Epigenetic regulation of POMC; implications for nutritional programming, obesity and metabolic disease.

Proopiomelanocortin (POMC) is a key mediator of satiety. Epigenetic marks such as DNA methylation may modulate POMC expression and provide a biological link between early life exposures and later phenotype. Animal studies suggest epigenetic marks at POMC are influenced by maternal energy excess and restriction, prenatal stress and Triclosan exposure. Postnatal factors including energy excess, folate, vitamin A, conjugated linoleic acid and leptin may also affect POMC methylation. Recent human studies suggest POMC DNA methylation is influenced by maternal nutrition in early pregnancy and associated with childhood and adult obesity. Studies in children propose a link between POMC DNA methylation and elevated lipids and insulin, independent of body habitus. This review brings together evidence from animal and human studies and suggests that POMC is sensitive to nutritional programming and is associated with a wide range of weight-related and metabolic outcomes.

Premenopausal abnormal uterine bleeding and risk of endometrial cancer.

BACKGROUND: Endometrial biopsies are undertaken in premenopausal women with abnormal uterine bleeding but the risk of endometrial cancer or atypical hyperplasia is unclear. OBJECTIVES: To conduct a systematic literature review to establish the risk of endometrial cancer and atypical hyperplasia in premenopausal women with abnormal uterine bleeding. SEARCH STRATEGY: Search of PubMed, Embase and the Cochrane Library from database inception to August 2015. SELECTION CRITERIA: Studies reporting rates of endometrial cancer and/or atypical hyperplasia in women with premenopausal abnormal uterine bleeding. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two reviewers and cross-checked. For each outcome, the risk and a 95% CI were estimated using logistic regression with robust standard errors to account for clustering by study. MAIN RESULTS: Sixty-five articles contributed to the analysis. Risk of endometrial cancer was 0.33% (95% CI 0.23-0.48%, n = 29 059; 97 cases) and risk of endometrial cancer or atypical hyperplasia was 1.31% (95% CI 0.96-1.80, n = 15 772; 207 cases). Risk of endometrial cancer was lower in women with heavy menstrual bleeding (HMB) (0.11%, 95% CI 0.04-0.32%, n = 8352; 9 cases) compared with inter-menstrual bleeding (IMB) (0.52%, 95% CI 0.23-1.16%, n = 3109; 14 cases). Of five studies reporting the rate of atypical hyperplasia in women with HMB, none identified any cases. CONCLUSIONS: The risk of endometrial cancer or atypical hyperplasia in premenopausal women with abnormal uterine bleeding is low. Premenopausal women with abnormal uterine bleeding should first undergo conventional medical management. Where this fails, the presence of IMB and older age may be indicators for further investigation. Further research into the risks associated with age and the cumulative risk of co-morbidities is needed. TWEETABLE ABSTRACT: Contrary to practice, premenopausal women with heavy periods or inter-menstrual bleeding rarely require biopsy.

Is consuming yoghurt associated with weight management outcomes? Results from a systematic review.

BACKGROUND: Yoghurt is part of the diet of many people worldwide and is commonly recognised as a 'health food'. Epidemiological studies suggest that yoghurt may be useful as part of weight management programs. In the absence of comprehensive systematic reviews, this systematic review investigated the effect of yoghurt consumption by apparently healthy adults on weight-related outcomes. METHODS: An extensive literature search was undertaken, as part of a wider scoping review, to identify yoghurt studies. A total of 13 631 records were assessed for their relevance to weight-related outcomes. RESULTS: Twenty-two publications were eligible according to the review protocol. Cohort studies (n=6) and cross-sectional studies (n=7) all showed a correlation between yoghurt and lower or improved body weight/composition. Six randomised controlled trials (RCTs) and one controlled trial had various limitations, including small size and short duration. One RCT showed significant effects of yoghurt on weight loss, but was confounded by differences in calcium intake. One trial showed nonsignificant weight gain and the remaining five trials showed nonsignificant weight losses that were greater in yoghurt consumers. CONCLUSIONS: Yoghurt consumption is associated with lower body mass index, lower body weight/weight gain, smaller waist circumference and lower body fat in epidemiological studies. RCTs suggest weight reduction effects, but do not permit determination of a cause-effect relationship. Well-controlled, adequately powered trials in research and community settings appear likely to identify a modest but beneficial effect of yoghurt consumption for prevention of weight gain and management of obesity. The ready availability of yoghurt (a nutrient-dense food) and its ease of introduction to most diets suggests that educating the public to eat yoghurt as part of a balanced and healthy diet may potentially contribute to improved public health. Future carefully designed RCTs could provide proof of principle and large community-based studies could determine the practical impact of yoghurt on body weight/composition.

