Publications by authors named "Andrew Prentice"

291 Publications

Thiamine deficiency in Gambian women of reproductive age.

Ann N Y Acad Sci 2021 Sep 20. Epub 2021 Sep 20.

MRC Unit The Gambia at London School of Hygiene & Tropical Medicine, Banjul, The Gambia.

Thiamine deficiency disorders are associated with a variety of clinical symptoms affecting the nervous and cardiovascular systems. There is growing recognition that thiamine deficiency can occur in populations well beyond the classical region of South Asia, and at-risk populations include those who receive a large proportion of their energy from polished white rice (or other low-thiamine staple foods) and with low dietary diversity. Reports of thiamine deficiency in West Africa over the last century have suggested that this has historically been an issue in this population, but in more recent decades, these reports have been limited to prison populations. To understand if thiamine deficiency might be an unrecognized problem in the communities of this region, erythrocyte samples collected during the wet and dry seasons from 226 women of reproductive age (mean age = 28 years old) were assessed for thiamine status by measuring the erythrocyte transketolase activity coefficient (ETKac). Overall, 35.8% of the sample was at high risk of thiamine deficiency (ETKac ≥ 1.25). Risk of thiamine deficiency was significantly higher in the wet (47.9%) compared with the dry season (22.9%) (P < 0.001). To our knowledge, this is the first report of biochemical thiamine deficiency in a free-living population in West Africa in the 21st century and suggests that further investigation is warranted.
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http://dx.doi.org/10.1111/nyas.14695DOI Listing
September 2021

Impact of Personal Cooling on Performance, Comfort and Heat Strain of Healthcare Workers in PPE, a Study From West Africa.

Front Public Health 2021 1;9:712481. Epub 2021 Sep 1.

Environmental Extremes Laboratory, University of Brighton, Eastbourne, United Kingdom.

Personal protective equipment (PPE) is an essential component of safely treating suspected or confirmed SARS-CoV-2 patients. PPE acts as a barrier to heat loss, therefore increasing the risk of thermal strain which may impact on cognitive function. Healthcare workers (HCWs) need to be able to prioritize and execute complex tasks effectively to ensure patient safety. This study evaluated pre-cooling and per-cooling methods on thermal strain, thermal comfort and cognitive function during simulated emergency management of an acutely unwell patient. This randomized controlled crossover trial was run at the Clinical Services Department of the Medical Research Unit The Gambia. Each participant attended two sessions (Cool and Control) in standard PPE. Cool involved pre-cooling with an ice slurry ingestion and per-cooling by wearing an ice-vest external to PPE. Twelve participants completed both sessions. There was a significant increase in tympanic temperature in Control sessions at both 1 and 2 h in PPE ( = 0.01). No significant increase was seen during Cool. Effect estimate of Cool was -0.2°C (95% CI -0.43; 0.01, = 0.06) post 1 h and -0.28°C (95% CI -0.57; 0.02, = 0.06) post 2 h on tympanic temperature. Cool improved thermal comfort ( < 0.001), thermal sensation ( < 0.001), and thirst ( = 0.04). No difference on cognitive function was demonstrated using multilevel modeling. Thermal strain in HCWs wearing PPE can be safely reduced using pre- and per-cooling methods external to PPE.
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http://dx.doi.org/10.3389/fpubh.2021.712481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440920PMC
September 2021

Plasma lipids and growth faltering: A longitudinal cohort study in rural Gambian children.

Sci Adv 2021 Sep 17;7(38):eabj1132. Epub 2021 Sep 17.

Core Metabolomics and Lipidomics Laboratory, Wellcome Trust-MRL Institute of Metabolic Science, University of Cambridge, Cambridge, UK.

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http://dx.doi.org/10.1126/sciadv.abj1132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448443PMC
September 2021

Aflatoxin Exposure during Early Life Is Associated with Differential DNA Methylation in Two-Year-Old Gambian Children.

Int J Mol Sci 2021 Aug 20;22(16). Epub 2021 Aug 20.

School of Medicine, University of Leeds, Leeds LS2 9JT, UK.

: DNA methylation is an epigenetic control mechanism that may be altered by environmental exposures. We have previously reported that in utero exposure to the mycotoxin and liver carcinogen aflatoxin B1 from the maternal diet, as measured using biomarkers in the mothers' blood, was associated with differential DNA methylation in white blood cells of 6-month-old infants from The Gambia. : Here we examined aflatoxin B1-associated differential DNA methylation in white blood cells of 24-month-old children from the same population ( = 244), in relation to the child's dietary exposure assessed using aflatoxin albumin biomarkers in blood samples collected at 6, 12 and 18 months of age. HM450 BeadChip arrays were used to assess DNA methylation, with data compared to aflatoxin albumin adduct levels using two approaches; a continuous model comparing aflatoxin adducts measured in samples collected at 18 months to DNA methylation at 24 months, and a categorical time-dose model that took into account aflatoxin adduct levels at 6, 12 and 18 months, for comparison to DNA methylation at 24 months. : Geometric mean (95% confidence intervals) for aflatoxin albumin levels were 3.78 (3.29, 4.34) at 6 months, 25.1 (21.67, 29.13) at 12 months and 49.48 (43.34, 56.49) at 18 months of age. A number of differentially methylated CpG positions and regions were associated with aflatoxin exposure, some of which affected gene expression. Pathway analysis highlighted effects on genes involved with with inflammatory, signalling and growth pathways. : This study provides further evidence that exposure to aflatoxin in early childhood may impact on DNA methylation.
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http://dx.doi.org/10.3390/ijms22168967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396526PMC
August 2021

Stunting of Growth in Developing Countries.

World Rev Nutr Diet 2021 5;123:14-27. Epub 2021 Aug 5.

MRC Unit, The Gambia at London School of Hygiene and Tropical Medicine, Banjul, Gambia.

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http://dx.doi.org/10.1159/000516450DOI Listing
August 2021

Seasonal modulation of antibody response to diphtheria-tetanus-pertussis vaccination in infants: a cohort study in rural Gambia.

BMC Public Health 2021 07 22;21(1):1442. Epub 2021 Jul 22.

