Exploiting the layer-by-layer nanoarchitectonics for the fabrication of polymer capsules : A toolbox to provide multifunctional properties to target complex pathologies

Polymer capsules fabricated via the layer-by-layer (LbL) approach have attracted a great deal of attention for biomedical applications thanks to their tunable architecture. Compared to alternative methods, in which the precise control over the final properties of the systems is usually limited, the intrinsic versatility of the LbL approach allows the functionalization of all the constituents of the polymeric capsules following relatively simple protocols. In fact, the final properties of the capsules can be adjusted from the inner cavity to the outer layer through the polymeric shell, resulting in therapeutic, diagnostic, or theranostic (i.e., combination of therapeutic and diagnostic) agents that can be adapted to the particular characteristics of the patient and face the challenges encountered in complex pathologies. The biomedical industry demands novel biomaterials capable of targeting several mechanisms and/or cellular pathways simultaneously while being tracked by minimally invasive tech-niques, thus highlighting the need to shift from monofunctional to multifunctional polymer capsules. In the present review, those strategies that permit the advanced functionalization of polymer capsules are accordingly introduced. Each of the constituents of the capsule (i.e., cavity, multilayer membrane and outer layer) is thor-oughly analyzed and a final overview of the combination of all the strategies toward the fabrication of multi-functional capsules is presented. Special emphasis is given to the potential biomedical applications of these multifunctional capsules, including particular examples of the performed in vitro and in vivo validation studies. Finally, the challenges in the fabrication process and the future perspective for their safe translation into the clinic are summarized.Peer reviewe

An Analysis of the Economic Costs of Seeking the Death Penalty in Washington (Report)

Professor Boruchowitz and colleagues published the results of a seven-month study into the costs of the death penalty in Washington state and has found a more than $1 million price break in cases where capital punishment is not sought

An Analysis of the Economic Costs of Seeking the Death Penalty in Washington (Report)

Professor Boruchowitz and colleagues published the results of a seven-month study into the costs of the death penalty in Washington state and has found a more than $1 million price break in cases where capital punishment is not sought

Geometrothermodynamics of the Kehagias-Sfetsos Black Hole

The application of information geometric ideas to statistical mechanics using a metric on the space of states, pioneered by Ruppeiner and Weinhold, has proved to be a useful alternative approach to characterizing phase transitions. Some puzzling anomalies become apparent, however, when these methods are applied to the study of black hole thermodynamics. A possible resolution was suggested by Quevedo et al. who emphasized the importance of Legendre invariance in thermodynamic metrics. They found physically consistent results for various black holes when using a Legendre invariant metric, which agreed with a direct determination of the properties of phase transitions from the specific heat. Recently, information geometric methods have been employed by Wei et al. to study the Kehagias-Sfetsos (KS) black hole in Horava-Lifshitz gravity. The formalism suggests that a coupling parameter in this theory plays a role analogous to the charge in Reissner-Nordstrom (RN) black holes or angular momentum in the Kerr black hole and calculation of the specific heat shows a singularity which may be interpreted as a phase transition. When the curvature of the Ruppeiner metric is calculated for such a theory it does not, however, show a singularity at the phase transition point. We show that the curvature of a particular Legendre invariant ("Quevedo") metric for the KS black hole is singular at the phase transition point. We contrast the results for the Ruppeiner, Weinhold and Quevedo metrics and in the latter case investigate the consistency of taking either the entropy or mass as the thermodynamic potential.Comment: v2: some references adde

Strong field gravitational lensing in scalar tensor theories

Strong field gravitational lensing in the Brans-Dicke theory has been studied. The deflection angle for photons passing very close to the photon sphere is estimated for the static spherically symmetric space-time of the theory and the position and magnification of the relativistic images are obtained. Modeling the super massive central object of the galaxy by the Brans-Dicke space-time, numerical values of different strong lensing observable are estimated. It is found that against the expectation there is no significant scalar field effect in the strong field observable lensing parameters. This observation raises question on the potentiality of the strong field lensing to discriminate different gravitational theories.Comment: 20 pages, accepted in Class. Quantum Grav., final versio

Black Holes in Ho\v{r}ava Gravity with Higher Derivative Magnetic Terms

We consider Horava gravity coupled to Maxwell and higher derivative magnetic terms. We construct static spherically symmetric black hole solutions in the low-energy approximation. We calculate the horizon locations and temperatures in the near-extremal limit, for asymptotically flat and (anti-)de Sitter spaces. We also construct a detailed balanced version of the theory, for which we find projectable and non-projectable, non-perturbative solutions.Comment: 17 pages. v2: Up to date with published version; some minor remarks and more reference

