Stability of child appetitive traits and association with diet quality at 5 years and 9-11 years old: Findings from the ROLO longitudinal birth cohort study.

BACKGROUND: We explored change in child appetitive traits from 5 to 9-11 years old and examined associations between appetitive traits at both timepoints and child diet quality. METHODS: This is secondary analyses of the ROLO longitudinal birth cohort study, including mother-child dyads from the 5 and 9-11-year old follow-up. The Children's Eating Behaviour Questionnaire measured child appetitive traits, with 167 children having matched data for both timepoints. The Healthy Eating Index (HEI) measured diet quality. Linear mixed models and multiple linear regression were completed. RESULTS: Mean (SD) score for 'Emotional Overeating' (1.63 (0.51) vs. 1.99 (0.57), p = <0.001) and 'Enjoyment of Food' (3.79 (0.72) vs. 3.98 (0.66), p = <0.001) increased from 5 to 9-11 years. Mean score for 'Desire to Drink' (2.63 (0.94) vs. 2.45 (0.85), p = 0.01), 'Satiety Responsiveness (3.07 (0.66) vs. 2.71 (0.66), p = <0.001), 'Slowness Eating' (3.02 (0.77) vs. 2.64 (0.78), p = <0.001), and 'Food Fussiness' (3.00 (1.04) vs. 2.81 (0.96), p = 0.001) decreased. At 5-years-old, 'Food Responsiveness' and 'Enjoyment of Food' were positively associated with HEI and 'Desire to Drink', 'Satiety Responsiveness' and 'Food Fussiness' were negatively associated with HEI. At 9-11-years, 'Enjoyment of Food' was positively and 'Desire to Drink' and 'Food 'Fussiness' were negatively associated with HEI. CONCLUSIONS: Food approach appetitive traits increased over time, whereas food avoidant appetitive traits tended to decrease. At both time points 'Food Fussiness' and 'Desire to Drink" were inversely associated with HEI. Further research on how appetitive traits track over childhood and how this relates to dietary quality and weight is warranted.

Case report: Glycaemic management and pregnancy outcomes in a woman with an insulin receptor mutation, p.Met1180Lys.

BACKGROUND: Heterozygous insulin receptor mutations (INSR) are associated with insulin resistance, hyperglycaemia and hyperinsulinaemic hypoglycaemia in addition to hyperandrogenism and oligomenorrhoea in women. Numerous autosomal dominant heterozygous mutations involving the INSR ß-subunit tyrosine kinase domain resulting in type A insulin resistance have been previously described. We describe the phenotype, obstetric management and neonatal outcomes in a woman with type A insulin resistance caused by a mutation in the ß-subunit of the INSR. CASE PRESENTATION: We describe a woman with a p.Met1180Lys mutation who presents with hirsutism, oligomenorrhoea and diabetes at age 20. She has autoimmune thyroid disease, Coeliac disease and positive GAD antibodies. She is overweight with no features of acanthosis nigricans and is treated with metformin. She had 11 pregnancies treated with insulin monotherapy (n = 2) or combined metformin and insulin therapy (n = 9). The maximum insulin dose requirement was 134 units/day or 1.68 units/kg/day late in the second pregnancy. Mean birthweight was on the 37th centile in INSR positive offspring (n = 3) and the 94th centile in INSR negative offspring (n = 1). CONCLUSION: The p.Met1180Lys mutation results in a phenotype of diabetes, hirsutism and oligomenorrhoea. This woman had co-existent autoimmune disease. Her insulin dose requirements during pregnancy were similar to doses observed in women with type 2 diabetes. Metformin may be used to improve insulin sensitivity in women with this mutation. Offspring inheriting the mutation tended to be smaller for gestational age.

Dietary intakes of iron, folate, and vitamin B12 during pregnancy and correlation with maternal hemoglobin and fetal growth: findings from the ROLO longitudinal birth cohort study.

