Assessment of the implantation of day-2 human embryos by morphometric nonsubjective parameters

Discuss: You can discuss this article with its authors and with other ASRM members at http:// fertstertforum.com/molinai-implantation-morphometric-nonsubjective/Objective: To demonstrate the usefulness of image analysis in designing objective embryonic morphometric variables. Design: Retrospective study of 214 top-quality day-2 embryo photographs from 50 double-embryo transfers resulting in no pregnancy (group 0) and 57 resulting in twin pregnancy (group 1). Setting: Human reproduction unit. Patient(s): Study of 107 in vitro fertilization intracytoplasmic sperm injection (IVF ICSI) cycles in women age<36 years with doubleembryo transfer of top-quality embryos. Only the first cycle of IVF ICSI was included. Intervention(s): Standard IVF ICSI protocols. Main Outcome Measure(s): The embryo photographs were analyzed using the ImageJ program. The effects of the embryo variables and the clinical variables on embryo implantation were evaluated using a stepwise dichotomous logistic regression. Result(s): Significant differences were observed, owing to the women's ages, internal perimeter, roundness factor, and zona pellucida thickness. Embryos with smaller internal perimeter, circular shape, and thinner zona pellucida were more likely to implant. Conclusion(s): Morphometric variables lower the subjectivity of the current embryo grading systems. These variables are nonsubjective factors to consider when predicting implantation. Embryo image analysis is an accurate tool that can improve IVF ICSI outcomes and reduce the number of twin pregnancies. (Fertil Steril 2014;102:1022 8. 2014 by American Society for Reproductive Medicine.) Key Words: Embryo selection, embryo score, morphological and morphometric embryo variables, images analysis, embryo implantation, embryo grading systemsMolina Botella, MI.; Martinez-Sanchez, JV.; Pertusa, J.; Balasch Parisi, S.; Iniesta, I.; Pellicer, A. (2014). Assessment of the implantation of day-2 human embryos by morphometric nonsubjective parameters. Fertility and Sterility. 102(4):1022-1027. doi:10.1016/j.fertnstert.2014.06.026S10221027102

