New and combined treatments for cirrhosis and portal hypertension: effects on hemodynamics and hepatic fibrosis in experimental animal models

La cirrosi, la causa més freqüent d'hipertensió portal (HTP) en els països occidentals, és considerada una malaltia amb múltiples fases, que evoluciona des d'etapes inicials asimptomàtiques a un estat de cirrosi descompensada amb diverses manifestacions clíniques, les quals representen la principal causa de mort i de trasplantament hepàtic a tot el món. Per tant, caldria adaptar les diferents teràpies per a la cirrosi a cadascuna de les fases de la malaltia. Malgrat els avenços realitzats en les últimes dècades per entendre millor la fisiopatologia de la HTP i poder desenvolupar noves estratègies farmacològiques, fins al moment, els beta-bloquejants no selectius (BBNS) continuen sent la base del tractament dels pacients cirròtics amb HTP per a reduir la pressió portal (PP) i prevenir l'hemorràgia per varius. Aquesta tesi doctoral se centra en l'estudi de noves estratègies terapèutiques per al tractament de la cirrosi hepàtica en diferents etapes de la malaltia. Concretament, hem provat dos nous potencials fàrmacs orals, sols o en combinació amb d'altres fàrmacs convencionals, per veure la seva eficàcia en diversos models d'experimentació animal d'HTP: el model de lligadura de la vena porta (LVP), el de lligadura del conducte biliar (LCB), i el model d'intoxicació per tetraclorur de carboni (CCl4). Tres estudis conformen aquesta tesi. En el primer estudi, es va avaluar la utilitat de la droxidopa, un fàrmac pro-adrenèrgic que ja s'utilitza en humans per a altres indicacions, en el tractament de les alteracions hemodinàmiques i renals associades a la cirrosi hepàtica; en el segon estudi, es van testar combinacions de droxidopa amb d'altres fàrmacs que disminueixen la PP (BBNS o estatines), per tal d'intentar aconseguir un efecte sinèrgic i, en el tercer estudi, es va dur a terme una comparació, pel que fa a la reducció de la PP i la toxicitat, de l'efecte de les estatines convencionals (simvastatina, atorvastatina) amb el NCX 6560, una atorvastatina alliberadora d'òxid nítric (ON). La droxidopa va produir un efecte diürètic i natriürètic destacat, i va millorar les alteracions sistèmiques i hemodinàmiques de les rates amb HTP mitjançant l'augment de la pressió arterial mitjana i la resistència de l'artèria mesentèrica superior conjuntament amb una reducció del flux sanguini en l'artèria mesentèrica superior. El tractament crònic amb propranolol més droxidopa va reduir la PP, tot mantenint l'increment en la diüresi i la natriüresi de la droxidopa. Ni la combinació aguda de carvedilol més droxidopa, ni la combinació amb atorvastatina, van aconseguir un efecte sinèrgic. La comparació entre les diferents estatines va mostrar un major efecte tòxic d'aquests fàrmacs en un model que reprodueix una funció hepàtica deteriorada i colèstasi (especialment amb el tractament amb simvastatina), i el NCX 6560 va millorar la HTP de manera similar a l'atorvastatina en dos models cirròtics (LCB i CCl4), però amb menor toxicitat i un millor perfil vasoprotector intrahepàtic. En conjunt, els resultats d'aquesta tesi apunten a un potencial ús terapèutic de la droxidopa per al tractament dels pacients cirròtics amb ascites refractària i síndrome hepatorenal tipus 2, fins i tot en aquells pacients que estan en tractament amb propranolol, i a un ús més segur del NCX 6560 en el potencial tractament a llarg termini de la HTP amb estatines.Cirrhosis, the most frequent cause of portal hypertension (PHT) in Western countries, is considered a multistage disease progressing from asymptomatic initial stages to decompensated cirrhosis with multiple clinical manifestations, which are a leading cause of death and liver transplantation worldwide. Therefore, therapies in liver cirrhosis should be adapted to each stage of the disease. Although many advances has been made in the last decades to understand the pathophysiology of PHT and develop new pharmacological approaches, up to now, non-selective beta-blockers (NSBB) still remain the mainstay of treatment in cirrhotic patient with PHT in order to reduce portal pressure (PP) and prevent variceal bleeding. The present doctoral thesis focuses on the study of new therapeutic strategies for the management of liver cirrhosis at different stages of the disease. In particular, two potential oral new drugs were tested, alone or in combination with other conventional drugs, to see their efficacy in several experimental animal models of PHT: the portal vein ligation (PVL), the bile duct ligation (BDL), and the carbon tetrachloride (CCl4) models. Three studies constitute this thesis. In the first study, the pro-adrenergic drug droxidopa, already used in humans for other indications, was evaluated for the management of the hemodynamic and renal alterations associated with liver cirrhosis; in the second study, combinations of droxidopa with other PP-lowering drugs (NSBB or statins) were performed in order to achieve a synergistic effect and, in the third study, a comparison of conventional statins (simvastatin, atorvastatin) with the nitric oxide (NO)-donating atorvastatin NCX 6560, in terms of PP lowering effect and toxicity, was also carried out. Droxidopa produced a marked diuretic and natriuretic effect, and improved the systemic and hemodynamic alterations of portal hypertensive rats by increasing mean arterial pressure and superior mesenteric artery resistance and by reducing superior mesenteric artery blood flow. A chronic treatment with propranolol plus droxidopa reduced PP, maintaining the increase in diuresis and natriuresis caused by droxidopa. Neither the acute combination of carvedilol plus droxidopa nor the combination with atorvastatin achieved a synergistic effect. The comparison among statins showed a magnified toxic effect of these drugs in a model that mimics a deteriorated liver function and cholestasis (especially with simvastatin treatment), and NCX 6560 improved PHT similarly to atorvastatin in two cirrhotic models (BDL and CCl4), but with less toxicity and a better intrahepatic vasoprotective profile. Altogether, the results presented in this thesis point to a potential therapeutic use of droxidopa in the management of cirrhotic patients with refractory ascites and type-2 hepatorenal syndrome, even in those patients on propranolol therapy, and to a safer use of NCX 6560 in the potential long-term statin treatment of PHT

