A Sex Perspective in Neurodegenerative Diseases: microRNAs as Possible Peripheral Biomarkers

Sex is a significant variable in the prevalence and incidence of neurological disorders. Sex differences exist in neurodegenerative disorders (NDs), where sex dimorphisms play important roles in the development and progression of Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. In the last few years, some sex specific biomarkers for the identification of NDs have been described and recent studies have suggested that microRNA (miRNA) could be included among these, as influenced by the hormonal and genetic background. Failing to consider the possible differences between males and females in miRNA evaluation could introduce a sex bias in studies by not considering some of these sex-related biomarkers. In this review, we recapitulate what is known about the sex-specific differences in peripheral miRNA levels in neurodegenerative diseases. Several studies have reported sex-linked disparities, and from the literature analysis miR-206 particularly has been shown to have a sex-specific involvement. Hopefully, in the near future, patient stratification will provide important additional clues in diagnosis, prognosis, and tailoring of the best therapeutic approaches for each patient. Sex-specific biomarkers, such as miRNAs, could represent a useful tool for characterizing subgroups of patients.     

Ethanol from corn: a technical and economical assessment based on different scenarios

A dry-grind ethanol from corn process analysis is performed. After defining a complete model of the process, a pinch technology analysis is carried out to optimise energy and water demands. The so-defined base case is then discussed in terms of production costs and process profitability. A detailed sensitivity analysis on the most important process and financial variables is carried out. The possibility to adopt different alternatives for heat and power generation combined to the process is evaluated.     

Biodegradation paths of Mater‐Bi®/kenaf biodegradable composites

Composites obtained from biodegradable polymers and natural–organic fillers are attracting increasing interest, thanks to the environmental advantages they promise. On the other hand, the real biodegradation performance of a biodegradable polymer/natural organic filler composite should be assessed by performing specific biodegradation tests. These are often carried out under laboratory conditions, but more realistic conditions should be taken into account. In this work, a systematic study on the biodegradation of kenaf fiber‐filled Mater‐Bi® composites in different environments is presented, and some interesting parameters for the understanding of the optimum way to obtain a fast degradation of the composites can be extrapolated. In particular, it was found that the presence of the fibers, the environmental conditions, and the manufacturing procedures of the composites can significantly affect the biodegradation behavior. The results can be used to determine the most suitable disposal environments for biodegradation of Mater‐Bi®‐based wastes. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

In Vitro and In Silico Characterization of an Antimalarial Compound with Antitumor Activity Targeting Human DNA Topoisomerase IB

Human DNA topoisomerase IB controls the topological state of supercoiled DNA through a complex catalytic cycle that consists of cleavage and religation reactions, allowing the progression of fundamental DNA metabolism. The catalytic steps of human DNA topoisomerase IB were analyzed in the presence of a drug, obtained by the open-access drug bank Medicines for Malaria Venture. The experiments indicate that the compound strongly and irreversibly inhibits the cleavage step of the enzyme reaction and reduces the cell viability of three different cancer cell lines. Molecular docking and molecular dynamics simulations suggest that the drug binds to the human DNA topoisomerase IB-DNA complex sitting inside the catalytic site of the enzyme, providing a molecular explanation for the cleavage-inhibition effect. For all these reasons, the aforementioned drug could be a possible lead compound for the development of an efficient anti-tumor molecule targeting human DNA topoisomerase IB.     

A non dominated ranking Multi Objective Genetic Algorithm and electre method for unequal area facility layout problems

The unequal area facility layout problem (UA-FLP) comprises a class of extremely difficult and widely applicable optimization problems arising in diverse areas and meeting the requirements for real-world applications. Genetic Algorithms (GAs) have recently proven their effectiveness in finding (sub) optimal solutions to many NP-hard problems such as UA-FLP. A main issue in such approach is related to the genetic encoding and to the evolutionary mechanism implemented, which must allow the efficient exploration of a wide solution space, preserving the feasibility of the solutions and ensuring the convergence towards the optimum. In addition, in realistic situations where several design issues must be taken into account, the layout problem falls in the broader framework of multi-objective optimization problems. To date, there are only a few multi-objective FLP approaches, and most of them employ over-simplified optimization techniques which eventually influence the quality of the solutions obtained and the performance of the optimization procedure. In this paper, this difficulty is overcome by approaching the problem in two subsequent steps: in the first step, the Pareto-optimal solutions are determined by employing Multi Objective Genetic Algorithm (MOGA) implementing four separate fitness functions within a Pareto evolutionary procedure, following the general structure of Non-dominated Ranking Genetic Algorithm (NRGA) and the subsequent selection of the optimal solution is carried out by means of the multi-criteria decision-making procedure Electre. This procedure allows the decision maker to express his preferences on the basis of the knowledge of candidate solution set. Quantitative and qualitative objectives are considered referring to the slicing-tree layout representation scheme. The numerical results obtained outperform previous referenced approaches, thus confirming the effectiveness of the procedure proposed.     

