Generic Delivery of Payload of Nanoparticles Intracellularly via Hybrid Polymer Capsules for Bioimaging Applications

Towards the goal of development of a generic nanomaterial delivery system and delivery of the ‘as prepared’ nanoparticles without ‘further surface modification’ in a generic way, we have fabricated a hybrid polymer capsule as a delivery vehicle in which nanoparticles are loaded within their cavity. To this end, a generic approach to prepare nanomaterials-loaded polyelectrolyte multilayered (PEM) capsules has been reported, where polystyrene sulfonate (PSS)/polyallylamine hydrochloride (PAH) polymer capsules were employed as nano/microreactors to synthesize variety of nanomaterials (metal nanoparticles; lanthanide doped inorganic nanoparticles; gadolinium based nanoparticles, cadmium based nanoparticles; different shapes of nanoparticles; co-loading of two types of nanoparticles) in their hollow cavity. These nanoparticles-loaded capsules were employed to demonstrate generic delivery of payload of nanoparticles intracellularly (HeLa cells), without the need of individual nanoparticle surface modification. Validation of intracellular internalization of nanoparticles-loaded capsules by HeLa cells was ascertained by confocal laser scanning microscopy. The green emission from Tb3+ was observed after internalization of LaF3:Tb3+(5%) nanoparticles-loaded capsules by HeLa cells, which suggests that nanoparticles in hybrid capsules retain their functionality within the cells. In vitro cytotoxicity studies of these nanoparticles-loaded capsules showed less/no cytotoxicity in comparison to blank capsules or untreated cells, thus offering a way of evading direct contact of nanoparticles with cells because of the presence of biocompatible polymeric shell of capsules. The proposed hybrid delivery system can be potentially developed to avoid a series of biological barriers and deliver multiple cargoes (both simultaneous and individual delivery) without the need of individual cargo design/modification

A Functional Magnetic Resonance Imaging Assessment of Small Animals Phobia Using Virtual Reality as a Stimulus

[EN] Background: To date, still images or videos of real animals have been used in functional magnetic resonance imaging protocols to evaluate the brain activations associated with small animals phobia. Objective: The objective of our study was to evaluate the brain activations associated with small animals phobia through the use of virtual environments. This context will have the added benefit of allowing the subject to move and interact with the environment, giving the subject the illusion of being there. Methods: We have analyzed the brain activation in a group of phobic people while they navigated in a virtual environment that included the small animals that were the object of their phobia. Results: We have found brain activation mainly in the left occipital inferior lobe (P<.05 corrected, cluster size=36), related to the enhanced visual attention to the phobic stimuli; and in the superior frontal gyrus (P<.005 uncorrected, cluster size=13), which is an area that has been previously related to the feeling of self-awareness. Conclusions: In our opinion, these results demonstrate that virtual stimulus can enhance brain activations consistent with previous studies with still images, but in an environment closer to the real situation the subject would face in their daily lives.This study was funded by Vicerrectorado de Investigación de la Universitat Politècnica de València, Spain, PAID-06-2011, RN 1984; by the Ministerio de Educación y Ciencia Spain, Project Game Teen (TIN2010-20187); and partially by projects Consolider-C (SEJ2006-14301/PSIC), “CIBER of Physiopathology of Obesity and Nutrition, an initiative of ISCIII”, the Excellence Research Program PROMETEO (Generalitat Valenciana. Conselleria de Educación, 2008-157), and the Consolider INGENIO program (CSD2007-00012). Generalitat Valenciana, under a VALi+d Grant, supported the work of MC.Clemente Bellido, M.; Rey Solaz, B.; Rodríguez Pujadas, A.; Breton Lopez, J.; Barros Loscertales, A.; Baños, RM.; Botella, C.... (2014). A Functional Magnetic Resonance Imaging Assessment of Small Animals Phobia Using Virtual Reality as a Stimulus. JMIR Serious Games. 2(1)(6):1-12. https://doi.org/10.2196/games.2836S1122(1)

Brain Changes in Long-Term Zen Meditators Using Proton Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging: A Controlled Study

