Deuterated reagents in multicomponent reactions to afford deuterium-labeled products.

The utility of bio-isosteres is broad in drug discovery and methodology herein enables the preparation of deuterium-labeled products is the most fundamental of known bio-isosteric replacements. As such we report the use of both [D1]-aldehydes and [D2]-isonitriles across 8 multicomponent reactions (MCRs) to give diverse arrays of deuterated products. A highlight is the synthesis of several FDA-approved calcium channel blockers, selectively deuterated at a t 1/2 limiting metabolic soft-spot via use of [D1]-aldehydes. Surrogate pharmacokinetic analyses of microsomal stability confirm prolongation of t 1/2 of the new deuterated analogs. We also report the first preparation of [D2]-isonitriles from [D3]-formamides via a modified Leuckart-Wallach reaction and their use in an MCR to afford products with [D2]-benzylic positions and likely significantly enhanced metabolic stability, a key parameter for property-based design efforts.

Pregnenolone 16-Alpha Carbonitrile, an Agonist of Rodent Pregnane X Receptor, Regulates Testosterone Biosynthesis in Rodent Leydig Cells.

Leydig cells (LCs) in the testes produce the male sex hormone testosterone (T). Several xenobiotics, including clinical drugs, supplements, and environmental chemicals, are known to disrupt T homeostasis. Notably, some of these xenobiotics are known to activate the pregnane X receptor (PXR), a ligand-dependent nuclear receptor. However, it is currently unknown whether PXR is expressed in LCs and whether PXR activation alters T synthesis in rodent LCs. Therefore, in this study, we sought to determine whether PXR is expressed in rodent LCs and whether pregnenolone 16-alpha carbonitrile (PCN), the prototype agonist of rodent PXR, regulates T biosynthesis in rodent LCs. Hormonal as well as protein and gene expression analyses were conducted in rat primary LCs and MA-10 mouse Leydig cells. Results showed that PXR was expressed at the mRNA and protein level in both rat primary LCs and MA-10 cells. Incubation of rat primary LCs with PCN resulted in a significant decrease in T secretion. This PCN-induced decrease in T secretion was associated with decreased protein expression of key steroidogenic enzymes such as 3ß-HSD and CYP17A1. RNA-seq results from MA-10 cells showed that PCN down-regulated the transcripts of steroidogenic enzymes and proteins involved in the T synthesis pathway. Together, these results suggest that PCN, an agonist of rodent PXR, can regulate T biosynthesis in rodent LCs by down-regulating the expression of the steroidogenic enzymes involved in T biosynthesis. Our results are significant as they provide a potential novel mechanism for disruption of testosterone homeostasis by a variety of xenobiotics.

A hot-Jupiter progenitor on a super-eccentric retrograde orbit.

Giant exoplanets orbiting close to their host stars are unlikely to have formed in their present configurations1. These 'hot Jupiter' planets are instead thought to have migrated inward from beyond the ice line and several viable migration channels have been proposed, including eccentricity excitation through angular-momentum exchange with a third body followed by tidally driven orbital circularization2,3. The discovery of the extremely eccentric (e = 0.93) giant exoplanet HD 80606 b (ref. 4) provided observational evidence that hot Jupiters may have formed through this high-eccentricity tidal-migration pathway5. However, no similar hot-Jupiter progenitors have been found and simulations predict that one factor affecting the efficacy of this mechanism is exoplanet mass, as low-mass planets are more likely to be tidally disrupted during periastron passage6-8. Here we present spectroscopic and photometric observations of TIC 241249530 b, a high-mass, transiting warm Jupiter with an extreme orbital eccentricity of e = 0.94. The orbit of TIC 241249530 b is consistent with a history of eccentricity oscillations and a future tidal circularization trajectory. Our analysis of the mass and eccentricity distributions of the transiting-warm-Jupiter population further reveals a correlation between high mass and high eccentricity.

Moving together: Increasing physical activity in older adults with an intergenerational technology-based intervention. A feasibility study.

