Synthesis and characterization of a new cyclodextrin derivative with improved properties to design oral dosage forms

This work aimed to synthesize a novel β-cyclodextrin derivative, itaconyl-β-cyclodextrin to evaluate whether albendazole inclusion complexes with the new β-cyclodextrin derivative-improved albendazole dissolution efficiency and its anthelminthic activity. The new derivative was thoroughly evaluated and characterized, and an average degree of substitution of 1.4 per cyclodextrin molecule was observed. Albendazole:itaconyl-β-cyclodextrin complexes were prepared by spray drying procedures and investigated using phase solubility diagrams, dissolution efficiency, X-ray diffraction, differential scanning calorimetry, Fourier transform infrared, scanning electronic microscopy, mass spectrometry, and nuclear magnetic resonance spectroscopy. Phase solubility diagrams and mass spectrometry studies showed that the inclusion complex was formed in an equimolar ratio. Stability constant values were 602 M −1 in water, and 149 M −1 in HCl 0.1 N. Nuclear magnetic resonance experiments of the inclusion complex showed correlation signals between the aromatic and propyl protons of albendazole and the itaconyl-β-cyclodextrin inner protons. The studies indicated solid structure changes of albendazole included in itaconyl-β-cyclodextrin. The maximum drug release was reached at 15 min, and the inclusion complex solubility was 88-fold higher than that of the pure drug. The in vitro anthelmintic activity assay showed that the complex was significantly more effective than pure albendazole.Fil: García, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Priotti, Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Codina, Ana Victoria. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Vasconi, María Delia. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaFil: Hinrichsen, Lucila Isabel. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Leonardi, Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Lamas, Maria Celina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentin

New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering multiple myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells

[EN] Monoclonal gammopathy of uncertain significance (MGUS) and smoldering multiple myeloma (SMM) are plasma cell disorders with a risk of progression of approximately 1% and 10% per year, respectively. We have previously shown that the proportion of bone marrow (BM) aberrant plasma cells (aPCs) within the BMPC compartment (aPC/BMPC) as assessed by flow cytometry (FC) contributes to differential diagnosis between MGUS and multiple myloma (MM). The goal of the present study was to investigate this parameter as a marker for risk of progression in MGUS (n = 407) and SMM (n = 93). Patients with a marked predominance of aPCs/BMPC (> or = 95%) at diagnosis displayed a significantly higher risk of progression both in MGUS and SMM (P or = 95%) as the most important independent variable, together with DNA aneuploidy and immunoparesis, for MGUS and SMM, respectively. Using these independent variables, we have identified 3 risk categories in MGUS (PFS at 5 years of 2%, 10%, and 46%, respectively; P< .001) and SMM patients (PFS at 5 years of 4%, 46%, and 72%, respectively; P < .001). Our results show that multiparameter FC evaluation of BMPC at diagnosis is a valuable tool that could help to individualize the follow-up strategy for MGUS and SMM patients

Certainties and uncertainties affecting the postdoctoral phase of the scientific career in Argentina

