Benchmarking a self-consistent field theory for small amphiphilic molecules

DOI: 10.1039/C2SM26352A (Paper) Soft Matter, 2012, 8, 9877-9885 This journal is © The Royal Society of Chemistry 2012A minimalist self-consistent field theory for small amphiphilic molecules is presented. The equations for this model are less involved than those for block copolymers and are easily implemented computationally. A new convergence technique based on a variant of Anderson mixing is also presented which allows the equations to be solved more rapidly than block copolymer self-consistent field theory. The computational speed up and simplicity of equations result from a lack of configurational degrees of freedom in the amphiphilic molecular model. The omission of polymeric flexibility leads to qualitatively different predictions compared to known diblock copolymer behaviour.University of Waterloo International Work Study Progra

Is the propensity to emit alarm calls associated with health status?

This work was supported by the National Geographic Society, UCLA (Faculty Senate and the Division of Life Sciences), a RMBL research fellowship, and by the National Science Foundation (NSF) (IDBR-0754247, and DEB-1119660 and 1557130 to D.T.B., as well as DBI-0242960, 0731346, and 1226713 to the RMBL).Peer reviewedPublisher PD

A health impact assessment of the UK soft drinks industry levy: a comparative risk assessment modelling study

Background In March, 2016, the UK government proposed a tiered levy on sugar-sweetened beverages (SSBs; high, moderate, and no tax for drinks with >8g, 5g to 8g, and <5g sugar per 100ml). We estimate the effect of possible industry responses to the levy on obesity, diabetes, and dental caries. Methods We modelled three possible industry responses: (1) reformulation to reduce sugar concentration, (2) increasing product price, and (3) changing the market share of high-, mid-, and low-sugar drinks. For each response, we defined a better and worse case health scenario. We developed a comparative risk assessment model to estimate the UK health impact of each scenario. Findings The best modelled scenario for health is SSB reformulation, resulting in 144,000 (95% uncertainty interval: 5,100 to 306,700) fewer adults and children with obesity in the UK, 19,000 (6,900 to 32,700) fewer incident cases of diabetes per year, and 269,000 (82,200 to 470,900) fewer decayed, missing, or filled teeth annually. Increasing the price of SSBs and changes to market share to increase the proportion of low-sugar drinks sold would also result in population health benefits, but to a lesser extent. The greatest benefit for obesity and oral health would be among individuals under 18 years, with people over 65 years experiencing the largest absolute decreases in diabetes incidence. Interpretation The health impact of the soft drink levy is dependent on its implementation by industry. There is uncertainty as to how industry will react and in the estimation of health outcomes. Health gains could be maximised by significant product reformulation with additional benefits possible if the levy is passed onto purchasers through raising the price of high- and mid-sugar drinks, and through activities to increase the market share of low-sugar products.RT and AK have previously done work on sugar-sweetened beverage taxes funded by the Union of European Soft Drinks Associations. MR is chair of Sustain and the Children's Food Campaign, which have campaigned for sugar drink taxes in the UK. MR is funded by the British Heart Foundation, grant number 006/PSS/CORE/2016/OXFORD. ADMB and OTM are members of the Faculty of Public Health, which has a position statement supporting sugary drink taxes. ADMB is funded by the Wellcome Trust, grant number 102730/Z/13/Z. OTM is a member of the UK Health Forum, which has also supported a UK sugar drinks tax. OTM is supported by a Wellcome Trust Clinical Doctoral Fellowship. SAJ was the independent Chair of the Department of Health Public Health Responsibility Deal Food Network from 2010 to 2015. SAJ is funded by the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care Oxford. The views expressed are those of the authors and not necessarily those of the National Health Service, National Institute for Health Research, or the Department of Health. PS is funded by the British Heart Foundation, grant number FS/15/34/31656. TB is funded the Health Research Council of New Zealand (16/443). AE declares no competing interests

5-fluorouracil and folinic acid-induced mucositis: no effect of oral glutamine supplementation.

