Evidence that heparin but not hirudin reduces PAI-1 expression in cultured human endothelial cells

Heparin and other antithrombotic drugs besides their anticoagulant action could have a profibrinolytic effect. We have analyzed the effect of unfractionated heparin (UFH) and hirudin on PAI-1 gene expression in human umbilical vein endothelial cells (HUVEC). Cells were stimulated with UFH (1 and 10 IU/ml) and hirudin (20 and 100 TIU/ml). Samples were obtained before and 2, 6, and 24 hours after stimulation. mRNA analysis was conducted by reverse transcription followed by polymerase chain reaction, and PAI-1 antigen was determined by ELISA. Addition of UFH (10 IU/ml) to HUVEC resulted in a decrease of PAI-1 mRNA at 6 hours (40% reduction) and 24 hours (60% reduction) and PAI-1 antigen. Hirudin, however, did not modify significantly the PAI-1 mRNA nor the inhibitor secretion. The addition of UFH (10 or 100 IU/ml) to endotoxin-stimulated HUVEC also reduced the increased PAI-1 mRNA and antigen secretion (45%), whereas no effect could be observed with hirudin. Our results suggest that UFH, but not hirudin, by reducing the endothelial expression of PAI-1 might have a profibrinolytic effect

Gestão de processos de negócios em serviços de tecnologia e informação

En este trabajo definimos y simulamos procesos en una compañía que presta servicios de tecnología de la información con el propósito de mejorar la atención y las funciones definidas en cada proceso. Analizamos diversos trabajos con respecto a la gestión de procesos de negocios y simulación. Para nuestro modelo de desarrollo, diseñamos una metodología basada en la gestión de procesos de negocios. Los procesos y las actividades fueron modelados y simulados con la ayuda de una herramienta de software para estables los tiempos y el número deposibles estancias ejecutadas. Dichos tiempos y procesos pueden ser adaptados al nivel de rendimiento deseado. El resultado de dichos procesos contribuyó a la realización de actividades de negocio de tal manera que las mismas sean más eficientes con respecto al uso del tiempo y por lo tanto otorguen un servicio de alta calidad.In this work, we defined and simulated processes in a company which provides Information Technology services with the purpose of enhancing attention and functions defined for each process. We analyzed several works related to business management process and simulation. For model development, we designed a methodology based on Business Process Management. Processes and activities were modelled and simulated using a software tool establishing times and number of possible instances to be performed. These times and processes may be adapted to a desired level of performance. Resulting processes contribute to perform business activities in a more adequate way and be more time efficient in order to provide a higher quality service

Enhancement of Water Transport and Microstructural Changes Induced by High-Intesity Ultrasound Application on Orange Peel Drying