Application of high Power ultrasounds during red wine vinification

[EN] Wine colour is one of the main organoleptic characteristics influencing its quality. It is of special interest in red vinifications due to the economic resources that wineries have to invest for the extraction of the phenolic compounds responsible for wine colour, compounds that are mainly located inside the skin cell vacuoles, where the volatile compounds are also found. The transfer of phenolic compounds from grapes to must during vinification is closely related to the type of grapes and the winemaking technique. During traditional winemaking, grapes are crushed and skin macerated for several days, with pumps overs to facilitate the colour extraction. To increase this extraction, some chemical (maceration enzymes) or physical technologies (thermovinification, cryomaceration, flash-expansion) can be applied. In this work, a new methodology has been tested. This methodology consists in the application of high-power ultrasounds to crushed grapes to increase the extraction of phenolic compounds. Crushed grapes were treated with this non-thermal technology and vinified, with 3, 6 and 8days of skin maceration time, and the results were compared with a control vinification, where crushed grapes were not subjected to any treatment and were skin macerated during 8days. The wine chromatic characteristics (determined spectrophotometrically) and the individual phenolic compounds (anthocyanins and tannins, determined by HPLC) were followed during the maceration period, at the end of alcoholic fermentation and after two months in bottle. Also, the wine volatile compounds were determined by GC-MS. The wines made with ultrasound-treated grapes showed differences with the control wine, especially regarding total phenol content and tannin content. The wines elaborated with sonicated grapes and with only three days of skin maceration time presented similar concentration of anthocyanins and twice the concentration of tannins than control wines elaborated with 8days of skin maceration.This work was funded by the SME Instrument of the Horizon 2020 program from the European Commission.Baustista-Ortin A.B.; Jimenez-Martinez M.D; Jurado, R.; Iniesta, JA.; Terrades-Rocafull, LS.; Andrés Grau, AM.; Gomez-Plaza, E. (2017). Application of high Power ultrasounds during red wine vinification. International Journal of Food Science & Technology. 52(6):1314-1323. https://doi.org/10.1111/ijfs.13411S13141323526De Andrade Neves, N., de Araújo Pantoja, L., & dos Santos, A. S. (2013). Thermovinification of grapes from the Cabernet Sauvignon and Pinot Noir varieties using immobilized yeasts. European Food Research and Technology, 238(1), 79-84. doi:10.1007/s00217-013-2062-2Bautista-Ortín, A. B., Cano-Lechuga, M., Ruiz-García, Y., & Gómez-Plaza, E. (2014). Interactions between grape skin cell wall material and commercial enological tannins. Practical implications. Food Chemistry, 152, 558-565. doi:10.1016/j.foodchem.2013.12.009Bautista-Ortín, A. B., Martínez-Hernández, A., Ruiz-García, Y., Gil-Muñoz, R., & Gómez-Plaza, E. (2016). Anthocyanins influence tannin–cell wall interactions. Food Chemistry, 206, 239-248. doi:10.1016/j.foodchem.2016.03.045Bautista-Ortín, A. B., Fernández-Fernández, J. I., López-Roca, J. M., & Gómez-Plaza, E. (2004). Wine-making of High Coloured Wines: Extended Pomace Contact and Run-off of Juice Prior to Fermentation. Food Science and Technology International, 10(5), 287-295. doi:10.1177/1082013204047565Bautista-Ortin, A. B., Martinez-Cutillas, A., Ros-Garcia, J. M., Lopez-Roca, J. M., & Gomez-Plaza, E. (2005). Improving colour extraction and stability in red wines: the use of maceration enzymes and enological tannins. International Journal of Food Science and Technology, 40(8), 867-878. doi:10.1111/j.1365-2621.2005.01014.xBindon, K. A., Smith, P. A., Holt, H., & Kennedy, J. A. (2010). Interaction between Grape-Derived Proanthocyanidins and Cell Wall Material. 2. Implications for Vinification. Journal of Agricultural and Food Chemistry, 58(19), 10736-10746. doi:10.1021/jf1022274Busse-Valverde, N., Gómez-Plaza, E., López-Roca, J. M., Gil-Muñoz, R., Fernández-Fernández, J. I., & Bautista-Ortín, A. B. (2010). Effect of Different Enological Practices on Skin and Seed Proanthocyanidins in Three Varietal Wines. Journal of Agricultural and Food Chemistry, 58(21), 11333-11339. doi:10.1021/jf102265cBusse-Valverde, N., Gómez-Plaza, E., López-Roca, J. M., Gil-Muñoz, R., & Bautista-Ortín, A. B. (2011). The Extraction of Anthocyanins and Proanthocyanidins from Grapes to Wine during Fermentative Maceration Is Affected by the Enological Technique. Journal of Agricultural and Food Chemistry, 59(10), 5450-5455. doi:10.1021/jf2002188Cano-López, M., Pardo-Mínguez, F., Schmauch, G., Saucier, C., Teissedre, P.