How do we improve adolescent diet and physical activity in India and sub-Saharan Africa? Findings from the Transforming Adolescent Lives through Nutrition (TALENT) consortium.

OBJECTIVE: Adolescent diet, physical activity and nutritional status are generally known to be sub-optimal. This is an introduction to a special issue of papers devoted to exploring factors affecting diet and physical activity in adolescents, including food insecure and vulnerable groups. SETTING: Eight settings including urban, peri-urban and rural across sites from five different low- and middle-income countries. DESIGN: Focus groups with adolescents and caregivers carried out by trained researchers. RESULTS: Our results show that adolescents, even in poor settings, know about healthy diet and lifestyles. They want to have energy, feel happy, look good and live longer, but their desire for autonomy, a need to 'belong' in their peer group, plus vulnerability to marketing exploiting their aspirations, leads them to make unhealthy choices. They describe significant gender, culture and context-specific barriers. For example, urban adolescents had easy access to energy dense, unhealthy foods bought outside the home, whereas junk foods were only beginning to permeate rural sites. Among adolescents in Indian sites, pressure to excel in exams meant that academic studies were squeezing out physical activity time. CONCLUSIONS: Interventions to improve adolescents' diets and physical activity levels must therefore address structural and environmental issues and influences in their homes and schools, since it is clear that their food and activity choices are the product of an interacting complex of factors. In the next phase of work, the Transforming Adolescent Lives through Nutrition consortium will employ groups of adolescents, caregivers and local stakeholders in each site to develop interventions to improve adolescent nutritional status.

Barriers to adopting a Mediterranean diet in Northern European adults at high risk of developing cardiovascular disease.

BACKGROUND: Strong evidence links the consumption of a Mediterranean diet (MD) with a reduced cardiovascular disease (CVD) risk; however, there is uncertainty as to whether non-Mediterranean regions will adopt this diet. The present qualitative research aimed to investigate attitudes towards a MD in individuals at high CVD risk in a Northern European population. This information is needed to inform development of MD interventions in non-Mediterranean high-risk populations. METHODS: Focus groups (n = 12) were held with individuals at high CVD risk from Northern Europe (≥2 CVD risk factors, aged ≥50 years, no established CVD/type 2 diabetes). Attitudes to dietary change towards a MD were explored. Data were analysed using inductive thematic analysis. RESULTS: Sixty-seven adults participated (60% female, mean age 64 years). There was some awareness of the term MD but limited knowledge of its composition. Barriers to general dietary change were evident, including perception of expense, concern over availability, expectation of time commitment, limited knowledge, lack of cooking skills, amount and conflicting nature of media information on diets, changing established eating habits and resistance to dietary change. Barriers specific to MD adoption were also identified, including perceived difficulty living in a colder climate, perceived impact on body weight, acceptability of a MD and cultural differences. CONCLUSIONS: Knowledge of a MD was limited in this Northern European sample at high CVD risk. In addition to general barriers to dietary change, barriers specific to a MD were identified. These findings have implications for the development of interventions aiming to promote MD adoption in non-Mediterranean populations.

Cortical specialisation to social stimuli from the first days to the second year of life: A rural Gambian cohort.

Brain and nervous system development in human infants during the first 1000days (conception to two years of age) is critical, and compromised development during this time (such as from under nutrition or poverty) can have life-long effects on physical growth and cognitive function. Cortical mapping of cognitive function during infancy is poorly understood in resource-poor settings due to the lack of transportable and low-cost neuroimaging methods. Having established a signature cortical response to social versus non-social visual and auditory stimuli in infants from 4 to 6 months of age in the UK, here we apply this functional Near Infrared Spectroscopy (fNIRS) paradigm to investigate social responses in infants from the first postnatal days to the second year of life in two contrasting environments: rural Gambian and urban UK. Results reveal robust, localized, socially selective brain responses from 9 to 24 months of life to both the visual and auditory stimuli. In contrast at 0-2 months of age infants exhibit non-social auditory selectivity, an effect that persists until 4-8 months when we observe a transition to greater social stimulus selectivity. These findings reveal a robust developmental curve of cortical specialisation over the first two years of life.

A case of fatal Type I congenital disorders of glycosylation (CDG I) associated with low dehydrodolichol diphosphate synthase (DHDDS) activity.