The main aim of this work was to evaluate the effect of high-intensity ultrasound (US) on the drying kinetics of orange peel as well as its influence on the microstructural changes induced during drying. Convective drying kinetics of orange peel slabs were carried out at a relative humidity of 26.5±0.9%, 40 °C and 1 m/s with (AIR+US) and without (AIR) ultrasound application. In order to identify the US effect on water transport, drying kinetics were analyzed by taking the diffusion theory into account. Fresh, AIR and AIR+US dried samples were analyzed using Cryo-Scanning Electron Microscopy. Results showed that the drying kinetics of orange peel were significantly improved by US application, which involved a significant (p<0.05) improvement of mass transfer coefficient and effective moisture diffusivity. The effects on mass transfer properties were confirmed with microstructural observations. In the cuticle surface of flavedo, the pores were obstructed by the spread of the waxy components, this fact evidencing US effects on the air solid interfaces. Furthermore, the cells of the albedo were disrupted by US, as it created large intercellular air spaces facilitating water transfer through the tissue.The authors would like to acknowledge the financial support of MICINN and CEE (European Regional Development Fund) from projects Ref. DPI2009-14549-C04-04, PSE-060000-2009-003, and FP6-2004-FOOD-23140 HIGHQ RTE.García Pérez, JV.; Ortuño Cases, C.; Puig Gómez, CA.; Cárcel Carrión, JA.; Pérez Munuera, IM. (2012). Enhancement of Water Transport and Microstructural Changes Induced by High-Intesity Ultrasound Application on Orange Peel Drying. Food and Bioprocess Technology. 5(6):2256-2265. https://doi.org/10.1007/s11947-011-0645-0S2256226556Alandes, L., Perez-Munuera, I., Llorca, E., Quiles, A., & Hernando, I. (2009). Use of calcium lactate to improve structure of “Flor de Invierno” fresh-cut pears. Postharvest Biology and Technology, 53(3), 145–151.Anagnostopoulou, M. A., Kefalas, P., Papageorgiou, V. P., Assimopoulou, A. N., & Boskou, D. (2006). Radical scavenging activity of various extracts and fractions of sweet orange peel (Citrus sinensis). Food Chemistry, 94(1), 19–25.AOAC. (1997). Official methods of analysis. Arlington: Association of Official Analytical Chemist.Arslan, D., Özcan, M. M. (2011). Evaluation of drying methods with respect to drying kinetics, mineral content, and color characteristics of savory leaves. Food and Bioprocess Technology. doi: 10.1007/s11947-010-0498-y , in press.Cárcel, J. A., Garcia-Perez, J. V., Riera, E., & Mulet, A. (2007). Influence of high intensity ultrasound on drying kinetics of persimmon. Drying Technology, 25(1), 185–193.Chafer, M., Gonzalez-Martinez, C., Chiralt, A., & Fito, P. (2003). Microstructure and vacuum impregnation response of citrus peles. Food Research International, 36(1), 35–41.Chau, C., Sheu, F., Huang, Y., & Su, L. (2005). Improvement in intestinal function and health by the peel fibre derived from Citrus sinensis L cv Liucheng. Journal of the Science of Food & Agriculture, 85(7), 1211–1216.Crank J. (1975). The Mathematics of diffusion. Oxford (2nd ed.), UK: Clarendon Press.Cruz, R. M. S., Vieira, M. C., Fonseca, S. C., Silva, C. L. M. (2010). Impact of thermal blanching and thermosonication treatments on watercress (Nasturtium officinale) quality: thermosonication process optimization and microstructure evaluation. Food and Bioprocess Technology. doi: 10.1007/s11947-009-0220-0 , in press.Delgado, A. E., Zheng, L., & Sun, D.-W. (2010). Influence of ultrasound on freezing rate of immersion-frozen apples. Food and Bioprocess Technology, 2(3), 263–270.FAOSTAT (2010). FAO Statistical Databases. Food and Agriculture of the United Nations. Available at: http://faostat.fao.org/site/291/default.aspx . Accessed 15 January 2010.Fernandes, F. A. N., Gallao, M. I., & Rodrigues, S. (2008a). Effect of osmotic dehydration and ultrasound pre-treatment on cell structure: Melon dehydration. Food Science and Technology, 41(4), 604–610.Fernandes, F. A. N., Oliveira, F. I. P., & Rodrigues, S. (2008b). Use of ultrasound for dehydration of papayas. Food and Bioprocess Technology, 1(4), 339–345.Gabaldon-Leyva, C. A., Quintero-Ramos, A., Barnard, J., Balandrán-Quintana, R., Talamás-Abbud, R., & Jiménez-Castro, J. (2007). Effect of ultrasound on the mass transfer and physical changes in brine bell pepper at different temperatures. Journal of Food Engineering, 81(2), 374–379.Gallego-Juárez, J. A. (1998). Some