-L., López-Roca, J. M., & Gómez-Plaza, E. (2008). Effect of Micro-oxygenation on Color and Anthocyanin-Related Compounds of Wines with Different Phenolic Contents. Journal of Agricultural and Food Chemistry, 56(14), 5932-5941. doi:10.1021/jf8006147Carrera, C., Ruiz-Rodríguez, A., Palma, M., & Barroso, C. G. (2012). Ultrasound assisted extraction of phenolic compounds from grapes. Analytica Chimica Acta, 732, 100-104. doi:10.1016/j.aca.2011.11.032Castro-López, L. del R., Gómez-Plaza, E., Ortega-Regules, A., Lozada, D., & Bautista-Ortín, A. B. (2016). Role of cell wall deconstructing enzymes in the proanthocyanidin–cell wall adsorption–desorption phenomena. Food Chemistry, 196, 526-532. doi:10.1016/j.foodchem.2015.09.080Da Porto, C., Porretto, E., & Decorti, D. (2013). Comparison of ultrasound-assisted extraction with conventional extraction methods of oil and polyphenols from grape (Vitis vinifera L.) seeds. Ultrasonics Sonochemistry, 20(4), 1076-1080. doi:10.1016/j.ultsonch.2012.12.002Demirdöven, A., & Baysal, T. (2008). The Use of Ultrasound and Combined Technologies in Food Preservation. Food Reviews International, 25(1), 1-11. doi:10.1080/87559120802306157El Darra, N., Grimi, N., Maroun, R. G., Louka, N., & Vorobiev, E. (2012). Pulsed electric field, ultrasound, and thermal pretreatments for better phenolic extraction during red fermentation. European Food Research and Technology, 236(1), 47-56. doi:10.1007/s00217-012-1858-9Gagné, S., Saucier, C., & Gény, L. (2006). Composition and Cellular Localization of Tannins in Cabernet Sauvignon Skins during Growth. Journal of Agricultural and Food Chemistry, 54(25), 9465-9471. doi:10.1021/jf061946gGeffroy, O., Lopez, R., Serrano, E., Dufourcq, T., Gracia-Moreno, E., Cacho, J., & Ferreira, V. (2015). Changes in analytical and volatile compositions of red wines induced by pre-fermentation heat treatment of grapes. Food Chemistry, 187, 243-253. doi:10.1016/j.foodchem.2015.04.105Ghafoor, K. (2009). Optimization of Ultrasound Assisted Extraction of Phenolic Compounds and Antioxidants from Grape Peel through Response Surface Methodology. Journal of the Korean Society for Applied Biological Chemistry, 52(3), 295-300. doi:10.3839/jksabc.2009.052Gómez-Plaza, E., Mestre-Ortuño, L., Ruiz-García, Y., Fernández-Fernández, J. I., & López-Roca, J. M. (2012). Effect of Benzothiadiazole and Methyl Jasmonate on the Volatile Compound Composition of Vitis vinifera L. Monastrell Grapes and Wines. American Journal of Enology and Viticulture, 63(3), 394-401. doi:10.5344/ajev.2012.12011Knorr, D., Zenker, M., Heinz, V., & Lee, D.-U. (2004). Applications and potential of ultrasonics in food processing. Trends in Food Science & Technology, 15(5), 261-266. doi:10.1016/j.tifs.2003.12.001Labarbe, B., Cheynier, V., Brossaud, F., Souquet, J.-M., & Moutounet, M. (1999). Quantitative Fractionation of Grape Proanthocyanidins According to Their Degree of Polymerization. Journal of Agricultural and Food Chemistry, 47(7), 2719-2723. doi:10.1021/jf990029qMorel-Salmi, C., Souquet, J.-M., Bes, M., & Cheynier, V. (2006). Effect of Flash Release Treatment on Phenolic Extraction and Wine Composition. Journal of Agricultural and Food Chemistry, 54(12), 4270-4276. doi:10.1021/jf053153kPetropulos, V. I., Bogeva, E., Stafilov, T., Stefova, M., Siegmund, B., Pabi, N., & Lankmayr, E. (2014). Study of the influence of maceration time and oenological practices on the aroma profile of Vranec wines. Food Chemistry, 165, 506-514. doi:10.1016/j.foodchem.2014.05.144Rapp, A. (1988). Wine Aroma Substances from Gas Chromatographic Analysis. Modern Methods of Plant Analysis, 29-66. doi:10.1007/978-3-642-83340-3_3Romero-Cascales, I., Fernández-Fernández, J. I., López-Roca, J. M., & Gómez-Plaza, E. (2005). The maceration process during winemaking extraction of anthocyanins from grape skins into wine. European Food Research and Technology, 221(1-2), 163-167. doi:10.1007/s00217-005-1144-1Romero-Cascales, I., Fernández-Fernández, J. I., Ros-García, J. M., López-Roca, J. M., & Gómez-Plaza, E. (2008). Characterisation of the main enzymatic activities present in six commercial macerating enzymes and their effects on extracting colour during winemaking of Monastrell grapes. International Journal of Food Science & Technology, 43(7), 1295-1305. doi:10.1111/j.1365-2621.2007.01608.xRomero-Cascales, I., Ros-García, J. M., López-Roca, J. M., & Gómez-Plaza, E. (2012). The effect of a commercial pectolytic enzyme on grape skin cell wall degradation and colour evolution during the maceration process. Food Chemistry, 130(3), 626-631. doi:10.1016/j.foodchem.2011.07.091Souquet, J.-M., Cheynier, V., Brossaud, F., & Moutounet, M. (1996). Polymeric proanthocyanidins from grape skins. Phytochemistry, 43(2), 509-512. doi:10.1016/0031-9422(96)00301-9Tao, Y., Zhang, Z., & Sun, D.-W. (2014). Kinetic modeling of ultrasound-assisted extraction of phenolic compounds from grape marc: Influence of acoustic energy density and temperature. Ultrasonics Sonochemistry, 21(4), 1461-1469. doi:10.1016/j.ultsonch.2014.01.029Tiwari, B. K., Patras, A., Brunton, N., Cullen, P. J., & O’Donnell, C. P. (2010). Effect of ultrasound processing on anthocyanins and color of red grape juice. Ultrasonics Sonochemistry, 17(3), 598-604. doi:10.1016/j.ultsonch.2009.10.009Zhang, Q.-A., Shen, Y., Fan, X., Martín, J. F. G., Wang, X., & Song, Y. (2015). Free radical generation induced by ultrasound in red wine and model wine: An EPR spin-trapping study. Ultrasonics Sonochemistry, 27, 96-101. doi:10.1016/j.ultsonch.2015.05.003Zhang, Q.-A., Shen, Y., Fan, X.-H., & García Martín, J. F. (2015). Preliminary study of the effect of ultrasound on physicochemical properties of red wine. CyTA - Journal of Food, 14(1), 55-64. doi:10.1080/19476337.2015.104503

