Interplay of Luminophores and Photoinitiators during Synthesis of Bulk and Patterned Luminescent Photopolymer Blends.

Four-dimensional printing with embedded photoluminescence is emerging as an exciting area in additive manufacturing. Slim polymer films patterned with three-dimensional lattices of multimode cylindrical waveguides (waveguide-encoded lattices, WELs) with enhanced fields of view can be fabricated by localizing light as self-trapped beams within a photopolymerizable formulation. Luminescent WELs have potential applications as solar cell coatings and smart planar optical components. However, as luminophore-photoinitiator interactions are expected to change the photopolymerization kinetics, the design of robust luminescent photopolymer sols is nontrivial. Here, we use model photopolymer systems based on methacrylate-siloxane and epoxide homopolymers and their blends to investigate the influence of the luminophore Lumogen Violet (LV) on the photolysis kinetics of the Omnirad 784 photoinitiator through UV-vis absorbance spectroscopy. Initial rate analysis with different bulk polymers reveals differences in the pseudo-first-order rate constants in the absence and presence of LV, with a notable increase (∼40%) in the photolysis rate for the 1:1 blend. Fluorescence quenching studies, coupled with density functional theory calculations, establish that these differences arise due to electron transfer from the photoexcited LV to the ground-state photoinitiator molecules. We also demonstrate an in situ UV-vis absorbance technique that enables real-time monitoring of both waveguide formation and photoinitiator consumption during the fabrication of WELs. The in situ photolysis kinetics confirm that LV-photoinitiator interactions also influence the photopolymerization process during WEL formation. Our findings show that luminophores play a noninnocent role in photopolymerization and highlight the necessity for both careful consideration of the photopolymer formulation and a real-time monitoring approach to enable the fabrication of high-quality micropatterned luminescent polymeric films.

Comparing the effectiveness and cost-effectiveness of text-message reminders and telephone patient navigation to improve the uptake of faecal immunochemical test screening among non-responders in London: a randomised controlled trial protocol.

INTRODUCTION: Participation in bowel cancer screening is lower in regions where there is high ethnic diversity and/or socioeconomic deprivation. Interventions, such as text message reminders and patient navigation (PN), have the potential to increase participation in these areas. As such, there is interest in the comparative effectiveness of these interventions to increase bowel cancer screening participation, as well as their relative cost-effectiveness. METHODS AND ANALYSIS: This study will use a three-arm randomised controlled trial design to compare the effectiveness and cost-effectiveness of text message reminders and PN to increase the uptake of bowel cancer screening in London. Participants will be individuals who have not returned a completed faecal immunochemical test kit within 13 weeks of receiving a routine invitation from the London bowel cancer screening hub. Participants will be randomised (in a 1:1:1 ratio) to receive either (1) usual care (ie, 'no intervention'), (2) a text message reminder at 13 weeks, followed by repeated text message reminders at 15, 17 and 19 weeks (in the event of non-response) or (3) a text message reminder at 13 weeks, followed by PN telephone calls at 15, 17 and 19 weeks in the event of non-response. The primary endpoint will be participation in bowel cancer screening, defined as 'the return of a completed kit by week 24'. Statistical analysis will use multivariate logistic regression and will incorporate pairwise comparisons of all three groups, adjusted for multiple testing. ETHICS AND DISSEMINATION: Approvals to conduct the research have been obtained from University College London's Joint Research Office (Ref: 150666), the Screening Research, Innovation and Development Advisory Committee ('RIDAC', Ref: 2223 014 BCSP Kerrison), the Health Research Authority (Ref: 22/WM/0212) and the Confidentiality Advisory Group (Ref: 22/CAG/0140). Results will be conveyed to stakeholders, notably those managing the screening programme and published in peer-reviewed journals/presented at academic conferences. TRIAL REGISTRATION NUMBER: ISRCTN17245519.

Using a multistate mapping approach to surface hopping to predict the ultrafast electron diffraction signal of gas-phase cyclobutanone.

