Tamoxifen alters lysosomes of breast cancer cells by a mechanism independent of its anti-estrogenic activity

Breast cancer is one of the most important causes of morbidity and mortality worldwide. It has been shown that the cells of some tumors have an increased lysosomal biogenesis in response to metabolic alterations, which also has an impact on the integrity and/or lysosomal functionality, showing increased levels of lysosomal proteases, such as cathepsin D (CatD). It has been demonstrated that this enzyme induces apoptosis when is released into the cytoplasm. Since the lysosomes could play a role either as initiators or executors of apoptotic processes when the membrane integrity is altered, this organelle could be taken as a potential therapeutic target against tumors. In breast cancer cell lines positive to estrogen receptor RE (REα), CatD is positively regulated by this hormone, while in cell lines negative for REα the enzyme is constitutively overexpressed. Tamoxifen (TAM) is one of the most common anti-estrogenic drugs used in breast cancer therapy. It interacts with ER and inhibits transcriptional activity in the mammary gland. The aim of this study was to evaluate the effect of estrogens and tamoxifen on lysosomal acidification and CatD processing in breast cancer cells. Mammary cell lines MCF-7 (tumorigenic expressing REα), MDA-MB231 (tumorigenic non-expressing REα) and MCF-10A (non-tumorigenic) were treated in the presence or absence of 17-β-estradiol and/or TAM. For quantification of acidic lysosomes, cells were treated with Lysotracker. Cultures were subjected to immunoblot analysis and fluorescence microscopy. As expected, TAM blocked the effect of estrogen on CatD processing in MCF-7 cells. However, TAM used alone, also altered CatD processing and decreased the number of acidic lysosomes in both cell lines. Neither effect of TAM was observed on MCF-10A cell line. In addition, a decreased level of another lysosomal protein, GM2AP (related to the development of tumors), was observed in the cells due to TAM. All these results suggest that TAM has additional effects independent of its anti-estrogenic activity, possibly due to lysosomotropic action.Fil: Pereyra, Laura Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Ministerio de Salud. Instituto Nacional del Cáncer; ArgentinaFil: Bannoud, Nadia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Guarniolo, D.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Chapana, Agostina Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Carvelli, Flavia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaXXXVI Reunión Científica Anual de la Sociedad de Biología de CuyoMendozaArgentinaSociedad de Biología de Cuy

Castration causes an increase in lysosomal size and upregulation of cathepsin D expression in principal cells along with increased secretion of procathepsin D and prosaposin oligomers in adult rat epididymis

In the epididymis, lysosomal proteins of the epithelial cells are normally targeted from the Golgi apparatus to lysosomes for degradation, although their secretion into the epididymal lumen has been documented and associated with sperm maturation. In this study, cathepsin D (CatD) and prosaposin (PSAP) were examined in adult epididymis of control, and 2-day castrated rats without (Ct) and with testosterone replacement (Ct+T) to evaluate their expression and regulation within epididymal epithelial cells. By light microscope-immunocytochemistry, a quantitative increase in size of lysosomes in principal cells of Ct animals was noted from the distal initial segment to the proximal cauda. Androgen replacement did not restore the size of lysosomes to control levels. Western blot analysis revealed a significant increase in CatD expression in the epididymis of Ct animals, which suggested an upregulation of its expression in principal cells; androgens restored levels of CatD to that of controls. In contrast, PSAP expression in Ct animals was not altered from controls. Additionally, an increase in procathepsin D levels was noted from samples of the epididymal fluid of Ct compared to control animals, accompanied by an increased complex formation with PSAP. Moreover, an increased oligomerization of prosaposin was observed in the epididymal lumen of Ct rats, with changes reverted to controls in Ct+T animals. Taken together these data suggest castration causes an increased uptake of substrates that are acted upon by CatD in lysosomes of principal cells and in the lumen by procathepsin D. These substrates may be derived from apoptotic cells noted in the lumen of proximal regions and possibly by degenerating sperm in distal regions of the epididymis of Ct animals. Exploring the mechanisms by which lysosomal enzymes are synthesized and secreted by the epididymis may help resolve some of the issues originating from epididymal dysfunctions with relevance to sperm maturation.Fil: Carvelli, Flavia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Aguilera, Andrea Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Zyla, Leila Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Pereyra, Laura Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Morales, Carlos R.. McGill University; CanadáFil: Hermo, Louis. McGill University; CanadáFil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; Argentin

Optimization and production of probiotic and antimycotoxin yeast biomass using bioethanol industry waste via response surface methodology

