A plasma metabolomic signature discloses human breast cancer

Purpose: Metabolomics is the comprehensive global study of metabolites in biological samples. In this retrospective pilot study we explored whether serum metabolomic profile can discriminate the presence of human breast cancer irrespective of the cancer subtype. Methods: Plasma samples were analyzed from healthy women (n = 20) and patients with breast cancer after diagnosis (n = 91) using a liquid chromatographymass spectrometry platform. Multivariate statistics and a Random Forest (RF) classifier were used to create a metabolomics panel for the diagnosis of human breast cancer. Results: Metabolomics correctly distinguished between breast cancer patients and healthy control subjects. In the RF supervised class prediction analysis comparing breast cancer and healthy control groups, RF accurately classified 100% both samples of the breast cancer patients and healthy controls. So, the class error for both group in and the out-of-bag error were 0. We also found 1269 metabolites with different concentration in plasma from healthy controls and cancer patients; and basing on exact mass, retention time and isotopic distribution we identified 35 metabolites. These metabolites mostly support cell growth by providing energy and building stones for the synthesis of essential biomolecules, and function as signal transduction molecules. The collective results of RF, significance testing, and false discovery rate analysis identified several metabolites that were strongly associated with breast cancer. Conclusions: In breast cancer a metabolomics signature of cancer exists and can be detected in patient plasma irrespectively of the breast cancer type.Spanish Ministry of Economy and Competitiveness, Institute Carlos III (FIS grant) PI14/00328Generalitat de Catalunya 2014SGR168FEDER funds from the European Union ('Una manera de hacer Europa'

Indagación sobre el proyecto piloto DIME

Dispositivos Móviles en Educación (DIME) es un proyecto que tiene como principal objetivo indagar sobre el impacto de una de las tendencias mundiales más reconocidas actualmente en el ámbito de la Educación y las TIC: el aprendizaje móvil. A partir de este proyecto, se llevaron a cabo propuestas orientadas al desarrollo profesional de los docentes y al Proyecto Educativo Institucional, con eje en la colaboración, cooperación y comunicación entre las instituciones educativas participantes. El proyecto cumplió su cometido a modo de “laboratorio de prueba” y la experiencia resultó enriquecedora para quienes participaron en él, fundamentalmente para los estudiantes, sus intereses y expectativas. Entre otras cosas, permitió comprobar que es posible aprender y enseñar aprovechando la potencialidad de los dispositivos móviles.Fil: Tortosa, José Luis. Universidad Católica de Córdoba. Facultad de Educación; Argentin

Hypoxia-Inducible Factor-1 Alpha Expression Is Predictive of Pathological Complete Response in Patients with Breast Cancer Receiving Neoadjuvant Chemotherapy

Supplementary Materials The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/cancers14215393/s1, Table S1: Relation between HIF-1α expression and pAKT and pMAPK; Table S2: Logistic regression model as a predictive factor of response to treatment.To demonstrate the value of hypoxia-inducible factor-1α (HIF-1α) in predicting response in patients with breast cancer receiving standard neoadjuvant chemotherapy (NAC). Methods: Ninety-five women enrolled in two prospective studies underwent biopsies for the histopathological diagnosis of breast carcinoma before receiving NAC, based on anthracyclines and taxanes. For expression of HIF-1α, EGFR, pAKT and pMAPK, tumor samples were analyzed by immunohistochemistry in tissues microarrays. Standard statistical methods (Pearson chi-square test, Fisher exact test, Kruskal–Wallis test, Mann–Whitney test and Kaplan–Meier method) were used to study the association of HIF-1α with tumor response, survival and other clinicopathologic variables/biomarkers. Results: HIF-1α expression was positive in 35 (39.7%) cases and was significantly associated to complete pathological response (pCR) (p = 0.014). HIF-1α expression was correlated positively with tumor grade (p = 0.015) and Ki-67 expression (p = 0.001) and negativity with progesterone receptors (PR) (p = 0.04) and luminal A phenotype expression (p = 0.005). No correlation was found between HIF-1α expression and EGFR, pAKT and pMAPK. In terms of survival, HIF-1α expression was associated with a significantly shorter disease-free survival (p = 0.013), being identified as an independent prognostic factor in multivariate analysis. Conclusions: Overexpression of HIF-1α is a predictor of pCR and shorter DFS; it would be valuable to confirm these results in prospective studies

