Associations of diet quality and food consumption with serum biomarkers for lipid and amino acid metabolism in Finnish children: the PANIC study.

PURPOSE: To investigate the associations of overall diet quality and dietary factors with serum biomarkers for lipid and amino acid metabolism in a general population of children. METHODS: We studied 194 girls and 209 boys aged 6-8 years participating in the Physical Activity and Nutrition in Children study. Food consumption was assessed by 4-day food records and diet quality was quantified by the Finnish Children Healthy Eating Index (FCHEI). Fasting serum fatty acids, amino acids, apolipoproteins, as well as lipoprotein particle sizes were analyzed with high-throughput nuclear magnetic resonance spectroscopy. Data were analyzed using linear regression adjusted for age, sex, and body fat percentage. RESULTS: FCHEI was directly associated with the ratio of polyunsaturated (PUFA) to saturated fatty acids (SFA) (PUFA/SFA), the ratio of PUFA to monounsaturated fatty acids (MUFA) (PUFA/MUFA), the ratio of PUFA to total fatty acids (FA) (PUFA%), the ratio of omega-3-fatty acids to total FA (omega-3 FA%), and inversely associated with the ratio of MUFA to total FA (MUFA%), alanine, glycine, histidine and very-low density lipoprotein (VLDL) particle size. Consumption of vegetable oils and vegetable-oil-based margarine (≥ 60% fat) was directly associated with PUFA/SFA, PUFA/MUFA, PUFA%, the ratio of omega-6 FA to total FA (omega-6 FA%), and inversely associated with SFA, MUFA, SFA to total FA (SFA%), MUFA%, alanine and VLDL particle size. Consumption of high-fiber grain products directly associated with PUFA/SFA, PUFA/MUFA, omega-3 FA%, omega-6 FA%, PUFA% and inversely associated with SFA and SFA%. Fish consumption directly related to omega-3 FA and omega-3 FA%. Consumption of sugary products was directly associated with histidine and VLDL particle size. Vegetable, fruit, and berry consumption had direct associations with VLDL particle size and the ratio of apolipoprotein B to apolipoprotein A1. Consumption of low fat (< 1%) milk was directly associated with phenylalanine. A higher consumption of high-fat (≥ 1%) milk was associated with lower serum MUFA/SFA and higher SFA%. Sausage consumption was directly related to SFA% and histidine. Red meat consumption was inversely associated with glycine. CONCLUSIONS: Better diet quality, higher in intake of dietary sources of unsaturated fat and fiber, and lower in sugary product intake were associated with more favorable levels of serum biomarkers for lipid and amino acid metabolism independent of adiposity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01803776, registered March 3, 2013.

Psychological well-being of children and adolescents with inflammatory bowel disease.

OBJECTIVES: Prior studies on the psychological well-being in pediatric inflammatory bowel disease (PIBD) have reported controversial results. Our aim was to compare the psychological well-being and lifestyle factors in patients with PIBD and their controls and to assess the role of contributing disease characteristics. METHODS: This cross-sectional study included 60 PIBD patients aged 6-17 years (26 with Crohn's disease [CD], 34 with ulcerative colitis [UC] or unclassified colitis [IBD-U]) from two university hospitals in Finland, and their age- and sex-matched healthy controls. Psychological well-being was assessed with three measures: a questionnaire on overall psychological well-being (PSWB) and for adolescents also Beck Depression Inventory (BDI Ia) and Perceived Stress Scale (PSS). In addition to disease characteristics and pain, we assessed physical activity, sleep, screen time, and social well-being. RESULTS: Controls were more likely of stressing more (odds ratio [OR] = 3.67, 95% confidence interval [95% CI] 95% CI = 1.02-13.14), but other measures of psychological well-being did not differ statistically significantly between patients and controls. In CD, a clinically more active disease associated with inferior psychological well-being in adolescents (BDI [ρ = 0.63, p = 0.021], PSS [ρ = 0.70, p = 0.008], PSWB [ρ = 0.56, p = 0.049]). Longer time from diagnosis correlated with better psychological well-being on BDI (ρ = -0.39, p = 0.024) and PSS (ρ = -0.38, p = 0.034). Lifestyle was more sedentary in PIBD (less physical activity in children OR = 0.82, 95% CI = 0.68-0.99 and more screen time in adolescents OR = 1.18, 95% CI = 1.00-1.40). CONCLUSION: Although the clinical features of PIBD are potentially a burden for psychological well-being, many young patients cope well with their disease. Individual variation in well-being is remarkable, making supportive measures challenging.

