Glucose-6-phosphate-dehydrogenase deficiency as a risk factor in proliferative disorder development

Glucose-6-phosphate dehydrogenase (G6PD) is an important site of metabolic control in the pentose phosphate pathway (PPP) which provides reducing power (NADPH) and pentose phosphates. The former is mainly involved in the detoxification of chemical reactive species; the latter in the regulation of cell proliferation. G6PD deficiency is the most common enzymopathy in the human population, characterized by decreased G6PD activity, mainly in red blood cells, but actually also in nucleated cells. This decreased activity is not due to enzyme synthesis impairment, but rather to reduced enzyme stability, which leads to a shortening of its half-life. Therefore, a major problem is to understand the underlying mechanisms linking G6PD deficiency to oxidative stress and cell proliferation. In order to address this issue, in the present study we utilized, as an experimental model, fibroblasts isolated from pterygium, an ocular proliferative lesion, from G6PD normal and deficient (PFs+ and PFs-, respectively) patients. Our choice was determined by the fact that pterygium is believed to be caused by chronic oxidative stress induced by UV exposure, and that pterygium fibroblasts resemble a tumorigenic phenotype. As controls we utilized fibroblasts isolated from conjunctiva from G6PD normal and deficient patients (NCFs+ and NCFs-, respectively) who had undergone cataract surgery. 
Growth rate analysis revealed that PFs grow faster than NCFs, but while NCFs- grow more slowly than NCFs+, PFs- and PFs+ grow at the same rate. This was associated with significantly lower G6PD activity in NCFs+ compared to NCFs-, while no significant differences in the G6PD activity of PFs+ and PFs- were noted. This result was supported by the finding that in PFs-, G6PD mRNA levels were significantly higher than in PFs+. Another interesting finding of this study was increased green autofluorescence in both NCFs- and PFs- compared to corresponding positive cells, indicative of pronounced oxidative stress in deficient cells. Finally, abnormal accumulation of neutral lipids, mainly cholesterol esters was observed both in PFs- and PFs+ compared to NCFs- and NCFs+. Though further studies are necessary for better understanding the exact mechanism which links G6PD to oxidative stress and cell proliferation, our data allow to speculate on the role of G6PD on tumorigenesis, and to consider G6PD-deficient subjects at major risk to develop common and dreaded proliferative disorders, such as atherosclerosis and cancer. 
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Prediction of late/early arrivals in container terminals - A qualitative approach

Vessel arrival uncertainty in ports has become a very common problem worldwide. Although ship operators have to notify the Estimated Time of Arrival (ETA) at predetermined time intervals, they frequently have to update the latest ETA due to unforeseen circumstances. This causes a series of inconveniences that often impact on the efficiency of terminal operations, especially in the daily planning scenario. Thus, for our study we adopted a machine learning approach in order to provide a qualitative estimate of the vessel delay/advance and to help mitigate the consequences of late/early arrivals in port. Using data on delays/advances at the individual vessel level, a comparative study between two transshipment container terminals is presented and the performance of three algorithmic models is evaluated. Results of the research indicate that when the distribution of the outcome is bimodal the performance of the discrete models is highly relevant for acquiring data characteristics. Therefore, the models are not flexible in representing data when the outcome distribution exhibits unimodal behavior. Moreover, graphical visualisation of the importance-plots made it possible to underline the most significant variables which might explain vessel arrival uncertainty at the two European ports

A Bus Allocation Model for Major Industrial Disasters

The presented research is part of a broader project DIEM-SSP—Disasters and Emergencies Management for Safety and Security in Industrial Plants –aiming at managing major industrial emergencies by considering both medical and engineering/logistics issues. When a disaster occurs, it is necessary to immediately provide relief plans. Many decisions must be made in very short time, which may have a relevant impact on the consequences of the disaster. For an efficient and smart exploitation of available resources, it is necessary to mitigate damages. From a logistics point of view, one of the major issues in the event of a major industrial disaster (fire, explosion or toxic gas dispersion) is to evacuate the external population that can be affected by the disaster to specific evacuation areas. The purpose of the research is to determine the optimal number and allocation of vehicles (buses) which must be involved in order to evacuate the population located in a defined risk area around the emergency site and the optimal location for evacuation areas. For that reasons, a dynamic version of the bus allocation problem is proposed using a mixed-integer programming model