Differences reported in the lifespan and aging of male Wistar rats maintained on diets containing fat with different fatty acid profiles (virgin olive, sunflower or fish oils) are not reflected by histopathological lesions found at death in central nervous and endocrine systems

The present study was designed to examine if dietary fat sources that have shown differences in lifespan and if some aging-related aspects can modulate the range of histopathologic changes in central nervous and endocrine systems that occur during the lifespan of Wistar rats. Moreover, it was attempted to gain insight into the relationship between longevity and the development of the different pathological changes, as well as possible interaction with diet. In order to achieve this, male Wistar rats were randomly assigned to three experimental groups fed semisynthetic and isoenergetic diets from weaning until death with different dietary fat sources, namely virgin olive, sunflower, or fish oil. An individual follow-up until death of each animal was performed. Incidence, severity, and burden of specific or group (i.e., neoplastic or non-neoplastic proliferative and nonproliferative) of lesions was calculated along with individual’s disease and individual organ lesion burden. Most of the histopathological lesions found have been described in previous studies. Neoplasms, and in particular pituitary adenomas followed by brain tumors, were the most prevalent lesions found in the rats and the main cause of death involving both systems. Incidence of brain lesions was associated with age-at-death. Assayed dietary fats did not present differential effects on pathological changes occurring in endocrine and central nervous systems throughout rat lifespan.Spanish Government AGL2008-01057Government of Andalusia AGR83

A Diet Rich in Saturated Fat and Cholesterol Aggravates the Effect of Bacterial Lipopolysaccharide on Alveolar Bone Loss in a Rabbit Model of Periodontal Disease

María D. Navarro-Hortal is a FPU fellow from the Spanish Ministry of Educación y Formación Profesional. The research group was partially supported by the Visiting Scholar Program from the University of Granada. The authors acknowledge Nutraceutical Translations for English language editing of this manuscript.Increasing evidence connects periodontitis with a variety of systemic diseases, including metabolic syndrome, atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). The proposal of this study was to evaluate the role of diets rich in saturated fat and cholesterol in some aspects of periodontal diseases in a lipopolysaccharide (LPS)-induced model of periodontal disease in rabbits and to assess the influence of a periodontal intervention on hyperlipidemia, atherosclerosis, and NAFLD progression to non-alcoholic steatohepatitis. Male rabbits were maintained on a commercial standard diet or a diet rich in saturated fat (3% lard w/w) and cholesterol (1.3% w/w) (HFD) for 40 days. Half of the rabbits on each diet were treated 2 days per week with intragingival injections of LPS from Porphyromonas gingivalis. Morphometric analyses revealed that LPS induced higher alveolar bone loss (ABL) around the first premolar in animals receiving standard diets, which was exacerbated by the HFD diet. A higher score of acinar inflammation in the liver and higher blood levels of triglycerides and phospholipids were found in HFD-fed rabbits receiving LPS. These results suggest that certain dietary habits can exacerbate some aspects of periodontitis and that bad periodontal health can contribute to dyslipidemia and promote NAFLD progression, but only under certain conditions.Ministry of Education, Culture and Sport (Spain)Spanish GovernmentTraslados Temporales FPU (University of Kings College of London

Rail corrugation growth accounting for the flexibility and rotation of the wheel set and the non-Hertzian and non-steady-state effects at contact patch

