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Movie S2 from Liver Metastasis Is Facilitated by the Adherence of Circulating Tumor Cells to Vasc... more Movie S2 from Liver Metastasis Is Facilitated by the Adherence of Circulating Tumor Cells to Vascular Fibronectin Deposits
AQ-WATCH (Air Quality: Worldwide Analysis and Forecasting of Atmospheric Composition for Health) ... more AQ-WATCH (Air Quality: Worldwide Analysis and Forecasting of Atmospheric Composition for Health) is an international consortium, which co-develops and co-produces tailored products and services derived from space and in situ observational data for improving air quality forecasts and attribution. For this purpose, AQ-WATCH develops a supply chain leading to innovative downstream products and services for providing air quality information tailored to the identified needs of international users. This presentation will focus on one of the AQ-WATCH products, the AQ-WATCH air quality forecast system. Air quality forecast models provided by the AQ-WATCH consortium are set up for the focus regions in Asia and the Americas, based on the templates of Copernicus European and MarcoPolo-Panda Asian ensembles, but with much higher resolution and reliance on regional emission and observational information. The models are established over the focus regions using the meteorological and emission data...
BackgroundTherapies to interrupt progression of early COVID-19 remain elusive. Among them, conval... more BackgroundTherapies to interrupt progression of early COVID-19 remain elusive. Among them, convalescent plasma in hospitalized patients was unsuccessful, perhaps because antibody should be administered earlier. We advanced plasma infusions to the first 72 hours of symptoms to arrest COVID-19 progression.MethodsA randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against SARS-CoV2 in elderly subjects within 72 hours of mild COVID-19 symptoms. The primary endpoint was severe respiratory disease defined as a respiratory rate ≥30 and/or an O2sat<93% in room air. The study was interrupted at 76% of its projected sample size, because cases in the region decreased considerably and steady enrollment of study subjects became virtually impossible.Results160 patients underwent randomization. In the intention-to-treat analysis (ITT), 13/80(16.2%) patients receiving plasma vs. 25/80(31.2%) receiving placebo experienced severe respiratory disease [RR...
Gastroenterology, 2017
Background and aim: The large conductance Ca2+-activated K+ (BK) channel regulates smooth muscle ... more Background and aim: The large conductance Ca2+-activated K+ (BK) channel regulates smooth muscle contractility by modulating membrane potential, and age-associated changes in BK channel expression may contribute to the development of motility disorders of the gastrointestinal tract. Advanced glycation end products (AGEs) result from a slow chemical reaction between the sugars and amine groups in proteins, lipids, or DNA in the body. AGEs have been observed to accumulate in various organs with aging. In this study, we examined whether AGEs accumulation with aging would be related to BK-β1 subunits upregulation and contractile dysfunction of colonic SMCs. Methods: Male Sprague-Dawley (SD) rats were randomly divided into four experimental groups: juvenile, young, middleaged, and aged. Colonic transit time and colonic SM strip contractility in the groups were measured. Levels of AGEs and AGEs receptor (RAGE) in serum and colon muscle layer were tested. Primary cultured colonic smooth muscle cells (SMCs) were used in complementary in vitro studies. In the presence and absence of AGEs-BSA, SMC were treated with the ERK1/2 inhibitors PD98059 and U0126, the P38-MAPK inhibitors SB203580 and SB202190, or the PI3K inhibitors LY294002 or RAGE small interfering RNA (siRNA). BK-β1 subunits expression, BK channel currents, [Ca2+]i and myosin light chain (MLC) in SMC were also tested. Results: Colonic motility decreases in an age-dependent manner, while the serum AGEs and colonic SM RAGE and BK-β1 subunits expression increase in an age-dependent manner. In primary colonic SMCs, AGEs-BSA increased BK-β1 subunits expression in a time-and dose-dependent manner without changing the sigle BK channel currents. In addition, AGEs-BSA decrease intracellular Ca2+ concentrations and myosin light chain phosphorylation in a dose-dependent manner. The P38-MAPK inhibitors SB203580 and SB202190 could significantly inhibited AGEs-BSA induced BK-β1 subunits upregulation. After interfer RAGE expression with RAGE siRNA, AGEs-BSA induced BK-β1 subunits upregulation could also be partially reversed. Conclusions: This study suggested that AGEs/ RAGE participate in aging-associated colonic dysmotility by upregulation of BK channel β1subunit in colonic SMC. This effect depends on the activation of P38-MAPK pathway.