applications of air-borne power ultrasound to food processing. In M. J. W., Povey, T. J. Mason (Eds.), Ultrasound in Food Processing. UK: London, Chapman & Hall.Gallego-Juárez, J. A., Rodríguez-Corral, G., Gálvez-Moraleda, J. C., & Yang, T. S. (1999). A new high intensity ultrasonic technology for food dehydration. Drying Technology, 17(3), 597–608.Garau, M. C., Simal, S., Femenia, A., & Rosselló, C. (2006). Drying of orange skin: drying kinetics modelling and functional properties. Journal of Food Engineering, 75(2), 288–295.Garau, M. C., Simal, S., Rossello, C., & Femenia, A. (2007). Effect of air-drying temperature on physico-chemical properties of dietary fibre and antioxidant capacity of orange (Citrus aurantium v. Canoneta) by-products. Food Chemistry, 104(3), 1014–1024.Garcia-Perez, J. V., Cárcel, J. A., De la Fuente, S., & Riera, E. (2006). Ultrasonic drying of foodstuff in a fluidized bed. Parametric study. Ultrasonics, 44, 539–543.Garcia-Perez, J. V., Cárcel, J. A., Benedito, J., & Mulet, A. (2007). Power ultrasound mass transfer enhancement in food drying. Food and Bioproducts Proccessing, 85(3), 247–254.Guiné, R. P. F., Henrriques, F., Barroca, M. J. (2010). Mass transfer coefficients for the drying of pumpkin (Cucurbita moschata) and dried product quality. Food and Bioprocess Technology. doi: 10.1007/s11947-009-0275 , in press.Khalloufi, S., Almeida-Rivera, C., & Bongers, P. (2009). A theoretical model and its experimental validation to predict the porosity as a function of shrinkage and collapse phenomena during drying. Food Research International, 42(8), 1122–1130.Larrauri, J. A., Rupérez, P., Bravo, L., & Saura-Calixto, F. (1996). High dietary fibre powders from orange and lime peels: associated polyphenols and antioxidant capacity. Food Research International, 29(8), 757–762.Mujumdar, A. S., & Law, C. L. (2010). Drying technology: trends and applications in postharvest processing. Food and Bioprocess Technology, 3(6), 843–852.Mulet, A., Blasco, M., García-Reverter, J., & Garcia-Perez, J. V. (2005). Drying kinetics of Curcuma longa rhizomes. Journal of Food Science, 7(5), 318–323.Oliveira, F. I. P., Gallao, M. I., Rodrigues, S., Fernandes, F.A.N. (2010). Dehydration of malay apple (Syzygium malaccense L.) using ultrasound as a pretreatment. Food and Bioprocess Technology. doi: 10.1007/s11947-010-0351-3 , in press.Ortuño, C., Perez-Munuera, I., Puig, A., Riera, E., & Garcia-Perez, J.V. (2010). Influence of power ultrasound application on mass transport and microstructure of orange peel during hot air drying. Physics Procedia, 3, 153–159.Perry, R. H. & Chilton, C. H. (1973). Chemical Engineers’ Handbook. McGraw Hill (5th ed.), New York, US.Ruiz-López, I. I., Castillo-Zamudio, R. I., Salgado-Cervantes, M. A., Rodríguez-Jimenes, G. C., & García-Alvarado, M. A. (2010). Mass transfer modelling during osmotic dehydration of hexahedral pineapple slices in limited volume solutions. Food and Bioprocess Technology, 3(3), 427–433.Salvador, A., Salvador, L., Besada, C., Larrea, V., Hernando, I., & Perez-Munuera, I. (2008). Reduced effectiveness of the treatment for removing astringency in persimmon fruit when stored at 15 °C: Physiological and microstructural study. Postharvest Biology and Technology, 49(3), 340–347.Sanchez, E. S., Simal, S., Femenía, A., Benedito, J., & Roselló, C. (2001). Effect of acoustic brining on lipolysis and on sensory characteristics of Mahon cheese. Journal of Food Science, 66(6), 892–896.Sanchez, E. S., Simal, S., Femenía, A., Llul, P., & Roselló, C. (2001). Proteolysis of Mahon cheese as affected by acoustic-assited brining. European Food Research and Technology, 212(2), 147–152.Sharma, A., & Gupta, M. N. (2006). Ultrasonic pre-irradiation effect upon aqueous enzymatic oil extraction from almond and apricot seeds. Ultrasonics Sonochemistry, 13(6), 529–534.Simal, S., Rosello, C., & Mulet, A. (1998). Modelling of air drying in regular shaped bodies. Trends in Chemical Engineering, 4(4), 171–180.Simal, S., Femenia, A., & Garcia-Pascual, P. (2003). Simulation of the drying curves of a meat-based product: effect of the external resistance to mass transfer. Journal of Food Engineering, 58(2), 193–199.Singh, R. P., & Heldman, D. R. (2001). Introduction to Food Engineering. Academic Press (3rd ed.): San Diego.Toma, M., Vinatoru, M., Paniwnyk, L., & Mason, T. J. (2001). Investigation of the effects of ultrasound on vegetal tissues during solvent extraction. Ultrasonics Sonochemistry, 8(2), 137–142

