A., … Peres, L. E. P. (2012). The Tomato (Solanum Lycopersicum cv. Micro-Tom) Natural Genetic Variation Rg1 and the DELLA Mutant Procera Control the Competence Necessary to Form Adventitious Roots and Shoots. Journal of Experimental Botany, 63(15), 5689-5703. doi:10.1093/jxb/ers221Lozano, R., Gimenez, E., Cara, B., Capel, J., & Angosto, T. (2009). Genetic analysis of reproductive development in tomato. The International Journal of Developmental Biology, 53(8-9-10), 1635-1648. doi:10.1387/ijdb.072440rlMartin, K., Kopperud, K., Chakrabarty, R., Banerjee, R., Brooks, R., & Goodin, M. M. (2009). Transient expression inNicotiana benthamianafluorescent marker lines provides enhanced definition of protein localization, movement and interactionsin planta. The Plant Journal, 59(1), 150-162. doi:10.1111/j.1365-313x.2009.03850.xMartínez-Bello, L., Moritz, T., & López-Díaz, I. (2015). Silencing C19-GA 2-oxidases induces parthenocarpic development and inhibits lateral branching in tomato plants. Journal of Experimental Botany, 66(19), 5897-5910. doi:10.1093/jxb/erv300Meissner, R., Chague, V., Zhu, Q., Emmanuel, E., Elkind, Y., & Levy, A. A. (2000). A high throughput system for transposon tagging and promoter trapping in tomato. The Plant Journal, 22(3), 265-274. doi:10.1046/j.1365-313x.2000.00735.xMolinero-Rosales, N., Jamilena, M., Zurita, S., Gomez, P., Capel, J., & Lozano, R. (1999). FALSIFLORA, the tomato orthologue of FLORICAULA and LEAFY, controls flowering time and floral meristem identity. The Plant Journal, 20(6), 685-693. doi:10.1046/j.1365-313x.1999.00641.xMorea, E. G. O., da Silva, E. M., e Silva, G. F. F., Valente, G. T., Barrera Rojas, C. H., Vincentz, M., & Nogueira, F. T. S. (2016). Functional and evolutionary analyses of the miR156 and miR529 families in land plants. BMC Plant Biology, 16(1). doi:10.1186/s12870-016-0716-5Mounet, F., Moing, A., Garcia, V., Petit, J., Maucourt, M., Deborde, C., … Lemaire-Chamley, M. (2009). Gene and Metabolite Regulatory Network Analysis of Early Developing Fruit Tissues Highlights New Candidate Genes for the Control of Tomato Fruit Composition and Development. Plant Physiology, 149(3), 1505-1528. doi:10.1104/pp.108.133967Nir, I., Shohat, H., Panizel, I., Olszewski, N., Aharoni, A., & Weiss, D. (2017). The Tomato DELLA Protein PROCERA Acts in Guard Cells to Promote Stomatal Closure. The Plant Cell, 29(12), 3186-3197. doi:10.1105/tpc.17.00542Ohad, N., Shichrur, K., & Yalovsky, S. (2007). The Analysis of Protein-Protein Interactions in Plants by Bimolecular Fluorescence Complementation. Plant Physiology, 145(4), 1090-1099. doi:10.1104/pp.107.107284Ori, N., Cohen, A. R., Etzioni, A., Brand, A., Yanai, O., Shleizer, S., … Eshed, Y. (2007). Regulation of LANCEOLATE by miR319 is required for compound-leaf development in tomato. Nature Genetics, 39(6), 787-791. doi:10.1038/ng2036Pal, S., Zhao, J., Khan, A., Yadav, N. S., Batushansky, A., Barak, S., … Rachmilevitch, S. (2016). Paclobutrazol induces tolerance in tomato to deficit irrigation through diversified effects on plant morphology, physiology and metabolism. Scientific Reports, 6(1). doi:10.1038/srep39321Palatnik, J. F., Wollmann, H., Schommer, C., Schwab, R., Boisbouvier, J., Rodriguez, R., … Weigel, D. (2007). Sequence and Expression Differences Underlie Functional Specialization of Arabidopsis MicroRNAs miR159 and miR319. Developmental Cell, 13(1), 115-125. doi:10.1016/j.devcel.2007.04.012Parapunova, V., Busscher, M., Busscher-Lange, J., Lammers, M., Karlova, R., Bovy, A. G., … de Maagd, R. A. (2014). Identification, cloning and characterization