In some clinical situations the endogenous production of glutamine may be insufficient to maintain optimal tissue structure and function such that glutamine becomes a conditionally essential amino acid. Studies in laboratory animals have demonstrated that glutamine supplementation can reduce the incidence and severity of cytotoxic-induced mucositis. This study examined the role of oral glutamine supplementation in the management of mucositis caused by 5-fluorouracil (5-FU) and folinic acid. Twenty-eight patients with gastrointestinal cancers were randomised to receive 16 g of glutamine per day for 8 days, or placebo, in a randomised double-blind trial before crossing over to the alternative supplement during the second treatment cycle. The supplement was well tolerated with no apparent adverse effects, but failed to have any significant effect on oral mucositis assessed by the patients or investigator. The possible reasons for this apparent lack of benefit are discussed

The association between dietary macronutrient intake and fibrogen growth factor 21 in a sample of White UK adults with elevated cardiometabolic risk markers

Increased levels of Fibrogen growth factor 21 (FGF21) is an emerging risk marker for cardiometabolic (CM) disease(1). Little detail is known about the impact of the human diet on FGF21 levels. The aim of this investigation was to assess potential associations between mean daily dietary macronutrient intake and FGF21 levels in a sample of 10 healthy normal-weight and overweight Caucasian adults aged 32–60 (80 % male) at increased CM risk(2). This pilot study received ethical approval from Liverpool John Moores University Research Ethics Committee (16/ELS/029) and was registered with ClinicalTrials.gov (Ref. NCT03257085). Participants were randomly allocated to one of two groups and asked to either consume 50 % energy from CHO for a duration of 8 weeks. Blood plasma samples were col- lected at baseline (BL), interim point (IP) and endpoint (EP) after a 12-hour overnight fast, immediately processed and frozen at −80°C. Thawed plasma samples were analysed via Quantikine® enzyme-linked immunosorbent assay (ELISA) (R&D Systems) for FGF21 levels. Two-way mixed ANOVA and Pearson’s partial correlation adjusted for estimated weekly moderate and vigorous activity was undertaken using IBM SPSS 24®. There were no effects for diet between groups or over time (data not shown). Significant correlations between macronutrient intakes and FGF21 levels were found for both groups at IP, but not at BL or EP. Moderate and significant positive correlations were found in the overall group for intake (g/d) for glucose (rpartial = ·699, p = ·04) and fructose (rpartial = ·686, p = ·04) and strong and significant positive correlations for non-milk extrinsic sugars (rpartial = ·742, p = ·02). Strong and significant positive correlations were also found in the LC group for glucose intake (g/d) (rpartial = ·980, p = ·02) and fructose (rpartial = ·967, p = ·03) and for protein (rpartial =·998, p=·002) after adjusting for physical activity. Mean carbohydrate intake (g/d) was 160·0 (s.d. 124·5) overall and 44·2 (s.d. 14·9) in the LC group at IP. Mean protein intake (g/d) was 113·2 (21·4) 130·0 (s.d. 15·9) overall and in the LC group at IP. Mean FGF21 levels were 179·9 pg/mL (s.d. 144·9) in the overall group and 94.4 pg/ML (s.d. 48.6) in the LC group at IP. %TE Intake (g/d) PROT FAT CHO GLU FRU NMES PROT FAT rrrrrrrrrrr −·214 ·623 ·635 −·326 −·491 ·448 ·699* ·686* ·742* −·606 −·496 ·143 ·637 ·937 ·427 −·059 ·722 ·980* ·967* ·919 ·998** −·080 Total kcal CHO NMES T LC CHO-Total carbohydrates, FAT-Total fat, FRU-Fructose, GLUC-Glucose, LC-low-carbohydrate, high-fat group, NMES-non-milk extrinsic sugars, PROT-protein, T – total, %TE – percentage total energy, *p < ·05 **p < ·005. In conclusion, low-carbohydrate diets provide the opportunity to assess responses to even small amounts of CHO, which are likely to be replaced in part by proteins. Despite low overall intakes of fructose and glucose in the LC group, strong and positive correlations with FGF21 levels were observed. The lower levels of FGF21 in the LC compared to the overall group are in line with findings that FGF21 levels are elevated with high-carbohydrate, low-protein diets with dietary fats having only minor impact(3). However, the majority of studies have still been undertaken using rodent models. The impact of dietary macronutrients on FGF21 levels as novel CMR marker in humans and the mechanism behind this relationship warrant further investigation. 1. Lakhani I, Gong M, Wong W et al. (2018) Metabolism 2018 Feb 1. pii: S0026-0495(18)30023-4. [Epub ahead of print]. 2. Jebb S, Lovegrove J, Griffin B et al. (2010) Am J Clin Nutr 92, 748–58. 3. Solon-Biet S, Cogger V, Pulpitel T et al. (2016) Cell Metab 24, 555–565

Plasma free fatty acids do not provide the link between obesity and insulin resistance or β-cell dysfunction: results of the Reading, Imperial, Surrey, Cambridge, Kings (RISCK) study