Heart failure in COVID-19 patients: prevalence, incidence and prognostic implications

Aims: Data on the impact of COVID-19 in chronic heart failure (CHF) patients and its potential to trigger acute heart failure (AHF) are lacking. The aim of this work was to study characteristics, cardiovascular outcomes and mortality in patients with confirmed COVID-19 infection and a prior diagnosis of heart failure (HF). Further aims included the identification of predictors and prognostic implications for AHF decompensation during hospital admission and the determination of a potential correlation between the withdrawal of HF guideline-directed medical therapy (GDMT) and worse outcomes during hospitalization. Methods and results: Data for a total of 3080 consecutive patients with confirmed COVID-19 infection and follow-up of at least 30 days were analysed. Patients with a previous history of CHF (n = 152, 4.9%) were more prone to the development of AHF (11.2% vs. 2.1%; P < 0.001) and had higher levels of N-terminal pro brain natriuretic peptide. In addition, patients with previous CHF had higher mortality rates (48.7% vs. 19.0%; P < 0.001). In contrast, 77 patients (2.5%) were diagnosed with AHF, which in the vast majority of cases (77.9%) developed in patients without a history of HF. Arrhythmias during hospital admission and CHF were the main predictors of AHF. Patients developing AHF had significantly higher mortality (46.8% vs. 19.7%; P < 0.001). Finally, the withdrawal of beta-blockers, mineralocorticoid receptor antagonists and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with a significant increase in in-hospital mortality. Conclusions: Patients with COVID-19 have a significant incidence of AHF, which is associated with very high mortality rates. Moreover, patients with a history of CHF are prone to developing acute decompensation after a COVID-19 diagnosis. The withdrawal of GDMT was associated with higher mortalit

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Bacterioruberin extracts from a genetically modified hyperpigmented Haloferax volcanii strain: antioxidant activity and bioactive properties on sperm cells

