New Chaucer Studies: Pedagogy and Profession

The beginnings of New Chaucer Studies: Pedagogy and Profession are found in many energetic conversations about the state of our field and our profession at the New Chaucer Society&rsquo;s 2018 Congress in Toronto. Concerned about the sustainability of medieval studies, the editors imagined a journal that not only addressed these pressing issues but also helped diminish the isolation many medievalists feel. Most of all, they sought to rethink how different forms of academic labor are defined and valued. The resulting journal rests on two pillars of accessibility: open access and peer review. Available through the University of California&rsquo;s Scholarship publishing platform, the journal is freely available regardless of institutional affiliation. And by encouraging a peer-review process of constructive criticism and intellectual dialogue, the journal promotes fresh perspectives. The journal&rsquo;s first issue presents timely and thoughtful contributions by Anthony Bale, Andrew James Johnston, Dan Kline, and Carolyn Dinshaw.</p

Diclofenac and other non-steroidal anti-inflammatory drugs (NSAIDs) are competitive antagonists of the human P2X3 receptor

Introduction: The P2X3 receptor (P2X3R), an ATP-gated non-selective cation channel of the P2X receptor family, is expressed in sensory neurons and involved in nociception. P2X3R inhibition was shown to reduce chronic and neuropathic pain. In a previous screening of 2000 approved drugs, natural products, and bioactive substances, various non-steroidal anti-inflammatory drugs (NSAIDs) were found to inhibit P2X3R-mediated currents.Methods: To investigate whether the inhibition of P2X receptors contributes to the analgesic effect of NSAIDs, we characterized the potency and selectivity of various NSAIDs at P2X3R and other P2XR subtypes using two-electrode voltage clamp electrophysiology.Results: We identified diclofenac as a hP2X3R and hP2X2/3R antagonist with micromolar potency (with IC50 values of 138.2 and 76.7 µM, respectively). A weaker inhibition of hP2X1R, hP2X4R, and hP2X7R by diclofenac was determined. Flufenamic acid (FFA) inhibited hP2X3R, rP2X3R, and hP2X7R (IC50 values of 221 µM, 264.1 µM, and ∼900 µM, respectively), calling into question its use as a non-selective ion channel blocker, when P2XR-mediated currents are under study. Inhibition of hP2X3R or hP2X2/3R by diclofenac could be overcome by prolonged ATP application or increasing concentrations of the agonist α,β-meATP, respectively, indicating competition of diclofenac and the agonists. Molecular dynamics simulation showed that diclofenac largely overlaps with ATP bound to the open state of the hP2X3R. Our results suggest a competitive antagonism through which diclofenac, by interacting with residues of the ATP-binding site, left flipper, and dorsal fin domains, inhibits the gating of P2X3R by conformational fixation of the left flipper and dorsal fin domains. In summary, we demonstrate the inhibition of the human P2X3 receptor by various NSAIDs. Diclofenac proved to be the most effective antagonist with a strong inhibition of hP2X3R and hP2X2/3R and a weaker inhibition of hP2X1R, hP2X4R, and hP2X7R.Discussion: Considering their involvement in nociception, inhibition of hP2X3R and hP2X2/3R by micromolar concentrations of diclofenac, which are rarely reached in the therapeutic range, may play a minor role in analgesia compared to the high-potency cyclooxygenase inhibition but may explain the known side effect of taste disturbances caused by diclofenac

Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection

The potential for ischemic preconditioning to reduce infarct size was first recognized more than 30 years ago. Despite extension of the concept to ischemic postconditioning and remote ischemic conditioning and literally thousands of experimental studies in various species and models which identified a multitude of signaling steps, so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome as the primary endpoint in patients. Many potential reasons for this disappointing lack of clinical translation of cardioprotection have been proposed, including lack of rigor and reproducibility in preclinical studies, and poor design and conduct of clinical trials. There is, however, universal agreement that robust preclinical data are a mandatory prerequisite to initiate a meaningful clinical trial. In this context, it is disconcerting that the CAESAR consortium (Consortium for preclinicAl assESsment of cARdioprotective therapies) in a highly standardized multi-center approach of preclinical studies identified only ischemic preconditioning, but not nitrite or sildenafil, when given as adjunct to reperfusion, to reduce infarct size. However, ischemic preconditioning—due to its very nature—can only be used in elective interventions, and not in acute myocardial infarction. Therefore, better strategies to identify robust and reproducible strategies of cardioprotection, which can subsequently be tested in clinical trials must be developed. We refer to the recent guidelines for experimental models of myocardial ischemia and infarction, and aim to provide now practical guidelines to ensure rigor and reproducibility in preclinical and clinical studies on cardioprotection. In line with the above guideline, we define rigor as standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment

The effects of group sport on Type A behaviour in primary school children

M.A.This research has been undertaken against the background of Coronary Heart Disease (CHD) as being one of the major causes of death in South Africa. An indepth literature study made it evident that, despite intervention programs that have been successful in reducing the CHD rate, it still remains a number one killer. This could possibly be attributed to CHD prevention programs that historically have focused on biologically related lifestyle factors, and neglected a very important adjuvant risk factor for CHD, namely Type A behaviour. The aim of this dissertation was to study the viability of changing Type A behaviour in childhood through group sport participation in view of the fact that the Type A behaviour pattern (TABP) already present in childhood, has to date not been addressed as a primary preventative possibility. Group sport was chosen as an intervention by nature of it being co-operative, socially supportive and successful in the improvement of a number of relevant factors. Sport has also been demonstrated to be an appropriate outlet for aggressive impulses apparent in Type A behaviour. Twenty subjects participated in the intervention program that took place over a period of eight weeks. A second group of ten Type A subjects served as a no-treatment control group. The intervention was carried out at a primary school in Johannesburg. The results of the study revealed that Type A behaviour (TAB) was not reduced, save for the impatience component, by participation in group sport. Aggressive potential and anxiety in the Type A child, were also not reduced. It is concluded that the intervention of group sport in the reduction of TAB was not successful, and that future studies should investigate an intervention that is successful for the reduction of the TABP in childhood

Lessons from a face-to-face meeting on embedding Aboriginal and Torres Strait Islander perspectives: 'A contract of intimacy'

This paper presents the findings from a conversation between an Aboriginal educator and a non-Indigenous pre-service educator about the importance and complexities of building productive partnerships. Although the participants focused on the challenges and benefits of building relationships between Aboriginal and Torres Strait Islander educators and non-Indigenous educators in Australian early years settings, the more significant outcome of the meeting was the personal connection two young women were able to make when a friendship began to develop. The project was intended to enable an opportunity for the participants ‘to engage in reflexivity on their pedagogic work’, something Mills (2012) understands as crucial to the support of social justice and transformation in the classroom