Orthopedic surgery increases atherosclerotic lesions and necrotic core area in ApoE-/- mice

Background and aims Observational studies show a peak incidence of cardiovascular events after major surgery. For example, the risk of myocardial infarction increases 25-fold early after hip replacement. The acuteness of this increased risk suggests abrupt enhancement in plaque vulnerability, which may be related to intra-plaque inflammation, thinner fibrous cap and/or necrotic core expansion. We hypothesized that acute systemic inflammation following major orthopedic surgery induces such changes. Methods ApoE−/− mice were fed a western diet for 10 weeks. Thereafter, half the mice underwent mid-shaft femur osteotomy followed by realignment with an intramedullary K-wire, to mimic major orthopedic surgery. Mice were sacrificed 5 or 15 days post-surgery (n = 22) or post-saline injection (n = 13). Serum amyloid A (SAA) was measured as a marker of systemic inflammation. Paraffin embedded slides of the aortic root were stained to measure total plaque area and to quantify fibrosis, calcification, necrotic core, and inflammatory cells. Results Surgery mice showed a pronounced elevation of serum amyloid A (SAA) and developed increased plaque and necrotic core area already at 5 days, which reached significance at 15 days (p = 0.019; p = 0.004 for plaque and necrotic core, respectively). Macrophage and lymphocyte density significantly decreased in the surgery group compared to the control group at 15 days (p = 0.037; p = 0.024, respectively). The density of neutrophils and mast cells remained unchanged. Conclusions Major orthopedic surgery in ApoE−/− mice triggers a systemic inflammatory response. Atherosclerotic plaque area is enlarged after surgery mainly due to an increase of the necrotic core. The role of intra-plaque inflammation in this response to surgical injury remains to be fully elucidated. © 2016 Elsevier Ireland Lt

Non-reflecting boundary conditions and tensile instability in smooth particle hydrodynamics

This thesis aimed at the understanding and further development of smoothed particle hydrodynamics (SPH). The first part described the implementations of non-reflecting boundary conditions for elastic- waves in SPH. The second part contains a stability analysis of the semi-discrete SPH equations and a new method for stabilising basic SPH in tension

Current State of Conservation Knowledge on Threatened Amphibian Species in Peru

This study documents the current state of conservation knowledge on threatened amphibian species in Peru. Following the International Union for the Conservation of Nature (IUCN) classification system, we considered species in the following categories: Critically Endangered, Endangered, Vulnerable, and Near Threatened. Even though only the first three categories are regarded as threatened by IUCN, we included the fourth category to make comparisons with the list of threatened species issued by the Peruvian government. We used the Global Amphibian Assessment\u27s database and the list issued in Peru for this comparison. We conducted separate field surveys in 17 regions of Peru to evaluate the presence/absence of threatened amphibian species and species that are potentially threatened. We also used the Declining Amphibian Database-DAPTF, to compare our results with previous assessments on population declines, and the World Wildlife Fund\u27s Wildfinder database, to determine in which Neotropical ecoregion each species occurs. We compiled data on 83 species, 44 of which are recognized as threatened by the IUCN and/or the Peruvian government. The remaining 39 species should be re-assessed as they face various threats. A re-evaluation of current estimates is needed as only 8% of all species recorded in Peru are recognized as threatened by the government, whereas the global estimate of threatened species is about 32%. In addition to using IUCN criteria, this re-assessment should follow national guidelines standardized in Peru and be in accordance with the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). Because the habitat of almost 40% of threatened species reported herein still remains unprotected, and data on chytridiomycosis and other threats are lacking for most taxa, it is crucial to develop strategies for habitat conservation and research on disease dynamics in natural populations

Contributions of upper gut hormones and motility to the energy intake-suppressant effects of intraduodenal nutrients in healthy, lean men - a pooled-data analysis

