Current progress and challenges of nanoparticle-based therapeutics in pain management

Pain is a widespread and growing health problem worldwide that exerts a considerable social and economic impact on both patients and healthcare systems and, therefore, on society in general. Although current treatment modalities include a wide variety of pharmacological and non-pharmacological approaches, due to the complexity of pain and individual differences in clinical response these options are not always effective in mitigating and relieving pain. In addition, some pain drugs such as non-steroidal anti-inflammatory drugs (NSAIDs), local anesthetics and opioids show several unfavorable side effects. Therefore, current research advances in this medical field are based on the development of potential treatments to address many of the unmet needs and to overcome the existing limitations in pain management. Nanoparticle drug delivery systems present an exciting opportunity as alternative platforms to improve efficacy and safety of medications currently in use. Herein, we review a broad range of nanoparticle formulations (organic nanostructures and inorganic nanoparticles), which have been developed to encapsulate an array of painkillers, paying special attention to the key advantages that these systems offer, (compared to the use of the free drug), as well as to the more relevant results of preclinical studies in animal models. Additionally, we will briefly discuss the impact of some of these nanoformulations in clinical trials

Correlations in the three-dimensional Lyman-alpha forest contaminated by high column density absorbers

Correlations measured in three dimensions in the Lyman-alpha forest are contaminated by the presence of the damping wings of high column density (HCD) absorbing systems of neutral hydrogen (HI; having column densities $N(\mathrm{HI}) > 1.6\times10^{17}\,\mathrm{atoms}\,\mathrm{cm}^{-2}$), which extend significantly beyond the redshift-space location of the absorber. We measure this effect as a function of the column density of the HCD absorbers and redshift by measuring 3D flux power spectra in cosmological hydrodynamical simulations from the Illustris project. Survey pipelines exclude regions containing the largest damping wings. We find that, even after this procedure, there is a scale-dependent correction to the 3D Lyman-alpha forest flux power spectrum from residual contamination. We model this residual using a simple physical model of the HCD absorbers as linearly biased tracers of the matter density distribution, convolved with their Voigt profiles and integrated over the column density distribution function. We recommend the use of this model over existing models used in data analysis, which approximate the damping wings as top-hats and so miss shape information in the extended wings. The simple 'linear Voigt model' is statistically consistent with our simulation results for a mock residual contamination up to small scales ($|k| < 1\,h\,\mathrm{Mpc}^{-1}$). It does not account for the effect of the highest column density absorbers on the smallest scales (e.g., $|k| > 0.4\,h\,\mathrm{Mpc}^{-1}$ for small damped Lyman-alpha absorbers; HCD absorbers with $N(\mathrm{HI}) \sim 10^{21}\,\mathrm{atoms}\,\mathrm{cm}^{-2}$). However, these systems are in any case preferentially removed from survey data. Our model is appropriate for an accurate analysis of the baryon acoustic oscillations feature. It is additionally essential for reconstructing the full shape of the 3D flux power spectrum.Comment: 13 pages, 11 figures. Minor changes to match version published in MNRA

An Emulator for the Lyman-alpha Forest

We present methods for interpolating between the 1-D flux power spectrum of the Lyman-$\alpha$ forest, as output by cosmological hydrodynamic simulations. Interpolation is necessary for cosmological parameter estimation due to the limited number of simulations possible. We construct an emulator for the Lyman-$\alpha$ forest flux power spectrum from $21$ small simulations using Latin hypercube sampling and Gaussian process interpolation. We show that this emulator has a typical accuracy of 1.5% and a worst-case accuracy of 4%, which compares well to the current statistical error of 3 - 5% at $z < 3$ from BOSS DR9. We compare to the previous state of the art, quadratic polynomial interpolation. The Latin hypercube samples the entire volume of parameter space, while quadratic polynomial emulation samples only lower-dimensional subspaces. The Gaussian process provides an estimate of the emulation error and we show using test simulations that this estimate is reasonable. We construct a likelihood function and use it to show that the posterior constraints generated using the emulator are unbiased. We show that our Gaussian process emulator has lower emulation error than quadratic polynomial interpolation and thus produces tighter posterior confidence intervals, which will be essential for future Lyman-$\alpha$ surveys such as DESI.Comment: 28 pages, 10 figures, accepted to JCAP with minor change