Using the recently developed multistate mapping approach to surface hopping (multistate MASH) method combined with SA(3)-CASSCF(12,12)/aug-cc-pVDZ electronic structure calculations, the gas-phase isotropic ultrafast electron diffraction (UED) of cyclobutanone is predicted and analyzed. After excitation into the n-3s Rydberg state (S2), cyclobutanone can relax through two S2/S1 conical intersections, one characterized by compression of the CO bond and the other by dissociation of the α-CC bond. Subsequent transfer into the ground state (S0) is then achieved via two additional S1/S0 conical intersections that lead to three reaction pathways: α ring-opening, ethene/ketene production, and CO liberation. The isotropic gas-phase UED signal is predicted from the multistate MASH simulations, allowing for a direct comparison to the experimental data. This work, which is a contribution to the cyclobutanone prediction challenge, facilitates the identification of the main photoproducts in the UED signal and thereby emphasizes the importance of dynamics simulations for the interpretation of ultrafast experiments.

Maternal age is related to offspring DNA methylation: A meta-analysis of results from the PACE consortium.

Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta-analyzed epigenome-wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5-10 years old) from the Pregnancy and Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites in 13 loci with DNAm associated with maternal age (PFDR < 0.05). Eight of these CpGs were located near/in the MTNR1B gene, coding for a melatonin receptor. Regional analysis identified them together as a differentially methylated region consisting of 9 CpGs in/near MTNR1B, at which higher DNAm was associated with greater maternal age (PFDR = 6.92 × 10-8) in newborns. In childhood blood samples, these differences in blood DNAm of MTNR1B CpGs were nominally significant (p < 0.05) and retained the same positive direction, suggesting persistence of associations. Maternal age was also positively associated with higher DNA methylation at three CpGs in RTEL1-TNFRSF6B at birth (PFDR < 0.05) and nominally in childhood (p < 0.0001). Of the remaining 10 CpGs also persistent in childhood, methylation at cg26709300 in YPEL3/BOLA2B in external data was associated with expression of ITGAL, an immune regulator. While further study is needed to establish causality, particularly due to the small effect sizes observed, our results potentially support offspring DNAm as a mechanism underlying associations of maternal age with child health.

Haem iron versus ferrous iron salts to treat iron deficiency anaemia in Gambian children: protocol for randomised controlled trial {1}.

BACKGROUND: The World Health Organization recommends universal iron supplementation for children aged 6-23 months in countries where anaemia is seen in over 40% of the population. Conventional ferrous salts have low efficacy due to low oral absorption in children with inflammation. Haem iron is more bioavailable, and its absorption may not be decreased by inflammation. This study aims to compare daily supplementation with haem iron versus ferrous sulphate on haemoglobin concentration and serum ferritin concentration after 12 weeks of supplementation. METHODS: This will be a two-arm, randomised controlled trial. Gambian children aged 6-12 months with anaemia will be recruited within a predefined geographical area and recruited by trained field workers. Eligible participants will be individually randomised using a 1:1 ratio within permuted blocks to daily supplementation for 12 weeks with either 10.0 mg of elemental iron as haem or ferrous sulphate. Safety outcomes such as diarrhoea and infection-related adverse events will be assessed daily by the clinical team (see Bah et al. Additional file 4_Adverse event eCRF). Linear regression will be used to analyse continuous outcomes, with log transformation to normalise residuals as needed. Binary outcomes will be analysed by binomial regression or logistic regression, Primary analysis will be by modified intention-to-treat (i.e., those randomised and who ingested at least one supplement dose of iron), with multiple imputations to replace missing data. Effect estimates will be adjusted for baseline covariates (C-reactive protein, alpha-1-acid glycoprotein, haemoglobin, ferritin, soluble transferrin receptor). DISCUSSION: This study will determine if therapeutic supplementation with haem iron is more efficacious than with conventional ferrous sulphate in enhancing haemoglobin and ferritin concentrations in anaemic children aged 6-12 months. TRIAL REGISTRATION: Pan African Clinical Trial Registry PACTR202210523178727.

