This abstract was presented as the Nutrition and Optimum Life Course Theme Highlight.

The n-3 polyunsaturated fatty acids (n-3 PUFA), eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), are known for their beneficial roles in regulating inflammation(1). The omega 3 index (O3I) refers to the percentage of EPA+DHA within the erythrocyte membrane with respect to total fatty acids and is a recognised biomarker for cardiovascular disease(2). An O3I >8% is proposed to confer the greatest level of cardioprotection(2). Fish is the richest dietary source of n-3 PUFAs and has been noted as one of the main predictors of a higher O3I(3). Current UK dietary guidelines recommend the consumption of two portions of fish per week; albeit the efficacy of these recommendations in raising the O3I is unknown(4). The aim of this study was to investigate the influence of consuming two portions of fish per week on the O3I amongst low fish consuming women of childbearing age.

Data were analysed from the iFish study(5), an 8-week randomised controlled trial where low fish consuming women, were randomly assigned to consume either no fish (n = 18) or 2 portions of tuna (n = 8) or sardines (n = 9) per week. Total n-3 PUFA concentrations of the fish provided in the intervention were 6.47g/100g for sardines and 4.57g/100g for tuna. Fasting blood samples were collected at baseline and post-intervention. The O3I was determined in red blood cells in the control and two portions of fish groups by OmegaQuant Europe. Analysis of covariance, adjusting for age, BMI, and baseline O3I, examined the effect of the fish intervention on the O3I. Chi-square test was used to compare the O3I between groups when categorised as at risk (<4%), intermediate risk (48%) and low risk (>8%).

Participants had a mean ± SD age of 25.5 ± 6.4 years. Baseline median (IQR) O3I of the cohort was 5.7 (5.2, 6.7) %. There was no significant difference in the O3I between treatment groups at baseline. Consumption of two portions of fish significantly increased the O3I when compared to the consumption of no fish [6.73 (5.41, 7.38) % vs 5.58 (5.12, 6.49) %, respectively, p = 0.034]. Those consuming two portions of sardines, an oily fish high in n-3 PUFAs, had a significantly greater O3I when compared to those consuming two portions of tuna [7.38 (6.83, 8.37) % vs 5.61 (5.29, 6.79) %, respectively, p<0.001]. Post-intervention, the proportion of participants in the low risk O3I category (>8%) was greater in the two portions of fish group when compared to the control group; albeit this did not reach statistical significance (p = 0.104).

In support of the current dietary guidelines, increasing fish consumption of low consumers to two portions of any fish per week will increase the O3I. Future research should determine the potential cardioprotective properties of a higher O3I as a result of consuming fish.

Dietary intake can influence immune function indirectly by affecting the gut microbiota composition and metabolism(1). Fish consumption has been shown to positively regulate the gut microbiota in humans(2,3);albeit in those studies fish was consumed in high amounts (500-750g/week) and immune function was not investigated. This study investigated the effect of consuming the UK dietary recommendation for fish(4) (2 portions [140-280g/week], one of which is oily) on the gut microbiota alpha diversity. Further, we examined if changes (pre- to post-intervention) in the gut microbiota composition were associated with changes in immune cytokine concentrations.

An 8-week randomised controlled trial in low fish consuming women of childbearing age (n = 41; median age 23y) investigated the effect of consuming 1 or 2 portions of fish (tuna or sardines)/week compared to not consuming fish. A blood sample was collected to measure inflammatory cytokines (tumour necrosis factor-a, interleukin [IL]-1b, IL-5, IL-6, IL-17A and IL-22) pre-and post-intervention. Faecal samples were collected at both timepoints and extracted DNA was used to determine gut microbiota compositional profiles using 16S metagenomic sequencing (Illumina, USA). Statistical analysis investigated significant differences in changes in gut microbiota alpha diversity and compositional relative abundances between fish intervention (N = 26) and control (N = 15), then secondary analysis stratified by portion size (1 vs 2 portions) and type of fish (tuna vs sardines). Differences in cytokines between fish intervention and control were assessed by Mann-Whitney U. Spearman rank coefficient assessed associations between the changes in gut microbiota relative abundances with cytokine changes in fish and control groups.

Fish consumption increased gut microbiota alpha diversity indices (Chao1 [7.37±41.23], Simpson [0.003±0.163], Shannon [0.07±0.33], phylogenetic diversity [0.35±2.59], observed species [9.00±40.06]), albeit this was not significant compared to the control group (p>0.05). Consumption of fish, specifically sardines, for 8 weeks significantly reduced Bacteroidetes (-4.77±4.88%) when compared to control (+4.15±7.58%) (p<0.01). No significant differences were observed between the change in relative abundances of gut microbiota at genus-level taxa or inflammatory cytokines between the fish intervention and control. In the fish intervention group, increases in IL-17A, IL-22 and IL-6 concentrations were positively correlated with changes in Alistipes, Rhodococcus, Haemophilus, Barnesiella and Akkermansia relative abundances (p<0.05).

