Liposomes and nanotechnology in drug development: focus on neurological targets

Neurological diseases represent a medical, social, and economic problem of paramount importance in developed countries. Although their etiology is generally known, developing therapeutic interventions for the central nervous system is challenging due to the impermeability of the blood-brain barrier. Thus, the fight against neurological diseases usually struggles "at the gates" of the brain. Flooding the bloodstream with drugs, where only a minor fraction reaches its target therapeutic site, is an inefficient, expensive, and dangerous procedure, because of the risk of side effects at nontargeted sites. Currently, advances in the field of nanotechnology have enabled development of a generation of multifunctional molecular platforms that are capable of transporting drugs across the blood-brain barrier, targeting specific cell types or functional states within the brain, releasing drugs in a controlled manner, and enabling visualization of processes in vivo using conventional imaging systems. The marriage between drug delivery and molecular imaging disciplines has resulted in a relatively new discipline, known as theranostics, which represents the basis of the concept of personalized medicine. In this study, we review the concepts of the blood-brain barrier and the strategies used to traverse/bypass it, the role of nanotechnology in theranostics, the wide range of nanoparticles (with emphasis on liposomes) that can be used as stealth drug carriers, imaging probes and targeting devices for the treatment of neurological diseases, and the targets and targeting strategies envisaged in the treatment of different types of brain pathology

Symmetrical Pyridinium-Phanes and –Diazacyclophanes — Promising Heterocyclic Scaffolds for the Development of Anti-Leishmanial Agents

There is an urgent need for better drugs for a more successful fight against leishmaniasis, one of the most important neglected diseases caused by the parasite Leishmania. We have recently synthesized several symmetrical pyridinium compounds belonging to two different series: bis-pyridinium and bis-quinolinium acyclic structures and bis-pyridinium diazacyclophanes derivatives. The first series of bis-pyridinium derivatives have been found to display activity against promastigotes and intracellular amastigotes of Leishmania donovani and Leishmania major, with EC50 values lower than 1 μM. The majority of compounds show a similar behavior in both Leishmania species, being slightly more active against intracellular amastigotes of L. major. The series of bis-pyridinium diazacyclophanes can be considered as rigid analogues of the previous bis-cationic ones. The activity of these compounds has also been evaluated against promastigotes and intracellular amastigotes of L. donovani and L. major. All the diazacyclophanes are more active against L. major, with EC50 values of between 1 and 17 μM in intracellular amastigotes, and in some cases they present a higher selectivity index than the reference anti-leishmanial drugs such as amphotericin B and miltefosine. In conclusion, these bis-quaternary compounds represent promising candidates as potential therapeutic agents against leishmaniasis

El poblamiento de la edad del cobre en la tierra llana de Huelva

Se presentan en este trabajo los resultados del Proyecto Tierra Llana de Huelva referidos a la ocupación de la Edad del Cobre. Proponemos una permanencia del sistema del poblamiento durante el Calcolítico y Bronce Pleno, y su ruptura hacia el Bronce Final, periodo en el que se estructura el territorio en turno a centros hegemónicos.____________________________They are presented in this work the results of the project Flat Earth of Huelva referred to the occupation of the Copper Age. We propose a permanency of the system of the settlement during the Calcolithic time and Middle-Bronze Age, and their rupture toward the Final Bronze Age, in the one that the territory appears structured to hegemonic centers

A distributed and energy‑efficient KNN for EEG classification with dynamic money‑saving policy in heterogeneous clusters

Universidad de Granada/CBUASpanish Ministry of Science, Innovation, and Universities under Grants PGC2018-098813-B-C31,PID2022-137461NB-C32ERDF fund. Funding for open access charge: University of Granada/ CBU

Designing an Advanced Regional Research Network

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Niebla, de Oppidum a Madina

In this paper we study excavation results and studies carried out in the Niebla Ar-chaeological Urban Proyect. The relationship between the Niebla (Huelva province, southwest Spain) settlement and the configuration of an urban model from the Late Bronze Age to Medieval Time, explains the importance that the urban concept have been througth the time in the Huelva Countryside, and we analize the diferent eco-nomic interactive models beetwen the city and its territory.En este trabajo se estudian los resultados de las excavaciones y estudios realizados en el Proyecto de Arqueología Urbana en Niebla (Huelva). El papel desempeñado por el asentamiento de Niebla en la configuración de un modelo de ciudad con orígenes en el Bronce Final y su evolución a lo largo de las etapas preromana, romana y medieval, explica el rango que el concepto urbano ha tenido a lo largo de este periodo en la campiña de Huelva, y se analizan las causas que provocan los dis­tintos modelos por la interacción de relaciones económicas y sociales entre mundo urbano y su territorio

Reproductive efficiency of entomopathogenic nematodes as scavengers. Are they able to fight for insect’s cadavers?