A practical guide to cross-cultural and multi-sited data collection in the biological and behavioural sciences.

Researchers in the biological and behavioural sciences are increasingly conducting collaborative, multi-sited projects to address how phenomena vary across ecologies. These types of projects, however, pose additional workflow challenges beyond those typically encountered in single-sited projects. Through specific attention to cross-cultural research projects, we highlight four key aspects of multi-sited projects that must be considered during the design phase to ensure success: (1) project and team management; (2) protocol and instrument development; (3) data management and documentation; and (4) equitable and collaborative practices. Our recommendations are supported by examples from our experiences collaborating on the Evolutionary Demography of Religion project, a mixed-methods project collecting data across five countries in collaboration with research partners in each host country. To existing discourse, we contribute new recommendations around team and project management, introduce practical recommendations for exploring the validity of instruments through qualitative techniques during piloting, highlight the importance of good documentation at all steps of the project, and demonstrate how data management workflows can be strengthened through open science practices. While this project was rooted in cross-cultural human behavioural ecology and evolutionary anthropology, lessons learned from this project are applicable to multi-sited research across the biological and behavioural sciences.

Blood pressure and the hypertension care cascade in The Gambia: Findings from a nationwide survey.

Community treatment of hypertension in sub-Saharan Africa is hampered by gaps at several stages of the care cascade. We compared blood pressure (BP) levels (systolic, diastolic and pulse pressures) in four groups of participants by hypertension and treatment status. We conducted a nationally representative survey of adults 35 years and older using a multistage sampling strategy based on the 2013 Gambia Population and Housing Census. The BP measurements were taken in triplicate 5 min apart, and the average of the last two measurements was used for analysis. Systolic and diastolic BP levels and pulse pressure were compared by hypertension status using mean and 95% confidence intervals (CI). 53.1% of the sample were normotensive with mean systolic BP (SBP) of 119.2 mmHg (95% CI, 118.7-119.6) and diastolic BP (DBP) of 78.1 mmHg (77.8-78.3). Among individuals with hypertension, mean SBP was 148.7 mmHg (147.7-149.7) among those unaware of their hypertension, 152.2 mmHg (151.0-153.5) among treated individuals and was highest in untreated individuals at 159.3 mmHg (157.3-161.2). The findings were similar for DBP levels, being 93.9 mmHg (93.4-94.4) among the unaware, 95.1 mmHg (94.4-95.8) among the treated and highest at 99.1 mmHg (98.1-100.2) in untreated participants. SBP and DBP were higher in men, and SBP was as expected higher in those aged ≥55 years. BP level was similar in urban and rural areas. Our data shows high BP levels among participants with hypertension including those receiving treatment. Efforts to reduce the health burden of hypertension will require inputs at all levels of the care cascade.

Validation of the Emergency Department-Paediatric Early Warning Score (ED-PEWS) for use in low- and middle-income countries: A multicentre observational study.

Early recognition of children at risk of serious illness is essential in preventing morbidity and mortality, particularly in low- and middle-income countries (LMICs). This study aimed to validate the Emergency Department-Paediatric Early Warning Score (ED-PEWS) for use in acute care settings in LMICs. This observational study is based on previously collected clinical data from consecutive children attending four diverse settings in LMICs. Inclusion criteria and study periods (2010-2021) varied. We simulated the ED-PEWS, consisting of patient age, consciousness, work of breathing, respiratory rate, oxygen saturation, heart rate, and capillary refill time, based on the first available parameters. Discrimination was assessed by the area under the curve (AUC), sensitivity and specificity (previously defined cut-offs < 6 and ≥ 15). The outcome measure was for each setting a composite marker of high urgency. 41,917 visits from Gambia rural, 501 visits from Gambia urban, 2,608 visits from Suriname, and 1,682 visits from Tanzania were included. The proportion of high urgency was variable (range 4.6% to 24.9%). Performance ranged from AUC 0.80 (95%CI 0.70-0.89) in Gambia urban to 0.62 (95%CI 0.55-0.67) in Tanzania. The low-urgency cut-off showed a high sensitivity in all settings ranging from 0.83 (95%CI 0.81-0.84) to 1.00 (95%CI 0.97-1.00). The high-urgency cut-off showed a specificity ranging from 0.71 (95%CI 0.66-0.75) to 0.97 (95%CI 0.97-0.97). The ED-PEWS has a moderate to good performance for the recognition of high urgency children in these LMIC settings. The performance appears to have potential in improving the identification of high urgency children in LMICs.

