Bolus tube feeding suppresses food intake and circulating ghrelin concentrations in healthy subjects in a short-term placebo-controlled trial

Background: previous investigations suggest continuous tube feeding (TF) schedules do not suppress appetite and food intake, but bolus TF has been little studied. OBJECTIVE: We tested the hypothesis that 1) bolus TF does not suppress appetite and food intake and 2) there is no interrelation between food intake and appetite mediators (including ghrelin). Design: a single-blind, placebo-controlled trial within which 6 healthy men [body mass index (in kg/m(2)): 21.1 +/- 1.61] received 3 d of bolus TF (6.93 +/- 0.38 MJ/d of 4.18 kJ/mL multinutrient feed). For 2 d before and after TF, placebo boluses (&lt;0.4 MJ/d) were given by tube. Hourly tracking of appetite, weighed measurements of daily ad libitum food intake, and metabolic and hormonal (including ghrelin) measurements were undertaken. Results: total energy intake was significantly increased with bolus TF (18.2 +/- 1.86 MJ; P = 0.0005) despite a partial reduction in food intake compared with placebo periods (P = 0.013) and during the TF period (by 15%; P = 0.007). There was little change in hunger and fullness with bolus TF, and within-day temporal patterns did not differ whether TF or placebo was given. Changes in fasting concentrations of ghrelin (1003.6-756.0 pmol/L; P = 0.013) and other mediators (including leptin, insulin, and glucose) were significantly related to subsequent daily food intake (eg, ghrelin: r(2) = 0.81, P = 0.022). Conclusions: in this short-term study, subjects maintained appetite ratings during bolus TF by a significant reduction in food intake and changes in ghrelin and some appetite mediators related to subsequent daily food intake. Longer-term studies are required to fully ascertain the effect of TF on appetite, food intake, and appetite mediators<br/

Adiposity, fitness, health-related quality of life and the reallocation of time between children’s school day activity behaviours: a compositional data analysis

Sedentary time (ST), light (LPA), and moderate-to-vigorous physical activity (MVPA) constitute the range of school day activity behaviours. This study investigated whether the composition of school activity behaviours was associated with health indicators, and the predicted changes in health when time was reallocated between activity behaviours. Accelerometers were worn for 7-days between October and December 2010 by 318 UK children aged 10–11, to provide estimates of school day ST, LPA, and MVPA. BMI z-scores and percent waist-to-height ratio were calculated as indicators of adiposity. Cardiorespiratory fitness (CRF) was assessed using the 20-m shuttle run test. The PedsQL™ questionnaire was completed to assess psychosocial and physical health-related quality of life (HRQL). Log-ratio multiple linear regression models predicted health indicators for the mean school day activity composition, and for new compositions where fixed durations of time were reallocated from one activity behaviour to another, while the remaining behaviours were unchanged. The school day activity composition significantly predicted adiposity and CRF (p = 0.04–0.002), but not HRQL. Replacing MVPA with ST or LPA around the mean activity composition predicted higher adiposity and lower CRF. When ST or LPA were substituted with MVPA, the relationships with adiposity and CRF were asymmetrical with favourable, but smaller predicted changes in adiposity and CRF than when MVPA was replaced. Predicted changes in HRQL were negligible. The school day activity composition significantly predicted adiposity and CRF but not HRQL. Reallocating time from ST and LPA to MVPA is advocated through comprehensive school physical activity promotion approaches. Trial registration: ISRCTN03863885.</p

Capturing the geography of children’s active and sedentary behaviours at home: the HomeSPACE measurement tool

Children spend much of their time at home, indoors and sedentary. This study reports on the development, exploratory factor analysis, validity and reliability of the HomeSPACE Instrument. The instrument assesses features of the home physical environment that influence children’s sedentary behaviour and physical activity, and the family influences that create this environment. The space and equipment audit achieved good to excellent criterion validity and test-retest reliability for equipment, outdoor features and home design measures (Study 1, n = 36 parents). Family influence scales showed acceptable internal consistency and test-retest reliability (Study 2, n = 96 parents). Factor analysis highlighted fifteen scales to assess the importance, preferences and supportiveness of the home environment for activity. The HomeSPACE Instrument extends previous tools to provide a valid and reliable assessment of home influences on children’s sedentary behaviour and physical activity, that is adaptable for varying home physical environments

Use of human milk fortifier in preterm infants in the community: practical experience from clinical cases