Department of Women and Children's Health, King's College London, St Thomas' Hospital, 10th Floor North Wing, London, SE1 7EH, UK.

Background: In rural Gambia, rates of malnutrition and infection are higher during the annual rainy/'hungry' season (June-October) in comparison to the dry/'harvest' season (November-May). The effects of this seasonal pattern on an infant's immune development and their capacity to respond to childhood vaccinations remain unclear. The aim of the current analysis was to determine whether antibody responses to diphtheria-tetanus-pertussis (DTP) vaccinations in infants differ between seasons.

Methods: Infants received the DTP vaccine at 8, 12 and 16 weeks of age and antibody titres were measured in blood samples collected at 12 (n = 710) and 24 (n = 662) weeks of age. Mean DTP antibody titres, adjusted for maternal and infant confounders, were compared by t-tests and the effect sizes of the mean differences were calculated between seasons at mid-gestation (20 weeks gestation) and first vaccination (8 weeks of infant age).

Results: A smaller number of infants received their first vaccination during the rainy/hungry season months compared to the dry/harvest season (n = 224 vs. n = 486). At 12 weeks, infants vaccinated during the rainy/hungry season had lower weight-for-length Z-scores (p = 0.01) and were more likely to be anaemic (p < 0.001). Their mothers, however, were pregnant mostly during the dry/harvest season, had higher weight gain (p < 0.001) and were less likely to be anaemic during pregnancy (p < 0.001). At 12 weeks, infants vaccinated during the rainy/hungry season had significantly higher mean diphtheria, tetanus and pertussis antibody titres; by 62.3, 16.9 and 19.7%, respectively (all, p < 0.001). However, at 24 weeks, they had lower mean anti-diphtheria titres (by 20.6%, p < 0.001) compared with infants vaccinated during the dry/harvest season, and no differences were observed in mean tetanus and pertussis antibody titres by vaccination season.

Conclusions: Infant antibody response to the primary dose of the DTP vaccine was influenced by both season of pregnancy and infancy, although effects were diminished following three doses. Environmental exposures, including nutrition, to both the mother and infant are hypothesised as likely drivers of these seasonal effects.
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http://dx.doi.org/10.1186/s12889-021-11383-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296693PMC
July 2021

Intense and Mild First Epidemic Wave of Coronavirus Disease, The Gambia.

Emerg Infect Dis 2021 Aug;27(8):2064-2072

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is evolving differently in Africa than in other regions. Africa has lower SARS-CoV-2 transmission rates and milder clinical manifestations. Detailed SARS-CoV-2 epidemiologic data are needed in Africa. We used publicly available data to calculate SARS-CoV-2 infections per 1,000 persons in The Gambia. We evaluated transmission rates among 1,366 employees of the Medical Research Council Unit The Gambia (MRCG), where systematic surveillance of symptomatic cases and contact tracing were implemented. By September 30, 2020, The Gambia had identified 3,579 SARS-CoV-2 cases, including 115 deaths; 67% of cases were identified in August. Among infections, MRCG staff accounted for 191 cases; all were asymptomatic or mild. The cumulative incidence rate among nonclinical MRCG staff was 124 infections/1,000 persons, which is >80-fold higher than estimates of diagnosed cases among the population. Systematic surveillance and seroepidemiologic surveys are needed to clarify the extent of SARS-CoV-2 transmission in Africa.
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http://dx.doi.org/10.3201/eid2708.204954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314844PMC
August 2021

Impact of dietary aflatoxin on immune development in Gambian infants: a cohort study.

BMJ Open 2021 07 20;11(7):e048688. Epub 2021 Jul 20.

School of Medicine, University of Leeds, Leeds, UK

Background: Chronic aflatoxin (AF) exposure has been shown to occur at high levels in children from sub-Saharan Africa (SSA), and has been associated with growth retardation and immune dysfunction. Our objective was to investigate the impact of AF exposure on immune development in early infancy using thymic size and antibody (Ab) response to vaccination as indicators of immune function.

Methods: A total of 374 infants born between May 2011 and December 2012 were enrolled into the current study. These infants were recruited from a larger, randomised trial examining the impact of nutritional supplementation of mothers and infants on infant immune development (the Early Nutrition and Immune Development Trial). Thymic size (Thymic Index, TI) was measured by sonography at 1 week, 8 weeks, 24 weeks and 52 weeks of infant age. Infants were given the diphtheria-tetanus-pertussis (DTP) vaccine at 8 weeks, 12 weeks and 16 weeks of age, and Ab responses to each vaccine measured at 12 weeks and 24 weeks of age. AF-albumin (AF-alb) adduct levels in infant blood were measured by ELISA as the biomarker of AF exposure.

Results: The geometric mean (GM) level of AF-alb increased with age. Only half of infants had detectable AF-alb with a GM of 3.52 pg/mg at 24 weeks, increasing to 25.39 pg/mg at 52 weeks, when 98% of infants had AF-alb >limit of detection. Significant negative association of AF-alb level with TI was seen in infants during the first 24 weeks, especially at 8 weeks of age (p<0.001), which is the time point of fastest thymus growth. There were no associations between AF exposure level and Ab response to pertussis and tetanus, but a significant positive correlation was observed between AF-alb level and Ab titre to diphtheria (p<0.005).

Conclusions: High levels of AF exposure during early infancy may impact on infant immune development.

Trial Registration Number: ISRCTN49285450.
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http://dx.doi.org/10.1136/bmjopen-2021-048688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292809PMC
July 2021

Characteristics of Distinct Dietary Patterns in Rural Bangladesh: Nutrient Adequacy and Vulnerability to Shocks.

Nutrients 2021 Jun 15;13(6). Epub 2021 Jun 15.

Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.