En la etapa posdoctoral varios desafíos e interrogantes determinan nuestra consolidación como investigadores. Sobre la base de reuniones con ocho investigadores formados, identifcamos algunas certezas e incertidumbres de esta etapa. También destacamos herramientas para lograr buenos antecedentes académicos y poder acceder a la Carrera de Investigador Científco (CIC) del Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). La principal certeza fue que hay que publicar: es fundamental para la trasmisión del conocimiento a la comunidad y es el aspecto más valorado por el CONICET. Sin embargo, publicar implica mucho más que redactar un manuscrito. Es fundamental la contribución conceptual y la originalidad de nuestro trabajo. Identifcamos la incertidumbre que nos genera cómo administrar el tiempo para lograr varias publicaciones de alto impacto y realizar otras actividades como formar recursos humanos, hacer docencia o pedir subsidios o estadías en el exterior, durante los siete años de becas que normalmente disponemos (cinco para doctorarnos y dos de posdoctorado). Otras incertidumbres son el cambio constante y la exigencia creciente de requisitos para ingresar a la CIC. Además, la poca estabilidad de los recursos para investigar y la necesidad de buscar ideas originales son incertidumbres importantes en esta etapa. Quienes quieran desarrollar una carrera científica en la Argentina tendrán que delinear una estrategia. Proponemos perfles de becarios posdoctorales 'exitosos' a fn de encontrar alternativas efcientes para acceder a una posición y un buen desarrollo de la carrera de científco en el CONICET. Para generar un debate enriquecedor, valoraremos su opinión en una encuesta que diseñamos especialmente (goo.gl/forms/k185nQG8ABxjL4bo2, abierta hasta 31 de marzo de 2019). La encuesta está dirigida a becarios doctorales, posdoctorales e investigadores con un cargo permanente, y nos permitirá abrir el abanico de perfles y opiniones. Este debate servirá de guía a jóvenes que quieran desempeñarse exitosamente como científcos en nuestro país.In the postdoctoral stage several challenges and questions define our development and consolidation as researchers. Based on the guidance of trained researchers, we identified various certainties and uncertainties during this phase. We also highlight several tools to achieve a good academic performance and obtain a position as researchers of the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). The main certainty was that publishing is a 'must': it is essential to transmit the knowledge to the community and it is the most valued aspect by the CONICET. However, a publication involves much more than writing a manuscript. Detecting the conceptual contribution and the originality of our work is fundamental. One of the uncertainties identified was producing several high-impact publications, while performing other activities (e.g., human resources training, teaching, grant applications and stays abroad) during the seven years that fellowships usually last (five for Ph.D. and two for postdoctoral fellowships). Other uncertainties are the constantly changing rules and the increasing requisites to meet CONICET conditions for researchers. Besides, the scarce stability of resources to research and the need to develop original ideas are particularly uncertain at this stage. Those wanting to develop a scientific career in Argentina must outline a strategy. We propose ‘successful’ postdoctoral fellows’ profiles to find pathways towards a permanent position at the CONICET scientific career, with good development prospects. As a way to open a fruitful debate, your survey feedback will be highly valued. Said survey is available at (goo.gl/forms/k185nQG8ABxjL4bo2, until March 31st, 2019), addressed to doctoral students, postdoctoral fellows and researchers with permanent positions. This will allow opening the range of profiles and opinions. This debate may be a guide for those young researchers willing to perform successfully as Scientists within our country

15 relats: El racó de l’escriptura 2023

15 relats. El racó de l’escriptura (2023) és el volum recopilatori dels contes realitzats per l’alumnat del taller impartit enguany en la Seu Universitària Ciutat d’Alacant en col·laboració amb la Universitat Permanent de la Universitat d’Alacant (UPUA)

Comunicación pública de la ciencia y arqueología del centro-oeste de la provincia de Santa Cruz

En el centro-oeste de Santa Cruz (Patagonia, Argentina) se han desarrollado investigaciones arqueológicas desde hace más de 40 años. Desde sus inicios, el equipo de trabajo estableció vínculos con las comunidades de Perito Moreno, Gobernador Gregores y Lago Posadas y se desarrollaron charlas y talleres con distintos actores sociales de estas localidades. A partir de diversos factores, en los últimos años se sistematizaron las tareas de gestión y extensión. En particular, se han realizado distintas actividades en las localidades mencionadas y en el Área Metropolitana de Buenos Aires, en las que han participado estudiantes y docentes de distintos niveles educativos, autoridades, emprendedores turísticos, representantes de las comunidades originarias y otros pobladores locales. En este artículo, en primer lugar, se resumen las experiencias del equipo de trabajo en relación con la comunicación pública de la ciencia a lo largo de aproximadamente cuatro décadas. En particular se consideran los distintos tipos de actividades llevadas a cabo y los vínculos establecidos con las distintas localidades y los actores sociales participantes. Asimismo, se relaciona esta trayectoria de trabajo con las coyunturas locales y otros aspectos contextuales que incidieron en su desarrollo. Por último, se reflexiona sobre las características de nuestra propia experiencia en la comunicación pública de la ciencia atendiendo a sus alcances y limitaciones

Prospective Latin American cohort evaluating outcomes of patients with COVID-19 and abnormal liver tests on admission

