131 research outputs found

    Estudio exploratorio del efecto de variables edafoclimáticas en la viticultura de riego y secano interior región del Maule

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    153 p.El presente estudio exploratorio analiza las distintas variables edafoclimáticas del cultivo de la Vitis vinífera L. de los sistemas productivos con y sin riego, del centro sur de la Región del Maule, bajo una dimensión espacio – temporal por medio de la utilización de Sistemas de Información Geográficas (SIG), identificando aquellas variables que presentaron un mayor grado de asociación entre ellas por medio del Análisis Factorial de Componentes Principales, así como su grado de diferenciación entre los años por medio del análisis de varianza (ANDEVA), con el propósito de vislumbrar fluctuaciones en el patrón normal de rendimiento y parámetros de madurez del fruto de la vid, en las distintas condiciones de sitio (centros vitícolas), durante las temporadas 2006 al 2010.El estudio espacial permitió reconocer el valor de cada una de las variables climáticas (temperatura, precipitación), suelo (orientación, pendiente) y de cultivo (manejos agronómicos, edad y densidad de plantación, actividad vegetativa del cultivo), como los registros de productividad (producción e índice de madurez) de cada una de las locaciones o centro productivos vitícolas. Por su parte, la dimensión temporal permitió identificar las fluctuaciones de dichas variables, como de los parámetros de productividad durante las temporadas 2005 al 2010, en condiciones de secano y riego.El análisis de dicha información digital concluyó que las condiciones climáticas son determinantes en los resultados finales de producción y calidad de la uva, y los niveles de actividad vegetativa del cultivo de la vid, en ambos sistemas productivos (con y sin riego), especialmente durante la ocurrencia del evento climático La Niña, cuyo efecto generó fuertes fluctuaciones en las magnitudes de dichos parámetros de productividad y expresión vegetativa, sobretodo en la condición productiva de secano./ABSTRACT: This exploratory study examines the different soil and climatic variables are the cultivation of Vitis vinifera L. production systems with and without irrigation, the South Central of the Region Maule, in one dimension temporal-space through the use Geographic Information Systems (GIS), identifying those variables that showed a higher degree of association between them by means of Principal Component Factor Analysis, and the degree of differentiation between the years through the analysis of variance (ANOVA), in order to discern fluctuations in the normal pattern of yield and maturity parameters of the fruit of the vine, in different site conditions (wine centers) during the seasons 2006 to 2010. The spatial study allowed us to recognize the value of each of the variables (temperature, precipitation), soil (orientation, slope) and crop (agricultural management, age and density planting, crop vegetative activity), as records of productivity (production and rate of maturity) of each center locations or wine products. For its part, the temporal dimension identified fluctuations of the variables and the parameters of productivity during 2006 and 2010 in rainfed and irrigation conditions.The analysis concluded that digital information that weather conditions are crucial to the final results of production and quality of the grape, and the activity vegetative levels of the crop of grapes, in both production systems (with and without irrigation), especially during the occurrence of La Niña climate event, the effect of which generated strong fluctuations in the magnitudes of these parameters of productivity and vegetative expression, especially in rainfed productive conditio

    Platelets promote macrophage polarization toward pro-inflammatory phenotype and increase survival of septic mice

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    We investigated the contribution of human platelets to macrophage effector properties in the presence of lipopolysaccharide (LPS), as well as the beneficial effects and time frame for platelet transfusion in septic animals. Our results show that platelets sequester both pro-(TNF-α/IL-6) and anti-(IL-10) inflammatory cytokines released by monocytes. Low LPS concentrations (0.01 ng/mL) induced M2 macrophage polarization by decreasing CD64 and augmenting CD206 and CD163 expression; yet, the presence of platelets skewed monocytes toward type 1 macrophage (M1) phenotype in a cell-contact-dependent manner by the glycoprotein Ib (GPIb)-CD11b axis. Accordingly, platelet-licensed macrophages showed increased TNF-α levels, bacterial phagocytic activity, and a reduced healing capability. Platelet transfusion increased inducible nitric oxide synthase (iNOS)+ macrophages, improving bacterial clearance and survival rates in septic mice up to 6 h post-infection, an effect that was abolished by CD11b and GPIb blockade. Our results demonstrate that platelets orchestrate macrophage effector responses, improving the clinical outcome of sepsis in a narrow but relevant time frame.Fil: Carestia, Agostina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. University of Calgary; CanadáFil: Mena, Hebe Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Olexen, Cinthia Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Ortiz Wilczyñski, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Errasti, Andrea Emilse. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacologia; ArgentinaFil: Gomez, Ricardo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; ArgentinaFil: Jenne, Craig N.. University of Calgary; CanadáFil: Carrera Silva, Eugenio Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

    Structural use of fiber-reinforced self-compacting concrete with recycled aggregates: case study of a foundation wall in Spain

