Progress in Stimuli-Responsive Biomaterials for Treating Cardiovascular and Cerebrovascular Diseases.

Cardiovascular and cerebrovascular diseases (CCVDs) describe abnormal vascular system conditions affecting the brain and heart. Among these, ischemic heart disease and ischemic stroke are the leading causes of death worldwide, resulting in 16% and 11% of deaths globally. Although several therapeutic approaches are presented over the years, the continuously increasing mortality rates suggest the need for more advanced strategies for their treatment. One of these strategies lies in the use of stimuli-responsive biomaterials. These "smart" biomaterials can specifically target the diseased tissue, and after "reading" the altered environmental cues, they can respond by altering their physicochemical properties and/or their morphology. In this review, the progress in the field of stimuli-responsive biomaterials for CCVDs in the last five years, aiming at highlighting their potential as early-stage therapeutics in the preclinical scenery, is described.

A survey of Circular Economy initiatives in Portuguese central public sector organisations: National outlook for implementation.

The Circular Economy (CE) is generally understood as an opportunity to transform the current unsustainable linear economic system by redesigning the way organisations provide goods and services rethinking how society consumes and uses those resources. In this context, the public sector is mainly recognised as an actor enabling the implementation of a sustainable CE through governmental interventions and policy initiatives. However, there is a lack of studies considering the public sector at an organisational level. CE in organisations includes a wide range of different practices that are important to examine in order to analyse the CE implementation process. Consequently, this study aims to characterise the current state of implementing circular practices and supporting strategies in central public sector organisations. To fulfil this aim, a questionnaire survey was sent to the organisations pertaining to the Portuguese Central Public Administration, as surveys are valuable tools to systematically collect information on various topics. The results demonstrate a relatively low level of implementation. Circular practices such as purchasing remanufactured or used items, using sharing platforms, increasing the efficiency of buildings, adopting green human resources and collaborative initiatives for circularity, and assessing and communicating about CE activities have presented low levels of adoption. At the same time, waste collection for recycling and dematerialisation practices showed good implementation levels. There is, thus, immense potential for further implementation of circularity in central public sector organisations in Portugal. This research contributes to deepening the understanding of the extent to which circular practices are embedded in public sector organisations and identifying the main implementation strengths and weaknesses. This research has the potential to help practitioners and researchers in the transition towards circularity in identifying circular opportunities in their organisations and in building a vision to further implement circularity in public sector organisations.

Experimental Reconstruction of the Few-Photon Nonlinear Scattering Matrix from a Single Quantum Dot in a Nanophotonic Waveguide.

Coherent photon-emitter interfaces offer a way to mediate efficient nonlinear photon-photon interactions, much needed for quantum information processing. Here we experimentally study the case of a two-level emitter, a quantum dot, coupled to a single optical mode in a nanophotonic waveguide. We carry out few-photon transport experiments and record the statistics of the light to reconstruct the scattering matrix elements of one- and two-photon components. This provides direct insight to the complex nonlinear photon interaction that contains rich many-body physics.

In Vitro Assays for Nanoparticle-Cancer Cell Interaction Studies.

Nanotechnology is a rapid-growing field with an extreme potential to revolutionize cancer treatments. However, despite the rapid advances, the clinical translation is still scarce. One of the main hurdles contributing for this setback is the lack of reliable in vitro models for preclinical testing capable of predicting the outcomes in an in vivo setting. In fact, the use of 2D monolayers, considered the gold-standard in vitro technique, leads to the creation of misleading data that might not be completely observed in in vivo or clinical setting. Thus, there is the need to use more complex models capable of better mimicking the tumor microenvironment. For that purpose, the development and use of multicellular tumor spheroids, three-dimensional (3D) cell cultures which recapitulate numerous aspects of the tumors, represents an advantageous approach to test the developed anticancer therapies. In this chapter, we identify and discuss the advantages of the use of these 3D cellular models compared to the 2D models and how they can be utilized to study nanoparticle-cancer cell interaction in a more reliable way to predict the treatment outcome in vivo.

Multiphoton Scattering Tomography with Coherent States.

In this work we develop an experimental procedure to interrogate the single- and multiphoton scattering matrices of an unknown quantum system interacting with propagating photons. Our proposal requires coherent state laser or microwave inputs and homodyne detection at the scatterer's output, and provides simultaneous information about multiple-elastic and inelastic-segments of the scattering matrix. The method is resilient to detector noise and its errors can be made arbitrarily small by combining experiments at various laser powers. Finally, we show that the tomography of scattering has to be performed using pulsed lasers to efficiently gather information about the nonlinear processes in the scatterer.

Sustainability reporting in public sector organisations: Exploring the relation between the reporting process and organisational change management for sustainability.

