An epigenome-wide association study of child appetitive traits and DNA methylation

The etiology of childhood appetitive traits is poorly understood. Early-life epigenetic processes may be involved in the developmental programming of appetite regulation in childhood. One such process is DNA methylation (DNAm), whereby a methyl group is added to a specific part of DNA, where a cytosine base is next to a guanine base, a CpG site. We meta-analyzed epigenome-wide association studies (EWASs) of cord blood DNAm and early-childhood appetitive traits. Data were from two independent cohorts: the Generation R Study (n = 1,086, Rotterdam, the Netherlands) and the Healthy Start study (n = 236, Colorado, USA). DNAm at autosomal methylation sites in cord blood was measured using the Illumina Infinium HumanMethylation450 BeadChip. Parents reported on their child's food responsiveness, emotional undereating, satiety responsiveness and food fussiness using the Children's Eating Behaviour Questionnaire at age 4–5 years. Multiple regression models were used to examine the association of DNAm (predictor) at the individual site- and regional-level (using DMRff) with each appetitive trait (outcome), adjusting for covariates. Bonferroni-correction was applied to adjust for multiple testing. There were no associations of DNAm and any appetitive trait when examining individual CpG-sites. However, when examining multiple CpGs jointly in so-called differentially methylated regions, we identified 45 associations of DNAm with food responsiveness, 7 associations of DNAm with emotional undereating, 13 associations of DNAm with satiety responsiveness, and 9 associations of DNAm with food fussiness. This study shows that DNAm in the newborn may partially explain variation in appetitive traits expressed in early childhood and provides preliminary support for early programming of child appetitive traits through DNAm. Investigating differential DNAm associated with appetitive traits could be an important first step in identifying biological pathways underlying the development of these behaviors.</p

Perceptions of COVID-19 Vaccines: Lessons from Selected Populations Who Experience Discrimination in the Australian Healthcare System

COVID-19 vaccination is particularly challenging among populations who have experienced discrimination in healthcare settings. This paper presents qualitative findings from in-depth interviews about COVID-19 vaccination conducted in Australia between October 2020 and November 2021. Data from four different studies are presented; each population has unique experiences of discrimination within the healthcare system: Aboriginal people; people who inject drugs (PWID); people living with HIV (PLHIV); and gay and bisexual men (GBM). Analyses were guided by the behavioural and social determinants model that forms the basis of the World Health Organization’s “data for action: achieving high uptake of COVID-19 vaccines” interim guidance. All populations viewed vaccination as necessary for community protection, although narratives of community care were most common among Aboriginal people. Concerns about vaccine safety were expressed by all participant groups, although participants living with HIV and GBM were more trusting of vaccines possibly because of their ongoing and usually positive past experiences with biomedical technologies for HIV management and sexual health. Aboriginal participants reported distrust of mainstream government and participants who inject drugs expressed a more generalised suspicion about COVID-19 and its origins. Practical problems related to transport, booking appointments for vaccination and so forth, were more common among participants living with HIV and GBM, possibly because these specific interviews were conducted throughout 2021 when vaccines were more available, whereas data for the other populations were collected before the vaccine rollout. Findings show that vaccine willingness is shaped by past experiences of discrimination in healthcare setting, but different histories of discrimination can differently impact vaccine willingness. Promotional messaging and delivery must take account of these important differences so to not treat these populations homogenously

Center on Disability Studies eNewsletter, September 2022

Welcome to the September 2022 issue of the CDS eNewsletter. Special highlights in this issue include: Featured Artist Lynnell Mateaki RDS Seeks Manuscript Review Board Members Exhibitor Release #PacRim2023 Introducing Deaf in Government Partnership #PacRim2023 Call for Presentation Proposals #PacRim2023 Legislative Forum Dates | Hawaiʻi DD Council Hawaiʻi's Path to Employment First Seminar Recording Now Available 2022-2023 CDS Community Advisory Council Introduction Website Launch Project Hoʻokuʻi V: Kūlia i ka Nuʻu Fall Announcements with Project Hōkūlani eNewsletterSpecial eNewsletter highlights include: Featured Artist Lynnell Mateaki; RDS Seeks Disability Studies Call for Reviewers; Pac Rim Exhibitor Invitation; Pac Rim Call for Proposals; Hawaiʻi State Council on Developmental Disabilities Legislative Forums; Presentation Hawaiʻi's Path to Employment First with Patrick Gartside available; Introducing 2022-2023 Community Advisory Council; Project Hoʻokuʻi V: Kūlia i ka Nuʻu Website Launch; and Project Hōkūlani 2022 Summer eNewsletter Release, Hōkūlani Insider

Validity of new child-specific thoracic gas volume prediction equations for air-displacement plethysmography

BACKGROUND: To determine the validity of the recently developed child-specific thoracic gas volume (TGV) prediction equations for use in air-displacement plethysmography (ADP) in diverse pediatric populations. METHODS: Three distinct populations were studied: European American and African American children living in Birmingham, Alabama and European children living in Lisbon, Portugal. Each child completed a standard ADP testing protocol, including a measured TGV according to the manufactures software criteria. Measured TGV was compared to the predicted TGV from current adult-based ADP proprietary equations and to the recently developed child-specific TGV equations of Fields et al. Similarly, percent body fat, derived using the TGV prediction equations, was compared to percent body fat derived using measured TGV. RESULTS: Predicted TGV from adult-based equations was significantly different from measured TGV in girls from each of the three ethnic groups (P < 0.05), however child-specific TGV estimates did not significantly differ from measured TGV in any of the ethnic or gender groups. Percent body fat estimates using adult-derived and child-specific TGV estimates did not differ significantly from percent body fat measures using measured TGV in any of the groups. CONCLUSION: The child-specific TGV equations developed by Fields et al. provided a modest improvement over the adult-based TGV equations in an ethnically diverse group of children