Early iron supplementation in exclusively breastfed Gambian infants: a randomized controlled trial.

Objective: To investigate the effect of daily iron supplementation for 14 weeks on the serum iron concentration and other markers of iron status in exclusively breastfed infants in Gambia. Methods: A placebo-controlled, randomized, double-blind trial was performed in rural Gambia between 3 August 2021 and 9 March 2022. Overall, 101 healthy, exclusively breastfed infants aged 6 to 10 weeks were recruited at vaccination clinics and through community health workers. Infants were randomized to receive iron supplementation (7.5 mg/day as ferrous sulfate in sorbitol solution) or placebo for 98 days. Venous blood samples were collected at baseline and on day 99 to assess the serum iron concentration and other markers of iron and haematological status. Findings: At day 99, the serum iron concentration was significantly higher in the iron supplementation group than the placebo group (crude difference in means: 2.5 µmol/L; 95% confidence interval: 0.6 to 4.3) and there were significant improvements in other iron and haematological markers. There were 10 serious adverse events (five in each group), 106 non-serious adverse events (54 with iron supplementation; 52 with placebo) and no deaths. There was no marked difference between the groups in maternally reported episodes of diarrhoea, fever, cough, skin infection, eye infection or nasal discharge. Conclusion: In exclusively breastfed Gambian infants, iron supplementation from 6 weeks of age was associated with a significant improvement in markers of iron status at around 6 months of age. There was no indication of adverse effects on growth or infections.

A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation.

Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P < 0.05) and 1107 regions. Forty CpGs were located within known quantitative trait loci for gene expression traits in blood, and trait enrichment analysis suggested a strong association with immune-related, transcriptional control, and blood pressure regulation phenotypes. Decreasing fertility rates worldwide with the concomitant increased proportion of first-born children highlights a potential reflection of birth order-related epigenomic states on changing disease incidence trends.

Prevalence of hypertension, diabetes, obesity, multimorbidity, and related risk factors among adult Gambians: a cross-sectional nationwide study.

BACKGROUND: As countries progress through economic and demographic transition, chronic non-communicable diseases (NCDs) overtake a previous burden of infectious diseases. We investigated the prevalence of hypertension, diabetes, obesity, and multimorbidity in older adults in The Gambia. METHODS: We embedded a survey on NCDs into the nationally representative 2019 Gambia National Eye Health Survey of adults aged 35 years or older. We measured anthropometrics, capillary blood glucose, and blood pressure together with sociodemographic information, personal and family health history, and information on smoking and alcohol consumption. Hypertension was defined as systolic blood pressure of 140 mmHg or more, diastolic blood pressure of 90 mmHg or more, or receiving treatment for hypertension. Diabetes was defined as fasting capillary blood glucose of 7 mmol/L or more, random blood glucose of 11·1mmol/L or more, or previous diagnosis or treatment for diabetes. Overweight was defined as BMI of 25-29·9 kg/m2 and obesity as 30 kg/m2 or more. Multimorbidity was defined as the coexistence of two or more conditions. We calculated weighted crude and adjusted estimates for each outcome by sex, residence, and selected sociodemographic factors. FINDINGS: We analysed data from 9188 participants (5039 [54·8%] from urban areas, 6478 [70·5%] women). The prevalence of hypertension was 47·0%; 2259 (49·3%) women, 2052 (44·7%) men. The prevalence increased with age, increasing from 30% in those aged 35-45 years to over 75% in those aged 75 years and older. Overweight and obesity increased the odds of hypertension, and underweight reduced the odds. The prevalence of diabetes was 6·3% (322 [7·0%] women, 255 [5·6%] men), increasing from 3·8% in those aged 35-44 years to 9·1% in those aged 65-75 years, and then declining. Diabetes was much more common among urban residents, especially in women (peaking at 13% by age 65 years). Diabetes was strongly associated with BMI and wealth index. The prevalence of obesity was 12·0% and was notably higher in women than men (880 [20·2%] vs 170 [3·9%]). Multimorbidity was present in 932 (10·7%), and was more common in women than men (694 [15·9] vs 238 [5·5]). The prevalence of smoking was 9·7%; 5 (0·1%) women, 889 (19·3%) men. Alcohol consumption in the past year was negligible. INTERPRETATION: We have documented high levels of NCDs and associated risk factors in Gambian adults. This presents a major stress on the country's fragile health system that requires an urgent, concerted, and targeted mutisectoral strategy. FUNDING: The Queen Elizabeth Diamond Jubilee Trust and Wellcome Trust.

