Development, characterization and sterilisation of Nanocellulose-alginate-(hyaluronic acid)- bioinks and 3D bioprinted scaffolds for tissue engineering.

3D-bioprinting is an emerging technology of high potential in tissue engineering (TE), since it shows effective control over scaffold fabrication and cell distribution. Biopolymers such as alginate (Alg), nanofibrillated cellulose (NC) and hyaluronic acid (HA) offer excellent characteristics for use as bioinks due to their excellent biocompatibility and rheological properties. Cell incorporation into the bioink requires sterilisation assurance, and autoclave, ß-radiation and γ-radiation are widely used sterilisation techniques in biomedicine; however, their use in 3D-bioprinting for bioinks sterilisation is still in their early stages. In this study, different sterilisation procedures were applied on NC-Alg and NC-Alg-HA bioinks and their effect on several parameters was evaluated. Results demonstrated that NC-Alg and NC-Alg-HA bioinks suffered relevant rheological and physicochemical modifications after sterilisation; yet, it can be concluded that the short cycle autoclave is the best option to sterilise both NC-Alg based cell-free bioinks, and that the incorporation of HA to the NC-Alg bioink improves its characteristics. Additionally, 3D scaffolds were bioprinted and specifically characterized as well as the D1 mesenchymal stromal cells (D1-MSCs) embedded for cell viability analysis. Notably, the addition of HA demonstrates better scaffold properties, together with higher biocompatibility and cell viability in comparison with the NC-Alg scaffolds. Thus, the use of MSCs containing NC-Alg based scaffolds may become a feasible tissue engineering approach for regenerative medicine.

Topological thermalization via vortex formation in ultrafast quenches.

We investigate the thermalization of a two-component scalar field across a second-order phase transition under extremely fast quenches. We find that vortices start developing once the thermal bath sets the control parameter to its final value in the nonsymmetric phase. Specifically, we find that vortices emerge as the fluctuating field relaxes and departs macroscopically from its symmetric configuration. The density of primordial vortices at the relaxation time is a decreasing function of the final temperature of the quench. Subsequently, vortices and antivortices annihilate at a rate that eventually determines the total thermalization time. This rate decreases if the theory contains a discrete anisotropy term, which otherwise leaves the primordial vortex density unaffected. Our results thus establish a link between the topological processes involved in the vortex dynamics and the delay in the thermalization of the system.

Quasiresonant van der Waals Interaction between Nonidentical Atoms.

We present a time-dependent quantum calculation of the van der Waals interaction between a pair of dissimilar atoms, one of which is initially excited while the other one is in its ground state. For small detuning, the interaction is predominantly mediated at all distances by the exchange of doubly resonant photons between the two atoms. We find that it presents both temporal and spatial oscillations. Spatially oscillating terms depend on the resonant frequencies of both atoms, while the frequency of the time oscillations is given by their detuning. We analyze the physical content of our findings and discuss to what extent previous conflicting stationary approaches provide compatible results. A proper account of causality is found essential in order to obtain the correct result.

Transfer of linear momentum from the quantum vacuum to a magnetochiral molecule.

In a recent publication we have shown using a QED approach that, in the presence of a magnetic field, the quantum vacuum coupled to a chiral molecule provides a kinetic momentum directed along the magnetic field. Here we explain the physical mechanisms which operate in the transfer of momentum from the vacuum to the molecule. We show that the variation of the molecular kinetic energy originates from the magnetic energy associated with the vacuum correction to the magnetization of the molecule. We carry out a semiclassical calculation of the vacuum momentum and compare the result with the QED calculation.