To examine the antioxidant activity of Bacterioruberin (Bctr)-rich extracts isolated from a hyperpigmented-genetically modified Haloferaxvolcanii strain (HVLON3) and to investigate the effect on cold-sensitive ram sperm cells.Methods and Results: The strain HVLON3 produces higher Bctr amounts than most haloarchaea (220 ± 13 mg/g DW). HVLON3-Bctr extract hashigher antioxidant activity than β-carotene (3-fold) as evaluated using 2,2 diphenyl-1-picrylhydrazyl combined with Electron ParamagneticResonance analysis (EC50 4.5 x 10-5 mol l-1 vs. 13.9 x 10-5 mol l-1, respectively). Different concentrations of HVLON3-Bctr extracts were assayedon ram sperm after freezing/thawing and physiologically relevant parameters were examined. Extracts containing 7 and 20 μmol l-1 Bctrsignificantly improved cell viability (p<0.0001), total and progressive motility (p<0.0001) and sperm velocities (p=0.0172 for curvilinear velocityVCL, p=0.0268 for average path velocity VAP and p=0.0181 for straight-line velocity VSL) and did not affect other parameters evaluated.Conclusions: HVLON3 is an excellent source of natural microbial C50 carotenoids with applicability in Biotechnology, Biomedical and Veterinaryfields. HVLON3 Bctr-extract improves the quality of cryopreserved ram sperm cells and could be applied to increase insemination yields.Significance and Impact of the Study: This study provides insight on the bioactive properties of a bioproduct derived from haloarchaea(carotenoids) which are so far underexploited.Fil: Zalazar, Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Pagola, Pablo. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; ArgentinaFil: Miró, María Victoria. Universidad Nacional de Mar del Plata. Instituto de Biología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Físicas de Mar del Plata. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Físicas de Mar del Plata; ArgentinaFil: Churio, Maria Sandra. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Físicas de Mar del Plata. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Físicas de Mar del Plata; ArgentinaFil: Cerletti, Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Martinez, Celeste. Universidad Nacional de Mar del Plata. Instituto de Biología; ArgentinaFil: Iniesta-Cuerda, M.. Universidad de Castilla-La Mancha. Instituto de Investigación en Recursos Cinegéticos; EspañaFil: Soler, A.J.. Universidad de Castilla-La Mancha. Instituto de Investigación en Recursos Cinegéticos; EspañaFil: Cesari, A.. Universidad Nacional de Mar del Plata. Instituto de Biología; ArgentinaFil: de Castro, Rosana Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentin

Tumor xenograft modeling identifies an association between TCF4 loss and breast cancer chemoresistance

Understanding the mechanisms of cancer therapeutic resistance is fundamental to improving cancer care. There is clear benefit from chemotherapy in different breast cancer settings; however, knowledge of the mutations and genes that mediate resistance is incomplete. In this study, by modeling chemoresistance in patientderived xenografts (PDXs), we show that adaptation to therapy is genetically complex and identify that loss of transcription factor 4 (TCF4; also known as ITF2) is associated with this process. A triple-negative BRCA1-mutaied PDX was used to study the genetics of chemoresistance. The PDX was treated in parallel with four chemotherapies for five iterative cycles. Exome sequencing identified few genes with de novo or enriched mutations in common among the different therapies, whereas many common depleted mutations/ genes were observed. Analysis of somatic mutations from The Cancer Genome Atlas (TCGA) supported the prognostic relevance of the identified genes. A mutation in TCF4 was found de novo in all treatments, and analysis of drug sensitivity profiles across cancer cell lines supported the link to chemoresistance. Loss of TCF4 conferred chemoresistance in breast cancer cell models, possibly by altering cell cycle regulation. Targeted sequencing in chemoresistant tumors identified an intronic variant of TCF4 that may represent an expression quantitative trait locus associated with relapse outcome in TCGA. Immunohistochemical studies suggest a common loss of nuclear TCF4 expression post-chemotherapy. Together, these results from tumor xenograft modeling depict a link between altered TCF4 expression and breast cancer chemoresistance

