Impact of Magnetite Nanowires on In Vitro Hippocampal Neural Networks

Nanomaterials design, synthesis, and characterization are ever-expanding approaches toward developing biodevices or neural interfaces to treat neurological diseases. The ability of nanomaterials features to tune neuronal networks’ morphology or functionality is still under study. In this work, we unveil how interfacing mammalian brain cultured neurons and iron oxide nanowires’ (NWs) orientation affect neuronal and glial densities and network activity. Iron oxide NWs were synthesized by electrodeposition, fixing the diameter to 100 nm and the length to 1 μm. Scanning electron microscopy, Raman, and contact angle measurements were performed to characterize the NWs’ morphology, chemical composition, and hydrophilicity. Hippocampal cultures were seeded on NWs devices, and after 14 days, the cell morphology was studied by immunocytochemistry and confocal microscopy. Live calcium imaging was performed to study neuronal activity. Using random nanowires (R-NWs), higher neuronal and glial cell densities were obtained compared with the control and vertical nanowires (V-NWs), while using V-NWs, more stellate glial cells were found. R-NWs produced a reduction in neuronal activity, while V-NWs increased the neuronal network activity, possibly due to a higher neuronal maturity and a lower number of GABAergic neurons, respectively. These results highlight the potential of NWs manipulations to design ad hoc regenerative interfaces

Thermal route for the synthesis of maghemite/hematite core/shell nanowires

Nowadays, iron oxide-based nanostructures are key materials in many technological areas. Their physical and chemical properties can be tailored by tuning the morphology. In particular, the possibility of increasing the specific surface area has turned iron oxide nanowires (NWs) into promising functional materials in many applications. Among the different possible iron oxide NWs that can be fabricated, maghemite/hematite iron oxide core/shell structures have particular importance since they combine the magnetism of the inner maghemite core with the interesting properties of hematite in different technological fields ranging from green energy to biomedical applications. However, the study of these iron oxide structures is normally difficult due to the structural and chemical similarities between both iron oxide polymorphs. In this work, we propose a route for the synthesis of maghemite/hematite NWs based on the thermal oxidation of previously electrodeposited iron NWs. A detailed spectroscopic analysis based on Raman, Mossbauer, and X-ray absorption shows that the ratio of both oxides can be controlled during fabrication. Transmission electron microscopy has been used to check the core/shell structure of the NWs. The biocompatibility and capability of internalization of these NWs have also been proven to show the potential of these NWs in biomedical applications

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

Iron oxide nanomateriales and their interaction with biological systems

Tesis de la Universidad Complutense de Madrid, Facultad de Ciencias Físicas, Departamento de Física de Materiales, leída el 20-04-2018Los óxidos de hierro son materiales con un gran potencial en campos como la ingeniería, medio ambiente o biomedicina. En este último, la posibilidad de construir y utilizar nanoestructuras de óxido de hierro compatibles con sistemas biológicos está aumentando en todas las principales áreas de la investigación en cardiología, neurología, y cáncer. Sin embargo, el desarrollo de tales aplicaciones también exige enfrentarse a retos importantes como es avanzar en la comprensión de las interacciones entre las nanoestructuras con distintos sistemas biológicos, destacando la adhesión y la internalización en células vivas. Dentro de las diferentes nanoestructuras, en esta tesis doctoral se han estudiado las nanopartículas (NPs) y nanohilos (NWs) de óxido de hierro y su interacción con células de tumor cerebral y de hipocampo, respectivamente. En el primer caso, se ha estudiado la capacidad de internalización de NPs con objeto de aumentar el contraste de las imágenes de resonancia magnética (MRI). En el caso de NWs, debido a la alta relación de aspecto que presentan con respecto a las NPs, pueden ser de gran utilidad en aplicaciones como guiado o manipulación celular y como dispositivos en redes neuronales. Existen estudios de la interacción de NWs con células disociadas de hipocampo donde se ha analizado su efecto en la morfología de la red. En cambio existe muy poca bibliografía a cerca del estudio de la actividad de la red neuronal en sustratos de NWs. En el caso de los NWs de óxido de hierro, por primera vez, se muestra un estudio de los cambios en la morfología y la actividad de la red del hipocampo considerando diferentes dimensiones y orientaciones de NWs. Los resultados obtenidos aportan información novedosa sobre de las interacciones NP-medio y NP-membrana celular para MRI y de cómo el uso de diferentes NWs puede afectar a las redes neuronales.Depto. de Física de MaterialesFac. de Ciencias FísicasTRUEunpu

Nanomateriales de óxido de hierro y su interacción con sistemas biológicos

Tesis doctoral inédita leída en la Universidad Complutense de Madrid. Fecha de lectura: 20-4-2020

Influence of Coating and Size of Magnetic Nanoparticles on Cellular Uptake for In Vitro MRI

Iron oxide nanoparticles (IONPs) are suitable materials for contrast enhancement in magnetic resonance imaging (MRI). Their potential clinical applications range from diagnosis to therapy and follow-up treatments. However, a deeper understanding of the interaction between IONPs, culture media and cells is necessary for expanding the application of this technology to different types of cancer therapies. To achieve new insights of these interactions, a set of IONPs were prepared with the same inorganic core and five distinct coatings, to study their aggregation and interactions in different physiological media, as well as their cell labelling efficiency. Then, a second set of IONPs, with six different core sizes and the same coating, were used to study how the core size affects cell labelling and MRI in vitro. Here, IONPs suspended in biological media experience a partial removal of the coating and adhesion of molecules. The FBS concentration alters the labelling of all types of IONPs and hydrodynamic sizes ≥ 300 nm provide the greatest labelling using the centrifugation-mediated internalization (CMI). The best contrast for MRI results requires a core size range between 12–14 nm coated with dimercaptosuccinic acid (DMSA) producing R2* values of 393.7 s−1 and 428.3 s−1, respectively. These findings will help to bring IONPs as negative contrast agents into clinical settings

Impact of magnetite nanowires on in vitro hippocampal neural networks

2023 Descuento MDPINanomaterials design, synthesis, and characterization are ever-expanding approaches toward developing biodevices or neural interfaces to treat neurological diseases. The ability of nanomaterials features to tune neuronal networks’ morphology or functionality is still under study. In this work, we unveil how interfacing mammalian brain cultured neurons and iron oxide nanowires’ (NWs) orientation affect neuronal and glial densities and network activity. Iron oxide NWs were synthesized by electrodeposition, fixing the diameter to 100 nm and the length to 1 µm. Scanning electron microscopy, Raman, and contact angle measurements were performed to characterize the NWs’ morphology, chemical composition, and hydrophilicity. Hippocampal cultures were seeded on NWs devices, and after 14 days, the cell morphology was studied by immunocytochemistry and confocal microscopy. Live calcium imaging was performed to study neuronal activity. Using random nanowires (R-NWs), higher neuronal and glial cell densities were obtained compared with the control and vertical nanowires (V-NWs), while using V-NWs, more stellate glial cells were found. R-NWs produced a reduction in neuronal activity, while V-NWs increased the neuronal network activity, possibly due to a higher neuronal maturity and a lower number of GABAergic neurons, respectively. These results highlight the potential of NWs manipulations to design ad hoc regenerative interfaces.European CommissionMinisterio de Ciencia e Innovación (España)Comunidad de MadridDepto. de Física de MaterialesFac. de Ciencias FísicasTRUEpubDescuento UC