Saccharomyces cerevisiae RC016 presents probiotic and mycotoxin adsorbent properties for use as feed additive. The improvement of S. cerevisiae RC016 biomass production using an agro-industrial waste such as Dried Distillers'Grains and Solubles (DDGs) that pollute the environment can contribute to sustainable development of the process and reduce the costs of large-scale production. In order to avoid theobstruction of the fermentor?s stirring mechanism with solid particles a novel pre treatment of DDGs was conducted to concentrate carbon sources levels. The design of experiments were performed using four factor-three-level Box-Behnken design (carbon source concentration, nitrogen source concentration, yeast extract concentration and incubation time) coupled with response surface methodology to evaluate theinteraction between two factors in order to determine the optimum process conditions. A quadratic model was suggested for the predictionof biomass production. The F-value and p-value of the model indicated that it was statistically significant at 95 percent confidence interval. Inaddition, R2 value of the model indicated an acceptable accuracy. The results were validated at bioreactor level showing that the specific growthrate on the optimized medium (0.34h-1) increased 112.5% compared to the initial non-optimized medium (0.16h-1), the duplication time showeda decrease of 52.9%. Optimization enabled productivity (0.451gL-1h-1) nine times higher than the initial one (0.062gL-1h-1), thus 65% more biomass was obtained (5.20gL-1). The use of biomass DDGse derived from bioethanol production promotes the sustainable and green way of biomass production.Fil: Fochesato, Analía Silvia. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Microbiología e Inmunología. Cátedra de Micología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Galvagno, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Dogi, Cecilia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Microbiología e Inmunología. Cátedra de Micología; ArgentinaFil: Cerrutti, Patricia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Industrias. Carrera de Especialista en Area de Bromatología y Tecnología de la Industrialización de Alimentos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gonzalez Pereyra, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Microbiología e Inmunología. Cátedra de Micología; ArgentinaFil: Flores, Marcelo David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Planta Piloto de Procesos Industriales Microbiológicos; ArgentinaFil: Cavaglieri, Lilia Reneé. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Microbiología e Inmunología. Cátedra de Micología; Argentin

Rendimiento y composición proteica del grano de trigo (Triticum aestivum L.) en respuesta a condiciones contrastantes de disponibilidad de agua y nitrógeno en inicio de floració

The area of wheat cropping in La Pampa province is included in the Region V South of Argentina for production of that cereal, where water and nitrogen low availabilities are the main limiting factors for wheat grain yield. The present work was aimed at analyzing grain yield and changes in grain protein composition of four genotypes of Triticum aestivum L. subjected to different availability levels of water and nitrogen. The assay was performed in pots under greenhouse condition and utilizing wheat cultivars ACA 315, Baguette Premium 11, Klein Proteo and DM Cronox. At the start of flowering half of the pots were fertilized with 100 kg N ha-1 and, until grain harvest, half of the pots were kept at 50 and the other half at 100% field capacity. Grain yield components, greenness index, grain protein concentration, grain nitrogen content and gliadins and glutenins concentration in flour were the variables determined in the assay. DM Cronox was the cultivar that expressed the highest grain yield. Under conditions of limiting water availability, the gluteninrich fraction increased and that of gliadins decreased in two of the genotypes, whereas addition of nitrogen led to an increase only in the glutenin content. Concentrations of protein fractions are associated to grain nitrogen content, mainly for gliadins. The change in wheat grain protein fractions upon variation of water and nitrogen availabilities depends on the genotype environment relationship. DOI: http://dx.doi.org/10.19137/semiarida.2017(02).3750La provincia de La Pampa se ubica en la Región Triguera V Sur, siendo las principales limitantes para la producción triguera la baja disponibilidad de agua y nitrógeno. En el presente trabajo se analizó el rendimiento y los cambios en la composición proteica del grano de cuatro genotipos de Triticum aestivum L. bajo diferentes condiciones de disponibilidad de agua y nitrógeno. Se trabajó en invernáculo con los cultivares ACA 315, Baguette Premium 11, Klein Proteo y DM Cronox. En inicio de floración la mitad de las macetas fueron fertilizadas con 100 Kg N.ha-1. Hasta la cosecha la mitad de las macetas se mantuvieron al 50 y la otra mitad al 100% de capacidad de campo. Se determinaron los componentes del rendimiento, índice de verdor, concentración de proteína, contenido de nitrógeno en grano y concentración de gliadinas y gluteninas en harinas. El cultivar DM Cronox, expresó el mayor rendimiento. En condiciones hídricas limitantes, en dos genotipos, aumentó la fracción rica en gluteninas y disminuyó la de gliadinas, mientras que ante el agregado de nitrógeno sólo aumentó la de gluteninas. La concentración de las fracciones proteicas está asociada al contenido de nitrógeno en grano, principalmente las gliadinas. El cambio en las fracciones proteicas del grano de trigo, al variar la disponibilidad de agua y de nitrógeno depende de la relación genotipo ambiente. DOI: http://dx.doi.org/10.19137/semiarida.2017(02).375

Assessing the performance of analytical methods for propolis – A collaborative trial by the international honey commission