Accepted: 8 August 2016We have previously identified pyloric pressures and plasma cholecystokinin (CCK) concentrations as independent determinants of energy intake following administration of intraduodenal lipid and intravenous CCK. We evaluated in healthy men whether these parameters also determine energy intake in response to intraduodenal protein, and whether, across the nutrients, any predominant gastrointestinal (GI) factors exist, or many factors make small contributions. Data from nine published studies, in which antropyloroduodenal pressures, GI hormones, and GI /appetite perceptions were measured during intraduodenal lipid or protein infusions, were pooled. In all studies energy intake was quantified immediately after the infusions. Specific variables for inclusion in a mixed-effects multivariable model for determination of independent predictors of energy intake were chosen following assessment for collinearity, and within-subject correlations between energy intake and these variables were determined using bivariate analyses adjusted for repeated measures. In models based on all studies, or lipid studies, there were significant effects for amplitude of antral pressure waves, premeal glucagon-like peptide-1 (GLP-1) and time-to-peak GLP-1 concentrations, GLP-1 AUC and bloating scores (P < 0.05), and trends for basal pyloric pressure (BPP), amplitude of duodenal pressure waves, peak CCK concentrations, and hunger and nausea scores (0.05 < P ≤ 0.094), to be independent determinants of subsequent energy intake. In the model including the protein studies, only BPP was identified as an independent determinant of energy intake (P < 0.05). No single parameter was identified across all models, and effects of the variables identified were relatively small. Taken together, while GI mechanisms contribute to the regulation of acute energy intake by lipid and protein, their contribution to the latter is much less. Moreover, the effects are likely to reflect small, cumulative contributions from a range of interrelated factors.Gudrun Schober, Kylie Lange, Robert E. Steinert, Amy T. Hutchison, Natalie D. Luscombe-Marsh, Maria F. Landrock, Michael Horowitz, Radhika V. Seimon and Christine Feinle-Bisse

Automatic Detection of Modality with ITGETARUNS

In this paper we present a system for modality detection which is then used for Subjectivity and Factuality evaluation. The system has been tested lately on a task for Subjectivity and Irony detection in Italian tweets , where the performance was 10th and 4th, respectively, over 27 participants overall. We will focus our paper on an internal evaluation where we considered three national newspapers Il Corriere, Repubblica, Libero. This task was prompted by a project on the evaluation of press stylistic features in political discourse. The project used newspaper articles from the same sources over a period of three months, thus including latest political 2013 governmental crisis. We intended to produce a similar experiment and evaluate results in comparison with previous 2011 crisis. In this evaluation, we focused on Subjectivity, Polarity and Factuality which include Modality evaluation. Final graphs at the end of the paper will show results confirming our previous findings about differences in style, with Il Corriere emerging as the most atypical

IL-17A promotes intracellular growth of Mycobacterium by inhibiting apoptosis of infected macrophages

The fate of infected macrophages is a critical aspect of immunity to mycobacteria. By depriving the pathogen of its intracellular niche, apoptotic death of the infected macrophage has been shown to be an important mechanism to control bacterial growth. Here, we show that IL-17 inhibits apoptosis of Mycobacterium bovis BCG- or Mycobacterium tuberculosis-infected macrophages thus hampering their ability to control bacterial growth. Mechanistically, we show that IL-17 inhibits p53, and impacts on the intrinsic apoptotic pathway, by increasing the Bcl2 and decreasing Bax expression, decreasing cytochrome c release from the mitochondria, and inhibiting caspase-3 activation. The same effect of IL-17 was observed in infected macrophages upon blockade of p53 nuclear translocation. These results reveal a previously unappreciated role for the IL-17/p53 axis in the regulation of mycobacteria-induced apoptosis and can have important implications in a broad spectrum of diseases where apoptosis of the infected cell is an important host defense mechanism.Fundação para a Ciência e Tecnologia, Portugal. Project grants: PTDC/SAU-MII/101977/2008 (to AGC), PTDC/BIA-BCM/102776/2008 (to MS) and HMSP-ICT/0024/2010 (to RA) and co-funded by Programa Operacional Regional do Norte (ON.2 – O Novo Norte), Quadro de Referência Estratégico Nacional (QREN), through the Fundo Europeu de Desenvolvimento Regional (FEDER). Personal Grants: SFRH/BPD/33036/2006 to AC; SFRH/BD/33573/200