The aetiology of rickets-like lower limb deformities in Malawian children.

UNLABELLED: Debilitating rickets-like lower limb deformities are common in children throughout the world, particularly in Malawi, Africa where the causes are unknown. We have identified that Blount disease and calcium deficiency rickets are the likely causes of these deformities and propose calcium supplementation as a potential treatment of Malawian rickets. INTRODUCTION: Surgical correction of rickets-like lower limb deformities is the most common paediatric operation performed at Beit Cure Orthopaedic Hospital, Malawi. The aim of this study was to investigate the aetiology of these deformities. METHODS: Children with a tibio-femoral angle of deformity >20° were enrolled (n = 42, 3.0-15.0 years). Anthropometric and early life and well-being data were collected. Early morning serum and urine samples were collected on the morning of the operation for markers of calcium and phosphate homeostasis. Knee radiographs were obtained, and the children were diagnosed with either Blount (BD, n = 22) or evidence of rickets disease (RD, n = 20). As BD is a mechanical rather than metabolic disease, BD were assumed to be biochemically representative of the local population and thus used as a local reference for RD. RESULTS: There were no differences in anthropometry or early life experiences between BD and RD. Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D, total alkaline phosphatase and urinary phosphate were significantly higher and serum phosphate, 25-hydroxyvitamin D (25OHD) and tubular maximal reabsorption of phosphate significantly lower in RD than BD. There was no difference in serum calcium, fibroblast growth factor 23 or markers of iron status between groups. All children had 25OHD > 25 nmol/L. CONCLUSIONS: Vitamin D deficiency is not implicated in the aetiology of RD or BD in Malawian children. The cause of RD in Malawi is likely to be dietary calcium deficiency leading to elevated PTH resulting in increased losses of phosphate from the bone and glomerular filtrate. The causes of BD remain unclear; there was no evidence in support of previously suggested risk factors such as being overweight or starting to walk early. Prior to surgical intervention, supplementation with calcium should be considered for children with RD.

Using fNIRS to Study Working Memory of Infants in Rural Africa.

A pilot study was conducted to assess the feasibility of using fNIRS as an alternative to behavioral assessments of cognitive development with infants in rural Africa. We report preliminary results of a study looking at working memory in 12-16-month-olds and discuss the benefits and shortcomings for the potential future use of fNIRS to investigate the effects of nutritional insults and interventions in global health studies.

Predictors of 25(OH)D half-life and plasma 25(OH)D concentration in The Gambia and the UK.

