Marine Drugs, Vol. 14, Pages 91: Effect of Chitosan Properties on Immunoreactivity

Chitosan is a widely investigated biopolymer in drug and gene delivery, tissue engineering and vaccine development. However, the immune response to chitosan is not clearly understood due to contradicting results in literature regarding its immunoreactivity. Thus, in this study, we analyzed effects of various biochemical properties, namely degree of deacetylation (DDA), viscosity/polymer length and endotoxin levels, on immune responses by antigen presenting cells (APCs). Chitosan solutions from various sources were treated with mouse and human APCs (macrophages and/or dendritic cells) and the amount of tumor necrosis factor-α (TNF-α) released by the cells was used as an indicator of immunoreactivity. Our results indicate that only endotoxin content and not DDA or viscosity influenced chitosan-induced immune responses. Our data also indicate that low endotoxin chitosan (<0.01 EU/mg) ranging from 20 to 600 cP and 80% to 97% DDA is essentially inert. This study emphasizes the need for more complete characterization and purification of chitosan in preclinical studies in order for this valuable biomaterial to achieve widespread clinical application.

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Sustainability, Vol. 8, Pages 463: System Merits or Failures? Policies for Transition to Sustainable P and N Systems in The Netherlands and Finland

Nitrogen (N) and phosphorus (P) cycles are absolutely vital in maintaining sustainable food systems. Human activities disturb the natural balance of these cycles by creating enormous additional nutrient fluxes, causing eutrophication of waterways and pollution in land systems. To tackle this problem, sustainable nutrient management is required. This paper addresses sustainable nutrient management in two countries: The Netherlands and Finland. We adopt a critical perspective on resource politics, especially towards opportunistic policy strategies for the pollutant management of N and P. Two research questions are considered. First, what are the key systemic and policy failures that occurred in the N and P systems in the Netherlands and Finland between 1970 and 2015? And second, which lessons can be drawn when addressing the policy responses in the two countries to cope with these failures? The cases are analyzed within Weber and Rohracher's framework that addresses "failures" preventing sustainable transitions. The results show that a number of failures occurred, besides market failures (over-exploitation of the commons, externalization of costs): lack of directionality, policy coordination, institutions, capabilities, infrastructure, demand articulation, and reflexivity. Policy responses in both countries resulted in ponderous policy frameworks that were adequate to tackle nutrient problems from the industrial sector and municipalities. However, both countries provided only a moderate response in terms of system-wide integrated policy frameworks to cope with sectoral-transcending issues. The agricultural use of N and P, in contrast to detergents, has not been subjected to strong regulatory measures.

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Sensors, Vol. 16, Pages 674: Bootstrapping Security Policies for Wearable Apps Using Attributed Structural Graphs

We address the problem of bootstrapping security and privacy policies for newly-deployed apps in wireless body area networks (WBAN) composed of smartphones, sensors and other wearable devices. We introduce a framework to model such a WBAN as an undirected graph whose vertices correspond to devices, apps and app resources, while edges model structural relationships among them. This graph is then augmented with attributes capturing the features of each entity together with user-defined tags. We then adapt available graph-based similarity metrics to find the closest app to a new one to be deployed, with the aim of reusing, and possibly adapting, its security policy. We illustrate our approach through a detailed smartphone ecosystem case study. Our results suggest that the scheme can provide users with a reasonably good policy that is consistent with the user's security preferences implicitly captured by policies already in place.

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Applied Sciences, Vol. 6, Pages 146: Tests and Analysis of the Compressive Performance of an Integrated Masonry Structure of a Brick-Stem-Insulating Layer

This paper proposes, for low buildings, an integrated wall structure of a brick-stem-insulating layer, which plays a major part in both heat preservation and force bearing. The research team has tested the thermal performance of the structure, the results of which are satisfying. To further study the force-bearing performance, the paper carries out compressive tests of specimens of different structural design, with two types of bricks, i.e., clay and recycled concrete bricks; three types of stems, i.e., square-shaped wood, square-shaped steel pipe and circular steel pipe; and one type of insulating layer, i.e., fly ash masonry blocks. Afterward, the force bearing performance, damage that occurred, compressive deformation and ductility of all of the specimens are compared. On the sideline, the structure is applied in the construction of a pilot residence project, yielding favorable outcomes. The results indicate that in comparison with a brick wall with an insulating layer sandwiched in between, the integrated wall structure of bricks and fly ash blocks is a more preferable choice in terms of compressive performance and ductility. The integrated wall structure of brick-stem-fly ash blocks delivers much better performance to this end. Note that regarding the stem's contribution to compressive strength, circular steel pipe is highest, followed by square-shaped steel pipe and then square-shaped wood. The compressive performance of the sandwiched blocks surpasses that of the two brick wall pieces combined by a large margin.

