Assessing infant cognition in field settings using eye-tracking: A pilot cohort trial in Sierra Leone

OBJECTIVES: To investigate the feasibility of eye-tracking-based testing of the speed of visual orienting in malnourished young children at rural clinics in Sierra Leone. DESIGN: Prospective dual cohort study nested in a cluster-randomised trial. SETTING: 8 sites participating in a cluster-randomised trial of supplementary feeding for moderate acute malnutrition (MAM). PARTICIPANTS: For the MAM cohort, all infants aged 7-11 months at the eight sites were enrolled, 138 altogether. For controls, a convenience sample of all non-malnourished infants aged 7-11 months at the same sites were eligible, 60 altogether. A sample of 30 adults at the sites also underwent eye-tracking tests as a further control. INTERVENTIONS: Infants with MAM were provided with supplementary feeding. OUTCOME MEASURES: The primary outcomes were feasibility and reliability of eye-tracking-based testing of saccadic reaction time (SRT). Feasibility was assessed by the percent of successful tests in the infants. Reliability was measured with intraclass correlation coefficients (ICCs). Secondary outcomes were mean SRT based on nutritional state as well as and changes in mean SRT after supplementary feeding of MAM children. RESULTS: Infants exhibited consistent orienting to targets on a computer screen (\u3e95% of valid trials). Mean SRTs had moderate stability within visits (ICCs 0.60-0.69) and across the 4-week test-retest interval (0.53) in infants; the adult control group had greater SRT stability (within visit ICC=0.92). MAM infants had a trend toward higher adjusted SRT at baseline (difference=12.4 ms, 95% CI -2 to 26.9, p=0.09) and improvement in SRT 4 weeks thereafter (difference=-14 ms, 95% CI -26.2 to -1.7, p=0.025) compared with age-matched controls. CONCLUSIONS: The results demonstrate the feasibility of eye-tracking-based testing in a resource-poor field setting and suggest eye-tracking measures have utility in the detection of group level effects of supplementary feeding

Assessing infant cognition in field settings using eye-tracking: a pilot cohort trial in Sierra Leone

Objectives To investigate the feasibility of eye-tracking-based testing of the speed of visual orienting in malnourished young children at rural clinics in Sierra Leone. Design Prospective dual cohort study nested in a cluster-randomised trial. Setting 8 sites participating in a cluster-randomised trial of supplementary feeding for moderate acute malnutrition (MAM). Participants For the MAM cohort, all infants aged 7-11 months at the eight sites were enrolled, 138 altogether. For controls, a convenience sample of all non-malnourished infants aged 7-11 months at the same sites were eligible, 60 altogether. A sample of 30 adults at the sites also underwent eye-tracking tests as a further control. Interventions Infants with MAM were provided with supplementary feeding. Outcome measures The primary outcomes were feasibility and reliability of eye-tracking-based testing of saccadic reaction time (SRT). Feasibility was assessed by the percent of successful tests in the infants. Reliability was measured with intraclass correlation coefficients (ICCs). Secondary outcomes were mean SRT based on nutritional state as well as and changes in mean SRT after supplementary feeding of MAM children. Results Infants exhibited consistent orienting to targets on a computer screen (>95% of valid trials). Mean SRTs had moderate stability within visits (ICCs 0.60-0.69) and across the 4-week test-retest interval (0.53) in infants; the adult control group had greater SRT stability (within visit ICC=0.92). MAM infants had a trend toward higher adjusted SRT at baseline (difference=12.4 ms, 95% CI -2 to 26.9, p=0.09) and improvement in SRT 4 weeks thereafter (difference=-14 ms, 95% CI -26.2 to -1.7, p=0.025) compared with age-matched controls. Conclusions The results demonstrate the feasibility of eye-tracking-based testing in a resource-poor field setting and suggest eye-tracking measures have utility in the detection of group level effects of supplementary feeding.</p

The One Nutrition in Complex Environments (ONCE) study protocol: a cluster-randomized multi-level multi-sectoral intervention to improve nutrition in Uganda