Electronic health records (EHRs) in clinical research and platform trials: Application of the innovative EHR-based methods developed by EU-PEARL

Electronic health records; Platform trialsRegistros médicos electrónicos; Pruebas de plataformaRegistres mèdics electrònics; Proves de plataformaObjective Electronic Health Record (EHR) systems are digital platforms in clinical practice used to collect patients’ clinical information related to their health status and represents a useful storage of real-world data. EHRs have a potential role in research studies, in particular, in platform trials. Platform trials are innovative trial designs including multiple trial arms (conducted simultaneously and/or sequentially) on different treatments under a single master protocol. However, the use of EHRs in research comes with important challenges such as incompleteness of records and the need to translate trial eligibility criteria into interoperable queries. In this paper, we aim to review and to describe our proposed innovative methods to tackle some of the most important challenges identified. This work is part of the Innovative Medicines Initiative (IMI) EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project’s work package 3 (WP3), whose objective is to deliver tools and guidance for EHR-based protocol feasibility assessment, clinical site selection, and patient pre-screening in platform trials, investing in the building of a data-driven clinical network framework that can execute these complex innovative designs for which feasibility assessments are critically important. Methods ISO standards and relevant references informed a readiness survey, producing 354 criteria with corresponding questions selected and harmonised through a 7-round scoring process (0–1) in stakeholder meetings, with 85% of consensus being the threshold of acceptance for a criterium/question. ATLAS cohort definition and Cohort Diagnostics were mainly used to create the trial feasibility eligibility (I/E) criteria as executable interoperable queries. Results The WP3/EU-PEARL group developed a readiness survey (eSurvey) for an efficient selection of clinical sites with suitable EHRs, consisting of yes-or-no questions, and a set-up of interoperable proxy queries using physicians’ defined trial criteria. Both actions facilitate recruiting trial participants and alignment between study costs/timelines and data-driven recruitment potential. Conclusion The eSurvey will help create an archive of clinical sites with mature EHR systems suitable to participate in clinical trials/platform trials, and the interoperable proxy queries of trial eligibility criteria will help identify the number of potential participants. Ultimately, these tools will contribute to the production of EHR-based protocol design.“EU-PEARL has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 853966-2. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA and CHILDREN'S TUMOR FOUNDATION, GLOBAL ALLIANCE FOR TB DRUG DEVELOPMENT NON PROFIT ORGANISATION, SPRINGWORKS THERAPEUTICS INC.