PURPOSE: Dietary micronutrient intakes of iron, folate and vitamin B12 are known to influence hemoglobin. Low maternal hemoglobin (maternal anemia) has been linked to low birthweight and other adverse health outcomes in the fetus and infant. Our primary aim was to explore relationships between maternal dietary micronutrient intakes, maternal full blood count (FBC) parameters and fetal abdominal circumference (AC) and estimated fetal weight (EFW) growth trajectories. Secondarily, we aimed to assess relationships between maternal dietary micronutrient intakes, maternal hemoglobin values and placental weight and birthweight. METHODS: Mother-child pairs (n = 759) recruited for the ROLO study were included in this analysis. Maternal dietary micronutrient intakes were calculated from food diaries completed during each trimester of pregnancy. FBC samples were collected at 13- and 28-weeks' gestation. Fetal ultrasound measurements were recorded at 20- and 34-weeks' gestation. Growth trajectories for AC and EFW were estimated using latent class trajectory mixture models. RESULTS: Dietary intakes of iron and folate were deficient for all trimesters. Mean maternal hemoglobin levels were replete at 13- and 28-weeks' gestation. Dietary iron, folate and vitamin B12 intakes showed no associations with fetal growth trajectories, placental weight or birthweight. Lower maternal hemoglobin concentrations at 28 weeks' gestation were associated with faster rates of fetal growth and larger placental weights and birthweights. CONCLUSION: The negative association between maternal hemoglobin at 28 weeks' gestation and accelerated fetal and placental growth may be due to greater consumption of maternal iron and hemoglobin by fetuses' on faster growth trajectories in addition to placental biochemical responses to lower oxygen states.

Growth reference charts for children with hypochondroplasia.

Hypochondroplasia (HCH) is a rare skeletal dysplasia causing mild short stature. There is a paucity of growth reference charts for this population. Anthropometric data were collected to generate height, weight, and head circumference (HC) growth reference charts for children with a diagnosis of HCH. Mixed longitudinal anthropometric data and genetic analysis results were collected from 14 European specialized skeletal dysplasia centers. Growth charts were generated using Generalized Additive Models for Location, Scale, and Shape. Measurements for height (983), weight (896), and HC (389) were collected from 188 (79 female) children with a diagnosis of HCH aged 0-18 years. Of the 84 children who underwent genetic testing, a pathogenic variant in FGFR3 was identified in 92% (77). The data were used to generate growth references for height, weight, and HC, plotted as charts with seven centiles from 2nd to 98th, for ages 0-4 and 0-16 years. HCH-specific growth charts are important in the clinical care of these children. They help to identify if other comorbidities are present that affect growth and development and serve as an important benchmark for any prospective interventional research studies and trials.

Once-weekly TransCon CNP (navepegritide) in children with achondroplasia (ACcomplisH): a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-escalation trial.

Background: TransCon CNP (navepegritide) is an investigational prodrug of C-type natriuretic peptide (CNP) designed to allow for continuous CNP exposure with once-weekly dosing. This 52-week phase 2 (ACcomplisH) trial assessed the safety and efficacy of TransCon CNP in children with achondroplasia. Methods: ACcomplisH is a global, randomised, double-blind, placebo-controlled, dose-escalation trial. Study participants were recruited between June 10, 2020, and September 24, 2021. Eligible participants were prepubertal, aged 2-10 years, with genetically confirmed achondroplasia, and randomised 3:1 to once-weekly subcutaneous injections of TransCon CNP (6, 20, 50, or 100 µg CNP/kg/week) or placebo for 52 weeks. Primary objectives were safety and annualised growth velocity (AGV). ACcomplisH is registered with ClinicalTrials.gov (NCT04085523) and Eudra (CT 2019-002754-22). Findings: Forty-two participants received TransCon CNP at doses of 6 µg (n = 10; 7 female), 20 µg (n = 11; 3 female), 50 µg (n = 10; 3 female), or 100 µg (n = 11; 6 female) CNP/kg/week, with 15 receiving placebo (5 female). Treatment-emergent adverse events (TEAEs) were mild or moderate with no grade 3/4 events reported. There were 2 serious TEAEs that were assessed as not related to TransCon CNP. Eleven injection site reactions occurred in 8 participants receiving TransCon CNP and no symptomatic hypotension occurred. TransCon CNP demonstrated a dose-dependent improvement in AGV. At 52 weeks, TransCon CNP 100 µg CNP/kg/week significantly improved AGV vs placebo (least squares mean [95% CI] 5.42 [4.74-6.11] vs 4.35 [3.75-4.94] cm/year; p = 0.0218), and improved achondroplasia-specific height SDS from baseline (least squares mean [95% CI] 0.22 [0.02-0·41] vs -0·08 [-0.25 to 0.10]; p = 0.0283). All participants completed the randomised period and continued in the ongoing open-label extension period receiving TransCon CNP 100 µg CNP/kg/week. Interpretation: This phase 2 trial suggests that TransCon CNP is effective, safe, with low injection site reaction frequency, and may provide a novel, once-weekly treatment option for children with achondroplasia. These results support TransCon CNP at 100 µg CNP/kg/week in the ongoing pivotal trial. Funding: Ascendis Pharma, A/S.