UNLABELLED: Predictors of 25(OH)D3 half-life were factors associated with vitamin D metabolism, but were different between people in The Gambia and the UK. Country was the strongest predictor of plasma 25(OH)D concentration, probably as a marker of UVB exposure. 25(OH)D3 half-life may be applied as a tool to investigate vitamin D expenditure. INTRODUCTION: The aim of this study was to investigate predictors of 25(OH)D3 half-life and plasma 25(OH)D concentration. METHODS: Plasma half-life of an oral tracer dose of deuterated-25(OH)D3 was measured in healthy men aged 24-39 years, resident in The Gambia, West Africa (n = 18) and in the UK during the winter (n = 18), countries that differ in calcium intake and vitamin D status. Plasma and urinary markers of vitamin D, calcium, phosphate and bone metabolism, nutrient intakes and anthropometry were measured. RESULTS: Normally distributed data are presented as mean (SD) and non-normal data as geometric mean (95% CI). Gambian compared to UK men had higher plasma concentrations of 25(OH)D (69 (13) vs. 29 (11) nmol/L; P < 0.0001); 1,25(OH)2D (181 (165, 197) vs. 120 (109, 132) pmol/L; P < 0.01); and parathyroid hormone (PTH) (50 (42, 60) vs. 33 (27, 39); P < 0.0001). There was no difference in 25(OH)D3 half-life (14.7 (3.5) days vs. 15.6 (2.5) days) between countries (P = 0.2). In multivariate analyses, 25(OH)D, 1,25(OH)2D, vitamin D binding protein and albumin-adjusted calcium (Caalb) explained 79% of variance in 25(OH)D3 half-life in Gambians, but no significant predictors were found in UK participants. For the countries combined, Caalb, PTH and plasma phosphate explained 39 % of half-life variability. 1,25(OH)2D, weight, PTH and country explained 81% of variability in 25(OH)D concentration; however, country alone explained 74%. CONCLUSION: Factors known to affect 25(OH)D metabolism predict 25(OH)D3 half-life, but these differed between countries. Country predicted 25(OH)D, probably as a proxy measure for UVB exposure and vitamin D supply. This study supports the use of 25(OH)D half-life to investigate vitamin D metabolism.

Ethnic differences in urinary calcium and phosphate excretion between Gambian and British older adults.

UNLABELLED: Ethnic differences in renal calcium and phosphate excretion exist, which may depend on differences in their dietary intakes and regulatory factors. We report highly significant differences in urinary calcium and phosphate excretion between white British and Gambian adults after statistical adjustment for mineral intakes, indicating an independent effect of ethnicity. INTRODUCTION: Populations vary in their risk of age-related osteoporosis. There are racial or ethnic differences in the metabolism of the bone-forming minerals calcium (Ca) and phosphate (P), with a lower renal Ca and P excretion in African-Americans compared to white counterparts, even at similar intakes and rates of absorption. Also, Africans in The Gambia have a lower Ca excretion compared to white British subjects, groups known to differ in their dietary Ca intake. Here, we report on differences in urinary Ca and P excretion between Gambian and white British adults while allowing for known predictors, including dietary intakes. METHODS: Participants were healthy white British (n = 60) and Gambian (n = 61) men and women aged 60-75 years. Fasting blood and 2-h urine samples were collected. Markers of Ca and P metabolism were analysed. Dietary intake was assessed with country-specific methods. RESULTS: White British older adults had higher creatinine-corrected urinary Ca and P excretion (uCa/uCr, uP/uCr) and lower tubular maximum of Ca and P compared to Gambian counterparts. The predictors of urinary Ca and P differed between groups. Multiple regression analysis showed that dietary Ca and Ca/P were predictors of uCa/uCr and uP/uCr, respectively. Ethnicity remained a significant predictor of uCa/uCr and uP/uCr after adjustment for diet and other factors. CONCLUSIONS: Gambian older adults have higher renal Ca conservation than British counterparts. Dietary mineral intakes were predictors of the differences in urinary Ca and P excretion, but ethnicity remained a highly significant predictor after statistical adjustment. This suggests that ethnicity has an independent effect on renal Ca and P handling.

ESHRE guideline: management of women with endometriosis.