Alanine aminotransferase cutoffs for the pediatric fatty liver disease: Major impact of the reference population.

OBJECTIVES AND STUDY: The often-recommended alanine aminotransferase (ALT) cutoffs (girls 21 U/l, boys 25 U/l) are based on a NHANES cohort. A novel concept of metabolic dysfunction associated steatotic liver disease (MASLD) emphasizes the role of ALT. We tested the prevalence of increased ALT and MASLD in children with overweight or obesity applying population-based and NHANES-based cut-offs. METHODS: Six- to seventeen-year-old children underwent data collection in a prospective Physical Activity and Nutrition in Children (PANIC) study. ALT 95th percentiles were calculated from 1167 separate measurements considering various confounders. Test cohort comprised 1044 children with overweight/obesity. RESULTS: ALT values increased at puberty onset (p = 0.031) and correlated negatively with age in girls (r = -0.222, p < 0.001). Particularly overall and central obesity increased ALT, whereas underweight or metabolic abnormalities had smaller effect. After applying the tested exclusions, the age-related ALT 95th percentiles were 24-29 U/l for girls and 29-32 U/l for boys. In 6-8-year-old children with overweight/obesity, the prevalence of increased ALT and MASLD were 21.6% and 2.4% with age-specific PANIC cutoffs. In older children, when NHANES-based cutoffs were used, there was a trend for higher prevalence of increased ALT and MASLD in all age groups for both sexes, reaching significance for increased ALT in 12-16-year-old boys (NHANES 63.5%, 95% confidence interval [CI]: 56.4%-70.0% vs. PANIC 47.1%, 95% CI [40.1%-54.2%]) and 9-11-year-old girls (60.0% [49.4%-69.8%] vs. 31.8% [22.8%-42.3%]), respectively. Increased ALT/MASLD were more common in boys than in girls, and in boys these increased with age, whereas in girls these peaked at age 9-12 years. CONCLUSION: A reference population impacts on the prevalence of increased ALT and MASLD. Considering this help optimizing screening while avoiding unnecessary investigations and surveillance. The prospective part of this study is registered in clinicaltrials.gov; identifier NCT01803776.

Maternal gestational hypertension, smoking and pre-eclampsia are associated with metabolic dysfunction-associated fatty liver disease in overweight offspring.

INTRODUCTION: Due to a steep increase in obesity, metabolic dysfunction-associated fatty liver disease (MAFLD) has also become the most common chronic hepatic condition among children and adolescents. Various maternal and pregnancy-related factors have also been implicated in the development of MAFLD, but human studies remain scarce. MATERIAL AND METHODS: Comprehensive data of 460 overweight or obese children aged 2-16 years were collected and combined with data on selected maternal and pregnancy-related factors for a case-control study. MALFD was defined as alanine aminotransferase >2× upper limit of normal. Children with and without MAFLD were compared regarding to the study variables and multivariable regression analysis was utilized. RESULTS: Median age of the study children was 11.8 (quartiles 9.1-14.2) years; 44% were girls and 17.8% had MAFLD. Children with MAFLD were older (12.7 vs. 11.6 years, p = 0.002), while the groups did not differ age-standardized body mass index (BMI-SDS) or gender. Factors associated with MAFLD in a multivariable model considering also the offspring's present BMI-SDS, sex, and maternal prepregnancy overweight, were child's older age (odds ratio [OR] 1.16, 95% confidence interval [CI]: 1.06-1.28), maternal gestational smoking (OR 2.01, 95% CI: 1.16-3.47), gestational hypertension (OR 3.44, 95% CI: 1.08-11.0) and pre-eclampsia (OR 2.93, 95% CI: 1.15-7.45). There was no significant association between MAFLD and maternal BMI, birth anthropometrics or perinatal complications. CONCLUSIONS: Maternal smoking, gestational hypertension and pre-eclampsia were associated with MAFLD among overweight or obese children. Further prospective studies are needed to verify causal relationships.

