PAMAM-based dendrimers for diverse biomedical applications

Existe una gran necesidad de nuevos tratamientos en determinadas patologías tales como el cáncer o las infecciones resistentes. Entre algunas de las nuevas terapias más prometedoras se encuentran génica y celular, pero ambas tienen serios problemas que resolver antes de pasar a la clínica. Para resolver algunos de estos problemas, recientemente se han combinado vectores virales con células madre (células madre mesenquimales especialmente). Sin embargo, ya que son células complejas de crecer con los métodos y medios de cultivo estándar, la técnica tiene que ser mejorado antes de ser poder ser utilizado en ensayos clínicos. Vectores sintéticos tales como polímeros, aunque más seguros que los virus, generalmente no poseen la eficacia requerida para los tratamiento de terapia génica. En este ámbito, los dendrímeros son polímeros sintéticos tridimensionales, altamente ramificados y con una estructura química bien definida. En particular, los dendrímeros basados en PAMAM (poli(amidoamina)) han sido ampliamente investigados por sus aplicaciones biológicas y han mostrado ser portadores de propiedades clínicamente relevantes que les hacen valiosos para ser utilizados en terapia génica o celular. Se ha demostrado que los dendrímeros basados en PAMAM también pueden facilitar la localización de antibióticos en el interior de bacterias, y por lo tanto, pueden ser utilizados para mejorar la actividad antimicrobiana. Además, pueden ser altamente tóxicos para determinadas bacterias mediante la disrupción de la membrana citoplasmática. Controlando la funcionalidad y carga a través de la elección de los grupos periféricos, el tamaño del dendrímero y el nivel de recubrimiento con PEG, se pueden modular las interacciones con la superficie bacteriana y su actividad antibacteriana y citotóxica para las células huésped. En este proyecto se han estudiado las propiedades biomédicas de derivados de PAMAM y su influencia sobre el crecimiento bacteriano y celular. Nuestros resultados muestran que, aunque el dendrímero PAMAM completamente recubierto con PEG disminuye el crecimiento de Pseudomonas y que tiene potencial para ser empleado como un agente antibacteriano, en el caso de las células madre mesenquimales, el crecimiento celular se incrementa sin alterar sus patrones de pluripotencialidad y podría ser de gran ayuda para las futuras estrategias de terapia celular

Market Places working or collaborative Tourism Platform

Dada la importancia que han cobrado las plataformas peer to peer de turismo colaborativo, este trabajo tratará de identificar los modelos de negocio existentes, así como el funcionamiento y perspectivas de futuro de las plataformas pertenecientes a los principales ámbitos en los que destaca la economía colaborativa en el sector turístico (alojamiento, transporte y restauración), a través de un análisis cualitativo basado en entrevistas en profundidad. Los resultados permiten concluir que existe una transición de modelos no lucrativos en los comienzos, a lucrativos a medida que va incrementándose la demanda y la tendencia que apuntan es a que todas las plataformas, en el futuro, serán de pago. las diferencias encontradas en cada una de ellas con respecto a su funcionamiento y fin social ponen de manifiesto la necesidad de realizar una clasificación teniendo en cuenta estas diferencias y ajustar el marco legal según la tipología de cada una de ellas para que pueda existir una convivencia justa y pacífica con las empresas turísticas tradicionalesGiven the importance of collaborative tourism, this work will try to identify the existing business models, as well as the operation and future perspectives of the platforms belonging to the main areas in which the collaborative economy in the tourism sector stands out (accommodation, transport and restaurant service). a qualitative analysis based on in-depth interviews is developed. The results allow to conclude that there is a transition from nonprofit models in the beginning to lucrative as demand increases. The trend is that all platforms will be of payment in the future. The differences found with respect to its functioning and social purpose highlight the need to make a classification and adjust the legal framework according to their type so that there can be a fair and peaceful coexistence with traditional tourism companie

Syllabi y tests de progreso ó progress tests

Los alumnos de la Universidad Libre, en la Facultad de Ciencias de la Educación, en la carrera de Licenciatura en Humanidades e Idiomas, por varios factores pueden ser partidarios de abandonar la Licenciatura, ya sea por la falta de coherencia entre los programas, los libros y los tests de progreso aplicados a los estudiantes

Efficacy of prompted voiding for reversing urinary incontinence in older adults hospitalized in a functional recovery unit: Study protocol

Aims: To assess the efficacy of a prompted voiding programme for restoring urinary continence at discharge in hospitalized older adults who presented with reversible urinary incontinence (UI) on admission to a functional recovery unit (FRU). To assess the maintenance of the outcomes achieved after hospitalization. To identify modifiable and unmodifiable factors associated with the success of the prompted voiding programme. Design: Quasi-experimental, pre-/post-intervention study without a control group. Methods: Participants were aged 65 and over with a history of reversible UI in the previous year who had been admitted to a FRU and were on a prompted voiding programme throughout their hospitalization period. The sample consisted of 221 participants. A non-probabilistic sampling method, in order of recruitment after signing the informed consent form, was used. The primary outcomes were UI assessed at discharge and 1 month, 3 months and 6 months after discharge. Funding was granted in July 2019 by the Spain Health Research Fund (PI19/00168, Ministry of Health). The proposal was approved by the Spanish Research Ethics Committee. Discussion: The prompted voiding programme described can reverse UI or decrease the frequency and amount of urine loss in hospitalized older adults. Impact: Urinary incontinence is highly prevalent in hospitalized older adults. There is a need for care aimed at prevention, recovery and symptom control. Prompted voiding is a therapy provided by the nursing team during hospitalization and can also be provided by family caregivers at home after receiving proper training by the nursing team. Prompted voiding will enhance the health, functional ability and quality of life of older adults with UI, resulting in the reduction of associated healthcare costs and the risk of developing complicationsThis study has been funded by Instituto de Salud Carlos III through the project “PI19/00168” (Co-funded by European Regional Development Fund/ European Social Fund “A way to make Europe”/“Investing in your future”

Deep Phenotypic Characterisation of CTCs by Combination of Microfluidic Isolation (IsoFlux) and Imaging Flow Cytometry (ImageStream)

Ines Aznar-Peralta holds a "Garantia Juvenil" fellowship (contract number 8040), and M. Carmen Garrido-Navas has a postdoctoral fellowship funded by the Ministry of Economy, Competitiveness, Enterprises and Universities (DOC_01682).The isolation of circulating tumour cells (CTCs) in colorectal cancer (CRC) mostly relies on the expression of epithelial markers such as EpCAM, and phenotypic characterisation is usually performed under fluorescence microscopy with only one or two additional markers. This limits the ability to detect different CTC subpopulations based on multiple markers. The aim of this work was to develop a novel protocol combining two platforms (IsoFluxTM and ImageStream®X) to improve CTC evaluation. Cancer cell lines and peripheral blood from healthy donors were used to evaluate the efficiency of each platform independently and in combination. Peripheral blood was extracted from 16 early CRC patients (before loco-regional surgery) to demonstrate the suitability of the protocol for CTC assessment. Additionally, peripheral blood was extracted from nine patients one month after surgery to validate the utility of our protocol for identifying CTC subpopulation changes over time. Results: Our protocol had a mean recovery efficiency of 69.5% and a limit of detection of at least four cells per millilitre. We developed an analysis method to reduce noise from magnetic beads used for CTC isolation. CTCs were isolated from CRC patients with a median of 37 CTCs (IQ 13.0–85.5) at baseline. CTCs from CRC patients were significantly (p < 0.0001) larger than cytokeratin (CK)-negative cells, and patients were stratified into two groups based on BRAFV600E and PD-L1 expression on CK-positive cells. The changes observed over time included not only the number of CTCs but also their distribution into four different subpopulations defined according to BRAFV600E and PD-L1 positivity. We developed a novel protocol for semi-automatic CTC isolation and phenotypic characterisation by combining two platforms. Assessment of CTCs from early CRC patients using our protocol allowed the identification of two clusters of patients with changing phenotypes over time."Garantia Juvenil" fellowship 8040Ministry of Economy, Competitiveness, Enterprises and Universities DOC_0168

CD24 Expression Is Increased in 5-Fluorouracil-Treated Esophageal Adenocarcinoma Cells

The cancer stem cell (CSC) model suggests that there are subsets of cells within a tumor with increased proliferation and self-renewal capacity, which play a key role in therapeutic resistance. The importance of cyclooxygenase-2 (COX-2) in carcinogenesis has been previously established and the use of COX-2 inhibitors as celecoxib has been shown to exert antitumor effects. The present study investigated whether treatment of esophageal adenocarcinoma (EAC) cells with 5-fluorouracil (5-FU) or the growth of tumor spheres increased the proportion of CSCs and also if treatment with celecoxib was able to reduce the putative CSC markers in this tumor. OE19 and OE33 EAC cells surviving 5-FU exposure exhibited an increase in CSC markers CD24 and ABCG2 and also an increased resistance to apoptosis. EAC cell lines had the capacity to form multiple spheres displaying typical CSC functionalities such as self-renewal and increased CD24 levels. In addition, after the induction of differentiation, cancer cells reached levels of CD24 similar to those observed in the parental cells. Treatment with celecoxib alone or in combination with 5-FU also resulted in a reduction of CD24 expression. Moreover, celecoxib inhibited the growth of tumor spheres. These findings showing a reduction in CSC markers induced by celecoxib suggest that the COX-2 inhibitor might be a candidate for combined chemotherapy in the treatment of EAC. However, additional clinical and experimental studies are needed

Hepatocellular carcinoma risk-stratification based on ASGR1 in circulating epithelial cells for cancer interception

Purpose: Lack of diagnostic and prognostic biomarkers in hepatocellular carcinoma impedes stratifying patients based on their risk of developing cancer. The aim of this study was to evaluate phenotypic and genetic heterogeneity of circulating epithelial cells (CECs) based on asialoglycoprotein receptor 1 (ASGR1) and miR-122-5p expression as potential diagnostic and prognostic tools in patients with hepatocellular carcinoma (HCC) and liver cirrhosis (LC). Methods: Peripheral blood samples were extracted from LC and HCC patients at different disease stages. CECs were isolated using positive immunomagnetic selection. Genetic and phenotypic characterization was validated by double immunocytochemistry for cytokeratin (CK) and ASGR1 or by in situ hybridization with miR-122-5p and CECs were visualized by confocal microscopy. Results: The presence of CECs increased HCC risk by 2.58-fold, however, this was only significant for patients with previous LC (p = 0.028) and not for those without prior LC (p = 0.23). Furthermore, the number of CECs lacking ASGR1 expression correlated significantly with HCC incidence and absence of miR-122-5p expression (p = 0.014; r = 0.23). Finally, overall survival was significantly greater for patients at earlier cancer stages (p = 0.018), but this difference was only maintained in the group with the presence of CECs (p = 0.021) whereas progression-free survival was influenced by the absence of ASGR1 expression. Conclusion: Identification and characterization of CECs by ASGR1 and/or miR- 122-5p expression may be used as a risk-stratification tool in LC patients, as it was shown to be an independent prognostic and risk-stratification marker in LC and early disease stage HCC patients.Regional Ministry of Health of AndalusiaMinistry of Economy, Competitiveness, Enterprises and Universities PC-0522-2016 PC-0267-2017 PC-0033-2017Health Institute Carlos III (ISCIII) DOC_01682 CD18/0012

Related Factors of Anemia in Critically Ill Patients: A Prospective Multicenter Study

Anemia; Blood; Practice managementAnemia; Sangre; Gestión prácticaAnèmia; Sang; Gestió pràcticaAnemia is common in critically ill patients; almost 95% of patients admitted to intensive care units (ICUs) have hemoglobin levels below normal. Several causes may explain this phenomenon as well as the tendency to transfuse patients without adequate cause: due to a lack of adherence to protocols, lack of supervision, incomplete transfusion request forms, or a lack of knowledge about the indications, risks, and costs of transfusions. Daily sampling to monitor the coagulation parameters and the acid–base balance can aggravate anemia as the main iatrogenic factor in its production. We studied the association and importance of iatrogenic blood loss and other factors in the incidence of anemia in ICUs. We performed a prospective, observational, multicenter study in five Spanish hospitals. A total of 142 patients with a median age of 58 years (IQI: 48–69), 71.83% male and 28.17% female, were admitted to ICUs without a diagnosis of iatrogenic anemia. During their ICU stay, anemia appeared in 66.90% of the sample, 95 patients, (95% CI: 58.51–74.56%). Risk factors associated with the occurrence of iatrogenic anemia were arterial catheter insertion (72.63% vs. 46.81%, p-value = 0.003), venous catheter insertion (87.37% vs. 72.34%, p-value = 0.023), drainages (33.68% vs. 12. 77%, p-value = 0.038), and ICU stay, where the longer the stay, the higher the rate of iatrogenic anemia (p-value < 0.001). We concluded that there was a statistical significance in the production of iatrogenic anemia due to the daily sampling for laboratory monitoring and critical procedures in intensive care units. The implementation of patient blood management programs could address these issues

Efecto de la suplementación con vitamina E en los ácidos grasos poliinsaturados y en la expresión de genes relacionados con el metabolismo lipídico en L. Thoracis de corderos ligeros

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