Modular Approach to Selected Configuration Interaction in an Arbitrary Spin Basis: Implementation and Comparison of Approaches.

A modular selected configuration interaction (SCI) code has been developed that is based on the existing Monte-Carlo configuration interaction code (MCCI). The modularity allows various selection protocols to be implemented with ease and allows for fair comparison between wave functions built via different criteria. We have initially implemented adaptations of existing SCI theories, which are based on either energy- or coefficient-driven selection schemes. These codes have been implemented not only in the basis of Slater determinants (SDs) but also in the basis of configuration state functions (CSFs) and extended to state-averaged regimes. This allows one to take advantage of the reduced dimensionality of the wave function in the CSF basis and also the guarantee of pure spin states. All SCI methods were found to be able to predict potential energy surfaces to high accuracy, producing compact wave functions, when compared to full configuration interaction (FCI) for a variety of bond-breaking potential energy surfaces. The compactness of the error-controlled adaptive configuration interaction approach, particularly in the CSF basis, was apparent with nonparallelity errors within chemical accuracy while containing as little as 0.02% of the FCI CSF space. The size-to-accuracy was also extended to FCI spaces approaching one billion configurations.

Epidemiology of multimorbidity in low-income countries of sub-Saharan Africa: Findings from four population cohorts.

We investigated prevalence and demographic characteristics of adults living with multimorbidity (≥2 long-term conditions) in three low-income countries of sub-Saharan Africa, using secondary population-level data from four cohorts; Malawi (urban & rural), The Gambia (rural) and Uganda (rural). Information on; measured hypertension, diabetes and obesity was available in all cohorts; measured hypercholesterolaemia and HIV and self-reported asthma was available in two cohorts and clinically diagnosed epilepsy in one cohort. Analyses included calculation of age standardised multimorbidity prevalence and the cross-sectional associations of multimorbidity and demographic/lifestyle factors using regression modelling. Median participant age was 29 (Inter quartile range-IQR 22-38), 34 (IQR25-48), 32 (IQR 22-53) and 37 (IQR 26-51) in urban Malawi, rural Malawi, The Gambia, and Uganda, respectively. Age standardised multimorbidity prevalence was higher in urban and rural Malawi (22.5%;95% Confidence intervals-CI 21.6-23.4%) and 11.7%; 95%CI 11.1-12.3, respectively) than in The Gambia (2.9%; 95%CI 2.5-3.4%) and Uganda (8.2%; 95%CI 7.5-9%) cohorts. In multivariate models, females were at greater risk of multimorbidity than males in Malawi (Incidence rate ratio-IRR 1.97, 95% CI 1.79-2.16 urban and IRR 2.10; 95%CI 1.86-2.37 rural) and Uganda (IRR- 1.60, 95% CI 1.32-1.95), with no evidence of difference between the sexes in The Gambia (IRR 1.16, 95% CI 0.86-1.55). There was strong evidence of greater multimorbidity risk with increasing age in all populations (p-value <0.001). Higher educational attainment was associated with increased multimorbidity risk in Malawi (IRR 1.78; 95% CI 1.60-1.98 urban and IRR 2.37; 95% CI 1.74-3.23 rural) and Uganda (IRR 2.40, 95% CI 1.76-3.26), but not in The Gambia (IRR 1.48; 95% CI 0.56-3.87). Further research is needed to study multimorbidity epidemiology in sub-Saharan Africa with an emphasis on robust population-level data collection for a wide variety of long-term conditions and ensuring proportionate representation from men and women, and urban and rural areas.