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    This paper is focused on the use of mixed recycled-aggregates (RA), replacing 100% of the natural coarse aggregates, for producing steel fiber reinforced self-compacting concrete (FR-SCC-RA) oriented to the construction of foundation walls. To this end, an extensive experimental program dedicated to the mechanical characterization of FR-SCC-RA foundation walls from the material and structural level was carried out. The former was developed on both molded specimens and cores extracted from the in-situ constructed FR-SCC-RA walls in Barcelona, Spain. The results lead to confirm that the use of RA resulted satisfactorily from both the concrete manufacturing and the mechanical performance, since no affectations on the design mechanical variables (i.e., compressive and flexural tensile strengths) were detected. Likewise, the results derived from the full-scale test evidenced that the residual loads of the slabs tested were significantly higher than those calculated based on the test results of the prismatic core samples. The main outcome derived from the experimental research program is that FR-SCC-RA might be a suitable material for this structural typology and that the tested slabs presented a sufficient post-cracking residual capacity -due to the incorporation of structural fibers- for avoiding fragile failures. These conclusions could be extended to other countries where similar restrictive regulations and standards are present, regarding the use of RA and FRC for structural applications.The authors would like to thank the Agency for Management of University and Research Grants (AGAUR), Barcelona, Spain and the company ESCOFET 1886, S.A., Barcelona, Spain, for the economic support within the Industrial Doctorate Programme of Dr. Francisco Mena. This study was also fund by the Spanish Ministry of Science and Innovation under the scope of project CREEF (PID2019-108978RB-C32). Likewise, the authors wish to thank the Structure Technology Laboratory Luis Agulló Lab Staff, belonging to Barcelona Tech, Spain.Peer ReviewedPostprint (published version

    Basal VEGF-A and ACE Plasma Levels of Metastatic Colorectal-Cancer Patients Have Prognostic Value for First-Line Treatment with Chemotherapy Plus Bevacizumab

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    The identification of factors that respond to anti-angiogenic therapy would represent a significant advance in the therapeutic management of metastatic-colorectal-cancer (mCRC) patients. We previously reported the relevance of VEGF-A and some components of the renin–angiotensin-aldosterone system (RAAS) in the response to anti-angiogenic therapy in cancer patients. Therefore, this prospective study aims to evaluate the prognostic value of basal plasma levels of VEGF-A and angiotensin-converting enzyme (ACE) in 73 mCRC patients who were to receive bevacizumab-based therapies as a first-line treatment. We found that high basal VEGF-A plasma levels were significantly associated with worse overall survival (OS) and progression-free survival (FPS). On the other hand, low ACE levels were significantly associated with poor OS. Importantly, a simple scoring system combining the basal plasma levels of VEGF-A and ACE efficiently stratified mCRC patients, according to OS, into high-risk or low-risk groups, prior to their treatment with bevacizumab. In conclusion, our study supports that VEGF-A and ACE may be potential biomarkers for selecting those mCRC patients who will most benefit from receiving chemotherapy plus bevacizumab treatment in first-line therapy. Additionally, our data reinforce the notion of a close association between the RAAS and the anti-angiogenic response in cancer

    The Combination of Neutrophil–Lymphocyte Ratio and Platelet–Lymphocyte Ratio with Liquid Biopsy Biomarkers Improves Prognosis Prediction in Metastatic Pancreatic Cancer

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    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a highly inflammatory microenvironment and liquid biopsy has emerged as a promising tool for the noninvasive analysis of this tumor. In this study, plasma was obtained from 58 metastatic PDAC patients, and neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), circulating cell-free DNA (cfDNA) concentration, and circulating RAS mutation were determined. We found that NLR was significantly associated with both overall survival (OS) and progression-free survival. Remarkably, NLR was an independent risk factor for poor OS. Moreover, NLR and PLR positively correlated, and combination of both inflammatory markers significantly improved the prognostic stratification of metastatic PDAC patients. NLR also showed a positive correlation with cfDNA levels and RAS mutant allelic fraction (MAF). Besides, we found that neutrophil activation contributed to cfDNA content in the plasma of metastatic PDAC patients. Finally, a multi-parameter prognosis model was designed by combining NLR, PLR, cfDNA levels, RAS mutation, RAS MAF, and CA19-9, which performs as a promising tool to predict the prognosis of metastatic PDAC patients. In conclusion, our study supports the idea that the use of systemic inflammatory markers along with circulating tumor-specific markers may constitute a valuable tool for the clinical management of metastatic PDAC patients

    A phase 2 study of panitumumab with irinotecan as salvage therapy in chemorefractory KRAS exon 2 wild-type metastatic colorectal cancer patients

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    Targeted agents are standard treatment for RAS wild-type metastatic colorectal cancer in the first- and second-line settings. This phase 2 study determined the benefit of targeting the epidermal growth factor receptor (EGFR) with panitumumab plus irinotecan in irinotecan-refractory patients. KRAS exon-2 wild-type patients failing prior irinotecan received panitumumab (6 mg/kg) and irinotecan (180 mg/m²) every 2 weeks. The primary endpoint was the overall response rate (ORR). Secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS). KRAS exon-2 status was evaluated centrally, along with NRAS, BRAF mutations, epiregulin, amphiregulin, PTEN and EGFR copy number status, and correlated with efficacy. Sixty-one patients were treated. Among the 46 wild-type RAS patients, the ORR was 15.2% (seven partial responses), with median PFS of 3.8 months (95% CI 2.7-4.3) and median OS of 12.5 months (95% CI 6.7-15.9). Wild-type BRAF patients showed a 13.0% response rate. No significant correlations between response and baseline biomarker expression were identified. Common grade 3-4 adverse events were diarrhoea and rash (18.0% each), hypomagnesaemia and asthenia (8.2% each). The addition of panitumumab to irinotecan as salvage therapy is feasible but has limited activity in irinotecan-refractory metastatic colorectal cancer. No biomarkers predictive of response were identified

