270 research outputs found

    An unblinking gaze: Readerly response-ability and racial reconstructions in Toni Morrison\u27s \u27The Bluest Eye\u27 and \u27Beloved\u27

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    This thesis examines Toni Morrison\u27s reconstruction of racial representations in The Bluest Eye and Beloved. Morrison stresses the need for a transformation of current representations of black and white culture in her critical study, Playing in the Dark: Whiteness and the Literary Imagination, in which Morrison examines how black culture has been (mis)represented and (mis)perceived by white Western culture and discourse. She argues that idealized and valorized notions of whiteness, white identity, and white culture have been constructed from denigrating, binary oppositional (mis)perceptions of blackness, black identity, and black culture. These stereotypical (mis)perceptions maintain white cultural dominance over black bodies by promoting within black culture self-negating and racist notions of blackness. In her struggle to (re)theorize and transform these racist representations, Morrison examines white and black culture with an unblinking gaze (Russell 46) in The Bluest Eye and Beloved. She writes to repossess, re-name, re-own (46) and reconstruct representations of black identity and culture by showing how black people see themselves and white people being defined within Western culture. Morrison encourages readerly participation in her racial reconstructions by structuring her fragmented narratives with textual holes and spaces into which the reader must enter to work with Morrison in the telling of the story. This kind of participatory reading underlines the reader\u27s response-ability (Buying xi): the ability to enter the text and respond to it, first viscerally and then intellectually. This intimate and intense participation with Morrison and the text liberates our minds to the transformative potential of The Bluest Eye and Beloved regarding representation. Both novels critically interrogate concepts of whiteness and blackness and outline the detrimental effects of white cultural domination upon black and white identity and culture. As we piece together the main characters’ fragmented stories, we participate in their differing strategies of resistance to this cultural domination and in their struggle with concepts of love, identity, and meaning. By inviting her readers to participate in the interrogation and transformation of racial representations in her novels, Morrison broadens the spectrum of black and white cultural representations within the literary imagination

    What is the Most Effective Treatment for the Management of Dental Anxiety among Adults? A Systematic Review of Interventions

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    This review aimed to find the most effective intervention for the management of dental anxiety among adults by way of a systematic review of Randomised controlled trials. Compared to European and US counterparts, the number of studies concerning the management of dental anxiety in the United Kingdom is limited. Several interventions have been reported with varying modes of action and duration. Two main groups of interventions: pharmacological and psychological/behavioural have been implemented. The pharmacological interventions employ the use of centrally acting sedatives whereas the psychological/behavioural interventions serve to change the behavioural and learning effects of dental anxiety. A third group operationally defined as “Complementary” for the purpose of this review consists of holistic therapies such as acupuncture, music distraction and aromatherapy for in the management of dental anxiety. Although reduction of dental anxiety before and after dental treatment has been recorded historically in the majority of trials, these have mainly investigated psychological/behavioural interventions. Exploring more recent trials, this study uncovers the benefits of complementary interventions for managing dental anxiety in adults and computer based variants of psychological/behavioural interventions. None compared the efficacy of one type or group against the other. Also, outcomes such as avoidance of dental treatment and economic implication of interventions were scarcely evaluated thus evidence on this remains inconclusive. The need for further investigation of these outcomes as well as those in Complementary Therapies is justified

    Hsp90 Inhibition Suppresses NF-κB Transcriptional Activation via Sirt-2 in Human Lung Microvascular Endothelial Cells

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    The ability of anti-heat shock protein 90 (Hsp90) drugs to attenuate NF-κB-mediated transcription is the major basis for their anti-inflammatory properties. While the molecular mechanisms underlying this effect are not clear, they appear to be distinct in human endothelial cells. We now show for the first time that type 2 sirtuin (Sirt-2) histone deacetylase binds human NF-κB target gene promoter and prevents the recruitment of NF-κB proteins and subsequent assembly of RNA polymerase II complex in human lung microvascular endothelial cells. Hsp90 inhibitors stabilize the Sirt-2/promoter interaction and impose a “transcriptional block,” which is reversed by either inhibition or downregulation of Sirt-2 protein expression. Furthermore, this process is independent of NF-κB (p65) Lysine 310 deacetylation, suggesting that it is distinct from known Sirt-2-dependent mechanisms. We demonstrate that Sirt-2 is recruited to NF-κB target gene promoter via interaction with core histones. Upon inflammatory challenge, chromatin remodeling and core histone H3 displacement from the promoter region removes Sirt-2 and allows NF-κB/coactivator recruitment essential for RNA Pol II-dependent mRNA induction. This novel mechanism may have important implications in pulmonary inflammation

    Novel Mechanism of Attenuation of LPS-Induced NF-Kappab Activation by the Heat Shock Protein 90 Inhibitor, 17-N-Allylamino-17-Demethoxygeldanamycin, in Human Lung Microvascular Endothelial Cells

