Characteristics of patients returning to emergency departments in Naples, Italy

<p>Abstract</p> <p>Background</p> <p>Crowding in hospital Emergency Departments (EDs) is a problem in several countries. We evaluated the number and characteristics of patients who make repeated visits to the EDs in Naples, Italy.</p> <p>Methods</p> <p>All patients (≥ 16 years) who presented to the EDs of three randomly selected non-academic acute care public hospitals, within randomly selected week periods, were studied. The two outcomes of interest were the re-utilization, within 72 hours, of the ED and the number of visits in the previous year.</p> <p>Results</p> <p>Of the 1430 sampled patients, 51.9% self-reported multiple visits in the previous year and 10.9% and 1.6% used the ED for 3 and ≥4 times, respectively. The number of visits in the previous year was significantly higher in those who live closer to hospital, with a more severe burden of overall comorbidity, and who were on pharmacological treatment. Overall, 72-hours return visits were found in 215 patients (15.8%). Patients were more likely to re-use within 72 hours the ED if younger, were not on pharmacological treatment, attended the ED more times in the previous year, were referred by a physician, arrived at the ED by car driven by other person, had problems of longer duration prior to arrival at the ED, had a surgical ED discharge diagnosis, and were admitted to the hospital.</p> <p>Conclusion</p> <p>The data may assist policymakers in the development and implementation of protocols to track changes in the re-utilization of the ED for the high financial impact and for the benefit of the patients.</p

Experiencia de migración de la plataforma de educación virtual en la Facultad de Ciencias Agrarias UNR: análisis preliminar del proceso

La Cátedra de Informática de la Facultad de Ciencias Agrarias (FCA), encargada de la administración de su Campus Virtual (CVFCAgr), ha participado activamente en su consolidación desde el 2005. En 2017, el Ministerio de Educación Nacional declaró por resolución N° 2641 que las actividades a distancia desarrolladas en entidades educativas deberán estar enmarcadas en un Sistema Institucional de Educación a Distancia (SIED) validado. En 2019, la Universidad Nacional de Rosario crea su propio SIED. El CV-FCAgr está implementado en una plataforma no validada por el SIED UNR. Luego de que las autoridades de FCA y la Cátedra de Informática, que asesora a la comunidad respecto a educación a distancia (EaD), evaluaran la viabilidad de un cambio, se decidió llevar a cabo una migración a la nueva plataforma a fin de alinearse a las resoluciones ministeriales vigentes y a las políticas universitarias. Dada una presunta resistencia al cambio, debido a la gran consolidación de la plataforma actual, la planificación se estructuró en etapas paulatinas con el objetivo de dar comienzo al año lectivo 2023 en la nueva plataforma con el menor impacto posible. Los resultados, muestran a la mayoría de la comunidad educativa comprometida, abordando las diferentes etapas y ajustados a los tiempos propuestos según el plan de migración.Red de Universidades con Carreras en Informátic

Long lasting MDM2/Translocator protein modulator: a new strategy for irreversible apoptosis of human glioblastoma cells

The development of multi-target drugs and irreversible modulators of deregulated signalling proteins is the major challenge for improving glioblastoma multiforme (GBM) treatment. Reversible single-target drugs are not sufficient to sustain a therapeutic effect over time and may favour the activation of alternative signalling pathways and the onset of resistance phenomena. Thus, a multi-target compound that has a long-lasting mechanism of action might have a greater and longer life span of anti-proliferative activity. Recently, a dual-target indol-3ylglyoxyldipeptide derivative, designed to bind to the Translocator Protein (TSPO) and reactivate p53 function via dissociation from its physiological inhibitor, murine double minute 2 (MDM2), has been developed as a potent GBM pro-apoptotic agent. In this study, this derivative was chemically modified to irreversibly bind MDM2 and TSPO. The new compound elicited a TSPO-mediated mitochondrial membrane dissipation and restored p53 activity, triggering a long-lasting apoptosis of GBM cells. These effects were sustained over time, involved a stable activation of extracellular signal regulated kinases and were specifically observed in cancer cells, in which these protein kinases are deregulated. Dual-targeting and irreversible binding properties combined in the same molecule may represent a useful strategy to overcome the time-limited effects elicited by classical chemotherapies

Trazabilidad de la actividad académica virtual de la Facultad de Ciencias Agrarias en contexto de pandemia