The impact of macrosomia on cardiometabolic health in preteens: findings from the ROLO longitudinal birth cohort study.

BACKGROUND: Macrosomia (birthweight ≥ 4 kg or ≥ 4.5 kg) is strongly associated with a predisposition to childhood obesity, which in turn is linked with adverse cardiometabolic health. Despite this, there is a lack of longitudinal investigation on the impact of high birthweight on cardiometabolic outcomes in youth. The preteen period represents an important window of opportunity to further explore this link, to potentially prevent cardiometabolic profiles worsening during puberty. METHODS: This is a secondary analysis of 9-11-year-olds (n = 405) born to mothers in the ROLO longitudinal birth cohort study, who previously delivered an infant with macrosomia. Preteens were dichotomised into those born with and without macrosomia, using two common cut-off criteria (birthweight ≥ 4 kg (n = 208) and < 4 kg; ≥ 4.5 kg (n = 65) and < 4.5 kg). Cardiometabolic health was assessed using anthropometry, dual-energy x-ray absorptiometry, blood pressure, heart rate, cardiorespiratory endurance (20-m shuttle run test), and non-fasting serum biomarkers for a subgroup (n = 213). Statistical comparisons between the two groups were explored using independent t-tests, Mann-Whitney U tests, and Chi-square tests. Crude and adjusted linear regression models investigated associations between macrosomia and preteen cardiometabolic outcomes. RESULTS: In total, 29.3% (n = 119) of preteens had overweight/obesity based on their BMI z-score. Preteens born ≥ 4 kg had lower median (IQR) C3 concentrations (1.38 (1.22, 1.52) g/L vs. 1.4 (1.26, 1.6) g/L, p = 0.043) and lower median (IQR) ICAM-1 concentrations (345.39 (290.34, 394.91) ng/mL vs. 387.44 (312.91, 441.83) ng/mL, p = 0.040), than those born < 4 kg. Those born ≥ 4.5 kg had higher mean (SD) BMI z-scores (0.71 (0.99) vs. 0.36 (1.09), p = 0.016), and higher median (IQR) lean mass (24.76 (23.28, 28.51) kg vs. 23.87 (21.9, 26.79) kg, p = 0.021), than those born < 4.5 kg. Adjusted linear regression analyses revealed birthweight ≥ 4 kg was negatively associated with C3 concentration (g/L) (B = - 0.095, 95% CI = - 0.162, - 0.029, p = 0.005) and birthweight ≥ 4.5 kg was positively associated with weight z-score (B = 0.325, 95% CI = 0.018, 0.633, p = 0.038), height z-score (B = 0.391, 95% CI = 0.079, 0.703, p = 0.014), lean mass (kg) (B = 1.353, 95% CI = 0.264, 2.442, p = 0.015) and cardiorespiratory endurance (B = 0.407, 95% CI = 0.006, 0.808, p = 0.047). CONCLUSION: This study found no strong evidence to suggest that macrosomia is associated with adverse preteen cardiometabolic health. Macrosomia alone may not be a long-term cardiometabolic risk factor. Trial registration ISRCTN54392969 registered at  www.isrctn.com .

Relationship between parent-adolescent communication and parent involvement in adolescent Type 1 diabetes management, parent/family wellbeing and glycaemic control.

OBJECTIVES: This study investigated the relationship between parent-reported degree of openness and extent of problems in parent-adolescent communication and parent involvement in adolescent Type 1 diabetes management, parent and family wellbeing and adolescent glycaemic control. METHODS: A cross-sectional quantitative survey was conducted. Parents completed measures of parent-adolescent communication, parent monitoring of diabetes care, diabetes family responsibility, parent knowledge of diabetes care, parent activation, parent diabetes distress, and diabetes family conflict. RESULTS: In total, 146 parents/guardians (121 mothers, mean age 46.56 years, SD 5.18) of adolescents aged 11-17 years (mean age 13.9 years, SD 1.81) with Type 1 diabetes completed the survey. Open parent-adolescent communication was significantly correlated to adolescents' voluntarily disclosing diabetes-specific information to their parents more frequently, increased parental knowledge of their adolescent's diabetes care completion, parents feeling more capable and willing to take action in relation to their adolescent's diabetes health, lower levels of diabetes-related parental distress, less diabetes-specific family conflict, and optimal glycaemic control. DISCUSSION: Parent-adolescent communication has an important role to play in Type 1 diabetes healthcare management and psychosocial wellbeing during adolescence. Optimising open parent-adolescent communication represents a potentially useful target for interventional research and should be considered by healthcare professionals during healthcare encounters.