Introduction: Breast milk supplementation with a multicomponent Human Milk Fortifier (HMF) has been shown to be safe and effective in preterm infants in neonatal units, while there is little clinical evidence on its use post-discharge. This series of case-studies aimed to investigate practical use and experience of HMF supplementation in preterm infants with different conditions in the community. Methods: Preterm infants experiencing faltering growth were recruited from two UK neonatal units and supplemented with a novel HMF containing long-chain polyunsaturated fatty acids, medium-chain fatty acids, and anhydrous milk fat as source of beta-palmitate for >7 days in the community. Compliance with prescription, anthropometrics and growth, gastrointestinal (GI) tolerance, acceptability and safety were recorded at baseline, on day of hospital discharge and at the end of intervention. Results: Fourteen infants (mean age: 35weeks+4days (SD 2w+5d) were supplemented with HMF for 29days (SD2, range 15-55) in the community (mean intake 6.2g/d (SD2.6), 26.8kcal/d (SD11.4)), with n=12 being initiated in hospital (mean duration of supplementation=12days (SD11), range 0-37), n=1 on day of discharge and n=1 in the community. Mean compliance was 96% (SD13), with n=13 consuming 100% of HMF prescribed by their healthcare professional (HCP). Infants showed an increase in mean weight (+1.14kg SD0.58), length (+6.66cm SD3.91) and head circumference (+4.35cm SD2.86), with improvement in weight-for-age and length-for-age Z-scores compared to baseline. Mean growth velocity during the intervention period was 15.7g/kg/day (SD 8.62), being 18.0g/kg/day (SD 13) during hospital stay and 10.6g/kg/day (SD 4.4) in the community. Twelve infants (86%) met their growth goal at the end of intervention. There were no GI concerns with the use of HMF, with n=3 experiencing no GI symptoms and n=11 experiencing a few minor symptoms. Most parents (79%) found HMF easy to use and were satisfied overall. Conclusion: The novel HMF supported infants’ growth both during hospital stay and, in the community, whilst being well complied with and accepted overall. No tolerance concerns were reported in this study population. Clear guidelines and standardised protocol on how to use HMF post-discharge are needed

Amino acid formula containing synbiotics in infants with cow’s milk protein allergy: a systematic review and meta-analysis

Cow’s milk protein allergy (CMPA) is associated with dysbiosis of the infant gut microbiome, with allergic and immune development implications. Studies show benefits of combining synbiotics with hypoallergenic formulae, although evidence has never been systematically examined. This review identified seven publications of four randomised controlled trials comparing an amino acid formula (AAF) with an AAF containing synbiotics (AAF-Syn) in infants with CMPA (mean age 8.6 months; 68% male, mean intervention 27.3 weeks, n = 410). AAF and AAF-Syn were equally effective in managing allergic symptoms and promoting normal growth. Compared to AAF, significantly fewer infants fed AAF-Syn had infections (OR 0.35 (95% CI 0.19–0.67), p = 0.001). Overall medication use, including antibacterials and antifectives, was lower among infants fed AAF-Syn. Significantly fewer infants had hospital admissions with AAF-Syn compared to AAF (8.8% vs. 20.2%, p = 0.036; 56% reduction), leading to potential cost savings per infant of £164.05–£338.77. AAF-Syn was associated with increased bifidobacteria (difference in means 31.75, 95% CI 26.04–37.45, p 0.0001); reduced Eubacterium rectale and Clostridium coccoides (difference in means −19.06, 95% CI −23.15 to −14.97, p 0.0001); and reduced microbial diversity (p 0.05), similar to that described in healthy breastfed infants, and may be associated with the improved clinical outcomes described. This review provides evidence that suggests combining synbiotics with AAF produces clinical benefits with potential economic implications

Clustered Cardiometabolic Risk, Cardiorespiratory Fitness and Physical Activity in 10-11 Year-Old Children. The CHANGE! Project Baseline