Robust evidence supports the role of physical activity and exercise in increasing longevity, decreasing morbidity and helping older adults maintain the highest quality of life attainable. However, the majority of older adults are not sufficiently physically active and interventions are needed to change their behaviors. Familial or intergenerational contact has been positively linked to health and well-being in older adults. Therefore, this study aimed to i) establish acceptability and test the functionality and useability of a novel technology-driven intergenerational intervention targeting physical activity and age stereotypes, and ii) identify any potential issues with recruitment and retention. Four familial dyads (adult ≥ 65 and child 7-11 years) engaged with the intervention. Working collaboratively during a four-week trial, they combined daily step-counts (acquired via any activity of their choice, using PA trackers) to complete a virtual walk route using online platform World Walking. Thematic analysis of three post-intervention focus groups (one older adult; one child; one additional parental cohort) identified eight subthemes: Engagement; Provision of a Positive Experience; Participant Stimuli; Generated Outcomes; Operationality; Limitations; Mediators; Facilitators, and Perceptions. Participants enjoyed and successfully engaged with the intervention; when designing behaviour change interventions for older adults, flexibility within pre-established routines, individual choice, and avoiding rigidly imposed structures, is important. Strategies to challenge negative perceptions of older adults' engagement with technology and PA should be integrated into recruitment processes.

A cross-sectional study observing the association of psychosocial stress and dietary intake with gut microbiota genera and alpha diversity among a young adult cohort of black and white women in Birmingham, Alabama.

BACKGROUND: The relationships between psychosocial stress and diet with gut microbiota composition and diversity deserve ongoing investigation. The primary aim of this study was to examine the associations of psychosocial stress measures and dietary variables with gut microbiota genera abundance and alpha diversity among young adult, black and white females. The secondary aim was to explore mediators of psychosocial stress and gut microbiota diversity and abundance. METHODS: Data on 60 females who self-identified as African American (AA; n = 29) or European American (EA; n = 31) aged 21-45 years were included. Cortisol was measured in hair and saliva, and 16S analysis of stool samples were conducted. Discrimination experiences (recent and lifetime), perceived stress, and depression were evaluated based on validated instruments. Spearman correlations were performed to evaluate the influence of psychosocial stressors, cortisol measures, and dietary variables on gut microbiota genus abundance and alpha diversity measured by amplicon sequence variant (ASV) count. Mediation analyses assessed the role of select dietary variables and cortisol measures on the associations between psychosocial stress, Alistipes and Blautia abundance, and ASV count. RESULTS: AA females were found to have significantly lower ASV count and Blautia abundance. Results for the spearman correlations assessing the influence of psychosocial stress and dietary variables on gut microbiota abundance and ASV count were varied. Finally, diet nor cortisol was found to partially or fully mediate the associations between subjective stress measures, ASV count, and Alistipes and Blautia abundance. CONCLUSION: In this cross-sectional study, AA females had lower alpha diversity and Blautia abundance compared to EA females. Some psychosocial stressors and dietary variables were found to be correlated with ASV count and few gut microbiota genera. Larger scale studies are needed to explore the relationships among psychosocial stress, diet and the gut microbiome.

Looking Beyond the Growth Curve: A Retrospective Study on Nutrient Deficient Diets in Children with Severe Food Selectivity.

Severe food selectivity places children at risk for nutrient deficiencies and long-term medical complications, if unaddressed. However, poor nutrition in highly selective eaters is often overlooked when considering other behavioral or medical concerns. Additionally, studies regarding food selectivity are sparse and limited to children with developmental delays. This study further investigates the nutritional deficiencies and growth characteristics of children with severe food selectivity to assist pediatricians in the earlier identification of patients for nutrition screening. A retrospective chart review was completed for 13 patients admitted to a pediatric feeding program solely for table-textured food selectivity. Nutrition and anthropometric data from the medical record were analyzed. All patients were determined to be following an age-appropriate growth curve but had multiple micronutrient deficiencies. Additionally, 6 children were typically developing outside of the feeding context. Results suggest that children with food selectivity may require more intensive and earlier nutrition screening beyond their growth patterns.

Reducing fear and avoidance of memory loss improves mood and social engagement in community-based older adults: a randomized trial.

