Effects of increased wholegrain consumption on immune and inflammatory markers in healthy low habitual wholegrain consumers.

PURPOSE: Wholegrain (WG) consumption is associated with reduced risk of cardiovascular disease, but clinical data on inflammation and immune function is either conflicting or limited. The objective of this study was to assess the impact of increasing WG consumption to at least 80 g/day on markers of inflammation and glucose metabolism and on phenotypic and functional aspects of the immune system, in healthy, middle-aged adults with low habitual WG intake. METHODS: Subjects consumed a diet high in WG (>80 g/day) or low in WG (<16 g/day, refined grain diet) in a crossover study, with 6-week intervention periods, separated by a 4-week washout. Adherence to the dietary regimes was achieved by dietary advice and provision of a range of food products, with compliance verified by analysis of plasma alkylresorcinols (ARs). RESULTS: On the WG intervention, WG consumption reached 168 g/day (P < 0.001), accompanied by an increase in plasma ARs (P < 0.001) and fibre intake (P < 0.001), without affecting other aspects of dietary intake. On the WG arm, there were trends for lower ex vivo activation of CD4(+) T cells and circulating concentrations of IL-10, C-reactive protein, C-peptide, insulin and plasminogen activator inhibitor-1. The percentage of CD4(+) central memory T cells and circulating levels of adipsin tended to increase during the WG intervention. CONCLUSIONS: Despite the dramatic increase in WG consumption, there were no effects on phenotypic or functional immune parameters, markers of inflammation or metabolic markers.

Increased whole grain consumption does not affect blood biochemistry, body composition, or gut microbiology in healthy, low-habitual whole grain consumers.

BACKGROUND: Whole-grain (WG) foods have been suggested to reduce the risk of cardiovascular disease, but studies are inconsistent and effects on cardiovascular risk markers are not clear. OBJECTIVE: The objective of this study was to assess the impact of increasing WG consumption to at least 80 g/d on overall dietary intake, body composition, blood pressure (BP), blood lipids, blood glucose, gastrointestinal microbiology, and gastrointestinal symptoms in healthy, middle-aged adults with habitual WG intake <24 g/d. METHODS: Eligible subjects [12 men, 21 women, aged 40-65 y, body mass index (BMI): 20-35 kg/m(2)] were identified through use of food frequency questionnaires and subsequently completed 3-day food diaries (3DFDs) to confirm habitual WG consumption. Subjects consumed diets high in WG (>80 g/d) or low in WG [<16 g/d, refined-grain (RG) diet] in a crossover study with 6-wk intervention periods separated by a 4-wk washout. Adherence was achieved by specific dietary advice and provision of a range of cereal food products. The 3DFDs, diet compliance diaries, and plasma alkylresorcinols were used to verify compliance. RESULTS: During the WG intervention, consumption increased from 28 g/d to 168 g/d (P < 0.001), accompanied by an increase in plasma alkylresorcinols (P < 0.001) and total fiber intake (P < 0.001), without any effect on energy or other macronutrients. Although there were no effects on studied variables, there were trends toward increased 24-h fecal weight (P = 0.08) and reduction in body weight (P = 0.10) and BMI (P = 0.08) during the WG intervention compared with the RG period. CONCLUSION: A combination of dietary advice and provision of commercially available food items enabled subjects with a low-moderate habitual consumption of WG to substantially increase their WG intake, but there was little effect on blood biochemical markers, body composition, BP, fecal measurements, or gut microbiology. This trial was registered at www.controlled-trials.com as ISRCTN36521837.

Mouse maternal systemic inflammation at the zygote stage causes blunted cytokine responsiveness in lipopolysaccharide-challenged adult offspring.

