Creating the cultures of the future: cultural strategy, policy and institutions in Gramsci. Part three: Is there a theory of cultural policy in Gramsci’s prison notebooks?

In this article, I argue that Gramsci’s prison notes on questions of cultural strategy, policy and institutions, which have so far been largely overlooked by scholars, provide further analytical insights to those offered by his more general concepts. Together they enrich the theoretical underpinnings for critical frameworks of analysis as well as for radical practices of cultural strategy, cultural policy-making and cultural organisation. On the basis of a detailed analysis of these notes, I then answer the question of whether they amount to a theory of cultural policy

Lean and Obese Coronary Perivascular Adipose Tissue Impairs Vasodilation via Differential Inhibition of Vascular Smooth Muscle K+ Channels

OBJECTIVE: The effects of coronary perivascular adipose tissue (PVAT) on vasomotor tone are influenced by an obese phenotype and are distinct from other adipose tissue depots. The purpose of this investigation was to examine the effects of lean and obese coronary PVAT on end-effector mechanisms of coronary vasodilation and to identify potential factors involved. APPROACH AND RESULTS: Hematoxylin and eosin staining revealed similarities in coronary perivascular adipocyte size between lean and obese Ossabaw swine. Isometric tension studies of isolated coronary arteries from Ossabaw swine revealed that factors derived from lean and obese coronary PVAT attenuated vasodilation to adenosine. Lean coronary PVAT inhibited K(Ca) and KV7, but not KATP channel-mediated dilation in lean arteries. In the absence of PVAT, vasodilation to K(Ca) and KV7 channel activation was impaired in obese arteries relative to lean arteries. Obese PVAT had no effect on K(Ca) or KV7 channel-mediated dilation in obese arteries. In contrast, obese PVAT inhibited KATP channel-mediated dilation in both lean and obese arteries. The differential effects of obese versus lean PVAT were not associated with changes in either coronary KV7 or K(ATP) channel expression. Incubation with calpastatin attenuated coronary vasodilation to adenosine in lean but not in obese arteries. CONCLUSIONS: These findings indicate that lean and obese coronary PVAT attenuates vasodilation via inhibitory effects on vascular smooth muscle K(+) channels and that alterations in specific factors such as calpastatin are capable of contributing to the initiation or progression of smooth muscle dysfunction in obesity

Leptin augments coronary vasoconstriction and smooth muscle proliferation via a Rho kinase dependent pathway

Leptin has been implicated as a key upstream mediator of pathways associated with coronary vascular dysfunction and disease. The purpose of this investigation was to test the hypothesis that leptin modifies the coronary artery proteome and promotes increases in coronary smooth muscle contraction and proliferation via influences on Rho kinase signaling. Global proteomic assessment of coronary arteries from lean swine cultured with obese concentrations of leptin (30 ng/mL) for 3 days revealed significant alterations in the coronary artery proteome (68 proteins) and identified an association between leptin treatment and calcium signaling/contraction (four proteins) and cellular growth and proliferation (35 proteins). Isometric tension studies demonstrated that both acute (30 min) and chronic (3 days, serum-free media) exposure to obese concentrations of leptin potentiated depolarization-induced contraction of coronary arteries. Inhibition of Rho kinase significantly reduced leptin-mediated increases in coronary artery contractions. The effects of leptin on the functional expression of Rho kinase were time-dependent, as acute treatment increased Rho kinase activity while chronic (3 day) exposure was associated with increases in Rho kinase protein abundance. Proliferation assays following chronic leptin administration (8 day, serum-containing media) demonstrated that leptin augmented coronary vascular smooth muscle proliferation and increased Rho kinase activity. Inhibition of Rho kinase significantly reduced these effects of leptin. Taken together, these findings demonstrate that leptin promotes increases in coronary vasoconstriction and smooth muscle proliferation and indicate that these phenotypic effects are associated with alterations in the coronary artery proteome and dynamic effects on the Rho kinase pathway