El año pandémico, se ha constituido en un hito en diferentes ámbitos. Respecto a lo educativo, ha impulsado a docentes y estudiantes, a adentrarse en el manejo de las tecnologías de información y comunicación (TICs). El Campus Virtual de la Facultad de Ciencias Agrarias - UNR, se ha convertido en el eje principal de la actividad académica durante ese período. Con el fin de conocer el grado de actividad académica desde la virtualidad, se propusieron distintas acciones, con el objetivo general de estudiar y analizar la trazabilidad de las acciones de docentes y estudiantes en contexto de pandemia. Se analizó: el grado de conectividad de los usuarios, la identificación de los espacios virtuales donde interactuaron los diversos actores, y finalmente, los resultados de la implementación de mesas de exámenes virtuales. La experiencia y el análisis de la actividad académica virtual se valoró positivamente. A futuro, será un gran desafío incorporar las buenas experiencias desde la virtualidad, acompañadas de estrategias adecuadas para lograr aprendizajes significativos. Sin dudas, en las Ciencias Agrarias la presencialidad es una gran necesidad, pero a pesar de carecerla, la Facultad siguió de pie, avanzó en un camino lleno de incertidumbres, pero de muchos y valiosos aprendizajes.Red de Universidades con Carreras en Informátic

Virtualidad y presencialidad en el proceso evaluativo de exámenes finales de la asignatura Informática - Facultad de Ciencias Agrarias UNR

El aislamiento preventivo a raíz de la pandemia de COVID-19 se presentó como un reto para las instituciones de educación superior y en especial para carreras con alto contenido presencial como las dictadas en la Facultad de Ciencias Agrarias - UNR. Este artículo describe el proceso docente experimentado en la asignatura Informática, para adaptar la toma de exámenes finales a un formato no presencial. En este caso se efectuó un rediseño con implementación de instancias 100% virtuales a través de cuestionarios y evaluación individual por videollamada con presentación de pantalla. Los resultados analizados cuantitativamente muestran un desempeño eficiente de la innovación y en particular una percepción cualitativa docente de alta valoración a nivel de la calidad evaluativa. Esta experiencia docente desarrollada en la modalidad a distancia fue un descubrimiento que se utilizó como retroalimentación para adaptar la metodología de evaluación en la presencialidad.Red de Universidades con Carreras en Informátic

Evolución virtual de la Facultad de Ciencias Agrarias UNR : Uso y percepción docente

En la Facultad de Ciencias Agrarias de la Universidad Nacional de Rosario, se analizó la experiencia que se desarrolla en el Campus Virtual de la institución con el objetivo de: relevar sus características y usos, identificar tendencias y potencialidades, y conocer el grado de satisfacción de los usuarios. Se realizó una encuesta a través de un formulario electrónico. La misma, estuvo dirigida al cuerpo docente de la Facultad. Los resultados demostraron con claridad que los docentes participan activamente en experiencias b-learning. El 72% valoró muy positivamente el funcionamiento del Campus. El 51% manifiesta haber tomado las capacitaciones ofertadas por la cátedra de Informática de la facultad, y el 78% de los docentes capacitados ha aplicado esos conocimientos a sus procesos de enseñanza. Queda expuesto que un alto porcentaje usa el Campus Virtual para compartir materiales de estudios, pero no así aprovechando todas sus potencialidades. Muy pocos hacen uso de la variedad de recursos disponibles: clases virtuales con videotutoriales, sugerencia de sitios Webs, documentos colaborativos, foros, elaboración de FAQs, etc. Ese será el gran desafío a futuro, explotar todas las posibilidades disponibles en el Campus Virtual. También, se observó predisposición de la comunidad educativa en todo lo referente a las TICs.Red de Universidades con Carreras en Informátic

Combined inhibition of AKT/mTOR and MDM2 enhances Glioblastoma Multiforme cell apoptosis and differentiation of cancer stem cells

The poor prognosis of Glioblastoma Multiforme (GBM) is due to a high resistance to conventional treatments and to the presence of a subpopulation of glioma stem cells (GSCs). Combination therapies targeting survival/self-renewal signals of GBM and GSCs are emerging as useful tools to improve GBM treatment. In this context, the hyperactivated AKT/mammalian target of the rapamycin (AKT/mTOR) and the inhibited wild-type p53 appear to be good candidates. Herein, the interaction between these pathways was investigated, using the novel AKT/mTOR inhibitor FC85 and ISA27, which re-activates p53 functionality by blocking its endogenous inhibitor murine double minute 2 homologue (MDM2). In GBM cells, FC85 efficiently inhibited AKT/mTOR signalling and reactivated p53 functionality, triggering cellular apoptosis. The combined therapy with ISA27 produced a synergic effect on the inhibition of cell viability and on the reactivation of p53 pathway. Most importantly, FC85 and ISA27 blocked proliferation and promoted the differentiation of GSCs. The simultaneous use of these compounds significantly enhanced GSC differentiation/apoptosis. These findings suggest that FC85 actively enhances the downstream p53 signalling and that a combination strategy aimed at inhibiting the AKT/mTOR pathway and re-activating p53 signalling is potentially effective in GBM and in GSCs