A multi objective genetic algorithm for the facility layout problem based upon slicing structure encoding

This paper proposes a new multi objective genetic algorithm (MOGA) for solving unequal area facility layout problems (UA-FLPs). The genetic algorithm suggested is based upon the slicing structure where the relative locations of the facilities on the floor are represented by a location matrix encoded in two chromosomes. A block layout is constructed by partitioning the floor into a set of rectangular blocks using guillotine cuts satisfying the areas requirements of the departments. The procedure takes into account four objective functions (material handling costs, aspect ratio, closeness and distance requests) by means of a Pareto based evolutionary approach. The main advantage of the proposed formulation, with respect to existing referenced approaches (e.g. bay structure), is that the search space is considerably wide and the practicability of the layout designs is preserved, thus improving the quality of the solutions obtained.     

Immunotherapy in NSCLC Patients with Brain Metastases

Approximately 40% of unselected non-small cell lung cancer (NSCLC) patients develop brain metastases (BMs) during their disease, with considerable morbidity and mortality. The management of BMs in patients with NSCLC is a clinical challenge and requires a multidisciplinary approach to gain effective intracranial disease control. Over the last decade, immune checkpoint inhibitors (ICIs) have emerged as a game-changer in the treatment landscape of advanced NSCLC, with significant improvements in survival outcomes, although patients with BMs are mostly underrepresented in randomized clinical trials. Moreover, the safety and activity of ICIs and radiotherapy combinations compared with single-agent or sequential modalities is still under evaluation to establish the optimal management of these patients. The aim of this review is to summarize the state-of-the-art of clinical evidence of ICIs intracranial activity and the main challenges of incorporating these agents in the treatment armamentarium of NSCLC patients with BMs.     

Numerical Investigation of Funicular Liquid Bridge Interactions Between Spherical Particles

In industrial processing of wet particulate materials, the liquid governs the formation, growth, and breakup of particle agglomerates. Pendular liquid bridges between two particles have been extensively investigated in the literature. Despite the interest, the complexities in the funicular regime, which involve multiple spheres, have remained mostly uncovered. Validated numerical simulations are utilized herein to examine funicular liquid bridge shapes, interaction forces, and rupture conditions as functions of the liquid volume, pressure difference, interparticle distance, and contact angle for three-sphere and four-sphere arrangements, including the presence of a particle of different size. The agglomerate strength is quantitatively characterized for a broad range of conditions.     

Direct detection of antibiotic resistance genes in specimens of chicken and pork meat

Antibiotic resistance (AR) in bacteria, a major threat to human health, has emerged in the last few decades as a consequence of the selective pressure exerted by the widespread use of antibiotics in medicine, agriculture and veterinary practice and as growth promoters in animal husbandry. The frequency of 11 genes [tet(M), tet(O), tet(K), erm(A), erm(B), erm(C), vanA, vanB, aac (6')-Ie aph (2')-Ia, mecA, blaZ] encoding resistance to some antibiotics widely used in clinical practice was analysed in raw pork and chicken meat and in fermented sausages as well as in faecal samples from the relevant farm animals using a molecular approach based on PCR amplification of bacterial DNA directly extracted from specimens. Some of the 11 AR genes were highly prevalent, the largest number being detected in chicken meat and pig faeces. The genes found most frequently in meat were tet(K) and erm(B); vanB and mecA were the least represented. All 11 determinants were detected in faecal samples except mecA, which was found only in chicken faeces. erm(B) and erm(C) were detected in all faecal samples. The frequency of AR genes was not appreciably different in meat compared to faecal specimens of the relevant animal except for vanB, which was more prevalent in faeces. Our findings suggest that AR genes are highly prevalent in food-associated bacteria and that AR contamination is likely related to breeding rather than processing techniques. Finally, the cultivation-independent molecular method used in this work to determine the prevalence of AR genes in foods proved to be a rapid and reliable alternative to traditional tools.     

Controlled Liposome Delivery from Chitosan-Based Thermosensitive Hydrogel for Regenerative Medicine

This work describes the development of an injectable nanocomposite system based on a chitosan thermosensitive hydrogel combined with liposomes for regenerative medicine applications. Liposomes with good physicochemical properties are prepared and embedded within the chitosan network. The resulting nanocomposite hydrogel is able to provide a controlled release of the content from liposomes, which are able to interact with cells and be internalized. The cellular uptake is enhanced by the presence of a chitosan coating, and cells incubated with liposomes embedded within thermosensitive hydrogels displayed a higher cell uptake compared to cells incubated with liposomes alone. Furthermore, the gelation temperature of the system resulted to be equal to 32.6 °C; thus, the system can be easily injected in the target site to form a hydrogel at physiological temperature. Given the peculiar performance of the selected systems, the resulting thermosensitive hydrogels are a versatile platform and display potential applications as controlled delivery systems of liposomes for tissue regeneration.