Application of multilevel linear spline models for analysis of growth trajectories in a cohort with repeat antenatal and postnatal measures of growth: a prospective cohort study.

OBJECTIVES: To model trajectories of antenatal and postnatal growth using linear spline multilevel models. DESIGN: Prospective cohort study. SETTING: Maternity hospital in Dublin, Ireland. PARTICIPANTS: 720-759 mother-child pairs from the ROLO study (initially a randomised control trial of a low glycaemic index diet in pregnancy to prevent recurrence of macrosomia [birth weight >4 kg]). PRIMARY OUTCOMES: Trajectories of growth from 20 weeks gestation (abdominal circumference [AC], head circumference [HC] and weight) or birth (length/height) to 5 years. RESULTS: Over 50% of women had third-level education and 90% were of white ethnicity. Women were a mean (SD) age of 32 years (4.2) at recruitment. The best fitting model for AC, HC and weight included a model with 5 linear spline periods. The best fitting models for length/height included a model with 3 linear spline periods from birth to 6 months, 6 months to 2 years and 2 years to 5 years. Comparison of observed and predicted values for each model demonstrated good model fit. For all growth measures, growth rates were generally fastest in pregnancy or immediately post partum (for length/height), with rates of growth slowing after birth and becoming slower still as infancy and childhood progressed. CONCLUSION: We demonstrate the application of multilevel linear spline models for examining growth trajectories when both antenatal and postnatal measures of growth are available. The approach may be useful for cohort studies or randomised control trials with repeat prospective assessments of growth.

Including the child's voice in research from a longitudinal birth cohort: insights from the ROLO young person's advisory group.

BACKGROUND: Public and patient involvement (PPI) through Young Person's Advisory Groups (YPAG) enables children to provide guidance and insight into research activities. PPI is an important characteristic of research, however, to date, most collaboration has been with adults. Also, few YPAGs have been established within the Irish setting. The ROLO (Randomised cOntrol trial of a LOw glycaemic index diet in pregnancy to prevent macrosomia) YPAG was established in July 2020 to identify the research priorities of a group of healthy Irish children who are part of a longitudinal birth cohort. We aimed to describe this process and the key insights to date. METHODS: The ROLO study is a longitudinal birth cohort which has followed-up mother-child dyads at multiple timepoints over 10 years. Mothers actively involved in the study were contacted by the research team to invite their ROLO child and older sibling to participate in the YPAG. Meetings were conducted virtually between July 2020 and February 2022. Researchers encouraged free expression of views amongst the children regarding their research interests. Meetings were recorded, transcribed verbatim and analysed for themes based on the topics most frequently discussed and considered important to participants. RESULTS: In all, seven ROLO children and six older siblings attended four ROLO YPAG meetings. Participants were aged between nine to fifteen years old. Four key themes were identified; study children viewed their identity as part of a longitudinal birth cohort as positive and unique; study children considered the fitness test and body measurements as fun aspects related to their participation; all children considered the impact and use of social media as an important form of communication; and all participants expressed interest in attaining new health-related information and learning opportunities. Children suggested topics such as mental health, future viruses, organ transplants, cancer, and the effect of technology and chemicals on the body were important for future research. CONCLUSION: The ROLO YPAG offers promising scope for continued collaboration. The themes identified from the meetings contribute to a gap in the literature which will guide future research activities, particularly with children, in view of study design, relevance, and by communication strategies. Trial Details: ISRCTN54392969 registered at www.isrctn.com .

The ROLO pregnancy study took place in the National Maternity Hospital in Dublin Ireland. It started in 2007 and ended in 2011. The researchers recorded what women were eating. They also measured the weight of the baby at birth. Since then, ROLO mothers and their children were invited to come back to the study. Now the children of the study are 9­11 years of age.The researchers invited members of the ROLO study to speak with them. They wanted to know what research was important to them. They set up a group called the ROLO Family Advisory Committee in 2017. This group of parents and researchers meet once a year. The group thought it was important to include children as well. They made a new group called the ROLO Young Person's Advisory Group in 2020. The group has 7 ROLO children and 6 older siblings. The members are aged between 9 and 15-years-old. The children and researchers have met four times so far.The researchers found four key themes. Study children saw their identity as being part of a longitudinal birth cohort as positive and unique. Study children liked the fitness test and body measurements. All children thought that social media was an important form of communication. All children were interested in learning new information on how their bodies worked.Involving this group of children is important. It will make our research more relevant. Other researchers who want to involve children can learn from our experience.