of the tomato TCP transcription factor family. BMC Plant Biology, 14(1), 157. doi:10.1186/1471-2229-14-157Park, S. J., Jiang, K., Schatz, M. C., & Lippman, Z. B. (2011). Rate of meristem maturation determines inflorescence architecture in tomato. Proceedings of the National Academy of Sciences, 109(2), 639-644. doi:10.1073/pnas.1114963109Pharis, R. P., & King, R. W. (1985). Gibberellins and Reproductive Development in Seed Plants. Annual Review of Plant Physiology, 36(1), 517-568. doi:10.1146/annurev.pp.36.060185.002505Porri, A., Torti, S., Romera-Branchat, M., & Coupland, G. (2012). Spatially distinct regulatory roles for gibberellins in the promotion of flowering of Arabidopsis under long photoperiods. Development, 139(12), 2198-2209. doi:10.1242/dev.077164Preston, J. C., & Hileman, L. C. (2013). Functional Evolution in the Plant SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL) Gene Family. Frontiers in Plant Science, 4. doi:10.3389/fpls.2013.00080Reinecke, D. M., Wickramarathna, A. D., Ozga, J. A., Kurepin, L. V., Jin, A. L., Good, A. G., & Pharis, R. P. (2013). Gibberellin 3-oxidase Gene Expression Patterns Influence Gibberellin Biosynthesis, Growth, and Development in Pea. PLANT PHYSIOLOGY, 163(2), 929-945. doi:10.1104/pp.113.225987Rubio-Somoza, I., & Weigel, D. (2011). MicroRNA networks and developmental plasticity in plants. Trends in Plant Science, 16(5), 258-264. doi:10.1016/j.tplants.2011.03.001Rubio-Somoza, I., Zhou, C.-M., Confraria, A., Martinho, C., von Born, P., Baena-Gonzalez, E., … Weigel, D. (2014). Temporal Control of Leaf Complexity by miRNA-Regulated Licensing of Protein Complexes. Current Biology, 24(22), 2714-2719. doi:10.1016/j.cub.2014.09.058Salinas, M., Xing, S., Höhmann, S., Berndtgen, R., & Huijser, P. (2011). Genomic organization, phylogenetic comparison and differential expression of the SBP-box family of transcription factors in tomato. Planta, 235(6), 1171-1184. doi:10.1007/s00425-011-1565-ySarvepalli, K., & Nath, U. (2011). Hyper-activation of the TCP4 transcription factor in Arabidopsis thaliana accelerates multiple aspects of plant maturation. The Plant Journal, 67(4), 595-607. doi:10.1111/j.1365-313x.2011.04616.xSerrano-Mislata, A., Bencivenga, S., Bush, M., Schiessl, K., Boden, S., & Sablowski, R. (2017). DELLA genes restrict inflorescence meristem function independently of plant height. Nature Plants, 3(9), 749-754. doi:10.1038/s41477-017-0003-yShikata, M., & Ezura, H. (2016). Micro-Tom Tomato as an Alternative Plant Model System: Mutant Collection and Efficient Transformation. Methods in Molecular Biology, 47-55. doi:10.1007/978-1-4939-3115-6_5Stettler, R. F. (1964). DOSAGE EFFECTS OF THE LANCEOLATE GENE IN TOMATO. American Journal of Botany, 51(3), 253-264. doi:10.1002/j.1537-2197.1964.tb06628.xVarkonyi-Gasic, E., Wu, R., Wood, M., Walton, E. F., & Hellens, R. P. (2007). Protocol: a highly sensitive RT-PCR method for detection and quantification of microRNAs. Plant Methods, 3(1), 12. doi:10.1186/1746-4811-3-12Vendemiatti, E., Zsögön, A., Silva, G. F. F. e, de Jesus, F. A., Cutri, L., Figueiredo, C. R. F., … Peres, L. E. P. (2017). Loss of type-IV glandular trichomes is a heterochronic trait in tomato and can be reverted by promoting juvenility. Plant Science, 259, 35-47. doi:10.1016/j.plantsci.2017.03.006Vicente, M. H., Zsögön, A., de Sá, A. F. L., Ribeiro, R. V., & Peres, L. E. P. (2015). Semi-determinate growth habit adjusts the vegetative-to-reproductive balance and increases productivity and water-use efficiency in tomato ( Solanum lycopersicum ). Journal of Plant Physiology, 177, 11-19. doi:10.1016/j.jplph.2015.01.003Wang, J.