BACKGROUND: Type I congenital disorders of glycosylation (CDG-I) are mostly complex multisystemic diseases associated with hypoglycosylated serum glycoproteins. A subgroup harbour mutations in genes necessary for the biosynthesis of the dolichol-linked oligosaccharide (DLO) precursor that is essential for protein N-glycosylation. Here, our objective was to identify the molecular origins of disease in such a CDG-Ix patient presenting with axial hypotonia, peripheral hypertonia, enlarged liver, micropenis, cryptorchidism and sensorineural deafness associated with hypo glycosylated serum glycoproteins. RESULTS: Targeted sequencing of DNA revealed a splice site mutation in intron 5 and a non-sense mutation in exon 4 of the dehydrodolichol diphosphate synthase gene (DHDDS). Skin biopsy fibroblasts derived from the patient revealed ~20 % residual DHDDS mRNA, ~35 % residual DHDDS activity, reduced dolichol-phosphate, truncated DLO and N-glycans, and an increased ratio of [2-(3)H]mannose labeled glycoprotein to [2-(3)H]mannose labeled DLO. Predicted truncated DHDDS transcripts did not complement rer2-deficient yeast. SiRNA-mediated down-regulation of DHDDS in human hepatocellular carcinoma HepG2 cells largely mirrored the biochemical phenotype of cells from the patient. The patient also harboured the homozygous ALG6(F304S) variant, which does not cause CDG but has been reported to be more frequent in PMM2-CDG patients with severe/fatal disease than in those with moderate presentations. WES did not reveal other strong candidate causal genes. CONCLUSIONS: We describe a patient presenting with severe multisystem disease associated with DHDDS deficiency. As retinitis pigmentosa is the only clinical sign in previously reported cases, this report broadens the spectrum of phenotypes associated with this condition.

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.

Early life nutritional programming of health and disease in The Gambia.

Exposures during the early life (periconceptional, prenatal and early postnatal) period are increasingly recognized as playing an important role in the aetiology of chronic non-communicable diseases (NCD), including coronary heart disease, stroke, hypertension, Type 2 diabetes and osteoporosis. The 'Developmental Origins of Health and Disease' (DOHaD) hypothesis states that these disorders originate through unbalanced nutrition early in life and risk is highest when there is a 'mismatch' between the early- and later-life environments. Thus, the DOHaD hypothesis would predict highest risk in countries where an excess of infants are born with low birth weight and where there is a rapid transition to nutritional adequacy or excess in adulthood. Here, I will review data from work conducted in rural Gambia, West Africa. Using demographic data dating back to the 1940s, the follow-up of randomized controlled trials of nutritional supplementation in pregnancy and the 'experiment of nature' that seasonality in this region provides, we have investigated the DOHaD hypothesis in a population with high rates of maternal and infant under-nutrition, a high burden from infectious disease, and an emerging risk of NCDs.

The effects of maternal iron deficiency on infant fibroblast growth factor-23 and mineral metabolism.

Fibroblast growth factor-23 (FGF23), a phosphate(Phos)-regulating hormone, is abnormally elevated in hypophosphataemic syndromes and an elevated FGF23 is a predictor of mortality in kidney disease. Recent findings suggest iron deficiency as a potential mediator of FGF23 expression and murine studies have shown in utero effects of maternal iron deficiency on offspring FGF23 and phosphate metabolism. Our aim was to investigate the impact of maternal iron status on infant FGF23 and mineral metabolites over the first 2years of life. Infants born to mothers with normal (NIn=25,) and low (LIn=25) iron status during pregnancy, from a mother-infant trial (ISRCTN49285450) in rural Gambia, West Africa, had blood and plasma samples analysed at 12, 24, 52, 78 and 104weeks (wk) of age. Circulating intact-FGF23 (I-FGF23), Phos, total alkaline phosphatase (TALP) and haemoglobin (Hb) decreased and estimated glomerular filtration rate increased over time [all P≤0.0001)]. C-terminal-FGF23 (C-FGF23) and TALP were significantly higher in LI compared with NI, from 52wk for C-FGF23 [Beta coefficient (SE) 18.1 (0.04) %, P=0.04] and from 24wk for TALP [44.7 (29.6) U/L, P=0.04]. Infant Hb was the strongest negative predictor of C-FGF23 concentration [-21% (4%) RU/mL, P≤0.0001], Phos was the strongest positive predictor of I-FGF23 [32.0(3.9) pg/mL, P≤0.0001] and I-FGF23 did not predict C-FGF23 over time [-0.5% (0.5%), P=0.3]. In conclusion, this study suggests that poor maternal iron status is associated with a higher infant C-FGF23 and TALP but similar I-FGF23 concentrations in infants and young children. These findings further highlight the likely public health importance of preventing iron deficiency during pregnancy. Whether or not children who are born to iron deficient mothers have persistently high concentrations of these metabolites and are more likely to be at risk of impaired bone development and pre-disposed to rickets requires further research.