Nonsteroidal anti-inflammatory drugs as a targeted therapy for bone marrow failure in Ghosal hematodiaphyseal dysplasia.

Advances in genomic diagnostics hold promise for improved care of rare hematologic diseases. Here, we describe a novel targeted therapeutic approach for Ghosal hematodiaphyseal dysplasia, an autosomal recessive disease characterized by severe normocytic anemia and bone abnormalities due to loss-of-function mutations in thromboxane A synthase 1 (TBXAS1). TBXAS1 metabolizes prostaglandin H2 (PGH2), a cyclooxygenase (COX) product of arachidonic acid, into thromboxane A2. Loss-of-function mutations in TBXAS result in an increase in PGH2 availability for other PG synthases. The current treatment for Ghosal hematodiaphyseal dysplasia syndrome consists of corticosteroids. We hypothesize that nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit COX-1 and COX-2, could ameliorate the effects of TBXAS1 loss and improve hematologic function by reducing prostaglandin formation. We treated 2 patients with Ghosal hematodiaphyseal dysplasia syndrome, an adult and a child, with standard doses of NSAIDs (aspirin or ibuprofen). Both patients had rapid improvements concerning hematologic parameters and inflammatory markers without adverse events. Mass spectrometry analysis demonstrated that urinary PG metabolites were increased along with proinflammatory lipoxygenase (LOX) products 5-hydroxyeicosatetraenoic acid and leukotriene E4. Our data show that NSAIDs at standard doses surprisingly reduced both COX and LOX products, leading to the resolution of cytopenia, and should be considered for first-line treatment for Ghosal hematodiaphyseal dysplasia syndrome.

Steps Ahead: Optimising physical activity in adults with cystic fibrosis: A pilot randomised trial using wearable technology, goal setting and text message feedback.

BACKGROUND: Regular participation in physical activity (PA) is encouraged for people with Cystic Fibrosis (CF). This study aimed to assess the effectiveness of an intervention using wearable technology, goal setting and text message feedback on PA and health outcomes in people with CF. METHODS: This was a pilot randomised trial conducted at University Hospital Limerick. Participants were randomly assigned to the intervention (INT) or active comparator (AC). The 12-week intervention consisted of wearable technology (Fitbit Charge 2) which was remotely monitored, and participants set step count goals. Participants were sent a one-way text message once a week over 12 weeks to positively reinforce and encourage PA participation. The AC group received the wearable technology alone. Follow up was assessed at 24 weeks. Outcomes assessed were PA, aerobic capacity, lung function, sleep, quality of life and wellbeing. RESULTS: Step count increased significantly for the INT group over 12 weeks when compared to the AC group (p=0.019). The INT group had a 28% week-to-week percentage change (Weeks 1-12), while the AC group reduced by 1%, p=0.023. Within group changes demonstrated that VO2 peak (ml/kg/min) significantly increased for the INT group at 12 weeks (24.4 ±7.65 to 26.13 ±7.79, p=0.003) but not at 24 weeks (24.45 ±7.05, p=0.776). There were no significant differences observed for VO2 peak (ml/kg/min) for the AC group. There was no significant effect on lung function, sleep, well-being, or quality of life for either group. CONCLUSIONS: A personalised PA intervention using wearable technology, goal setting and text message feedback increased PA and aerobic capacity in people with CF. Integration of this intervention into usual care may encourage regular PA participation for people with CF.

Associations between maternal metabolic parameters during pregnancy and fetal and child growth trajectories from 20 weeks' gestation to 5 years of age: Secondary analysis from the ROLO longitudinal birth cohort study.

