The development of an emphatic educator : implementing psychodynamic pedagogy through drama in education

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Mateship and Money-Making: Shearing in Twentieth Century Australia

After the turmoil of the 1890s shearing contractors eliminated some of the frustration from shearers recruitment. At the same time closer settlement concentrated more sheep in small flocks in farming regions, replacing the huge leasehold pastoral empires which were at the cutting edge of wool expansion in the nineteenth century. Meanwhile the AWU succeeded in getting an award for the pastoral industry under the new arbitration legislation in 1907. Cultural and administrative influences, therefore, eased some of the bitter enmity which had made the annual shearing so unstable. Not all was plain sailing. A pattern of militancy re-emerged during World War I. Shearing shed unrest persisted throughout the interwar period and during World War II. In the 1930s a rival union with communist connections, the PWIU, was a major disruptive influence. Militancy was a factor in a major shearing strike in 1956, when the boom conditions of the early-1950s were beginning to fade. The economic system did not have satisfactory mechanisms to cope. Unionised shearers continued to be locked in a psyche of confrontation as wool profits eroded further in the 1970s. This ultimately led to the wide comb dispute, which occurred as wider pressures changed an economic order which had not been seriously challenged since Federation, and which the AWU had been instrumental in shaping. Shearing was always identified with bushworker ‘mateship’, but its larrikinism and irreverence to authority also fostered individualism, and an aggressive ‘moneymaking’ competitive culture. Early in the century, when old blade shearers resented the aggressive pursuit of tallies by fast men engaged by shearing contractors, tensions boiled over. While militants in the 1930s steered money-makers into collectivist versions of mateship, in the farming regions the culture of self-improvement drew others towards the shearing competitions taking root around agricultural show days. Others formed their own contracting firms and had no interest in confrontation with graziers. Late in the century New Zealanders arrived with combs an inch wider than those that had been standard for 70 years. It was the catalyst for the assertion of meritocracy over democracy, which had ruled since Federation

Monocyte and haematopoietic progenitor reprogramming as common mechanism underlying chronic inflammatory and cardiovascular diseases

A large number of cardiovascular events are not prevented by current therapeutic regimens. In search for additional, innovative strategies, immune cells have been recognized as key players contributing to atherosclerotic plaque progression and destabilization. Particularly the role of innate immune cells is of major interest, following the recent paradigm shift that innate immunity, long considered to be incapable of learning, does exhibit immunological memory mediated via epigenetic reprogramming. Compelling evidence shows that atherosclerotic risk factors promote immune cell migration by pre-activation of circulating innate immune cells. Innate immune cell activation via metabolic and epigenetic reprogramming perpetuates a systemic low-grade inflammatory state in cardiovascular disease (CVD) that is also common in other chronic inflammatory disorders. This opens a new therapeutic area in which metabolic or epigenetic modulation of innate immune cells may result in decreased systemic chronic inflammation, alleviating CVD, and its co-morbidities

Platelet Inhibition, Endothelial Function, and Clinical Outcome in Patients Presenting With ST-Segment-Elevation Myocardial Infarction Randomized to Ticagrelor Versus Prasugrel Maintenance Therapy: Long-Term Follow-Up of the REDUCE-MVI Trial

Background Off-target properties of ticagrelor might reduce microvascular injury and improve clinical outcome in patients with ST-segment-elevation myocardial infarction. The REDUCE-MVI (Evaluation of Microvascular Injury in Revascularized Patients with ST-Segment-Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel) trial reported no benefit of ticagrelor regarding microvascular function at 1 month. We now present the follow-up data up to 1.5 years. Methods and Results We randomized 110 patients with ST-segment-elevation myocardial infarction to either ticagrelor 90 mg twice daily or prasugrel 10 mg once a day. Platelet inhibition and peripheral endothelial function measurements includi

Unraveling interindividual variation of trimethylamine N-oxide and its precursors at the population level