Sustainability Reporting has become a key element in different organisations. Although there have been a number of academic publications discussing the adoption of sustainability reports in the public sector, their numbers have been quite low when compared to those focussing on corporate reports. Additionally, there has been little research on the link between sustainability reporting in Public Sector Organisations (PSOs) and Organisational Change Management for Sustainability (OCMS). This paper focuses on the contribution of sustainability reporting to OCMS. A survey was sent to all PSOs that have published at least one sustainability report based on the GRI guidelines. The study provides a critical analysis of the relation between sustainability reporting and OCMS in PSOs, including the drivers for reporting, the impacts on organisation change management, and the role of stakeholders in the process. Despite still lagging in sustainability reporting journey, PSOs are starting to use sustainability reporting as a communication tool, and this could drive organisational changes for sustainability.

Quantum spin dimers from chiral dissipation in cold-atom chains.

We consider the nonequilibrium dynamics of a driven dissipative spin chain with chiral coupling to a one-dimensional (1D) bosonic bath, and its atomic implementation with a two-species mixture of cold quantum gases. The reservoir is represented by a spin-orbit coupled 1D quasicondensate of atoms in a magnetized phase, while the spins are identified with motional states of a separate species of atoms in an optical lattice. The chirality of reservoir excitations allows the spins to couple differently to left- and right-moving modes, which in our atomic setup can be tuned from bidirectional to purely unidirectional. Remarkably, this leads to a pure steady state in which pairs of neighboring spins form dimers that decouple from the remainder of the chain. Our results also apply to current experiments with two-level emitters coupled to photonic waveguides.

Nonlinear quantum optomechanics via individual intrinsic two-level defects.

We propose to use the intrinsic two-level system (TLS) defect states found naturally in integrated optomechanical devices for exploring cavity QED-like phenomena with localized phonons. The Jaynes-Cummings-type interaction between TLS and mechanics can reach the strong coupling regime for existing nano-optomechanical systems, observable via clear signatures in the optomechanical output spectrum. These signatures persist even at finite temperature, and we derive an explicit expression for the temperature at which they vanish. Further, the ability to drive the defect with a microwave field allows for realization of phonon blockade, and the available controls are sufficient to deterministically prepare non-classical states of the mechanical resonator.

Role of the Nephrologist in Non-Kidney Solid Organ Transplant (NKSOT).

BACKGROUND: Chronic kidney disease (CKD) is a common complication of a non-kidney solid organ transplant (NKSOT). Identifying predisposing factors is crucial for an early approach and correct referral to nephrology. METHODS: This is a single-center retrospective observational study of a cohort of CKD patients under follow-up in the Nephrology Department between 2010 to 2020. Statistical analysis was performed between all the risk factors and four dependent variables: end-stage renal disease (ESKD); increased serum creatinine ≥50%; renal replacement therapy (RRT); and death in the pre-transplant, peri-transplant, and post-transplant periods. RESULTS: 74 patients were studied (7 heart transplants, 34 liver transplants, and 33 lung transplants). Patients who were not followed-up by a nephrologist in the pre-transplant (p < 0.027) or peri-transplant (p < 0.046) periods and those who had the longest time until an outpatient clinic follow-up (HR 1.032) were associated with a higher risk of creatinine increase ≥50%. Receiving a lung transplant conferred a higher risk than a liver or heart transplant for developing a creatinine increase ≥50% and ESKD. Peri-transplant mechanical ventilation, peri-transplant and post-transplant anticalcineurin overdose, nephrotoxicity, and the number of hospital admissions were significantly associated with a creatinine increase ≥50% and developing ESKD. CONCLUSIONS: Early and close follow-up by a nephrologist was associated with a decrease in the worsening of renal function.

Hybrid red blood cell membrane coated porous silicon nanoparticles functionalized with cancer antigen induce depletion of T cells.

Erythrocyte-based drug delivery systems have been investigated for their biocompatibility, long circulation time, and capability to transport cargo all around the body, thus presenting enormous potential in medical applications. In this study, we investigated hybrid nanoparticles consisting of nano-sized autologous or allogeneic red blood cell (RBC) membranes encapsulating porous silicon nanoparticles (PSi NPs). These NPs were functionalized with a model cancer antigen TRP2, which was either expressed on the surface of the RBCs by a cell membrane-mimicking block copolymer polydimethylsiloxane-b-poly-2-methyl-2-oxazoline, or attached on the PSi NPs, thus hidden within the encapsulation. When in the presence of peripheral blood immune cells, these NPs resulted in apoptotic cell death of T cells, where the NPs having TRP2 within the encapsulation led to a stronger T cell deletion. The deletion of the T cells did not change the relative proportion of CD4+ and cytotoxic CD8+ T cells. Overall, this work shows the combination of nano-sized RBCs, PSi, and antigenic peptides may have use in the treatment of autoimmune diseases.