Aims To investigate the relationship between adiposity and plasma free fatty acid levels and the influence of total plasma free fatty acid level on insulin sensitivity and β-cell function. Methods An insulin sensitivity index, acute insulin response to glucose and a disposition index, derived from i.v. glucose tolerance minimal model analysis and total fasting plasma free fatty acid levels were available for 533 participants in the Reading, Imperial, Surrey, Cambridge, Kings study. Bivariate correlations were made between insulin sensitivity index, acute insulin response to glucose and disposition index and both adiposity measures (BMI, waist circumference and body fat mass) and total plasma free fatty acid levels. Multivariate linear regression analysis was performed, controlling for age, sex, ethnicity and adiposity. Results After adjustment, all adiposity measures were inversely associated with insulin sensitivity index (BMI: β = −0.357; waist circumference: β = −0.380; body fat mass: β = −0.375) and disposition index (BMI: β = −0.215; waist circumference: β = −0.248; body fat mass: β = −0.221) and positively associated with acute insulin response to glucose [BMI: β = 0.200; waist circumference: β = 0.195; body fat mass β = 0.209 (P values <0.001)]. Adiposity explained 13, 4 and 5% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively. After adjustment, no adiposity measure was associated with free fatty acid level, but total plasma free fatty acid level was inversely associated with insulin sensitivity index (β = −0.133), acute insulin response to glucose (β = −0.148) and disposition index [β = −0.218 (P values <0.01)]. Plasma free fatty acid concentration accounted for 1.5, 2 and 4% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively. Conclusions Plasma free fatty acid levels have a modest negative association with insulin sensitivity, β-cell secretion and disposition index but no association with adiposity measures. It is unlikely that plasma free fatty acids are the primary mediators of obesity-related insulin resistance or β-cell dysfunction

Dietary carbohydrate intake, visceral adipose tissue and associated markers of cardiometabolic risk

Risk of cardiometabolic (CM) disease is characterised by elevated visceral adipose tissue (VAT) and a number of associated biomar- kers(1). Some dietary carbohydrates (CHO) have been found to contribute to VAT accumulation(2). Little is known about the impact of following a low-carbohydrate diet versus a high-carbohydrate diet on VAT, adiponectin (ADPN), leptin (LEPT) and leptin:adipo- nectin ratio (LAR). The aim of this investigation was to assess the impact of dietary carbohydrates (CHO) on VAT and emerging CM risk markers in a sample of 10 healthy normal-weight and overweight Caucasian adults aged 32–60 (80 % male) at increased CM risk(3). This pilot study received ethical approval from Liverpool John Moores University Research Ethics Committee (16/ELS/ 029) and was registered with ClinicalTrials.gov (Ref. NCT03257085). Participants were randomly allocated to one of two groups and asked to either consume 50 % energy from CHO (high-carb (HC)) for a duration of 8 weeks. VAT was ana- lysed via bioelectrical impedance (SECA mBCA 515). Blood plasma samples were collected at baseline (BL), interim point (IP) and endpoint (EP) after a 12-hour overnight fast, immediately processed and frozen at -80°C. Thawed plasma samples were analysed via immunoassay technology (Randox Evidence InvestigatorTM Metabolic Syndrome Arrays I and II) for ADPN and LEPT levels. Statistical analysis was undertaken using IBM SPSS 24®. Parametric data was analysed via two-way mixed ANOVA; non-parametric data was analysed via Mann-Whitney U test and Friedman test. Average daily carbohydrate intake in the LC group was 44·2 g at IP and 48·9 g at EP. There were no significant differences between groups at any time point for ADPN, LEPT, LAR or VAT and no significant inter- actions for time or group*time for ADPN, LEPT or LAR. However, in the LC group VAT decreased significantly between baseline and endpoint by 15 % (p = ·015) Over the course of the intervention ADPN and LEPT decreased non- significantly (by 4 % and 70 % respectively) in the LC group, whilst increasing non-significantly in the HC group (9 % and 65 % respectively). LAR increased in the HC group throughout the study, whilst LAR in the LC group decreased albeit not significantly. VAT (litre) ADPN (ng/mL) LEPT (ng/mL) LAR BL IP EP Median Median Median M SD M SD M SD BL IP EP BL IP EP BL IP EP LC 4·1a 1·2 3·8 1·3 3·5a 1·2 8·9 8·6 8·5 3·96 1·64 1·20 0·45 0·19 0·14 HC 2·7 0·1 1·6 0·3 2·5 0·1 11·3 13·4 12·3 0·97 1·1 1·60 0·07 0·07 0·46 ADPN = adiponectin, BL = baseline, EP = endpoint, HC = high-carbohydrate, moderate fat diet, IP = interim point, LAR = leptin:adiponectin ratio, LEPT = leptin, LC = low-carbohydrate, high-fat diet, VAT = visceral adipose tissue, ap = ·015. NB: interquartile ranges not provided for median values due to missing data. Higher LAR has been found to be a marker of increased CM risk(4). In conclusion, while the significant reduction in VAT in the LC group corresponds with the reduction of LAR further evidence is required to corroborate these findings. Previous evidence for LC is supportive for improved CM health from various biomarkers(5); LAR should be considered as a useful endocrine addition for future LC studies. 1. Krasimira A, Mozaffarian D & Pischon T (2018) Clin Chem 64, 142–153. 2. Rüttgers D, Fischer K, Koch M et al. (2015) Br J Nutr 114, 1929–1940. 3. Jebb S, Lovegrove J, Griffin B et al. (2010) Am J Clin Nutr 92, 748–58. 4. López-Jaramillo P, Gómez-Arbeláez D, López-López J et al. (2014) Horm Mol Biol Clin Investig 18, 37–45. 5. Bazzano L, Hi T, Reynolds K et al. (2014) Ann Intern Med 161, 309–318