Prediction models for voriconazole pharmacokinetics based on pharmacogenetics: AN exploratory study in a Spanish population

Individualisation of the therapeutic strategy for the oral antifungal agent voriconazole (VCZ) is extremely important for treatment optimisation. To date, regulatory agencies include CYP2C19 as the only major pharmacogenetic (PGx) biomarker in their dosing guidelines; however, the effect of other genes might be important for VCZ dosing prediction. We developed an exploratory PGx study to identify new biomarkers related to VCZ pharmacokinetics. We first designed a ‘clinical practice VCZ-AUC prediction model’ based on CYP2C19 to be used as a reference model in this study. We then designed a multifactorial polygenic prediction model and found that genetic variability in FMO3, NR1I2, POR, CYP2C9 and CYP3A4 partially contributes to VCZ total area under the concentration–time curve (AUC0–∞) interindividual variability, and its inclusion in VCZ AUC0–∞ prediction algorithms improves model precision. To our knowledge, there are no PGx studies specifically relating POR, FMO3 and NR1I2 polymorphisms to VCZ pharmacokinetic variability. Further research is needed in order to test the model proposed hereThe voriconazole bioequivalence study was funded by Labora- torios Normon (Madrid, Spain). The research project has been co- financed by the Ministerio de Economia y Competitividad within the INNPACTO program [IPT-2012-0576-090 0 0 0] and the European Regional Development Fund (ERDF ‘A way to achieve Europe’

Epigenetic inactivation of the p53-induced long noncoding RNA TP53 target 1 in human cancer

Maria de Lourdes Farré Vallve - Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia Experimental. Salvador, BA, Brasil. aCancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908 Barcelona, Catalonia, Spain; bCentro de Investigación Biomédica en Red (CIBER) Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto Salud Carlos III, 28029 Madrid, Spain; cEndocrine Division, Complejo Hospitalario Universitario de Santiago, 15706 Santiago de Compostela, Spain; dDivision of RNA Biology and Cancer (B150), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; eInstitute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany; fExperimental Dermatology and Skin Biology Group, Ramón y Cajal Institute for Biomedical Research (IRYCIS), Ramón y Cajal University Hospital, 28034 Madrid, Spain; gBionanotechnology Laboratory, Bernardo O’Higgins University, Santiago 8370854, Chile; hPathology Department, Hospital Universitari de Bellvitge, IDIBELL, L’Hospitalet de Llobregat, 08907 Barcelona, Catalonia, Spain; iDepartment of Medical Oncology, Catalan Institute of Oncology (ICO), IDIBELL, L’Hospitalet de Llobregat, 08908 Barcelona, Catalonia, Spain; jUnit of Nutrition and Cancer, Cancer Epidemiology Research Program, ICO, IDIBELL, 08908 Barcelona, Catalonia, Spain; kDepartment of Molecular Oncology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 113-8510 Tokyo, Japan; lProgram Against Cancer Therapeutic Resistance (ProCURE), ICO, IDIBELL, L’Hospitalet del Llobregat, 08908 Barcelona, Catalonia, Spain; mLaboratory of Experimental Pathology (LAPEX), Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (CPQGM/ FIOCRUZ) and National Institute of Science and Technology of Tropical Diseases (INCT/DT), 40296710 Salvador, Bahia, Brazil; nDivision of Cancer Research, Department of Thoracic Surgery, Medical Center–University of Freiburg, 79106 Freiburg, Germany; oFaculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; pGerman Cancer Consortium (DKTK), 79106 Freiburg, Germany; qDepartament de Ciències Fisiològiques II, Escola de Medicina, Universitat de Barcelona, 08907 Barcelona, Catalonia, Spain; and rInstitució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Catalonia, SpainSubmitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-03-24T13:39:17Z No. of bitstreams: 1 Lagares AD Epigenetic inactivation....pdf: 3833209 bytes, checksum: fcc6c212b11319a6cc7ba1aa1a191854 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-03-24T13:57:19Z (GMT) No. of bitstreams: 1 Lagares AD Epigenetic inactivation....pdf: 3833209 bytes, checksum: fcc6c212b11319a6cc7ba1aa1a191854 (MD5)Made available in DSpace on 2017-03-24T13:57:19Z (GMT). No. of bitstreams: 1 Lagares AD Epigenetic inactivation....pdf: 3833209 bytes, checksum: fcc6c212b11319a6cc7ba1aa1a191854 (MD5) Previous issue date: 2016Bellvitge Biomedical Research Institute (IDIBELL). L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program (PEBC). Barcelona, Catalonia, SpainBellvitge Biomedical Research Institute (IDIBELL). L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program (PEBC). Barcelona, Catalonia, Spain / Instituto Salud Carlos III. Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de la Obesidad y Nutrición (CIBERobn). Madrid, Spain / Complejo Hospitalario Universitario de Santiago. Endocrine Division. Santiago de Compostela, SpainBellvitge Biomedical Research Institute (IDIBELL). L’Hospitalet de Llobregat. Cancer Epigenetics and Biology Program (PEBC). Barcelona, Catalonia, Spain. Múltipla - ver em NotasLong noncoding RNAs (lncRNAs) are important regulators of cellular homeostasis. However, their contribution to the cancer phenotype still needs to be established. Herein, we have identified a p53-induced lncRNA, TP53TG1, that undergoes cancer-specific promoter hypermethylation-associated silencing. In vitro and in vivo assays identify a tumor-suppressor activity for TP53TG1 and a role in the p53 response to DNA damage. Importantly, we show that TP53TG1 binds to the multifaceted DNA/RNA binding protein YBX1 to prevent its nuclear localization and thus the YBX1-mediated activation of oncogenes. TP53TG1 epigenetic inactivation in cancer cells releases the transcriptional repression of YBX1-targeted growth-promoting genes and creates a chemoresistant tumor. TP53TG1 hypermethylation in primary tumors is shown to be associated with poor outcome. The epigenetic loss of TP53TG1 therefore represents an altered event in an lncRNA that is linked to classical tumoral pathways, such as p53 signaling, but is also connected to regulatory networks of the cancer cell