STUDY QUESTION: What is the optimal management of women with endometriosis based on the best available evidence in the literature? SUMMARY ANSWER: Using the structured methodology of the Manual for ESHRE Guideline Development, 83 recommendations were formulated that answered the 22 key questions on optimal management of women with endometriosis. WHAT IS KNOWN ALREADY: The European Society of Human Reproduction and Embryology (ESHRE) guideline for the diagnosis and treatment of endometriosis (2005) has been a reference point for best clinical care in endometriosis for years, but this guideline was in need of updating. STUDY DESIGN, SIZE, DURATION: This guideline was produced by a group of experts in the field using the methodology of the Manual for ESHRE Guideline Development, including a thorough systematic search of the literature, quality assessment of the included papers up to January 2012 and consensus within the guideline group on all recommendations. To ensure input from women with endometriosis, a patient representative was part of the guideline development group. In addition, patient and additional clinical input was collected during the scoping and review phase of the guideline. PARTICIPANTS/MATERIALS, SETTING, METHODS: NA. MAIN RESULTS AND THE ROLE OF CHANCE: The guideline provides 83 recommendations on diagnosis of endometriosis and on the treatment of endometriosis-associated pain and infertility, on the management of women in whom the disease is found incidentally (without pain or infertility), on prevention of recurrence of disease and/or painful symptoms, on treatment of menopausal symptoms in patients with a history of endometriosis and on the possible association of endometriosis and malignancy. LIMITATIONS, REASONS FOR CAUTION: We identified several areas in care of women with endometriosis for which robust evidence is lacking. These areas were addressed by formulating good practice points (GPP), based on the expert opinion of the guideline group members. WIDER IMPLICATIONS OF THE FINDINGS: Since 32 out of the 83 recommendations for the management of women with endometriosis could not be based on high level evidence and therefore were GPP, the guideline group formulated research recommendations to guide future research with the aim of increasing the body of evidence. STUDY FUNDING/COMPETING INTEREST(S): The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the implementation of the guideline. The guideline group members did not receive payment. All guideline group members disclosed any relevant conflicts of interest (see Conflicts of interest). TRIAL REGISTRATION NUMBER: NA.

Optical imaging of brain activation in Gambian infants.

We used optical topography (OT) to investigate cognitive function in infants in rural Gambia. Images of changes in oxyhaemoglobin and deoxyhaemoglobin concentrations were reconstructed using a multispectral algorithm which uses the finite element method (FEM) to model the propagation of light through scattering tissue using the diffusion equation. High quality OT data enabled us to reconstruct images with robust representation of haemodynamic changes. OT is a feasible neuroimage technology for this resource-poor setting.

Intact fibroblast growth factor 23 and fragments in plasma from Gambian children.

UNLABELLED: Fibroblast growth factor 23 (FGF23) is grossly elevated in Gambian children with rickets and, at a lower prevalence, in those without bone deformities. We used western blotting to mimic the detection capabilities of the C-terminal FGF23 enzyme-linked immunosorbent assay (ELISA). Only intact FGF23 hormone was present in Gambian plasma samples from children with and without rickets. INTRODUCTION: Elevated circulating FGF23 concentrations have been detected in plasma samples from Gambian children using the C-terminal Immutopics ELISA. The Immutopics ELISA detects both the intact FGF23 hormone and the C-terminal fragment. The aim of this study was to determine whether the elevated FGF23 concentrations as detected by the ELISA were predominantly due to a high proportion of intact FGF23 hormone and/or C-terminal FGF23 fragments. METHODS: Stored, frozen plasma samples from previous studies of Gambian children with known concentrations of FGF23 as determined by C-terminal Immutopics ELISA assay, were selected for western blotting analysis: from children with rickets-like bone deformities (n = 4) and local controls (n = 4), with elevated >900 RU/ml (n = 2) and normal <30 RU/ml (n = 2; from each group). The anti-FGF23 polyclonal antibody that recognizes the C-terminal of FGF23 (as used in the Immutopics kit) was used as the primary antibody and the anti-IgG polyclonal antibody conjugated to horseradish peroxidase (HRP) was used as the secondary antibody. RESULTS: Firstly, C-terminal FGF23 fragments, although detectable in standards from the Immutopics ELISA kit, were not in the Gambian plasma samples. Secondly, there was no difference in the size of FGF23 molecules present in plasma from children with rickets-like bone deformities and children from the local community. CONCLUSIONS: Western blotting has provided evidence that elevated FGF23 concentrations, as determined by the C-terminal Immutopics ELISA, measured in Gambian children with and without rickets-like bone deformities was not caused by an increased proportion of circulating inactive C-terminal fragments.

Acute response to oral calcium loading in pregnant and lactating women with a low calcium intake: a pilot study.

