Single Cut Integration

We present an analytic technique for evaluating single cuts for one-loop integrands, where exactly one propagator is taken to be on shell. Our method extends the double-cut integration formalism of one-loop amplitudes to the single-cut case. We argue that single cuts give meaningful information about amplitudes when taken at the integrand level. We discuss applications to the computation of tadpole coefficients.Comment: v2: corrected typo in abstrac

Dietary intakes of flavan-3-ols and cardiovascular health: a field synopsis using evidence mapping of randomized trials and prospective cohort studies

Background: There is considerable interest in the impact of increased flavan-3-ol intake on cardiovascular disease (CVD) and diabetes outcomes. Through evidence mapping, we determined the extent of the evidence base to initiate a future systematic review investigating the impact of flavan-3-ol intake on CVD and diabetes outcomes. Methods: We developed a research protocol, convened a technical expert panel (TEP) to refine the specific research questions, conducted a systematic search in multiple databases, double-screened abstracts and full-text articles, performed data extractions, and synthesized the data. We focused on randomized controlled trials (RCTs) and prospective cohort studies which assessed intakes of flavan-3-ol from foods, beverages, and supplement/extract sources on biomarkers and clinical outcomes of CVD and diabetes. Results: Of 257 eligible articles, 223 and 34 publications contributed to 226 RCTs and 39 prospective cohort studies, respectively. In RCTs, the most frequently studied interventions were cocoa-based products (23.2%); berries (16.1%); tea in the form of green tea (13.9%), black tea (7.2%), or unspecified tea (3.6%); and red wine (11.2%). Mean total flavan-3-ol intake was highest in the cocoa-based trials (618.7 mg/day) and lowest in the interventions feeding red wine (123.7 mg/day). The most frequently reported outcomes were intermediate biomarkers including serum lipid levels (63.4%), blood glucose (50.9%), blood pressure (50.8%), flow-mediated dilation (21.9%), and high-sensitivity C-reactive protein (21.9%). The included 34 prospective cohort studies predominantly examined exposures to flavan-3-ols (26%), cocoa-based products (23.2%), berries (16.1%), and green tea (13.9%) and CVD incidence and mortality. Conclusion: Through a systematic, evidence-based approach, evidence mapping on flavan-3-ol intake and CVD outcomes demonstrated sufficient data relating to flavan-3ol intake and biomarkers and clinical outcomes of CVD and diabetes. The current evidence base highlights the distribution of available data which both support the development of a future systematic review and identified the research need for future long-term RCTs

Socio-cultural influences on the behaviour of South Asian women with diabetes in pregnancy: qualitative study using a multi-level theoretical approach

BACKGROUND: Diabetes in pregnancy is common in South Asians, especially those from low-income backgrounds, and leads to short-term morbidity and longer-term metabolic programming in mother and offspring. We sought to understand the multiple influences on behaviour (hence risks to metabolic health) of South Asian mothers and their unborn child, theorise how these influences interact and build over time, and inform the design of culturally congruent, multi-level interventions. METHODS: Our sample for this qualitative study was 45 women of Bangladeshi, Indian, Sri Lankan, or Pakistani origin aged 21-45 years with a history of diabetes in pregnancy, recruited from diabetes and antenatal services in two deprived London boroughs. Overall, 17 women shared their experiences of diabetes, pregnancy, and health services in group discussions and 28 women gave individual narrative interviews, facilitated by multilingual researchers, audiotaped, translated, and transcribed. Data were analysed using the constant comparative method, drawing on sociological and narrative theories. RESULTS: Key storylines (over-arching narratives) recurred across all ethnic groups studied. Short-term storylines depicted the experience of diabetic pregnancy as stressful, difficult to control, and associated with negative symptoms, especially tiredness. Taking exercise and restricting diet often worsened these symptoms and conflicted with advice from relatives and peers. Many women believed that exercise in pregnancy would damage the fetus and drain the mother's strength, and that eating would be strength-giving for mother and fetus. These short-term storylines were nested within medium-term storylines about family life, especially the cultural, practical, and material constraints of the traditional South Asian wife and mother role and past experiences of illness and healthcare, and within longer-term storylines about genetic, cultural, and material heritage - including migration, acculturation, and family memories of food insecurity. While peer advice was familiar, meaningful, and morally resonant, health education advice from clinicians was usually unfamiliar and devoid of cultural meaning. CONCLUSIONS: 'Behaviour change' interventions aimed at preventing and managing diabetes in South Asian women before and during pregnancy are likely to be ineffective if delivered in a socio-cultural vacuum. Individual education should be supplemented with community-level interventions to address the socio-material constraints and cultural frames within which behavioural 'choices' are made