COVID-19 in hospitalized HIV-positive and HIV-negative patients : A matched study

CatedresObjectives: We compared the characteristics and clinical outcomes of hospitalized individuals with COVID-19 with [people with HIV (PWH)] and without (non-PWH) HIV co-infection in Spain during the first wave of the pandemic. Methods: This was a retrospective matched cohort study. People with HIV were identified by reviewing clinical records and laboratory registries of 10 922 patients in active-follow-up within the Spanish HIV Research Network (CoRIS) up to 30 June 2020. Each hospitalized PWH was matched with five non-PWH of the same age and sex randomly selected from COVID-19@Spain, a multicentre cohort of 4035 patients hospitalized with confirmed COVID-19. The main outcome was all-cause in-hospital mortality. Results: Forty-five PWH with PCR-confirmed COVID-19 were identified in CoRIS, 21 of whom were hospitalized. A total of 105 age/sex-matched controls were selected from the COVID-19@Spain cohort. The median age in both groups was 53 (Q1-Q3, 46-56) years, and 90.5% were men. In PWH, 19.1% were injecting drug users, 95.2% were on antiretroviral therapy, 94.4% had HIV-RNA < 50 copies/mL, and the median (Q1-Q3) CD4 count was 595 (349-798) cells/μL. No statistically significant differences were found between PWH and non-PWH in number of comorbidities, presenting signs and symptoms, laboratory parameters, radiology findings and severity scores on admission. Corticosteroids were administered to 33.3% and 27.4% of PWH and non-PWH, respectively (P = 0.580). Deaths during admission were documented in two (9.5%) PWH and 12 (11.4%) non-PWH (P = 0.800). Conclusions: Our findings suggest that well-controlled HIV infection does not modify the clinical presentation or worsen clinical outcomes of COVID-19 hospitalization