Boletin Del Museo Del Prado, 2013
espanolEste articulo estudia el programa de enmarcado que se llevo a cabo en el Museo del Prado p... more espanolEste articulo estudia el programa de enmarcado que se llevo a cabo en el Museo del Prado por la familia Cano durante la primera mitad del siglo XX. Este proceso se vincula con la transformacion de las salas del Museo, con la implicacion de la Direccion y del Real Patronato y con un importante patrocinio por parte de destacados miembros de la nobleza espanola de la epoca de alfonso XIII. por primera vez se publican los dibujos preparatorios de los marcos que, unidos a informacion documental recientemente recuperada, explican el ambicioso programa de enmarcado que abarcaba desde la seleccion de obras hasta la financiacion y ejecucion final de los marcos. EnglishThis article examines the reframing campaign undertaken by the Cano family that took place in the Museo del Prado during the first half of the twentieth century. This process was a consequence of the remodeling of the Museum's galleries and was promoted by the Directors, the Real Patronato and supported through the sponsorship of members of the Spanish nobility. The preparatory drawings for these frames are published here for the first time. These drawings together with new documentary evedence help explain the procedure, from the selection of paintings to be reframed, to the financing and manufacture of the frames.
Galeria Antiqvaria Arte Contemporaneo Antiguedades Mercado Coleccionismo, 2002
La finalidad de este documento es proporcionar al lector, primero, una rápida ojeada a la trayect... more La finalidad de este documento es proporcionar al lector, primero, una rápida ojeada a la trayectoria histórica de la atención a las NEE (más concretamente de las altas capacidades); segundo, una conceptualización de las altas capacidades y sus necesidades educativas específicas tomando como punto de referencia algunos de lo más eminentes autores y corrientes psicopedagógicas actuales o del pasado reciente; y por último, facilitar ejemplos prácticos desde la perspectiva del docente de cómo acometer la difícil tarea de atender las necesidades educativas específicas de los alumnos/as con mayor capacidad intelectual dentro del aula y sacar provecho de estas capacidades favoreciendo el desarrollo de los demás alumnos/as.
Clinical Infectious Diseases, 2003
We describe a patient who had growth hormone receptor-expressing carcinoid tumors develop in the ... more We describe a patient who had growth hormone receptor-expressing carcinoid tumors develop in the distal colon and rectum after he received recombinant human growth hormone therapy for human immunodeficiency virus-related lipodystrophy. This case report serves as a cautionary note regarding the use of potentially oncogenic recombinant human growth hormone therapy to treat human immunodeficiency virus-positive persons. Habitus changes due to abnormal fat distribution (i.e., lipodystrophy) are some of the long-term side effects of HAART used in the treatment of HIV infection. One investigational approach to treating HIV-related lipodystrophy involves the use of recombinant human growth hormone (rhGH) [1, 2]. The reported side effects of growth hormone (GH) therapy include sodium retention and edema, arthralgia, myalgia, carpal tunnel syndrome, diabetes, and enhanced HIV replication. Recently, a case of squamous cell carcinoma was documented in a person being treated with rhGH [3]. We describe a patient who developed growth hormone receptor-expressing carcinoid tumors in the distal colon and rectum after receiving rhGH therapy for HIV-related lipodystrophy. A 40-year-old obese man (weight, 119 kg; height, 182 cm; and body mass index, 36), who had an absolute CD4 cell count of 584 cells/mL and a nondetectable HIV-1 load, experienced lipodystrophy while being treated with a HAART regimen that
Experimental Eye Research, 1998