Associations between physical fitness and cerebellar gray matter volume in adolescents.

Despite the importance of the developing cerebellum on cognition, the associations between physical fitness and cerebellar volume in adolescents remain unclear. We explored the associations of physical fitness with gray matter (GM) volume of VI, VIIb and Crus I & II, which are cerebellar lobules related to cognition, in 40 (22 females; 17.9 ± 0.8 year-old) adolescents, and whether the associations were sex-specific. Peak oxygen uptake (V̇O2peak ) and power were assessed by maximal ramp test on a cycle ergometer, muscular strength with standing long jump (SLJ), speed-agility with the shuttle-run test (SRT), coordination with the Box and Block Test (BBT) and neuromuscular performance index (NPI) as the sum of SLJ, BBT and SRT z-scores. Body composition was measured using a dual-energy X-ray absorptiometry. Cerebellar volumes were assessed by magnetic resonance imaging. V̇O2peak relative to lean mass was inversely associated with the GM volume of the cerebellum (standardized regression coefficient (ß) = -0.038, 95% confidence interval (CI) -0.075 to 0.001, p = 0.044). Cumulative NPI was positively associated with the GM volume of Crus I (ß = 0.362, 95% CI 0.045 to 0.679, p = 0.027). In females, better performance in SRT was associated with a larger GM volume of Crus I (ß = -0.373, 95% CI -0.760 to -0.028, p = 0.036). In males, cumulative NPI was inversely associated with the GM volume of Crus II (ß = -0.793, 95% CI -1.579 to -0.008 p = 0.048). Other associations were nonsignificant. In conclusion, cardiorespiratory fitness, neuromuscular performance and speed-agility were associated with cerebellar GM volume, and the strength and direction of associations were sex-specific.

Cross-sectional and longitudinal associations between the 24-hour movement behaviours, including muscle and bone strengthening activity, with bone and lean mass from childhood to adolescence.

BACKGROUND: This study aimed to assess whether moderate-to-vigorous physical activity (MVPA), sport and exercise as a proxy measure of muscle and bone strengthening activity, sedentary behaviour, and sleep were associated with total-body-less-head (TBLH) bone mineral content (BMC) and TBLH lean mass cross-sectionally and longitudinally from age 6 to 9 years and age 9 to 11 years to age 15 to 17 years. METHODS: We used longitudinal data from a population sample of Finnish children from the Physical Activity and Nutrition in Children study (age 6 to 9 years: n = 478, 229 females; age 9 to 11 years: n = 384, 197 females; age 15 to 17 years: n = 222, 103 females). Linear regression analysed the cross-sectional and longitudinal associations between accelerometer-assessed MVPA, sedentary time and sleep, and questionnaire-assessed sport and exercise participation and screen time with dual-energy X-ray absorptiometry-assessed TBLH BMC and lean mass. RESULTS: In females, MVPA at age 6 to 9 years was positively associated with TBLH BMC at age 15 to 17 years (ß = 0.008, p = 0.010). Sport and exercise at age 9 to 11 years was positively associated with TBLH BMC (ß = 0.020, p = 0.002) and lean mass (ß = 0.343, p = 0.040) at age 15 to 17 years. MVPA at age 9 to 11 years was positively associated with TBLH lean mass (ß = 0.272, p = 0.004) at age 15 to 17 years. In males, sleep at age 6 to 9 years was positively associated with TBLH lean mass (ß = 0.382, p = 0.003) at age 15 to 17 years. Sport and exercise at age 9 to 11 years was positively associated with TBLH BMC (ß = 0.027, p = 0.012) and lean mass (ß = 0.721, p < 0.001) at age 15 to 17 years. CONCLUSIONS: Promoting engagement in the 24-hour movement behaviours in childhood, particularly sport and exercise to strengthen muscle and bone, is important in supporting bone and lean mass development in adolescence. TRIAL REGISTRATION: NCT01803776; first trial registration date: 04/03/2013.

Increased adiposity in juvenile idiopathic arthritis - A comparison of the bioelectrical impedance analysis and dual-energy X-ray absorptiometry for the assessment of body composition.