UNLABELLED: This pilot study in women from The Gambia with low habitual calcium intakes showed differences in calciotropic hormones between pregnant, lactating and non-pregnant, non-lactating women similar to those in Western women. The response to oral calcium loading indicates a high degree of calcium conservation independent of reproductive status. INTRODUCTION: In pregnancy and early lactation, parathyroid hormone (PTH) concentrations may be suppressed. Uncertainty exists about how calcium metabolism is regulated, particularly when calcium intake is low. METHODS: We investigated fasting markers of calcium metabolism and the acute calcemic and calciuric responses after an oral calcium load in 30 pregnant, lactating or non-pregnant, non-lactating (NPNL) Gambian women with low habitual calcium intakes. Women received 1 g elemental calcium (CaCO3) at 0 min. Blood was collected at -30 and 180 min. Urine was collected from -60 to 0, 0-120 and 120-240 min. Samples were analysed (blood: ionized calcium (iCa); plasma (p): total calcium (tCa), phosphate (P), creatinine (Cr), PTH, 1,25-dihydroxyvitamin D (1,25(OH)2D), osteocalcin (OC), ß C-terminal cross-linked telopeptide of type 1 collagen (ßCTX), cyclic adenosine monophosphate (cAMP); urine (u): Ca, P, Cr, cAMP). RESULTS: Pre-loading, groups did not differ significantly in iCa, pP, uCa/Cr and uP/Cr. pOC concentrations were significantly lower and NcAMP and p1,25(OH)2D higher in pregnant women; pPTH and pßCTX in lactating women were higher than in NPNL women. Post-loading, iCa, ptCa and uCa/Cr concentrations increased; pPTH, NcAMP, ßCTX and uP/Cr decreased in all groups, but the magnitude of change did not differ significantly between groups. CONCLUSION: Differences between pregnant, lactating and NPNL Gambian women in pPTH, NcAMP and p1,25(OH)2D and bone markers were similar to Western women. However, the response to calcium loading indicates that there may be no differences in renal and intestinal calcium economy associated with reproductive status, potentially due to a high degree of calcium conservation associated with low intakes.

Bone mass, body composition and vitamin D status of ARV-naïve, urban, black South African women with HIV infection, stratified by CD4 count.

UNLABELLED: This is the first report examining vitamin D status and bone mass in African women with HIV infection using dual-energy X-ray absorptiometry (DXA) with an appropriate HIV-negative control group. Unlike previous publications, it demonstrates no difference in bone mineral density (BMD) or vitamin D status in HIV-positive patients, at different disease stages, vs. HIV-negative subjects. INTRODUCTION: Low bone mass and poor vitamin D status have been reported among HIV-positive patients; suggesting HIV or its treatment may increase the risk of osteoporosis, a particular concern for women in countries with high HIV prevalence such as South Africa. We describe bone mass and vitamin D status in urban premenopausal South African women, who were HIV positive but not on antiretroviral therapy (ARV). METHODS: This study is a cross-sectional measurement of BMD and body composition by DXA and vitamin D status by serum 25-hydroxyvitamin D (25(OH)D) concentration. Subjects were recruited into three groups: HIV negative (n = 98) and HIV positive with preserved CD4 cell count (non-ARV; n = 74) or low CD4 cell counts prior to ARV initiation (pre-ARV; n = 75). RESULTS: The mean (standard deviation (SD)) age of women was 32.1 (7.2) years. Mean CD4 (SD) counts (×10(6)/l) were 412 (91) and 161 (69) in non-ARV and pre-ARV groups (p < 0.0001). Pre-ARV women were significantly lighter and had lower mean BMI than the other two groups (p < 0.002). The pre-ARV group also had significantly less fat and lean mass compared with non-ARV and HIV-negative subjects (p ≤ 0.05). After full adjustment, there were no significant differences in BMD at any site (p > 0.05) between the groups, nor was vitamin D status significantly different between groups (p > 0.05); the mean (SD) cohort 25(OH)D being 60 (18) nmol/l. CONCLUSION: Contrary to previous studies, these HIV-positive women did not have lower BMD or 25(OH)D concentrations than HIV-negative controls, despite the pre-ARV group being lighter with lower BMI.

Proceedings of the Rank Forum on Vitamin D.

