Aryl hydrocarbon receptor activation during in vitro and in vivo digestion of raw and cooked broccoli (brassica oleracea var. Italica)

Broccoli is rich in glucosinolates, which can be converted upon chewing and processing into Aryl hydrocarbon Receptor (AhR) ligands. Activation of AhR plays an important role in overall gut homeostasis but the role of broccoli processing on the generation of AhR ligands is still largely unknown. In this study, the effects of temperature, cooking method (steaming versus boiling), gastric pH and further digestion of broccoli on AhR activation were investigated in vitro and in ileostomy subjects. For the in vitro study, raw, steamed (t = 3 min and t = 6 min) and boiled (t = 3 min and t = 6 min) broccoli were digested in vitro with different gastric pH. In the in vivo ileostomy study, 8 subjects received a broccoli soup or a broccoli soup plus an exogenous myrosinase source. AhR activation was measured in both in vitro and in vivo samples by using HepG2-Lucia™ AhR reporter cells. Cooking broccoli reduced the AhR activation measured after gastric digestion in vitro, but no effect of gastric pH was found. Indole AhR ligands were not detected or detected at very low levels both after intestinal in vitro digestion and in the ileostomy patient samples, which resulted in no AhR activation. This suggests that the evaluation of the relevance of glucosinolates for AhR modulation in the gut cannot prescind from the way broccoli is processed, and that broccoli consumption does not necessarily produce substantial amounts of AhR ligands in the large intestine

Surfaces, depths and hypercubes: Meyerholdian scenography and the fourth dimension

An appreciation of Meyerhold’s engagement with theatrical space is fundamental to understanding his directorial and pedagogic practice. This article begins by establishing Meyerhold’s theoretical and practical engagement with theatre as a fundamentally scenographic process, arguing for a reconceptualisation of the director as ‘director-scenographer’. Focusing on the construction of depth and surface in Meyerholdian theatre, the article goes on to identify trends in the director’s approach to space, with an emphasis on the de-naturalisation of depth on stage. This denaturalisation is seen as taking three forms: the rejection of depth as a prerequisite in theatrical space, the acknowledgement of the two-dimensional surface as surface, and the restructuring of depth space into a series of restricted planes. The combination of these trends indicates a consistent and systematic process of experimentation in Meyerhold’s work. In addition, this emphasis on depth and surface, and the interaction between the two, also highlights the contextualisation of Meyerhold’s practice within the visual, philosophical and scientific culture of the early twentieth century, echoing the innovations in n-dimensional geometry and particularly, the model of the fourth spatial dimension seen in the work of Russian philosopher P. D. Ouspensky

Protocol for the economic evaluation of metacognitive therapy for cardiac rehabilitation participants with symptoms of anxiety and/or depression

INTRODUCTION: Cardiac rehabilitation (CR) is offered to reduce the risk of further cardiac events and to improve patients' health and quality of life following a cardiac event. Psychological care is a common component of CR as symptoms of depression and/or anxiety are more prevalent in this population, however evidence for the cost-effectiveness of current interventions is limited. Metacognitive therapy (MCT), is a recent treatment development that is effective in treating anxiety and depression in mental health settings and is being evaluated in CR patients. This protocol describes the planned approach to the economic evaluation of MCT for CR patients. METHODS AND ANALYSIS: The economic evaluation work will consist of a within-trial analysis and an economic model. The PATHWAY Group MCT study has been prospectively designed to collect comprehensive self-reported resource use and health outcome data, including the EQ-5D, within a randomised controlled trial study design (UK Clinical Trials Gateway). A within-trial economic evaluation and economic model will compare the cost-effectiveness of MCT plus usual care (UC) to UC, from a health and social care perspective in the UK. The within-trial analysis will use intention-to-treat and estimate total costs and quality-adjusted life-years (QALYs) for the trial follow-up. Single imputation will be used to impute missing baseline variables. Multiple imputation will be used to impute values missing at follow-up. Items of resource use will be multiplied by published national healthcare costs. Regression analysis will be used to estimate net costs and net QALYs and these estimates will be bootstrapped to generate 10 000 net pairs of costs and QALYs to inform the probability of cost-effectiveness. A decision analytical economic model will be developed to synthesise trial data with the published literature over a longer time frame. Sensitivity analysis will explore uncertainty. Guidance of the methods for economic models will be followed and dissemination will adhere to reporting guidelines. ETHICS AND DISSEMINATION: The economic evaluation includes a within-trial analysis. The trial which included the collection of this data was reviewed and approved by Ethics. Ethics approval was obtained by the Preston Research Ethics Committee (project ID 156862). The modelling analysis is not applicable for Ethics as it will use data from the trial (secondary analysis) and the published literature. Results of the main trial and economic evaluation will be published in the peer-reviewed National Institute for Health Research (NIHR) journals library (Programme Grants for Applied Research), submitted to a peer-reviewed journal and presented at appropriate conferences. TRIAL REGISTRATION NUMBER: ISRCTN74643496; Pre-results

