Gemcitabine-Loaded Magnetically Responsive Poly("-caprolactone) Nanoparticles against Breast Cancer

A reproducible and efficient interfacial polymer disposition method has been used to formulatemagnetite/poly("-caprolactone) (core/shell) nanoparticles (average size 125 nm, production performance 90%). To demonstrate that the iron oxide nuclei were satisfactorily embedded within the polymeric solid matrix, a complete analysis of these nanocomposites by, e.g., electron microscopy visualizations, energy dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy, electrophoresis, and contact angle goniometry was conducted. The magnetic responsive behaviour of these nanoparticles was quantitatively characterized by the hysteresis cycle and qualitatively investigated by visualization of the colloid under exposure to a 0.4 T magnet. Gemcitabine entrapment into the polymeric shell reported adequate drug loading values ( 11%), and a biphasic and pH-responsive drug release profile ( four-fold faster Gemcitabine release at pH 5.0 compared to pH 7.4). Cytotoxicity studies in MCF-7 human breast cancer cells proved that the half maximal inhibitory concentration of Gem-loaded nanocomposites was two-fold less than that of the free drug. Therefore, these core/shell nanoparticles could have great possibilities as a magnetically targeted Gemcitabine delivery system for breast cancer treatment.FEDER, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+i), Instituto de Salud Carlos III (FIS, Spain) PI19/0147

Magnetic Nanoparticules in Cancer Diagnosis and Treatment

Los avances en el campo de la nanotecnología incluyen el desarrollo de nuevas nanopartículas que están siendo usadas en el en el campo de la oncología, no sólo como nuevos vehiculizadores de drogas capaces de dirigirlas a lugares específicos al mismo tiempo que disminuyen sus efectos sistémicos, sino como mediadores para generar calor localizado (hipertermia) como terapia antitumoral y para la localización y visualización de este tipo de patología. En este contexto, las nanopartículas que incorporan núcleos magnéticos confiriéndoles propiedades paramagnéticas están cobrando gran relevancia en el campo del diagnóstico tumoral y también en el del tratamiento ya sea sólo para aplicar la hipertermia o para combinarla con fenómenos de direccionamiento de drogas citotóxicas mediante la adición en la superficie de la nanopartícula de moléculas que reconocen algún tipo de biomarcador de cáncer (“targeting activo”). El principal objetivo de esta revisión es presentar los avances más relevantes en el desarrollo de nanoplataformas que incorporan núcleos magnéticos y que representan una nueva estrategia para el tratamiento y/o diagnóstico del cáncer (teragnosis) indicando los principales ensayos in vitro e in vivo y especialmente los ensayos clínicos más significativos que tiene como base esta nueva concepción terapéutica dentro del campo de la oncología.The advances in the field of nanotechnology include the development of new nanoparticles that are being used inside oncology, not only as new drugs transporters that are able to direct them to specific locations at the same time decreasing their systemic effects, furthermore, they generate localized heat (hyperthermia) as an antitumor therapy and for the localization and visualization of this type of pathology. In this context, nanoparticles with magnetic cores that have paramagnetic properties are gaining importance in the field of tumor diagnosis and also in the treatment, either only for applying hyperthermia phenomena or to combine them with targeting phenomenom of cytotoxic drugs by the addition of molecules onto the nanoparticle surface that recognize some kind of cancer biomarker (active targeting). The main objective of this review is to show the most relevant advances in the development of nanoplatforms that have magnetic cores and are a new strategy for the cancer treatment and/or diagnosis (theragnosis) by the mention of the main in vitro and in vivo assays, specially the clinical trials most important of this new therapeutic concept inside within the field of oncology

Responding to the challenges of Water and Global Warming: Environmental Hydrogeology and Global Change Research Group (HYGLO-Lab)

[EN] The current Global Warming of planet Earth is probably the most important geological phenomenon in the last 20,000 years of its history and for human race. This process is having nowadays notable effects on the climate, ecosystems and natural resources. Possibly the most important renewable geological resource is water. One of the most strategic phases of the water cycle is groundwater. Despite its low visibility, quantitatively (and qualitatively too) it is essential for life on Planet Earth. Foreseeable consequences on groundwater due to climate change and sea level rise will be very significant. Hydrogeology can provide answers to many of the questions that are beginning to be raised in relation to these impacts and their effects. Environmental hydrogeology is a way of understanding the set of disciplines mixed in Hydrogeology as a Science of Nature. The HYGLO-Lab Research Group of the IGME-CSIC National Center attempts, through its lines of research, with a double global and local component, to provide answers to some of these questions.Peer reviewe

