Hybrid hydrogels support neural cell culture development under magnetic actuation at high frequency.

The combination of hydrogels and magnetic nanoparticles, scarcely explored to date, offers a wide range of possibilities for innovative therapies. Herein, we have designed hybrid 3D matrices integrating natural polymers, such as collagen, chitosan (CHI) and hyaluronic acid (HA), to provide soft and flexible 3D networks mimicking the extracellular matrix of natural tissues, and iron oxide nanoparticles (IONPs) that deliver localized heat when exposed to an alternating magnetic field (AMF). First, colloidally stable nanoparticles with a hydrodynamic radius of ∼20 nm were synthesized and coated with either CHI (NPCHI) or HA (NPHA). Then, collagen hydrogels were homogeneously loaded with these coated-IONPs resulting in soft (E0 ∼ 2.6 kPa), biodegradable and magnetically responsive matrices. Polymer-coated IONPs in suspension preserved primary neural cell viability and neural differentiation even at the highest dose (0.1 mg Fe/mL), regardless of the coating, even boosting neuronal interconnectivity at lower doses. Magnetic hydrogels maintained high neural cell viability and sustained the formation of highly interconnected and differentiated neuronal networks. Interestingly, those hydrogels loaded with the highest dose of NPHA (0.25 mgFe/mg polymer) significantly impaired non-neuronal differentiation with respect to those with NPCHI. When evaluated under AMF, cell viability slightly diminished in comparison with control hydrogels magnetically stimulated, but not compared to their counterparts without stimulation. Neuronal differentiation under AMF was only affected on collagen hydrogels with the highest dose of NPHA, while non-neuronal differentiation regained control values. Taken together, NPCHI-loaded hydrogels displayed a superior performance, maybe benefited from their higher nanomechanical fluidity. STATEMENT OF SIGNIFICANCE: Hydrogels and magnetic nanoparticles are undoubtedly useful biomaterials for biomedical applications. Nonetheless, the combination of both has been scarcely explored to date. In this study, we have designed hybrid 3D matrices integrating both components as promising magnetically responsive platforms for neural therapeutics. The resulting collagen scaffolds were soft (E0 ∼ 2.6 kPa) and biodegradable hydrogels with capacity to respond to external magnetic stimuli. Primary neural cells proved to grow on these substrates, preserving high viability and neuronal differentiation percentages even under the application of a high-frequency alternating magnetic field. Importantly, those hydrogels loaded with chitosan-coated iron oxide nanoparticles displayed a superior performance, likely related to their higher nanomechanical fluidity.

A Comparative Study of Ultrasmall Calcium Carbonate Nanoparticles for Targeting and Imaging Atherosclerotic Plaque.

Atherosclerosis is a complex disease that can lead to life-threatening events, such as myocardial infarction and ischemic stroke. Despite the severity of this disease, diagnosing plaque vulnerability remains challenging due to the lack of effective diagnostic tools. Conventional diagnostic protocols lack specificity and fail to predict the type of atherosclerotic lesion and the risk of plaque rupture. To address this issue, technologies are emerging, such as noninvasive medical imaging of atherosclerotic plaque with customized nanotechnological solutions. Modulating the biological interactions and contrast of nanoparticles in various imaging techniques, including magnetic resonance imaging, is possible through the careful design of their physicochemical properties. However, few examples of comparative studies between nanoparticles targeting different hallmarks of atherosclerosis exist to provide information about the plaque development stage. Our work demonstrates that Gd (III)-doped amorphous calcium carbonate nanoparticles are an effective tool for these comparative studies due to their high magnetic resonance contrast and physicochemical properties. In an animal model of atherosclerosis, we compare the imaging performance of three types of nanoparticles: bare amorphous calcium carbonate and those functionalized with the ligands alendronate (for microcalcification targeting) and trimannose (for inflammation targeting). Our study provides useful insights into ligand-mediated targeted imaging of atherosclerosis through a combination of in vivo imaging, ex vivo tissue analysis, and in vitro targeting experiments.

A Comprehensive Introduction to Magnetic Resonance Imaging Relaxometry and Contrast Agents.