[EN] In this work, a simulation tool is developed to analyse the growth of rail corrugation consisting of several models connected in a feedback loop in order to account for both the short-term dynamic vehicle track interaction and the long-term damage. The time-domain vehicle track interaction model comprises a flexible rotating wheel set model, a cyclic track model based on a substructuring technique and a non-Hertzian and non-steady-state three-dimensional wheel rail contact model, based on the variational theory by Kalker. Wear calculation is performed with Archard s wear model by using the contact parameters obtained with the non-Hertzian and non-steady-state three-dimensional contact model. The aim of this paper is to analyse the influence of the excitation of two coinciding resonances of the flexible rotating wheel set on the rail corrugation growth in the frequency range from 20 to 1500 Hz, when contact conditions similar to those that can arise while a wheel set is negotiating a gentle curve are simulated. Numerical results show that rail corrugation grows only on the low rail for two cases in which two different modes of the rotating wheel set coincide in frequency. In the first case, identified by using the Campbell diagram, the excitation of both the backward wheel mode and the forward third bending mode of the wheel set model (B-F modes) promotes the growth of rail corrugation with a wavelength of 110mm for a vehicle velocity of 142 km/h. In the second case, the excitation of both the backward wheel mode and the backward third bending mode (B-B modes) gives rise to rail corrugation growth at a wavelength of 156 mm when the vehicle velocity is 198 km/h.The authors acknowledge the financial contribution by the Spanish Ministry of Economy and Competitiveness through the project TRA2010-15669.Vila Tortosa, MP.; Baeza González, LM.; Martínez Casas, J.; Carballeira, J. (2014). Rail corrugation growth accounting for the flexibility and rotation of the wheel set and the non-Hertzian and non-steady-state effects at contact patch. Vehicle System Dynamics. 52:92-108. https://doi.org/10.1080/00423114.2014.881513S9210852Grassie, S. L., & Kalousek, J. (1993). Rail Corrugation: Characteristics, Causes and Treatments. Proceedings of the Institution of Mechanical Engineers, Part F: Journal of Rail and Rapid Transit, 207(1), 57-68. doi:10.1243/pime_proc_1993_207_227_02Hempelmann, K., Hiss, F., Knothe, K., & Ripke, B. (1991). The formation of wear patterns on rail tread. Wear, 144(1-2), 179-195. doi:10.1016/0043-1648(91)90014-lHempelmann, K., & Knothe, K. (1996). An extended linear model for the prediction of short pitch corrugation. Wear, 191(1-2), 161-169. doi:10.1016/0043-1648(95)06747-7GRASSIE, S. L., & ELKINS, J. A. (1998). RAIL CORRUGATION ON NORTH AMERICAN TRANSIT SYSTEMS. Vehicle System Dynamics, 29(sup1), 5-17. doi:10.1080/00423119808969548Egana, J. I., Vinolas, J., & Seco, M. (2006). Investigation of the influence of rail pad stiffness on rail corrugation on a transit system. Wear, 261(2), 216-224. doi:10.1016/j.wear.2005.10.004Igeland, A. (1996). Railhead Corrugation Growth Explained by Dynamic Interaction between Track and Bogie Wheelsets. Proceedings of the Institution of Mechanical Engineers, Part F: Journal of Rail and Rapid Transit, 210(1), 11-20. doi:10.1243/pime_proc_1996_210_322_02Gómez, I., & Vadillo, E. G. (2003). A linear model to explain short pitch corrugation on rails. Wear, 255(7-12), 1127-1142. doi:10.1016/s0043-1648(03)00282-5Collette, C., Vanhonacker, P., Bastaits, R., & Levy, D. (2008). Comparison between time and frequency studies of a corrugated curve of RER Paris network. Wear, 265(9-10), 1249-1258. doi:10.1016/j.wear.2008.01.030Daniel, W. J. T., Horwood, R. J., Meehan, P. A., & Wheatley, N. (2008). Analysis of rail corrugation in cornering. Wear, 265(9-10), 1183-1192. doi:10.1016/j.wear.2008.02.030Fayos, J., Baeza, L., Denia, F. D., & Tarancón, J. E. (2007). An Eulerian coordinate-based method for analysing the structural vibrations of a solid of revolution rotating about its main axis. Journal of Sound and Vibration, 306(3-5), 618-635. doi:10.1016/j.jsv.2007.05.051Baeza, L., & Ouyang, H. (2011). A railway track dynamics model based on modal substructuring and a cyclic boundary condition. Journal of Sound and Vibration, 330(1), 75-86. doi:10.1016/j.jsv.2010.07.023Kalker, J. J. (1990). Three-Dimensional Elastic Bodies in Rolling Contact. Solid Mechanics and Its Applications. doi:10.1007/978-94-015-7889-9Xie, G., & Iwnicki, S. D. (2008). Simulation of wear on a rough rail using a time-domain wheel–track interaction model. Wear, 265(11-12), 1572-1583. doi:10.1016/j.wear.2008.03.016Igeland, A., & Ilias, H. (1997). Rail head corrugation growth predictions based on non-linear high frequency vehicle/track interaction. Wear, 213(1-2), 90-97. doi:10.1016/s0043-1648(97)00172-5Vila, P., Fayos, J., & Baeza, L. (2011). Simulation of the evolution of rail corrugation using a rotating flexible wheelset model. Vehicle System Dynamics, 49(11), 1749-1769. doi:10.1080/00423114.2011.552619Popp, K., Kruse, H., & Kaiser, I. (1999). Vehicle-Track Dynamics in the Mid-Frequency Range. Vehicle System Dynamics, 31(5-6), 423-464. doi:10.1076/vesd.31.5.423.8363Johnson, K. L. (1985). Contact Mechanics. doi:10.1017/cbo9781139171731Hiensch, M., Nielsen, J. C. O., & Verheijen, E. (2002). Rail corrugation in The Netherlands—measurements and simulations. Wear, 253(1-2), 140-149. doi:10.1016/s0043-1648(02)00093-5Jin, X., Xiao, X., Wen, Z., Guo, J., & Zhu, M. (2009). An investigation into the effect of train curving on wear and contact stresses of wheel and rail. Tribology International, 42(3), 475-490. doi:10.1016/j.triboint.2008.08.004Ilias, H., & Müller, S. (1994). A discrete-continuous track-model for wheelsets rolling over short wavelength sinusoidal rail irregularities. Vehicle System Dynamics, 23(sup1), 221-233. doi:10.1080/0042311930896951