Evaluating the hypertension care cascade in middle-aged and older adults in The Gambia: findings from a nationwide survey.

Background: Hypertension is a major public health problem in sub-Saharan Africa with poor treatment coverage and high case-fatality rates. This requires assessment of healthcare performance to identify areas where intervention is most needed. To identify areas where health resources should be most efficiently targeted, we assessed the hypertension care cascade i.e., loss and retention across the various stages of care, in Gambian adults aged 35 years and above. Methods: This study was embedded within the nationally representative 2019 Gambia National Eye Health Survey of adults ≥35 years. We constructed a hypertension care cascade with four categories: prevalence of hypertension (defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, and/or current use of medication prescribed for hypertension); those aware of their diagnosis; those treated; and those with a controlled blood pressure (defined as blood pressure <140/90 mmHg). Analyses were age- and sex-standardised to the population structure of The Gambia. Logistic regression was used to assess the socio-demographic factors associated with prevalence, awareness, treatment and control of hypertension. Findings: Of 9171 participants with data for blood pressure, the prevalence of hypertension was 47.0%. Among people with hypertension, the prevalence of awareness was 54.7%, the prevalence of hypertension treatment was 32.5%, and prevalence of control was 10.0% with little difference between urban and rural residence. The cascade of care performance was better in women. However, there was no difference in achieving blood pressure control between men and women who were receiving treatment. Female sex, older age and higher body mass index were associated with higher hypertension awareness whilst having an occupation compared to being unemployed was associated with higher odds of being treated. Patients in the underweight category had higher odds of achieving blood pressure control. Interpretation: There is a high prevalence of hypertension and low performance of the health care system that impact on the hypertension care cascade among middle-aged and older adults in The Gambia. Addressing the full cascade will be paramount especially in reducing the mounting prevalence and improving diagnosis of patients with hypertension, where the greatest dividends will be gained. Funding: The Queen Elizabeth Diamond Jubilee Trust, Wellcome Trust.

DNA methylation at the suppressor of cytokine signaling 3 (SOCS3) gene influences height in childhood.

Human height is strongly influenced by genetics but the contribution of modifiable epigenetic factors is under-explored, particularly in low and middle-income countries (LMIC). We investigate links between blood DNA methylation and child height in four LMIC cohorts (n = 1927) and identify a robust association at three CpGs in the suppressor of cytokine signaling 3 (SOCS3) gene which replicates in a high-income country cohort (n = 879). SOCS3 methylation (SOCS3m)-height associations are independent of genetic effects. Mendelian randomization analysis confirms a causal effect of SOCS3m on height. In longitudinal analysis, SOCS3m explains a maximum 9.5% of height variance in mid-childhood while the variance explained by height polygenic risk score increases from birth to 21 years. Children's SOCS3m is associated with prenatal maternal folate and socio-economic status. In-vitro characterization confirms a regulatory effect of SOCS3m on gene expression. Our findings suggest epigenetic modifications may play an important role in driving child height in LMIC.

The influence of early environment and micronutrient availability on developmental epigenetic programming: lessons from the placenta.