Factibilidad de la interpretación de espirometrías en preescolares según criterios ATS/ERS / Spirometry interpretation feasibility among pre-school children according to the European Respiratory Society and American Thoracic Society Guidelines

Introducción: La espirometría es el examen más utilizado para evaluar la función pulmonar. El año 2007 se publicaron guías que definieron criterios de aceptabilidad y repetibilidad para su realización e interpretación en preescolares. Nuestro objetivo fue describir las espirometrías de pacientes de este grupo etario según el cumplimiento de estos criterios. Pacientes y Método: Se revisaron las espirometrías basales de pacientes de 2 a 5 años realizadas en el Laboratorio de Función Pulmonar Pediátrico de la P. Universidad Católica de Chile derivados por tos o sibilancias recurrentes o persistentes. Se consideraron solo las obtenidas en pacientes que la realizaban por primera vez. Se analizaron según criterios internacionales. Resultados: Se obtuvieron 93 espirometrías (edad promedio 57,4 ± 8,6 meses, 48 varones): 44 (47%) tuvieron todos los criterios aceptables, 87 (93%) obtuvieron un tiempo espiratorio ≥ 0,5 segundos, 67 (72%) de los pacientes tuvieron un flujo espiratorio de final de espiración en valor ≤ 10% del flujo espiratorio máximo. La variabilidad de las mediciones de capacidad vital forzada (CVF) y volumen espirado al primer segundo (VEF1) fue muy baja (coeficiente de correlación intraclase > 0,9). Conclusión: En nuestro centro fue factible cumplir criterios de aceptabilidad y repetibilidad en espirometrías en preescolares, semejante a descripciones previas. Al igual que en niños mayores, se recomienda realizar este examen en preescolares que requieren estudio de la función pulmonar.

Introduction: Spirometry is the most used test to evaluate pulmonary function. Guidelines that defined acceptability and repeatability criteria for its implementation and interpretation among preschoolers were published in 2007. Our objective was to quantify the actual compliance with these criteria among pre-school patients. Methods: A review was performed on the baseline spirometry measured in patients aged 2 to 5 years in the Pediatric Respiratory Laboratory of the Pontificia Universidad Catolica de Chile, who were admitted due to recurrent or persistent coughing or wheezing. Only those results obtained in patients who took the test for the first time were considered. They were analyzed by international standards. Results: A total of 93 spirometry results (mean age 57.4 ± 8.6 months, 48 males) were obtained, of which 44 (47%) met all acceptable criteria, 87 (93%) obtained expiratory time of ≥ 0.5 seconds, and 67 (72 %) of the patients had an end-expiratory flow of ≤ 10% from peak flow. The variation in the measurement of forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) was very low (intraclass correlation coefficient > 0.9). Conclusion: It was possible to meet the acceptability and repeatability criteria for spirometry among pre-school children in our Center, which was similar to previous reports. As in older children, this test is fully recommended for pre-school children who require lung function studies.

Casimir momentum of a chiral molecule in a magnetic field.

In a classical description, a neutral, polarizable object acquires a kinetic momentum when exposed to crossed electric and magnetic fields. In the presence of only a magnetic field no such momentum exists classically, although it is symmetry allowed for an object lacking mirror symmetry. We perform a full QED calculation to show that the quantum vacuum coupled to a chiral molecule provides it with a kinetic "Casimir" momentum directed along the magnetic field, and proportional to its molecular rotatory power and to the fine structure constant.

Polymeric drugs based on random copolymers with antimitotic activity.

Polymeric drugs based on random copolymers with antimitotic activity were obtained by free radical copolymerization of oleyl 2-acetamido-2-deoxy-α-d-glucopyranoside methacrylate (OAGMA) and 2-ethyl-(2-pyrrolidone) methacrylate (EPM) at low and high conversion and analyzed in terms of microstructure, physicochemical, and biological properties. Reactivity ratios of monomers were found to be r(OAGMA) = 1.34 and r(EPM) = 0.98, indicating the obtaining of statistical copolymers with random sequence distribution of the comonomeric units in the macromolecular chains. The glass transition temperature of the copolymers presents a negative deviation from the predicted values according to the Fox equation, suggesting a higher flexibility of the alternating diad. Copolymeric systems with OAGMA contents between 10-50 mol % presented thermosensitive behavior in a heating process showing cloud point temperatures (CPT) in the range 45-28 °C with increasing OAGMA content and hysteresis in one heating-and-cooling cycle. In vitro glycolipid release studies revealed the stability of the ester group in culture medium. The polymeric drugs with 30 and 50 mol % OAGMA presented antimitotic activity on a human glioblastoma line, but they were less toxic on normal human fibroblast cultures.

A study on partially biodegradable microparticles as carriers of active glycolipids.