A randomized phase II clinical trial of dendritic cell vaccination following complete resection of colon cancer liver metastasis

Surgically resectable synchronic and metachronic liver metastases of colon cancer have high risk of relapse in spite of standard-of-care neoadjuvant and adjuvant chemotherapy regimens. Dendritic cell vaccines loaded with autologous tumor lysates were tested for their potential to avoid or delay disease relapses (NCT01348256). Patients with surgically amenable liver metastasis of colon adenocarcinoma (n = 19) were included and underwent neoadjuvant chemotherapy, surgery and adjuvant chemotherapy. Fifteen patients with disease-free resection margins were randomized 1:1 to receive two courses of four daily doses of dendritic cell intradermal vaccinations versus observation. The trial had been originally designed to include 56 patients but was curtailed due to budgetary restrictions. Follow-up of the patients indicates a clear tendency to fewer and later relapses in the vaccine arm (median disease free survival –DFS-) 25.26 months, 95% CI 8. 74-n.r) versus observation arm (median DFS 9.53 months, 95% CI 5.32–18.88)

Engineering aspects of hydrothermal pretreatment: from batch to continuous operation, scale-up and pilot reactor under biorefinery concept

Different pretreatments strategies have been developed over the years mainly to enhance enzymatic cellulose degradation. In the new biorefinery era, a more holistic view on pretreatment is required to secure optimal use of the whole biomass. Hydrothermal pretreatment technology is regarded as very promising for lignocellulose biomass fractionation biorefinery and to be implemented at the industrial scale for biorefineries of second generation and circular bioeconomy, since it does not require no chemical inputs other than liquid water or steam and heat. This review focuses on the fundamentals of hydrothermal pretreatment, structure changes of biomass during this pretreatment, multiproduct strategies in terms of biorefinery, reactor technology and engineering aspects from batch to continuous operation. The treatise includes a case study of hydrothermal biomass pretreatment at pilot plant scale and integrated process design.The authors gratefully thank the Secretary of Public Education ofMexico – Mexican Science and Technology Council (SEP-CONACYT,Mexico) for the Basic Science Project -2015-01 (Ref. 254808), EnergySustainability Fund 2014-05 (CONACYT-SENER), Mexican Centre forInnovation in Bioenergy (Cemie-Bio), Cluster of Bioalcohols (Ref.249564) and the BMBF for the financial support (reference number:031B0660A).info:eu-repo/semantics/publishedVersio

Evaluating the Applicability of Data-Driven Dietary Patterns to Independent Samples with a Focus on Measurement Tools for Pattern Similarity

BACKGROUND: Diet is a key modifiable risk for many chronic diseases, but it remains unclear whether dietary patterns from one study sample are generalizable to other independent populations. OBJECTIVE: The primary objective of this study was to assess whether data-driven dietary patterns from one study sample are applicable to other populations. The secondary objective was to assess the validity of two criteria of pattern similarity. METHODS: Six dietary patterns-Western (n=3), Mediterranean, Prudent, and Healthy- from three published studies on breast cancer were reconstructed in a case-control study of 973 breast cancer patients and 973 controls. Three more internal patterns (Western, Prudent, and Mediterranean) were derived from this case-control study's own data. STATISTICAL ANALYSIS: Applicability was assessed by comparing the six reconstructed patterns with the three internal dietary patterns, using the congruence coefficient (CC) between pattern loadings. In cases where any pair met either of two commonly used criteria for declaring patterns similar (CC ≥0.85 or a statistically significant [P0.9) to their corresponding dietary pattern derived from the case-control study's data. Similar associations with risk for breast cancer were found in all pairs of dietary patterns that had high CC but not in all pairs of dietary patterns with statistically significant correlations. CONCLUSIONS: Similar dietary patterns can be found in independent samples. The P value of a correlation coefficient is less reliable than the CC as a criterion for declaring two dietary patterns similar. This study shows that diet scores based on a particular study are generalizable to other populations.This study was funded by Fundación Científica Asociación Española Contra el Cáncer (Scientific Foundation of the Spanish Association Against Cancer), the Spanish Ministry of Economy and Competitiveness (IJCI-2014-20900); Fundación Cerveza y Salud 2005 (Beer and Health Foundation 2005), Sociedad Española de Oncología Médica (Spanish Society of Medical Oncology), Federación de Mujeres con Cáncer de Mama (Association of Women with Breast Cancer) (EPY 1169-10 grant) and Association of Women with Breast Cancer from Elche (EPY 1394/15 grant)

Mutations in SCNM1 cause orofaciodigital syndrome due to minor intron splicing defects affecting primary cilia

Orofaciodigital syndrome (OFD) is a genetically heterogeneous ciliopathy characterized by anomalies of the oral cavity, face, and digits. We describe individuals with OFD from three unrelated families having bi-allelic loss-of-function variants in SCNM1 as the cause of their condition. SCNM1 encodes a protein recently shown to be a component of the human minor spliceosome. However, so far the effect of loss of SCNM1 function on human cells had not been assessed. Using a comparative transcriptome analysis between fibroblasts derived from an OFD-affected individual harboring SCNM1 mutations and control fibroblasts, we identified a set of genes with defective minor intron (U12) processing in the fibroblasts of the affected subject. These results were reproduced in SCNM1 knockout hTERT RPE-1 (RPE-1) cells engineered by CRISPR-Cas9-mediated editing and in SCNM1 siRNA-treated RPE-1 cultures. Notably, expression of TMEM107 and FAM92A encoding primary cilia and basal body proteins, respectively, and that of DERL2, ZC3H8, and C17orf75, were severely reduced in SCNM1-deficient cells. Primary fibroblasts containing SCNM1 mutations, as well as SCNM1 knockout and SCNM1 knockdown RPE-1 cells, were also found with abnormally elongated cilia. Conversely, cilia length and expression of SCNM1-regulated genes were restored in SCNM1-deficient fibroblasts following reintroduction of SCNM1 via retroviral delivery. Additionally, functional analysis in SCNM1-retrotransduced fibroblasts showed that SCNM1 is a positive mediator of Hedgehog (Hh) signaling. Our findings demonstrate that defective U12 intron splicing can lead to a typical ciliopathy such as OFD and reveal that primary cilia length and Hh signaling are regulated by the minor spliceosome through SCNM1 activity.This work was supported by a grant from the Spanish Ministry of Science and Innovation (PID2019-105620RB-I00/AEI/10.13039/501100011033)