BACKGROUND: Alzheimer's disease and related dementias (ADRD) are among the most feared age-related conditions. The aim of this study was to evaluate a brief psychological intervention to promote adaptive coping in older adults experiencing heightened fear of ADRD and investigate positive downstream effects on health-related secondary outcomes, including frequency of reported memory failures, psychosocial functioning, and quality of life. METHODS: Eighty-one older adults were recruited and randomized into REFRAME or active control intervention arms. Both groups received psycho-education and training in mindful monitoring of fears related to ADRD. The REFRAME group received an additional behavioral activation component intended to disrupt maladaptive avoidant coping (i.e., avoidance) strategies. Both groups completed 3-weeks of intervention exercises with accompanying questionnaires (baseline, mid- and post-intervention and 4-week follow-up). RESULTS: Adherence was strong (> 75%). We observed a significant reduction in ADRD-related fear and avoidance in both groups. Significant reductions were also observed for frequency of self-reported memory failures, anxiety, and depression. Depression was significantly reduced in the REFRAME group compared to the control group. Significant increases in participants' ability to participate in social activities and well-being were also observed. CONCLUSIONS: Findings suggest that a brief psychological intervention can mitigate ADRD-related fears and avoidant coping in older adults, and that benefits extend to broader health-related outcomes including anxiety, depression, social functioning, and well-being. Addressing ADRD-related fear has implications for healthy aging and risk reduction, as individuals may be more likely to engage in activities that are protective against ADRD but were previously avoided. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04821960 .

A cross-sectional study observing the association of psychosocial stress and dietary intake with gut microbiota genera and alpha diversity among a young adult cohort of black and white women in Birmingham, Alabama.

Background: The relationships between psychosocial stress and diet with gut microbiota composition and diversity deserve ongoing investigation. The primary aim of this study was to examine the associations of psychosocial stress measures and dietary variables with gut microbiota genera abundance and alpha diversity among young adult, black and white females. The secondary aim was to explore mediators of psychosocial stress and gut microbiota diversity and abundance. Methods: Data on 60 females who self-identified as African American (AA; n = 29) or European American (EA; n = 31) aged 21-45 years were included. Cortisol was measured in hair and saliva, and 16S analysis of stool samples were conducted. Discrimination experiences (recent and lifetime), perceived stress, and depression were evaluated based on validated instruments. Spearman correlations were performed to evaluate the influence of psychosocial stressors, cortisol measures, and dietary variables on gut microbiota genus abundance and alpha diversity measured by amplicon sequence variant(ASV) count. Mediation analyses assessed the mediating role of select dietary variables and cortisol measures on the associations between psychosocial stress, Alistipes and Blautia abundance, and ASV count. Results: AA females were found to have significantly lower ASV count and Blautia abundance. Results for the spearman correlations assessing the influence of psychosocial stress and dietary variables on gut microbiota abundance and ASV count were varied. Finally, diet nor cortisol was found to partially or fully mediate the associations between subjective stress measures, ASV count, and Alistipes and Blautia abundance. Conclusion: In this cross-sectional study, AA females had lower alpha diversity and Blautia abundance compared to EA females. Some psychosocial stressors and dietary variables were found to be correlated with ASV count and few gut microbiota genera. Larger scale studies are needed to explore the relationships among psychosocial stress, diet and the gut microbiome.

Battling the unknown: Using composite vignettes to portray lived experiences of COVID-19 and long-COVID.

Understanding the day-to-day lived experiences of individuals who have had or are still recovering from Coronavirus Disease-19 (COVID-19), whilst a complex challenge, presents the opportunity to listen and learn. Composite vignettes provide a novel approach to explore and present descriptive portrayals of the most commonly derived experiences and recovery journeys. The thematic analysis of 47 shared accounts (semi-structured interviews with adults aged ≥18 years; 40 females; 6-11 months post-COVID-19 infection) produced a series of four intricate character stories written through the lens of a single individual. Each vignette gives a voice to and captures a different experience trajectory. From the point of initial symptom development onwards, the vignettes depict how COVID-19 has affected everyday lives, focusing on the secondary non-biological socio-psychological effects and implications. The vignettes highlight in participants' own words: i) the potential negative implications of not addressing the psychological effects of COVID-19; ii) the lack of symptom and recovery linearity; iii) the ongoing 'lottery' of access to healthcare services; and iv) the highly variable, yet generally devastating, impacts that COVID-19 and consequent long-COVID has had across multiple facets of daily living.

3D-Printing Physical Activity in Youth: An Autotopographical Approach to Behaviour Change.

The conceptualisation and visualisation of physical activity through 3D-printed objects offers a unique means by which to elicit positive behaviour change. This study aimed to explore whether 3D-printed models of physical activity obtain autotopographical meaning in youths and the influence of such models on their sense of personal and social identity. Following participation in a seven-week faded intervention, whereby habitual physical activity was measured and used to create individual 3D models, the views of 61 participants (36 boys; 10.9 ± 3.0 years) were explored via semi-structured focus groups. Within the over-arching theme of '3D-Printed Models', key emergent sub-themes were structured around 'Autotopography', 'Reflection', 'In-group norms', and 'Significant others'. Investing meaning in the material representations facilitated social activation and self-reflection on their own behaviour, both of which are key elements of identity formation. The influential role of significant others (familial and peers) within initial model interpretation and their potential long-term efficacy as a behaviour change approach was highlighted. 3D-printed models present a novel concept and intervention approach and may represent a useful component within behaviour change engagement strategies in children and adolescents.