CARDIOVASCULAR AND HEMODYNAMIC EFFECTS OF GLUCAGON-LIKE PEPTIDE-1

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that has been shown to have hemodynamic and cardioprotective capacity in addition to its better characterized glucoregulatory actions. Because of this, emerging research has focused on the ability of GLP-1 based therapies to drive myocardial substrate selection, enhance cardiac performance and regulate heart rate, blood pressure and vascular tone. These studies have produced consistent and reproducible results amongst numerous laboratories. However, there are obvious disparities in findings obtained in small animal models versus those of higher mammals. This species dependent discrepancy calls to question, the translational value of individual findings. Moreover, few studies of GLP-1 mediated cardiovascular action have been performed in the presence of a pre-existing comorbidities (e.g. obesity/diabetes) which limits interpretation of the effectiveness of incretin-based therapies in the setting of disease. This review addresses cardiovascular and hemodynamic potential of GLP-1 based therapies with attention to species specific effects as well as the interaction between therapies and disease

Glucagon-like peptide-1 (7-36) but not (9-36) augments cardiac output during myocardial ischemia via a Frank-Starling mechanism

This study examined the cardiovascular effects of GLP-1 (7-36) or (9-36) on myocardial oxygen consumption, function and systemic hemodynamics in vivo during normal perfusion and during acute, regional myocardial ischemia. Lean Ossabaw swine received systemic infusions of saline vehicle or GLP-1 (7-36 or 9-36) at 1.5, 3.0, and 10.0 pmol/kg/min in sequence for 30 min at each dose, followed by ligation of the left circumflex artery during continued infusion at 10.0 pmol/kg/min. Systemic GLP-1 (9-36) had no effect on coronary flow, blood pressure, heart rate or indices of cardiac function before or during regional myocardial ischemia. Systemic GLP-1 (7-36) exerted no cardiometabolic or hemodynamic effects prior to ischemia. During ischemia, GLP-1 (7-36) increased cardiac output by approximately 2 L/min relative to vehicle-controls (p = 0.003). This response was not diminished by treatment with the non-depolarizing ganglionic blocker hexamethonium. Left ventricular pressure-volume loops measured during steady-state conditions with graded occlusion of the inferior vena cava to assess load-independent contractility revealed that GLP-1 (7-36) produced marked increases in end-diastolic volume (74 ± 1 to 92 ± 5 ml; p = 0.03) and volume axis intercept (8 ± 2 to 26 ± 8; p = 0.05), without any change in the slope of the end-systolic pressure-volume relationship vs. vehicle during regional ischemia. GLP-1 (9-36) produced no changes in any of these parameters compared to vehicle. These findings indicate that short-term systemic treatment with GLP-1 (7-36) but not GLP-1 (9-36) significantly augments cardiac output during regional myocardial ischemia, via increases in ventricular preload without changes in cardiac inotropy

Obesity Alters Molecular and Functional Cardiac Responses to Ischemia-Reperfusion and Glucagon-Like Peptide-1 Receptor Agonism

This study tested the hypothesis that obesity alters the cardiac response to ischemia/reperfusion and/or glucagon like peptide-1 (GLP-1) receptor activation, and that these differences are associated with alterations in the obese cardiac proteome and microRNA (miRNA) transcriptome. Ossabaw swine were fed normal chow or obesogenic diet for 6 months. Cardiac function was assessed at baseline, during a 30-minutes coronary occlusion, and during 2 hours of reperfusion in anesthetized swine treated with saline or exendin-4 for 24 hours. Cardiac biopsies were obtained from normal and ischemia/reperfusion territories. Fat-fed animals were heavier, and exhibited hyperinsulinemia, hyperglycemia, and hypertriglyceridemia. Plasma troponin-I concentration (index of myocardial injury) was increased following ischemia/reperfusion and decreased by exendin-4 treatment in both groups. Ischemia/reperfusion produced reductions in systolic pressure and stroke volume in lean swine. These indices were higher in obese hearts at baseline and relatively maintained throughout ischemia/reperfusion. Exendin-4 administration increased systolic pressure in lean swine but did not affect the blood pressure in obese swine. End-diastolic volume was reduced by exendin-4 following ischemia/reperfusion in obese swine. These divergent physiologic responses were associated with obesity-related differences in proteins related to myocardial structure/function (e.g. titin) and calcium handling (e.g. SERCA2a, histidine-rich Ca2+ binding protein). Alterations in expression of cardiac miRs in obese hearts included miR-15, miR-27, miR-130, miR-181, and let-7. Taken together, these observations validate this discovery approach and reveal novel associations that suggest previously undiscovered mechanisms contributing to the effects of obesity on the heart and contributing to the actions of GLP-1 following ischemia/reperfusion