BACKGROUND: The preimplantation embryo is sensitive to culture conditions in vitro and poor maternal diet in vivo. Such environmental perturbations can have long-lasting detrimental consequences for offspring health and physiology. However, early embryo susceptibility to other aspects of maternal health and their potential long-term influence into adulthood is relatively unexplored. In this study, we established an in vivo mouse model of maternal periconceptional systemic inflammation by intraperitoneal lipopolysaccharide (LPS) administration on the day of zygote formation and investigated the consequences into adulthood. RESULTS: In the short term, maternal LPS challenge induced a transient and typical maternal sickness response (elevated serum proinflammatory cytokines and hypoactive behaviour). Maternal LPS challenge altered preimplantation embryo morphogenesis and cell lineage allocation, resulting in reduced blastocyst inner cell mass (ICM) cell number and a reduced ICM:trophectoderm cell ratio. In the long term, diverse aspects of offspring physiology were affected by maternal LPS treatment. Whilst birthweight, growth and adult blood pressure were unaltered, reduced activity in an open-field behaviour test, increased fat pad:body weight ratio and increased body mass index were observed in male, but not female, offspring. Most importantly, the maternal LPS challenge caused corticosterone-independent blunting of the serum proinflammatory cytokine response to innate immune challenge in both male and female offspring. The suppressed state of innate immunity in challenged offspring was dose-dependent with respect to the maternal LPS concentration administered. CONCLUSIONS: These results demonstrate for the first time that the preimplantation embryo in vivo is sensitive to maternal systemic inflammation, with effects on blastocyst cell lineage allocation and consequences for behaviour, adiposity and innate immune response in adult offspring. Critically, we identify a novel mechanism mediated through maternal-embryonic interactions that confers plasticity in the development of the innate immune system, which is potentially important in setting postnatal tolerance to environmental pathogens. Our study extends the concept of developmental programming of health and disease to include maternal health at the time of conception.

Timing of surgical intervention for developmental dysplasia of the hip: a randomised controlled trial (Hip 'Op).

BACKGROUND: Developmental dysplasia of the hip (DDH) is a very common congenital disorder, and late-presenting cases often require surgical treatment. Surgical reduction of the hip may be complicated by avascular necrosis (AVN), which occurs as a result of interruption to the femoral head blood supply during treatment and can result in long-term problems. Some surgeons delay surgical treatment until the ossific nucleus (ON) has developed, whereas others believe that the earlier the reduction is performed, the better the result. Currently there is no definitive evidence to support either strategy. OBJECTIVES: To determine, in children aged 12 weeks to 13 months, whether or not delayed surgical treatment of a congenitally dislocated hip reduces the incidence of AVN at 5 years of age. The main clinical outcome measures were incidence of AVN and the need for a secondary surgical procedure during 5 years' follow-up. In addition, to perform (1) a qualitative evaluation of the adopted strategy and (2) a health economic analysis based on NHS and societal costs. DESIGN: Phase III, unmasked, randomised controlled trial with qualitative and health economics analyses. Participants were randomised 1 : 1 to undergo either early or delayed surgery. SETTING: Paediatric orthopaedic surgical centres in the UK. PARTICIPANTS: Children aged 12 weeks to 13 months with DDH, either newly diagnosed or following failed splintage, and who required surgery. We had a target recruitment of 636 children. INTERVENTIONS: Surgical reduction of the hip performed as per the timing allocated at randomisation. MAIN OUTCOME MEASURES: Primary outcome - incidence of AVN at 5 years of age (according to the Kalamchi and MacEwen classification). Secondary outcomes - need for secondary surgery, presence or absence of the ON at the time of primary treatment, quality of life for the main carer and child, and a health economics and qualitative analysis. RESULTS: The trial closed early after reaching < 5% of the recruitment target. Fourteen patients were randomised to early treatment and 15 to delayed treatment. Implementation of rescue strategies did not improve recruitment. No primary outcome data were collected, and no meaningful conclusions could be made from the small number of non-qualitative secondary outcome data. The qualitative work generated rich data around three key themes: (1) access to, and experiences of, primary and secondary care; (2) the impact of surgery on family life; and (3) participants' experiences of being in the trial. LIMITATIONS: Overoptimistic estimates of numbers of eligible patients seen at recruiting centres during the planning of the trial, as well as an overestimation of the recruitment rate, may have also contributed to unrealistic expectations on achievable patient numbers. FUTURE WORK: There may be scope for investigation using routinely available data. CONCLUSIONS: Hip 'Op has highlighted the importance of accurate advance information on numbers of available eligible patients, as well as support from all participating investigators when conducting surgical research. Despite substantial consultation with parents of children in the planning stage, the level of non-participation experienced during recruitment was much higher than anticipated. The qualitative work has emphasised the need for appropriate advice and robust support for parents regarding the 'real-life' aspects of managing children with DDH. TRIAL REGISTRATION: Current Controlled Trials ISRCTN76958754. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 63. See the NIHR Journals Library website for further project information.