Colorectal cancer triple co-culture spheroid model to assess the biocompatibility and anticancer properties of polymeric nanoparticles.

Colorectal cancer (CRC) is the third most common and the second deadliest type of cancer worldwide, urging the development of more comprehensive models and of more efficient treatments. Although the combination of nanotechnology with chemo- and immuno-therapy has represented a promising treatment approach, its translation to the clinic has been hampered by the absence of cellular models that can provide reliable and predictive knowledge about the in vivo efficiency of the formulation. Herein, a 3D model based on CRC multicellular tumor spheroids (MCTS) model was developed by combining epithelial colon cancer cells (HCT116), human intestinal fibroblasts and monocytes. The developed MCTS 3D model mimicked several tumor features with cells undergoing spatial organization and producing extracellular matrix, forming a mass of tissue with a necrotic core. Furthermore, monocytes were differentiated into macrophages with an anti-inflammatory, pro-tumor M2-like phenotype. For a combined chemoimmunotherapy effect, spermine-modified acetalated dextran nanoparticles (NPs) loaded with the chemotherapeutic Nutlin-3a (Nut3a) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were produced and tested in 2D cultures and in the MCTS 3D model. NPs were successfully taken-up by the cells in 2D, but in a significant less extent in the 3D model. However, these NPs were able to induce an anti-proliferative effect both in the 2D and in the 3D models. Moreover, Nut3a was able to partially shift the polarization of the macrophages present in the MCTS 3D model towards an anti-tumor M1-like phenotype. Overall, the developed MCTS 3D model showed to recapitulate key features of tumors, while representing a valuable model to assess the effect of combinatorial nano-therapeutic strategies in CRC. In addition, the developed NPs could represent a promising approach for CRC treatment.

Ecological risk assessment of sediment management areas: application to Sado Estuary, Portugal.

The purpose of this work was to integrate different methodologies to assess the potential ecological risk of estuarine sedimentary management areas, using the Sado Estuary in Portugal as case study. To evaluate the environmental risk of sediment contamination, an integrative and innovative approach was used involving assessment of sediment chemistry, sediment toxicity, benthic community structure, human driving forces and pressures and management areas organic load levels. The basis for decision-making for overall assessment was a statistical multivariate analysis appended into a score matrix tables, using a best expert judgment. The integrated approach allowed to identify from the 19 management areas analyzed, three with no risk but other three with high risk to cause adverse effects in the biota, related with the contaminants analyzed. The methodologies used showed to be effective as a support for decision making leading to future estuarine management recommendations.

Correction to "Targeted Reinforcement of Macrophage Reprogramming Toward M2 Polarization by IL-4-Loaded Hyaluronic Acid Particles".

[This corrects the article DOI: 10.1021/acsomega.8b03182.].

Targeted Reinforcement of Macrophage Reprogramming Toward M2 Polarization by IL-4-Loaded Hyaluronic Acid Particles.

Alteration of macrophage polarization from inflammatory (M1) to anti-inflammatory (M2) phenotype can have striking implications for the regeneration of injured tissues, treatment of inflammatory diseases, and relief of autoimmune disorders. Although certain cytokines like interleukin (IL)-4 and IL-13 are capable of inducing M2 macrophage polarization, their therapeutic potential in vivo is suffering from low efficacy due to their instability and poor access to target cells. Here, we report the synthesis of IL-4-loaded hyaluronic acid (HA) particle for the targeted delivery of cytokines through the high affinity of HA to CD44 receptors of macrophages. HA carriers composed of low, middle, and high molecular weight (MW) polymers were synthesized using divinyl sulfone (DVS) cross-linking. The MW of HA had a negligible effect on the physicochemical properties and biocompatibility of the macrophages, but as an indicative of M2 polarization, a significant change in the arginase-1 (Arg-1) activity, TNF-α release, and IL-10 secretion was observed for the HA particles prepared with high MW polymers. Therefore, these particles were loaded with IL-4 for simultaneous macrophage targeting and M1 to M2 reprogramming, evidenced by a remarkable increase in the Arg-1 to iNOS ratio, as well as CD163 and CD206 upregulation in the M1 macrophages, which were initially triggered by lipopolysaccharide and interferon-γ.

Hierarchical structured and programmed vehicles deliver drugs locally to inflamed sites of intestine.