The development of imaging technologies allowing noninvasive observation through solid bodies has represented a breakthrough in medical diagnosis, facilitating the comprehension of biomolecular events underlying disease and the development of more efficient therapeutic approaches. Some of the traditional limitations of these techniques are nowadays fading away thanks to the combination of imaging with nanotechnology, allowing the development of novel functional biomaterials that increase the sensitivity of detection, enable sensitivity to specific targets, and facilitate the combination of therapeutic and diagnostic functions (theragnosis) with molecular platforms functioning simultaneously as imaging probes and drug delivery carriers. The design of such functional biomaterials requires a comprehensive understanding of the principles that govern the generation of signal and modulation of contrast for a given imaging modality to exploit its capabilities to the maximal level. In this sense, magnetic resonance imaging (MRI) is a technique that presents a complex relationship between the detected signal and the physical-chemical properties of its sourcing matter, allowing the generation of multiple image contrasts. Thus, while magnetic resonance imaging is a highly versatile imaging modality, it requires specific knowledge of its physical principles to take advantage of all of its possibilities. This work reviews the origin of the image signal and contrast in MRI and the concepts of relaxometry and MRI contrast agents.

Mathematical achievement: the role of spatial and motor skills in 6-8 year-old children.

Several studies have tried to establish the factors that underlie mathematical ability across development. Among them, spatial and motor abilities might play a relevant role, but no studies jointly contemplate both types of abilities to account for mathematical performance. The present study was designed to observe the roles of spatial and motor skills in mathematical performance. A total of 305 children aged between 6 and 8 years took part in this study. A generalized linear regression model with mathematical performance as a dependent variable was performed. Results revealed that Block design (as a visuospatial reasoning measure) accounted for mathematical performance, especially among 6- and 7-year-olds but not in 8-year-olds. After controlling for the effect of the block design, mental rotation and manual dexterity predicted mathematical performance. These findings highlight the role of underlying cognitive (spatial) and motor abilities in supporting mathematical achievement in primary school children.

Developmental differences between 1st and 3rd year of Early Childhood Education (preschool) in mental rotation and its training.

Research has shown that mental rotation (MR) can be improved through training. However, studies with preschool children are very scarce, due in part to the lack of consensus as to the age at which this ability arises and can be trained, and due to the difficulties of working on the understanding of this ability when it begins to develop. The present study was designed to observe the effect of an MR training on 1st (3-4-year-old children) and 3rd year (5-6-year-old children) of Early Childhood Education (preschool), as well as the development of this ability between both courses. Finally, this study aimed to analyze the differential increase of the training effect in relation to the initial MR ability of the participants. The results showed a significant improvement in the participants who underwent training in 3rd year of preschool, with the trained group showing a marginal improvement in 1st year of preschool. The older group showed lower error rates in training performance than the younger group, the latter having a linear decrease in performance as the angular disparity increased. In addition, in relation to training, a greater increase of MR was observed in the 3rd year preschoolers with lower scores in the pretest. These results suggest that MR is in full development and that it is a spatial ability that can be trained at preschool ages. In addition, the possibility of enhancing this ability to a greater extent in preschoolers who exhibit lower initial MR level is especially relevant.

From What Age Is Mental Rotation Training Effective? Differences in Preschool Age but Not in Sex.

Currently, there is evidence that spatial skills training leads to an improvement of such skills, although studies with children in the Preschool stage are very scarce. This paper aims to examine the effectiveness of mental rotation (MR) training and sex differences in preschool children. Two experiments were carried out. Experiment 1 included 59 children of 1st course (aged between 3 and 4 years) and Experiment 2, 61 children of 2nd course (aged between 4 and 5 years) of Preschool Education, distributed into control and training groups. The results showed a significant improvement in the MR ability of the training group (measured through a different test than the one used for training) only in the older children, and a tendency toward significance in the younger participants. Moreover, no sex differences in MR or group differences across age groups were found. These results regarding MR training support the malleability of spatial skills approach, particularly in 4-5 year-old preschoolers. This malleability should be enhanced in our educational system, as well as the implementation of educational and social policies that tend toward equality between sexes in the development of spatial skills. This can promote an equitable access to academic careers requiring high spatial skills such as engineering, science, technology or mathematics, in which nowadays women are underrepresented.

[Clinical utility and psychometric properties of Prefrontal Symptoms Inventory (PSI) in acquired brain injury and degenerative dementias]. / Utilidad clínica y propiedades psicométricas del inventario de síntomas prefrontales (ISP) en el daño cerebral adquirido y las demencias degenerativas.