Food security in Bangladesh has improved in recent years, but the country is now facing a double burden of malnutrition while also being highly vulnerable to climate change. Little is known about how this may affect food supply to different sectors of the population. To inform this, we used a national dietary survey of 800 rural households to define dietary patterns using latent class analysis. Nutrient adequacy of dietary patterns and their potential vulnerability to climate shocks (based on diversity of calorie sources) were assessed. We fitted mixed effects logistic regression models to identify factors associated with dietary patterns. Four dietary patterns were identified: rice and low diversity; wheat and high diversity; pulses and vegetables; meat and fish. The wheat and high diversity and meat and fish patterns tended to be consumed by households with higher levels of wealth and education, while the rice and low diversity pattern was consumed by households with lower levels of wealth and education. The pulses and vegetables pattern was consumed by households of intermediate socio-economic status. While energy intake was high, fat and protein intake were suboptimal for all patterns except for the wheat and high diversity pattern. All patterns had fruit and vegetable intake below the WHO recommendation. The wheat and high diversity pattern was least vulnerable to shocks, while the rice and low diversity pattern was the most vulnerable, relying mainly on single cereal staples. The diets showed "double vulnerability" where the nutrient inadequate patterns were also those most vulnerable to shocks.
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http://dx.doi.org/10.3390/nu13062049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232582PMC
June 2021

Prevalence and co-existence of cardiometabolic risk factors and associations with nutrition-related and socioeconomic indicators in a national sample of Gambian women.

Sci Rep 2021 06 8;11(1):12057. Epub 2021 Jun 8.

GroundWork, 7306, Fläsch, Switzerland.

Cardiovascular diseases (CVD) are on the rise in Sub-Saharan Africa, and a large proportion of the adult population is thought to suffer from at least one cardiometabolic risk factor. This study assessed cardiometabolic risk factors and the contribution of nutrition-related indicators in Gambian women. The prevalence and co-existence of diabetes (elevated glycated hemoglobin (HbA1c ≥ 6.5%) or prediabetes (HbA1c ≥ 5.7% to < 6.5%), hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg), obesity (body mass index (BMI) ≥ 30.0) and inflammation (C-reactive protein (CRP) > 3 mg/L or alpha-1-acid glycoprotein (AGP) > 1 g/L) and the contribution of nutrition related and socioeconomic indicators were measured in non-pregnant women 15-49 years of age in the Gambia using data from a nationally representative cross-sectional stratified survey. Nationally, 54.5% (95% CI: 47.4, 61.4) of 1407 women had elevated HbA1c. Of these, 14.9% were diabetic and 85.1% were prediabetic. Moreover, 20.8% (95% CI 17.8, 20.0) of 1685 women had hypertension, 11.1% (95% CI 9.0, 13.7) of 1651 were obese and 17.2% (95% CI 5.1, 19.6) of 1401 had inflammation. At least one of the aforementioned cardiometabolic risk factor was present in 68.3% (95% CI 63.0, 73.1) of women. Obesity increased the risk of hypertension (aRR 1.84; 95% CI 1.40, 2.41), diabetes (aRR 1.91; 95% CI 1.29, 2.84), elevated HbA1c (aRR 1.31; 95% CI 1.14, 1.51) and inflammation (aRR 3.47; 95% CI 2.61, 4.61). Inflammation increased the risk of hypertension (aRR 1.42; 95% CI 1.14, 1.78). Aging increased the risk of hypertension, obesity and inflammation. Further, inadequate sanitation increased the risk for diabetes (aRR 1.65; 95% CI 1.17, 2.34) and iron deficiency increased the risk of elevated HbA1c (aRR 1.21; 95% CI 1.09, 1.33). The high prevalence of cardiometabolic risk factors and their co-existence in Gambian women is concerning. Although controlling obesity seems to be key, multifaceted strategies to tackle the risk factors separately are warranted to reduce the prevalence or minimize the risk of CVD.
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http://dx.doi.org/10.1038/s41598-021-91592-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187481PMC
June 2021

Variation in Human Milk Composition Is Related to Differences in Milk and Infant Fecal Microbial Communities.

Microorganisms 2021 May 27;9(6). Epub 2021 May 27.

Margaret Ritchie School of Family and Consumer Sciences, University of Idaho, Moscow, ID 83844, USA.

Previously published data from our group and others demonstrate that human milk oligosaccharide (HMOs), as well as milk and infant fecal microbial profiles, vary by geography. However, little is known about the geographical variation of other milk-borne factors, such as lactose and protein, as well as the associations among these factors and microbial community structures in milk and infant feces. Here, we characterized and contrasted concentrations of milk-borne lactose, protein, and HMOs, and examined their associations with milk and infant fecal microbiomes in samples collected in 11 geographically diverse sites. Although geographical site was strongly associated with milk and infant fecal microbiomes, both sample types assorted into a smaller number of community state types based on shared microbial profiles. Similar to HMOs, concentrations of lactose and protein also varied by geography. Concentrations of HMOs, lactose, and protein were associated with differences in the microbial community structures of milk and infant feces and in the abundance of specific taxa. Taken together, these data suggest that the composition of human milk, even when produced by relatively healthy women, differs based on geographical boundaries and that concentrations of HMOs, lactose, and protein in milk are related to variation in milk and infant fecal microbial communities.
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http://dx.doi.org/10.3390/microorganisms9061153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230061PMC
May 2021

Prevalence and predictors of vitamin D deficiency in young African children.

BMC Med 2021 05 20;19(1):115. Epub 2021 May 20.

Kenya Medical Research Institute (KEMRI) Centre for Geographic Medicine Coast, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.

Background: Children living in sub-Saharan Africa have a high burden of rickets and infectious diseases, conditions that are linked to vitamin D deficiency. However, data on the vitamin D status of young African children and its environmental and genetic predictors are limited. We aimed to examine the prevalence and predictors of vitamin D deficiency in young African children.

Methods: We measured 25-hydroxyvitamin D (25(OH)D) and typed the single nucleotide polymorphisms, rs4588 and rs7041, in the GC gene encoding the vitamin D binding protein (DBP) in 4509 children aged 0-8 years living in Kenya, Uganda, Burkina Faso, The Gambia and South Africa. We evaluated associations between vitamin D status and country, age, sex, season, anthropometric indices, inflammation, malaria and DBP haplotypes in regression analyses.