Introduction & objectives: The independent effect of liver biochemistries as a prognostic factor in patients with COVID-19 has not been completely addressed. We aimed to evaluate the prognostic value of abnormal liver tests on admission of hospitalized patients with COVID-19. Materials & methods: We performed a prospective cohort study including 1611 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through July 31, 2020 in 38 different Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters, including liver function tests, on admission and during hospitalization. All patients were followed until discharge or death. We fit multivariable logistic regression models, further post-estimation effect through margins and inverse probability weighting. Results: Overall, 57.8% of the patients were male with a mean age of 52.3 years, 8.5% had chronic liver disease and 3.4% had cirrhosis. Abnormal liver tests on admission were present on 45.2% (CI 42.7–47.7) of the cohort (n = 726). Overall, 15.1% (CI 13.4–16.9) of patients died (n = 244). Patients with abnormal liver tests on admission presented higher mortality 18.7% (CI 15.9–21.7), compared to those with normal liver biochemistries 12.2% (CI 10.1–14.6); P 30. Conclusions: The presence of abnormal liver tests on admission is independently associated with mortality and severe COVID-19 in hospitalized patients with COVID-19 infection and may be used as surrogate marker of inflammation.Fil: Mendizabal, Manuel. Universidad Austral. Hospital Universitario Austral; ArgentinaFil: Piñero, Federico. Universidad Austral. Hospital Universitario Austral; ArgentinaFil: Ridruejo, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Anders, Margarita. Hospital Aleman; ArgentinaFil: Silveyra, María Dolores. Sanatorio Anchorena; ArgentinaFil: Torre, Aldo. Centro Médico ABC; MéxicoFil: Montes, Pedro. Hospital Nacional Daniel A. Carrión; PerúFil: Urzúa, Alvaro. Hospital Clínico de la Universidad de Chile; ChileFil: Pages, Josefina. Universidad Austral. Hospital Universitario Austral; ArgentinaFil: Toro, Luis G.. Hospitales de San Vicente Fundación de Medellín y Rionegro; ColombiaFil: Díaz, Javier. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: Gonzalez Ballerga, Esteban. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Miranda Zazueta, Godolfino. Instituto Nacional de Ciencias Médicas y Nutrición; MéxicoFil: Peralta, Mirta. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Gutiérrez, Isabel. Centro Médico ABC; MéxicoFil: Michelato, Douglas. Hospital Especializado en Enfermedades Infecciosas Instituto Couto Maia; BrasilFil: Venturelli, Maria Grazia. Hospital Nacional Guillermo Almenara Irigoyen; PerúFil: Varón, Adriana. Fundación Cardio-Infantil; ColombiaFil: Vera Pozo, Emilia. Hospital Regional Dr. Teodoro Maldonado Carbo; EcuadorFil: Tagle, Martín. Clínica Anglo-Americana; PerúFil: García, Matías. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Tassara, Alfredo. Hospital Aleman; ArgentinaFil: Brutti, Julia. Sanatorio Anchorena; ArgentinaFil: Ruiz García, Sandro. Hospital de Víctor Lazarte Echegaray; PerúFil: Bustios, Carla. Clínica Delgado; PerúFil: Escajadillo, Nataly. Hospital Nacional Almanzor Aguinaga Asenjo; PerúFil: Macias, Yuridia. No especifíca;Fil: Higuera de la Tijera, Fátima. Hospital General de México “Dr. Eduardo Liceaga"; MéxicoFil: Gómez, Andrés J.. Hospital Universitario Fundación Santa Fé de Bogotá; ColombiaFil: Dominguez, Alejandra. Hospital Padre Hurtado; ChileFil: Castillo Barradas, Mauricio. Hospital de Especialidades del Centro Médico Nacional La Raza; MéxicoFil: Contreras, Fernando. No especifíca;Fil: Scarpin, Aldana. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Schinoni, Maria Isabel. Hospital Alianza; BrasilFil: Toledo, Claudio. Universidad Austral de Chile; ChileFil: Girala, Marcos. Universidad Nacional de Asunción; ParaguayFil: Mainardi, Victoria. Hospital Central De las Fuerzas Armadas; UruguayFil: Sanchez, Abel. Hospital Roosevelt; GuatemalaFil: Bessone, Fernando. Provincia de Santa Fe. Ministerio de Salud y Medio Ambiente - Rosario. Hospital Provincial del Centenario; ArgentinaFil: Rubinstein, Fernando Adrian. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Silva, Marcelo Oscar. Universidad Austral. Hospital Universitario Austral; Argentin

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality