Pulmonary delivery of antibiotic-loaded lipid nanoparticles for the treatment of Pseudomonas aeruginosa infections associated with cystic fibrosis

225 p.El objetivo principal de esta tesis doctoral es el desarrollo de nanopartículas lipídicas sólidas (SLN) y partículas lipídicas nanoestructuradas (NLC) como vehículos para facilitar la liberación de antibióticos, colistimetato sódico y tobramicina, tras su administración pulmonar para el tratamiento de la fibrosis quística. La primera etapa de este trabajo fue el desarrollo y optimización de nanopartículas lipídicas cargadas con colistimetato sódico (Colist-SLN y Colist-NLC) que mostraron actividad antimicrobiana contra cepas de Pseudomonas aeruginosa aisladas de pacientes con fibrosis quística. Tras realizar un estudio de biodistribución de las NLCs en ratones usando una torre de nebulización se observó una elevada retención en los pulmones hasta las 48 horas. En una segunda parte, se realizó un estudio de estabilidad de las partículas de acuerdo con la normativa ICH. Para ello se analizaron sus características físico-químicas (tamaño, PDI, potencial zeta, perfil de liberación) y su actividad antimicrobiana durante un año. Las Colist-NLCs presentaron una mejor estabilidad a 5¿C y 25¿C/60% de humedad relativa durante un año de almacenamiento frente a las SLNs. Por ello, en la última parte de este trabajo se optó por encapsular tobramicina en NLCs (Tb-NLCs), nanopartículas que presentaron actividad antibacteriana frente a P. aeruginosa y permanecieron en los pulmones de los ratones hasta las 48 horas después de su administración intratraqueal. En resumen, teniendo en cuenta los resultados de esta tesis se puede concluir que las NLCs, utilizadas como vehículo de antibióticos, parecen una alternativa prometedora para el tratamiento de la fibrosis quísticaNanoBioCe

Late-life depression accelerates cognitive impairment and tau-associated pathology in an Alzheimer´s disease model.

Clinical studies suggest that depression could be considered an important risk factor for the future development of cognitive impairment and Alzheimer's disease (AD). In fact, there is a strong association between late-life depression and AD. The age of AD onset has been shown to be accelerated in patients with mild cognitive impairment (MCI) with a history of depression, and women appear to be particularly more vulnerable to this condition. In addition, individuals with MCI who present depressive symptoms have an elevated burden of amyloid-beta (Aβ), the main toxic protein associated with Alzheimer's pathology, and a higher risk of developing AD compared to non-depressed MCI patients. Although it has been described that some transgenic models of AD can develop signs similar to depression in advanced stages, the induction of Alzheimer's pathology due to a depressive process has not been studied under experimental conditions to emulate late-life depression as a risk factor for AD. In this study, we induced chronic unpredictable mild stress (CUMS) in P301S tau transgenic mice to determine whether depression is a cause, rather than a consequence, of the development of AD pathology. Our results suggest that transgenic tau mice subjected to CUMS seem to develop a depressive state. This animals display enhanced cognitive impairment compared to controls. In addition, histological studies show increased tau deposition, suggesting that late-life depression could worse AD progression by accelerating tau aggregation and worsening clinical signs. The findings generated in this project could provide evidence of depression as a risk factor for AD, providing new insights on molecular mechanisms involved in AD onset and progression.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Selective miRNA inhibition in CD8+ cytotoxic T lymphocytes enhances HIV-1 specific cytotoxic responses

miRNAs dictate relevant virus-host interactions, offering new avenues for interventions to achieve an HIV remission. We aimed to enhance HIV-specific cytotoxic responses—a hallmark of natural HIV control— by miRNA modulation in T cells. We recruited 12 participants six elite controllers and six patients with chronic HIV infection on long-term antiretroviral therapy ("progressors"). Elite controllers exhibited stronger HIV-specific cytotoxic responses than the progressors, and their CD8+T cells showed a miRNA (hsa-miR-10a-5p) significantly downregulated. When we transfected ex vivo CD8(+) T cells from progressors with a synthetic miR-10a-5p inhibitor, miR-10a-5p levels decreased in 4 out of 6 progressors, correlating with an increase in HIV-specific cytotoxic responses. The effects of miR-10a-5p inhibition on HIV-specific CTL responses were modest, short-lived, and occurred before day seven after modulation. IL-4 and TNF-α levels strongly correlated with HIV-specific cytotoxic capacity. Thus, inhibition of miR-10a-5p enhanced HIV-specific CD8(+) T cell capacity in progressors. Our pilot study proves the concept that miRNA modulation is a feasible strategy to combat HIV persistence by enhancing specific cytotoxic immune responses, which will inform new approaches for achieving an antiretroviral therapy-free HIV remission

Normative database for separate inner retinal layers thickness using spectral domain optical coherence tomography in Caucasian population

Purpose: Develop the first normative database of the thickness of every inner retinal layer in the macular area in a healthy, Caucasian population between 18 to 87 years old, using Spectralis Optical Coherence Tomography (OCT). Methods: On this transversal, observational study, 300 patients between 18 to 87 years old and without an ophthalmological condition were recruited. Macular OCT scans were performed on all patients (Spectralis OCT, Heidelberg Engineering). An axial length measurement, and keratometry were performed using an optical biometer. The volume and thickness of the different macular sectors of the inner retinal layers (retinal nerve fiber layer (RNFL), ganglion cells layer (CGL) and inner plexiform layer (IPL)) were analyzed with the Spectralis OCT segmentation software. An eye was randomly selected for each patient. Results: 297 patients (179 females and 118 males) were included in the study. The mean age was 56.07 years (range: 40.50-72). The multivariate analysis showed a positive correlation between the RNFL thickness and the axial length (p < 0.001). The mean central retinal thickness was 278.2 Mm (range: 266-291), the mean central RNFL thickness was 12.61 Mm (range: 11-14), the mean central CGL thickness was 17.63 Mm (range: 14-21) and the mean central IPL thickness was 22.02 Mm (range: 20-25). The multivariate analysis showed a negative correlation between age and CGL thickness and inner IPL thickness (p< 0.001). Conclusion: This study provides a normative database of the volume of each of the inner retinal layers on a Caucasian population

Sinus elevation by in situ utilization of bone scrapers : technique and results

Objectives: The objective was to present a novel technique for antrostomy performed before sinus elevation in atrophic maxilla for subsequent implant placement. Material and methods: The study included 10 sinus elevations performed by the proposed technique in nine consecutive patients presenting with inadequate posterior maxillary height. The technique is described, calculating the antrostomy surface area, volume of bone tissue obtained and final height attained in each case. A total of 16 implants were placed. Results: All ten elevations were accomplished. Mean antrostomy surface area was 0.55 mm2 , mean bone volume obtained was 0.56 cm3 and mean height attained was 11.7 mm from a baseline mean height of 5.6 mm. Out of the 16 implants, 14 were inserted immediately after the elevation and 2 were inserted in a second step, after ossification; 93.7% of the implants were osseointegrated at 6 months after prosthesis placement. Conclusion: The use of bone scrapers to create antrostomy for sinus elevation is a simple and very safe procedure. It provides a variable amount of particulate bone graft that is easily handled and highly useful for packing the cavity that will elevate the sinus membrane

Implementación del aprendizaje colaborativo utilizando la herramienta Nearpod en las clases prácticas de Alergología

Memoria ID-144. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2019-2020.[ES]Nearpod es una herramienta digital que permite la interacción profesor-alumno mediante dispositivo móviles, utilizando la conexión a internet, y posibilita la inserción de actividades en las presentaciones de contenidos. El objetivo general es mejorar el proceso de enseñanza aprendizaje en la docencia práctica de la asignatura de Alergologí

Estudio para la mejora de la calidad del Máster en Trabajo Social Comunitario, Gestión y Evaluación de Servicios Sociales en atención a las necesidades del alumnado egresado

Se presenta el informe sobre el desarrollo del proyecto de innovación en calidad llevado a cabo por un equipo interdisciplinar en la Facultad de Trabajo Social. A través de la creación de un cuestionario y un grupo de discusión se analiza la inserción laboral y satisfacción con la titulación de nuestros egresados

Ammonia levels in different kinds of sampling sites in the central Iberian Peninsula

Ponencia presentada en:2nd Iberian Meeting on Aerosol Science and Technology (RICTA 2014) celebrado en Tarragona del 7 al 9 de julio de 2014.Ammonia is the Secondary Inorganic Aerosol (SIC) gaseous precursor which has been studied to a lesser extent in the Madrid Metropolitan Area up to date. A study conducted in the city of Madrid with the aim of characterizing levels of ammonia took place in 2011. These campaigns formed part of a larger study conducted in 6 Spanish cities. A time series of weekly integrated ammonia measurements available at an EMEP rural site (Campisábalos) has been used to obtain information on the ammonia rural background in the region. The results point to traffic and waste treatment plants as the main ammonia sources in Madrid. Relevant seasonal differences have not been observed in the Metropolitan Area. The explanation can be related to the fall in the rural background levels during July 2011, which might conceal urban summer emission increases observed in other cities

Brexit : balance de situación y perspectivas

Tras casi tres años desde que se anunciara la celebración del referéndum sobre la permanencia del Reino Unido en la Unión Europea (UE) y dos de intensas negociaciones entre las partes, la no ratificación del Parlamento británico del acuerdo alcanzado por su Gobierno y por el resto de los socios europeos en noviembre del año pasado ha dado lugar a una situación extraordinariamente compleja, en la que, a escasos días de que se cumpla el plazo (el 29 de marzo de 2019) para la salida del Reino Unido establecido con la activación del artículo 50, no se vislumbra todavía un plan de consenso. a falta de una alternativa pactada, la salida sin acuerdo en la fecha prevista constituye —salvo prórroga— la actual opción por defecto. este documento ocasional hace balance de la situación actual y de las perspectivas que se abren en relación con el proceso de salida del Reino Unido de la UE, y recopila y actualiza algunos trabajos que se han venido realizando, en relación con el seguimiento regular de dicho proceso y con la estimación de sus potenciales efectos en la economía española, en la Dirección General de Economía y Estadística del Banco de España. Tras tomar nota del momento actual del proceso negociador, el documento revisa la evolución de la economía británica desde que se anunciara el inesperado resultado del referéndum en junio de 2016, así como las perspectivas económicas a medio plazo del país, que dependerán ante todo del tipo de relación comercial que se establezca en un futuro entre ambas áreas, así como de la manera más o menos abrupta en que se produzca la salidaAlmost three years on since the Brexit referendum and two since the intense negotiations between the parties began, the failure by the British Parliament to ratify the November 2018 agreement between the UK Government and the other EU governments has led to a situation of great complexity. With only a few days remaining until 29 March 2019, when the Article 50 deadline for withdrawal expires, no consensus plan has emerged yet. Without an alternative plan, a no-deal exit is – excepting postponement – the current default option. This Occasional Paper takes stock of the current situation and outlook for Brexit (i.e. the process of UK withdrawal from the EU) by drawing together a number of studies produced at the Banco de España in connection with the regular monitoring of the process and its potential effects on the Spanish economy. after noting where the current negotiations stand, the paper reviews UK economic developments since the surprise result of the referendum was announced in June 2016. It further lays out the medium-term outlook for the British economy, which hinges crucially on both the type of future trade relationship to be agreed between both areas and the degree of disruption caused by the withdrawal process. As regards Spain, the paper analyses several issues related to its trade and financial exposures to the UK and also provides estimates of the potential effects of Brexit on the Spanish economy under various hypothetical scenarios using the MTBE (i.e. the quarterly macroeconometric model of the Spanish Economy regularly used at the Banco de España for forecasting and policy analysis). Finally, mention is made of the contingency measures adopted, within their respective remits, by the European Commission and the Spanish Government, in the event of an abrupt no-deal exi

Wikipedia como herramienta de aprendizaje en la docencia de derecho del trabajo y de la seguridad social

Memoria ID12-0223. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2012-2013