Role of the vanins-myeloperoxidase axis in colorectal carcinogenesis

The presence of chronic inflammation in the colonic mucosa leads to an increased risk of cancer. Among proteins involved in the regulation of mucosal inflammation and that may contribute both to structural damage of the intestinal mucosa and to intestinal carcinogenesis, there are myeloperoxidase (MPO) and vanins. The infiltration of colonic mucosa by neutrophils may promote carcinogenesis through MPO, a key enzyme contained in the lysosomes of neutrophils that regulates local inflammation and the generation of reactive oxygen species (ROS) and mutagenic species. The human vanin gene family consists of three genes: vanin-1, vanin-2 and vanin-3. All vanin molecules are pantetheinases, that hydrolyze pantetheine into pantothenic acid (vitamin B5), and cysteamine, a sulfhydryl compound. Vanin-1 loss confers an increased resistance to stress and acute intestinal inflammation, while vanin-2 regulates adhesion and transmigration of activated neutrophils. The metabolic product of these enzymes has a prominent role in the inflammation processes by affecting glutathione levels, inducing ulcers through a reduction in mucosal blood flow and oxygenation, decreasing local defense mechanisms, and in carcinogenesis by damaging DNA and regulating pathways involved in cell apoptosis, metabolism and growth, as Nrf2 and HIF-1α

Emergency surgery and Limitation of therapeutic effort in relation to neurologic deterioration in elderly patients – a survey of European surgeons

Background. In emergency surgery, a very heterogeneous approach is required in the decision making process, especially when considering the patient’s postoperative quality of life as well as medical, ethical, and legal factors. In some cases, the presence of an Advance Directive (AD) form may potentially help resolve the surgeon’s dilemma. Objectives. The primary objective of this survey was to investigate the opinions of surgeons across a representative cross-section of European countries regarding the decision making process using a specific case scenario so as to identify similarities and differences in practice. A secondary objective was to identify the possibility of establishing a more uniform approach and best practice. Method. A survey was conducted of surgeons from a range of European countries. Questionnaires were designed to obtain an overview of decision making in relation to the Limitation of Therapeutic Effort (LTE) using a specific case study and the level of awareness and practical use of ADs. Surveys were distributed via email to the members of the ESTES (European Society for Trauma and Emergency Surgery) and AEC (Association of Spanish surgeons), with voluntary, anonymous participation. Conclusions. Clear and additional support in the form of legal and ethical guidance with clinical protocols for surgical practice in such case scenarios is necessary. Wider use of ADs, together with education about their role and support for patients and relatives, would benefit the type of patient described in our scenario. A multidisciplinary team should play a more active role in decision making in order to avoid surgical procedures that are potentially futile. The concepts of LTE and Quality of life need a broader understanding among surgeons as well as more consistent application

Inflammatory pathways in the early steps of colorectal cancer development

Colorectal cancer is a major cause of cancer-related death in many countries. Colorectal carcinogenesis is a stepwise process which, from normal mucosa leads to malignancy. Many factors have been shown to influence this process, however, at present, several points remain obscure. In recent years some hypotheses have been considered on the mechanisms involved in cancer development, expecially in its early stages. Tissue injury resulting from infectious, mechanical, or chemical agents may elicit a chronic immune response resulting in cellular proliferation and regeneration. Chronic inflammation of the large bowel (as in inflammatory bowel diseases), has been associated with the subsequent development of colorectal cancer. In this review we examine the inflammatory pathways involved in the early steps of carcinogenesis, with particular emphasis on colorectal. Firstly, we describe cells and proteins recently suggested as central in the mechanism leading to tumor development. Macrophages and neutrophils are among the cells mostly involved in these processes and proteins, as cyclooxygenases and resolvins, are crucial in these inflammatory pathways. Indeed, the activation of these pathways establishes an oxidative and anaerobic microenvironment with DNA damage to epithelial cells, and shifting from an aerobic to an anaerobic metabolism. Many cellular mechanisms, such as proliferation, apoptosis, and autophagy are altered causing failure to control normal mucosa repair and renewal

Use of recycled fillers in bituminous mixtures for road pavements

This paper reports the results of a laboratory investigation on the use of recycled fillers in bituminous mixtures for road pavements. The fillers were obtained by crushing and sieving (0.00-0.063 mm) Stabilized Bottom Ashes from municipal waste incinerators and Electric Arc Furnace Steel Slags. Moreover, a currently used calcareous filler was included in the research for comparative purposes. Two filler dosages were considered in the experiments. Laboratory tests aimed at investigating compaction properties, volumetric characteristics, and mechanical performance of the bituminous mixtures. The results suggest that both types of recycled filler are suitable to be used in bituminous mixtures, also demonstrating that in certain conditions the investigated fillers increase the performance of the corresponding mixtures in comparison to standard (calcareous) filler

A Development of a New Image Analysis Technique for Detecting the Flame Front Evolution in Spark Ignition Engine under Lean Condition