Comparison of the imaging performances for recently developed monolithic scintillators: CRY018 and CRY019 for dual isotope gamma ray imaging applications

The growing interest for new scintillation crystals with outstanding imaging performances (i.e. resolution and efficiency) has suggested the study of recently discovered scintillators named CRY018 and CRY019. The crystals under investigation are monolithic and have shown enhanced characteristics both for gamma ray spectrometry and for Nuclear Medicine imaging applications such as the dual isotope imaging. Moreover, the non-hygroscopic nature and the absence of afterglow make these scintillators even more attractive for the potential improvement in a wide range of applications. These scintillation crystals show a high energy resolution in the energy range involved in Nuclear Medicine, allowing the discrimination between very close energy values. Moreover, in order to prove their suitability of being powerful imaging systems, the imaging performances like the position linearity and the intrinsic spatial resolution have been evaluated obtaining satisfactory results thanks to the implementation of an optimized algorithm for the images reconstruction. © 2017 IOP Publishing Ltd and Sissa Medialab srl

acat1 cav 1 and prp expression in brains and skin fibroblasts from sarda breed sheep with scrapie resistant and scrapie susceptible genotype

Scrapie is an infective ovine neurodegenerative disease; the only identified component of the infectious agent being an aberrant isoform (PrPSc) of the cellular prion protein (PrPC). So far, no means for ante-mortem diagnosis are available for Scrapie as well as for any other mammal Transmissible Spongiform Encephalopaties. We recently found a strong relationship between cell susceptibility to scrapie-infection and intracellular cholesterol homeostasis alterations. In brain tissues as well as in ex vivo cultures of skin fibroblasts and PBMCs from healthy and scrapie-affected sheep carrying a scrapie-susceptible (ARQ/ARQ) genotype, the levels of cholesterol esters were consistently higher than in tissues and cultures derived from animals with a scrapie-resistant (ARR/ARR) genotype. Moreover, both uninfected and scrapie-affected ARQ/ARQ sheep showed abnormally low levels of high density lipoprotein-cholesterol (HDL-C) in their plasma, as compared to ARR/ARR animals. We now show that intracellular accumulation of cholesterol esters in fibroblasts derived from scrapie-susceptible sheep was accompanied by parallel alterations in the expression level of genes and gene products (ACAT1 and Cav-1) that are involved in the pathways leading to intracellular cholesterol esterification and trafficking. Comparative analysis of PrPc mRNA, showed an higher expression level in cells from animals carrying susceptible genotype, with or without Scrapie. Preliminary experiments also revealed the presence of PK-resistant PrP isoforms in the latter cultures. The data reported in the present paper suggest that accumulation of cholesterol esters in peripheral cells, together with the altered expression of some proteins implicated in intracellular cholesterol homeostasis, might serve to identify a distinctive lipid metabolic profile associated with increased susceptibility to develop prion disease following infection

Changes in cholesterol metabolism-related gene expression in peripheral blood mononuclear cells from Alzheimer patients