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

New and combined treatments for cirrhosis and portal hypertension: effects on hemodynamics and hepatic fibrosis in experimental animal models

La cirrosi, la causa més freqüent d’hipertensió portal (HTP) en els països occidentals, és considerada una malaltia amb múltiples fases, que evoluciona des d'etapes inicials asimptomàtiques a un estat de cirrosi descompensada amb diverses manifestacions clíniques, les quals representen la principal causa de mort i de trasplantament hepàtic a tot el món. Per tant, caldria adaptar les diferents teràpies per a la cirrosi a cadascuna de les fases de la malaltia. Malgrat els avenços realitzats en les últimes dècades per entendre millor la fisiopatologia de la HTP i poder desenvolupar noves estratègies farmacològiques, fins al moment, els beta-bloquejants no selectius (BBNS) continuen sent la base del tractament dels pacients cirròtics amb HTP per a reduir la pressió portal (PP) i prevenir l'hemorràgia per varius. Aquesta tesi doctoral se centra en l'estudi de noves estratègies terapèutiques per al tractament de la cirrosi hepàtica en diferents etapes de la malaltia. Concretament, hem provat dos nous potencials fàrmacs orals, sols o en combinació amb d’altres fàrmacs convencionals, per veure la seva eficàcia en diversos models d’experimentació animal d’HTP: el model de lligadura de la vena porta (LVP), el de lligadura del conducte biliar (LCB), i el model d’intoxicació per tetraclorur de carboni (CCl4). Tres estudis conformen aquesta tesi. En el primer estudi, es va avaluar la utilitat de la droxidopa, un fàrmac pro-adrenèrgic que ja s'utilitza en humans per a altres indicacions, en el tractament de les alteracions hemodinàmiques i renals associades a la cirrosi hepàtica; en el segon estudi, es van testar combinacions de droxidopa amb d’altres fàrmacs que disminueixen la PP (BBNS o estatines), per tal d'intentar aconseguir un efecte sinèrgic i, en el tercer estudi, es va dur a terme una comparació, pel que fa a la reducció de la PP i la toxicitat, de l’efecte de les estatines convencionals (simvastatina, atorvastatina) amb el NCX 6560, una atorvastatina alliberadora d'òxid nítric (ON). La droxidopa va produir un efecte diürètic i natriürètic destacat, i va millorar les alteracions sistèmiques i hemodinàmiques de les rates amb HTP mitjançant l'augment de la pressió arterial mitjana i la resistència de l’artèria mesentèrica superior conjuntament amb una reducció del flux sanguini en l'artèria mesentèrica superior. El tractament crònic amb propranolol més droxidopa va reduir la PP, tot mantenint l'increment en la diüresi i la natriüresi de la droxidopa. Ni la combinació aguda de carvedilol més droxidopa, ni la combinació amb atorvastatina, van aconseguir un efecte sinèrgic. La comparació entre les diferents estatines va mostrar un major efecte tòxic d'aquests fàrmacs en un model que reprodueix una funció hepàtica deteriorada i colèstasi (especialment amb el tractament amb simvastatina), i el NCX 6560 va millorar la HTP de manera similar a l'atorvastatina en dos models cirròtics (LCB i CCl4), però amb menor toxicitat i un millor perfil vasoprotector intrahepàtic. En conjunt, els resultats d’aquesta tesi apunten a un potencial ús terapèutic de la droxidopa per al tractament dels pacients cirròtics amb ascites refractària i síndrome hepatorenal tipus 2, fins i tot en aquells pacients que estan en tractament amb propranolol, i a un ús més segur del NCX 6560 en el potencial tractament a llarg termini de la HTP amb estatines.Cirrhosis, the most frequent cause of portal hypertension (PHT) in Western countries, is considered a multistage disease progressing from asymptomatic initial stages to decompensated cirrhosis with multiple clinical manifestations, which are a leading cause of death and liver transplantation worldwide. Therefore, therapies in liver cirrhosis should be adapted to each stage of the disease. Although many advances has been made in the last decades to understand the pathophysiology of PHT and develop new pharmacological approaches, up to now, non-selective beta-blockers (NSBB) still remain the mainstay of treatment in cirrhotic patient with PHT in order to reduce portal pressure (PP) and prevent variceal bleeding. The present doctoral thesis focuses on the study of new therapeutic strategies for the management of liver cirrhosis at different stages of the disease. In particular, two potential oral new drugs were tested, alone or in combination with other conventional drugs, to see their efficacy in several experimental animal models of PHT: the portal vein ligation (PVL), the bile duct ligation (BDL), and the carbon tetrachloride (CCl4) models. Three studies constitute this thesis. In the first study, the pro-adrenergic drug droxidopa, already used in humans for other indications, was evaluated for the management of the hemodynamic and renal alterations associated with liver cirrhosis; in the second study, combinations of droxidopa with other PP-lowering drugs (NSBB or statins) were performed in order to achieve a synergistic effect and, in the third study, a comparison of conventional statins (simvastatin, atorvastatin) with the nitric oxide (NO)-donating atorvastatin NCX 6560, in terms of PP lowering effect and toxicity, was also carried out. Droxidopa produced a marked diuretic and natriuretic effect, and improved the systemic and hemodynamic alterations of portal hypertensive rats by increasing mean arterial pressure and superior mesenteric artery resistance and by reducing superior mesenteric artery blood flow. A chronic treatment with propranolol plus droxidopa reduced PP, maintaining the increase in diuresis and natriuresis caused by droxidopa. Neither the acute combination of carvedilol plus droxidopa nor the combination with atorvastatin achieved a synergistic effect. The comparison among statins showed a magnified toxic effect of these drugs in a model that mimics a deteriorated liver function and cholestasis (especially with simvastatin treatment), and NCX 6560 improved PHT similarly to atorvastatin in two cirrhotic models (BDL and CCl4), but with less toxicity and a better intrahepatic vasoprotective profile. Altogether, the results presented in this thesis point to a potential therapeutic use of droxidopa in the management of cirrhotic patients with refractory ascites and type-2 hepatorenal syndrome, even in those patients on propranolol therapy, and to a safer use of NCX 6560 in the potential long-term statin treatment of PHT