Objective: To implement and measure the effects of a multi-level multi-sectoral social behavior change (SBC) intervention in Agago District of Northern Uganda and to determine the potential for scale-up. Intervention: Compare the Nutrition Impact and Positive Practice (NIPP) approach to a NIPP+ approach. The NIPP approach involves nutrition education and SBC, whereas the NIPP+ adds agricultural inputs, training, and tools to support improved farm and water quality practices. The intervention effect will be measured through lower levels of aflatoxin in grain, lower water contamination, and improved knowledge on nutrition and health. Design: This is a three-arm cluster-randomized controlled superiority trial (cRCT). The study arms include the following: group 1: NIPP; group 2: NIPP+, and group 3: control. Groups 1 and 2 will receive a 12-week intervention (NIPP or NIPP+) with active monitoring and longitudinal follow-up at 2, 6, and 12 months post-intervention. Additionally, an in-depth process and performance evaluation of each intervention arm will be undertaken using quantitative and qualitative methods. A total of 60 clusters from 5 subcounties of the Agago district will be randomly selected, and 15 households per cluster will be recruited using specific inclusion/exclusion criteria for a total of 900 households (300/arm). Respondents for the qualitative portion will be purposely selected. Analysis: We will collect data from all participants at 3 time points: baseline, endline, and 12 months post-intervention. The analysis will utilize intent-to-treat (ITT) using the initial randomization of the treatment arms to determine the overall impact of having the NIPP vs. NIPP+ vs. control. Mixed effects models will be used to determine the role of time-variant and invariant individual household, and community characteristics, as well as measures of exposure and integration on key outcome indicators. A difference-in-difference analysis (baseline/endline, baseline/12 months post-intervention, endline/12 months post-intervention) will also be used to triangulate findings

Host fecal mRNAs predicted environmental enteric dysfunction among children with moderate acute malnutrition in Sierra Leone

Examining the role of environmental enteric dysfunction (EED) in child growth requires noninvasive, field-appropriate biomarkers. Alternatives to the traditionally used lactulose:mannitol (L:M) test have been explored, but few studies have compared the L:M test to host fecal mRNA transcripts. The objectives of this study were to examine whether 1) host fecal mRNA transcripts could predict presence and severity of EED, measured using the L:M test, and 2) EED modifies the effect of specialized nutritious foods (SNFs) on recovery from moderate acute malnutrition (MAM). This substudy was nested within a cluster randomized trial comparing four SNFs in the treatment of MAM among children 6 to 59 months in Sierra Leone. EED was assessed at enrollment using the L:M test and 15 host fecal mRNA transcripts on 522 children. Recovery from MAM was defined as achieving mid-upper arm circumference ≥ 12.5 cm within 12 weeks of supplementation. Random forest classification models were used to examine prediction of presence and severity of EED by host fecal mRNA transcripts. Logistic regression was used to test for effect modification by L:M test variables including % lactulose excreted (%L). Eight host fecal mRNA transcripts (AQP9, REG3A, IFI30, DECR1, BIRC3, SELL, PIK3AP1, DEFA6) identified EED (%L ≥ 0.2) and severe EED (%L ≥ 0.45) with high sensitivity and specificity. The L:M test variables did not modify the effect of SNFs on recovery from MAM. In this study, we found host fecal mRNA transcripts that could be biomarkers of EED but did not find EED to modify the effect of SNFs on MAM treatment

Genomic, transcriptomic, and metabolomic profiles of hiPSC-derived dopamine neurons from clinically discordant brothers with identical PRKN deletions

We previously reported on two brothers who carry identical compound heterozygous PRKN mutations yet present with significantly different Parkinson’s Disease (PD) clinical phenotypes. Juvenile cases demonstrate that PD is not necessarily an aging-associated disease. Indeed, evidence for a developmental component to PD pathogenesis is accumulating. Thus, we hypothesized that the presence of additional genetic modifiers, including genetic loci relevant to mesencephalic dopamine neuron development, could potentially contribute to the different clinical manifestations of the two brothers. We differentiated human-induced pluripotent stem cells (hiPSCs) derived from the two brothers into mesencephalic neural precursor cells and early postmitotic dopaminergic neurons and performed wholeexome sequencing and transcriptomic and metabolomic analyses. No significant differences in the expression of canonical dopamine neuron differentiation markers were observed. Yet our transcriptomic analysis revealed a significant downregulation of the expression of three neurodevelopmentally relevant cell adhesion molecules, CNTN6, CNTN4 and CHL1, in the cultures of the more severely affected brother. In addition, several HLA genes, known to play a role in neurodevelopment, were differentially regulated. The expression of EN2, a transcription factor crucial for mesencephalic dopamine neuron development, was also differentially regulated. We further identified differences in cellular processes relevant to dopamine metabolism. Lastly, wholeexome sequencing, transcriptomics and metabolomics data all revealed differences in glutathione (GSH) homeostasis, the dysregulation of which has been previously associated with PD. In summary, we identified genetic differences which could potentially, at least partially, contribute to the discordant clinical PD presentation of the two brothers