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Vitamin D and the vitamin D receptor (VDR) have been shown to be important regulators of the immune system. In particular, vitamin D and VDR deficiency exacerbates experimental autoimmune diseases such as inflammatory bowel disease (IBD). IBD develops due to an immune-mediated attack by pathogenic T-cells that overproduce IL-17 and IFN-γ and a few regulatory cells. VDR knockout mice have twice as many T-cells making IL-17 and IFN-γ than wild-type mice. In addition, vitamin D and the VDR are required for normal numbers of regulatory T-cells (iNKT and CD8αα) that have been shown to suppress experimental IBD. In the absence of vitamin D and the VDR, autoimmunity occurs in the gastrointestinal tract due to increased numbers of IL-17 and IFN-γ secreting T-cells and a concomitant reduction in regulatory T-cells.
Obesity is a serious problem that affects children from diverse ethnic backgrounds in both industrialised and developing countries. Worldwide, an estimated twenty-two million children <5 years of age were overweight in 2007. In the UK if current trends continue an estimated one-quarter of all children <16 years of age will be obese by 2050. Recent evidence suggests that most obesity is established during the preschool years, and because one in five obese 4 year olds will become obese adults this situation has major implications for public health. The causes of obesity in preschool children are complex and multifactorial. Although 30–50% of the predisposition towards obesity in preschool children can be explained by genetic factors, environmental influences also play a crucial role. The preschool period in particular is a pivotal time during which long-term dietary and physical activity habits are established, with potential lifelong effects on health. However, research in this age-group is limited. Previous studies have aimed to improve diet, increase physical activity and achieve behavioural change. However, few of these studies have been successful and there is an urgent need, therefore, for the development of evidence-based interventions aimed at the prevention of preschool obesity.
The terminology used for describing intervention groups in randomised controlled trials (RCT) on the effect of intravenous fluid on outcome in abdominal surgery has been imprecise, and the lack of standardised definitions of the terms ‘standard’, ‘restricted’ and ‘liberal’ has led to some confusion and difficulty in interpreting the literature. The aims of this paper were to clarify these definitions and to use them to perform a meta-analysis of nine RCT on primarily crystalloid-based peri-operative intravenous fluid therapy in 801 patients undergoing elective open abdominal surgery. Patients who received more or less fluids than those who received a ‘balanced’ amount were considered to be in a state of ‘fluid imbalance’. When ‘restricted’ fluid regimens were compared with ‘standard or liberal’ fluid regimens, there was no difference in post-operative complication rates (risk ratio 0·96 (95% CI 0·56, 1·65), P=0·89) or length of hospital stay (weighted mean difference (WMD) −1·77 (95% CI −4·36, 0·81) d, P=0·18). However, when the fluid regimens were reclassified and patients were grouped into those who were managed in a state of fluid ‘balance’ or ‘imbalance’, the former group had significantly fewer complications (risk ratio 0·59 (95% CI 0·44, 0·81), P=0·0008) and a shorter length of stay (WMD −3·44 (95% CI −6·33, −0·54) d, P=0·02) than the latter. Using imprecise terminology, there was no apparent difference between the effects of fluid-restricted and standard or liberal fluid regimens on outcome in patients undergoing elective open abdominal surgery. However, patients managed in a state of fluid balance fared better than those managed in a state of fluid imbalance.
Non-alcoholic fatty liver disease (NAFLD) is now the most common liver disease in both adults and children worldwide. As a disease spectrum, NAFLD may progress from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. An estimated 20–35% of the general population has steatosis, 10% of whom will develop the more progressive non-alcoholic steatohepatitis associated with markedly increased risk of cardiovascular- and liver-related mortality. Development of NAFLD is strongly linked to components of the metabolic syndrome including obesity, insulin resistance, dyslipidaemia and type 2 diabetes. The recognition that NAFLD is an independent risk factor for CVD is a major public health concern. There is a great need for a sensitive non-invasive test for the early detection and assessment of the stage of NAFLD that could also be used to monitor response to treatment. The cellular and molecular aetiology of NAFLD is multi-factorial; genetic polymorphisms influencing NAFLD have been identified and nutrition is a modifiable environmental factor influencing NAFLD progression. Weight loss through diet and exercise is the primary recommendation in the clinical management of NAFLD. The application of systems biology to the identification of NAFLD biomarkers and factors involved in NAFLD progression is an area of promising research.