The purpose of this work was to investigate if MYC-dependent intracellular mitogenic pathway is a... more The purpose of this work was to investigate if MYC-dependent intracellular mitogenic pathway is active in cultures of human retinal pigment epithelial (hRPE) cells and whether myc antisense phosphorotioate oligonucleotides (c-myc-AS-ODN) are useful tools for inhibiting the proliferation of hRPE cells. Cultures of hRPE cells were established from adult human corneal donors. These cells were positively stained for cytokeratins and vimentin. Myc mRNA expression was determined by Northern blot analysis and it was determined by means of immunofluorescence if MYC was expressed. C-myc-AS-ODN effect on cell proliferation was estimated by evaluating the incorporation of 5-bromo-2h-deoxy-uridine into cellular DNA. Cell number was estimated by using a tetrazolium bromide based colorimetric method. Human RPE cells in culture expressed MYC and myc mRNA as well as prothymosin α mRNA-a gene whose transcription is under MYC control-indicating that MYC-dependent intracellular mitogenic pathway is active in these cells. In accordance with this, we found that blocking the expression of myc by the addition of c-myc-AS-ODN to the culture medium inhibited hRPE cell proliferation. The effect of the c-myc-AS-ODN was found to be sequence specific (the use of a control oligonucleotide with the same sequence but in an opposite direction had no effect) and dose-dependent (4 µ was the lowest effective dose tested). By using RT-PCR we found that the c-myc-AS-ODN inhibition of cell proliferation was related to a diminution in c-myc mRNA expression, and by immunofluorescence we detected a diminution in c-MYC protein staining in RPE cells after 48 hr of treatment with c-myc-AS-ODN. Furthermore, growth inhibition remained for at least 5 days after addition of a single dose of the c-myc-AS-ODN to the culture. We conclude that hRPE cell proliferation is under MYC control. Blocking the expression of myc by c-myc-AS-ODN inhibited hRPE cell proliferation. These findings establish a rationale for investigating the potential use of a c-myc-AS-ODN as a novel therapeutical tool in the treatment of Proliferative Vitreoretinopathy.
Movie S2 from Liver Metastasis Is Facilitated by the Adherence of Circulating Tumor Cells to Vasc... more Movie S2 from Liver Metastasis Is Facilitated by the Adherence of Circulating Tumor Cells to Vascular Fibronectin Deposits
AQ-WATCH (Air Quality: Worldwide Analysis and Forecasting of Atmospheric Composition for Health) ... more AQ-WATCH (Air Quality: Worldwide Analysis and Forecasting of Atmospheric Composition for Health) is an international consortium, which co-develops and co-produces tailored products and services derived from space and in situ observational data for improving air quality forecasts and attribution. For this purpose, AQ-WATCH develops a supply chain leading to innovative downstream products and services for providing air quality information tailored to the identified needs of international users. This presentation will focus on one of the AQ-WATCH products, the AQ-WATCH air quality forecast system. Air quality forecast models provided by the AQ-WATCH consortium are set up for the focus regions in Asia and the Americas, based on the templates of Copernicus European and MarcoPolo-Panda Asian ensembles, but with much higher resolution and reliance on regional emission and observational information. The models are established over the focus regions using the meteorological and emission data...
BackgroundTherapies to interrupt progression of early COVID-19 remain elusive. Among them, conval... more BackgroundTherapies to interrupt progression of early COVID-19 remain elusive. Among them, convalescent plasma in hospitalized patients was unsuccessful, perhaps because antibody should be administered earlier. We advanced plasma infusions to the first 72 hours of symptoms to arrest COVID-19 progression.MethodsA randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against SARS-CoV2 in elderly subjects within 72 hours of mild COVID-19 symptoms. The primary endpoint was severe respiratory disease defined as a respiratory rate ≥30 and/or an O2sat<93% in room air. The study was interrupted at 76% of its projected sample size, because cases in the region decreased considerably and steady enrollment of study subjects became virtually impossible.Results160 patients underwent randomization. In the intention-to-treat analysis (ITT), 13/80(16.2%) patients receiving plasma vs. 25/80(31.2%) receiving placebo experienced severe respiratory disease [RR...