Integration of systems biology with organs-on-chips to humanize therapeutic development

"Mice are not little people" - a refrain becoming louder as the gaps between animal models and human disease become more apparent. At the same time, three emerging approaches are headed toward integration: powerful systems biology analysis of cell-cell and intracellular signaling networks in patient-derived samples; 3D tissue engineered models of human organ systems, often made from stem cells; and micro-fluidic and meso-fluidic devices that enable living systems to be sustained, perturbed and analyzed for weeks in culture. Integration of these rapidly moving fields has the potential to revolutionize development of therapeutics for complex, chronic diseases, including those that have weak genetic bases and substantial contributions from gene-environment interactions. Technical challenges in modeling complex diseases with "organs on chips" approaches include the need for relatively large tissue masses and organ-organ cross talk to capture systemic effects, such that current microfluidic formats often fail to capture the required scale and complexity for interconnected systems. These constraints drive development of new strategies for designing in vitro models, including perfusing organ models, as well as "mesofluidic" pumping and circulation in platforms connecting several organ systems, to achieve the appropriate physiological relevance. Keywords: organs-on-chips; 3D liver culture; perfusion; drug development; inflammation; organ crosstalk; tissue chip; intestineUnited States. Defense Advanced Research Projects Agency (Award W911NF-12-2- 0039))National Institutes of Health (U.S.) (Grant UH3TR000496

Liver ‘organ on a chip’

© 2017 The liver plays critical roles in both homeostasis and pathology. It is the major site of drug metabolism in the body and, as such, a common target for drug-induced toxicity and is susceptible to a wide range of diseases. In contrast to other solid organs, the liver possesses the unique ability to regenerate. The physiological importance and plasticity of this organ make it a crucial system of study to better understand human physiology, disease, and response to exogenous compounds. These aspects have impelled many to develop liver tissue systems for study in isolation outside the body. Herein, we discuss these biologically engineered organoids and microphysiological systems. Keywords: Microphysiologic systems; Organoids; 3D culture systemsNational Institutes of Health (U.S.) (Grant UH3TR000496)National Institutes of Health (U.S.) (Grant UH3TR000503

‘Savage times come again’ : Morel, Wells, and the African Soldier, c.1885-1920

The African soldier trained in western combat was a figure of fear and revulsion in the late nineteenth and early twentieth centuries. My article examines representations of African soldiers in nonfictional writings by E.D. Morel about the Congo Free State (1885-1908), the same author’s reportage on African troops in post-First World War Germany, and H.G. Wells’s speculative fiction When the Sleeper Wakes (1899, 1910). In each text racist and anti-colonialist discourses converge in representing the African soldier as the henchman of corrupt imperialism. His alleged propensity for taboo crimes of cannibalism and rape are conceived as threats to white safety and indeed supremacy. By tracing Wells’s connections to the Congo reform campaign and situating his novel between two phases of Morel’s writing career, I interpret When the Sleeper Wakes as neither simply a reflection of past events in Africa or as a prediction of future ones in Europe. It is rather a transcultural text which reveals the impact of European culture upon the ‘Congo atrocities’, and the inscription of this controversy upon European popular cultural forms and social debates

The association of bone, fingernail and blood manganese with cognitive and olfactory function in Chinese workers

Occupational manganese (Mn) exposure has been associated with cognitive and olfactory dysfunction; however, few studies have incorporated cumulative biomarkers of Mn exposure such as bone Mn (BnMn). Our goal was to assess the cross-sectional association between BnMn, blood Mn (BMn), and fingernail Mn (FMn) with cognitive and olfactory function among Mn-exposed workers. A transportable in vivo neutron activation analysis (IVNAA) system was designed and utilized to assess BnMn among 60 Chinese workers. BMn and FMn were measured using inductively coupled plasma mass spectrometry. Cognitive and olfactory function was assessed using Animal and Fruit Naming tests, World Health Organization/University of California-Los Angeles Auditory Verbal Learning Test (AVLT) and the University of Pennsylvania Smell Identification Test (UPSIT). Additional data were obtained via questionnaire. Regression models adjusted for age, education, factory of employment, and smoking status (UPSIT only), were used to assess the relationship between Mn biomarkers and test scores. In adjusted models, increasing BnMn was significantly associated with decreased performance on average AVLT scores [β (95% confidence interval (CI)) = -0.65 (-1.21, -0.09)] and Animal Naming scores [β (95% CI) = -1.54 (-3.00, -0.07)]. Increasing FMn was significantly associated with reduced performance measured by the average AVLT [β (95% CI) = -0.35 (-0.70, -0.006)] and the difference in AVLT scores [β (95% CI) = -0.40 (-0.77, -0.03)]. BMn was not significantly associated with any test scores; no significant associations were observed with Fruit Naming or UPSIT tests. BnMn and FMn, but not BMn, are associated with cognitive function in Mn-exposed workers. None of th