Blood neutrophil activation markers in severe asthma: lack of inhibition by prednisolone therapy

BACKGROUND: Neutrophils are increased in the airways and in induced sputum of severe asthma patients. We determined the expression of activation markers from circulating neutrophils in severe asthma, and their supressibility by corticosteroids. METHODS: We compared blood neutrophils from mild, moderate-to-severe and severe steroid-dependent asthma, and non-asthmatics (n = 10 each). We examined the effect of adding or increasing oral prednisolone (30 mg/day;1 week). RESULTS: Flow cytometric expression of CD35 and CD11b, but not of CD62L or CD18, was increased in severe asthma. F-met-leu-phe increased CD11b, CD35 and CD18 and decreased CD62L expression in all groups, with a greater CD35 increase in severe asthma. In severe steroid-dependent asthma, an increase in prednisolone dose had no effect on neutrophil markers particularly CD62L, but reduced CD11b and CD62L on eosinophils. Phorbol myristate acetate-stimulated oxidative burst and IL-8 release by IL-1β, lipopolysaccharide and GM-CSF in whole blood from mild but not severe asthmatics were inhibited after prednisolone. There were no differences in myeloperoxidase or neutrophil elastase release from purified neutrophils. CONCLUSION: Because blood neutrophils in severe asthma are activated and are not inhibited by oral corticosteroids, they may be important in the pathogenesis of severe asthma

Human eosinophil adhesion and degranulation stimulated with eotaxin and RANTES in vitro: Lack of interaction with nitric oxide

<p>Abstract</p> <p>Background</p> <p>Airway eosinophilia is considered a central event in the pathogenesis of asthma. The toxic components of eosinophils are thought to be important in inducing bronchial mucosal injury and dysfunction. Previous studies have suggested an interaction between nitric oxide (NO) and chemokines in modulating eosinophil functions, but this is still conflicting. In the present study, we have carried out functional assays (adhesion and degranulation) and flow cytometry analysis of adhesion molecules (VLA-4 and Mac-1 expression) to evaluate the interactions between NO and CC-chemokines (eotaxin and RANTES) in human eosinophils.</p> <p>Methods</p> <p>Eosinophils were purified using a percoll gradient followed by immunomagnetic cell separator. Cell adhesion and degranulation were evaluated by measuring eosinophil peroxidase (EPO) activity, whereas expression of Mac-1 and VLA-4 was detected using flow cytometry.</p> <p>Results</p> <p>At 4 h incubation, both eotaxin (100 ng/ml) and RANTES (1000 ng/ml) increased by 133% and 131% eosinophil adhesion, respectively. L-NAME alone (but not D-NAME) also increased the eosinophil adhesion, but the co-incubation of L-NAME with eotaxin or RANTES did not further affect the increased adhesion seen with chemokines alone. In addition, L-NAME alone (but not D-NAME) caused a significant cell degranulation, but it did not affect the CC-chemokine-induced cell degranulation. Incubation of eosinophils with eotaxin or RANTES, in absence or presence of L-NAME, did not affect the expression of VLA-4 and Mac-1 on eosinophil surface. Eotaxin and RANTES (100 ng/ml each) also failed to elevate the cyclic GMP levels above baseline in human eosinophils.</p> <p>Conclusion</p> <p>Eotaxin and RANTES increase the eosinophil adhesion to fibronectin-coated plates and promote cell degranulation by NO-independent mechanisms. The failure of CC-chemokines to affect VLA-4 and Mac-1 expression suggests that changes in integrin function (avidity or affinity) are rather involved in the enhanced adhesion.</p

Determinants of the urinary and serum metabolome in children from six European populations

Background Environment and diet in early life can affect development and health throughout the life course. Metabolic phenotyping of urine and serum represents a complementary systems-wide approach to elucidate environment–health interactions. However, large-scale metabolome studies in children combining analyses of these biological fluids are lacking. Here, we sought to characterise the major determinants of the child metabolome and to define metabolite associations with age, sex, BMI and dietary habits in European children, by exploiting a unique biobank established as part of the Human Early-Life Exposome project (http://www.projecthelix.eu). Methods Metabolic phenotypes of matched urine and serum samples from 1192 children (aged 6–11) recruited from birth cohorts in six European countries were measured using high-throughput 1H nuclear magnetic resonance (NMR) spectroscopy and a targeted LC-MS/MS metabolomic assay (Biocrates AbsoluteIDQ p180 kit). Results We identified both urinary and serum creatinine to be positively associated with age. Metabolic associations to BMI z-score included a novel association with urinary 4-deoxyerythronic acid in addition to valine, serum carnitine, short-chain acylcarnitines (C3, C5), glutamate, BCAAs, lysophosphatidylcholines (lysoPC a C14:0, lysoPC a C16:1, lysoPC a C18:1, lysoPC a C18:2) and sphingolipids (SM C16:0, SM C16:1, SM C18:1). Dietary-metabolite associations included urinary creatine and serum phosphatidylcholines (4) with meat intake, serum phosphatidylcholines (12) with fish, urinary hippurate with vegetables, and urinary proline betaine and hippurate with fruit intake. Population-specific variance (age, sex, BMI, ethnicity, dietary and country of origin) was better captured in the serum than in the urine profile; these factors explained a median of 9.0% variance amongst serum metabolites versus a median of 5.1% amongst urinary metabolites. Metabolic pathway correlations were identified, and concentrations of corresponding metabolites were significantly correlated (r > 0.18) between urine and serum. Conclusions We have established a pan-European reference metabolome for urine and serum of healthy children and gathered critical resources not previously available for future investigations into the influence of the metabolome on child health. The six European cohort populations studied share common metabolic associations with age, sex, BMI z-score and main dietary habits. Furthermore, we have identified a novel metabolic association between threonine catabolism and BMI of children