Entomopathogenic nematodes (EPNs) and their bacterial partners are well-studied insect pathogens, and their persistence in soils is one of the key parameters for successful use as biological control agents in agroecosystems. Free-living bacteriophagous nematodes (FLBNs) in the genus Oscheius, often found in soils, can interfere in EPN reproduction when exposed to live insect larvae. Both groups of nematodes can act as facultative scavengers as a survival strategy. Our hypothesis was that EPNs will reproduce in insect cadavers under FLBN presence, but their reproductive capacity will be severely limited when competing with other scavengers for the same niche. We explored the outcome of EPN - Oscheius interaction by using freeze-killed larvae of Galleria mellonella. The differential reproduction ability of two EPN species (Steinernema kraussei and Heterorhabditis megidis), single applied or combined with two FLBNs (Oscheius onirici or Oscheius tipulae), was evaluated under two different infective juvenile (IJ) pressure: low (3IJs/host) and high (20IJs/host). EPNs were able to reproduce in insect cadavers even in the presence of potential scavenger competitors, although EPN progeny was lower than that recorded in live larvae. Hence, when a highly susceptible host is available, exploiting cadavers by EPN might limit the adaptive advantage conferred by the bacteria partner, and might result in an important trade-off on long-term persistence. Contrary to our hypothesis, for most of the combinations, there were not evidences of competitive relationship between both groups of nematodes in freeze-killed larvae, probably because their interactions are subject to interference by the microbial growth inside the dead host. Indeed, evidences of possible beneficial effect of FLBN presence were observed in certain EPN-FLBN treatments compared with single EPN exposure, highlighting the species-specific and context dependency of these multitrophic interactions occurring in the soil.Research Subject Categories::FORESTRY, AGRICULTURAL SCIENCES and LANDSCAPE PLANNING::Soil science::Soil biology; Research Subject Categories::NATURAL SCIENCES::Biology::Terrestrial, freshwater and marine ecology::Ethology and behavioural ecology; Research Subject Categories::NATURAL SCIENCES::Biology::Terrestrial, freshwater and marine ecology::Terrestrial ecologyinfo:eu-repo/semantics/publishedVersio

Vampire: A Smart Energy Meter for Synchronous Monitoring in a Distributed Computer System

This paper presents the design and implementation of a low-cost system oriented to the synchronised and real-time surveillance and monitoring of electrical parameters of different computer devices. To measure energy consumption in a computer system, it is proposed to use, instead of a general-purpose wattmeter, one designed ad-hoc and synchronously collects the energy consumption of its various nodes or devices. The implementation of the devised system is based on the confluence of several technologies or tools widely used in the Internet of Things. Thus, this article the intelligent objects are the power meters, whose connections are based on the low-cost ESP32 microcontroller. The message transmission between devices is carried out with the standard message queuing telemetry transport (MQTT) protocol, the measurements are grouped in a database on an InfluxDB server that store the sensor data as time series, and Grafana is used as a graphical user interface. The efficiency of the proposed energy monitoring system is demonstrated by the experimental results of a real application that successfully and synchronously records the voltage, current, active power and cumulative energy consumption of a distributed cluster that includes a total of 60 cores.Spanish Ministry of Science, Innovation, and Universities under grants PGC2018–098813-B-C31 and PID2022–137461NB-C31ERDF fun

Nivel de eficiencia del uso de recursos por las organizaciones públicas. Caso: sistemas sanitarios españoles

Objectives: This paper seeks to detect, in the Spanish health system, which health services are efficient, and which are not, as well as propose corrective measures that allow inefficient health services to achieve efficiency. Methods: This paper applies the Data Envelopment Analysis (DEA) methodology, which allows obtaining natural and managerial efficiencies, as well as deviations from inefficient units in relation to efficient ones and proposing corrective measures that imply only budgetary (natural) modifications or changes in the policies of resource management (management). Results: Through the efficiencies, or the lack of them, the health services of the 17 Spanish autonomous communities are classified into four groups: With high, medium-high, medium-low or low natural or managerial efficiency. Conclusions: The lack of natural efficiency can be corrected with a greater budgetary endowment and the lack of managerial efficiency with a budget cut and changes in resource management policies. This tendency contrary to the adjustments is precisely what gives this work of interest and novelty with respect to others that apply the DEA in different sectors such as those that study the impact on the environment of resource consumption. Another important aspect of this study is the possibility of applying it to other countries with similar political structures.Objetivos: Con este trabajo se persigue detectar, en el sistema sanitario español, que servicios sanitarios son eficientes y cuáles no, así como proponer medidas correctoras que permitan a los servicios sanitarios ineficientes alcanzar la eficiencia. Metodología: Este trabajo aplica la metodología del análisis envolvente de datos (DEA), que permite obtener las eficiencias natural y gerencial, así como las desviaciones de las unidades ineficientes con relación a las eficientes, y proponer medidas correctoras que impliquen únicamente modificaciones presupuestarias (natural) o cambios en las políticas de gestión de recursos (gerencial). Resultados: A través de las eficiencias, o la falta de ellas, los servicios sanitarios de las 17 comunidades autónomas españolas se clasifican en cuatro grupos: Con eficiencia natural o gerencial alta, media-alta, media-baja o baja. Conclusiones: La falta de eficiencia natural puede corregirse con una mayor dotación presupuestaria, la falta de eficiencia gerencial con un recorte presupuestario y cambios en las políticas de gestión de recursos. Esta tendencia contraria de los ajustes es precisamente la que dota este trabajo del interés y novedad con respectos a otros que aplican el DEA en sectores diferentes como aquellos que estudian el impacto en el medioambiente de los consumos de recursos. Otro aspecto importante de este estudio es la posibilidad de aplicarlo a otros países con estructuras políticas similares