Functionalization and Characterization of Magnetic Nanoparticles for the Detection of Ferritin Accumulation in Alzheimer's Disease

Early diagnosis in Alzheimer's disease (AD), prior to the appearance of marked clinical symptoms, is critical to prevent irreversible neuronal damage and neural malfunction that lead to dementia and death. Therefore, there is an urgent need to generate new contrast agents which reveal by a noninvasive method the presence of some of the pathological signs of AD. In the present study, we demonstrate for the first time a new nanoconjugate composed of magnetic nanoparticles bound to an antiferritin antibody, which has been developed based on the existence of iron deposits and high levels of the ferritin protein present in areas with a high accumulation of amyloid plaques (particularly the subiculum in the hippocampal area) in the brain of a transgenic mouse model with five familial AD mutations. Both in vitro and after intravenous injection, functionalized magnetic nanoparticles were able to recognize and bind specifically to the ferritin protein accumulated in the subiculum area of the AD transgenic mice.Fil: Fernández Cabada, Tamara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Politécnica de Madrid; EspañaFil: Martínez Serrano, Alberto. Consejo Superior de Investigaciones Científicas; España. Universidad Autónoma de Madrid; EspañaFil: Cussó, Lorena. Instituto de Investigacion Sanitaria Gregorio Marañón; España. Universidad Carlos III de Madrid; España. Centro de Investigación Biomédica en Red de Salud Mental; EspañaFil: Desco, Manuel. Instituto de Investigacion Sanitaria Gregorio Marañón; España. Centro de Investigación Biomédica en Red de Salud Mental; España. Universidad Carlos III de Madrid; EspañaFil: Ramos Gómez, Milagros. Universidad Politécnica de Madrid; Españ

All roads lead to Rome: Results of non-invasive respiratory therapies applied in a tertiary-care hospital without an Intermediate Care Unit during the COVID-19 pandemic

Documento escrito por un elevado número de autores/as, solo se referencia el/la que aparece en primer lugar y los/as autores/as pertenecientes a la UC3M.Introducción: Las terapias respiratorias no invasivas (TRNI) fueron ampliamente utilizadas en la primera ola de la pandemia de COVID-19, en escenarios distintos según los medios disponibles. El objetivo fue presentar la supervivencia a 90 días y los factores asociados a esta de los pacientes tratados con TRNI en un centro de tercer nivel sin Unidad de Cuidados Respiratorios Intermedios. Como objetivo secundario comparar los resultados obtenidos de las distintas terapias. Métodos: Estudio observacional de pacientes tratados con TRNI fuera de un ambiente de Cuidados Intensivos o Unidad de Cuidados Respiratorios Intermedios, diagnosticados de COVID-19 y con síndrome de distrés respiratorio agudo por criterios radiológicos y de ratio SpO2/FiO2. Se desarrolló un modelo multivariante de regresión logística para determinar las variables independientemente asociadas, y se compararon los resultados de la terapia de alto flujo con cánula nasal y la presión positiva continua en la vía aérea. Resultados: Se trataron 107 pacientes y sobrevivieron 85 (79,4%) a los 90 días. Antes de iniciar la TRNI el ratio medio de SpO2/FiO2 fue de 119,8 ± 59,4. Un mayor score de SOFA se asoció significativamente a la mortalidad (OR 2,09; IC95% 1,34 - 3,27), mientras que la autopronación fue un factor protector (OR 0,23; IC95% 0,06 - 0,91). La terapia de alto flujo con cánula nasal fue utilizada en 63 sujetos (58,9%), y la presión positiva continua en la vía aérea en 41 (38,3%). No se encontraron diferencias entre ellas. Conclusión: Aproximadamente cuatro de cada cinco pacientes tratados con TRNI sobrevivieron a los 90 días, y no se encontraron diferencias significativas entre la terapia de alto flujo con cánula nasal y la presión positiva continua en la vía aérea.Introduction: Non-invasive respiratory therapies (NRT) were widely used in the first wave of the COVID-19 pandemic in different settings, depending on availability. The objective of our study was to present 90-day survival and associated factors in patients treated with NRT in a tertiary hospital without an Intermediate Respiratory Care Unit. The secondary objective was to compare the outcomes of the different therapies. Methods: Observational study of patients treated with NRT outside of an intensive care or intermediate respiratory care unit setting, diagnosed with COVID-19 and acute respiratory distress syndrome by radiological criteria and SpO2/FiO2 ratio. A multivariate logistic regression model was developed to determine independently associated variables, and the outcomes of high flow nasal cannula and continuous positive airway pressure were compared. Results: In total, 107 patients were treated and 85 (79.4%) survived at 90 days. Before starting NRT, the mean SpO2/FiO2 ratio was 119.8 ± 59.4. A higher SOFA score was significantly associated with mortality (OR 2,09; 95% CI 1.34-3.27), while self-pronation was a protective factor (OR 0.23; 95% CI 0.06-0.91). High flow nasal cannula was used in 63 subjects (58.9%), and continuous positive airway pressure in 41 (38.3%), with no differences between them. Conclusion: Approximately 4 out of 5 patients treated with NRT survived to 90 days, and no significant differences were found between high flow nasal cannula and continuous positive airway pressure

Imagen molecular en medicina

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Limitaciones tecnológicas de la tomografía por emisión de positrones (PET) para pequeños animales de laboratorio