Current state-of-the-art and gaps in platform trials:10 things you should know, insights from EU-PEARL

Platform trials bring the promise of making clinical research more efficient and more patient centric. While their use has become more widespread, including their prominent role during the COVID-19 pandemic response, broader adoption of platform trials has been limited by the lack of experience and tools to navigate the critical upfront planning required to launch such collaborative studies. The European Union-Patient-cEntric clinicAl tRial pLatform (EU-PEARL) initiative has produced new methodologies to expand the use of platform trials with an overarching infrastructure and services embedded into Integrated Research Platforms (IRPs), in collaboration with patient representatives and through consultation with U.S. Food and Drug Administration and European Medicines Agency stakeholders. In this narrative review, we discuss the outlook for platform trials in Europe, including challenges related to infrastructure, design, adaptations, data sharing and regulation. Documents derived from the EU-PEARL project, alongside a literature search including PubMed and relevant grey literature (e.g., guidance from regulatory agencies and health technology agencies) were used as sources for a multi-stage collaborative process through which the 10 more important points based on lessons drawn from the EU-PEARL project were developed and summarised as guidance for the setup of platform trials. We conclude that early involvement of critical stakeholder such as regulatory agencies or patients are critical steps in the implementation and later acceptance of platform trials. Addressing these gaps will be critical for attaining the full potential of platform trials for patients. Funding: Innovative Medicines Initiative 2 Joint Undertaking with support from the European Union's Horizon 2020 research and innovation programme and EFPIA.</p

The Relevance and Insights on 1,4-Naphthoquinones as Antimicrobial and Antitumoral Molecules: A Systematic Review

Natural product derivatives are essential in searching for compounds with important chemical, biological, and medical applications. Naphthoquinones are secondary metabolites found in plants and are used in traditional medicine to treat diverse human diseases. Considering this, the synthesis of naphthoquinone derivatives has been explored to contain compounds with potential biological activity. It has been reported that the chemical modification of naphthoquinones improves their pharmacological properties by introducing amines, amino acids, furan, pyran, pyrazole, triazole, indole, among other chemical groups. In this systematic review, we summarized the preparation of nitrogen naphthoquinones derivatives and discussed their biological effect associated with redox properties and other mechanisms. Preclinical evaluation of antibacterial and/or antitumoral naphthoquinones derivatives is included because cancer is a worldwide health problem, and there is a lack of effective drugs against multidrug-resistant bacteria. The information presented herein indicates that naphthoquinone derivatives could be considered for further studies to provide drugs efficient in treating cancer and multidrug-resistant bacteria