Although not statistically significant, consistent findings suggest that fish intake, in line with dietary guidelines, may have favourable impact on gut microbiota. Sardines, oily fish rich in n-3 polyunsaturated fatty acids, may have health benefits in disease states where Bacteroidetes is elevated; nevertheless, further research is required in a larger cohort over a longer period.

Findings from animal models suggest early exposure to polyunsaturated fatty acids (PUFAs) during pregnancy may influence developmental plasticity including adiposity(1). Birth cohort studies examining associations between offspring weight and maternal n-3 PUFA status or maternal fish intakes, the richest dietary source of n-3 PUFAs have been few and have yielded inconsistent findings. Some have reported lower weight at birth and throughout childhood with increasing maternal fish intakes and n-3 PUFA status(2), whilst others have observed positive or null associations(3,4). These have focused on the first few years of life and have been conducted within low fish-consuming populations. Our study provides novel data by examining associations between maternal fish consumption and prenatal PUFA (n-3 & n-6) status and offspring weight at birth and throughout childhood (7 & 13 years) in a high fish-eating population.

Pregnant women were enrolled in the Seychelles Child Development Study Nutrition Cohort 2 between 2008-2011. Serum PUFAs were quantified in maternal blood collected at 28-weeks’ gestation and in cord blood collected at delivery using gas-chromatography tandem mass spectrometry. Maternal fish consumption was assessed at 28-weeks’ gestation using a Fish Use Questionnaire. Childbirth weight (kg) was measured at delivery and classified according to WHO growth standards(5) (n = 1185). Child height (m), weight (kg), waist and hip circumference (cm) were recorded at 7 (n = 1167) and 13 (n = 878) years. Statistical analysis was conducted using logistic and multiple linear regression adjusting for child sex, gestational age, maternal age, BMI, alcohol use, socioeconomic status, and parity. Models at 7 & 13 years were additionally adjusted for child height and fish intakes.

Women were consuming on average 8.49 ± 4.51 fish meals/week during pregnancy. No significant associations were found between maternal fish intakes and anthropometric outcomes at birth, 7 & 13 years. No significant associations were observed between maternal PUFAs and offspring weight at birth. At both 7 & 13 years, however, higher maternal total n-6 PUFAs were associated with increased child weight [7yr; β = 0.070, p = 0.003, 13yr; β = 0.097, p = 0.004], waist circumference [7yr; β = 0.086, p = 0.003, 13yr; β = 0.105, p = 0.004], and hip circumference [7yr; β = 0.062, p = 0.027, 13yr; β = 0.090, p = 0.013]. No significant associations were found between cord n-6 PUFAs and birth weight. In quartile analysis, cord docosahexaenoic acid (DHA; C22:6n-3) concentrations <0.071mg/ml were associated with a higher risk of large for gestational age (LGA; >90th percentile) when compared to cord DHA concentrations >0.129mg/ml [OR 4.17, p = 0.017]. There were no significant associations between cord PUFAs and anthropometric outcomes at 7 & 13 years.

These findings suggest lower cord DHA, an n-3 PUFA, may be associated with higher risk of LGA at birth whilst higher n-6 PUFAs during pregnancy may be associated with adiposity development throughout childhood. Future work is needed to determine the potential long-term metabolic consequences of such associations.

Maternal fish consumption exposes the fetus to beneficial nutrients and potentially adverse neurotoxicants. The current study investigated associations between maternal fish consumption and child neurodevelopmental outcomes. Maternal fish consumption was assessed in the Seychelles Child Development Study Nutrition Cohort 1 (n 229) using 4-day food diaries. Neurodevelopment was evaluated at 9 and 30 months, and 5 and 9 years with test batteries assessing twenty-six endpoints and covering multiple neurodevelopmental domains. Analyses used multiple linear regression with adjustment for covariates known to influence child neurodevelopment. This cohort consumed an average of 8 fish meals/week and the total fish intake during pregnancy was 106·8 (sd 61·9) g/d. Among the twenty-six endpoints evaluated in the primary analysis there was one beneficial association. Children whose mothers consumed larger quantities of fish performed marginally better on the Kaufman Brief Intelligence Test (a test of nonverbal intelligence) at age 5 years (β 0·003, 95 % CI (0, 0·005)). A secondary analysis dividing fish consumption into tertiles found no significant associations when comparing the highest and lowest consumption groups. In this cohort, where fish consumption is substantially higher than current global recommendations, maternal fish consumption during pregnancy was not beneficially or adversely associated with children’s neurodevelopmental outcomes.