Gastroenterology, 2017
Background and aim: The large conductance Ca2+-activated K+ (BK) channel regulates smooth muscle ... more Background and aim: The large conductance Ca2+-activated K+ (BK) channel regulates smooth muscle contractility by modulating membrane potential, and age-associated changes in BK channel expression may contribute to the development of motility disorders of the gastrointestinal tract. Advanced glycation end products (AGEs) result from a slow chemical reaction between the sugars and amine groups in proteins, lipids, or DNA in the body. AGEs have been observed to accumulate in various organs with aging. In this study, we examined whether AGEs accumulation with aging would be related to BK-β1 subunits upregulation and contractile dysfunction of colonic SMCs. Methods: Male Sprague-Dawley (SD) rats were randomly divided into four experimental groups: juvenile, young, middleaged, and aged. Colonic transit time and colonic SM strip contractility in the groups were measured. Levels of AGEs and AGEs receptor (RAGE) in serum and colon muscle layer were tested. Primary cultured colonic smooth muscle cells (SMCs) were used in complementary in vitro studies. In the presence and absence of AGEs-BSA, SMC were treated with the ERK1/2 inhibitors PD98059 and U0126, the P38-MAPK inhibitors SB203580 and SB202190, or the PI3K inhibitors LY294002 or RAGE small interfering RNA (siRNA). BK-β1 subunits expression, BK channel currents, [Ca2+]i and myosin light chain (MLC) in SMC were also tested. Results: Colonic motility decreases in an age-dependent manner, while the serum AGEs and colonic SM RAGE and BK-β1 subunits expression increase in an age-dependent manner. In primary colonic SMCs, AGEs-BSA increased BK-β1 subunits expression in a time-and dose-dependent manner without changing the sigle BK channel currents. In addition, AGEs-BSA decrease intracellular Ca2+ concentrations and myosin light chain phosphorylation in a dose-dependent manner. The P38-MAPK inhibitors SB203580 and SB202190 could significantly inhibited AGEs-BSA induced BK-β1 subunits upregulation. After interfer RAGE expression with RAGE siRNA, AGEs-BSA induced BK-β1 subunits upregulation could also be partially reversed. Conclusions: This study suggested that AGEs/ RAGE participate in aging-associated colonic dysmotility by upregulation of BK channel β1subunit in colonic SMC. This effect depends on the activation of P38-MAPK pathway.
Boletin Del Museo Del Prado, 2013
espanolEste articulo estudia el programa de enmarcado que se llevo a cabo en el Museo del Prado p... more espanolEste articulo estudia el programa de enmarcado que se llevo a cabo en el Museo del Prado por la familia Cano durante la primera mitad del siglo XX. Este proceso se vincula con la transformacion de las salas del Museo, con la implicacion de la Direccion y del Real Patronato y con un importante patrocinio por parte de destacados miembros de la nobleza espanola de la epoca de alfonso XIII. por primera vez se publican los dibujos preparatorios de los marcos que, unidos a informacion documental recientemente recuperada, explican el ambicioso programa de enmarcado que abarcaba desde la seleccion de obras hasta la financiacion y ejecucion final de los marcos. EnglishThis article examines the reframing campaign undertaken by the Cano family that took place in the Museo del Prado during the first half of the twentieth century. This process was a consequence of the remodeling of the Museum's galleries and was promoted by the Directors, the Real Patronato and supported through the sponsorship of members of the Spanish nobility. The preparatory drawings for these frames are published here for the first time. These drawings together with new documentary evedence help explain the procedure, from the selection of paintings to be reframed, to the financing and manufacture of the frames.