OBJECTIVE: To examine the association between maternal metabolic parameters in pregnancy and growth trajectories up to 5 years of age. METHODS: Data from mother-child pairs who participated in the ROLO study, a randomized trial examining the impact of a low glycaemic index diet on the recurrence of macrosomia, were analysed. Fetal and child growth trajectories were developed from longitudinal measurements from 20 weeks gestation up to 5 years of age. We examined associations between maternal fasting glucose, insulin, HOMA-IR and leptin, taken in early pregnancy (14-16 weeks) and late pregnancy (28 weeks), and weight (kg) and abdominal circumference (cm) trajectories using linear spline multilevel models. RESULTS: We found no strong evidence of associations between any maternal metabolic parameters and fetal to childhood weight and abdominal circumference trajectories from 20 weeks gestation to 5 years. CONCLUSION: In a cohort of women with obesity with infants at risk of macrosomia, maternal metabolic markers were not strongly associated with trajectories of weight or abdominal circumference from 20 weeks gestation to 5 years of age.

Maternal dietary quality during pregnancy and child appetitive traits at 5-years-old: Findings from the ROLO longitudinal birth cohort study.

Maternal diet during pregnancy is an important determinant of birth outcomes and offspring health. The relationship between maternal diet quality during pregnancy and the development of appetitive traits in early childhood has not been extensively researched. We examined associations of maternal diet quality during pregnancy with child appetitive traits at 5 years old. This is a secondary analysis of the ROLO longitudinal birth cohort study. We assessed maternal diet during pregnancy using 3-day food diaries and evaluated diet quality using the Alternative Healthy Eating Index, modified for pregnancy (AHEI-P). Children's appetitive traits at 5-years-old were assessed using the Child Eating Behaviour Questionnaire (CEBQ) (n = 306). Average AHEI-P score over trimesters was calculated and stratified into tertiles. Maternal and child characteristics were examined across AHEI-P tertiles. Multiple linear regression was conducted to explore associations between maternal AHEI-P scores in each trimester and child appetitive traits at 5-years-old. Women with low AHEI-P scores were younger at childbirth and had higher BMI. In adjusted linear regression maternal AHEI-P was negatively associated with child 'Desire to Drink' (Trimester 1: B = -0.014, 95% CI = -0.025, -0.002, p = 0.017; Trimester 2: B = -0.013, 95% CI = -0.025, -0.001, p = 0.035). Trimester 3 AHEI-P was not associated with any child appetitive traits. Maternal diet quality in pregnancy may provide an early opportunity to positively influence the development of offspring's appetitive traits.

Using genetic variation to disentangle the complex relationship between food intake and health outcomes.

Diet is considered as one of the most important modifiable factors influencing human health, but efforts to identify foods or dietary patterns associated with health outcomes often suffer from biases, confounding, and reverse causation. Applying Mendelian randomization in this context may provide evidence to strengthen causality in nutrition research. To this end, we first identified 283 genetic markers associated with dietary intake in 445,779 UK Biobank participants. We then converted these associations into direct genetic effects on food exposures by adjusting them for effects mediated via other traits. The SNPs which did not show evidence of mediation were then used for MR, assessing the association between genetically predicted food choices and other risk factors, health outcomes. We show that using all associated SNPs without omitting those which show evidence of mediation, leads to biases in downstream analyses (genetic correlations, causal inference), similar to those present in observational studies. However, MR analyses using SNPs which have only a direct effect on the exposure on food exposures provided unequivocal evidence of causal associations between specific eating patterns and obesity, blood lipid status, and several other risk factors and health outcomes.

Ecological factors and childhood eating behaviours at 5 years of age: findings from the ROLO longitudinal birth cohort study.

BACKGROUND: Individual differences in children eating behaviours have been linked with childhood overweight and obesity. The determinants of childhood eating behaviours are influenced by a complex combination of hereditary and ecological factors. This study examines if key ecological predictors of childhood overweight; maternal socio-economic status (SES), children's screen time, and childcare arrangements, are associated with eating behaviours in children aged 5-years-old. METHODS: This is secondary, cross-sectional analysis of the ROLO (Randomized COntrol Trial of LOw glycemic diet in pregnancy) study, using data from the 5-year follow-up (n = 306). Weight, height, and body mass index (BMI) were obtained from mothers and children at the 5-year follow-up. Children's BMI z-scores were calculated. SES was determined using maternal education level and neighborhood deprivation score. Information on children's screen time and childcare arrangements were collected using lifestyle questionnaires. Children's eating behaviours were measured using the Children's Eating Behaviour Questionnaire (CEBQ). Multiple linear regression, adjusted for potential confounders, assessed associations between maternal SES, screen time and children's eating behaviours. One-way ANOVA, independent sample t-tests and Spearman's correlation examined childcare exposure and children's eating behaviour. RESULTS: Mothers in the lowest SES group had higher BMI and were younger than those in the highest SES group (p = < 0.001, p = 0.03 respectively). In adjusted analysis, the lowest SES group was associated with a 0.463-point higher mean score for 'Desire to Drink' (95% CI = 0.054,0.870, p = 0.027) and higher 'Slowness to Eat' (B = 0.388, 95% CI = 0.044,0.733, p = 0.027) when compared with the highest SES group. Screen time (hours) was associated with higher 'Food Fussiness' (B = 0.032, 95% CI = 0.014,0.051, p = 0.001). Those who attended childcare had higher scores for 'Desire to Drink'(p = 0.046). No relationship was observed between longer duration (years) spent in childcare and eating behaviours. CONCLUSIONS: In this cohort, the ecological factors examined had an influence on children's eating behaviours aged 5-years-old. Our results illustrate the complexity of the relationship between the child's environment, eating behaviour and children's body composition. Being aware of the ecological factors that impact the development of eating behaviours, in the pre-school years is vital to promote optimal childhood appetitive traits, thus reducing the risk of issues with excess adiposity long-term.