Simulating the effect of high column density absorbers on the one-dimensional Lyman-alpha forest flux power spectrum

We measure the effect of high column density absorbing systems of neutral hydrogen (HI) on the one-dimensional (1D) Lyman-alpha forest flux power spectrum using cosmological hydrodynamical simulations from the Illustris project. High column density absorbers (which we define to be those with HI column densities $N(\mathrm{HI}) > 1.6 \times 10^{17}\,\mathrm{atoms}\,\mathrm{cm}^{-2}$) cause broadened absorption lines with characteristic damping wings. These damping wings bias the 1D Lyman-alpha forest flux power spectrum by causing absorption in quasar spectra away from the location of the absorber itself. We investigate the effect of high column density absorbers on the Lyman-alpha forest using hydrodynamical simulations for the first time. We provide templates as a function of column density and redshift, allowing the flexibility to accurately model residual contamination, i.e., if an analysis selectively clips out the largest damping wings. This flexibility will improve cosmological parameter estimation, e.g., allowing more accurate measurement of the shape of the power spectrum, with implications for cosmological models containing massive neutrinos or a running of the spectral index. We provide fitting functions to reproduce these results so that they can be incorporated straightforwardly into a data analysis pipeline.Comment: 11 pages, 6 figures. Minor changes to match version published in MNRA

Controlled release of bupivacaine using hybrid thermoresponsive nanoparticles activated via photothermal heating

Near-infrared (NIR) responsive nanoparticles are of great interest in the biomedical field as antennas for photothermal therapy and also as triggers for on-demand drug delivery. The present work reports the preparation of hollow gold nanoparticles (HGNPs) with plasmonic absorption in the NIR region covalently bound to a thermoresponsive polymeric shell that can be used as an on-demand drug delivery system for the release of analgesic drugs. The photothermal heating induced by the nanoparticles is able to produce the collapse of the polymeric shell thus generating the release of the local anesthetic bupivacaine in a spatiotemporally controlled way. Those HGNPs contain a 10 wt.% of polymer and present excellent reversible heating under NIR light excitation. Bupivacaine released at physiological temperature (37 °C) showed a pseudo-zero order release that could be spatiotemporally modified on-demand after applying several pulses of light/temperature above and below the lower critical solution temperature (LCST) of the polymeric shell. Furthermore, the nanomaterials obtained did not displayed detrimental effects on four mammalian cell lines at doses up to 0.2 mg/mL. From the results obtained it can be concluded than this type of hybrid thermoresponsive nanoparticle can be used as an externally activated on-demand drug delivery system

Smart dressings based on nanostructured fibers containing natural origin antimicrobial, anti-inflammatory, and regenerative compounds

A fast and effective wound healing process would substantially decrease medical costs, wound care supplies, and hospitalization significantly improving the patients’ quality of life. The search for effective therapeutic approaches seems to be imperative in order to avoid the aggravation of chronic wounds. In spite of all the efforts that have been made during the recent years towards the development of artificial wound dressings, none of the currently available options combine all the requirements necessary for quick and optimal cutaneous regeneration. Therefore, technological advances in the area of temporary and permanent smart dressings for wound care are required. The development of nanoscience and nanotechnology can improve the materials and designs used in topical wound care in order to efficiently release antimicrobial, anti-inflammatory and regenerative compounds speeding up the endogenous healing process. Nanostructured dressings can overcome the limitations of the current coverings and, separately, natural origin components can also overcome the drawbacks of current antibiotics and antiseptics (mainly cytotoxicity, antibiotic resistance, and allergies). The combination of natural origin components with demonstrated antibiotic, regenerative, or anti-inflammatory nanostructured materials is a promising approach to fulfil all the requirements needed for the next generation of bioactive wound dressings. Microbially compromised wounds have been treated with different essential oils, honey, cationic peptides, aloe vera, plant extracts, and other natural origin occurring antimicrobial, anti-inflammatory, and regenerative components but the available evidence is limited and insufficient to be able to draw reliable conclusions and to extrapolate those findings to the clinical practice. The evidence and some promising preliminary results indicate that future comparative studies are justified but instead of talking about the beneficial or inert effects of those natural origin occurring materials, the scientific community leads towards the identification of the main active components involved and their mechanism of action during the corresponding healing, antimicrobial, or regenerative processes and in carrying out systematic and comparative controlled tests. Once those natural origin components have been identified and their efficacy validated through solid clinical trials, their combination within nanostructured dressings can open up new avenues in the fabrication of bioactive dressings with outstanding characteristics for wound care. The motivation of this work is to analyze the state of the art in the use of different essential oils, honey, cationic peptides, aloe vera, plant extracts, and other natural origin occurring materials as antimicrobial, anti-inflammatory and regenerative components with the aim of clarifying their potential clinical use in bioactive dressings. We conclude that, for those natural occurring materials, more clinical trials are needed to reach a sufficient level of evidence as therapeutic agents for wound healing management.properties together wit