Functional near infrared spectroscopy (fNIRS) to assess cognitive function in infants in rural Africa.

Cortical mapping of cognitive function during infancy is poorly understood in low-income countries due to the lack of transportable neuroimaging methods. We have successfully piloted functional near infrared spectroscopy (fNIRS) as a neuroimaging tool in rural Gambia. Four-to-eight month old infants watched videos of Gambian adults perform social movements, while haemodynamic responses were recorded using fNIRS. We found distinct regions of the posterior superior temporal and inferior frontal cortex that evidenced either visual-social activation or vocally selective activation (vocal > non-vocal). The patterns of selective cortical activation in Gambian infants replicated those observed within similar aged infants in the UK. These are the first reported data on the measurement of localized functional brain activity in young infants in Africa and demonstrate the potential that fNIRS offers for field-based neuroimaging research of cognitive function in resource-poor rural communities.

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.

The effect of delay in collection and processing on RNA integrity in human placenta: experiences from rural Africa.

This paper examines the relationship between time to processing and RNA quality in placentas collected from women in a field setting in rural Gambia. Placental samples were collected from the villages and transferred to the laboratory. RNA was extracted using Trizol and integrity assessed using the RNA integrity number (RIN). Values were inversely correlated with delay in processing. Expression levels of candidate genes increased with decreasing RIN. Normalising to a housekeeper gene removed this artefact. We propose a cut-off point of 90 min from delivery, after which samples cannot be used for gene expression analysis.

Evidence for metabolic endotoxemia in obese and diabetic Gambian women.

OBJECTIVE: Emerging evidence from animal models suggests that translocation of bacterial debris across a leaky gut may trigger low-grade inflammation, which in turn drives insulin resistance. The current study set out to investigate this phenomenon, termed 'metabolic endotoxemia', in Gambian women. METHODS: In a cross-sectional study, we recruited 93 age-matched middle-aged urban Gambian women into three groups: lean (body mass index (BMI): 18.5-22.9 kg m(-2)), obese non-diabetic (BMI: 30.0 kg m(-2)) and obese diabetic (BMI: 30.0 kg m(-2) and attending a diabetic clinic). We measured serum bacterial lipopolysaccharide (LPS) and endotoxin-core IgM and IgG antibodies (EndoCAb) as measures of endotoxin exposure and interleukin-6 (IL-6) as a marker of inflammation. RESULTS: Inflammation (IL-6) was independently and positively associated with both obesity and diabetes (F=12.7, P<0.001). LPS levels were highest in the obese-diabetic group compared with the other two groups (F=4.4, P<0.02). IgM EndoCAb (but not total IgM) was highly significantly reduced in the obese (55% of lean value) and obese diabetic women (30% of lean; F=21.7, P<0.0001 for trend) compared with lean women. CONCLUSION: These data support the hypothesis that gut-derived inflammatory products are associated with obesity and diabetes. Confirmation of these findings and elucidation of the role of the microbiota, gut damage and the pathways for translocation of bacterial debris, could open new avenues for prevention and treatment of type 2 diabetes.

Disproportionate early fetal growth predicts postnatal thymic size in humans.

Prenatal events can affect neonatal thymus size and adult immune function. The causal insults are unknown, although fetal nutrient restriction is suspected. We used ultrasound at three time points during pregnancy (14, 19 and 30 weeks) to measure the growth of six fetal dimensions in rural Bangladeshi women participating in the Maternal and Infant Nutrition Interventions, Matlab study. Postnatal ultrasound was used to calculate thymic index (TI) at birth, 2, 6 and 12 m. Of the 3267 women recruited, 2861 participated by providing data at least at one fetal biometry and one TI time point. Patterns of fetal growth were summarized using principal components calculated from fetal dimension z-scores. Random effects regression, controlling for infant size and season of measurement were used to relate these patterns to TI. We found that smaller leg length relative to head circumference, characteristic of head-sparing growth restriction, was predictive of lower TI. This association was significant at all time points but strongest in earlier pregnancy. Each standard deviation increase in leg-head proportion was associated with an increase in TI of ∼5%. We conclude that growth patterns typical of poor fetal nutrition are associated with poor thymic development. The greater strength of this association in the first trimester is consistent with a period of vulnerability during the early ontogeny of the thymus and suggests that preventative intervention would need to be given in early pregnancy.

Randomized clinical trial of ropivacaine wound infusion following laparoscopic colorectal surgery.