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Nutrients, Vol. 8, Pages 277: A Mixed Flavonoid-Fish Oil Supplement Induces Immune-Enhancing and Anti-Inflammatory Transcriptomic Changes in Adult Obese and Overweight Women—A Randomized Controlled Trial

Flavonoids and fish oils have anti-inflammatory and immune-modulating influences. The purpose of this study was to determine if a mixed flavonoid-fish oil supplement (Q-Mix; 1000 mg quercetin, 400 mg isoquercetin, 120 mg epigallocatechin (EGCG) from green tea extract, 400 mg n3-PUFAs (omega-3 polyunsaturated fatty acid) (220 mg eicosapentaenoic acid (EPA) and 180 mg docosahexaenoic acid (DHA)) from fish oil, 1000 mg vitamin C, 40 mg niacinamide, and 800 µg folic acid) would reduce complications associated with obesity; that is, reduce inflammatory and oxidative stress markers and alter genomic profiles in overweight women. Overweight and obese women (n = 48; age = 40–70 years) were assigned to Q-Mix or placebo groups using randomized double-blinded placebo-controlled procedures. Overnight fasted blood samples were collected at 0 and 10 weeks and analyzed for cytokines, C-reactive protein (CRP), F2-isoprostanes, and whole-blood-derived mRNA, which was assessed using Affymetrix HuGene-1_1 ST arrays. Statistical analysis included two-way ANOVA models for blood analytes and gene expression and pathway and network enrichment methods for gene expression. Plasma levels increased with Q-Mix supplementation by 388% for quercetin, 95% for EPA, 18% for DHA, and 20% for docosapentaenoic acid (DPA). Q-Mix did not alter plasma levels for CRP (p = 0.268), F2-isoprostanes (p = 0.273), and cytokines (p > 0.05). Gene set enrichment analysis revealed upregulation of pathways in Q-Mix vs. placebo related to interferon-induced antiviral mechanism (false discovery rate, FDR < 0.001). Overrepresentation analysis further disclosed an inhibition of phagocytosis-related inflammatory pathways in Q-Mix vs. placebo. Thus, a 10-week Q-Mix supplementation elicited a significant rise in plasma quercetin, EPA, DHA, and DPA, as well as stimulated an antiviral and inflammation whole-blood transcriptomic response in overweight women.

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Water, Vol. 8, Pages 196: The Status of Domestic Water Demand: Supply Deficit in the Kathmandu Valley, Nepal

United Nations Sustainable Development Goal 6 targets access to water and sanitation for all people in the next 15 years. However, for developing countries such as Nepal, it is more challenging to achieve this goal given its poor infrastructure and high population growth. To assess the water crisis in the most developed and populated area of Nepal, the Kathmandu Valley, we estimated available water resources and domestic water demand in the valley. We estimated a supply deficit of 102 million liters per day (MLD) in 2016, after completion of the first phase of the Melamchi Water Supply Project (MWSP). If the MWSP is completed within the specified timeframe, and sufficient treatment and distribution infrastructure is developed, then there would be no water deficit by 2023–2025. This indicates that the MWSP will make a significant contribution to the valley's water security. However, emphasis must be given to utilizing all of the water available from the MWSP by developing sufficient water treatment and distribution infrastructure. Alternate mitigation options, such as planning land use for potential recharge, introducing micro- to macro-level rainwater harvesting structures, conjunctive use of surface and groundwater resources, and water demand-side management, would also be helpful.

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Processes, Vol. 4, Pages 16: Process Intensification via Membrane Reactors, the DEMCAMER Project

This paper reports the findings of a FP7 project (DEMCAMER) that developed materials (catalysts and membranes) and new processes for four industrially relevant reaction processes. In this project, active, stable, and selective catalysts were developed for the reaction systems of interest and their production scaled up to kg scale (TRL5 (TRL: Technology Readiness Level)). Simultaneously, new membranes for gas separation were developed; in particular, dense supported thin palladium-based membranes for hydrogen separation from reactive mixtures. These membranes were successfully scaled up to TRL4 and used in various lab-scale reactors for water gas shift (WGS), using both packed bed and fluidized bed reactors, and Fischer-Tropsch (FTS) using packed bed reactors and in prototype reactors for WGS and FTS. Mixed ionic-electronic conducting membranes in capillary form were also developed for high temperature oxygen separation from air. These membranes can be used for both Autothermal Reforming (ATR) and Oxidative Coupling of Methane (OCM) reaction systems to increase the efficiency and the yield of the processes. The production of these membranes was scaled up to TRL3–4. The project also developed adequate sealing techniques to be able to integrate the different membranes in lab-scale and prototype reactors.