Changes in organic matter, nitrogen, phosphorus and cations in soil as a result of fire and water erosion in a Mediterranean landscape

10 páginas, 7 figuras, 9 tablas.Fire affects large parts of the dry Mediterranean shrubland, resulting in erosion and losses of plant nutrients. We have attempted to measure these effects experimentally on a calcareous hillside representative of such shrubland. Experimental fires were made on plots (4 m x 20 m) in which the fuel was controlled to obtain two different fire intensities giving means of soil surface temperature of 439 degrees C and 232 degrees C with temperatures exceeding 100 degrees C lasting for 36 min and 17 min. The immediate and subsequent changes induced by fire on the soil's organic matter content and other soil chemical properties were evaluated, together with the impact of water erosion. Seven erosive rain events, which occurred after the experimental fires (from August 1995 to December 1996), were selected, and on them runoff and sediment produced from each plot were measured. The sediments collected were weighed and analysed. Taking into account the variations induced by fire on the soil properties and their losses by water erosion, estimates of the net inputs and outputs of the soil system were made. Results show that the greatest losses of both soil and nutrients took place in the 4 months immediately after the fire. Plots affected by the most intense fire showed greater losses of soil (4077 kg ha(-1)) than those with moderate fire intensity (3280 kg ha(-1)). The unburned plots produced the least sediment (72.8 kg ha(-1)). Organic matter and nutrient losses by water erosion were related to the degree of fire intensity. However, the largest losses of N-NH4+ and N-NO3- by water erosion corresponded to the moderate fire (8.1 and 7.5 mg N m(-2), respectively).Peer reviewe

Estimates for the ergodic measure and polynomial stability of plane stochastic curve shortening flow

We establish moment estimates for the invariant measure of a stochastic partial differential equation describing motion by mean curvature flow in (1+1) dimension, leading to polynomial stability of the associated Markov semigroup. We also prove maximal dissipativity for the related Kolmogorov operator

Modelling magnetic flux emergence in the solar convection zone

[Abridged] Bipolar magnetic regions are formed when loops of magnetic flux emerge at the solar photosphere. Our aim is to investigate the flux emergence process in a simulation of granular convection. In particular we aim to determine the circumstances under which magnetic buoyancy enhances the flux emergence rate (which is otherwise driven solely by the convective upflows). We use three-dimensional numerical simulations, solving the equations of compressible magnetohydrodynamics in a horizontally-periodic Cartesian domain. A horizontal magnetic flux tube is inserted into fully developed hydrodynamic convection. We systematically vary the initial field strength, the tube thickness, the initial entropy distribution along the tube axis and the magnetic Reynolds number. Focusing upon the low magnetic Prandtl number regime (Pm<1) at moderate magnetic Reynolds number, we find that the flux tube is always susceptible to convective disruption to some extent. However, stronger flux tubes tend to maintain their structure more effectively than weaker ones. Magnetic buoyancy does enhance the flux emergence rates in the strongest initial field cases, and this enhancement becomes more pronounced when we increase the width of the flux tube. This is also the case at higher magnetic Reynolds numbers, although the flux emergence rates are generally lower in these less dissipative simulations because the convective disruption of the flux tube is much more effective in these cases. These simulations seem to be relatively insensitive to the precise choice of initial conditions: for a given flow, the evolution of the flux tube is determined primarily by the initial magnetic field distribution and the magnetic Reynolds number.Comment: 12 pages, 15 figures, 2 tables. Accepted for publication in Astronomy and Astrophysic