The Rank Forum on Vitamin D was held on 2nd and 3rd July 2009 at the University of Surrey, Guildford, UK. The workshop consisted of a series of scene-setting presentations to address the current issues and challenges concerning vitamin D and health, and included an open discussion focusing on the identification of the concentrations of serum 25-hydroxyvitamin D (25(OH)D) (a marker of vitamin D status) that may be regarded as optimal, and the implications this process may have in the setting of future dietary reference values for vitamin D in the UK. The Forum was in agreement with the fact that it is desirable for all of the population to have a serum 25(OH)D concentration above 25 nmol/l, but it discussed some uncertainty about the strength of evidence for the need to aim for substantially higher concentrations (25(OH)D concentrations>75 nmol/l). Any discussion of 'optimal' concentration of serum 25(OH)D needs to define 'optimal' with care since it is important to consider the normal distribution of requirements and the vitamin D needs for a wide range of outcomes. Current UK reference values concentrate on the requirements of particular subgroups of the population; this differs from the approaches used in other European countries where a wider range of age groups tend to be covered. With the re-emergence of rickets and the public health burden of low vitamin D status being already apparent, there is a need for urgent action from policy makers and risk managers. The Forum highlighted concerns regarding the failure of implementation of existing strategies in the UK for achieving current vitamin D recommendations.

Implementation of long-term non-participant reminders for flexible sigmoidoscopy screening.

The clinical effectiveness of screening is highly dependent on uptake. Previous randomised controlled trials suggest that non-participant reminders, which highlight the opportunity to re-book an appointment, can improve participation. The present analysis examines the impact of implementing these reminders within the English Flexible Sigmoidoscopy (FS) Screening Programme, which offers once-only FS screening to adults aged 55-59 years. We assessed the screening status of 26,339 individuals invited for once-only FS screening in England. A total of 10,952 (41.6%) had attended screening, and were subsequently ineligible. The remaining 15,387 had not attended screening, and were selected to receive a reminder, 1-2 years after their invitation. Descriptive statistics were used to assess the increase in uptake and the adenoma detection rate (ADR) of those who self-referred, six months after the delivery of the final reminder. Pearson's Chi-Square was used to compare the ADR between those who attended when invited and those who self-referred. Of the 15,387 adults eligible to receive a reminder, 13,626 (88.6%) were sent a reminder as intended (1,761 were not sent a reminder, due to endoscopy capacity). Of these, 8.0% (n = 1,086) booked and attended an appointment, which equated to a 4.1% increase in uptake from 41.6% at baseline, to 45.7% at follow-up. The ADR was significantly higher for those who self-referred, compared with those who attended when invited (13.3% and 9.5%, respectively; X 2 = 16.138, p = 0.000059). The implementation of non-participant reminders led to a moderate increase in uptake. Implementing non-participant reminders could help mitigate the negative effects of COVID-19 on uptake.

Early-life nutritional and environmental determinants of thymic size in infants born in rural Bangladesh.

AIM: The aim was to assess the impact of nutritional status and environmental exposures on infant thymic development in the rural Matlab region of Bangladesh. METHODS: In a cohort of N(max) 2094 infants born during a randomized study of combined interventions to improve maternal and infant health, thymic volume (thymic index, TI) was assessed by ultrasonography at birth and at 8, 24 and 52 weeks of age. Data on birth weight, infant anthropometry and feeding status were also collected. RESULTS: At all ages, TI was positively associated with infant weight and strongly associated with the month of measurement. Longer duration of exclusive breastfeeding resulted in a larger TI at 52 weeks. TI at birth and at 8 weeks correlated positively with birth weight, but by 24 and 52 weeks and when adjusted for infant weight this effect was no longer present. Thymic size was not affected by pre-natal maternal supplementation or by socioeconomic status but was correlated to arsenic exposure during pregnancy. CONCLUSION: In this population of rural Bangladeshi infants, thymic development is influenced by both nutritional and environmental exposures early in life. The long-term functional implications of these findings warrant further investigation.

No effect of monthly supplementation with 12000 IU, 24000 IU or 48000 IU vitamin D3 for one year on muscle function: The vitamin D in older people study.

