Realism and representations of the working class in contemporary British cinema.

This thesis examines the history of social realism and the representation of the working-class in contemporary British cinema. Opening with a critical history, of the political and social context of British social realist film-making since the 1960’s British New Wave era, it moves the grounds of the discussion to social realism in the 1980s and 1990s. The main chapters are dedicated to individual case studies. Three distinctive approaches are applied towards these case studies: the auteurist approach is applied to the works of Ken Loach, and exposes how his politics is reflected in the films, whilst revealing the consistency and changes of his approach towards the subject-matter. In the second chapter, the aesthetic approach is used to examine how the new trend of ‘social art-cinema’ affected the concept of social realism. It will discuss how social realism employs the style and aesthetic of art cinema, to enhance the subjective representation in the film. In the last chapter, the new subjective approach is used to study films that deal with the issue of asylum seekers, immigrants and immigration. This thesis will reveal the complexity and flexibility of the concept of social realism, by analysing its use in contemporary British cinema from these three perspectives. The significance of social realism is its ability to add to the film a sense of immediacy, a sense of ‘here and now’. It can enhance the objectivity of the film, or by integrating with art-cinema aesthetic, enhance the subjectivity of the issue. Social realism needs to be considered with the nature of the medium of cinema, to capture and reflect elements of the social-political structures which make up society

ダパグリフロジン投与における肥満２型糖尿病患者の治療満足度への影響：a patient reported outcome study (PRO study).

Background: The benefits of sodium glucose cotransporters 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus include plasma glucose control, reduction in body weight and blood pressure, and low risk of hypoglycemia, although they may also cause genitourinary infections, polyuria, or volume depletion. It is not clear whether dapagliflozin, an SGLT2 inhibitor, improves treatment satisfaction among patients in a comprehensive way despite the negative side effects. This study assessed the effect of dapagliflozin on glycosylated hemoglobin (HbA1c), body weight, and treatment satisfaction in overweight patients with type 2 diabetes mellitus treated with oral hypoglycemic agents. Methods: This multicenter, open-label, single-arm observational study included patients with type 2 diabetes mellitus administering dapagliflozin 5 or 10 mg per day for 14 weeks. Changes in treatment satisfaction were evaluated using a new version of the Oral Hypoglycemic Agent-Questionnaire (OHA-Q ver. 2) consisting of 23 items. Correlation between treatment satisfaction and HbA1c levels and body weight were analyzed using the Spearman's rank-correlation coefficient. Results: Of the 221 patients enrolled, 188 completed the study. Mean HbA1c decreased from 7.8 ± 0.7% (62.1 ± 7.5 mmol/mol) to 7.3 ± 0.8% (55.9 ± 8.7 mmol/mol) (change - 0.6 ± 0.7%, P < 0.001) and body weight decreased from 82.5 ± 14.6 to 80.7 ± 14.8 kg (change - 2.3 ± 2.8 kg, P < 0.001). OHA-Q ver. 2 was validated as well, the mean OHA-Q ver. 2 total score increased from 44.3 ± 9.4 to 46.6 ± 9.8 (best score 69, worst score 0; change 2.3 ± 6.6, P < 0.001). The change in body weight significantly correlated with the OHA-Q ver. 2 total score (Spearman's ρ = - 0.17, P = 0.035). The change in HbA1c levels significantly correlated with the satisfaction subscale score (Spearman's ρ = - 0.19, P = 0.011). Conclusions: Dapagliflozin significantly improved treatment satisfaction among patients with type 2 diabetes mellitus for 14 weeks. Body weight loss significantly correlated with treatment satisfaction.Trial registration UMIN-CTR: UMIN000016304.博士（医学）・甲第694号・平成31年3月15日© The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

Glucotoxicity Induces Insulin Promoter DNA Methylation in Beta Cells

Recent studies have implicated epigenetics in the pathophysiology of diabetes. Furthermore, DNA methylation, which irreversibly deactivates gene transcription, of the insulin promoter, particularly the cAMP response element, is increased in diabetes patients. However, the underlying mechanism remains unclear. We aimed to investigate insulin promoter DNA methylation in an over-nutrition state. INS-1 cells, the rat pancreatic beta cell line, were cultured under normal-culture-glucose (11.2 mmol/l) or experimental-high-glucose (22.4 mmol/l) conditions for 14 days, with or without 0.4 mmol/l palmitate. DNA methylation of the rat insulin 1 gene (Ins1) promoter was investigated using bisulfite sequencing and pyrosequencing analysis. Experimental-high-glucose conditions significantly suppressed insulin mRNA and increased DNA methylation at all five CpG sites within the Ins1 promoter, including the cAMP response element, in a time-dependent and glucose concentration-dependent manner. DNA methylation under experimental-high-glucose conditions was unique to the Ins1 promoter; however, palmitate did not affect DNA methylation. Artificial methylation of Ins1 promoter significantly suppressed promoter-driven luciferase activity, and a DNA methylation inhibitor significantly improved insulin mRNA suppression by experimental-high-glucose conditions. Experimental-high-glucose conditions significantly increased DNA methyltransferase activity and decreased ten-eleven-translocation methylcytosine dioxygenase activity. Oxidative stress and endoplasmic reticulum stress did not affect DNA methylation of the Ins1 promoter. High glucose but not palmitate increased ectopic triacylglycerol accumulation parallel to DNA methylation. Metformin upregulated insulin gene expression and suppressed DNA methylation and ectopic triacylglycerol accumulation. Finally, DNA methylation of the Ins1 promoter increased in isolated islets from Zucker diabetic fatty rats. This study helps to clarify the effect of an over-nutrition state on DNA methylation of the Ins1 promoter in pancreatic beta cells. It provides new insights into the irreversible pathophysiology of diabetes

Fructose induces glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1 and insulin secretion: Role of adenosine triphosphate-sensitive K[+] channels

Adenosine triphosphate-sensitive K[+] (K[ATP]) channels play an essential role in glucose-induced insulin secretion from pancreatic β-cells. It was recently reported that the K[ATP] channel is also found in the enteroendocrine K-cells and L-cells that secrete glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), respectively. In the present study, we investigated the involvement of the K[ATP] channel in fructose-induced GIP, GLP-1 and insulin secretion in mice. Fructose stimulated GIP secretion, but pretreatment with diazoxide, a K[ATP] channel activator, did not affect fructose-induced GIP secretion under streptozotocin-induced hyperglycemic conditions. Fructose significantly stimulated insulin secretion in Kir6.2[+/+] mice, but not in mice lacking K[ATP] channels (Kir6.2[−/−]), and fructose stimulated GLP-1 secretion in both Kir6.2[+/+]mice and Kir6.2[−/−] mice under the normoglycemic condition. In addition, diazoxide completely blocked fructose-induced insulin secretion inKir6.2[+/+] mice and in MIN6-K8 β-cells. These results show that fructose-induced GIP and GLP-1 secretion is K[ATP] channel-independent and that fructose-induced insulin secretion is K[ATP] channel-dependent