-W., Czech, B., & Weigel, D. (2009). miR156-Regulated SPL Transcription Factors Define an Endogenous Flowering Pathway in Arabidopsis thaliana. Cell, 138(4), 738-749. doi:10.1016/j.cell.2009.06.014Wilkie, J. D., Sedgley, M., & Olesen, T. (2008). Regulation of floral initiation in horticultural trees. Journal of Experimental Botany, 59(12), 3215-3228. doi:10.1093/jxb/ern188Yamaguchi, A., Wu, M.-F., Yang, L., Wu, G., Poethig, R. S., & Wagner, D. (2009). The MicroRNA-Regulated SBP-Box Transcription Factor SPL3 Is a Direct Upstream Activator of LEAFY, FRUITFULL, and APETALA1. Developmental Cell, 17(2), 268-278. doi:10.1016/j.devcel.2009.06.007Yamaguchi, N., Winter, C. M., Wu, M.-F., Kanno, Y., Yamaguchi, A., Seo, M., & Wagner, D. (2014). Gibberellin Acts Positively Then Negatively to Control Onset of Flower Formation in Arabidopsis. Science, 344(6184), 638-641. doi:10.1126/science.1250498Yamaguchi, S. (2008). Gibberellin Metabolism and its Regulation. Annual Review of Plant Biology, 59(1), 225-251. doi:10.1146/annurev.arplant.59.032607.092804Yamamoto, A., Nakamura, T., Adu-Gyamfi, J. J., & Saigusa, M. (2002). RELATIONSHIP BETWEEN CHLOROPHYLL CONTENT IN LEAVES OF SORGHUM AND PIGEONPEA DETERMINED BY EXTRACTION METHOD AND BY CHLOROPHYLL METER (SPAD-502). Journal of Plant Nutrition, 25(10), 2295-2301. doi:10.1081/pln-120014076Yanai, O., Shani, E., Russ, D., & Ori, N. (2011). Gibberellin partly mediates LANCEOLATE activity in tomato. The Plant Journal, 68(4), 571-582. doi:10.1111/j.1365-313x.2011.04716.xYu, S., Galvão, V. C., Zhang, Y.-C., Horrer, D., Zhang, T.-Q., Hao, Y.-H., … Wang, J.-W. (2012). Gibberellin Regulates the Arabidopsis Floral Transition through miR156-Targeted SQUAMOSA PROMOTER BINDING–LIKE Transcription Factors. The Plant Cell, 24(8), 3320-3332. doi:10.1105/tpc.112.101014Yuste-Lisbona, F. J., Quinet, M., Fernández-Lozano, A., Pineda, B., Moreno, V., Angosto, T., & Lozano, R. (2016). Characterization of vegetative inflorescence (mc-vin) mutant provides new insight into the role of MACROCALYX in regulating inflorescence development of tomato. Scientific Reports, 6(1). doi:10.1038/srep18796Zhang, S., Zhang, D., Fan, S., Du, L., Shen, Y., Xing, L., … Han, M. (2016). Effect of exogenous GA 3 and its inhibitor paclobutrazol on floral formation, endogenous hormones, and flowering-associated genes in ‘Fuji’ apple ( Malus domestica Borkh.). Plant Physiology and Biochemistry, 107, 178-186. doi:10.1016/j.plaphy.2016.06.005Zhang, X., Zou, Z., Zhang, J., Zhang, Y., Han, Q., Hu, T., … Ye, Z. (2010). Over-expression of sly-miR156a in tomato results in multiple vegetative and reproductive trait alterations and partial phenocopy of the sft mutant. FEBS Letters, 585(2), 435-439. doi:10.1016/j.febslet.2010.12.03

Consensus-based recommendations on physical activity and exercise in patients with diabetes at risk of foot ulcerations: a Delphi study

Background Patients with diabetes mellitus are exposed to important complications. Currently little evidence exist on the guidelines that these patients, at some risk of foot ulceration, should follow for physical exercise. Objectives To reach a consensus among multidisciplinary and international experts on physical activity/exercise recommendations for patients with diabetes, according to foot ulcer risk. Methods Using a three-round Delphi method, a panel composed of 28 multidisciplinary experts in the management of diabetic foot assessed 109 recommendations on physical activity/exercise for patients with diabetes mellitus, according