Objectives: The primary objective of this cross sectional pilot study was to report clustered risk scores combining traditional invasive with non invasive cardiometabolic risk markers in 10-11 year old children participating in the CHANGE! project at baseline. A secondary objective was to determine the relationship between clustered risk score and objectively measured physical activity (PA) and cardiorespiratory fitness (CRF). Methods: Habitual PA was measured using accelerometry and CRF (VO2peak) was assessed using an individually calibrated treadmill based protocol. Twenty-nine participants had valid data for all components of the clustered risk score, calculated using total cholesterol: high density lipoprotein-cholesterol (TC:HDL-C), glucose, systolic blood pressure (BP), LV Mass Index (g/m2.7), and trunk fat mass (g). Participants with a clustered risk score greater than 1SD above the mean, were categorised as ‘higher’ risk (n=6); all others were categorised as ‘normal’ risk. \ud \ud Results: Clustered risk score, controlling for somatic maturity and gender, was negatively correlated with VPA (r= -0.51, p=0.01), MVPA (r= -0.44, p=0.03) and VO2peak (r= -0.57, p<0.01). ANCOVA, with somatic maturity and gender as covariates, revealed that those in the ‘normal’ risk group were more fit than those in the ‘higher’ risk group [f (1,24)=4.518, p=0.044]). There were no statistically significant differences between risk groups and PA however mean data suggest that those in the ‘normal’ risk group accrued 4 minutes more daily VPA than the ‘higher’ risk group which may be clinically important. \ud \ud Conclusions: This provides further evidence of the importance of promoting CRF and VPA in children, to reduce cardiometabolic risk especially for those that are ‘higher’ risk

Somatic mutant clones colonize the human esophagus with age.

The extent to which cells in normal tissues accumulate mutations throughout life is poorly understood. Some mutant cells expand into clones that can be detected by genome sequencing. We mapped mutant clones in normal esophageal epithelium from nine donors (age range, 20 to 75 years). Somatic mutations accumulated with age and were caused mainly by intrinsic mutational processes. We found strong positive selection of clones carrying mutations in 14 cancer genes, with tens to hundreds of clones per square centimeter. In middle-aged and elderly donors, clones with cancer-associated mutations covered much of the epithelium, with NOTCH1 and TP53 mutations affecting 12 to 80% and 2 to 37% of cells, respectively. Unexpectedly, the prevalence of NOTCH1 mutations in normal esophagus was several times higher than in esophageal cancers. These findings have implications for our understanding of cancer and aging.Wellcome Trust Cancer Research U

Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus.

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability

Cardiorespiratory fitness predicts clustered cardiometabolic risk in 10-11.9 year olds

The aim of this study was to investigate levels of clustered cardiometabolic risk and the odds of being ‘at risk’ according to cardiorespiratory fitness status in children. Data from 88 10–11.9-year-old children (mean age 11.05 ± 0.51 years), who participated in either the REACH Year 6 or the Benefits of Fitness Circuits for Primary School Populations studies were combined. Waist circumference, systolic blood pressure, diastolic blood pressure, glucose, triglycerides, high-density lipoprotein cholesterol, adiponectin and C-reactive protein were assessed and used to estimate clustered cardiometabolic risk. Participants were classified as ‘fit’ or ‘unfit’ using recently published definitions (46.6 and 41.9 mL/kg/min for boys and girls, respectively), and continuous clustered risk scores between fitness groups were assessed. Participants were subsequently assigned to a ‘normal’ or ‘high’ clustered cardiometabolic risk group based on risk scores, and logistic regression analysis assessed the odds of belonging to the increased cardiometabolic risk group according to fitness. The unfit group exhibited significantly higher clustered cardiometabolic risk scores (p < 0.001) than the fit group. A clear association between fitness group and being at increased cardiometabolic risk (B = 2.509, p = 0.001) was also identified, and participants classed as being unfit were found to have odds of being classified as ‘at risk’ of 12.30 (95 % CI = 2.64–57.33).\ud \ud Conclusion Assessing cardiorespiratory fitness is a valid method of identifying children most at risk of cardiometabolic pathologies. The ROC thresholds could be used to identify populations of children most at risk and may therefore be used to effectively target a cardiometabolic risk-reducing public health intervention

Somatic Evolution in Non-neoplastic IBD-Affected Colon.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease associated with increased risk of gastrointestinal cancers. We whole-genome sequenced 446 colonic crypts from 46 IBD patients and compared these to 412 crypts from 41 non-IBD controls from our previous publication on the mutation landscape of the normal colon. The average mutation rate of affected colonic epithelial cells is 2.4-fold that of healthy colon, and this increase is mostly driven by acceleration of mutational processes ubiquitously observed in normal colon. In contrast to the normal colon, where clonal expansions outside the confines of the crypt are rare, we observed widespread millimeter-scale clonal expansions. We discovered non-synonymous mutations in ARID1A, FBXW7, PIGR, ZC3H12A, and genes in the interleukin 17 and Toll-like receptor pathways, under positive selection in IBD. These results suggest distinct selection mechanisms in the colitis-affected colon and that somatic mutations potentially play a causal role in IBD pathogenesis