Integrating Traditional and Agile Project Management Approaches: An Exploration into Hybrid Approaches

The need for flexibility contributes to rising use of agile project management approaches. Despite the aspiration to become agile, in practice, most organizations end up using hybrid approaches, a mix of traditional and agile project management. We conduct a qualitative exploratory analysis into the visual effects (VFX) industry, an exemplary case representative of a hybrid, non-software creative development environment. We identified an extensive set of aspects relevant to hybrid project management from existing literature. We then evaluated the presence of these aspects in the VFX industry. The findings suggest 36 aspects relevant in the context of hybrid project management, of which six emerged through our analysis. The presence of eight aspects remained inconclusive, opening future research possibilities. Our findings help project managers and researchers to better understand which project management aspects enable and inhibit organizations when moving from a traditional project management approach towards a more agile approach

Focused screening of a panel of cancer‐related genetic polymorphisms reveals new susceptibility loci for pediatric acute lymphoblastic leukemia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107514/1/pbc25011-sm-0001-SuppData-S1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/107514/2/pbc25011.pd

Oral and small intestinal sensitivity to fats in lean and obese humans : implications for energy intake regulation in obesity.

The research presented in this thesis focuses on the complex and interrelated oral and gastrointestinal mechanisms involved in the regulation of appetite and energy intake in lean and obese individuals. The three broad areas of research that have been investigated in the thesis include: i) the gastrointestinal motor and hormonal functions involved in the regulation of energy intake in healthy individuals; ii) the effects of oral and intraduodenal nutrients on gastrointestinal motility and hormone release, appetite and energy intake in obese compared with lean individuals; and iii) the effects of acute and prolonged energy restriction on gastrointestinal function, appetite and energy intake. Following ingestion of a meal, the interaction of nutrients with receptors in the small intestinal lumen modulates gastro-pyloroduodenal motility, stimulates the release of gastrointestinal hormones, and suppresses appetite and energy intake. It appears that modulation of gastrointestinal functions, that is, gastrointestinal motility and hormone release/suppression, mediate the regulation of appetite and acute energy intake in humans, at least in part. Changes in motility and hormone secretion occur concurrently with changes in appetite; however, there is little information regarding which, if any, of these factors are independent determinants of energy intake. In the study presented in Chapter 5, we determined independent predictors of energy intake and identified specific changes in gastrointestinal motor and hormone functions (i.e. stimulation of pyloric pressures and plasma cholecystokinin) that are associated with the suppression of acute energy intake in healthy lean males. The incidence of obesity is rapidly increasing and, currently, the therapies used for the prevention and management of obesity have limited long-term benefits. In addition, the available therapies have largely ignored the pivotal role of the gastrointestinal tract in the regulation of appetite. There is evidence that gastrointestinal function in obesity is modified, which may be the result of the eating habits of obese individuals and, in turn, may also contribute to the maintenance of obesity by causing insufficient suppression of energy intake. However, much of the literature relating to gastrointestinal function in the obese is inconclusive and controversial. A better understanding of any adaptations that occur in obesity is important, particularly in regards to treatment approaches for weight loss. There is also evidence that previous patterns of energy intake, in excess or in restriction, even when sustained for short periods, have the capacity to modify gastrointestinal function and energy intake. For example, in humans following a high fat diet for two weeks, gastric emptying and mouth-to-caecum transit in response to a high fat test meal were faster. In contrast, fasting had the opposite effect and a four-day fast slowed gastric emptying of a glucose drink in both lean and obese subjects, suggesting that a reduction in nutrient exposure may increase the sensitivity of gastrointestinal responses to nutrients in the obese. Although many studies have