Molecular View on the iRGD Peptide Binding Mechanism: Implications for Integrin Activity and Selectivity Profiles

Receptor-selective peptides are widely used as smart carriers for specific tumor-targeted delivery. A remarkable example is the cyclic nonapeptide iRGD (CRGDKPGDC, 1) that couples intrinsic cytotoxic effects with striking tumor-homing properties. These peculiar features are based on a rather complex multistep mechanism of action, where the primary event is the recognition of RGD integrins. Despite the high number of preclinical studies and the recent success of a phase I trial for the treatment of pancreatic ductal adenocarcinoma (PDAC), there is little information available about the iRGD three-dimensional (3D) structure and integrin binding properties. Here, we re-evaluate the peptide's affinity for cancer-related integrins including not only the previously known targets alpha v beta 3 and alpha v beta 5 but also the alpha v beta 6 isoform, which is known to drive cell growth, migration, and invasion in many malignancies including PDAC. Furthermore, we use parallel tempering in the well-tempered ensemble (PT-WTE) metadynamics simulations to characterize the in-solution conformation of iRGD and extensive molecular dynamics calculations to fully investigate its binding mechanism to integrin partners. Finally, we provide clues for fine-tuning the peptide's potency and selectivity profile, which, in turn, may further improve its tumor-homing properties

Selective Arylsulfonamide Inhibitors of ADAM-17: Hit Optimization and Activity in Ovarian Cancer Cell Models

Activated Leukocyte Cell Adhesion Mol. (ALCAM) is expressed at the surface of epithelial ovarian cancer (EOC) cells and is released in a sol. form (sALCAM) by ADAM-17-mediated shedding. This process is relevant to EOC cell motility and invasiveness, which is reduced by inhibitors of ADAM-17. In addn., ADAM-17 plays a key role in EGFR signalling and thus may represent a useful target in anticancer therapy. Herein we report our hit optimization effort to identify potent and selective ADAM-17 inhibitors, starting with previous mol. 1. A new series of secondary sulfonamido-based hydroxamates was designed and synthesized. The biol. activity of the newly synthesized compds. was tested in vitro on isolated enzymes and human EOC cell lines. The optimization process led to compd. 21, which showed an IC50 of 1.9 nM on ADAM-17 with greatly increased selectivity. This compd. maintained good inhibitory properties on sALCAM shedding in several in vitro assays

Targeting CXCR4 reverts the suppressive activity of T-regulatory cells in renal cancer

With the intent to identify biomarkers in renal cell carcinoma (RCC) the functional status of T-regulatory cells (Tregs) was investigated in primary RCC. Tregs were isolated from tumoral-(TT), peritumoral tissue-(PT) and peripheral blood-(PB) of 42 primary RCC patients and function evaluated through effector T cells (Teff) proliferation, cytokines release and demethylation of Treg Specific Region (TSDR). The highest value of Tregs was detected in TT with the uppermost amount of effector-Tregs-(CD4+CD25hiFOXP3hiCD45RA-). PB-RCC Tregs efficiently suppress Teff proliferation compared to healthy donor (HD)-Tregs and, at the intrapatient evaluation, TT-derived Tregs were the most suppressive. Higher demethylation TSDR was detected in TT- and PB-RCC Tregs vs HD-Tregs (P <0,001). CXCR4 is highly expressed on Tregs, thus we wished to modulate Tregs function through CXCR4 inhibition. CXCR4 antagonism, elicited by a new peptidic antagonist, Peptide-R29, efficiently reversed Tregs suppression of Teff proliferation. Thus Tregs functional evaluation precisely reflects Tregs status and may be a reliable biomarker of tumoral immune response. In addition, treatment with CXCR4 antagonist, impairing Tregs function, could improve the anticancer immune response, in combination with conventional therapy and/or immunotherapy such as checkpoints inhibitors