Raman Spectroscopy of Individual Cervical Exfoliated Cells in Premalignant and Malignant Lesions

Cervical cancer is frequent neoplasia. Currently, the diagnostic approach includes cervical cytology, colposcopy, and histopathology studies; combining detection techniques increases the sensitivity and specificity of the tests. Raman spectroscopy is a high-resolution technique that supports the diagnosis of malignancies. This study aimed to evaluate the Raman spectroscopy technique discriminating between healthy and premalignant/malignant cervical cells. We included 81 exfoliative cytology samples, 29 in the “healthy group” (negative cytology), and 52 in the “CIN group” (premalignant/malignant lesions). We obtained the nucleus and cytoplasm Raman spectra of individual cells. We tested the spectral differences between groups using Permutational Multivariate Analysis of Variance (PERMANOVA) and Canonical Analysis of Principal Coordinates (CAP). We found that Raman spectra have increased intensity in premalignant/malignant cells compared with healthy cells. The characteristic Raman bands corresponded to proteins and nucleic acids, in concordance with the increased replication and translation processes in premalignant/malignant states. We found a classification efficiency of 76.5% and 82.7% for cytoplasmic and nuclear Raman spectra, respectively; cell nucleus Raman spectra showed a sensitivity of 84.6% in identifying cervical anomalies. The classification efficiency and sensitivity obtained for nuclear spectra suggest that Raman spectroscopy could be helpful in the screening and diagnosis of premalignant lesions and cervical cancer

Enhanced Tolerance against a Fungal Pathogen and Insect Resistance in Transgenic Tobacco Plants Overexpressing an Endochitinase Gene from Serratia marcescens

In this study we cloned a chitinase gene (SmchiC), from Serratia marcescens isolated from the corpse of a Diatraea magnifactella lepidopteran, which is an important sugarcane pest. The chitinase gene SmchiC amplified from the S. marcescens genome was cloned into the transformation vector p2X35SChiC and used to transform tobacco (Nicotiana tabacum L. cv Petit Havana SR1). The resistance of these transgenic plants to the necrotrophic fungus Botrytis cinerea and to the pest Spodoptera frugiperda was evaluated: both the activity of chitinase as well as the resistance against B. cinerea and S. frugiperda was significantly higher in transgenic plants compared to the wild-type

La pandemia en/desde Jujuy: reflexiones situadas

Acaso no podrí amos afirmar que la pandemia llego a nuestra sociedad mundial causando un pandemo - nium?. En cierto modo, ma s alla del juego de palabras, gran parte de nosotros lo sentimos así . Es claro, una pandemia, es una enfermedad que afecta a la sociedad. Perturba intensamente la cotidianeidad, las ocupaciones, y, en general, lo que en estos dí as an oramos como la “vida normal” de todos. Si contraemos una enfermedad ma s o menos aguda, todas nuestras actividades se ven afectadas, se desordenan. Cuando ello ocurre, pra cticamente debemos concentrarnos, casi con exclusividad, en superar la afeccio n con la ayuda de profesionales de la salud, cualquiera sea el abordaje disciplinario que nos resulte ma s adecuado y confiable. Así , del mismo modo, la pandemia afecta a toda la comunidad, a todas sus actividades. Y, en este caso tambie n la principal preocupacio n es superar la afeccio n. Entonces hay que buscar alternativas para el resto de las tareas, que deben transcurrir entre los estrechos ma rgenes que nos permiten tanto el cuidado personal como el social, ambos imprescindibles.Fil: Aramayo, Anahí. Universidad Nacional de Jujuy; ArgentinaFil: Lopez, Andrea Noelia. Universidad Nacional de Jujuy; ArgentinaFil: Díaz, Rodrigo Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Unidad Ejecutora en Ciencias Sociales Regionales y Humanidades. Universidad Nacional de Jujuy. Unidad Ejecutora en Ciencias Sociales Regionales y Humanidades; ArgentinaFil: Astorga, Farid Diego. Universidad Nacional de Jujuy; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Assad, Lucas Gabriel. Universidad Nacional de Jujuy; ArgentinaFil: Hoyos, Gustavo Daniel. Universidad Nacional de Jujuy; ArgentinaFil: Balut, Jorgelina. No especifíca;Fil: Angulo Villán, Florencia Raquel. No especifíca;Fil: Brailovsky, Sofia Miriam. No especifíca;Fil: Carrizo, María José. No especifíca;Fil: Bustamante, Patricia. No especifíca;Fil: Jaled, Daniela Alejandra. No especifíca;Fil: Castillo, Silvina Ana Lia. No especifíca;Fil: Díaz, Enrique Antonio. No especifíca;Fil: Cieza, Fernanda. Universidad Nacional de Jujuy. Facultad de Humanidades y Ciencias Sociales; ArgentinaFil: Cuva, Cecilia Alejandra. Universidad Nacional de Jujuy. Facultad de Humanidades y Ciencias Sociales; ArgentinaFil: Rivas, Rosana Verónica. Universidad Nacional de Jujuy. Facultad de Humanidades y Ciencias Sociales; ArgentinaFil: Altea, Laura. Universidad Nacional de Jujuy. Facultad de Humanidades y Ciencias Sociales; ArgentinaFil: Garzon, Analia Soledad. Universidad Nacional de Jujuy. Facultad de Humanidades y Ciencias Sociales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mamani, Claudia. Universidad Nacional de Jujuy. Facultad de Humanidades y Ciencias Sociales; ArgentinaFil: Villarroel, Viviana Mabel. Universidad Nacional de Jujuy. Facultad de Humanidades y Ciencias Sociales; ArgentinaFil: Costas Frison, Celeste. No especifíca;Fil: Montenegro, Erica Maricel. No especifíca;Fil: Guzmán, Vilma Roxana. No especifíca;Fil: Donaire, Claudia. No especifíca;Fil: Herrera, Ana Soledad. No especifíca;Fil: Cardozo, Juana Griselda. No especifíca;Fil: Nieva, Nuria Noelia. No especifíca;Fil: Miranda , Ana Lía. Universidad Nacional de Jujuy; ArgentinaFil: Patagua, Patricia Evangelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Unidad Ejecutora en Ciencias Sociales Regionales y Humanidades. Universidad Nacional de Jujuy. Unidad Ejecutora en Ciencias Sociales Regionales y Humanidades; ArgentinaFil: Gomez, Carina Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Unidad Ejecutora en Ciencias Sociales Regionales y Humanidades. Universidad Nacional de Jujuy. Unidad Ejecutora en Ciencias Sociales Regionales y Humanidades; ArgentinaFil: Bustamante, Patricia. Universidad Nacional de Jujuy; ArgentinaFil: Navarro Suárez, Camila. Universidad Nacional de Jujuy; ArgentinaFil: Yufra, Laura Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Unidad Ejecutora en Ciencias Sociales Regionales y Humanidades. Universidad Nacional de Jujuy. Unidad Ejecutora en Ciencias Sociales Regionales y Humanidades; ArgentinaFil: Massari, María Justina. Universidad Nacional de Jujuy; ArgentinaFil: Cortez, Carla Melisa. Universidad Nacional de Jujuy; ArgentinaFil: Rovetta, Ana Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Zinger, Sabrina. Universidad Nacional de