INTRODUCTION: The cognitive, emotional and behavioural alterations secondary to acquired brain injury and degenerative dementias can be quantitatively and quantitatively appraised by administering self-reports that ask both patients and reliable informants about the difficulties patients have in their everyday life. SUBJECTS AND METHODS: The Prefrontal Symptoms Inventory (PSI) and the Modified Memory Failures in Everyday Life Questionnaire (MFE-30) were administered to 174 paired participants: 87 patients with brain damage or degenerative dementias and their 87 reliable informants. In addition to the psychometric goodness of the tests, the study also explored the clinical usefulness of applying these questionnaires to patients and their informants in order to obtain a rate of discrepancy in the scores as a measure of anosognosia. RESULTS: The results show how applying the PSI-20 (20 items) or the PSI (46 items), whether administered together with the MFE-30 (30 items) or not, is a very useful procedure for assessing the symptoms in individuals with acquired brain injury or degenerative dementias, since it yields a great deal of information about patients' difficulties in their daily life. CONCLUSIONS: We recommend that, in addition to the compulsory neuropsychological assessment, questionnaires or inventories of symptoms like those proposed here should be carried out, due to the fact that they offer a number of advantages from the clinical point of view, as well as being efficacious and effective in economic terms.

TITLE: Utilidad clinica y propiedades psicometricas del inventario de sintomas prefrontales (ISP) en el daño cerebral adquirido y las demencias degenerativas.Introduccion. Las alteraciones cognitivas, emocionales y comportamentales secundarias al daño cerebral adquirido y las demencias degenerativas pueden valorarse cuantitativa y cualitativamente mediante la administracion de autoinformes que interroguen ­a pacientes e informadores fiables­ sobre las dificultades de los pacientes en la vida cotidiana. Sujetos y metodos. Se administro el inventario de sintomas prefrontales (ISP) y el cuestionario de fallos de memoria en la vida cotidiana modificado (MFE-30) a 174 participantes emparejados: 87 pacientes con daño cerebral o demencias degenerativas y sus 87 informadores fiables. Se exploro, junto con la bondad psicometrica de las pruebas, la utilidad clinica de la aplicacion de estos cuestionarios a pacientes e informadores para obtener un indice de discrepancia de las puntuaciones como medida de la anosognosia. Resultados. Los resultados muestran como aplicar el ISP-20 (20 items) o el ISP (46 items), sean o no administrados conjuntamente con el MFE-30 (30 items), resulta un procedimiento muy util para la valoracion de la sintomatologia en los individuos con daño cerebral adquirido o demencias degenerativas, al proporcionar una gran cantidad de informacion sobre las dificultades de los pacientes en la vida cotidiana. Conclusiones. Se recomienda, junto con la obligada evaluacion neuropsicologica, la cumplimentacion de cuestionarios o inventarios de sintomas como los propuestos, dado que presentan ventajas desde el punto de vista clinico, ademas de resultar eficaces, efectivos y eficientes en terminos economicos.

[Prefrontal clinical symptoms in daily living: screening assessment by means of the short Prefrontal Symptoms Inventory (PSI-20)]. / Sintomatologia prefrontal en la vida diaria: evaluacion de cribado mediante el inventario de sintomas prefrontales abreviado (ISP-20).

INTRODUCTION: Estimation of daily symptoms of frontal dysfunction is considered to be essential in order to endow neuro-psychological assessments with ecological validity. The questionnaires available today were constructed to estimate executive problems in daily life in populations with neurological damage. There is a need for instruments focused on measuring these behaviours in the general population or in clinical populations with mild or moderate impairment. AIM: To examine the factorial validity and to find evidence of concurrent validity of the short version of the Prefrontal Symptoms Inventory. SUBJECTS AND METHODS: Three samples were obtained: the first, from the Internet (n = 504); the second, in a non-clinical population by means of paper and pencil (n = 1,257); and the third, from patients being treated for substance addiction (n = 602). A factorial analysis without restraints was used on the first sample and the results were submitted to confirmatory factorial analysis on the other two samples. RESULTS: The three-factor structure that was found was confirmed with excellent indicators of fit in the other two samples. Evidence of concurrent validity was found with quality of life and mental health tests. CONCLUSIONS: We propose a short questionnaire for detecting failures of a prefrontal origin in daily living, which improves on the psychometric qualities of similar tests, but is oriented towards severe neurological pathologies. The structural stability of the test ensures it can be used in the general population, for the early detection of cognitive impairment, and in clinical populations with mild or moderate deterioration. A set of criteria are proposed for use in interpreting the results.