Hydroxytyrosol Supplementation Modifies Plasma Levels of Tissue Inhibitor of Metallopeptidase 1 in Women with Breast Cancer

The etiology of breast cancer can be very different. Most antineoplastic drugs are not selective against tumor cells and also affect normal cells, leading to a wide variety of adverse reactions such as the production of free radicals by altering the redox state of the organisms. Therefore, the objective of this study was to elucidate if hydroxytyrosol (HT) (an antioxidant present in extra virgin olive oil) has a chemomodulatory effect when combined with the chemotherapeutic drugs epirubicin and cyclophosphamide followed by taxanes in breast cancer patients. Changes in plasma levels of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) throughout the chemotherapy treatment were studied. Both molecules are involved in cell proliferation, apoptosis, neoangiogenesis, and metastasis in breast cancer patients. Women with breast cancer were divided into two groups: a group of patients receiving a dietary supplement of HT and a control group of patients receiving placebo. The results showed that the plasma levels of TIMP-1 in the group of patients receiving HT were significantly lower than those levels found in the control group after the epirubicin-cyclophosphamide chemotherapy.This research was funded by Junta de Andalucía, Spain, Servicio Andaluz de Salud: Subvenciones para la financiacion de la Investigación, Desarrollo, e Innovación Biomédica en Ciencias de la Salud en Biomedicina, Grant number PI-0695-2012