Introduction: This work aimed to determine whether 1H magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) are correlated with years of meditation and psychological variables in long-term Zen meditators compared to healthy non-meditator controls. Materials and Methods: Design. Controlled, cross-sectional study. Sample. Meditators were recruited from a Zen Buddhist monastery. The control group was recruited from hospital staff. Meditators were administered questionnaires on anxiety, depression, cognitive impairment and mindfulness. 1H-MRS (1.5 T) of the brain was carried out by exploring four areas: both thalami, both hippocampi, the posterior superior parietal lobule (PSPL) and posterior cingulate gyrus. Predefined areas of the brain were measured for diffusivity (ADC) and fractional anisotropy (FA) by MR-DTI. Results: Myo-inositol (mI) was increased in the posterior cingulate gyrus and Glutamate (Glu), N-acetyl-aspartate (NAA) and N-acetyl-aspartate/Creatine (NAA/Cr) was reduced in the left thalamus in meditators. We found a significant positive correlation between mI in the posterior cingulate and years of meditation (r = 0.518; p = .019). We also found significant negative correlations between Glu (r =20.452; p = .045), NAA (r =20.617; p = .003) and NAA/Cr (r =20.448; P = .047) in the left thalamus and years of meditation. Meditators showed a lower Apparent Diffusion Coefficient (ADC) in the left posterior parietal white matter than did controls, and the ADC was negatively correlated with years of meditation (r =20.4850, p = .0066). Conclusions: The results are consistent with the view that mI, Glu and NAA are the most important altered metabolites. This study provides evidence of subtle abnormalities in neuronal function in regions of the white matter in meditators

The fate of children with microdeletion 22q11.2 syndrome and congenital heart defect: clinical course and cardiac outcome

BACKGROUND: This study aimed to evaluate the cardiac outcome for children with microdeletion 22q11.2 and congenital heart defect (CHD). METHODS: A total of 49 consecutive children with 22q11.2 and CHD were retrospectively identified. The CHD consisted of tetralogy of Fallot and variances (n = 22), interrupted aortic arch (n = 10), ventricular septal defect (n = 8), truncus arteriosus (n = 6), and double aortic arch (n = 1). Extracardiac anomalies were present in 46 of 47 children. RESULTS: The median follow-up time was 8.5 years (range, 3 months to 23.5 years). Cardiac surgical repair was performed for 35 children, whereas 5 had palliative surgery, and 9 never underwent cardiac surgery. The median age at repair was 7.5 months (range, 2 days to 5 years). The mean hospital stay was 35 days (range, 7-204 days), and the intensive care unit stay was 15 days (range, 3-194 days). Significant postoperative complications occurred for 26 children (74%), and surgery for extracardiac malformations was required for 21 patients (43%). The overall mortality rate was 22% (11/49), with 1-year survival for 86% and 5-year survival for 80% of the patients. A total of 27 cardiac reinterventions were performed for 16 patients (46%) including 15 reoperations and 12 interventional catheterizations. Residual cardiac findings were present in 25 patients (71%) at the end of the follow-up period. CONCLUSIONS: Children with microdeletion 22q11.2 and CHD are at high risk for mortality and morbidity, as determined by both the severity of the cardiac lesions and the extracardiac anomalies associated with the microdeletion

Mesoporous silica nanoparticles with tunable pore size for tailored gold nanoparticles

The aim of this paper was to verify a possible correlation between the pore-size of meso- porous silica nanoparticles (MSNs) and the sizes of gold nanoparticles (AuNPs) obtained by an impreg- nation of gold(III) chloride hydrate solution in the MSNs, followed by a specific thermal treatment. Mesoporous silica nanoparticles with tunable pore diameter were synthesized via a surfactant-assisted method. Tetraethoxysilane as silica precursor, cetyl- trimethylammonium bromide (CTAB) as surfactant and toluene as swelling agent were used. By varying the CTAB–toluene molar ratio, the average dimension of the pores could be tuned from 2.8 to 5.5 nm. Successively, thiol groups were grafted on the surface of the MSNs. Finally, the thermal evolution of the gold salt, followed by ‘‘in situ’’ X-ray powder diffraction (XRPD) and thermogravimetric analysis (TGA), revealed an evident correlation among the degradation of the thiol groups, the pore dimension of the MSNs and the size of the AuNPs. The samples were characterized by means of nitrogen adsorption– desorption, transmission electron microscopy, small- angle X-ray scattering, XRPD ‘‘in situ’’ by synchro- tron radiation, and ‘‘ex situ’’ by conventional tech- niques, diffuse reflectance infrared Fourier transform spectroscopy, and TGA