La visualización y cuantificación de la función de determinados órganos en animales de laboratorio mediante PET está demostrando ser una herramienta de gran relevancia para la caracterización del fenotipo de animales transgénicos y noqueados, en el estudio de modelos de enfermedades humanas, así como para el descubrimiento y desarrollo de nuevos medicamentos y sondas bioquímicas. Para poder utilizar la PET en animales de laboratorio de un modo análogo al que se aplica en humanos es necesario contemplar el factor de escala en el tamaño del vóxel así como mantener una similar estadística de contaje. En este trabajo se apuntan los problemas que estos requerimientos representan tanto para el diseño técnico de los tomógrafos como para la realización de los experimentos, y desde esta perspectiva se analizan las soluciones tecnológicas más relevantes. Finalmente, se comentan brevemente algunas características de sistemas disponibles hoy comercialmente (microPET y FOCUS, HiDAC, eXplore VISTA, MOSAIC, YAP-(S)PET y rPET)Publicad

A novel R-package graphic user interface for the analysis of metabonomic profiles

Background Analysis of the plethora of metabolites found in the NMR spectra of biological fluids or tissues requires data complexity to be simplified. We present a graphical user interface (GUI) for NMR-based metabonomic analysis. The "Metabonomic Package" has been developed for metabonomics research as open-source software and uses the R statistical libraries. /Results The package offers the following options: Raw 1-dimensional spectra processing: phase, baseline correction and normalization. Importing processed spectra. Including/excluding spectral ranges, optional binning and bucketing, detection and alignment of peaks. Sorting of metabolites based on their ability to discriminate, metabolite selection, and outlier identification. Multivariate unsupervised analysis: principal components analysis (PCA). Multivariate supervised analysis: partial least squares (PLS), linear discriminant analysis (LDA), k-nearest neighbor classification. Neural networks. Visualization and overlapping of spectra. Plot values of the chemical shift position for different samples. Furthermore, the "Metabonomic" GUI includes a console to enable other kinds of analyses and to take advantage of all R statistical tools. /Conclusion We made complex multivariate analysis user-friendly for both experienced and novice users, which could help to expand the use of NMR-based metabonomics

Modification of the TASMIP x-ray spectral model for the simulation of microfocus x-ray sources

The availability of accurate and simple models for the estimation of x-ray spectra is of great importance for system simulation, optimization, or inclusion of photon energy information into data processing. There is a variety of publicly available tools for estimation of x-ray spectra in radiology and mammography. However, most of these models cannot be used directly for modeling microfocus x-ray sources due to differences in inherent filtration, energy range and/or anode material. For this reason the authors propose in this work a new model for the simulation of microfocus spectra based on existing models for mammography and radiology, modified to compensate for the effects of inherent filtration and energy range.The research was supported by the Innovative Medicines Initiative Joint Undertaking under Grant Agreement No. 115337, which comprises financial contributions from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. This work was also partially funded by the AMIT project (CEN-20101014) from the CDTI-CENIT program, projects TEC2010-21619-C04-01, TEC2011-28972-C02-01, and PI11/00616 from the Spanish Ministerio de Ciencia e Innovación. A. Sisniega is funded by an FPU grant from the Spanish Ministerio de Educación.Publicad

Waking-like Brain Function in Embryos

Background: Experience-dependent plastic changes in the brain underlying complex forms of learning are generally initiated when organisms are awake, and this may limit the earliest developmental time at which learning about external events can take place. It is not known whether waking-like brain function is present prenatally in higher vertebrate (bird or mammal)embryos, or whether embryos have brain circuitry that can selectively turn on a waking-like state in response to salient external sensory stimulation. Results: Combining submillimeter-resolution brain positron emission tomography (PET), structural X-ray computed tomography (CT) of the skeleton for fine-scale embryo aging, and noninvasive behavioral recording of chicken embryos in the egg revealed unexpectedly wide variation in prenatal brain activity, inversely related to behavioral activity, which developed into different sleep-like fetal brain states. Brief prenatal exposure to a salient chicken vocalization (eliciting strong postnatal behavioral responses) increased higher-brain activity significantly more than a spectrally and temporally matching ‘‘nonvocal’’ noise analog. Patterns of correlated activity between the brainstem and higher-brain areas resembling awake, posthatching animals were seen exclusively in chicken-stimulated embryos. Conclusions: Waking-like brain function is present in a latent but inducible state during the final 20% of embryonic life, selectively modulated by context-dependent monitoring circuitry. These data also reveal the developmental emergence of sleep-like behavior and its linkage to metabolic brain states and highlight problems with assigning embryo brain states based on behavioral observations.Fundación BBVA, Cátedra de Biomedicina (Spain)National Science and Engineering Research Council of CanadaCanadian Fund for InnovationScuola Internazionale Superiore di Studi Avanzati (Trieste, Italia)En prens

Impact of optical tissue clearing on the Brillouin signal from biological tissue samples

Brillouin spectroscopy is a well-established technology in condensed matter physics to characterize the mechanical properties of inert materials, and it has been extended very recently to the study of biological samples. Transparency is beneficial for samples to be properly analyzed by Brillouin spectroscopy. Here, we explored the efficacy of optical tissue clearing techniques to improve the acquisition of Brillouin spectra from biological tissues in order to analyze their biomechanical properties. We describe the first application of Brillouin scattering to optically cleared biological tissues with CUBIC protocol. We conclude that, within the range of error, tissue clearing does not modify the mechanical properties of the studied biological tissues.Ministerio de Ciencia, Innovación y Universidades, the Pro CNIC Foundation, Severo Ochoa Center of Excellence (SEV-2015-0505); ISCIII-FIS grants PI18/00462 co-financed by ERDF, European Union (FEDER) Funds from the European Commission, European Union, “A way of making Europe”; MINECO/FEDER (MAT2015-65356-C3-1-R); Comunidad de Madrid Vol. 10, No. 6 | 1 Jun 2019 | BIOMEDICAL OPTICS EXPRESS 2681 (PHAMA 2.0-CM S2013/MIT-2740); CIBER de Salud Mental (CIBERSAM) and COSTaction CA16124