to their risk of foot ulcer. Consensus was assumed when 80% of responses matched the same category (agreement/disagreement). Results Twenty-nine experts participated in the first and second rounds of consultation, and twenty-eight did so in the third, reaching final agreement on 86 of the 109 recommendations considered (78.9%). The study, thus, generated a consensus set of recommendations concerning different aspects of diabetic footcare before, during, and after exercise (e.g. when to examine the foot, how to assess it, what type of sock and insole to use, what types of exercise to perform, and when it is advisable to return to activity after an ulceration). Conclusion This Delphi study generated recommendations based on the consensus of international experts on physical activity and exercise by patient with diabetes at risk of ulceration. Recommendations considered the state of the foot and the patient's history and status before physical activity and included information on intensity, duration, frequency, and progressions of physical activity/exercise, and the use of custom-made plantar orthoses, shoe prescription, and the convenience of returning to physical activity after an ulceration

El estudio PROPRESE: resultados de un nuevo modelo organizativo en atención primaria para pacientes con cardiopatía isquémica crónica basado en una intervención multifactorial

ResumenObjetivoComparando los resultados obtenidos en los estudios EUROASPIRE I y EUROASPIRE III en pacientes con cardiopatía isquémica se muestra que el grado de control de los factores de riesgo mayores es mejorable. El objetivo de este estudio es evaluar la eficacia de una intervención multifactorial orientada a la mejora del grado de control en estos pacientes en el ámbito de la atención primaria.MétodosEn este estudio de intervención aleatorizado, con 1 año de seguimiento, se reclutó a pacientes con diagnóstico de cardiopatía isquémica (145 en el grupo de intervención y 1.461 en el grupo control). Se aplicó una intervención organizativa mixta basada en la mejora de la relación profesional sanitario-paciente (de acuerdo a los modelos del Chronic Care, el Stanford Expert Patient Programme y el Kaiser Permanente) y en la formación profesional continuada. Los principales resultados fueron el efecto sobre el tabaquismo, el colesterol unido a lipoproteínas de baja densidad (cLDL), la presión arterial sistólica (PAS) y la presión arterial diastólica (PAD) a través de un análisis multivariable.ResultadosLas características de los pacientes fueron: edad (68,4±11,8 años), varones (71,6%), diabetes mellitus (51,3%), dislipemia (68,5%), hipertensión arterial (76,7%), no fumadores (76,1%); cLDL < 100mg/dl (46,9%); PAS < 140mmHg (64,5%); PAD < 90 (91,2%). El análisis multivariable mostró que el riesgo para el buen control en el grupo de intervención fue tabaquismo, riesgo relativo ajustado (RRa): 15,7 (intervalo de confianza del 95% [IC95%], 4,2–58,7); p < 0,001; cLDL, RRa: 2,98 (IC95%, 1,48–6,02); p < 0,002; PAS, RRa: 1.97 (IC95%, 1,21–3,23); p < 0,007, y PAD; RRa: 1,51 (IC95%, 0,65–3,50); p < 0,342.ConclusionesUna intervención multifactorial basada en el modelo de paciente crónico centrada en atención primaria y que facilite la toma de decisiones compartidas con los pacientes y la formación de los profesionales mejora el grado de control de los factores de riesgo cardiovascular (tabaquismo, cLDL y PAS). Las estrategias de mejora en la atención de la cronicidad pueden ser una herramienta eficaz para conseguir mejores resultados.AbstractObjectiveComparison of the results