BACKGROUND: Wound infusions with local anaesthesia have been used with varying success following laparotomy for colonic resections. This trial sought to determine the efficacy of ropivacaine wound infusion following laparoscopic colonic surgery. METHODS: Forty-eight consecutive patients undergoing elective laparoscopic colorectal resection were randomized to receive either a local anaesthetic wound infusion (ropivacaine 0.5%) or normal saline for a period of 72 h. The primary endpoint was postoperative pain as assessed by analgesic consumption, while secondary endpoints assessed were visual analogue pain scores, respiratory function, gastrointestinal function, length of stay and postoperative complications. RESULTS: There was no difference in mean postoperative analgesic consumption between the two groups over 72 h (143 mEq morphine control vs 94 mEq intervention; p = 0.108). Likewise, there was no difference in daily postoperative analgesic consumption or visual analogue pain scores between the two groups. Patients in the ropivacaine group experienced less reduction in their postoperative forced expiratory volume at 1 s on day 1 (mean difference FEV1 0.4 l; p = 0.015). There was no difference between the two groups with respect to return of gut function and postoperative complications. CONCLUSIONS: In this study, local anaesthetic wound infusion with ropivacaine following elective laparoscopic colorectal surgery improves early respiratory function, but does not appear to provide an improvement in postoperative analgesia or other clinically relevant postoperative outcomes.

Guanosine diphosphate-mannose:GlcNAc2-PP-dolichol mannosyltransferase deficiency (congenital disorders of glycosylation type Ik): five new patients and seven novel mutations.

BACKGROUND: In type I congenital disorders of glycosylation (CDG I), proteins necessary for the biosynthesis of the lipid-linked oligosaccharide (LLO) required for protein N-glycosylation are defective. A deficiency in guanosine diphosphate-mannose: GlcNAc(2)-PP-dolichol mannosyltransferase-1 (MT-1) causes CDG Ik (OMIM 608540), and only five patients, with severe multisystemic clinical presentations, have been described with this disease. Objective To characterise genetic, biochemical and clinical data in five new CDG Ik cases and compare these findings with those of the five previously described patients. Methods LLO biosynthesis was examined in skin biopsy fibroblasts, mannosyltransferases were assayed in microsomes prepared from these cells, and ALG1-encoding MT-1 was sequenced at the DNA and complementary DNA levels. Clinical data for the five new patients were collated. RESULTS: Cells from five patients with non-typed CDG I revealed accumulations of GlcNAc(2)-PP-dolichol, the second intermediate in the biosynthesis of LLO. Assay of MT-1, -2 and -3, the first three mannosyltransferases required for extension of this intermediate, demonstrated only MT-1 to be deficient. DNA sequencing of ALG1 revealed nine different mutations, seven of which have not been previously reported. Clinical presentations are severe, with dysmorphias, CNS involvement and ocular disturbances being prevalent. CONCLUSIONS: 5 patients with CDG Ik are described, and their identification reveals that in France, this disease and CDG Ib (mannose phosphate isomerase deficiency: OMIM 602579) are the most frequently diagnosed CDG I after CDG Ia (phosphomannomutase 2 deficiency: OMIM 601785) and substantiate previous observations indicating that this disease presents at the severe end of the CDG I clinical spectrum.

Influence of selected factors on the dietary compositions of three targeted and co-occurring temperate species of reef fishes: implications for food partitioning.

The dietary compositions of three medium to large targeted fish species, which co-occur over reefs in temperate waters of south-western Australia, were determined. These data were then used to ascertain statistically the extent to which body size, season and habitat influence the diets of these species and the degree to which food resources were partitioned among and within those species, and thus reduced the potential of interspecific and intraspecific competition. On the west coast, Bodianus frenchii (Labridae) and Epinephelides armatus (Serranidae) spent their whole life over prominent limestone reefs, as did Glaucosoma hebraicum (Glaucosomatidae) in all but juvenile life, when it lived over low-relief, limestone substrata. The dietary composition of each species changed with increasing body size, which, in G. hebraicum, was particularly pronounced at c. 300 mm total length (L(T)) and therefore at the size when this species shifts habitat. When the three species co-occurred over the same reefs, their dietary compositions were significantly different, with that of B. frenchii being by far the most discrete, reflecting a far greater contribution by sedentary taxa. Thus, the diet of B. frenchii was distinguished from those of the other two species in containing substantial volumes of bivalve and gastropod molluscs and echinoid echinoderms and essentially no teleosts. Although the diets of G. hebraicum and particularly E. armatus were dominated by teleosts, and especially for larger individuals, the former species ingested greater volumes of cephalopods and small crustaceans. The pointed jaws of B. frenchii, with their forwardly directed and interlocking anterior incisors, are ideally adapted for biting and retaining their invertebrate prey, which are attached to or reside within reef crevices. In contrast, the mouths of G. hebraicum and E. armatus are broader and rounder and contain numerous small, slender and inward-pointing teeth. These teeth, in conjunction with prominent backward-curved canines in E. armatus, facilitate the capture and retention of fish prey. Observations in situ indicate that G. hebraicum is a suction feeder, while E. armatus is predominantly a ram feeder. Although reef environments on the west and south coasts differ, the diet of B. frenchii on these coasts differed only slightly. Interspecific differences in diet, combined with size-related changes in dietary compositions and the occupation of different habitats by juvenile and adult G. hebraicum, reduce the potential for competition for food resources among and within B. frenchii, G. hebraicum and E. armatus and thus helps facilitate the coexistence of these species which historically have been abundant over reefs in south-western Australia.

