Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.

Iodine, through the thyroid hormones, is required for the development of the auditory cortex and cochlea (the sensory organ for hearing). Deafness is a well-documented feature of endemic cretinism resulting from severe iodine deficiency. However, the range of effects of suboptimal iodine intake during auditory development on the hearing ability of children is less clear. We therefore aimed to systematically review the evidence for the association between iodine exposure (i.e., intake/status/supplementation) during development (i.e., pregnancy and/or childhood) and hearing outcomes in children. We searched PubMed and Embase and identified 330 studies, of which 13 were included in this review. Only three of the 13 studies were of low risk of bias or of good quality, this therefore limited our ability to draw firm conclusions. Nine of the studies (69%) were in children (one RCT, two non-RCT interventions and six cross-sectional studies) and four (31%) were in pregnant women (one RCT, one cohort study and two case reports). The RCT of iodine supplementation in mildly iodine-deficient pregnant women found no effect on offspring hearing thresholds. However, hearing was a secondary outcome of the trial and not all women were from an iodine-deficient area. Iodine supplementation of severely iodine-deficient children (in both non-RCT interventions) resulted in improved hearing thresholds. Five of six cross-sectional studies (83%) found that higher iodine status in children was associated with better hearing. The current evidence base for the association between iodine status and hearing outcomes is limited and further good-quality research on this topic is needed.

Advances in technology enabled the development of a web-based, pictorial FFQ to collect parent-report dietary intakes of 7-year-old children in the Growing Up in Singapore Towards healthy Outcomes study. This study aimed to compare intakes estimated from a paper-FFQ and a web-FFQ and examine the relative validity of both FFQ against 3-d diet records (3DDR). Ninety-two mothers reported food intakes of their 7-year-old child on a paper-FFQ, a web-FFQ and a 3DDR. A usability questionnaire collected participants’ feedback on the web-FFQ. Correlations and agreement in energy, nutrients and food groups intakes between the dietary assessments were evaluated using Pearson’s correlation, Lin’s concordance, Bland–Altman plots, Cohen’s κ and tertile classification. The paper- and web-FFQ had good correlations (≥ 0·50) and acceptable-good agreement (Lin’s concordance ≥ 0·30; Cohen’s κ ≥ 0·41; ≥ 50 % correct and ≤ 10 % misclassification into same or extreme tertiles). Compared with 3DDR, both FFQ showed poor agreement (< 0·30) in assessing absolute intakes except micronutrients (web-FFQ had acceptable-good agreement), but showed acceptable-good ability to classify children into tertiles (κ ≥ 0·21; ≥ 40 % and ≤ 15 % correct or misclassification). Bland–Altman plots suggest good agreement between web-FFQ and 3DDR in assessing micronutrients and several food groups. The web-FFQ was well-received, and majority (81 %) preferred the web-FFQ over the paper-FFQ. The newly developed web-FFQ produced intake estimates comparable to the paper-FFQ, has acceptable-good agreement with 3DDR in assessing absolute micronutrients intakes and has acceptable-good ability to classify children according to categories of intakes. The positive acceptance of the web-FFQ makes it a feasible tool for future dietary data collection.

Dietary patterns high in fat contribute to the onset of cardiometabolic disease through the accrual of adipose tissue (AT). Lycopene, a carotenoid shown to exert multiple health benefits, may disrupt these metabolic perturbations. The purpose of the present study was to evaluate AT development and obesity-associated metabolic outcomes in the neonate and weanling offspring of Sprague-Dawley mothers fed a high-fat diet (HFD = 50 % fat) with and without lycopene supplementation. Sprague-Dawley rats consumed either a normal fat diet (NFD; 25 % fat) or HFD throughout gestation. Upon delivery, half of HFD mothers were transitioned to an HFD supplemented with 1 % lycopene (HFDL). At postnatal day 14 (P14), P25, and P35, pups were euthanised, body weight was recorded, and visceral white AT (WAT) and brown AT (BAT) mass were determined. Serum redox status, adipokines, glucose and inflammatory biomarkers were evaluated, as well as BAT mRNA expression of uncoupling protein 1 (UCP1). The HFD was effective in inducing weight gain as evident by significantly greater BW and WAT in the HFD group compared to the NFD group across all time points. Compared to HFD, the HFDL group exhibited significantly greater BAT with concomitant reductions in WAT mass, serum lipid peroxides and serum glucose. No significant differences were observed in serum adipokines, inflammatory markers or UCP1 expression despite the aforementioned alterations in AT development. Results suggest that dietary lycopene supplementation may influence metabolic outcomes during the weaning and post-weaning periods. Additional research is warranted to elucidate molecular mechanisms by which lycopene influences AT biology.

Background: Medulloblastoma (MB) is the most common solid malignant pediatric brain neoplasm. Group 3 (G3) MB, particularly MYC amplified G3 MB, is the most aggressive subgroup with the highest frequency of children presenting with metastatic disease, and is associated with a poor prognosis. To further our understanding of the role of MSI1 in MYC amplified G3 MB, we performed an unbiased integrative analysis of eCLIP binding sites, with changes observed at the transcriptome, the translatome, and the proteome after shMSI1 inhibition. Methods: Primary human pediatric MBs, SU_MB002 and HD-MB03 were kind gifts from Dr. Yoon-Jae Cho (Harvard, MS) and Dr. Till Milde (Heidelberg) and cultured for in vitro and in vivo experiments. eCLIP, RNA-seq, Polysome-seq, and TMT-MS were completed as previously described. Results:MSI1 is overexpressed in G3 MB. shRNA Msi1 interference resulted in a reduction in tumour burden conferring a survival advantage to mice injected with shMSI1 G3MB cells. Robust ranked multiomic analysis (RRA) identified an unconventional gene set directly perturbed by MSI1 in G3 MB. Conclusions: Our robust unbiased integrative analysis revealed a distinct role for MSI1 in the maintenance of the stem cell state in G3 MB through post-transcriptional modification of multiple pathways including identification of unconventional targets such as HIPK1.