from the EUROASPIRE I to the EUROASPIRE III, in patients with coronary heart disease, shows that the prevalence of uncontrolled risk factors remains high. The aim of the study was to evaluate the effectiveness of a new multifactorial intervention in order to improve health care for chronic coronary heart disease patients in primary care.MethodsIn this randomized clinical trial with a 1-year follow-up period, we recruited patients with a diagnosis of coronary heart disease (145 for the intervention group and 1461 for the control group). An organizational intervention on the patient-professional relationship (centered on the Chronic Care Model, the Stanford Expert Patient Programme and the Kaiser Permanente model) and formative strategy for professionals were carried out. The main outcomes were smoking control, low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP). A multivariate analysis was performed.ResultsThe characteristics of patients were: age (68.4±11.8 years), male (71.6%), having diabetes mellitus (51.3%), dyslipidemia (68.5%), arterial hypertension (76.7%), non-smokers (76.1%); LDL-C < 100mg/dL (46.9%); SBP < 140mmHg (64.5%); DBP < 90 (91.2%). The multivariable analysis showed the risk of good control for intervention group to be: smoking, adjusted relative risk (aRR): 15.70 (95% confidence interval [95%CI], 4.2–58.7); P < .001; LDL-C, aRR: 2.98 (95%CI, 1.48–6.02); P < .002; SPB, aRR: 1.97 (95%CI, 1.21–3.23); P < .007, and DBP: aRR: 1.51 (95%CI, 0.65–3.50); P < .342.ConclusionsAn intervention based on models for chronic patients focused in primary care and involving patients in medical decision making improves cardiovascular risk factors control (smoking, LDL-C and SBP). Chronic care strategies may be an efficacy tool to help clinicians to involve the patients with a diagnosis of CHD to reach better outcomes

NEMA NU 4-2008 Comparison of preclinical PET imaging systems

The National Electrical Manufacturers Association (NEMA) standard NU 4-2008 for performance measurements of smallanimal tomographs was recently published. Before this standard, there were no standard testing procedures for preclinical PET systems, and manufacturers could not provide clear specifications similar to those available for clinical systems under NEMA NU 2-1994 and 2-2001. Consequently, performance evaluation papers used methods that were modified ad hoc from the clinical PET NEMA standard, thus making comparisons between systems difficult. Methods: We acquired NEMA NU 4-2008 performance data for a collection of commercial animal PET systems manufactured since 2000: micro- PET P4, microPET R4, microPET Focus 120, microPET Focus 220, Inveon, ClearPET, Mosaic HP, Argus (formerly eXplore Vista), VrPET, LabPET 8, and LabPET 12. The data included spatial resolution, counting-rate performance, scatter fraction, sensitivity, and image quality and were acquired using settings for routine PET. Results: The data showed a steady improvement in system performance for newer systems as compared with first-generation systems, with notable improvements in spatial resolution and sensitivity. Conclusion: Variation in system design makes direct comparisons between systems from different vendors difficult. When considering the results from NEMA testing, one must also consider the suitability of the PET system for the specific imaging task at hand.This work was funded by the Natural Sciences and Engineering Research Council of Canada under Discovery Grant 341628-2007. No other potential conflict of interest relevant to this article was reported.En prens