Academic freedom in Europe: time for a Magna Charta?

This paper is a preliminary attempt to establish a working definition of academic freedom for the European Union states. The paper details why such a definition is required for the European Union and then examines some of the difficulties of defining academic freedom. By drawing upon experience of the legal difficulties beset by the concept in the USA and building on previous analyses of constitutional and legislative protection for academic freedom, and of legal regulations concerning institutional governance and academic tenure, a working definition of academic freedom is then derived. The resultant definition which, it is suggested, could form the basis for a European Magna Charta Libertatis Academicae, goes beyond traditional discussions of academic freedom by specifying not only the rights inherent in the concept but also its accompanying duties, necessary limitations and safeguards. The paper concludes with proposals for how the definition might be tested and carried forward

Vaccenic acid suppresses intestinal inflammation by increasing anandamide and related N-acylethanolamines in the JCR:LA-cp rat

Vaccenic acid (VA), the predominant ruminantderived trans fat in the food chain, ameliorates hyperlipidemia, yet mechanisms remain elusive. We investigated whether VA could influence tissue endocannabinoids (ECs) by altering the availability of their biosynthetic precursor, arachidonic acid (AA), in membrane phospholipids (PLs). JCR:LA-cp rats were assigned to a control diet with or without VA (1% w/w), cis-9, trans-11 conjugated linoleic acid (CLA) (1% w/w) or VA+CLA (1% + 0.5% w/w) for 8 weeks. VA reduced the EC, 2-arachidonoylglycerol (2-AG), in the liver and visceral adipose tissue (VAT) relative to control diet (P 0.05). Interestingly, VA increased jejunal concentrations of anandamide and those of the noncannabinoid signaling molecules, oleoylethanolamide and palmitoylethanolamide, relative to control diet (P < 0.05). This was consistent with a lower jejunal protein abundance (but not activity) of their degrading enzyme, fatty acid amide hydrolase, as well as the mRNA expression of TNFα and interleukin 1β (P < 0.05). The ability of VA to reduce 2-AG in the liver and VAT provides a potential mechanistic explanation to alleviate ectopic lipid accumulation. The opposing regulation of ECs and other noncannabinoid lipid signaling molecules by VA suggests an activation of benefit via the EC system in the intestine

Academic freedom: in justification of a universal ideal

This paper examines the justification for, and benefits of, academic freedom to academics, students, universities and the world at large. The paper surveys the development of the concept of academic freedom within Europe, more especially the impact of the reforms at the University of Berlin instigated by Wilhelm von Humboldt. Following from this, the paper examines the reasons why the various facets of academic freedom are important and why the principle should continue to be supported

The Interplay of Obesity, Dyslipidemia and Immune Dysfunction: A Brief Overview on Pathophysiology, Animal Models, and Nutritional Modulation

Obesity has emerged as a leading global health concern. It is characterized by chronic low-grade inflammation, which impairs insulin signaling, lipid metabolism and immune function. Recent findings from animal and clinical studies have begun to elucidate the underlying mechanisms of immune dysfunction seen in the context of obesity. Here, we provide a brief review on the current understanding of the interplay between obesity, dyslipidemia and immunity. We also emphasize the advantages and shortcomings of numerous applicable research models including rodents and large animal swine that aim at unraveling the molecular basis of disease and clinical manifestations. Although there is no perfect model to answer all questions at once, they are often used to complement each other. Finally, we highlight some emerging nutritional strategies to improve immune function in the context of obesity with a particular focus on choline and foods that contains high amounts of choline

Effect of High-Fat and Low-Fat Dairy Products on Cardiometabolic Risk Factors and Immune Function in a Low Birthweight Swine Model of Diet-Induced Insulin Resistance

Although dairy intake has been shown to have a neutral or some beneficial effect on major cardiometabolic risk factors, the impact of dairy, and especially dairy fat, on immune function remains to be investigated. To understand the effect of consuming dairy fat on cardiometabolic risk factors and immune function, we used an established low birthweight (LBW) swine model of diet-induced insulin resistance to compare high-fat and low-fat dairy products to a control high-fat diet (CHF). LBW piglets were randomized to consume one of the 3 experimental HF diets: (1) CHF, (2) CHF diet supplemented with 3 servings/day of high-fat dairy (HFDairy) and (3) CHF diet supplemented with 3 servings/day of low-fat dairy (LFDairy). As comparison groups, normal birthweight (NBW) piglets were fed a CHF (NBW-CHF) or standard pig grower diet (NBW-Chow). A total of 35 pigs completed the study and were fed for a total of 7 weeks, including 1 week of CHF transition diet. At 12 weeks of age, piglets were euthanized. Fasting blood and tissue samples were collected. Ex vivo cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with pokeweed (PWM), phytohemagglutinin (PHA) and phorbol myristate acetate-ionomycin (PMA-I) were assessed. As expected, LBW-CHF piglets showed early signs of insulin resistance (HOMA-IR, P model = 0.08). Feeding high-fat dairy products improved fasting plasma glucose concentrations more than low-fat dairy compared to LBW-CHF (P &lt; 0.05). Irrespective of fat content, dairy consumption had neutral effect on fasting lipid profile. We have also observed lower production of IL-2 after PWM and PHA stimulation as well as lower production of TNF-α and IFN-γ after PWM stimulation in LBW-CHF than in NBW-Chow (all, P &lt; 0.05), suggesting impaired T cell and antigen presenting cell function. While feeding high-fat dairy had minimal effect on immune function, feeding low-fat dairy significantly improved the production of IL-2, TNF-α and IFN-γ after PWM stimulation, IL-2 and IFN-γ after PHA stimulation as well as TNF-α after PMA-I stimulation compared to LBW-CHF (all, P &lt; 0.05). These data provide novel insights into the role of dairy consumption in counteracting some obesity-related cardiometabolic and immune perturbations