addressed aspects of gastrointestinal function in the obese, there is a lack of studies that have evaluated gastric emptying and gastrointestinal hormone release specifically GLP-1 and GIP, given the risk of diabetes in obesity, as well as previous patterns of nutrient intake concurrently. In the study presented in Chapter 6, we evaluated the effects of oral ingestion of a nutrient liquid on gastric emptying, oro-caecal transit, plasma GLP-1 and GIP, appetite and energy intake, as well as, habitual energy and fat intake in lean, overweight and obese individuals. We reported no differences in gastric emptying, intragastric distribution or oro-caecal transit between the lean, overweight and obese groups. After the drink, blood glucose and plasma insulin were greater in the obese, when compared with both the lean and overweight groups, however, there were no differences in plasma GLP-1 or GIP concentrations, appetite and energy intake at the buffet meal or habitual energy intake between the groups. In the obese, the magnitude of the rise in blood glucose was inversely related to the gastric emptying, suggesting that obesity per se, in the absence of differences in habitual energy intake, has no effect on gastric emptying or incretin hormone release and that gastric emptying influences postprandial blood glucose in the obese. In Chapter 7, we investigated the hypothesis that gastrointestinal and oral sensitivity to fat is compromised in the obese and directly related to their high fat/energy consumption. For this purpose, we investigated the effects of an intraduodenal infusion (to bypass gastric emptying), of a fatty acid (oleic acid) on gastrointestinal function, appetite and energy intake, and relationships with habitual energy intake and oral fatty acid detection threshold in lean and obese individuals. We report that pyloric pressure, which plays a major role in the regulation of gastric emptying, was lower in response to intraduodenal oleic acid infusion, with trends for reduced cholecystokinin stimulation and energy intake responses in the obese compared with lean. Oral fatty acid detection thresholds were higher in obese compared with lean subjects, and obese subjects also had greater habitual energy and fat intakes than lean subjects. The results suggest that the ability to detect fats both orally and within the gastrointestinal tract is compromised in obese males, probably due to their increased fat consumption. In the study presented in Chapter 8, we evaluated the hypothesis that in obese individuals, the effects of duodenal fat on gastrointestinal motor and hormone function, and appetite would be enhanced by a short period on a very low calorie diet. We demonstrated that following a 70% four-day very low calorie diet there was a significant increase in pyloric pressure and the stimulation of PYY and suppression of ghrelin was greater during an intraduodenal lipid infusion. In addition, following the four-day very low calorie diet, appetite perceptions and energy intake in response to intraduodenal lipid were reduced, indicating that gastrointestinal function, appetite and energy intake in obese can be enhanced over a short period. Given that gastrointestinal function is sensitive to changes even over short periods of dietary restriction, it is important to determine whether these changes are maintained in the long term in order to determine the efficacy of energy restriction therapies for obesity. To maintain dietary restriction and weight loss in the longer term, we used a 30%, as opposed to 70%, energy-restricted diet. In the study presented in Chapter 9, we evaluated the effects of an acute (in lean and obese) and prolonged (in obese only) 30% energy restriction on gastrointestinal function and appetite in response to an intraduodenal lipid infusion. In contrast to the previous 70% very low calorie diet study, there were no differences in gastrointestinal motor or hormonal function in the obese following the acute or prolonged 30% dietary restriction period, although there was a trend for energy intake to be reduced. However, in the lean, there was a decrease in plasma CCK and an increase in ghrelin concentrations following the acute period of dietary restriction with no differences in gastrointestinal motility or energy intake, suggesting that a 30% energy-restricted diet diminishes gastrointestinal hormone responses in lean, but not obese, which may suggest that obese are less sensitive to this caloric restriction. These observations will contribute to the advances in basic appetite physiology and will have clinical implications for further development of dietary interventions for the treatment of obesity.Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 201