Contraction amplitude is a relevant predictor of bolus transit during sitting viscous solution swallows in healthy individuals : preliminary results of a multicenter study using high resolution impedance manometry (HRIM)

Q1Q1https://orcid.org/0000-0002-9219-4548https://orcid.org/0000-0003-1222-0636https://orcid.org/0000-0002-4523-7947Revista Internacional - Indexad

Polyfunctional T cell responses in children in early stages of chronic Trypanosoma cruzi infection contrast with monofunctional responses of long-term infected adults

Background: Adults with chronic Trypanosoma cruzi exhibit a poorly functional T cell compartment, characterized by monofunctional (IFN-γ-only secreting) parasite-specific T cells and increased levels of terminally differentiated T cells. It is possible that persistent infection and/or sustained exposure to parasites antigens may lead to a progressive loss of function of the immune T cells. Methodology/Principal Findings: To test this hypothesis, the quality and magnitude of T. cruzi-specific T cell responses were evaluated in T. cruzi-infected children and compared with long-term T. cruzi-infected adults with no evidence of heart failure. The phenotype of CD4+ T cells was also assessed in T. cruzi-infected children and uninfected controls. Simultaneous secretion of IFN-γ and IL-2 measured by ELISPOT assays in response to T. cruzi antigens was prevalent among T. cruzi-infected children. Flow cytometric analysis of co-expression profiles of CD4+ T cells with the ability to produce IFN-γ, TNF-α, or to express the co-stimulatory molecule CD154 in response to T. cruzi showed polyfunctional T cell responses in most T. cruzi-infected children. Monofunctional T cell responses and an absence of CD4+TNF-α+-secreting T cells were observed in T. cruzi-infected adults. A relatively high degree of activation and differentiation of CD4+ T cells was evident in T. cruzi-infected children. Conclusions/Significance: Our observations are compatible with our initial hypothesis that persistent T. cruzi infection promotes eventual exhaustion of immune system, which might contribute to disease progression in long-term infected subjects.Fil: Albareda, María Cecilia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: de Rissio, Ana María. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Tomas, Gonzalo. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Serjan, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Alvarez, María Gabriela. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Viotti, Rodolfo Jorge. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Fichera, Laura Edith. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Esteva, Mónica Inés. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Potente, Daniel Fernando. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Armenti, Alejandro. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Tarleton, Rick L.. University of Georgia; Estados UnidosFil: Laucella, Susana Adriana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Sequential Isotopic Signature Along Gladius Highlights Contrasted Individual Foraging Strategies of Jumbo Squid (Dosidicus gigas)

International audienceBackground: Cephalopods play a major role in marine ecosystems, but knowledge of their feeding ecology is limited. In particular, intra- and inter-individual variations in their use of resources has not been adequatly explored, although there is growing evidence that individual organisms can vary considerably in the way they use their habitats and resources. Methodology/Principal Findings: Using d13C and d15N values of serially sampled gladius (an archival tissue), we examined high resolution variations in the trophic niche of five large (.60 cm mantle length) jumbo squids (Dosidicus gigas) that were collected off the coast of Peru. We report the first evidence of large inter-individual differences in jumbo squid foraging strategies with no systematic increase of trophic level with size. Overall, gladius d13C values indicated one or several migrations through the squid's lifetime (,8-9 months), during which d15N values also fluctuated (range: 1 to 5%). One individual showed an unexpected terminal 4.6% d15N decrease (more than one trophic level), thus indicating a shift from higher- to lower-trophic level prey at that time. The data illustrate the high diversity of prey types and foraging histories of this species at the individual level. Conclusions/Significance: The isotopic signature of gladii proved to be a powerful tool to depict high resolution and ontogenic variations in individual foraging strategies of squids, thus complementing traditional information offered by stomach content analysis and stable isotopes on metabolically active tissues. The observed differences in life history strategies highlight the high degree of plasticity of the jumbo squid and its high potential to adapt to environmental changes