AIM: Higher adiposity and increased risk of cardiovascular diseases have been reported in juvenile idiopathic arthritis (JIA), but body composition measurements have produced inconsistent results. This controlled cross-sectional study assessed body composition with two methods to evaluate adiposity in children with JIA. METHODS: We measured body composition by dual- energy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) from 79 JIA-patients in two Finish university hospitals in 2017-2019. Their age- and sex-matched controls (n = 79) were selected from the Physical Activity and Nutrition in Children- study and through National Registry. RESULTS: Body fat percentage measured by BIA was higher (mean, SD) in patients compared to controls (23.1 ± 9.3% vs. 20.1 ± 7.5%, p = 0.047). Also, using DXA, there was a tendency of higher body fat percentage in patients (27.1 ± 9.1% vs. 24.6 ± 8.6, p = 0.106). BIA and DXA showed strong correlation (r from 0.810 to 0.977) in all body composition variables. CONCLUSION: Increased adiposity was observed in patients with JIA. Evaluation of body composition should be included in the multidisciplinary care of JIA to reduce the possible risk of cardiovascular diseases in adulthood. BIA could be a useful tool for assessing body composition due to its clinical availability and safety.

Sources of vitamin D and determinants of serum 25-hydroxyvitamin D in Finnish adolescents.

PURPOSE: To study the intake and sources of vitamin D and determinants of serum 25-hydroxyvitamin D (S-25(OH)D) in Finnish adolescents. METHODS: We studied 265 adolescents (117 girls) aged 15-17 years attending 8-year examinations of the PANIC Study, assessed diet using food records and other lifestyle factors by questionnaires, and analyzed S-25(OH)D by chemiluminescence immunoassay and determinants of S-25(OH)D using multivariate linear regression. RESULTS: Mean (standard deviation) of total vitamin D intake from food and supplements was 19.2 (13.1) µg/d, and that of dietary vitamin D intake was 9.9 (5.4) µg/d. Milk fortified with vitamin D was the main dietary source of vitamin D, providing 45% of daily intake. Altogether, 29% of the adolescents used no vitamin D supplements and 25% did not meet the recommended total vitamin D intake of 10 µg/d. Mean (standard deviation) of S-25(OH)D was 62.0 (18.8) nmol/l, and S-25(OH)D was < 50 nmol/l in 29.5% of the adolescents. Vitamin D intake from supplements was the main determinant of S-25(OH)D (ß = 0.465, p < 0.001), followed by consumption of milk products (ß = 0.251, p < 0.001), consumption of meat products (ß = 0.179, p = 0.002), travels to sunny countries (ß = 0.178, p = 0.002), and average daylight time (ß = 0.162, p = 0.004). CONCLUSION: Most of the adolescents had vitamin D intake at the recommended level, although a fourth did not meet the recommended total vitamin D intake of 10 µg/d and almost a third had S-25(OH)D < 50 nmol/l. More attention should be paid to the sufficient intake of vitamin D in adolescents who do not use vitamin D supplements or fortified milk products. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01803776, registered March 3, 2013.

Cross-sectional associations between physical fitness and biomarkers of inflammation in children-The PANIC study.

BACKGROUND: Systemic low-grade inflammation has been proposed as an underlying pathophysiological mechanism for cardiometabolic diseases. We investigated the associations of physical fitness with a systemic low-grade inflammatory state in a population sample of children. METHODS: Altogether 391 children aged 6-9 years were examined. Cardiorespiratory fitness (maximal power output, Wmax ) was assessed by a maximal cycle ergometer test and neuromuscular fitness by hand grip strength, sit-up, standing long jump, 50-meter shuttle run, static balance, sit-and-reach, and box and block tests. Body fat percentage (BF%) and lean mass (LM) were assessed by dual-energy X-ray absorptiometry (DXA). High sensitivity C-reactive protein (hs-CRP), leptin, leptin receptor, high molecular weight adiponectin (HMW-adiponectin), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and glycoprotein acetyls (GlycA) were assessed from fasting blood samples. The modified inflammatory score (IS) was calculated using the population-specific z-scores and formula (z hs-CRP + z leptin + z IL-6 + z TNF-α + z GlycA)-z leptin receptor-z HMW-adiponectin. The data were analyzed using linear regression analyses. RESULTS: Higher Wmax /kg of body mass (ß = -0.416, 95% CI = -0.514 to -0.318), higher number of completed sit-ups (ß = -0.147, 95% CI = -0.244 to -0.049), a longer distance jumped in the standing long jump test (ß = -0.270, 95% CI = -0.371 to -0.169), and a shorter time in the 50-meter shuttle run test (ß = 0.123, 95% CI = 0.022 to 0.223) were associated with lower IS. None of these associations remained statistically significant after adjustment for BF%. CONCLUSIONS: Higher physical fitness is associated with a more favorable inflammatory biomarker profile in children. However, the associations were explained by BF%.