Perivascular adipose tissue and coronary vascular disease

Coronary perivascular adipose tissue is a naturally occurring adipose tissue depot that normally surrounds the major coronary arteries on the surface of the heart. Although originally thought to promote vascular health and integrity, there is a growing body of evidence to support that coronary perivascular adipose tissue displays a distinct phenotype relative to other adipose depots and is capable of producing local factors with the potential to augment coronary vascular tone, inflammation, and the initiation and progression of coronary artery disease. The purpose of the present review is to outline previous findings about the cardiovascular effects of coronary perivascular adipose tissue and the potential mechanisms by which adipose-derived factors may influence coronary vascular function and the progression of atherogenesis

Creating the cultures of the future: cultural strategy, policy and institutions in Gramsci. Part one: Gramsci and cultural policy studies: some methodological reflections

Gramsci’s writings have rarely been discussed and used systematically by scholars in cultural policy studies, despite the fact that in cultural studies, from which the field emerged, Gramsci has been a major source of theoretical concepts. Cultural policy studies were, in fact, theorised as an anti-Gramscian project between the late 1980s and the early 1990s, when a group of scholars based in Australia advocated a major political and theoretical reorientation of cultural studies away from hegemony theory and radical politicisation, and towards reformist-technocratic engagement with the policy concerns of contemporary government and business. Their criticism of the ‘Gramscian tradition’ as inadequate for the study of cultural policy and institutions has remained largely unexamined in any detail for almost twenty years and seems to have had a significant role in the subsequent neglect of Gramsci’s contribution in this area of study. This essay, consisting of three parts, is an attempt to challenge such criticism and to provide an analysis of Gramsci’s writings, with the aim of proposing a more systematic contribution of his work to the theoretical development of cultural policy studies. In Part One, I question the use of the notion of ‘Gramscian tradition’ made by its critics and challenge the claim that it was inadequate for the study of cultural policy and institutions. In parts Two and Three, I consider Gramsci’s specific writings on questions of cultural strategy, policy and institutions, which have so far been overlooked by scholars, arguing that they provide further analytical insights to those offered by his more general concepts. More specifically, in Part Two, I consider Gramsci’s pre-prison writings and political practice in relation to questions of cultural strategy and institutions. I argue that the analysis of these early texts, which were written in the years in which Gramsci was active in party organisation and leadership, is fundamental not only for understanding the nature of Gramsci’s early and continued involvement with questions of cultural strategy and institutions, but also as a key for deciphering and interpreting cultural policy themes that he later developed in the prison notebooks, and which originated in earlier debates. Finally, in Part Three, I carry out a detailed analysis of Gramsci’s prison notes on questions of cultural strategy, policy and institutions, which enrich the theoretical underpinnings for critical frameworks of analysis as well as for radical practices of cultural strategy, cultural policy-making and cultural organisation. I then answer the question of whether Gramsci’s insights amount to a theory of cultural policy

Validating a benchmarking tool for audit of early outcomes after operations for head and neck cancer

INTRODUCTION In 2013 all UK surgical specialties, with the exception of head and neck surgery, published outcome data adjusted for case mix for indicator operations. This paper reports a pilot study to validate a previously published risk adjustment score on patients from separate UK cancer centres. METHODS A case note audit was performed of 1,075 patients undergoing 1,218 operations for head and neck squamous cell carcinoma under general anaesthesia in 4 surgical centres. A logistic regression equation predicting for all complications, previously validated internally at sites A-C, was tested on a fourth external validation sample (site D, 172 operations) using receiver operating characteristic curves, Hosmer-Lemeshow goodness of fit analysis and Brier scores. RESULTS Thirty-day complication rates varied widely (34-51%) between the centres. The predictive score allowed imperfect risk adjustment (area under the curve: 0.70), with Hosmer-Lemeshow analysis suggesting good calibration. The Brier score changed from 0.19 for sites A-C to 0.23 when site D was also included, suggesting poor accuracy overall. CONCLUSIONS Marked differences in operative risk and patient case mix captured by the risk adjustment score do not explain all the differences in observed outcomes. Further investigation with different methods is recommended to improve modelling of risk. Morbidity is common, and usually has a major impact on patient recovery, ward occupancy, hospital finances and patient perception of quality of care. We hope comparative audit will highlight good performance and challenge underperformance where it exists.</p