The aim of herein work is to develop an automatized algorithm for detecting, as objectively as possible, the flame front evolution of lean/ultra-lean mixtures ignited by low temperature plasma-based ignition systems. The low luminosity characterizing the latter conditions makes both kernel formation and combustion development difficult to detect accurately. Therefore, to estimate the igniter capability to efficiently ignite the mixture, ever more performing tools are required. The present work proposes a new image analysis technique, based on a dual-exposure fusion algorithm and on Convolutional Neural Networks (CNNs), to process low brightness images captured via high-speed camera on an optical engine. The performance of the proposed algorithm (PA) is compared to the one of a base reference (BR) algorithm used by the same research group for the imaging analysis. The comparison shows the capability of PA to quantify the flame radius of consecutive combustion cycles with lower dispersion if compared to BR and to correctly detect some events considered as misfires or anomalies by BR. Moreover, the proposed method shows greater capability to detect, in advance, the kernel formation with respect to BR, thus allowing a more detailed analysis of the performance of the igniters. A metric quantitative analysis is carried out, as well, to confirm the above-mentioned results. Therefore, PA results to be more suitable for analyzing ultra-lean combustions, heavily investigated to meet the increasingly stringent legislation on the internal combustion engines. Finally, the proposed algorithm allows us to automatically estimate the flame front evolution, regardless of the user’s interpretation of the phenomenon

Fishing out collective memory of migratory schools

Animals form groups for many reasons but there are costs and benefit associated with group formation. One of the benefits is collective memory. In groups on the move, social interactions play a crucial role in the cohesion and the ability to make consensus decisions. When migrating from spawning to feeding areas fish schools need to retain a collective memory of the destination site over thousand of kilometers and changes in group formation or individual preference can produce sudden changes in migration pathways. We propose a modelling framework, based on stochastic adaptive networks, that can reproduce this collective behaviour. We assume that three factors control group formation and school migration behaviour: the intensity of social interaction, the relative number of informed individuals and the preference that each individual has for the particular migration area. We treat these factors independently and relate the individuals' preferences to the experience and memory for certain migration sites. We demonstrate that removal of knowledgable individuals or alteration of individual preference can produce rapid changes in group formation and collective behavior. For example, intensive fishing targeting the migratory species and also their preferred prey can reduce both terms to a point at which migration to the destination sites is suddenly stopped. The conceptual approaches represented by our modelling framework may therefore be able to explain large-scale changes in fish migration and spatial distribution

The effects of fibers on the performance of bituminous mastics for road pavements

The experimental investigation herein described is aimed at understanding the effects of cellulose-based fibers on the mechanical properties of bituminous mastics for paving applications. Three bitumen (two of which modified with SBS polymers), a calcareous filler and four different types of fiber with varying content were used to prepare the investigated mastics. The filler to bitumen ratio was maintained constant. The laboratory investigations were focused on empirical tests (Needle Penetration and Ring and Ball – R&B – Temperature) and dynamic-mechanical tests, the latter performed in a wide range of temperatures. Results suggest that fibers improve the behavior of mastics for hot mix asphalts, particularly with respect to the prevention of rutting phenomena at high service temperatures

Myeloperoxidase expression in human colonic mucosa is related to systemic oxidative balance in healthy subjects

Objectives: To improve understanding of the preclinical stage of colonic inflammation by exploring the existence of a link between early inflammatory changes in the colonic mucosa and the systemic redox balance. Methods: Clinical characteristics, a fasting blood draw, and mucosal biopsies from the right, left, and sigmoid-rectum colonic tracts collected from 28 healthy individuals (14/14 males/females) who underwent colonoscopy. Myeloperoxidase (MPO) positive cells infiltrating colonic mucosa specimens were assessed by immunohistochemistry, and patients divided into high or low MPO expressing cells/optical field groups (MPOhighor MPOlow, respectively).The systemic oxidative balance has been studied through derived-Reactive Oxygen Metabolites (d-ROMs), Biological Antioxidant Potential (BAP), and Lipoperoxide-cholesterol Oxidizing (LP-CHOLOX) tests on serum. Results: MPOhighpatients demonstrated an increased systemic oxidative stress compared to MPOlowindividuals (P = 0.035), especially when MPO is referred to the left-sided colonic mucosa (P = 0.007). MPOlowsubjects in the sigmoid-rectum showed a significant higher antioxidant capacity in the serum (P < 0.02). Sex-specific differences in MPO expression (male and female: 4.6 \ub1 3.2 and 2.6 \ub1 1.5 MPO-positive cells/optical field, respectively, P = 0.044), and a decreasing gradient in MPO expression moving from the cecum to the rectum (ascendant, descendant, and sigmoid-rectum: 3.7 \ub1 2.8, 3.1 \ub1 1.7, and 1.4 \ub1 0.5, respectively, P = 0.012) were also found and discussed. Discussion: The study is the first demonstrating a connection between systemic redox balance and MPO expression in the colonic mucosa, according to the colonic tract and patient gender. Further research evaluating the MPO expression in the human colon and its relationship with pathological conditions could benefit from these results