Results: Median age was 23.9 months (interquartile range [IQR] 12.3, 35.9). Prevalence of vitamin D deficiency using 25(OH)D cut-offs of < 30 nmol/L and < 50 nmol/L was 0.6% (95% CI 0.4, 0.9) and 7.8% (95% CI 7.0, 8.5), respectively. Overall median 25(OH)D level was 77.6 nmol/L (IQR 63.6, 94.2). 25(OH)D levels were lower in South Africa, in older children, during winter or the long rains, and in those with afebrile malaria, and higher in children with inflammation. 25(OH)D levels did not vary by stunting, wasting or underweight in adjusted regression models. The distribution of Gc variants was Gc1f 83.3%, Gc1s 8.5% and Gc2 8.2% overall and varied by country. Individuals carrying the Gc2 variant had lower median 25(OH)D levels (72.4 nmol/L (IQR 59.4, 86.5) than those carrying the Gc1f (77.3 nmol/L (IQR 63.5, 92.8)) or Gc1s (78.9 nmol/L (IQR 63.8, 95.5)) variants.

Conclusions: Approximately 0.6% and 7.8% of young African children were vitamin D deficient as defined by 25(OH)D levels < 30 nmol/L and < 50 nmol/L, respectively. Latitude, age, season, and prevalence of inflammation and malaria should be considered in strategies to assess and manage vitamin D deficiency in young children living in Africa.
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http://dx.doi.org/10.1186/s12916-021-01985-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136043PMC
May 2021

The Role of Nutrition in COVID-19 Susceptibility and Severity of Disease: A Systematic Review.

J Nutr 2021 07;151(7):1854-1878

Medical Research Council (MRC) Unit The Gambia at the London School of Hygiene & Tropical Medicine, Fajara, The Gambia.

Background: Many nutrients have powerful immunomodulatory actions with the potential to alter susceptibility to coronavirus disease 2019 (COVID-19) infection, progression to symptoms, likelihood of severe disease, and survival.

Objective: The aim was to review the latest evidence on how malnutrition across all its forms (under- and overnutrition and micronutrient status) may influence both susceptibility to, and progression of, COVID-19.

Methods: We synthesized information on 13 nutrition-related components and their potential interactions with COVID-19: overweight, obesity, and diabetes; protein-energy malnutrition; anemia; vitamins A, C, D, and E; PUFAs; iron; selenium; zinc; antioxidants; and nutritional support. For each section we provide: 1) a landscape review of pertinent material; 2) a systematic search of the literature in PubMed and EMBASE databases, including a wide range of preprint servers; and 3) a screen of 6 clinical trial registries. All original research was considered, without restriction to study design, and included if it covered: 1) severe acute respiratory syndrome coronavirus (CoV) 2 (SARS-CoV-2), Middle East respiratory syndrome CoV (MERS-CoV), or SARS-CoV viruses and 2) disease susceptibility or 3) disease progression, and 4) the nutritional component of interest. Searches took place between 16 May and 11 August 2020.

Results: Across the 13 searches, 2732 articles from PubMed and EMBASE, 4164 articles from the preprint servers, and 433 trials were returned. In the final narrative synthesis, we include 22 published articles, 38 preprint articles, and 79 trials.

Conclusions: Currently there is limited evidence that high-dose supplements of micronutrients will either prevent severe disease or speed up recovery. However, results of clinical trials are eagerly awaited. Given the known impacts of all forms of malnutrition on the immune system, public health strategies to reduce micronutrient deficiencies and undernutrition remain of critical importance. Furthermore, there is strong evidence that prevention of obesity and type 2 diabetes will reduce the risk of serious COVID-19 outcomes. This review is registered at PROSPERO as CRD42020186194.
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http://dx.doi.org/10.1093/jn/nxab059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194602PMC
July 2021

Association of common TMPRSS6 and TF gene variants with hepcidin and iron status in healthy rural Gambians.

Sci Rep 2021 04 13;11(1):8075. Epub 2021 Apr 13.

Nutrition Theme, MRC Unit, The Gambia at London School of Hygiene & Tropical Medicine, Atlantic Boulevard, Fajara, P.O. Box 273, Banjul, The Gambia.

Genome-wide association studies in Europeans and Asians have identified numerous variants in the transmembrane protease serine 6 (TMPRSS6) and transferrin (TF) genes that are associated with changes in iron status. We sought to investigate the effects of common TMPRSS6 and TF gene SNPs on iron status indicators in a cohort of healthy Africans from rural Gambia. We measured iron biomarkers and haematology traits on individuals participating in the Keneba Biobank with genotype data on TMPRSS6 (rs2235321, rs855791, rs4820268, rs2235324, rs2413450 and rs5756506) and TF (rs3811647 and rs1799852), n = 1316. After controlling for inflammation, age and sex, we analysed the effects of carrying either single or multiple iron-lowering alleles on iron status. TMPRSS6 rs2235321 significantly affected plasma hepcidin concentrations (AA genotypes having lower hepcidin levels; F ratio 3.7, P = 0.014) with greater impact in individuals with low haemoglobin or ferritin. No other TMPRSS6 variant affected hepcidin. None of the TMPRSS6 variants nor a TMPRSS6 allele risk score affected other iron biomarkers or haematological traits. TF rs3811647 AA carriers had 21% higher transferrin (F ratio 16.0, P < 0.0001), 24% higher unsaturated iron-binding capacity (F ratio 12.8, P < 0.0001) and 25% lower transferrin saturation (F ratio 4.3, P < 0.0001) compared to GG carriers. TF rs3811647 was strongly associated with transferrin, unsaturated iron-binding capacity (UIBC) and transferrin saturation (TSAT) with a single allele effect of 8-12%. There was no association between either TF SNP and any haematological traits or iron biomarkers. We identified meaningful associations between TMPRSS6 rs2235321 and hepcidin and replicated the previous findings on the effects of TF rs3811647 on transferrin and iron binding capacity. However, the effects are subtle and contribute little to population variance. Further genetic and functional studies, including polymorphisms frequent in Africa populations, are needed to identify markers for genetically stratified approaches to prevention or treatment of iron deficiency anaemia.
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http://dx.doi.org/10.1038/s41598-021-87565-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044158PMC
April 2021

Identification of methylation changes associated with positive and negative growth deviance in Gambian infants using a targeted methyl sequencing approach of genomic DNA.

FASEB Bioadv 2021 Apr 5;3(4):205-230. Epub 2021 Feb 5.