Galeria Antiqvaria Arte Contemporaneo Antiguedades Mercado Coleccionismo, 2002
La finalidad de este documento es proporcionar al lector, primero, una rápida ojeada a la trayect... more La finalidad de este documento es proporcionar al lector, primero, una rápida ojeada a la trayectoria histórica de la atención a las NEE (más concretamente de las altas capacidades); segundo, una conceptualización de las altas capacidades y sus necesidades educativas específicas tomando como punto de referencia algunos de lo más eminentes autores y corrientes psicopedagógicas actuales o del pasado reciente; y por último, facilitar ejemplos prácticos desde la perspectiva del docente de cómo acometer la difícil tarea de atender las necesidades educativas específicas de los alumnos/as con mayor capacidad intelectual dentro del aula y sacar provecho de estas capacidades favoreciendo el desarrollo de los demás alumnos/as.
Clinical Infectious Diseases, 2003
We describe a patient who had growth hormone receptor-expressing carcinoid tumors develop in the ... more We describe a patient who had growth hormone receptor-expressing carcinoid tumors develop in the distal colon and rectum after he received recombinant human growth hormone therapy for human immunodeficiency virus-related lipodystrophy. This case report serves as a cautionary note regarding the use of potentially oncogenic recombinant human growth hormone therapy to treat human immunodeficiency virus-positive persons. Habitus changes due to abnormal fat distribution (i.e., lipodystrophy) are some of the long-term side effects of HAART used in the treatment of HIV infection. One investigational approach to treating HIV-related lipodystrophy involves the use of recombinant human growth hormone (rhGH) [1, 2]. The reported side effects of growth hormone (GH) therapy include sodium retention and edema, arthralgia, myalgia, carpal tunnel syndrome, diabetes, and enhanced HIV replication. Recently, a case of squamous cell carcinoma was documented in a person being treated with rhGH [3]. We describe a patient who developed growth hormone receptor-expressing carcinoid tumors in the distal colon and rectum after receiving rhGH therapy for HIV-related lipodystrophy. A 40-year-old obese man (weight, 119 kg; height, 182 cm; and body mass index, 36), who had an absolute CD4 cell count of 584 cells/mL and a nondetectable HIV-1 load, experienced lipodystrophy while being treated with a HAART regimen that
Experimental Eye Research, 1998
The purpose of this work was to investigate if MYC-dependent intracellular mitogenic pathway is a... more The purpose of this work was to investigate if MYC-dependent intracellular mitogenic pathway is active in cultures of human retinal pigment epithelial (hRPE) cells and whether myc antisense phosphorotioate oligonucleotides (c-myc-AS-ODN) are useful tools for inhibiting the proliferation of hRPE cells. Cultures of hRPE cells were established from adult human corneal donors. These cells were positively stained for cytokeratins and vimentin. Myc mRNA expression was determined by Northern blot analysis and it was determined by means of immunofluorescence if MYC was expressed. C-myc-AS-ODN effect on cell proliferation was estimated by evaluating the incorporation of 5-bromo-2h-deoxy-uridine into cellular DNA. Cell number was estimated by using a tetrazolium bromide based colorimetric method. Human RPE cells in culture expressed MYC and myc mRNA as well as prothymosin α mRNA-a gene whose transcription is under MYC control-indicating that MYC-dependent intracellular mitogenic pathway is active in these cells. In accordance with this, we found that blocking the expression of myc by the addition of c-myc-AS-ODN to the culture medium inhibited hRPE cell proliferation. The effect of the c-myc-AS-ODN was found to be sequence specific (the use of a control oligonucleotide with the same sequence but in an opposite direction had no effect) and dose-dependent (4 µ was the lowest effective dose tested). By using RT-PCR we found that the c-myc-AS-ODN inhibition of cell proliferation was related to a diminution in c-myc mRNA expression, and by immunofluorescence we detected a diminution in c-MYC protein staining in RPE cells after 48 hr of treatment with c-myc-AS-ODN. Furthermore, growth inhibition remained for at least 5 days after addition of a single dose of the c-myc-AS-ODN to the culture. We conclude that hRPE cell proliferation is under MYC control. Blocking the expression of myc by c-myc-AS-ODN inhibited hRPE cell proliferation. These findings establish a rationale for investigating the potential use of a c-myc-AS-ODN as a novel therapeutical tool in the treatment of Proliferative Vitreoretinopathy.