Using Radiological Data to Estimate Ischemic Stroke Severity

Background Risk-adjusted poststroke mortality has been proposed for use as a measure of stroke care quality. Although valid measures of stroke severity (e.g., the National Institutes of Health Stroke Scale [NIHSS]) are not typically available in administrative datasets, radiology reports are often available within electronic health records. We sought to examine whether admission head computed tomography data could be used to estimate stroke severity. Materials and Methods Using chart review data from a cohort of acute ischemic stroke patients (1998-2003), we developed a radiographic measure ([BIS]) of stroke severity in a two-third development set and assessed in a one-third validation set. The retrospective NIHSS was dichotomized as mild/moderate (<10) and severe (≥10). We compared the association of this radiographic score with NIHSS and in-hospital mortality at the patient level. Results Among 1348 stroke patients, 86.5% had abnormal findings on initial head computed tomography. The c-statistic for the BIS for modeling severe stroke (development, .581; validation, .579) and in-hospital mortality (development, .623; validation, .678) were generated. Conclusions Although the c-statistics were only moderate, the BIS provided significant risk stratification information with a 2-variable score. Until administrative data routinely includes a valid measure of stroke severity, radiographic data may provide information for use in risk adjustment

Discrete choice experiment to investigate preferences for psychological intervention in cardiac rehabilitation

OBJECTIVE: Cardiac rehabilitation (CR) is offered to people who recently experienced a cardiac event, and often comprises of exercise, education and psychological care. This stated preference study aimed to investigate preferences for attributes of a psychological therapy intervention in CR. METHODS: A discrete choice experiment (DCE) was conducted and recruited a general population sample and a trial sample. DCE attributes included the modality (group or individual), healthcare professional providing care, information provided prior to therapy, location and the cost to the National Health Service (NHS). Participants were asked to choose between two hypothetical designs of therapy, with a separate opt-out included. A mixed logit model was used to analyse preferences. Cost to the NHS was used to estimate willingness to pay (WTP) for aspects of the intervention design. RESULTS: Three hundred and four participants completed the DCE (general public sample (n=262, mean age 47, 48% female) and trial sample (n=42, mean age 66, 45% female)). A preference for receiving psychological therapy was demonstrated by both samples (general population WTP £1081; 95% CI £957 to £1206). The general population appeared to favour individual therapy (WTP £213; 95% CI £160 to £266), delivered by a CR professional (WTP £48; 9% % CI £4 to £93) and with a lower cost (β=-0.002; p<0.001). Participants preferred to avoid options where no information was received prior to starting therapy (WTP -£106; 95% CI -£153 to -£59). Results for the location attribute were variable and challenging to interpret. CONCLUSIONS: The study demonstrates a preference for psychological therapy as part of a programme of CR, as participants were more likely to opt-in to therapy. Results indicate that some aspects of the delivery which may be important to participants can be tailored to design a psychological therapy. Preference heterogeneity is an issue which may prevent a 'one-size-fits-all' approach to psychological therapy in CR

Measurement of unique magnetic and superconducting phases in oxygen-doped high-temperature superconductors La_2-xSr_xCuO_4+y

We present a combined magnetic neutron scattering and muon spin rotation study of the nature of the magnetic and superconducting phases in electronically phase separated La(2-x)Sr(x)CuO(4+y), x = 0.04, 065, 0.09. For all samples, we find long-range modulated magnetic order below T_N ~ T_c = 39 K. In sharp contrast wit oxygen-stoichiometric La(2-x)Sr(x)CuO(4), we find that the magnetic propagation vector as well as the ordered magnetic moment is independent of Sr content and consistent with that of the 'striped' cuprates. Our study provides direct proof that superoxygenation in La(2-x)Sr(x)CuO(4+y) allows the spin stripe ordered phase to emerge and phase separate from superconducting regions with the hallmarks of optimally doped oxygen-stoichiometric La(2-x)Sr(x)CuO(4)