Department of Pathology University of Cambridge Cambridge UK.

Low birthweight and reduced height gain during infancy (stunting) may arise at least in part from adverse early life environments that trigger epigenetic reprogramming that may favor survival. We examined differential DNA methylation patterns using targeted methyl sequencing of regions regulating gene activity in groups of rural Gambian infants: (a) low and high birthweight (DNA from cord blood ( = 16 and  = 20, respectively), from placental trophoblast tissue ( = 21 and  = 20, respectively), and DNA from peripheral blood collected from infants at 12 months of age ( = 23 and  = 17, respectively)), and, (b) the top 10% showing rapid postnatal length gain (high,  = 20) and the bottom 10% showing slow postnatal length gain (low,  = 20) based on z score change between birth and 12 months of age (LAZ) (DNA from peripheral blood collected from infants at 12 months of age). Using BiSeq analysis to identify significant methylation marks, for birthweight, four differentially methylated regions (DMRs) were identified in trophoblast DNA, compared to 68 DMRs in cord blood DNA, and 54 DMRs in 12-month peripheral blood DNA. Twenty-five DMRs were observed to be associated with high and low length for age (LAZ) at 12 months. With the exception of five loci (associated with two different genes), there was no overlap between these groups of methylation marks. Of the 194 CpG methylation marks contained within DMRs, 106 were located to defined gene regulatory elements (promoters, CTCF-binding sites, transcription factor-binding sites, and enhancers), 58 to gene bodies (introns or exons), and 30 to intergenic DNA. Distinct methylation patterns associated with birthweight between comparison groups were observed in DNA collected at birth (at the end of intrauterine growth window) compared to those established by 12 months (near the infancy/childhood growth transition). The longitudinal differences in methylation patterns may arise from methylation adjustments, changes in cellular composition of blood or both that continue during the critical postnatal growth period, and in response to early nutritional and infectious environmental exposures with impacts on growth and longer-term health outcomes.
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http://dx.doi.org/10.1096/fba.2020-00101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019263PMC
April 2021

Comparison of Two Approaches for the Metataxonomic Analysis of the Human Milk Microbiome.

Front Cell Infect Microbiol 2021 25;11:622550. Epub 2021 Mar 25.

Department of Nutrition and Food Science, Complutense University of Madrid, Madrid, Spain.

Recent work has demonstrated the existence of large inter-individual and inter-population variability in the microbiota of human milk from healthy women living across variable geographical and socio-cultural settings. However, no studies have evaluated the impact that variable sequencing approaches targeting different 16S rRNA variable regions may have on the human milk microbiota profiling results. This hampers our ability to make meaningful comparisons across studies. In this context, the main purpose of the present study was to re-process and re-sequence the microbiome in a large set of human milk samples (n = 412) collected from healthy women living at diverse international sites (Spain, Sweden, Peru, United States, Ethiopia, Gambia, Ghana and Kenya), by targeting a different 16S rRNA variable region and reaching a larger sequencing depth. Despite some differences between the results obtained from both sequencing approaches were notable (especially regarding alpha and beta diversities and Proteobacteria representation), results indicate that both sequencing approaches revealed a relatively consistent microbiota configurations in the studied cohorts. Our data expand upon the milk microbiota results we previously reported from the INSPIRE cohort and provide, for the first time across globally diverse populations, evidence of the impact that different DNA processing and sequencing approaches have on the microbiota profiles obtained for human milk samples. Overall, our results corroborate some similarities regarding the microbial communities previously reported for the INSPIRE cohort, but some differences were also detected. Understanding the impact of different sequencing approaches on human milk microbiota profiles is essential to enable meaningful comparisons across studies.

Clinical Trial Registration: www.clinicaltrials.gov, identifier NCT02670278.
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http://dx.doi.org/10.3389/fcimb.2021.622550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027255PMC
July 2021

Key genetic variants associated with variation of milk oligosaccharides from diverse human populations.

Genomics 2021 Jul 6;113(4):1867-1875. Epub 2021 Apr 6.

Department of Animal, Veterinary, and Food Sciences, University of Idaho, Moscow, ID 83844, USA. Electronic address:

Human milk oligosaccharides (HMO), the third most abundant component of human milk, are thought to be important contributors to infant health. Studies have provided evidence that geography, stage of lactation, and Lewis and secretor blood groups are associated with HMO profile. However, little is known about how variation across the genome may influence HMO composition among women in various populations. In this study, we performed genome-wide association analyses of 395 women from 8 countries to identify genetic regions associated with 19 different HMO. Our data support FUT2 as the most significantly associated (P < 4.23 to P < 4.5) gene with seven HMO and provide evidence of balancing selection for FUT2. Although polymorphisms in FUT3 were also associated with variation in lacto-N-fucopentaose II and difucosyllacto-N-tetrose, we found little evidence of selection on FUT3. To our knowledge, this is the first report of the use of genome-wide association analyses on HMO.
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http://dx.doi.org/10.1016/j.ygeno.2021.04.004DOI Listing
July 2021

Long-term impact of West African food system responses to COVID-19.

Nat Food 2020 Dec 19;1:768-770. Epub 2020 Nov 19.

Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.

The COVID-19 pandemic continues to impact health and livelihoods in West Africa. Exposure of food system fragilities by the pandemic presents the opportunity for regional-specific reforms to deliver healthy diets for all and promote resilience to future shocks.
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http://dx.doi.org/10.1038/s43016-020-00191-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610541PMC
December 2020

Common Variants in the Gene Alter Hepcidin but not Plasma Iron in Response to Oral Iron in Healthy Gambian Adults: A Recall-by-Genotype Study.

Curr Dev Nutr 2021 Mar 24;5(3):nzab014. Epub 2021 Feb 24.

MRC Unit The Gambia at London School of Hygiene & Tropical Medicine, Fajara, Banjul, The Gambia.

Background: The role of genetic determinants in mediating iron status in Africans is not fully understood. Genome-wide association studies in non-African populations have revealed genetic variants in the transmembrane protease serine 6 gene () that are associated with the risk of anemia.

Objectives: To investigate the effects of risk alleles for low iron status, namely rs2235321, rs855791, and rs4820268, on responses to oral iron in healthy Gambian adults.