Maternal thyroid hormones facilitate optimal foetal neurodevelopment; however, the exact role of the thyroid hormones on specific cognitive outcomes is unknown. The present study aimed to investigate associations between maternal thyroid function and neurodevelopmental outcomes in the Seychelles Child Development Study (SCDS) Nutrition 2 cohort (n 1328). Maternal free thyroid hormones (fT3, fT4 and fTSH) were assessed at 28 weeks’ gestation with a range of child cognitive outcomes analysed at 20 months. Dietary iodine intake was analysed for a subset of women through a Food Frequency Questionnaire. Linear regression analysis was used to test associations between serum concentrations of maternal thyroid hormones and child neurodevelopment outcomes. Thyroid hormones were analysed as continuous data and categorised as quintiles. 95% of mothers had optimal thyroid function based on fTSH concentrations. Overall, the present study shows that maternal thyroid function is not associated with neurodevelopmental outcomes in this high fish-eating population. However, a positive association, using quintiles for fT3, was reported for the Mental Developmental Index, between Q3 v. Q4 (β 0⋅073; P 0⋅043) and for Q3 v. Q5 (β value 0⋅086; P 0⋅018). To conclude, mothers in our cohort, who largely have optimal thyroid function and iodine intakes, appear able to regulate thyroid function throughout pregnancy to meet neurodevelopmental needs. However, it is possible that minor imbalances of fT3, as indicated from our secondary analysis, may impact offspring neurodevelopment. Further investigation of the relationship between maternal thyroid function and infant neurodevelopment is warranted, particularly in populations with different dietary patterns and thereby iodine intakes.

Optimal maternal long-chain PUFA (LCPUFA) status is essential for the developing fetus. The fatty acid desaturase (FADS) genes are involved in the endogenous synthesis of LCPUFA. The minor allele of various FADS SNP have been associated with increased maternal concentrations of the precursors linoleic acid (LA) and α-linolenic acid (ALA), and lower concentrations of arachidonic acid (AA) and DHA. There is limited research on the influence of FADS genotype on cord PUFA status. The current study investigated the influence of maternal and child genetic variation in FADS genotype on cord blood PUFA status in a high fish-eating cohort. Cord blood samples (n 1088) collected from the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2) were analysed for total serum PUFA. Of those with cord PUFA data available, maternal (n 1062) and child (n 916), FADS1 (rs174537 and rs174561), FADS2 (rs174575), and FADS1-FADS2 (rs3834458) were determined. Regression analysis determined that maternal minor allele homozygosity was associated with lower cord blood concentrations of DHA and the sum of EPA + DHA. Lower cord blood AA concentrations were observed in children who were minor allele homozygous for rs3834458 (β = 0·075; P = 0·037). Children who were minor allele carriers for rs174537, rs174561, rs174575 and rs3834458 had a lower cord blood AA:LA ratio (P < 0·05 for all). Both maternal and child FADS genotype were associated with cord LCPUFA concentrations, and therefore, the influence of FADS genotype was observed despite the high intake of preformed dietary LCPUFA from fish in this population.

OBJECTIVES/GOALS: The University of Rochester CTSI Research Education Hub is designed to: 1) connect the local research community with essential internal and external educational resources; 2) create a community of inquiry and collaboration across the translational science workforce pipeline within the university. METHODS/STUDY POPULATION: The Research Education Hub (RE-Hub) utilizes the university’s widely used Learning Management System (LMS), Blackboard, and accessible to anyone at the university with a BlackBoard account. The RE-Hub greets users with an overview, an introduction of key local faculty experts in relevant research methodologies, and links to institutional research programs and helpdesks. Users are provided with curated educational resources organized by topic areas including, but not limited to, research methodology, statistical analysis, and grantsmanship. Discussion boards were created for users to ask general research questions and to connect with others in the translational research community. RESULTS/ANTICIPATED RESULTS: The RE-Hub was designed in Fall 2019 with the purpose of increasing utilization of university resources, including workshops, seminars, methods forums and consultation resources to improve translational science at the university. The RE-Hub was designed to be flexible and responsive to the changing needs of the local research community. User feedback will be used to identify improvements in the organization and content of the RE-Hub. Future improvements will include additional topic areas that span translational competencies, additional materials added to existing topic areas, and facilitation of better collaboration and integration of career development programs and grantsmanship resources. DISCUSSION/SIGNIFICANCE OF IMPACT: The Research Education Hub provides the University of Rochester translational science research community with a space to explore educational resources, to interact with colleagues and ask research related questions, and to help develop and/or improve other educational programs at the university.