Prevalence of overweight and obesity in children aged 6–13 years—alarming increase in obesity in Cracow, Poland

This study in children aged 6–13 years (n = 1,499) was performed between October 2008 and March 2009. Height and weight measurements were taken to calculate BMI. The prevalence of overweight and obesity was determined by means of IOTF cut-offs with respect to age. Alarming is the fact that the percentage of obese children in Cracow increased dramatically from 1.04% in boys and 0.20% in girls in 1971 to 7% in boys and 3.6% in girls in 2009. In this report, a higher percentage of overweight boys was observed in rural boys (28.14%) than in urban ones (27.31%). Obesity was identified in an almost twice as high percentage of urban boys (7.78%) as in rural ones (3.52%). A higher percentage of overweight girls was registered in rural areas (16.49%) than in urban ones (16.09%). Obesity was prevailing in rural girls (4.12%) relative to their urban counterparts (3.44%). The highest number of overweight urban boys was diagnosed in the group of 12-year-olds (n = 48) and rural boys in the group of 10-year-olds (n = 39), as well as in urban girls aged 11 (n = 17) and rural girls aged 9 (n = 9). The highest number of obesity was observed in rural boys aged 12 (n = 3) and in urban boys aged 9 and 10 (n = 9 in both groups). In the group of girls, obesity prevailed in urban 9-year-olds (n = 5) and in rural 7-year-olds (n = 5). Conclusions: Overweight and obesity affect boys almost twice as frequently as girls. Obesity is twice as frequent in urban boys as in their rural peers

Results of a feasibility randomised controlled trial (RCT) for WATCH IT: a programme for obese children and adolescents

Background: In the evaluation of childhood obesity interventions, few researchers undertake a rigorous feasibility stage in which the design and procedures of the evaluation process are examined. Consequently, phase III studies often demonstrate methodological weaknesses. Purpose: Our aim was to conduct a feasibility trial of the evaluation of WATCH IT, a community obesity intervention for children and adolescents. We sought to determine an achievable recruitment rate; acceptability of randomisation, assessment procedures, and dropout rate; optimal outcome measures for the definitive trial; and a robust sample size calculation. Method: Our goal was to recruit 70 participants over 6 months, randomise them to intervention or control group, and retain participation for 12 months. Assessments were taken prior to randomisation and after 6 and 12 months. Procedures mirrored those intended for a full-scale trial, but multiple measures of similar outcomes were included as a means to determine those most appropriate for future research. Acceptability of the research and impact of the research on the programme were ascertained through interviewing participants and staff. Results: We recruited 70 participants and found that randomisation and data collection procedures were acceptable. Self-referral (via media promotion) was more effective than professional referral. Blinding of assessors was sustained to a reasonable degree, and optimal outcome measures for a full-scale trial were identified. Estimated sample size was significantly greater than sample sized reported in published trials. There was some negative impact on the existing programme as a result of the research, a lesson for designers of future trials. Limitations: We successfully recruited socially disadvantaged families, but the majority of families were of White British nationality. The composition of the participants was an added valuable lesson, suggesting that recruitment strategies to obtain a more heterogeneous ethnic sample warrant consideration in future research. Conclusions: This study provided us with confidence that we can run a phase III multi-centre trial to test the effectiveness of WATCH IT. Importantly, it was invaluable in informing the design not only of that trial but also of future evaluations of childhood obesity treatment interventions