Methods: Using a recall-by-genotype design, participants were selected from a pregenotype cohort of 3000 individuals in the Keneba Biobank (Medical Research Council Unit The Gambia at the London School of Hygiene & Tropical Medicine). Participants were invited to participate in the study based on 9 genotype combinations obtained from 3 single nucleotide polymorphisms (SNPs): rs2235321, rs855791, and rs4820268. The participants fasted overnight and then ingested a single oral dose of ferrous sulfate (130 mg elemental iron). Blood samples were collected prior to iron ingestion and at 2 and 5 h after the oral iron dose. The effects of genotype on hepcidin and plasma iron parameters were assessed.

Results: A total of 251 individuals were enrolled. Homozygous carriers of the major alleles at each of the SNPs had higher plasma hepcidin at baseline (rs2235321: GG compared with AA = 9.50 compared with 6.60 ng/ml,  = 0.035; rs855791: GG compared with AG = 9.50 compared with 4.96 ng/mL,  = 0.015; rs4820268: AA compared with GG = 9.50 compared with 3.27 ng/mL,   = 0.002) and at subsequent timepoints. In most subjects, hepcidin concentrations increased following iron ingestion (overall group mean = 4.98 ± 0.98 ng/mL at 5 h,  < 0.001), but double heterozygotes at rs2235321 and rs855791 showed no increase (0.36 ± 0.40 ng/mL at 5 h,  = 0.667).

Conclusions: This study revealed that common variants influence hepcidin concentrations, but not iron status indicators either at baseline or following a large oral dose of iron. These results suggest that genetic variations in the gene are unlikely to be important contributors to variations in iron status in Africans.This study was registered at clinicaltrials.gov (# NCT03341338).
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http://dx.doi.org/10.1093/cdn/nzab014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994066PMC
March 2021

Ethnic inequalities in older adults bowel cancer awareness: findings from a community survey conducted in an ethnically diverse region in England.

BMC Public Health 2021 03 16;21(1):513. Epub 2021 Mar 16.

Research Department of Behavioural Science and Health, University College London, London, WC1E 7HB, UK.

Background: To date, research exploring the public's awareness of bowel cancer has taken place with predominantly white populations. To enhance our understanding of how bowel cancer awareness varies between ethnic groups, and inform the development of targeted interventions, we conducted a questionnaire study across three ethnically diverse regions in Greater London, England.

Methods: Data were collected using an adapted version of the bowel cancer awareness measure. Eligible adults were individuals, aged 60+ years, who were eligible for screening. Participants were recruited and surveyed, verbally, by staff working at 40 community pharmacies in Northwest London, the Harrow Somali association, and St. Mark's Bowel Cancer Screening Centre. Associations between risk factor, symptom and screening awareness scores and ethnicity were assessed using multivariate regression.

Results: 1013 adults, aged 60+ years, completed the questionnaire; half were of a Black, Asian or Minority ethnic group background (n = 507; 50.0%). Participants recognised a mean average of 4.27 of 9 symptoms and 3.99 of 10 risk factors. Symptom awareness was significantly lower among all ethnic minority groups (all p's < 0.05), while risk factor awareness was lower for Afro-Caribbean and Somali adults, specifically (both p's < 0.05). One in three adults (n = 722; 29.7%) did not know there is a Bowel Cancer Screening Programme. Bowel screening awareness was particularly low among Afro-Caribbean and Somali adults (both p's < 0.05).

Conclusion: Awareness of bowel cancer symptoms, risk factors and screening varies by ethnicity. Interventions should be targeted towards specific groups for whom awareness of screening and risk factors is low.
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http://dx.doi.org/10.1186/s12889-021-10536-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967942PMC
March 2021

Identification of nutritionally modifiable hormonal and epigenetic drivers of positive and negative growth deviance in rural African fetuses and infants: Project protocol and cohort description.

Gates Open Res 2020 24;4:25. Epub 2020 Feb 24.

Department of Anthropology, University of Colorado, Boulder, CO, 80309, USA.

Growth retardation (stunting, wasting and poor organ development) among children in low-income countries has major short and long-term health consequences yet very little is known about the nutritional and environmental influences on the key hormonal axes regulating child growth in these settings, nor the tempo and timing of faltering episodes. Here we describe the study protocol and provide a cohort description of the Hormonal and Epigenetic Regulators of Growth (HERO-G) study. This prospective cohort study from rural Gambia, West Africa, followed mothers and children longitudinally from pre-conception, through pregnancy, delivery, and to two years of child age A total of 251 eligible mother-infant pairs were recruited into the HERO-G study, with 206 (82%) followed up until two years of age. Women were seen at scheduled antenatal appointments at 20, 28 and 36 weeks of gestation, and at delivery, where possible. Between one week and 12 months of age, infants were visited every second day for collection of detailed anthropometry and morbidity data. Infants identified as about to enter a growth faltering episode at these visits entered a more detailed 20-day protocol, with the collection of dried blood spots, anthropometry and body composition. All infants were seen for scheduled clinic visits at 3, 6, 9, 12, 18 and 24 months of age for clinical examination and venous blood draw. Data from the HERO-G study is being used to explore three major mechanistic pathways influencing growth: 1) genome-wide investigations for signatures of epigenetic effects on any loci that might affect growth; 2) frequent anthropometric measurement coupled with non-invasive monitoring for rapid identification and interrogation of real-time faltering patterns and aetiology; 3) focused measurement of hormones and cytokines that act together in an integrated manner, both and after birth, to coordinate patterns of growth with immune activation, inflammation, and nutritional status.
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http://dx.doi.org/10.12688/gatesopenres.13101.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921526PMC
February 2020

Antenatal iron supplementation, FGF23, and bone metabolism in Kenyan women and their offspring: secondary analysis of a randomized controlled trial.

Am J Clin Nutr 2021 05;113(5):1104-1114

Wageningen University, Division of Human Nutrition and Health, P.O. Box 17, 6700 AA Wageningen, The Netherlands.