Secondary Hyperparathyroidism in Children with Mucolipidosis Type II (I-Cell Disease): Irish Experience.

Mucolipidosis type II (ML II) is an autosomal recessive lysosomal targeting disorder that may present with features of hyperparathyroidism. The aim of this study was to describe in detail the clinical cases of ML II presenting to a tertiary referral centre with biochemical and/or radiological features of hyperparathyroidism. There were twenty-three children diagnosed with ML II in the Republic of Ireland from July 1998 to July 2021 inclusive (a 23-year period). The approximate incidence of ML II in the Republic of Ireland is, therefore, 1 per 64,000 live births. Medical records were available and were reviewed for 21 of the 23 children. Five of these had been identified as having biochemical and/or radiological features of hyperparathyroidism. Of these five, three children were born to Irish Traveller parents and two to non-Traveller Irish parents. All five children had radiological features of hyperparathyroidism (on skeletal survey), with evidence of antenatal fractures in three cases and an acute fracture in one. Four children had biochemical features of secondary hyperparathyroidism. Three children received treatment with high dose Vitamin D supplements and two who had antenatal/acute fractures were managed with minimal handling. We observed resolution of secondary hyperparathyroidism in all cases irrespective of treatment. Four of five children with ML II and hyperparathyroidism died as a result of cardiorespiratory failure at ages ranging from 10 months to 7 years. Biochemical and/or radiological evidence of hyperparathyroidism is commonly identified at presentation of ML II. Further studies are needed to establish the pathophysiology and optimal management of hyperparathyroidism in this cohort. Recognition of this association may improve diagnostic accuracy and management, facilitate family counseling and is also important for natural history data.

De-novo designed ß-lysine derivatives can both augment and diminish the proliferation rates of E. coli through the action of Elongation Factor P.

An investigation into the effect of modified ß-lysines on the growth rates of eubacterial cells is reported. It is shown that the effects observed are due to the post translational modification of Elongation Factor P (EFP) with these compounds catalysed by PoxA. PoxA was found to be remarkably promiscuous, which allowed the activity of a wide range of exogenous ß-lysines to be examined. Two chain-elongated ß-lysine derivatives which differ in aminoalkyl chain length by only 2 carbon units exhibited opposing biological activities - one promoting growth and the other retarding it. Both compounds were shown to operate through modification of EFP.

Accuracy of the ActivPAL and Fitbit Charge 2 in measuring step count in Cystic Fibrosis.

BACKGROUND: Physical activity (PA) is important in Cystic Fibrosis (CF) management. Fitness wearables are becoming increasingly popular as measurement tools of PA; however, the accuracy of these devices should first be evaluated. OBJECTIVE: The purpose of this study was to assess the accuracy of the ActivPAL and Fitbit Charge 2 as a measure of step count in Cystic Fibrosis. METHODS: Twenty-one participants were recruited from an adult CF Center in Ireland for a single session of testing. Participants walked for 5 min at five pre-determined speeds in a controlled testing environment (2, 2.5, 3, 3.5 and 4 miles per hour on a treadmill) and at three self-selected speeds in a corridor (slow, medium, and fast). They concurrently wore an accelerometer (ActivPAL) and fitness wearable (Fitbit Charge 2), and both were compared to visual observations. Step count is the outcome being assessed. RESULTS: The ActivPAL under-estimated step count by 0.63% across treadmill speeds and 1.1% across self-selected walking speeds. The Fitbit Charge 2 underestimated the step count by 2.97% across treadmill speeds and by 6.3% across self-selected walking speeds. Very strong correlations were found between the ActivPAL and visual observations (r: 0.93 to 0.99), while the Fitbit Charge 2 ranged from weak to very strong correlations when compared to visual observations (r: 0.34 to 0.84). CONCLUSION: The ActivPAL and Fitbit Charge 2 demonstrated acceptable validity for step count measurement in CF. These devices can be used for tracking PA during interventions in people with CF.