Center on Disability Studies eNewsletter, June 2023

Welcome to our summer newsletter. In this issue we highlight many events and happenings sponsored by CDS during June and July that you don’t want to miss out on. Disability Pride Month is also celebrated each year in July. Disability Pride initially started as a day of celebration in 1990, the year that the Americans with Disabilities Act (ADA) was signed into law. It is also an opportunity to raise awareness about improving access and inclusion. The first official Disability Pride celebration occurred in 2015 to commemorate the ADA’s 25th anniversary and the Disability Pride Flag was originally designed in 2019 by Ann Magill, who with feedback within the disabled community, refined its visual elements in 2021 to be more accessible. You can read more about how the disability pride flag helps increase the community’s visibility at https://go.hawaii.edu/qEX

Precision medicine in cats:novel niemann-pick type C1 diagnosed by whole-genome sequencing

State-of-the-art health care includes genome sequencing of the patient to identify genetic variants that contribute to either the cause of their malady or variants that can be targeted to improve treatment. The goal was to introduce state-of-the-art health care to cats using genomics and a precision medicine approach. To test the feasibility of a precision medicine approach in domestic cats, a single cat that presented to the University of Missouri, Veterinary Health Center with an undiagnosed neurologic disease was whole-genome sequenced. The DNA variants from the cat were compared to the DNA variant database produced by the 99 Lives Cat Genome Sequencing Consortium. Approximately 25× genomic coverage was produced for the cat. A predicted p.H441P missense mutation was identified in NPC1, the gene causing Niemann-Pick type C1 on cat chromosome D3.47456793 caused by an adenine-to-cytosine transversion, c.1322A>C. The cat was homozygous for the variant. The variant was not identified in any other 73 domestic and 9 wild felids in the sequence database or 190 additionally genotyped cats of various breeds. The successful effort suggested precision medicine is feasible for cats and other undiagnosed cats may benefit from a genomic analysis approach. The 99 Lives DNA variant database was sufficient but would benefit from additional cat sequences. Other cats with the mutation may be identified and could be introduced as a new biomedical model for NPC1. A genetic test could eliminate the disease variant from the population

Role of Soluble Epoxide Hydrolase in Postischemic Recovery of Heart Contractile Function

Cytochrome P450 epoxygenases metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs) which are converted to dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (Ephx2, sEH). To examine the functional role of sEH in the heart, mice with targeted disruption of the Ephx2 gene were studied. Hearts from sEH null mice have undetectable levels of sEH mRNA and protein and cannot convert EETs to DHETs. sEH null mice have normal heart anatomy and basal contractile function, but have higher fatty acid epoxide:diol ratios in plasma and cardiomyocyte cell culture media compared with wild type (WT). sEH null hearts have improved recovery of left ventricular developed pressure (LVDP) and less infarction compared with WT hearts after 20 minutes ischemia. Perfusion with the putative EET receptor antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (10 to 100 nmol/L) before ischemia abolishes this cardioprotective phenotype. Inhibitor studies demonstrate that perfusion with phosphatidylinositol-3 kinase (PI3K) inhibitors wortmannin (200 nmol/L) or LY294002 (5 μmol/L), the ATP-sensitive K+ channel (KATP) inhibitor glibenclamide (1 μmol/L), the mitochondrial KATP (mitoKATP) inhibitor 5-hydroxydecanoate (100 to 200 μmol/L), or the Ca2+-sensitive K+ channel (KCa) inhibitor paxilline (10 μmol/L) abolishes the cardioprotection in sEH null hearts. Consistent with increased activation of the PI3K cascade, sEH null mice exhibit increased cardiac expression of glycogen synthase kinase-3β (GSK-3β) phospho-protein after ischemia. Together, these data suggest that targeted disruption of sEH increases the availability of cardioprotective EETs that work by activating PI3K signaling pathways and K+ channels

Early-onset progressive retinal atrophy associated with an IQCB1 variant in African black-footed cats (Felis nigripes)

African black-footed cats (Felis nigripes) are endangered wild felids. One male and full-sibling female African black-footed cat developed vision deficits and mydriasis as early as 3 months of age. The diagnosis of early-onset progressive retinal atrophy (PRA) was supported by reduced direct and consensual pupillary light reflexes, phenotypic presence of retinal degeneration, and a non-recordable electroretinogram with negligible amplitudes in both eyes. Whole genome sequencing, conducted on two unaffected parents and one affected offspring was compared to a variant database from 51 domestic cats and a Pallas cat, revealed 50 candidate variants that segregated concordantly with the PRA phenotype. Testing in additional affected cats confirmed that cats homozygous for a 2 base pair (bp) deletion within IQ calmodulin-binding motif-containing protein-1 (IQCB1), the gene that encodes for nephrocystin-5 (NPHP5), had vision loss. The variant segregated concordantly in other related individuals within the pedigree supporting the identification of a recessively inherited early-onset feline PRA. Analysis of the black-footed cat studbook suggests additional captive cats are at risk. Genetic testing for IQCB1 and avoidance of matings between carriers should be added to the species survival plan for captive management