A transdiagnostic meta-analysis of acute augmentations to psychological therapy.

At least half of all patients with mental health disorders do not respond adequately to psychological therapy. Acutely enhancing particular biological or psychological processes during psychological therapy may improve treatment outcomes. However, previous studies are confined to specific augmentation approaches, typically assessed within single diagnostic categories. Our objective was to assess to what degree acute augmentations of psychological therapy reduce psychiatric symptoms and estimate effect sizes of augmentation types (for example, brain stimulation or psychedelics). We searched Medline, PsycINFO and Embase for controlled studies published between database inception and 25 May 2022. We conducted a preregistered random-effects meta-analysis (PROSPERO CRD42021236403). We identified 108 studies (N = 5,889). Acute augmentation significantly reduced the severity of mental health problems (Hedges' g = -0.27, 95% CI: [-0.36, -0.18]; P < 0.0001), particularly for the transdiagnostic dimensions 'Fear' and 'Distress'. This result survived a trim-and-fill analysis to account for publication bias. Subgroup analyses revealed that pharmacological, psychological and somatic augmentations were effective, but to varying degrees. Acute augmentation approaches are a promising route to improve outcomes from psychological therapy.

Mixed-Methods Systematic Review to Identify Facilitators and Barriers for Parents/Carers to Engage Pre-School Children in Community-Based Opportunities to Be Physically Active.

Background: Low physical activity levels in young children is a major concern. For children aged 0-5 years, engagement with opportunities to be physically active are often driven by the adults responsible for the child's care. This systematic review explores the barriers and facilitators to parents/caregivers engaging pre-school children in community-based opportunities for physical activity, within real-world settings, or as part of an intervention study. Methods: EBSCOhost Medline, CINHAL plus, EBSCOhost SPORTDiscus, Web of Science, ProQuest, and ASSIA were systematically searched for quantitative and qualitative studies published in English between 2015 and 16 May 2022. Data extracted from 16 articles (485 parents/carers; four countries) were quality-assessed using the Mixed Methods Assessment Tool and coded and themed via thematic analysis. Results: Nine themes (eight core, one minor) were identified and conceptualised into a socio-ecological model, illustrating factors over four levels: Individual-beliefs and knowledge (and parental parameters); Interpersonal-social benefits, social network, and family dynamic; Community-organisational factors and affordability; and Built and Physical Environment-infrastructure. Discussion: The findings provide valuable insights for practitioners and policy makers who commission, design, and deliver community-based physical activity opportunities for pre-school children. Developing strategies and opportunities that seek to address the barriers identified, as well as build on the facilitators highlighted by parents, particularly factors related to infrastructure and affordability, are imperative for physical activity promotion in pre-school children. The perspectives of fathers, socioeconomic and geographical differences, and the importance parents place on physical activity promotion all need to be explored further.

Dietary inflammation score is associated with perceived stress, depression, and cardiometabolic health risk factors among a young adult cohort of women.

BACKGROUND AND AIMS: One of the most pressing issues in the field of cardiometabolic disease is the growing co-occurrence of poor mental health. A whole foods-based, hypothesis-driven dietary inflammation score (DIS) was created to better understand the association between dietary patterns, inflammation, and physiological health. However, this diet quality scoring method has not been observed in young adults, nor has its association with mental health been observed. This study 1) examined differences in cardiometabolic health measures by dietary inflammation score (DIS) tertiles and 2) examined the association between DIS and psychosocial stress variables, perceived stress, and depression. METHODS: Psychosocial and food frequency questionnaires, demographics, anthropometrics, and clinical measures were collected from sixty-two metabolically healthy African American and European American females, ages 18-45, from 2014 to 2016 in Birmingham, AL. Analysis of Variance was used to observe differences in all cardiometabolic variables by DIS tertile. Linear regression was used to observe the relationship between independent, continuous variable DIS and dependent variables, depression, and perceived stress. RESULTS: There were significant differences between DIS tertiles for cardiometabolic and psychosocial stress measures. DIS was significantly positively associated with depression after controlling for body fat percentage (P = 0.003) and education, income, and race (P = 0.01). DIS was significantly associated with perceived stress after controlling for body fat percentage (P = 0.0004), and education, income, and race (P = 0.0005). CONCLUSION: This study is significant for its contribution in understanding how cardiometabolic health differs by DIS tertile, and how dietary inflammation scores are associated with depression and perceived stress among young adult women.