Orally administrable drug delivery vehicles are developed to manage incurable inflammatory bowel disease (IBD), however, their therapeutic outcomes are compromised by the side effects of systemic drug exposure. Herein, we use hyaluronic acid functionalized porous silicon nanoparticle to bridge enzyme-responsive hydrogel and pH-responsive polymer, generating a hierarchical structured (nano-in-nano-in-micro) vehicle with programmed properties to fully and sequentially overcome the multiple obstacles for efficiently delivering drugs locally to inflamed sites of intestine. After oral administration, the pH-responsive matrix protects the embedded hybrid nanoparticles containing drug loaded hydrogels against the spatially variable physiological environments of the gastrointestinal tract until they reach the inflamed sites of intestine, preventing premature drug release. The negatively charged hybrid nanoparticles selectively target the inflamed sites of intestine, and gradually release drug in response to the microenvironment of inflamed intestine. Overall, the developed hierarchical structured and programmed vehicles load, protect, transport and release drugs locally to inflamed sites of intestine, contributing to superior therapeutic outcomes. Such strategy could also inspire the development of numerous hierarchical structured vehicles by other porous nanoparticles and stimuli-responsive materials for the local delivery of various drugs to treat plenty of inflammatory gastrointestinal diseases, including IBD, gastrointestinal cancers and viral infections.

In vitro evaluation of biodegradable lignin-based nanoparticles for drug delivery and enhanced antiproliferation effect in cancer cells.

Currently, nanosystems have been developed and applied as promising vehicles for different biomedical applications. We have developed three lignin nanoparticles (LNPs): pure lignin nanoparticles (pLNPs), iron(III)-complexed lignin nanoparticles (Fe-LNPs), and Fe3O4-infused lignin nanoparticles (Fe3O4-LNPs) with round shape, narrow size distribution, reduced polydispersity and good stability at pH 7.4. The LNPs showed low cytotoxicity in all the tested cell lines and hemolytic rates below 12% after 12 h of incubation. Additionally, they induced hydrogen peroxide production in a small extent and time-dependent manner, and the interaction with the cells increased over time, exhibiting a dose-dependent cell uptake. Concerning the drug loading, pLNPs showed the capacity to efficiently load poorly water-soluble drugs and other cytotoxic agents, e.g. sorafenib and benzazulene (BZL), and improve their release profiles at pH 5.5 and 7.4 in a sustained manner. Furthermore, the BZL-pLNPs presented an enhanced antiproliferation effect in different cells compared to the pure BZL and showed a maximal inhibitory concentration ranging from 0.64 to 12.4 µM after 24 h incubation. Overall, LNPs are promising candidates for drug delivery applications, and the superparamagnetic behavior of Fe3O4-LNPs makes them promising for cancer therapy and diagnosis, such as magnetic targeting and magnetic resonance imaging.

Advancing in the management of chronic kidney disease: the results of implementing a quick resolution consultation.

BACKGROUND: Currently, chronic kidney disease (CKD) is understood as global important public health problem, a situation that requires a new approach. OBJECTIVES: To show the results obtained after implementing a quick resolution consultation for CKD management. METHODS: Results were analysed during 6 month time period. RESULTS: A total of 9.61% of received proposals were referred to primary care without in-person visits. In addition, 28.05% of patients were initially evaluated through high resolution clinics and 62.33% were directly referred to other clinics. From the initial 28.05% mentioned, once evaluated, treatment adjusted and informed about the disease, 70% were referred over to primary care for monitoring and the remaining 30% were given specialist appointments. As a consequence, 70.65% of patients were selected for monitoring by nephrology from all proposals received, and 29.35% for primary care monitoring. We observed a significant decrease in the delay until the first medical appointment. CONCLUSIONS: Quick resolution consultations demonstrated to be an efficient tool for CKD management. Its implementation allowed both low consumption of health care resources, selected patients with high risk of progressive cardiovascular disease for long term monitoring, and offered not only an initial evaluation and adjustment of treatment with information provided to those who would be monitored by primary care, but also diminished primary care delays significantly.

Relativistic Lagrangian model of a nematic liquid crystal interacting with an electromagnetic field.

We develop a relativistic variational model for a nematic liquid crystal interacting with an electromagnetic field. The constitutive relation for a general anisotropic uniaxial diamagnetic and dielectric medium is analyzed. We discuss light wave propagation in this moving uniaxial medium, for which the corresponding optical metrics are identified explicitly. A Lagrangian for the coupled system of a nematic liquid crystal and the electromagnetic field is constructed, from which a complete set of equations of motion for the system is derived. The canonical energy-momentum and spin tensors are systematically obtained. We compare our results with those within the nonrelativistic models. As an application of our general formalism, we discuss the so-called Abraham-Minkowski controversy on the momentum of light in a medium.