OBJECTIVES/GOALS: Physician-scientists play a vital role in biomedical research but this chosen career path has many challenges, such as long training periods and funding. The University of Rochester (UR) CTSI pipeline programs address this by enabling medical trainees to partake in enriched research experiences. METHODS/STUDY POPULATION: The UR CTSI TL1 is a training grant from the National Center for Advancing Translational Science (NCATS), which funds predoctoral trainees. The TL1-funded physician-scientist pipeline includes the Academic Research Track (ART) year-out program and the Medical Science Training Program (MSTP). We describe the characteristics and training outcomes of TL1-funded trainees. We also obtained testimonials of current and former trainees regarding their career component decision-making, and their perception of programs, in order to identify how best to address the challenges of the physician-scientist workforce, and to facilitate the transition between the clinic and bench. RESULTS/ANTICIPATED RESULTS: From 2006-2019, the UR CTSI has had 56 ART trainees and 17 MSTP trainees complete training; six trainees have transitioned into the MSTP after completing the ART program. As of 2019, 63 of 67 graduated trainees (94%) have continued their engagement in CTS after graduation. Importantly, our programs have facilitated the careers of 31 women (39.7%) and 12 under-represented minorities (15.4%). We will present a breadth of qualitative data to inform which parts of the TL1-related programs have been successful, and which parts could use programmatic improvement to aid the transition into the physician-scientist workforce. DISCUSSION/SIGNIFICANCE OF IMPACT: Physician-scientist training barriers in the US have resulted in a shortage of these professionals in the clinical and translation workforce. Our data show the UR CTSI has been successful in addressing several of these challenges via the TL1-funded ART, MSTP, and ART/MSTP dual program pipeline.

The association of MeHg exposure through fish consumption on human autoimmunity remains unclear. Fish also contain n-3 long chain polyunsaturated fatty acids (LCPUFA) that are known to regulate inflammation and mitigate autoimmune disease symptoms. We studied the association of low-level exposure to methylmercury (MeHg) through fish consumption in the SCDS. We examined this association at age 19 years in the SCDS Main Cohort (n = 497). We measured MeHg exposure at 3 time points [prenatal, weighted average (6 months to 19 years) and concurrent (19 years) and LCPUFA status and a panel of 13 autoimmune markers at age 19 years. The autoimmune markers included antinuclear antibodies (ANA), anti-dsDNA and anti-RNP, and total (non-specific) immunoglobulins (Ig) IgG, IgA, and IgM. A combined ANA variable was also calculated based on being within or above reference range for any of the ANA markers; 56% of the subjects met this criterion. Multivariable regression models adjusted for prenatal MeHg, sex and waist circumference, with and without adjustment for LCPUFA, were fit for the three MeHg exposure metrics and each immune marker. Mean (SD) prenatal, weighted average and concurrent MeHg was 6.84 (4.55), 7.46 (2.82), and 10.23 (6.02) ppm, respectively. Combined ANA was positively associated with concurrent MeHg following adjustment for the n6:n3 LCPUFA ratio (β = 0.036, 95%; CI: 0.001, 0.073). Prenatal and average MeHg exposures were not significantly associated with any individual ANA. IgM was negatively associated with concurrent (β = -0.016, 95%CI: -0.016, -0.002), and average (β = -0.042, 95%CI: -0.042, -0.009) MeHg exposure in the models adjusted for n-3, n-6 LCPUFA and when separately adjusted for the n6:n3 LCPUFA ratio. Total (19-year) n-3 PUFA status was negatively associated with anti-RNP (β = -20.355, 95%CI: -36.89, -4.34) and IgG (β = -1.384, 95%CI: -2.682, -0.087). Total n-3 LCPUFA was associated with lower markers of autoimmunity. MeHg exposure at 19 years was associated with higher ANA and lower IgM but only following adjustment for LCPUFA. The clinical significance of these findings is unclear and further research is warranted to determine if these associations precede autoimmune disease development.

Optimal maternal polyunsaturated fatty acid (PUFA) status is essential for foetal development. The desaturase enzymes, encoded by the fatty acid desaturase (FADS) genes, are involved in the endogenous synthesis of long chain (LC)PUFA and influence maternal LCPUFA concentrations. The minor allele of various FADS SNPs has been associated with increased maternal concentrations of the precursors linoleic acid (LA) and α-linolenic acid (ALA), and lower concentrations of the LCPUFA arachidonic acid (AA) and docosahexaenoic acid (DHA); however, there is limited research to date on the influence of FADS genotype on cord PUFA status. The aim of the current study was to investigate the influence of maternal and child genetic variation on cord blood PUFA status in a high fish-eating cohort.