Body fat percentage assessment using skinfold thickness agrees with measures obtained by DXA scan in African American and Caucasian American women.

Dual-energy x-ray absorptiometry (DXA) is considered to have high accuracy in estimating fat mass; however, DXA is not always available. We hypothesized that the equations most commonly used for predicting body fat percentage (BF%) using skinfold thickness agree with direct measures of BF% obtained by DXA scan in African American (AA) and Caucasian American (CA) women. Data from 42 women from Alabama who were 21 to 45 years of age, who self-identify as AA (n = 20) or CA (n = 22) were included. BF% was estimated using DXA scan and through 6 different skinfold thickness equations. Agreement between DXA-BF% and BF% based on the skinfold thickness equations was assessed following the Bland-Altman method (bias and agreement limits). Agreement analysis showed in both AA and CA women that the BF%-Siri equation reflects better agreement and lower mean differences (bias) with BF%-DXA than the BF%-Brozek equation after applying 4 body density (BD) equations. Limits showed that BF%-Siri and BF%-Brozek predictive equations overestimate BF% compared with DXA-BF% in both AA and CA women. In AAs, equations that overestimated less were Wilmore and Behnke-Siri (by 1.81%) and Durnin and Womersley-Siri (by 2.5%) equations. Regarding CAs, equations that overestimated less were Durnin and Womersley-Siri (by 2.74%) and Wilmore and Behnke-Siri (by 3.11%) equations. The results of this study show that the BF%-Siri equation is a more accurate alternative than the BF%-Brozek equation for the calculation of BF%. In the calculation of BD, the Wilmore and Behnke equation in AA women and Durnin and Womersley in CA women were those that overestimated BF% to a lesser degree.

Pharmacist authors of emergency medicine organization work products pertaining to pharmacotherapy.

PURPOSE: Despite the expertise that emergency medicine (EM) pharmacists bring to multidisciplinary teams in the emergency department (ED) setting, they are not commonly present on writing groups for guidelines, policies, or task forces pertaining to EM pharmacotherapy. The purpose of this article is to quantify EM pharmacist involvement on author bylines of guidelines, position statements, and other official documents that specifically encompass EM pharmacotherapy. METHODS: Official work products released between January 1, 2010, and May 1, 2021, were collected from the American College of Emergency Physicians (ACEP), Society for Academic Emergency Medicine (SAEM), and American Academy of Emergency Medicine (AAEM) and the table of contents of the following journals: Annals of Emergency Medicine, Academic Emergency Medicine, and Journal of Emergency Medicine. A modified Delphi approach was used to gain consensus amongst the authors on which work products to include in the initial review and which works pertained to pharmacotherapy. The primary endpoint was the percentage of pharmacists listed as authors on EM work products pertaining to pharmacotherapy. RESULTS: Overall, 76 EM work products were identified. Forty-seven work products with a total of 248 authors contained at least 1 recommendation pertaining to pharmacotherapy. Of these 47 EM work products, 23 (49%) were from AAEM, 16 (34%) were from Annals of Emergency Medicine (published on behalf of ACEP), 5 (11%) were from Journal of Emergency Medicine (published on behalf of AAEM), and 3 (6%) were from SAEM. The median number of authors per work product was 4. There were 5 pharmacists listed on work products (2% of the total of 248 authors). Additionally, there were 9 nonpharmacist/nonphysician authors (4% of the total). CONCLUSION: Pharmacist inclusion on author lists of recently published EM work products pertaining to pharmacotherapy is extremely low. Given their unique knowledge pertaining to EM pharmacotherapy, an effort should be made to increase inclusion of pharmacists as authors of EM work products with recommendations that pertain to pharmacotherapy.

Protocol for a randomised controlled trial investigating an intervention to boost decentering in response to distressing mental experiences during adolescence: the decentering in adolescence study (DECADES).