Cardiomyocyte antihypertrophic effect of adipocyte tissue conditioned medium from rats and its abrogation by obesity is mediated by the leptin to adiponectin ratio

White adipocytes are known to function as endocrine organs by secreting a plethora of bioactive adipokines which can regulate cardiac function including the development of hypertrophy. We determined whether adipose tissue conditioned medium (ATCM) generated from the epididymal regions of normal rats can affect the hypertrophic response of cultured rat ventricular myocytes to endothelin-1 (ET-1) administration. Myocytes were treated with ET-1 (10 nM) for 24 hours in the absence or presence of increasing ATCM concentrations. ATCM supressed the hypertrophic response to ET-1 in a concentration-dependent manner, an effect enhanced by the leptin receptor antagonist and attenuated by an antibody against the adiponectin AdipoR1 receptor. Antihypertrophic effects were also observed with ATCM generated from perirenal-derived adipose tissue. However, this effect was absent in ATCM from adipose tissue harvested from corpulent JCR:LA-cp rats. Detailed analyses of adipokine content in ATCM from normal and corpulent rats revealed no differences in the majority of products assayed, although a significant increase in leptin concentrations concomitant with decreased adiponectin levels was observed, resulting in a 11 fold increase in the leptin to adiponectin ratio in ATCM from JCR:LA-cp. The antihypertrophic effect of ATCM was associated with increased phosphorylation of AMP-activated protein kinase (AMPK), an effect abrogated by the AdipoR1 antibody. Moreover, the antihypertrophic effect of ATCM was mimicked by an AMPK activator. There was no effect of ET-1 on mitogen-activated protein kinase (MAPK) activities 24 hour after its addition either in the presence or absence of ATCM. Our study suggests that adipose tissue from healthy subjects exerts antihypertrophic effects via an adiponectin–dependent pathway which is impaired in obesity, most likely due to adipocyte remodelling resulting in enhanced leptin and reduced adiponectin levels

Differential expression of hypothalamic metabolic and inflammatory genes in response to short-term calorie restriction in juvenile obese- and lean-prone JCR rats

Background: Childhood obesity is an important early predictor of adult obesity and associated comorbidities. Common forms of obesity are underpinned by both environmental and genetic factors. However, the rising prevalence of obesity in genetically stable populations strongly suggests that contemporary lifestyle is a premier factor to the disease. In pediatric population, the current treatment/prevention options for obesity are lifestyle interventions such as caloric restriction (CR) and increase physical activity. In obese individuals, CR improves many metabolic parameters in peripheral tissues. Little is known about the effect of CR on the hypothalamus. This study aimed to assess the effect of CR on hypothalamic metabolic gene expression of young obese- and lean-prone animals. Methods: Male juvenile JCR:LA-cp obese-prone rats were freely fed (Obese-FF) or pair fed (Obese-FR) to lean-prone, free-feeding animals (Lean-FF). A group of lean-prone rats (Lean-FR) were matched for relative average degree of CR to Obese-FR rats. Results: In free-feeding conditions, obese-prone rats consumed more energy than lean-prone rats (P<0.001) and showed greater increases in body weight, fat mass, plasma glucose, insulin and lipids (P<0.01). These metabolic differences were associated with alterations of feeding-related neuropeptides expression in the hypothalamus, as well as pro-inflammatory cytokines and oxidative stress markers. When submitted to the same degree of CR, the two genotypes responded differently; hypothalamic inflammatory and oxidative stress gene expression was improved in Obese-FR, while it was worsened in Lean-FR rats. Conclusions: We demonstrate in JCR rats that the metabolic and inflammatory response of the brain to CR is genotype dependent

Comparison of residual cancer burden, American Joint Committee on Cancer staging and pathologic complete response in breast cancer after neoadjuvant chemotherapy: results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657)

Purpose: Several pathologic staging systems characterize residual tumor in patients undergoing neoadjuvant chemotherapy for breast cancer. Pathologic complete response (pCR) is now accepted by the Food and Drug Administration as an endpoint for granting accelerated drug approval. Two other systems of post-neoadjuvant pathologic tumor staging—residual cancer burden (RCB) and the American Joint Committee on Cancer post-neoadjuvant therapy staging system (yAJCC)—have been developed to characterize residual tumors when patients do not achieve pCR. The optimal system and the ways in which these systems complement each other have not been fully determined. Methods: Using data from the I-SPY 1 TRIAL, we compared pCR, RCB, and yAJCC as predictors of early recurrence-free survival (RFS) to identify ways to improve post-neoadjuvant pathologic evaluation. Results: Among 162 patients assessed, pCR identified patients at lowest risk of recurrence, while RCB and yAJCC identified patients at highest risk. Hormone-receptor (HR) and HER2 subtypes further improved risk prediction. Recursive partitioning indicated that triple-negative or HER2+ patients with yAJCC III or RCB 3 have the highest recurrence risk, with an RFS of 27%. Our analysis also highlighted discrepancies between RCB and yAJCC stratification: 31% of patients had discrepant RCB and yAJCC scores. We identified differential treatment of lymph node involvement and tumor cellularity as drivers of these discrepancies. Conclusions: These data indicate that there is benefit to reporting both RCB and yAJCC for patients in order to identify those at highest risk of relapse