Effects of 2-year dietary and physical activity intervention on cognition in children-a nonrandomized controlled trial.

BACKGROUND AND OBJECTIVE: We investigated the effects of a combined dietary and PA intervention on cognition in children and whether changes in diet quality, PA, sedentary behavior (SB), and sedentary time (ST) are associated with changes in cognition. METHODS: We conducted a 2-year nonrandomized controlled trial in 504 children aged 6-9 years at baseline. The children were allocated to a combined dietary and PA intervention group (n = 237) or a control group (n = 160) without blinding. INTERVENTIONS: The children and their parents allocated to the intervention group had six dietary counseling sessions of 30-45 min and six PA counseling sessions of 30-45 min during the 2-year intervention period. The children were also encouraged to participate in after-school exercise clubs. Cognition was assessed by the Raven's Colored Progressive Matrices. We assessed dietary factors by 4 days food records and computed the Baltic Sea Diet Score (BSDS) as a measure of diet quality. PA and ST were assessed by a combined heart rate and body movement monitor, types of PA and SB by a questionnaire. RESULTS: The intervention had no effect on cognition. Increased BSDS and consumption of low-fat milk and decreased consumption of red meat and sausages were associated with improved cognition over 2 years. Increased organized sports, ST, and reading were positively, while unsupervised PA, computer use, and writing were negatively associated with cognition. CONCLUSION: Combined dietary and PA intervention had no effect on cognition. Improved diet quality and increased organized sports and reading were associated with improved cognition.

Physical activity volume and intensity distribution in relation to bone, lean and fat mass in children.

Considering physical activity (PA) volume and intensity may provide novel insights into the relationships of PA with bone, lean, and fat mass. This study aimed to assess the associations of PA volume, PA intensity distribution, including moderate-to-vigorous PA (MVPA) with total-body-less-head bone mineral content (BMC), lean, and fat mass in children. A population sample of 290 Finnish children (158 females) aged 9-11 years from the Physical Activity and Nutrition in Children (PANIC) Study was studied. PA, including MVPA, was assessed with a combined heart rate and movement sensor, and the uniaxial acceleration was used to calculate average-acceleration (a proxy metric for PA volume) and intensity-gradient (reflective of PA intensity distribution). Linear regression analyzed the associations of PA volume, PA intensity and MVPA with BMC, lean mass, and fat mass assessed by dual-energy X-ray absorptiometry. PA volume was positively associated with BMC in females (unstandardised regression coefficient [ß] = 0.26) and males (ß = 0.47), and positively associated with lean (ß = 7.33) and negatively associated with fat mass in males (ß = -20.62). PA intensity was negatively associated with BMC in males (ß = -0.13). MVPA was positively associated with lean mass in females and males (ß = 0.007 to 0.012), and negatively associated with fat mass in females and males (ß = -0.030 to -0.029). PA volume may be important for improving BMC in females and males, and increasing lean and reducing fat mass in males, whereas MVPA may be important for favorable lean and fat outcomes in both sexes.

Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.

ACE2 expression in adipose tissue is associated with cardio-metabolic risk factors and cell type composition-implications for COVID-19.