TITLE: Sintomatologia prefrontal en la vida diaria: evaluacion de cribado mediante el inventario de sintomas prefrontales abreviado (ISP-20).Introduccion. La estimacion de sintomas cotidianos de disfuncion frontal se considera imprescindible para aportar validez ecologica a las evaluaciones neuropsicologicas. Los cuestionarios disponibles se construyeron para estimar problemas ejecutivos en la vida diaria en poblaciones con daño neurologico. Se requieren instrumentos enfocados a medir estos comportamientos en la poblacion general o en poblaciones clinicas con fallos leves o moderados. Objetivo. Estudiar la validez factorial y encontrar indicios de validez concurrente de la version abreviada del inventario de sintomas prefrontales. Sujetos y metodos. Se obtuvieron tres muestras: la primera, a traves de Internet (n = 504); la segunda, en poblacion no clinica mediante lapiz y papel (n = 1.257), y la tercera, de pacientes en tratamiento por adiccion a sustancias (n = 602). Se utilizo un metodo de analisis factorial sin restricciones sobre la primera muestra y los resultados se sometieron a analisis factorial confirmatorio sobre las otras dos muestras. Resultados. La estructura de tres factores encontrada se confirmo con excelentes indicadores de ajuste en las otras dos muestras. Se hallaron indicios de validez concurrente con pruebas de calidad de vida y salud mental. Conclusiones. Se propone un cuestionario breve para la deteccion de fallos de origen prefrontal en la vida diaria, que mejora las cualidades psicometricas de tests similares, pero orientados a patologias neurologicas graves. La estabilidad estructural de la prueba garantiza la utilidad en la poblacion general, para la deteccion precoz del deterioro cognitivo, y en poblaciones clinicas con deterioro leve o moderado. Se proponen baremos para la interpretacion de resultados.

[Cognitive reserve in substance addicts in treatment: relation to cognitive performance and activities of daily living]. / Reserva cognitiva en adictos a sustancias en tratamiento: relacion con el rendimiento cognitivo y las actividades cotidianas.

INTRODUCTION: The concept of cognitive reserve has gradually attracted more interest as a greater body of evidence has been collected on its relationship with the resistance of the brain to decline in its functioning when faced with neurological threats or disorders. Although a large amount of research has been conducted on (degenerative, traumatic, psychopathological) conditions, very few studies relate cognitive reserve with substance addiction, a multidimensional process with a clear neurological base. AIMS: To explore the cognitive reserve of patients undergoing treatment for addiction to drugs of abuse by relating it with their cognitive performance in neuropsychological tests and in activities of daily living. PATIENTS AND METHODS: The study involved a sample of 57 patients being treated for substance abuse at a centre set up for this specific purpose. The cognitive reserve questionnaire, the Montreal cognitive assessment and the prefrontal symptoms inventory were administered, and variables related with the addiction were collected. RESULTS: A positive relation was found between the cognitive reserve and the time of abstinence, and a negative one was seen with the severity of the addiction. Significant differences were observed according to the cognitive reserve in neuropsychological performance (especially in certain cognitive domains) and in daily activities. CONCLUSIONS: The cognitive reserve appears as a variable related to addiction and the cognitive deficits that accompany it. It is thus a potential target for rehabilitation activities and is linked to the environmental enrichment paradigm, as a strategy for enhancing resistance against the cognitive impairment that favours and maintains the addiction, and for lowering the reinforcing potential of the behaviour of consuming.

TITLE: Reserva cognitiva en adictos a sustancias en tratamiento: relacion con el rendimiento cognitivo y las actividades cotidianas.Introduccion. El concepto de reserva cognitiva ha ido ganando interes en la medida en que se ha acumulado evidencia sobre su relacion con la resistencia del cerebro a declinar en su funcionamiento ante amenazas o alteraciones neurologicas. Aunque se ha estudiado en un gran numero de alteraciones (degenerativas, traumaticas, psicopatologicas), pocos trabajos relacionan la reserva cognitiva con la adiccion a sustancias, un proceso multidimensional con clara base neurologica. Objetivo. Explorar la reserva cognitiva de pacientes en tratamiento por adiccion a drogas, relacionandolo con su rendimiento cognitivo en pruebas neuropsicologicas y en actividades de la vida diaria. Pacientes y metodos. Muestra de 57 pacientes en tratamiento por adiccion a sustancias en un centro especifico. Se administraron el cuestionario de reserva cognitiva, la evaluacion cognitiva de Montreal y el inventario de sintomas prefrontales, y se recogieron variables relacionadas con la adiccion. Resultados. Se encontro una relacion positiva entre la reserva cognitiva y el tiempo de abstinencia, y negativa con la gravedad de la adiccion. Aparecieron diferencias significativas segun la reserva cognitiva en rendimiento neuropsicologico (especialmente en ciertos dominios cognitivos) y en actividades cotidianas. Conclusiones. La reserva cognitiva aparece como una variable relacionada con la adiccion y los deficits cognitivos que la acompañan; resulta ser una potencial diana de las actividades rehabilitadoras, vinculada al paradigma de enriquecimiento ambiental, como estrategia para potenciar la resistencia frente al deterioro cognitivo que favorece y mantiene la adiccion y para disminuir el potencial reforzador de la conducta de consumo.