Age-Related Loss in Bone Mineral Density of Rats Fed Lifelong on a Fish Oil-Based Diet Is Avoided by Coenzyme Q10 Addition

During aging, bone mass declines increasing osteoporosis and fracture risks. Oxidative stress has been related to this bone loss, making dietary compounds with antioxidant properties a promising weapon. Male Wistar rats were maintained for 6 or 24 months on diets with fish oil as unique fat source, supplemented or not with coenzyme Q10 (CoQ10), to evaluate the potential of adding this molecule to the n-3 polyunsaturated fatty acid (n-3 PUFA)-based diet for bone mineral density (BMD) preservation. BMD was evaluated in the femur. Serum osteocalcin, osteopontin, receptor activator of nuclear factor-κB ligand, ostroprotegerin, parathyroid hormone, urinary F2-isoprostanes, and lymphocytes DNA strand breaks were also measured. BMD was lower in aged rats fed a diet without CoQ10 respect than their younger counterparts, whereas older animals receiving CoQ10 showed the highest BMD. F2-isoprostanes and DNA strand breaks showed that oxidative stress was higher during aging. Supplementation with CoQ10 prevented oxidative damage to lipid and DNA, in young and old animals, respectively. Reduced oxidative stress associated to CoQ10 supplementation of this n-3 PUFA-rich diet might explain the higher BMD found in aged rats in this group of animals.This work was supported by the Spanish Ministry of Education and Science (AGL2008-01057) and the Autonomous Government of Andalusia (AGR832). A.V.-L. is recipient of a grant for doctors from University of Granada’s own plan

Heart Histopathology and Mitochondrial Ultrastructure in Aged Rats Fed for 24 Months on Different Unsaturated Fats (Virgin Olive Oil, Sunflower Oil or Fish Oil) and Affected by Different Longevity

Diet plays a decisive role in heart physiology, with lipids having especial importance in pathology prevention and development. This study aimed to investigate how dietary lipids varying in lipid profile (virgin olive oil, sunflower oil or fish oil) affected the heart of rats during aging. Heart histopathology, mitochondrial morphometry, and oxidative status were assessed. Typical histopathological features associated with aging, such as valvular lesions, endomyocardical hyperplasia, or papillary muscle calcification, were found at a low extent in all the experimental groups. The most relevant finding was that inflammation registered by fish oil group was lower compared to the other treatments. At the ultrastructural level, heart mitochondrial area, perimeter, and aspect ratio were higher in fish oil-fed rats than in those fed on sunflower oil. Concerning oxidative stress markers, there were differences only in coenzyme Q levels and catalase activity, lower in sunflower oil-fed animals compared with those fed on fish oil. In summary, dietary intake for a long period on dietary fats with different fatty acids profile led to differences in some aspects associated with the aging process at the heart. Fish oil seems to be the fat most protective of heart during aging.This research was supported by R + D grants from the Spanish Ministry of Education and Science [AGL2008-01057] and the Government of Andalusia [AGR832]

Accessibility in video games: a systematic review

Video games are software products with several purposes that are growing in strength and weight in society. However, thereis one noticeable problem about them; in most cases, their developers most often do not take into consideration peoplewith disabilities when they are creating video game applications. People with disabilities are thus partially or completelyexcluded from their use. Prior to any additional work, it is required to have an updated state of the art about this topic. Thispaper shows the results of a systematic literature review conducted to define the current status of video games accessibility.The type of review is broader than usual, so it is a systematic mapping study (a specific class of systematic review). Besideselaborating the state of the art (qualitative information), we identified and analyzed related works (45 relevant studies) toprovide quantitative information of the performed search (including graphs and tables), such as the number of articles foundby phases, their sources, their research type, the research questions answered, the kind of disability addressed, and the typeand year of publications. None of the studied initiatives can guarantee universally accessible video game applications. Ourproposal is to create an integral software engineering methodology that considers accessibility guidelines, techniques, strategies,human factors, etc. in the video game software development process.European Commisio