Catch-up growth following intra-uterine growth-restriction programmes an insulin-resistant phenotype in adipose tissue.

BACKGROUND: It is now widely accepted that the early-life nutritional environment is important in determining susceptibility to metabolic diseases. In particular, intra-uterine growth restriction followed by accelerated postnatal growth is associated with an increased risk of obesity, type-2 diabetes and other features of the metabolic syndrome. The mechanisms underlying these observations are not fully understood. AIM: Using a well-established maternal protein-restriction rodent model, our aim was to determine if exposure to mismatched nutrition in early-life programmes adipose tissue structure and function, and expression of key components of the insulin-signalling pathway. METHODS: Offspring of dams fed a low-protein (8%) diet during pregnancy were suckled by control (20%)-fed dams to drive catch-up growth. This 'recuperated' group was compared with offspring of dams fed a 20% protein diet during pregnancy and lactation (control group). Epididymal adipose tissue from 22-day and 3-month-old control and recuperated male rats was studied using histological analysis. Expression and phosphorylation of insulin-signalling proteins and gene expression were assessed by western blotting and reverse-transcriptase PCR, respectively. RESULTS: Recuperated offspring at both ages had larger adipocytes (P<0.001). Fasting serum glucose, insulin and leptin levels were comparable between groups but increased with age. Recuperated offspring had reduced expression of IRS-1 (P<0.01) and PI3K p110β (P<0.001) in adipose tissue. In adult recuperated rats, Akt phosphorylation (P<0.01) and protein levels of Akt-2 (P<0.01) were also reduced. Messenger RNA expression levels of these proteins were not different, indicating a post-transcriptional effect. CONCLUSION: Early-life nutrition programmes alterations in adipocyte cell size and impairs the protein expression of several insulin-signalling proteins through post-transcriptional mechanisms. These indices may represent early markers of insulin resistance and metabolic disease risk

Postnatal catch-up growth programs central and peripheral insulin resistance in male mice

Aims: Intra-uterine growth restriction (IUGR) followed by accelerated postnatal growth is associated with an increased risk of obesity and type 2 diabetes. We aimed to determine central and peripheral insulin sensitivity in mice that underwent IUGR followed by post-natal catch-up growth and investigate potential molecular mechanisms underpinning their physiology. Methods: We used a C57/bl6J mouse model of maternal diet-induced IUGR (maternal diet 8 % protein) followed by cross fostering to a normal nutrition dam (maternal diet 20% protein) and litter size manipulation, to cause accelerated post-natal catch-up growth. We performed intra-cerebroventricular insulin injection and hyperinsulinemic-euglycemic clamps to examine the effect of this early nutritional manipulation on central and peripheral insulin resistance. Furthermore, we performed quantitative real time PCR and western blotting to examine the expression of key insulin signalling components in discrete regions of the hypothalamus. Results: We showed that IUGR followed by accelerated postnatal growth caused impaired glucose tolerance and peripheral insulin resistance. In addition, these “recuperated” animals were resistant to the anorectic effects of central insulin administration. This central insulin resistance was associated with reduced protein levels of the P110beta subunit of PI 3-kinase and increased serine phosphorylation of IRS-1 in the arcuate nucleus (ARC) of the hypothalamus. Ptpn1 (PTP1B) expression was also increased specifically in this region of the hypothalamus. Conclusions: Mice that undergo IUGR followed by catch-up growth display peripheral and central insulin resistance in adulthood. Recuperated offspring show changes in expression/phosphorylation of components of the insulin signalling pathway in the ARC. These defects may contribute to the resistance to the anorectic effects of central insulin as well as impaired glucose homeostasis seen in these animals