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

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

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Multivariate analysis of toxicological and environmental properties of soil nematicides

BACKGROUND In intensive agriculture, the use of pesticides and soil fumigants is necessary to produce economically viable crops worldwide. However, this practice may involve undesirable effects on human health and the environment. In 1995, methyl bromide was restricted by the Montreal Protocol because of possible ozone depletion. The objective of this study was to compare intrinsic environmental and toxicological properties of 11 active substances with nematicidal properties, some of them recognized as methyl bromide alternatives. RESULTS Four groups of active substances were discriminated by a series of principal component analyses (PCAs) (a) high toxicity to non-target fauna, humans and animals and medium persistence in the environment (cadusafos, ethoprophos and fenamiphos); (b) high toxicity to humans, animals and non-target fauna and high persistence (carbofuran and fosthiazate); (c) low toxicity to non-target fauna, humans and animals and low persistence (carbosulfan, benfuracarb and oxamyl); (d) low toxicity to humans, animals and non-target fauna and medium persistence in the environment (1,3-dichloropropene, chloropicrin and methyl bromide). CONCLUSION Evaluating the multiple aspects of toxicological and environmental properties of active substances through PCA is proposed as a helpful tool for initially comparing the complex toxicological behaviour of active substances as plant protection products. © 2008 Society of Chemical Industry

Impact of drinking water treatment processes on the residues of plant protection products for consumer and aquatic risk assessment: theoretical and experimental studies

Abstract Pesticides residues can occur in ground and surface waters, and potentially react with chemicals used for water disinfection treatments, such as chlorine. This can lead to the formation of unknown reaction products, which can be more toxic and/or persistent than the active substances themselves, and therefore become a potential risk for human health and environment. Thus, in the framework of the EU Regulation 1107/2009, the identification of these by‐products and their potential risk should be assessed. Within the European Food Risk Assessment (EU‐FORA) Fellowship Programme, the fellow studied the behaviour of herbicides belonging to the families of imidazolinones and sulfonylureas in waters treated with chlorine disinfectants. Due to their physicochemical properties, these herbicides are susceptible of reaching natural waters. In fact, some of them have been detected in water monitoring programmes. During the experimental part of the present work programme, reactions between the active substances and the most used chlorine disinfecting reactants (hypochlorite and chloramines) were performed. Degradation kinetic parameters such as half‐lives and degradation constants were calculated. Results showed that herbicide degradation was both pH and chlorine/chloramines concentration dependent. In order to identify the degradation by‐products, high‐resolution mass spectrometry experiments were performed, and a possible route of formation of these compounds was proposed. Finally, their risk assessment was carried out by using tox/ecotoxicological properties determined by QSAR methodology and FOCUS modelling for hazard and exposure assessment, respectively. These results will contribute to the definition of a risk assessment scheme for pesticides by‐products potentially occurring in drinking water

Relationships between nematode diversity, plant biomass, nutrient cycling and soil suppressiveness in fumigated soils

Nematodes interact with many other organisms as participants in several links of the soil food web, playing important roles in essential soil processes. Due to their high abundance and diversity of responses to soil disturbance, nematodes are suitable indicators of soil condition. With the aim of inferring soil fumigation effects on agroecosystem functioning, soil nematode diversity, soil properties, plant growth, and soil suppressiveness were monitored in a commercial strawberry farm and its surroundings for two consecutive growing seasons in southern Spain. Our results show that nematode diversity was low in fumigated soils throughout the whole season and, although yearly recovery occurred within the treated fields, fumigated soils showed a permanent perturbed condition. The nematode community was more closely associated to nutrient cycling in non-cropped than in cropped soils, and the link between plant biomass and nematode community structure was weak. Non-treated furrows within the treated fields were a reservoir of both beneficial and plant-parasitic nematodes, but such difference between furrows and beds was not enough to maintain more suppressive soil assemblages in the furrows. Treated soils were less suppressive than unmanaged soils, and there was a positive and significant correlation between soil suppressiveness and soil food web structure and diversity. © 2014 Elsevier Masson SAS