This paper describes a study on the preparation and characterisation of partially biodegradable microparticles of poly(epsilon-caprolactone)/poly(ethyl methacrylate) (PCL/PEMA) as carriers of synthetic glycolipids with antimitotic activity against brain tumour cells. Microparticles prepared by suspension polymerisation of methacrylate in the presence of already polymerised PCL showed a predominantly spherical but complex morphology, with segregation of PCL micro/nano-domains towards the surface. Small diameter discs were prepared by compression moulding of blends of microparticles and the active principle under mild conditions. The in vitro behaviour of the discs and release of the glycolipid were studied in different simulated fluid models. Ingress of fluids increased with increasing hydrophobicity of the medium. Release of the glycolipid was sustained in all fluids, the most prolonged profile being in human synovial fluid and phosphate-buffered saline modified with 20 vol.% dioxane. Slow disintegration of the discs and partial degradation of the microparticles was evident in accelerated studies. The antimitotic activity of glycolipid released from the discs was proved against a human glioblastoma line. This activity, along with selectivity against human fibroblasts, could be controlled by the amount of drug charged in the disc.

Polymeric drugs based on bioactive glycosides for the treatment of brain tumours.

Polymeric drugs carrying glycolipids have been designed as target macromolecules for the treatment of brain tumours. A methacrylate derivative of oleyl 2-acetamido-2-deoxy-alpha-D-glucopyranoside (OAGMA) has been prepared and the corresponding glycopolymer obtained by free radical polymerisation. To modulate the hydrophobic character of the polymeric drug, the acrylic glycomonomer was copolymerised with vinyl pyrrolidone (VP). Reactivity ratios obtained by performing copolymerisation reactions inside the NMR apparatus were r(OAGMA)=5.94 and r(VP)=0.01, indicating the much higher reactivity of the glycomonomer. The hydrolytical release of oleyl 2-acetamido-2-deoxy-alpha-D-glucopyranoside (OAG) from the copolymeric drugs was produced in vitro by the ester enzymatic hydrolysis using enzyme/buffered solutions. The cytotoxicity of OAG and OAGMA tested against a human glioblastoma line and normal fibroblasts revealed a concentration dependent selectivity towards tumour cells versus fibroblasts. The antimitotic activity of the copolymeric drugs was also confirmed. The addition of the eluates of the copolymeric systems collected at 1 and 2 days produced a significant decrease in cellular viability of the glioblastoma cells without affecting that of normal fibroblasts. On the contrary, fibroblasts were able to adhere and proliferate onto the copolymeric systems showing normal morphology and revealing a good biocompatibility of the copolymeric drugs against healthy cells.

The genotype interactions of methylenetetrahydrofolate reductase and renin-angiotensin system genes are associated with myocardial infarction.

We analyzed the evolution with age of the frequencies of the I/D polymorphism of the angiotensin I-converting enzyme (ACE), a1166c of the angiotensin II AT1 receptor (AT1R), M235T of the angiotensinogen (AGT) and A225V of their methylenetetrahydrofolate reductase (MTHFR) gene in a healthy (H) population and the subsequent comparison to age- and sex-matched groups of myocardial infarction (MI) subjects. A total of 472 H subjects were divided into three groups < 30, 30-55 and > 55 years old and 277 individuals with MI into two groups 30-55 and > 55 years old. The evolution with age showed that the AGT M allele (P < 0.001) and the MTHFR V allele (P < 0.05) frequency decreased with age in H men. The comparison between healthy and MI groups showed that the MM genotype frequency increased in MI men > 55 years (OR =4.16; 95% CI; 1.72-10.1) The cc genotype showed a similar behaviour (OR = 3.96; 95% CI; 1.21-12.9). In men, all the combinations with MM genotype presented a high risk, with OR values between 1.10 and 7.22. In women, the cc genotype increased in the MI > 55 group (OR = 6.66; 95% CI; 2.02-21.9). All the combinations with the cc genotype showed OR values between 1.71 and 13.3. The MM genotype in men and cc genotype in men and women, are independent risk factors for MI. We propose that the study of the allele frequency evolution in an H population at different ages is essential to determine risk factors for MI in case-control studies, since data from isolated age-matched groups can be misinterpreted.