Vitamin D plays a role in muscle function through genomic and non-genomic processes. The objective of this RCT was to determine the effect of monthly supplemental vitamin D3 onmuscle function in 70+ years old adults. Participants (n = 379) were randomized to receive, 12,000 IU, 24,000 IU or 48,000 IU of vitamin D3 monthly for 12 months. Standardized Hand Grip Strength (GS) and Timed-Up and Go (TUG) were measured before and after vitamin D3 supplementation. Fasting total plasma 25 hydroxyvitamin D (25OHD) and Parathyroid Hormone (PTH) concentrations were measured by Liquid Chromatography Tandem Mass Spectrometry (LC-MSMS) and immunoassay, respectively. Baseline plasma 25OHD concentrations were 41.3 (SD 19.9), 39.5 (SD 20.6), 38.9 (SD 19.7) nmol/L; GS values were 28.5 (SD 13.4), 28.8 (SD 13.0) and 28.1 (SD 12.1) kg and TUG test values were 10.8 (SD 2.5), 11.6 (SD 2.9) and 11.9 (SD 3.6) s for the 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively. Baseline plasma 25OHD concentration < 25 nmol/L was associated with lower GS (P = 0.003). Post-interventional plasma 25OHD concentrations increased to 55.9 (SD 15.6), 64.6 (SD15.3) and 79.0 (SD 15.1) nmol/L in the 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively and there was a significant dose-related response in post-interventional plasma 25OHD concentration (p<0.0001). Post-interventional GS values were 24.1 (SD 10.1), 26.2 (SD10.6) and 25.7 (SD 9.4) kg and TUG test values were 11.5 (SD 2.6), 12.0 (SD 3.7) and 11.9 (SD 3.2) s for 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively. The change (Δ) in GS and TUG from pre to post-intervention was not different between treatment groups before and after the adjustment for confounders, suggesting no effect of the intervention. Plasma 25OHD concentration was not associated with GS and TUG test after supplementation. In conclusion, plasma 25OHD concentration < 25 nmol/L was associated with lower GS at baseline. However, monthly vitamin D3 supplementation with 12,000 IU, 24,000 IU and 48,000 IU, for 12 months had no effect on muscle function in older adults aged 70+ years. Trial Registration : EudraCT 2011-004890-10 and ISRCTN35648481.

Evolutionary origins of the obesity epidemic: natural selection of thrifty genes or genetic drift following predation release?

This article challenges Speakman's hypothesis that the modern genetic predisposition to obesity has arisen through random genetic drift in the two million years following predation release. We present evidence in support of the hypothesis that a mixture of famines and seasonal food shortages in the post-agricultural era have exerted natural selection in favour of fat storage; an effect most likely mediated through fertility, rather than viability, selection. We conclude that, far from being time to call off the search, recently developed genetic and bioinformatic methods will soon provide a definitive resolution to this long-standing 'thrifty gene' controversy.

Use of bioelectrical impedance analysis to assess body composition in rural Gambian children.

OBJECTIVE: To validate the Tanita BC-418MA Segmental Body Composition Analyser and four-site skinfold measurements for the prediction of total body water (TBW), percentage fat-free mass (%FFM) and percentage body fat (%BF) in a population of rural Gambian children. SUBJECTS/METHODS: One hundred and thirty-three healthy Gambian children (65 males and 68 females). FFM estimated by the inbuilt equations supplied with the Tanita system was assessed by comparison with deuterium oxide dilution and novel prediction equations were produced. Deuterium oxide dilution was also used to develop equations for %BF based on four-site skinfolds (biceps, triceps, subscapular and suprailiac). RESULTS: The inbuilt equations underestimated FFM compared to deuterium oxide dilution in all the sex and age categories (P<0.003), with greater accuracy in younger children and in males. The best prediction of %FFM was obtained from the variables height, weight, sex, impedance, age and four skinfold thickness measurements (adjusted R(2)=0.84, root mean square error (MSE)=2.07%). CONCLUSIONS: These data suggest that the Tanita instrument may be a reliable field assessment technique in African children, when using population and gender-specific equations to convert impedance measurements into estimates of FFM.