Cord blood samples collected from mother-child pairs (n = 1088) taking part in the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2) were analysed for total serum PUFA. Maternal (n = 1088) and child genotype (n = 592) were determined for the FADS SNPs rs174537, rs174561, rs174575, and rs3834458. Regression analysis determined associations between maternal and child FADS genotype and cord PUFA status. In all regression models, the major allele homozygote genotype for each SNP was used as the reference group.

Directions of significant associations were as predicted. In mothers, the minor allele homozygote genotype for SNPs rs174537, rs174561 and rs3834458 was associated with lower cord DHA and lower total n-3 PUFA when compared to the major allele homozygous genotype (p < 0.05 for all). The heterozygous genotype was associated with increased concentrations of LA compared to the reference genotype for rs174561 (p = 0.021) and rs383448 (p = 0.023). In children, the heterozygous genotype was associated with lower AA concentrations and lower cord n-6:n-3 ratio for all SNPs (p < 0.05 for all) compared to those with the major allele homozygous genotype. A lower cord AA:LA ratio was also observed for children heterozygous for rs174547, rs174561 and rs174575 (p < 0.05 for all). Contrary to expected, there were no associations between cord PUFA concentrations and child minor allele homozygous genotype.

The current study indicates that variation in maternal and child FADS genotype influences cord PUFA concentrations, despite the high intake of preformed dietary LCPUFA from fish in this population. The sample size for minor allele homozygous children was likely too small to observe any statistically significant associations in the current analysis. Further research is needed to determine whether increased dietary intake can compensate for lower PUFA status as a result of FADS genotype.

Choline is an essential nutrient that is found in many food sources and plays a critical role in the development of the central nervous system. Animal studies have shown that choline status pre- and postnatally can have long-lasting effects on attention and memory; however, effects in human subjects have not been well studied. The aim of the present study was to examine the association between plasma concentrations of free choline and its related metabolites in children and their neurodevelopment in the Seychelles Child Development Nutrition Study, an ongoing longitudinal study assessing the development of children born to mothers with high fish consumption during pregnancy. Plasma concentrations of free choline, betaine, dimethylglycine (DMG), methionine and homocysteine and specific measures of neurodevelopment were measured in 210 children aged 5 years. The children's plasma free choline concentration (9·17 (sd 2·09) μmol/l) was moderately, but significantly, correlated with betaine (r 0·24; P= 0·0006), DMG (r 0·15; P= 0·03), methionine (r 0·24; P= 0·0005) and homocysteine (r 0·19; P= 0·006) concentrations. Adjusted multiple linear regression revealed that betaine concentrations were positively associated with Preschool Language Scale – total language scores (β = 0·066; P= 0·04), but no other associations were evident. We found no indication that free choline concentration or its metabolites, within the normal physiological range, are associated with neurodevelopmental outcomes in children at 5 years of age. As there is considerable animal evidence suggesting that choline status during development is associated with cognitive outcome, the issue deserves further study in other cohorts.

Background: Anxiety and depression are common in older adult public housing residents and frequently co-occur. To understand anxiety and depression more fully in this socioeconomically disadvantaged population, this study relies on the Social Antecedent Model of Psychopathology to characterize anxiety and depression symptoms concurrently.

Methods: 190 public housing residents aged 60 years and older in Rochester, New York, participated in a research interview during which they reported on variables across the six stages of the Social Antecedent Model. GAD-7 and PHQ-9 assessed anxiety and depression symptoms, respectively.

Results: In these older adult residents, anxiety and depression symptom severity scores were correlated (r = 0.61; p < 0.001). Correlates of anxiety and depression symptom severity were similar for both outcomes and spanned the six stages of the Social Antecedent Model. Multivariate linear regression models identified age, medical comorbidity, mobility, social support, maladaptive coping, and recent life events severity as statistically significant correlates. The regression models accounted for 43% of anxiety and 48% of depression symptom variability.

Conclusions: In public housing residents, late-life anxiety and depression symptoms were moderately correlated. Anxiety symptom severity correlates were largely consistent with those found for depression symptom severity. The broad distribution of correlates across demographic, social, medical, and behavioral domains suggests that the context of late-life anxiety and depression symptomatology in public housing is complex and that multidisciplinary collaborative care approaches may be warranted in future interventions.