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    Heat shock protein (hsp) 90 inhibition attenuates NF-kappaB activation and blocks inflammation. However, the precise mechanism of NF-kappaB regulation by hsp90 in the endothelium is not clear. We investigated the mechanisms of hsp90 inhibition by 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) on NF-kappaB activation by LPS in primary human lung microvascular endothelial cells. Transcriptional activation of NF-kappaB was measured by luciferase reporter assay, gene expression by real-time RT-PCR, DNA binding of transcription factors by chromatin immunoprecipitation assay, protein-protein interaction by coimmunoprecipitation/immunoblotting, histone deacetylase (HDAC)/histone acetyltransferase enzyme activity by fluorometry, and nucleosome eviction by partial microccocal DNase digestion. In human lung microvascular endothelial cells, 17-AAG-induced degradation of IKBalpha was accomplished regardless of the phosphorylation/ubiquitination state of the protein. Hence, 17-AAG did not block LPS-induced NF-kappaB nuclear translocation and DNA binding activity. Instead, 17-AAG blocked the recruitment of the coactivator, cAMP response element binding protein binding protein, and prevented the assembly of a transcriptionally competent RNA polymerase II complex at the kappaB elements of the IKBalpha (an NF-kappaB-responsive gene) promoter. The effect of LPS on IKBalpha mRNA expression was associated with rapid deacetylation of histone-H3(Lys9) and a dramatic down-regulation of core histone H3 binding. Even though treatment with an HDAC inhibitor produced the same effect as hsp90 inhibition, the effect of 17-AAG was independent of HDAC. We conclude that hsp90 inhibition attenuates NF-kappaB transcriptional activation by preventing coactivator recruitment and nucleosome eviction from the target promoter in human lung endothelial cells

    Clinicians' Views of Patient-initiated Follow-up in Head and Neck Cancer: a Qualitative Study to Inform the PETNECK2 Trial

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    Aims Current follow-up for head and neck cancer (HNC) is ineffective, expensive and fails to address patients' needs. The PETNECK2 trial will compare a new model of patient-initiated follow-up (PIFU) with routine scheduled follow-up. This article reports UK clinicians' views about HNC follow-up and PIFU, to inform the trial design. Materials and methods Online focus groups with surgeons (ear, nose and throat/maxillofacial), oncologists, clinical nurse specialists and allied health professionals. Clinicians were recruited from professional bodies, mailing lists and personal contacts. Focus groups explored views on current follow-up and acceptability of the proposed PIFU intervention and randomised controlled trial design (presented by the study co-chief investigator), preferences, margins of equipoise, potential organisational barriers and thoughts about the content and format of PIFU. Data were interpreted using inductive thematic analysis. Results Eight focus groups with 34 clinicians were conducted. Clinicians highlighted already known limitations with HNC follow-up – lack of flexibility to address the wide-ranging needs of HNC patients, expense and lack of evidence – and agreed that follow-up needs to change. They were enthusiastic about the PETNECK2 trial to develop and evaluate PIFU but had concerns that PIFU may not suit disengaged patients and may aggravate patient anxiety/fear of recurrence and delay detection of recurrence. Anticipated issues with implementation included ensuring a reliable route back to clinic and workload burden on nurses and allied health professionals. Conclusions Clinicians supported the evaluation of PIFU but voiced concerns about barriers to help-seeking. An emphasis on patient engagement, psychosocial issues, symptom reporting and reliable, quick routes back to clinic will be important. Certain patient groups may be less suited to PIFU, which will be evaluated in the trial. Early, meaningful, ongoing engagement with clinical teams and managers around the trial rationale and recruitment process will be important to discourage selective recruitment and address risk-averse behaviour and potential workload burden.Members of the PETNECK2 Research Team: A. Karwath; B. Main; C. Gaunt; C. Greaves; D. Moore; E. Watson; G. Gkoutos; G. Ozakinci; J. Wolstenholme; J. Dretzke; J. Brett; J. Duda; L. Matheson; L.-R. Cherrill; M. Calvert; P. Kiely; P. Gaunt; S. Chernbumroong; S. Mittal; S. Thomas; S. Winter; W. Won

    Mammographic density and serum 25-hydroxyvitamin D levels

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    Background: Vitamin D, which influences cellular proliferation and breast tissue characteristics, has been inversely correlated with breast cancer risk. Dietary vitamin D intake has been associated with lower mammographic density (MD), a strong intermediate marker of breast cancer risk. Findings: We examined the relationship between MD and serum 25-hydroxyvitamin D [25(OH)D], an integrated measure of vitamin D status from dietary sources and sunlight exposure, in a multi-ethnic cohort of women undergoing screening mammography. We recruited women age 40–60 years without a history of breast cancer at the time of their routine screening mammogram, and conducted in-person interviews and collected blood specimens. We enrolled 195 women from 2007–2008, 120 gave blood, and 114 were evaluable, including 25% white, 41% African American, 18% African Caribbean, and 16% Hispanic. We digitized mammograms and calculated percent density, dense area, and non-dense area on cranial-caudal images. We measured serum 25(OH)D in batched, archived specimens. Median serum 25(OH)D was 22 ng/ml (range, 8–66 ng/ml). In univariable analysis, higher serum 25(OH)D was associated with white race, higher educational level, ever breast feeding, and blood draw during the summer. After adjusting for body mass index and other confounders, we found no association between serum 25(OH)D and different measures of MD. However, when stratified by season, 25(OH)D was inversely associated with dense area during July-December (p = 0.034). Conclusions: Overall, our findings suggest that circulating vitamin D, a potentially modifiable breast cancer risk factor, is not associated with MD; the seasonal effects we observed need to be replicated in larger cohorts
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