    The synthetic phospholipid C8-C1P determines pro-angiogenic and pro-reparative features in human macrophages restraining the proinflammatory M1-like phenotype

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    Monocytes (Mo) are highly plastic myeloid cells that differentiate into macrophages after extravasation, playing a pivotal role in the resolution of inflammation and regeneration of injured tissues. Wound-infiltrated monocytes/macrophages are more pro-inflammatory at early time points, while showing anti-inflammatory/pro-reparative phenotypes at later phases, with highly dynamic switching depending on the wound environment. Chronic wounds are often arrested in the inflammatory phase with hampered inflammatory/repair phenotype transition. Promoting the tissue repair program switching represents a promising strategy to revert chronic inflammatory wounds, one of the major public health loads. We found that the synthetic lipid C8-C1P primes human CD14+ monocytes, restraining the inflammatory activation markers (HLA-DR, CD44, and CD80) and IL-6 when challenged with LPS, and preventing apoptosis by inducing BCL-2. We also observed increased pseudo-tubule formation of human endothelial-colony-forming cells (ECFCs) when stimulated with the C1P-macrophages secretome. Moreover, C8-C1P-primed monocytes skew differentiation toward pro-resolutive-like macrophages, even in the presence of inflammatory PAMPs and DAMPs by increasing anti-inflammatory and pro-angiogenic gene expression patterns. All these results indicate that C8-C1P could restrain M1 skewing and promote the program of tissue repair and pro-angiogenic macrophage

    Metabolic shift underlies tumor progression and immune evasion in S-nitrosoglutathione reductase-deficient cancer

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    S-nitrosoglutathione reductase (GSNOR) is a denitrosylase enzyme that has been suggested to play a tumor suppressor role, although the mechanisms responsible are still largely unclear. In this study, we show that GSNOR deficiency in tumors is associated with poor prognostic histopathological features and poor survival in patients with colorectal cancer (CRC). GSNOR-low tumors were characterized by an immunosuppressive microenvironment with exclusion of cytotoxic CD8+ T cells. Notably, GSNOR-low tumors exhibited an immune evasive proteomic signature along with an altered energy metabolism characterized by impaired oxidative phosphorylation (OXPHOS) and energetic dependence on glycolytic activity. CRISPR-Cas9-mediated generation of GSNOR gene knockout (KO) CRC cells confirmed in vitro and in vivo that GSNOR-deficiency conferred higher tumorigenic and tumor-initiating capacities. Moreover, GSNOR-KO cells possessed enhanced immune evasive properties and resistance to immunotherapy, as revealed following xenografting them into humanized mouse models. Importantly, GSNOR-KO cells were characterized by a metabolic shift from OXPHOS to glycolysis to produce energy, as indicated by increased lactate secretion, higher sensitivity to 2-deoxyglucose (2DG), and a fragmented mitochondrial network. Real-time metabolic analysis revealed that GSNOR-KO cells operated close to their maximal glycolytic rate, as a compensation for lower OXPHOS levels, explaining their higher sensitivity to 2DG. Remarkably, this higher susceptibility to glycolysis inhibition with 2DG was validated in patient-derived xenografts and organoids from clinical GSNOR-low tumors. In conclusion, our data support the idea that metabolic reprogramming induced by GSNOR deficiency is an important mechanism for tumor progression and immune evasion in CRC and that the metabolic vulnerabilities associated with the deficiency of this denitrosylase can be exploited therapeutically. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

    Proyecto de emprendimiento para la creación de la micro empresa Piensa En Verde, dedicada a la elaboración y comercialización del jarabe Digestin Plus, ubicada en el municipio de Jinotepe, departamento de Carazo, durante el segundo semestre del año 2019

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    Proyecto de emprendimiento para la micro empresa Piensa En Verde dedicada a la elaboración y comercialización del jarabe Digestin Plus. Digestin plus, nombre asignado al jarabe de marañón y miel, innovado por el grupo multidisciplinario de la FAREM, Carazo, que está conformado por diferentes carreras como es mercadotecnia, contabilidad y administración de empresa, al realizarse un conjunto de ideas para al proyecto se tomó una decisión por mayoría de votos. Este es un jarabe 100% natural, ya que no contiene ningún tipo de conservante químico, puesto que una de las tantas funciones que tiene la miel es esa. La combinación de estos 2 componentes como es el marañón y la miel han creado un poderoso jarabe que tiene como propósito estimular al organismo luego que las personas ingieran comidas con muchos condimentos que causan espasmos estomacales y problemas gastrointestinales, este ayudara a que el sistema digestivo pueda facilitar la digestión de estos alimento

    Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

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    SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation
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