Trimethylamine N-oxide (TMAO) is a circulating microbiome-derived metabolite implicated in the development of atherosclerosis and cardiovascular disease (CVD). We investigated whether plasma levels of TMAO, its precursors (betaine, carnitine, deoxycarnitine, choline), and TMAO-to-precursor ratios are associated with clinical outcomes, including CVD and mortality. This was followed by an in-depth analysis of their genetic, gut microbial, and dietary determinants. The analyses were conducted in five Dutch prospective cohort studies including 7834 individuals. To further investigate association results, Mendelian Randomization (MR) was also explored. We found only plasma choline levels (hazard ratio [HR] 1.17, [95% CI 1.07; 1.28]) and not TMAO to be associated with CVD risk. Our association analyses uncovered 10 genome-wide significant loci, including novel genomic regions for betaine (6p21.1, 6q25.3), choline (2q34, 5q31.1), and deoxycarnitine (10q21.2, 11p14.2) comprising several metabolic gene associations, for example, CPS1 or PEMT. Furthermore, our analyses uncovered 68 gut microbiota associations, mainly related to TMAO-to-precursors ratios and the Ruminococcaceae family, and 16 associations of food groups and metabolites including fish-TMAO, meat-carnitine, and plant-based food-betaine associations. No significant association was identified by the MR approach. Our analyses provide novel insights into the TMAO pathway, its determinants, and pathophysiological impact on the general population.Molecular Epidemiolog

Immunometabolic control of trained immunity

Contains fulltext : 232180.pdf (Publisher’s version ) (Open Access)Innate immune cells can adopt long-term inflammatory phenotypes following brief encounters with exogenous (microbial) or endogenous stimuli. This phenomenon is named trained immunity and can improve host defense against (recurrent) infections. In contrast, trained immunity can also be maladaptive in the context of chronic inflammatory disorders, such as atherosclerosis. Key to future therapeutic exploitation of this mechanism is thorough knowledge of the mechanisms driving trained immunity, which can be used as pharmacological targets. These mechanisms include profound changes in intracellular metabolism, which are closely intertwined with epigenetic reprogramming at the level of histone modifications. Glycolysis, glutamine replenishment of the tricarboxylic acid cycle with accumulation of fumarate, and the mevalonate pathway have all been identified as critical pathways for trained immunity in monocytes and macrophages. In this review, we provide a state-of-the-art overview of how these metabolic pathways interact with epigenetic programs to develop trained immunity

Trained immunity and atherosclerotic cardiovascular disease

PURPOSE OF REVIEW: The two major challenges in cardiovascular medicine are to refine risk prediction and to improve pharmacological prevention and treatment. The concept of innate immune memory, which is called trained immunity, has the potential to improve clinical practice in these regards. RECENT FINDINGS: Monocytes and macrophages have the capability to develop a long-term proinflammatory and proatherogenic phenotype after brief exposure to inflammatory stimuli, such as oxidized low-density lipoprotein particles. This innate immune memory develops because of rewiring of intracellular metabolic pathways and epigenetic reprogramming of histone modifications. The persistence of circulating hyperresponsive monocytes in vivo is explained by the fact that training occurs in myeloid progenitor cells in the bone marrow. Several recent studies reported the presence of monocytes with a trained immune phenotype in patients with established atherosclerosis, and in patients with an increased risk for atherosclerosis because of dyslipoproteinemia. SUMMARY: In monocytes and their bone marrow progenitors, metabolic and epigenetic reprogramming can induce trained immunity, which might contribute to the persistent nonresolving inflammation that characterizes atherosclerosis. These pathways offer exciting novel drug targets to improve the prevention and treatment of cardiovascular disease

[Clopidogrel cannot yet be exclusively for smokers]

Item does not contain fulltextDual antiplatelet therapy with acetylsalicylic acid and a P2Y12 receptor antagonist is the cornerstone of treatment in patients with acute coronary syndromes and patients undergoing coronary stenting. Two recent meta-analyses concluded that the efficacy of the P2Y12 receptor antagonist clopidogrel in reducing cardiovascular events is more pronounced in smokers than in non-smokers. Most probably, this is due to induction of cytochrome p450 1A2 by smoking, which accelerates conversion of clopidogrel to its active metabolite. These observations are of great interest. However, before these observations can be used to guide treatment in the clinical arena, the effect of smoking should be studied in prospective clinical trials, investigating not only its modulation of the efficacy but also of the bleeding complications of clopidogrel

Adenosine in health and disease. A human in vivo study on genetic, metabolic, and pharmacological determinants of the cardiovascular effects of adenosine.

Contains fulltext : 29991.pdf (publisher's version ) (Open Access)RU Radboud Universiteit Nijmegen, 11 april 2007Promotor : Smits, P. Co-promotor : Rongen, G.A.P.J.M.255 p

Metformin improves survival in intensive care unit patients, but why?

Contains fulltext : 125655.pdf (publisher's version ) (Open Access