INTRODUCTION: Decentering describes the ability to voluntarily adopt an objective self-perspective from which to notice internal, typically distressing, stressors (eg, difficult thoughts, memories and feelings). The reinforcement of this skill may be an active ingredient through which different psychological interventions accrue reductions in anxiety and/or depression. However, it is unclear if decentering can be selectively trained at a young age and if this might reduce psychological distress. The aim of the current trial is to address this research gap. METHODS AND ANALYSIS: Adolescents, recruited from schools in the UK and Ireland (n=57 per group, age range=16-19 years), will be randomised to complete 5 weeks of decentering training, or an active control group that will take part in a combination of light physical exercise and cognitive training. The coprimary training outcomes include a self-reported decentering inventory (ie, the Experiences Questionnaire) and the momentary use of decentering in response to psychological stressors, using experience sampling. The secondary mental health outcomes will include self-reported inventories of depression and anxiety symptoms, as well as psychological well-being. Initial statistical analysis will use between-group analysis of covariance to estimate the effect of training condition on self-rated inventories, adjusted for baseline scores. Additionally, experience sampling data will be examined using hierarchical linear models. ETHICS AND DISSEMINATION: This study was approved by the Cambridge Psychology Research Ethics Committee, University of Cambridge (PRE.2019.109). Findings will be disseminated through typical academic routes including poster/paper presentations at (inter)national conferences, academic institutes and through publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN14329613.

Moving Forward: Understanding Correlates of Physical Activity and Sedentary Behaviour during COVID-19 in Children and Adolescents-An Integrative Review and Socioecological Approach.

Novel coronavirus disease 2019 (COVID-19) pandemic restrictions have negatively impacted physical activity (PA) and sedentary time/behaviour. This integrative review systematically explored the socioecological factors that impacted and influenced these movement behaviours in children and adolescents during the pandemic. Five electronic databases were systematically searched in January 2021, with data extracted from 16 articles (n = 18,352; 5-17 years; 12 countries). Risk-of-bias was assessed using the Mixed Methods Assessment Tool (MMAT), with correlates identified, coded, and themed via thematic analysis. A socioecological model of during-pandemic PA and sedentary time/behaviour was conceptualised and mapped to the Capability, Opportunity, Motivation, and Behaviour (COM-B) model of behaviour-change mechanisms, illustrating influences over five levels: Individual (biological)-age and sex; Individual (psychological)-mental health, and cognition, motivation, and behaviour; Social-family factors, and structured support; Environmental-area of residence and resources; and Policy-COVID-19-related rules. For sedentary time/behaviour, individual-(age and sex), social-(family factors) and policy-(COVID-19-related rules) level factors may be important correlates. There were no age or sex associations with PA levels, though there was some indication that sedentary time/behaviour increased with age. Interventions seeking to enhance young people's movement behaviours during periods of enforced restrictions should focus on enhancing opportunities on a social and environmental level.

Oral Aversion in Infants With Congenital Heart Disease: A Single-Center Retrospective Cohort Study.

OBJECTIVES: Neonates undergoing cardiac surgery are at risk for oral aversion (OA). OA is not well described outside of the index hospitalization and impacts patients and families. We evaluated the prevalence of OA at 1 year old after neonatal cardiopulmonary bypass (CPB) surgery. DESIGN: Retrospective cohort study. SETTING: Single quaternary care hospital. SUBJECTS: Our cohort included 157 neonates who underwent CPB surgery from 2014 to 2017 and had follow-up data available at 1 year old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three feeding experts reviewed the medical record to define children with OA; 30% of charts were evaluated in triplicate for validation. Neonates with and without OA were compared in univariate analysis, and risk factors for OA were explored in a limited multivariable analysis. OA was present at 1 year in 37 patients (23.6%) and other feeding difficulties were present in an additional 29 patients (18.5%). Thirty-eight patients (24.2%) had a feeding tube, including 12 (7.6%) with a gastrostomy tube. Factors associated with OA at 1 year included total ICU days, duration of mechanical ventilation, total number of nil per os days, and number of postoperative days (PODs) until oral feeding initiation (all p < 0.0001). Number of POD until oral feeding initiation remained independently associated with OA at 1 year in multivariable analysis (adjusted odds ratio, 1.08; 95% CI, 1.04-1.12; p < 0.0001). Infants with any oral intake at discharge had lower odds of OA at 1 year (0.21; 95% CI, 0.08-0.5; p = 0.0003). At hospital discharge, 132 patients (84.1%) were taking some oral feeds, and 128 patients (81.5%) received tube feeding. CONCLUSIONS: OA and other feeding difficulties are common at 1 year old in neonates undergoing CPB surgery. Delayed exposure to oral intake may be a modifiable risk factor for OA and efforts to improve early oral feeding could lead to better functional outcomes.