Synthesis,Molecular Modeling and Biological Evaluation of Metabolically Stable Analogues of the Endogenous Fatty Acid Amide Palmitoylethanolamide

Palmitoylethanolamide (PEA) belongs to the class of N-acylethanolamine and is an endogenous lipid potentially useful in a wide range of therapeutic areas; products containing PEA are licensed for use in humans as a nutraceutical, a food supplement, or food for medical purposes for its analgesic and anti-inflammatory properties demonstrating efficacy and tolerability. However, the exogenously administered PEA is rapidly inactivated; in this process, fatty acid amide hydrolase (FAAH) plays a key role both in hepatic metabolism and in intracellular degradation. So, the aim of the present study was the design and synthesis of PEA analogues that are more resistant to FAAH-mediated hydrolysis. A small library of PEA analogues was designed and tested by molecular docking and density functional theory calculations to find the more stable analogue. The computational investigation identified RePEA as the best candidate in terms of both synthetic accessibility and metabolic stability to FAAH-mediated hydrolysis. The selected compound was synthesized and assayed ex vivo to monitor FAAH-mediated hydrolysis and to confirm its anti-inflammatory properties. ¹H-NMR spectroscopy performed on membrane samples containing FAAH in integral membrane protein demonstrated that RePEA is not processed by FAAH, in contrast with PEA. Moreover, RePEA retains PEA’s ability to inhibit LPS-induced cytokine release in both murine N9 microglial cells and human PMA-THP-1 cells.     

Drying of Herbal Product in Closed System

A new product from a low temperature drying method that reduces the loss of highly volatile essential oils is presented. The proposed drying method consists of evaporation/sublimation of water and aromatic substances in a dryer with a closed drying agent cycle. In parallel, the evaporated compounds are continuously condensed in a heat exchanger. As a result of the drying process, high-quality dried plants and Fluidolat as liquid phase containing water and volatile organic compounds are obtained. The aim of presented investigations was to optimize the developed technology for the herb lavender.     

Copper‐Catalyzed Asymmetric Conjugate Addition of Dimethylzinc to Acyl‐N‐methylimidazole Michael Acceptors: Scope,Limitations and Iterative Reactions

An efficient copper‐catalyzed enantioselective conjugate addition of dimethylzinc to unsaturated 2‐acyl‐N‐methylimidazoles has been achieved using a chiral bidentate hydroxyalkyl‐NHC ligand. The reactions proceed with excellent regioselectivity (1,4 vs. 1,6 and 1,8) in extended conjugated systems to afford the 1,4‐adducts in high enantioselectivities. This regioselectivity could be ascertained by DFT studies highlighting the crucial role of the imidazole ring. Thanks to the development of efficient protocols to regenerate the unsaturated 2‐acyl‐N‐methylimidazole moiety, an iterative process has been developed ultimately leading to 3,5,7 all‐syn or anti‐anti polydeoxypropionate stereodiads.

     

Dietary assessment of pre-school children from Federal District Brazil

The objective was to assess food consumption among children attending non-profit nurseries in the Federal District, Brazil.A representative sample was obtained and stratified by income. Food intake among 678 children, between 4 and 82 months old, was analyzed in nine nurseries using the 24-h dietary recall and direct food weighing methods. In children under 13 months old mean intake was above AI between 93.6 to 100% for carbohydrates, proteins, vitamins B1, B2, B12, B6, and zinc. In children from 7-12 months 56.5% presented iron consumption below EAR. Calcium intake was above AI for 35.4% of children over 1 year old. For vitamins with EAR values, the prevalence of inadequate consumption was 53.2% for vitamin E, and 90% for folate for children over 12 months old. Iron and zinc intake was above UL for 6.4% and 32.5% of children under 1 year old, and 1.5% and 5.3% for the remaining children, respectively. Lipid percentage distribution range among children between 13 and 47 months old was within the acceptable range for only 16.2%. Nonetheless, children between 36 and 82 months of both genders presented mean intake below energy requirements. Inadequate consumption observed for some nutrients points to the need for improvements in the standard of meals and nutritional assistance offered to children enrolled in charitably run nurseries in the Federal District.     