Propolis is a resinous beehive product with extraordinary bioactivity and chemical richness, linked with the botanical sources of the resin. The potential of this product keeps captivating the scientific community, conducting to continuous and growing research on plant sources, composition, or applications in agriculture, cosmetics, pharmacy, odontology, etc. In all cases, the quality assessment is a requirement and relies on methods to extract the bioactive substances from the raw propolis and quantify different components. Unfortunately, besides the absence of international quality requirements, there is also a lack of standardized analytical procedures, despite the presence of several methodologies with unknown reliability, often not comparable. To overcome the current status, the International Honey Commission established an inter-laboratory study, with propolis samples from around the globe, to harmonize analytical methods and evaluate their accuracy. A common set of protocols was matched between twelve laboratories from nine countries, for quantification of ash, wax, and balsamic content in raw propolis, and spectrophotometric evaluation of total phenolics, flavone/flavonol, and flavanone/ dihydroflavonol in the extract. A total of 3428 results (97% valid data), were used to assess the methods’ accuracy following ISO-5725 guidelines. The within-laboratory precision, revealed good agreement levels for the majority of the methods, with relative variance below 5%. As expected, the between-laboratory variance increased, but, with exception of the flavanone method that revealed a clear lack of consistency, all the others maintained acceptable variability levels, below 30%. Because the performance of ultrasounds procedures was low, they cannot be recommended until further improvements are made.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support by national funds FCT/MCTES to CIMO (UIDB/00690/2020). Thanks to the Programa Apíıcola Nacional 2020-2022 (National Beekeeping Program) for funding the project "Standardization of production procedures and quality parameters of bee products" and to Project PDR2020-1.0.1- FEADER-031734: “DivInA-Diversification and Innovation on Beekeeping Production”. National funding by FCT – Foundation for Science and Technology, through the institutional scientific employment program-contract with Soraia I. Falcão. A special thanks is given to Hartmut Scheiter and Allwex Food Trading GmbH, Bremen, Germany, for providing, handling and delivering the propolis blind samples.info:eu-repo/semantics/publishedVersio

Bioethanol production from grain sorghum (sorghum bicolor l. moench) at laboratory scale

En el presente trabajo se investigó la producción de bioetanol a partir de sorgo granífero, en respuesta a la necesidad de explorar otros materiales para obtener alcohol por fermentación. Se diseñó un protocolo experimental de laboratorio para evaluar el rendimiento en bioetanol en 7 genotipos. La producción de bioetanol varió de 428,13 a 481,5 ml.kg MS­1 después de 68 horas de fermentación. Los genotipos INTA Blanco y Antel INTA expresaron un rendimiento en bioetanol significativamente diferente. En esta investigación no pudo determinarse el efecto de las propiedades particulares del grano sobre la bioconversión. El alto rendimiento de bioetanol demuestra que el sorgo granífero puede ser una alternativa para diferentes regiones, ya que es un cultivo que se adapta a diferentes tipos de suelos y clima.The production of ethanol from grain sorghum was investigated in the present work, in response to the need of exploring other materials to obtain alcohol by fermentation. A laboratory experimental protocol was designed in order to evaluate ethanol yield, from grain in 7 genotypes. The ethanol production varied from 428,13 to 481,5 ml.kg MS­1 at 68 hours of fermentation. INTA Blanco and Antel INTA genotypes significantly differed in ethanol yield. Through this research it was not possible to determine the impact of particular grain properties on bioconversion. The high ethanol yield demonstrated that grain sorghum can be an alternative for different regions, since it is a crop that adapts to different soil types and climate.Fil: Picca, Aurora Maria Teresita. Universidad Nacional de La Pampa. Facultad de Agronomía; ArgentinaFil: Castaño Zubieta, Mirta Raquel. Universidad Nacional de La Pampa. Facultad de Agronomía; ArgentinaFil: Isasti, Julián José. Universidad Nacional de La Pampa. Facultad de Agronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pereyra Cardozo, María Clementina. Universidad Nacional de La Pampa. Facultad de Agronomía; ArgentinaFil: Fernandez, Miguel Angel. Universidad Nacional de La Pampa. Facultad de Agronomía; ArgentinaFil: Ferrari, Enzo David. Universidad Nacional de La Pampa. Facultad de Agronomía; ArgentinaFil: Domínguez, Rodolfo. Universidad Nacional de La Pampa. Facultad de Agronomía; ArgentinaFil: Paccapelo, Hector Antonio. Universidad Nacional de La Pampa. Facultad de Agronomía; Argentin

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Ensayos sobre aplicación de la Teoría del Estado en las algunas culturas del Perú antiguo

Investigations of State Theory on the cultures of ancient Peru.Capítulos de libro con investigaciones de Teoría del Estado sobre las culturas del Perú antiguo, realizado por docentes y estudiantes de la Escuela Profesional de Derecho de la Universidad Nacional del Altiplano de Puno.      

Ensayos sobre aplicación de la Teoría del Estado en las algunas culturas del Perú antiguo

Investigations of State Theory on the cultures of ancient Peru.Capítulos de libro con investigaciones de Teoría del Estado sobre las culturas del Perú antiguo, realizado por docentes y estudiantes de la Escuela Profesional de Derecho de la Universidad Nacional del Altiplano de Puno.