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MCA, Vol. 21, Pages 17: Three-Parameter Interval Grey Number Multi-Attribute Decision Making Method Based on Information Entropy

Aimed at the situation that the plan attribute value is a three-parameter interval grey number and that attribute weight is uncertain, a three-parameter interval grey number multi-attribute decision making method based on information entropy is proposed. In this study, we combine the three-parameter interval grey number decision-making problem with information entropy, build the distance entropy model of the three-parameter interval grey number, and provide a solution to the empowerment problem of the three-parameter interval grey number in grey decision-making problems. On this basis, we build the uncertainty decision making framework based on Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) thinking and obtain the comprehensive distances of plans from positive and negative ideal solutions through calculation. We thus determine the closeness, and, based on this value, organize these plans. Finally, we verify the feasibility and effectiveness of the proposed methods through case analysis.

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Sustainability, Vol. 8, Pages 464: Towards a Model of Sustainable Competitiveness of Health Organizations

Over the last decades, around the world, the concept of competitiveness was long debated by economists (and others), widely used and even sometimes overused. Although at the theoretical level, a number of determinant factors of health care organizations' competitiveness have been proposed, their diversity and the little empirical data available argues for the need to create and validate a model of competitiveness of health organizations. The purpose of this paper is (considering the theoretical approach) to shape a model of sustainable competitiveness of health organizations. In this respect, a 51 item questionnaire was designed and applied on a sample of 291 respondents from 12 Romanian health organizations. The exploratory factor analysis undertaken recovered more than 69% of the common variability of the initial 51 variables and revealed four factors/dimensions of sustainable competitiveness of health organizations (Economic Dimension, Quality Dimension, Social Dimension, and Strategic Dimension). Among the results of the exploratory factor analysis is also the empirical evidence on the contribution of leadership and managerial processes to enhance the influence of all other factors/dimensions in increasing the sustainable competitiveness of health organizations, thus bringing into focus the concept of sustainable management and leadership. Being just in the exploratory phase of our research, the proposed model can, and should, be improved, thus opening up further research directions.

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Current and future treatment of amyloid diseases

Abstract

There are more than 30 human proteins whose aggregation appears to cause degenerative maladies referred to as amyloid diseases or amyloidoses. These disorders are named after the characteristic cross-β-sheet amyloid fibrils that accumulate systemically or are localized to specific organs. In most cases, current treatment is limited to symptomatic approaches and thus disease-modifying therapies are needed. Alzheimer's disease is a neurodegenerative disorder with extracellular amyloid β-peptide (Aβ) fibrils and intracellular tau neurofibrillary tangles as pathological hallmarks. Numerous clinical trials have been conducted with passive and active immunotherapy, and small molecules to inhibit Aβ formation and aggregation or to enhance Aβ clearance; so far such clinical trials have been unsuccessful. Novel strategies are therefore required and here we will discuss the possibility of utilizing the chaperone BRICHOS to prevent Aβ aggregation and toxicity. Type 2 diabetes mellitus is symptomatically treated with insulin. However, the underlying pathology is linked to the aggregation and progressive accumulation of islet amyloid polypeptide as fibrils and oligomers, which are cytotoxic. Several compounds have been shown to inhibit islet amyloid aggregation and cytotoxicity in vitro. Future animal studies and clinical trials have to be conducted to determine their efficacy in vivo. The transthyretin (TTR) amyloidoses are a group of systemic degenerative diseases compromising multiple organ systems, caused by TTR aggregation. Liver transplantation decreases the generation of misfolded TTR and improves the quality of life for a subgroup of this patient population. Compounds that stabilize the natively folded, nonamyloidogenic, tetrameric conformation of TTR have been developed and the drug tafamidis is available as a promising treatment.

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Precision medicine in pheochromocytoma and paraganglioma: current and future concepts

Abstract

Pheochromocytoma and paraganglioma (PPGL) are rare diseases but are also amongst the most characterized tumour types. Hence, patients with PPGL have greatly benefited from precision medicine for more than two decades. According to current molecular biology and genetics-based taxonomy, PPGL can be divided into three different clusters characterized by: Krebs cycle reprogramming with oncometabolite accumulation or depletion (group 1a); activation of the (pseudo)hypoxia signalling pathway with increased tumour cell proliferation, invasiveness and migration (group 1b); and aberrant kinase signalling causing a pro-mitogenic and anti-apoptotic state (group 2). Categorization into these clusters is highly dependent on mutation subtypes. At least 12 different syndromes with distinct genetic causes, phenotypes and outcomes have been described. Genetic screening tests have a documented benefit, as different PPGL syndromes require specific approaches for optimal diagnosis and localization of various syndrome-related tumours. Genotype-tailored treatment options, follow-up and preventive care are being investigated. Future new developments in precision medicine for PPGL will mainly focus on further identification of driver mechanisms behind both disease initiation and malignant progression. Identification of novel druggable targets and prospective validation of treatment options are eagerly awaited. To achieve these goals, we predict that collaborative large-scale studies will be needed: Pheochromocytoma may provide an example for developing precision medicine in orphan diseases that could ultimately aid in similar efforts for other rare conditions.

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