Ageing is an inevitable biological process with gradual and spontaneous biochemical and physiological changes and increased susceptibility to diseases. The nutritional factor, zinc, may remodel these changes with subsequent healthy ageing, because zinc improves the inflammatory/immune response as shown by in vitro and in vivo studies. The intracellular zinc homeostasis is regulated by buffering metallothioneins (MT) and zinc transporters (ZnT and ZIP families) that mediate the intracellular zinc signalling assigning to zinc a role of ‘second messenger’. In ageing, the intracellular zinc homeostasis is altered, because high MT are unable to release zinc and some zinc transporters deputed to zinc influx (ZIP family) are defective leading to low intracellular zinc content for the immune efficiency. Physiological zinc supplementation in the elderly improves these functions. However, the choice of old subjects for zinc supplementation has to be performed in relation to the specific genetic background of MT and IL-6, because the latter is involved both in MTmRNA and in intracellular zinc homeostasis. Old subjects carrying GG genotypes (C–carriers) in the IL-6–174G/C locus display high IL-6, low intracellular zinc content, impaired innate immunity and enhanced MT. Old subjects carrying GC and CC genotypes (C+carriers) display satisfactory intracellular zinc content, adequate innate immunity and are more prone to reach longevity. Zinc supplementation in old C–carriers restores natural killer cell cytotoxicity and zinc status. The genetic variations of the IL-6−174G/C locus when associated with those of the MT1A+647A/C locus are useful tools for the choice of old people for zinc supplementation.
CHD is the leading cause of worldwide mortality. The prevalence of heart disease has been linked to the adoption of a sedentary lifestyle and the increased dietary dependence on saturated fats from animal sources and the intake of refined foods. Elevated blood cholesterol level is one of the major risk factors for CHD. While cholesterol-lowering drug therapy (statins) has been effective in reducing the risk of heart disease, there are those individuals who are unwilling or because of muscle pains or raised levels of liver or muscle enzymes are unable to take cholesterol-lowering medication. Fortunately, there is evidence linking a number of dietary components to CHD risk reduction. The strength of this evidence has prompted various regulatory bodies to advocate diet as the first line of defence for primary prevention of heart disease. It was therefore decided to combine four dietary components that have been shown to lower blood cholesterol concentrations (nuts, plant sterols, viscous fibre and vegetable protein) in a dietary portfolio in order to determine whether the combined effect is additive. In a metabolically-controlled setting this dietary portfolio has proved to be as effective as a starting dose of a first-generation statin cholesterol-lowering medication in reducing the risk of CHD. The dietary portfolio has also been shown to be effective in sustaining a clinically-significant effect in the long term under a ‘real-world’ scenario. However, success of the diet depends on compliance and despite the accessibility of the foods adherence has been found to vary greatly. Overall, the evidence supports the beneficial role of the dietary portfolio in reducing blood cholesterol levels and CHD risk.
Concerns about the over-prescription of peri-operative fluids, particularly normal saline, culminated in the recent publication of UK national guidelines on fluid prescription during and after surgery. A working group comprising members of the nutrition support team, surgeons, anaesthetists and pharmacists therefore sought to reduce the overall levels of fluid prescription and to limit normal saline usage in our large Teaching Hospital by producing written local fluid prescribing guidelines and holding a series of fluid prescription education sessions for consultants and junior staff. Ideally, the success of such measures would have been determined by studies on fluid balance, body weight and/or measured body water in large numbers of individual patients in a large cluster-randomised controlled trial. However, this would have proved logistically difficult and very costly especially as it is notoriously difficult to rely on the accuracy of daily fluid balance charts in large numbers of patients on busy post-operative surgical wards. We therefore undertook a pragmatic study, comparing historical data on fluid type/volume prescribed (from both individual and ward level pharmacy records), oedema status and clinical outcomes from 2002 with two prospective audits of similar data carried out during 2008 and 2009. Our data showed that in the comparable, elective surgical patients within each audit, there was a decline in total intravenous fluids prescribed over the first 5 post-operative days from 21·1 litres per patient in 2002 to 14·2 litres per patient in 2009 (P<0·05), while pharmacy records showed that the proportion of 0·9% saline supplied declined from 60% to 35% of all fluids supplied to the surgical wards involved, with a concomitant increase in the use of 4%/0·18% dextrose-saline and Hartmann's solution. Alongside these changes in fluid prescribing, the number of patients with clinically apparent oedema declined from 53% in 2002 to 36% in 2009; gut function returned more quickly (6 d in 2002 v. 4 d in 2009, P<0·05) and the length of stay improved from 13 d in 2002 to 10 d in 2009, P<0·05). Although we accept that other factors might have contributed to the observed changes in these clinical parameters, we believe that the measures to reduce fluid and saline administration were the major contributors to these improved clinical outcomes.