DNA methylation is the most commonly studied epigenetic mark in humans, as it is well recognised as a stable, heritable mark that can affect genome function and influence gene expression. Somatic DNA methylation patterns that can persist throughout life are established shortly after fertilisation when the majority of epigenetic marks, including DNA methylation, are erased from the pre-implantation embryo. Therefore, the period around conception is potentially critical for influencing DNA methylation, including methylation at imprinted alleles and metastable epialleles (MEs), loci where methylation varies between individuals but is correlated across tissues. Exposures before and during conception can affect pregnancy outcomes and health throughout life. Retrospective studies of the survivors of famines, such as those exposed to the Dutch Hunger Winter of 1944-45, have linked exposures around conception to later disease outcomes, some of which correlate with DNA methylation changes at certain genes. Animal models have shown more directly that DNA methylation can be affected by dietary supplements that act as cofactors in one-carbon metabolism, and in humans, methylation at birth has been associated with peri-conceptional micronutrient supplementation. However, directly showing a role of micronutrients in shaping the epigenome has proven difficult. Recently, the placenta, a tissue with a unique hypomethylated methylome, has been shown to possess great inter-individual variability, which we highlight as a promising target tissue for studying MEs and mixed environmental exposures. The placenta has a critical role shaping the health of the fetus. Placenta-associated pregnancy complications, such as preeclampsia and intrauterine growth restriction, are all associated with aberrant patterns of DNA methylation and expression which are only now being linked to disease risk later in life.

Early-set POMC methylation variability is accompanied by increased risk for obesity and is addressable by MC4R agonist treatment.

Increasing evidence points toward epigenetic variants as a risk factor for developing obesity. We analyzed DNA methylation of the POMC (pro-opiomelanocortin) gene, which is pivotal for satiety regulation. We identified sex-specific and nongenetically determined POMC hypermethylation associated with a 1.4-fold (confidence interval, 1.03 to 2.04) increased individual risk of developing obesity. To investigate the early embryonic establishment of POMC methylation states, we established a human embryonic stem cell (hESC) model. Here, hESCs (WA01) were transferred into a naïve state, which was associated with a reduction of DNA methylation. Naïve hESCs were differentiated via a formative state into POMC-expressing hypothalamic neurons, which was accompanied by re-establishment of DNA methylation patterning. We observed that reduced POMC gene expression was associated with increased POMC methylation in POMC-expressing neurons. On the basis of these findings, we treated POMC-hypermethylated obese individuals (n = 5) with an MC4R agonist and observed a body weight reduction of 4.66 ± 2.16% (means ± SD) over a mean treatment duration of 38.4 ± 26.0 weeks. In summary, we identified an epigenetic obesity risk variant at the POMC gene fulfilling the criteria for a metastable epiallele established in early embryonic development that may be addressable by MC4R agonist treatment to reduce body weight.

Socio-economic and food system drivers of nutrition and health transitions in The Gambia from 1990 to 2017.

In common with many nations undergoing a nutrition transition, micronutrient deficiencies, undernutrition and overnutrition coexist in The Gambia. Addressing these challenges simultaneously would require transformational changes in the country's food system. However, the evidence base that would enable informed decision-making in the Gambian food system has been scant, despite several sources of routinely-collected data being available. This descriptive study brings together data from four open-access global databases on food supply, political, economic, and demographic variables, and nutrition and health between 1990 and 2017 to study potential leverage points for improvement in the food system. It compares trends in food supply and nutritional outcomes in The Gambia against regional and global averages, and identifies potential drivers taken from a food systems framework. The data show that, over the past three decades, total energy supply has increased, and obesity is rising quickly, but iron deficiency persists in a proportion of the population. Overall diet composition is poor, with lower availability of fruit and vegetables and higher supply of sugar and oils compared to regional and global averages. Domestic production is low for most food groups and so a high dependence on imports from other countries bridges the gap in terms of energy supply. Measures of economic development, particularly GDP, were positively related with supply of cereals and animal source foods over time, but no such relationship was observed with fruit and vegetable supply. Food system policy to improve nutrition and health outcomes in The Gambia needs to focus on improving the diversity of food supply - especially fruit and vegetables - and maximizing national domestic production to reduce reliance on food imports. The use of open-source global datasets can be feasible in exploring food system characteristics and trends at the national level and could be applied in other contexts.