Jujuy; ArgentinaFil: Alba, Juan Pablo. Universidad Nacional de Jujuy; ArgentinaFil: Arrueta, Patricia Marisel. Universidad Nacional de Jujuy; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Constant, Juan. Universidad Nacional de Jujuy; ArgentinaFil: Gumiel, Silvina. Universidad Nacional de Jujuy; ArgentinaFil: Zazzarini, Susana. Universidad Nacional de Jujuy; ArgentinaFil: Valente, Verónica. Universidad Nacional de Jujuy; ArgentinaFil: Bergesio, Liliana del Carmen. Universidad Nacional de Jujuy. Facultad de Humanidades y Ciencias Sociales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; ArgentinaFil: González, Natividad María. Universidad Nacional de Jujuy. Facultad de Ciencias Económicas. Instituto de Investigaciones Económicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Nieva, Florencia Antonella. Universidad Nacional de Jujuy; ArgentinaFil: Callieri, Ivanna Gabriela. Universidad Nacional de Jujuy; ArgentinaFil: Montes, Elena Patricia. Universidad Nacional de Jujuy; ArgentinaFil: Civila Orellana, Fabiola Vanesa. Universidad Nacional de Jujuy; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Villarrubia Gómez, Álvaro Patricio. Universidad Nacional de Jujuy; ArgentinaFil: Quispe, Gloria. Universidad Nacional de Jujuy; ArgentinaFil: Cosme, María Cristina. Universidad Nacional de Jujuy; ArgentinaFil: Quispe, Ariadna Vanesa. Universidad Nacional de Jujuy; ArgentinaFil: Galián, Víctor Joel. Universidad Nacional de Jujuy; ArgentinaFil: Vazquez, Omar Eduardo. Universidad Nacional de Jujuy; ArgentinaFil: Cerpa, Daniela Soledad. Universidad Nacional de Jujuy; ArgentinaFil: Martínez, Luis Gustavo. Universidad Nacional de Jujuy; ArgentinaFil: Fernández, Laura Soledad. Universidad Nacional de Jujuy; ArgentinaFil: Tolaba, Gladys Sarai. Universidad Nacional de Jujuy; ArgentinaFil: Escalante, Norberto Oscar. Universidad Nacional de Jujuy; ArgentinaFil: Cazón, Mariela. Universidad Nacional de Jujuy; ArgentinaFil: Ugarte, María Adela. Universidad Nacional de Jujuy; ArgentinaFil: García Vargas, Alejandra. Universidad Nacional de Jujuy. Facultad de Humanidades y Ciencias Sociales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; ArgentinaFil: Gaona, Melina. Universidad Nacional de Quilmes. Departamento de Ciencias Sociales. Centro de Estudios de Historia, Cultura y Memoria; ArgentinaFil: Zubia, Gonzalo Federico. Universidad Nacional de Quilmes. Departamento de Ciencias Sociales. Centro de Estudios de Historia, Cultura y Memoria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kulemeyer, Jorge Alberto. No especifíca;Fil: Pantoja, Rodrigo. No especifíca;Fil: Paz, María Elisa. No especifíca;Fil: Rivero, Ariel Rodolfo. No especifíca;Fil: Rocabado, Cecilia Inés. Universidad Nacional de Jujuy; ArgentinaFil: Villagra, Gabriela Soledad. Instituto de Ciencia y Tecnología Regional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rodríguez, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Ciencia y Tecnología Regional; ArgentinaFil: Adi Barrionuevo, Ana Carolina. Universidad Nacional de Jujuy; ArgentinaFil: Adi Barrionuevo, Irene. Universidad Nacional de Jujuy; ArgentinaFil: Aramayo, Natalia. Universidad Nacional de Jujuy; ArgentinaFil: Fernández, Gabriel. Universidad Nacional de Jujuy; ArgentinaFil: Morales, Miriam Mariana. Universidad Nacional de Jujuy. Instituto de Ecorregiones Andinas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Ecorregiones Andinas; ArgentinaFil: Rios, Natalia Fatima. Facultad Latinoamericana de Ciencias Sociales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rocabado, Zaida Nadia. Universidad Nacional de Jujuy; ArgentinaFil: Sandoval, Cecilia. No especifíca;Fil: Soto, Mercedes. No especifíca;Fil: Osores, Noelia Andrea del Valle. No especifíca;Fil: Revollo, Jimena ;Citterio. No especifíca;Fil: Gutiérrez, Ivone Belén. Universidad Nacional de Jujuy; ArgentinaFil: Juste, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Unidad Ejecutora en Ciencias Sociales Regionales y Humanidades. Universidad Nacional de Jujuy. Unidad Ejecutora en Ciencias Sociales Regionales y Humanidades; ArgentinaFil: Vidal, José Fernando. Universidad Nacional de Jujuy; ArgentinaFil: Karasik, Gabriela Alejandra. Universidad Nacional de Jujuy. Facultad de Humanidades y Ciencias Sociales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; ArgentinaFil: Bruce, Beatriz Maria. Universidad Nacional de Jujuy; Argentin