A collaborative study of a method for the enumeration of probiotic bifidobacteria in animal feed

An enumeration method to be used as an official control method in the framework of Council Directive 70/524/EEC for probiotic bifidobacteria used as feed additives was validated. Seventeen laboratories in 11 European Countries carried out a collaborative study. A spread plate method following BS ISO 15214:1998 using four different agars, Man Rogosa Sharpe (MRS), acidified MRS, MRS with triphenyl tetrazolium chloride (TTC) and a selective bifidobacteria medium, was validated. Precision data in terms of repeatability (r) and reproducibility (R) of the method for each medium using different feeding stuffs with a high and a low inoculation level were determined. Bifidobacteria were present in the samples as a single component or in mixtures with other probiotics. The enumeration of bifidobacteria on all agars showed a relative standard deviation of repeatability (RSD(r)) between 1.2% and 6.3% and a relative standard deviation of reproducibility (RSD(R)) between 2.6% and 8.7%. MRS agar was preferred, followed by acidified MRS and MRS+TTC agar. The selective bifidobacteria medium gave similar counts as the MRS media. For routine analysis, the use of MRS agar with supplementation of cysteine hydrochloride (the selective bifidobacteria medium without antibiotics) is recommended. Depending on the presence and concentration of other probiotics such as enterococci, lactobacilli and pediococci, acidified MRS or MRS+TTC agar is recommended. The selective bifidobacteria medium was selective for bifidobacteria.An official control method for enumeration of probiotic bifidobacteria as a single component and in mixtures with other probiotic microorganisms in feeding stuffs was validated. The methodology is not applicable to mineral feed. The results are intended for consideration for adaptation as CEN and ISO standards.     

Hybridizing adaptive large neighborhood search with kernel search: a new solution approach for the nurse routing problem with incompatible services and minimum demand

The average age of the population has grown steadily in recent decades along with the number of people suffering from chronic diseases and asking for treatments. Hospital care is expensive and often unsafe, especially for older individuals. This is particularly true during pandemics as the recent SARS-CoV-2. Hospitalization at home has become a valuable alternative to face efficiently a huge increase in treatment requests while guaranteeing a high quality of service and lower risk to fragile patients. This new model of care requires the redefinition of health services organization and the optimization of scarce resources (e.g., available nurses). In this paper, we study a Nurse Routing Problem that tries to find a good balance between hospital costs reduction and the well-being of patients, also considering realistic operational restrictions like maximum working times for the nurses and possible incompatibilities between services jointly provided to the same patient. We first propose a Mixed Integer Linear Programming formulation for the problem and use some valid inequalities to strengthen it. A simple branch-and-cut algorithm is proposed and validated to derive ground benchmarks. In addition, to efficiently solve the problem, we develop an Adaptive Large Neighborhood Search hybridized with a Kernel Search and validate its performance over a large set of different realistic working scenarios. Computational tests show how our matheuristic approach manages to find good solutions in a reasonable amount of time even in the most difficult settings. Finally, some interesting managerial insights are discussed through an economic analysis of the operating context.     

Influence of Field Effects on the Performance of InGaAs-Based Terahertz Radiation Detectors

A detailed electrical characterization of high-performance bow-tie InGaAs-based terahertz detectors is presented along with simulation results. The local surface potential and tunnelling current were scanned over the surfaces of the detectors by means of Kelvin probe force microscopy (KPFM) and scanning tunnelling microscopy (STM), which also enabled the determination of the Fermi level. Current-voltage curves were measured and modelled using the Synopsys Sentaurus TCAD package to gain deeper insight into the processes involved in detector operation. In addition, we performed finite-difference time-domain (FDTD) simulations to reveal features related to changes in the electric field due to the metal detector contacts. The investigation revealed that field-effect-induced conductivity modulation is a possible mechanism contributing to the high sensitivity of the studied detectors.     

The ParTriCluster Algorithm for Gene Expression Analysis

Analyzing gene expression patterns is becoming a highly relevant task in the Bioinformatics area. This analysis makes it possible to determine the behavior patterns of genes under various conditions, a fundamental information for treating diseases, among other applications. A recent advance in this area is the Tricluster algorithm, which is the first algorithm capable of determining 3D clusters (genes × samples × timestamps), that is, groups of genes that behave similarly across samples and timestamps. However, even though biological experiments collect an increasing amount of data to be analyzed and correlated, the triclustering problem remains a bottleneck due to its NP-Completeness, so its parallelization seems to be an essential step towards obtaining feasible solutions. In this work we propose and evaluate the implementation of a parallel version of the Tricluster algorithm using the filter-labeled-stream paradigm supported by the Anthill parallel programming environment. The results show that our parallelization scales well with the data size, being able to handle severe load imbalances that are inherent to the problem. Further more, the parallelization strategy is applicable to any depth-first searches.     

Spatial Quality Evaluation of Pedestrian Streets

This paper presents an assessment of the spatial quality of a pedestrian street located in downtown Bauru, S~o Paulo State, Brazil, from the application of some urban sustainability indicators. Multi-method was used to evaluate the thermal comfort quality of users, urban accessibility and preservation of architectural heritage. The results show that the sustainability indicators, apart from being effective tools in identifying problems, can assist local managers in decision making, planning and monitoring of pedestrian public space. These indicators contribute to a broad diagnosis of the pedestrian street and also the formulation of programs, projects and municipal policies, aimed at providing a better life quality for pedestrians.