Background: Fibroblast growth factor-23 (FGF23) regulates body phosphate homeostasis primarily by increasing phosphaturia. It also acts as a vitamin D-regulating hormone. Maternal iron deficiency is associated with perturbed expression and/or regulation of FGF23 and hence might be implicated in the pathogenesis of hypophosphatemia-driven rickets in their offspring.

Objectives: We aimed to determine the effect of antenatal oral iron supplementation on FGF23 concentration and maternal and infant markers of bone-mineral regulation.

Methods: We performed a secondary analysis of a trial in which 470 rural Kenyan women with singleton pregnancies and hemoglobin concentrations ≥ 90 g/L were randomly allocated to daily, supervised supplementation with 60 mg elemental iron as ferrous fumarate or placebo from 13-23 weeks of gestation until 1 mo postpartum. As previously reported, iron supplementation improved iron status in mothers and neonates. For the present study, we reanalyzed all available plasma samples collected in mothers and neonates at birth, with primary outcomes being concentrations of FGF23, measured by 2 assays: 1 that detects intact hormone and C-terminal cleavage products (total-FGF23) and another that detects the intact hormone only (intact-FGF23).

Results: Analysis was performed on 433 women (n = 216, iron group; n = 217, placebo group) and 414 neonates (n = 207, iron group; n = 207, placebo group). Antenatal iron supplementation reduced geometric mean total-FGF23 concentrations in mothers and neonates by 62.6% (95% CI: 53.0%, 70.3%) and 15.2% (95% CI: -0.3%, 28.4%, P = 0.06), respectively. In addition, it increased geometric mean neonatal intact-FGF23 concentrations by 21.6% (95% CI: 1.2%, 46.1%), increased geometric mean maternal hepcidin concentrations by 136.4% (95% CI: 86.1%, 200.3%), and decreased mean maternal 25-hydroxyvitamin D concentrations by 6.1 nmol/L (95% CI: -11.0, -1.2 nmol/L).

Conclusions: Analysis of this randomized trial confirms that iron supplementation can reverse elevated FGF23 production caused by iron deficiency in iron-deficient mothers and their neonates. Further investigations are warranted to assess to what extent iron supplementation can prevent FGF23-mediated hypophosphatemic rickets or osteomalacia.
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http://dx.doi.org/10.1093/ajcn/nqaa417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106766PMC
May 2021

Multipathogen Analysis of IgA and IgG Antigen Specificity for Selected Pathogens in Milk Produced by Women From Diverse Geographical Regions: The INSPIRE Study.

Front Immunol 2020 11;11:614372. Epub 2021 Feb 11.

Antigen Discovery Incorporated, Irvine, CA, United States.

Breastfeeding provides defense against infectious disease during early life. The mechanisms underlying this protection are complex but likely include the vast array of immune cells and components, such as immunoglobulins, in milk. Simply characterizing the concentrations of these bioactives, however, provides only limited information regarding their potential relationships with disease risk in the recipient infant. Rather, understanding pathogen and antigen specificity profiles of milk-borne immunoglobulins might lead to a more complete understanding of how maternal immunity impacts infant health and wellbeing. Milk produced by women living in 11 geographically dispersed populations was applied to a protein microarray containing antigens from 16 pathogens, including diarrheagenic , spp. serovar Typhi, , and other pathogens of global health concern, and specific IgA and IgG binding was measured. Our analysis identified novel disease-specific antigen responses and suggests that some IgA and IgG responses vary substantially within and among populations. Patterns of antibody reactivity analyzed by principal component analysis and differential reactivity analysis were associated with either lower-to-middle-income countries (LMICs) or high-income countries (HICs). Antibody levels were generally higher in LMICs than HICs, particularly for and diarrheagenic antigens, although sets of , , and some antigens were more reactive in HICs. Differential responses were typically specific to canonical immunodominant antigens, but a set of nondifferential but highly reactive antibodies were specific to antigens possibly universally recognized by antibodies in human milk. This approach provides a promising means to understand how breastfeeding and human milk protect (or do not protect) infants from environmentally relevant pathogens. Furthermore, this approach might lead to interventions to boost population-specific immunity in at-risk breastfeeding mothers and their infants.
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http://dx.doi.org/10.3389/fimmu.2020.614372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905217PMC
July 2021

Malaria is a cause of iron deficiency in African children.

Nat Med 2021 04 22;27(4):653-658. Epub 2021 Feb 22.

Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

Malaria and iron deficiency (ID) are common and interrelated public health problems in African children. Observational data suggest that interrupting malaria transmission reduces the prevalence of ID. To test the hypothesis that malaria might cause ID, we used sickle cell trait (HbAS, rs334 ), a genetic variant that confers specific protection against malaria, as an instrumental variable in Mendelian randomization analyses. HbAS was associated with a 30% reduction in ID among children living in malaria-endemic countries in Africa (n = 7,453), but not among individuals living in malaria-free areas (n = 3,818). Genetically predicted malaria risk was associated with an odds ratio of 2.65 for ID per unit increase in the log incidence rate of malaria. This suggests that an intervention that halves the risk of malaria episodes would reduce the prevalence of ID in African children by 49%.
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http://dx.doi.org/10.1038/s41591-021-01238-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610676PMC
April 2021

Pregnancy-related interventions in mothers at risk for gestational diabetes in Asian India and low and middle-income countries (PRIMORDIAL study): protocol for a randomised controlled trial.

BMJ Open 2021 02 17;11(2):e042069. Epub 2021 Feb 17.

Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, Oxfordshire, UK

Introduction: Lifestyle modification is the mainstay of gestational diabetes mellitus (GDM) prevention. However, clinical trials evaluating the safety and efficacy of diet or physical activity (PA) in low-income and middle-income settings such as Africa and India are lacking. This trial aims to evaluate the efficacy of yoghurt consumption and increased PA (daily walking) in reducing GDM incidence in high-risk pregnant women.