Sleep duration and eating behaviours are associated with body composition in 5-year-old children: findings from the ROLO longitudinal birth cohort study.

Inadequate sleep and poor eating behaviours are associated with higher risk of childhood overweight and obesity. Less is known about the influence sleep has on eating behaviours and consequently body composition. Furthermore, whether associations differ in boys and girls has not been investigated extensively. We investigate associations between sleep, eating behaviours and body composition in cross-sectional analysis of 5-year-old children. Weight, height, BMI, mid upper arm circumference (MUAC), abdominal circumference (AC) and skinfold measurements were obtained. Maternal reported information on child's eating behaviour and sleep habits were collected using validated questionnaires. Multiple linear regression examined associations between sleep, eating behaviours and body composition. Sleep duration was negatively associated with BMI, with 1-h greater sleep duration associated with 0·24 kg/m2 (B = 0·24, CI -0·42, -0·03, P = 0·026) lower BMI and 0·21 cm lower (B = -0·21, CI -0·41, -0·02, P = 0·035) MUAC. When stratified by sex, girls showed stronger inverse associations between sleep duration (h) and BMI (kg/m2) (B = -0·32; CI -0·60, -0·04, P = 0·024), MUAC (cm) (B = -0·29; CI -0·58, 0·000, P = 0·05) and AC (cm) (B = -1·10; CI -1·85, -0·21, P = 0·014) than boys. Positive associations for 'Enjoys Food' and 'Food Responsiveness' with BMI, MUAC and AC were observed in girls only. Inverse associations between sleep duration and 'Emotional Undereating' and 'Food Fussiness' were observed in both sexes, although stronger in boys. Sleep duration did not mediate the relationship between eating behaviours and BMI. Further exploration is required to understand how sleep impacts eating behaviours and consequently body composition and how sex influences this relationship.

Physical Activity and Sedentary Behavior in Adults With Cystic Fibrosis: Association With Aerobic Capacity, Lung Function, Sleep, Well-Being, and Quality of Life.

BACKGROUND: Physical activity (PA) and sedentary behavior (SB) have marked impact on key prognostic indicators such as aerobic capacity and lung function in people with cystic fibrosis (CF) and may have associations with sleep, well-being, and health-related quality of life (HRQOL). METHODS: This observational study assessed PA, SB, aerobic capacity, spirometry, sleep, well-being, and HRQOL in adults with CF at University Hospital Limerick. PA and SB were assessed using an accelerometer that was worn for 7 days. A cardiopulmonary exercise test assessed aerobic capacity. Spirometry was performed according to American Thoracic Society guidelines. Well-being was measured by the AWESCORE, sleep quality by the Pittsburgh Sleep Quality Index (PSQI), and HRQOL using the CF Questionnaire-Revised. RESULTS: Thirty-three participants (13 males/20 females) were recruited. Mean age was 26.2 y (± 7.1 SD), with mean FEV1 72.9% of predicted (± 26.2 SD). Mean step count was 7,788 (± 3,583 SD). Over 75% of participants did not reach recommended PA targets (> 10,000 steps), with females being 25.5% less active than males. The PSQI indicated 48.5% of participants scored > 5, indicating poor sleep quality. Number of steps and SB demonstrated a moderate significant correlation with FEV1 (r = 0.45, P = .030; r = -0.37, P = .043, respectively) and sleep quality (r = -0.85, P < .001; r = 0.77, P < .001, respectively). [Formula: see text] peak expressed relative to body weight, and as a percentage of predicted, was significantly positively correlated with step count (r = 0.48, P = .007; r = 0.42, P = .02, respectively) but did not correlate with SB (P = .96). [Formula: see text] peak (L/min) strongly correlated with FEV1 (r = 0.75, P < .001). CONCLUSIONS: Most participants did not meet PA targets. PA levels correlated to aerobic capacity, FEV1, and self-reported sleep quality, and this should be considered in longitudinal studies and in PA interventions.