<p>Abstract</p> <p>Background</p> <p>Cholesterol homeostasis dysfunction has been reported to have role in the pathogenesis of Alzheimer disease (AD). Therefore, changes in cholesterol metabolism in blood components may help to develop new potential AD biomarkers. In this study changes in cholesterol metabolism-related gene expression genes were evaluated in peripheral blood mononuclear cells (PBMCs) from AD subjects, their first degree relatives (FDR) and two groups of age matched controls (C1 > 80 years, C2 < 60 years). The expression of three genes related to APP processing was also determined.</p> <p>Results</p> <p>Results showed significantly different behavior (P = 0.000) in the expression of all analyzed genes among the 4 groups. An inverse correlation emerged between the age of controls and the propensity of their PBMCs to express selected genes. Moreover, when gene expression was evaluated in PBMCs from AD patients and compared with that of PBMCs from healthy subjects of the same age, LDL-R and APP mRNAs were most abundant in AD as compared C1 whereas SREBP-2 and particularly nCEH were present at much lower mRNA levels in AD-PBMCs. This study describes for the first time a differential expression profile of cholesterol and APP related genes in PBMCs from AD patients and their FDR.</p> <p>Conclusions</p> <p>We suggest that the expressions of cholesterol homeostasis and APP processing related genes in PBMC could be proposed as possible biomarkers to evaluate AD risk. In addition, gene expression in PBMC could be also used for diagnosis and development of therapeutic strategies as well as for personalized prediction in clinical outcome of AD.</p

Il microcarcinoma papillare della tiroide. Implicazioni cliniche e strategia terapeutica

Gli Autori riportano la propria esperienza sulle implicazioni cli - niche e le strategie terapeutiche del microcarcinoma papillare della tiroide, valutando 412 pazienti sottoposti ad intervento chirurgico per patologia tiroidea. Essi sottolineano l’attuale problematica della diagnosi “incidentale” postoperatoria, la relativa strategia terapeutica adiuvante, il frequente riscontro di una patologia tiroidea benigna associata, fattori che giustificano, oltre le note motivazioni oncologi - che, la scelta della tiroidectomia totale di principio

Nutrient intakes in an Italian population of infants during the complementary feeding period

Objective: To describe the nutrient intakes of an Italian cohort of infants at 6, 9 and 12 months of age. Design: Dietary data were collected using a food diary at three follow-ups (6, 9 and 12 months of age of infants). The infants' dietary data were used to estimate nutrient intakes using the Italian food composition database integrated with data from nutritional labels and the literature. The mean and standard deviation, median and interquartile range, minimum and maximum, and 5th, 25th, 75th and 95th percentiles were calculated for the daily intake of twenty-eight nutrients, with sex differences evaluated using parametric/non-parametric statistical methods. Setting: A prospective population-based birth cohort.SubjectInfants (n 400) living in the urban area of Trieste (Italy). Results: The sex distribution was fairly balanced at each follow-up. The mean daily intakes of energy and the other twenty-seven nutrients considered were greater in males at all follow-ups. In particular, a significant statistical difference was observed in higher male consumption of cholesterol at 9 months and in energy and carbohydrate intakes at 12 months (P < 0·05). The mean daily intake of proteins was greater than that recommended by the Italian Dietary Reference Values at all follow-ups. Conclusions: These preliminary results provide a useful basis for understanding the nutrient intake patterns of infants in this area of Italy during the first year of life

Altered cholesterol ester cycle in ex vivo skin fibroblasts from Alzheimer patients

Recent studies in both animal and cell models of Alzheimer's disease (AD) indicated that sub-cellular cholesterol distribution seems to regulate amyloid-beta (A[beta]) generation in the brain. In particular, cholesterol-esters (CE), rather than total cholesterol levels, appear directly correlated with A[beta] production. Here we observed that, similarly to brain cells, skin fibroblasts obtained from AD patients produce and accumulate more CE than skin fibroblasts from age-matched healthy controls do. AD fibroblasts also exhibited a 2 fold increase in the expression of ACAT1, in addition to lower levels of SREBP2, nCEH, Caveolin-1 and ABCA1 mRNA levels, all of which are involved in the CE cycle. HMGCoA-reductase and LDL-receptor mRNAs levels did not show statistically significant changes in AD, compared to non-AD, cells. Furthermore, although APP mRNA did not significantly vary, neprilysin (NEP), the most important enzyme in the proteolysis of A[beta], was expressed at very low levels in skin fibroblasts of sporadic AD patients. Our results contribute to the concept that AD may be the consequence of a basic and systemic defect in the CE cycle. Moreover, our results identify new possible targets for the diagnosis, prevention, and cure or, at least, amelioration of the symptoms of AD