Methods And Analysis: The study is a 2×2 factorial, open-labelled, multicentre randomised controlled trial to be conducted in Vellore, South India and The Gambia, West Africa. 'High-risk' pregnant women (n=1856) aged ≥18 years and ≤16 weeks of gestational age, with at least one risk factor for developing GDM, will be randomised to either (1) yoghurt (2) PA (3) yoghurt +PA or (4) standard antenatal care. Participants will be followed until 32 weeks of gestation with total active intervention lasting for a minimum of 16 weeks. The primary endpoint is GDM incidence at 26-28 weeks diagnosed using International Association of the Diabetes and Pregnancy Study Groups criteria or elevated fasting glucose (≥5.1 mmol/L) at 32 weeks. Secondary endpoints include absolute values of fasting plasma glucose concentration at 32 weeks gestation, maternal blood pressure, gestational weight gain, intrapartum and neonatal outcomes. Analysis will be both by intention to treat and per-protocol. Continuous outcome measurements will be analysed using multiple linear regression and binary variables by logistic regression.

Ethics And Dissemination: The study is approved by Oxford Tropical Research Ethics Committee (44-18), ethics committees of the Christian Medical College, Vellore (IRB 11367) and MRCG Scientific Coordinating Committee (SCC 1645) and The Gambia Government/MRCG joint ethics committee (L2020.E15). Findings of the study will be published in peer-reviewed scientific journals and presented in conferences.

Trial Registration Number: ISRCTN18467720.
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http://dx.doi.org/10.1136/bmjopen-2020-042069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893661PMC
February 2021

A Novel method for the identification and quantification of weight faltering.

Am J Phys Anthropol 2021 05 1;175(1):282-291. Epub 2021 Jan 1.

Growth and Development Lab, Department of Anthropology, University of Colorado Boulder, Boulder, Colorado, USA.

Objective: We describe a new method for identifying and quantifying the magnitude and rate of short-term weight faltering episodes, and assess how (a) these episodes relate to broader growth outcomes, and (b) different data collection intervals influence the quantification of weight faltering.

Materials And Methods: We apply this method to longitudinal growth data collected every other day across the first year of life in Gambian infants (n = 124, males = 65, females = 59). Weight faltering episodes are identified from velocity peaks and troughs. Rate of weight loss and regain, maximum weight loss, and duration of each episode were calculated. We systematically reduced our dataset to mimic various potential measurement intervals, to assess how these intervals affect the ability to derive information about short-term weight faltering episodes. We fit linear models to test whether metrics associated with growth faltering were associated with growth outcomes at 1 year, and generalized additive mixed models to determine whether different collection intervals influence episode identification and metrics.

Results: Three hundred weight faltering episodes from 119 individuals were identified. The number and magnitude of episodes negatively impacted growth outcomes at 1 year. As data collection interval increases, weight faltering episodes are missed and the duration of episodes is overestimated, resulting in the rate of weight loss and regain being underestimated.

Conclusions: This method identifies and quantifies short-term weight faltering episodes, that are in turn negatively associated with growth outcomes. This approach offers a tool for investigators interested in understanding how short-term weight faltering relates to longer-term outcomes.
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http://dx.doi.org/10.1002/ajpa.24217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247282PMC
May 2021

Properties of Conjugated Materials from Quantum Chemistry Coupled to Molecular Dynamics Generated Ensembles.

J Phys Chem A 2020 Dec 15;124(51):10667-10677. Epub 2020 Dec 15.

Institute of Chemical Sciences, School of Engineering & Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS, United Kingdom.

We provide a set of molecular dynamics simulations employing a force field specifically parameterized for organic π-conjugated materials. The resulting conformation ensemble was coupled to quantum chemistry calculations, and quantities of interest for optoelectronic applications, namely, ground- and excited-state energies, oscillator strengths, and dipole moments were extracted. This combined approach allowed not only exploration of the configurational landscape but also of the resulting electronic properties of each frame within the simulation and thus probe the link between conformation and property. A study was made of the sampling and convergence requirements to yield reliable averages over the ensemble. Typically between 800 and 1000 conformations were sufficient to ensure convergence of properties. However, for some oligomers, more configurations were required to achieve convergence of the oscillator strength and magnitude of the dipole moment.
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http://dx.doi.org/10.1021/acs.jpca.0c07213DOI Listing
December 2020

Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.

Nat Genet 2020 12 23;52(12):1314-1332. Epub 2020 Nov 23.

Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.

Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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http://dx.doi.org/10.1038/s41588-020-00713-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610439PMC
December 2020

Dysglycemia in Children with Severe Acute Malnutrition: A Systematic Review and Meta-Analysis.

Adv Nutr 2021 06;12(3):959-968

Department of Biomedical Sciences, College of Medicine, University of Malawi, Blantyre, Malawi.

Dysglycemia is a common complication of severe acute malnutrition (SAM) in children. Its prevalence and impact on short- and long-term outcomes are not well described. This systematic review was undertaken to review the available evidence on dysglycemia (either hypo- or hyperglycemia) in hospitalized children with SAM. The 2 primary objectives of this systematic review were to understand the prevalence of hypoglycemia and hyperglycemia in children with SAM. A secondary objective was to understand the relation between dysglycemia and clinical outcomes like mortality in children with SAM. MEDLINE was searched with terms related to children, SAM, and dysglycemia. A meta-analysis of proportions was completed to determine the hypoglycemia prevalence and a standard meta-analysis was done to determine the relation between hypoglycemia and mortality. The certainty of the evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A total of 2148 articles were identified in the database search of which 16 met the inclusion criteria for the systematic review based on screening done by multiple reviewers. The overall prevalence of hypoglycemia in SAM across studies based on the meta-analysis of proportions was 9% (95% CI: 7%, 12%; I2 = 92%). Meta-analysis results showed that hypoglycemia was associated with a higher chance of mortality during hospitalization in children with SAM (OR: 4.29; 95% CI: 3.04, 6.05; I2 = 0%). According to the GRADE evaluation, the certainty of the evidence for the prevalence of hypoglycemia was low and for hyperglycemia was very low. For the relation between hypoglycemia and mortality, the certainty of the evidence was moderate. A meta-analysis was not carried out for the prevalence of hyperglycemia due to the wide range of definitions used for across studies, but the prevalence ranged from 2% to 38% in the literature. This systematic review highlights the need for further work in this area to include serial glucose measurements to understand the clinical importance of dysglycemia during hospitalization in children with SAM.
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http://dx.doi.org/10.1093/advances/nmaa138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166557PMC
June 2021
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