Cardiomyopathy in the congenital disorders of glycosylation (CDG): a case of late presentation and literature review.

The congenital disorders of glycosylation (CDG) are a recently described group of inherited multisystem disorders characterized by defects predominantly of N- and O-glycosylation of proteins. Cardiomyopathy in CDG has previously been described in several subtypes; it is usually associated with high morbidity and mortality and the majority of cases present in the first 2 years of life. This is the first case with presentation in late childhood and the article reviews current literature. An 11-year-old female with a background of learning difficulties presented in cardiac failure secondary to severe dilated cardiomyopathy. Prior to the diagnosis of CDG, her condition deteriorated; she required mechanical support (Excor Berlin Heart) and was listed for cardiac transplant. Investigations included screening for glycosylation disorders, and isoelectric focusing of transferrin revealed an abnormal type 1 pattern. Analysis of phosphomannomutase and phosphomannose isomerase showed normal enzyme activity, excluding PMM2 (CDG Ia) and MPI (CDG Ib). Lipid-linked oligosaccharide and mutational studies have not yet defined the defect. Despite aggressive therapy there were persistent difficulties achieving adequate anticoagulation and she developed multiple life-threatening thrombotic complications. She was removed from the transplant list and died from overwhelming sepsis 5 weeks following admission. This case emphasizes the need to screen all children with an undiagnosed cardiomyopathy for CDG, regardless of age, and where possible to exclude CDG before the use of cardiac bridging devices. It highlights the many practical and ethical challenges that may be encountered where clinical knowledge and experience are still evolving.

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.

Ethnic differences in the association between body mass index and impedance index (Ht2/Z) in adult women and men using a leg-to-leg bioimpedance method.

BACKGROUND: Ethnic differences in the association between body mass index (BMI) and body fat suggest that body composition varies across ethnic groups. OBJECTIVE: To investigate the association between impedance index - a measure of tissue resistivity - and BMI in adults of different ethnic groups (Asian Indians, West Africans and White Caucasians) living in their native countries. METHODS: Male (n=329) and female (n=277) adult subjects (18-50 years) living in urban areas in the UK, The Gambia and Pakistan were studied. Body weight and height were measured and BMI calculated. The same leg-to-leg bioimpedance instrument was used in each study and impedance index (height(2) (cm)/impedance (Omega)) used as measure of tissue resistivity. RESULTS: In women, Asian Indians and West Africans had a significantly greater increase in impedance index per unit increase in BMI compared with white Caucasians (P<0.001). In men, Asian Indians had a significantly lower impedance index compared with West Africans and white Caucasians (P<0.001). CONCLUSION: Different ethnic groups may have different tissue resistivity for the same BMI indicative of systematic differences in body composition.

New insights from MALDI-ToF MS, NMR, and GC-MS: mass spectrometry techniques applied to palynology.

The present study for the first time describes the application of matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-ToF MS) to palynology. With an accessible mass range of up to about 350,000 Da at subpicomolar range, this technique is ideal for the characterisation of bio-macromolecules, such as sporopollenin, found in fossil and extant pollen and spore walls, which often can only be isolated in very small quantities. At this stage, the limited solubility of sporopollenin allows for the identification of sections of this biopolymer, but with the optimisation of MALDI-ToF matrices, further structure elucidation will become possible. Furthermore, gas chromatography-mass spectrometry (GC-MS) and (1)H nuclear magnetic resonance ((1)H NMR) spectroscopy data obtained from a number of experiments revealed that some previously reported data were misinterpreted. These results add support to the hypothesis that common plasticizers were wrongly described as sporopollenin compounds.