N-(Anilinoethyl)amide Melatonergic Ligands with Improved Water Solubility and Metabolic Stability

The MT₂-selective melatonin receptor ligand UCM765 (N-(2-((3-methoxyphenyl)(phenyl)amino)ethyl)acetamide), showed interesting sleep inducing, analgesic and anxiolytic properties in rodents, but suffers from low water solubility and modest metabolic stability. To overcome these limitations, different strategies were investigated, including modification of metabolically liable sites, introduction of hydrophilic substituents and design of more basic derivatives. Thermodynamic solubility, microsomal stability and lipophilicity of new compounds were experimentally evaluated, together with their MT₁ and MT₂ binding affinities. Introduction of a m-hydroxymethyl substituent on the phenyl ring of UCM765 and replacement of the replacement of the N,N-diphenyl-amino scaffold with a N-methyl-N-phenyl-amino one led to highly soluble compounds with good microsomal stability and receptor binding affinity. Docking studies into the receptor crystal structure provided a rationale for their binding affinity. Pharmacokinetic characterization in rats highlighted higher plasma concentrations for the N-methyl-N-phenyl-amino derivative, consistent with its improved microsomal stability and makes this compound worthy of consideration for further pharmacological investigation.     

A simulative approach for evaluating alternative feeding scenarios in a kanban system

In accordance with the lean production philosophy, an assembly line may be supplied by means of a kanban system, which regulates and simplifies the flow of materials between the lines and the warehouses. This paper focuses on evaluation of feeding policies that differ from each other in term of the number of kanbans managed per feeding tour. A pure cost-based approach is thus proposed, which considers both inline inventories along with handling costs proportionate to the number of operators involved in the parts-feeding process. A multi-scenario simulative approach is applied in order to establish the number of operators required to avoid inline shortages. The scenario minimising total cost is then selected. The innovation introduced is a model for describing kanban arrivals and their requests for feeding, improving the potential of the simulation to describe real-life environments. Lastly, a case study from the automotive industry is presented in order to highlight the applicability of the proposed approach as well and the effects of alternative feeding policies on the total cost incurred.     

Consumer acceptance of reformulated food products: A systematic review and meta-analysis of salt-reduced foods

Food product reformulation is promoted as an effective strategy to reduce population salt intake and address the associated burden of chronic disease. Salt has a number of functions in food processing, including impacting upon physical and sensory properties. Manufacturers must ensure that reformulation of foods to reduce salt does not compromise consumer acceptability.

The aim of this systematic review is to determine to what extent foods can be reduced in salt without detrimental effect on consumer acceptability.

Fifty studies reported on salt reduction, replacement or compensation in processed meats, breads, cheeses, soups, and miscellaneous products. For each product category, levels of salt reduction were collapsed into four groups: <40%, 40–59%, 60–79% and ≥80%. Random effects meta-analyses conducted on salt-reduced products showed that salt could be reduced by approximately 40% in breads [mean change in acceptability for reduction <40% (?0.27, 95% confidence interval (CI) ?0.62, 0.08; p = 0.13)] and approximately 70% in processed meats [mean change in acceptability for reductions 60–69% (?0.18, 95% CI ?0.44, 0.07; p = 0.15)] without significantly impacting consumer acceptability. Results varied for other products.

These results will support manufacturers to make greater reductions in salt when reformulating food products, which in turn will contribute to a healthier food supply.     

Optical and electrical characterization of a gold nanoparticle dispersion in a chiral liquid crystal matrix

We report on the effect of gold nanoparticle (Au NP) dispersion in a chiral nematic liquid crystal (LC). Polarized optical microscopy and X-ray diffraction measurements evidence the insurgence of an order change in the LC host. Moreover, a comparative analysis based on dielectric and voltammetric spectroscopies performed on pure LC and on Au NP-doped LC shows that Au NP’s presence besides affecting LC order influences its electric properties: ion conductivity results importantly reduced, and beyond a threshold value of the applied field electrophoresis phenomena are induced.     

Built Conservation and the Unfinished Fabrics of Time

Differentiating between the static impulse to preserve and the more open-ended and imaginative process of conservation, Federica Goffi presents a building as ‘a fabric that, even when complete, is unfinished and open to change’. Associate Professor and Associate Director of Graduate Programs at the Azrieli School of Architecture and Urbanism at Carleton University in Ottawa, Goffi has written widely on the topic of time, particularly taking St Peter's in the Vatican by way of example.     

Inflammatory Cutaneous Diseases in Renal Transplant Recipients

Kidney transplant recipients frequently suffer from skin infections and malignancies, possibly due to the effects of long-term immunosuppressive therapy. While the relationships between immunosuppression and these pathological conditions have been widely investigated, little is known about the relative incidence and characteristics of inflammatory skin diseases in this type of patient. In this study, we analyze the incidence of a number of inflammatory cutaneous diseases in a cohort of patients who underwent kidney transplantation. Although our study shows a relatively low incidence of these pathologies in transplanted patients—in agreement with the general action of immunosuppressant therapies in reducing inflammation—we scored a different efficacy of the various immunosuppressive regimens on inflammatory and autoimmune skin diseases. This information can be key for designing immunosuppressive regimens and devising accurate follow-up protocols.