Cell Membrane-Coated Magnetic Nanocubes with a Homotypic Targeting Ability Increase Intracellular Temperature due to ROS Scavenging and Act as a Versatile Theranostic System for Glioblastoma Multiforme

In this study, hybrid nanocubes composed of magnetite (Fe3O4) and manganese dioxide (MnO2), coated with U-251 MG cell-derived membranes (CM-NCubes) are synthesized. The CM-NCubes demonstrate a concentration-dependent oxygen generation (up to 15%), and, for the first time in the literature, an intracellular increase of temperature (6 \ub0C) due to the exothermic scavenging reaction of hydrogen peroxide (H2O2) is showed. Internalization studies demonstrate that the CM-NCubes are internalized much faster and at a higher extent by the homotypic U-251 MG cell line compared to other cerebral cell lines. The ability of the CM-NCubes to cross an in vitro model of the blood-brain barrier is also assessed. The CM-NCubes show the ability to respond to a static magnet and to accumulate in cells even under flowing conditions. Moreover, it is demonstrated that 500 \ub5g mL 121 of sorafenib-loaded or unloaded CM-NCubes are able to induce cell death by apoptosis in U-251 MG spheroids that are used as a tumor model, after their exposure to an alternating magnetic field (AMF). Finally, it is shown that the combination of sorafenib and AMF induces a higher enzymatic activity of caspase 3 and caspase 9, probably due to an increment in reactive oxygen species by means of hyperthermia

Emergent Strain of Human Adenovirus Endemic in Iowa

We evaluated 76 adenovirus type 7 (Ad7) isolates collected in Iowa from 1992 to 2002 and found that genome type Ad7d2 became increasingly prevalent. By 2002, it had supplanted all other Ad7 genome types. The association of Ad7d2 with severe illness and death calls for heightened public health concern

Chronic Obstructive Pulmonary Disease (COPD) as a disease of early aging: Evidence from the EpiChron Cohort

Background Aging is an important risk factor for most chronic diseases. Patients with COPD develop more comorbidities than non-COPD subjects. We hypothesized that the development of comorbidities characteristically affecting the elderly occur at an earlier age in subjects with the diagnosis of COPD. Methods and findings We included all subjects carrying the diagnosis of COPD (n = 27, 617), and a similar number of age and sex matched individuals without the diagnosis, extracted from the 727, 241 records of individuals 40 years and older included in the EpiChron Cohort (Aragon, Spain). We compared the cumulative number of comorbidities, their prevalence and the mortality risk between both groups. Using network analysis, we explored the connectivity between comorbidities and the most influential comorbidities in both groups. We divided the groups into 5 incremental age categories and compared their comorbidity networks. We then selected those comorbidities known to affect primarily the elderly and compared their prevalence across the 5 age groups. In addition, we replicated the analysis in the smokers'' subgroup to correct for the confounding effect of cigarette smoking. Subjects with COPD had more comorbidities and died at a younger age compared to controls. Comparison of both cohorts across 5 incremental age groups showed that the number of comorbidities, the prevalence of diseases characteristic of aging and network''s density for the COPD group aged 56-65 were similar to those of non-COPD 15 to 20 years older. The findings persisted after adjusting for smoking. Conclusion Multimorbidity increases with age but in patients carrying the diagnosis of COPD, these comorbidities are seen at an earlier age

Improving outcomes for people with COPD by developing networks of general practices: evaluation of a quality improvement project in east London

BACKGROUND: Structured care for people with chronic obstructive pulmonary disease (COPD) can improve outcomes. Delivering care in a deprived ethnically diverse area can prove challenging. AIMS: Evaluation of a system change to enhance COPD care delivery in a primary care setting between 2010 and 2013 using observational data. METHODS: All 36 practices in one inner London primary care trust were grouped geographically into eight networks of 4-5 practices, each supported by a network manager, clerical staff and an educational budget. A multidisciplinary group, including a respiratory specialist and the community respiratory team, developed a 'care package' for COPD management, with financial incentives based on network achievements of clinical targets and supported case management and education. Monthly electronic dashboards enabled networks to track and improve performance. RESULTS: The size of network COPD registers increased by 10% in the first year. Between 2010 and 2013 completed care plans increased from 53 to 86.5%, pulmonary rehabilitation referrals rose from 45 to 70% and rates of flu immunisation from 81 to 83%, exceeding London and England figures. Hospital admissions decreased in Tower Hamlets from a historic high base. CONCLUSIONS: Investment of financial, organisational and educational resource into general practice networks was associated with clinically important improvements in COPD care in socially deprived, ethnically diverse communities. Key behaviour change included the following: collaborative working between practices driven by high-quality information to support performance review; shared financial incentives; and engagement between primary and secondary care clinicians