BACKGROUND: COVID-19 severity varies widely. Although some demographic and cardio-metabolic factors, including age and obesity, are associated with increasing risk of severe illness, the underlying mechanism(s) are uncertain. SUBJECTS/METHODS: In a meta-analysis of three independent studies of 1471 participants in total, we investigated phenotypic and genetic factors associated with subcutaneous adipose tissue expression of Angiotensin I Converting Enzyme 2 (ACE2), measured by RNA-Seq, which acts as a receptor for SARS-CoV-2 cellular entry. RESULTS: Lower adipose tissue ACE2 expression was associated with multiple adverse cardio-metabolic health indices, including type 2 diabetes (T2D) (P = 9.14 × 10-6), obesity status (P = 4.81 × 10-5), higher serum fasting insulin (P = 5.32 × 10-4), BMI (P = 3.94 × 10-4), and lower serum HDL levels (P = 1.92 × 10-7). ACE2 expression was also associated with estimated proportions of cell types in adipose tissue: lower expression was associated with a lower proportion of microvascular endothelial cells (P = 4.25 × 10-4) and higher proportion of macrophages (P = 2.74 × 10-5). Despite an estimated heritability of 32%, we did not identify any proximal or distal expression quantitative trait loci (eQTLs) associated with adipose tissue ACE2 expression. CONCLUSIONS: Our results demonstrate that individuals with cardio-metabolic features known to increase risk of severe COVID-19 have lower background ACE2 levels in this highly relevant tissue. Reduced adipose tissue ACE2 expression may contribute to the pathophysiology of cardio-metabolic diseases, as well as the associated increased risk of severe COVID-19.

Associations of diet quality, food consumption, eating frequency and eating behaviour with dental caries experience in Finnish children: a 2-year longitudinal study.

We examined cross-sectional and longitudinal associations of dietary factors with caries experience in a population sample of 487 children aged 6-9 years at baseline examinations of the Physical Activity and Nutrition in Children (PANIC) Study. Altogether, 406 of these children attended 2-year follow-up examinations. Food consumption and eating frequency were assessed using 4-day food records, diet quality using the Baltic Sea Diet Score (BSDS) and eating behaviour using the Children's Eating Behavior Questionnaire. Caries experience was examined clinically. The cross-sectional associations of dietary factors with caries experience at baseline were analysed using linear regression and the longitudinal associations of dietary factors with a change in caries experience over follow-up using generalised mixed-effects regression adjusted for other risk factors. A higher consumption of high-fibre grain products (standardised regression coefficient ß = -0·16, P = 0·003) and milk (ß = -0·11, P = 0·025) and higher BSDS (ß = -0·15, P = 0·007) were associated with lower caries experience, whereas a higher consumption of potatoes (ß = 0·11, P = 0·048) and emotional overeating (ß = 0·12, P = 0·025) were associated with higher caries experience. Higher snacking frequency (fixed coefficient ß = 0·07, P = 0·033), desire to drink (ß = 0·10, P = 0·046), slowness in eating (ß = 0·12, P = 0·027) and food fussiness (ß = 0·12, P = 0·018) were associated with higher caries experience, whereas enjoyment of food (ß = -0·12, P = 0·034) and higher BSDS (ß = -0·02, P = 0·051) were associated with lower caries experience.

Longitudinal and cross-sectional associations of adherence to 24-hour movement guidelines with cardiometabolic risk.

This study aimed to examine (1) adherence to 24 h movement guidelines over a 2 years follow-up in children aged 6-8 years and (2) association of this adherence with cardiometabolic risk factors. Physical activity and sleep were assessed by a monitor combining heart rate and accelerometry measurements. Screen time was reported by the parents. Body fat percentage, waist circumference, blood glucose, serum insulin, plasma lipids, and blood pressure were assessed, and a cardiometabolic risk score was calculated using z-scores. Children were classified as meeting the guidelines if they had on average ≥60 min/day of moderate-to-vigorous physical activity during the valid days; ≤120 min/day of screen time; and 9-11 h/day of sleep. In total, 485 children had valid data at baseline or at 2 years follow-up. Analyses were conducted using adjusted logistic and linear regression models. Most children adhered to the 24 h movement guidelines at baseline, but the adherence decreased over the 2 years follow-up. Meeting physical activity guidelines individually, or in combination with screen time and/or sleep, was longitudinally associated with a lower cardiometabolic risk score, insulin and waist circumference, and cross-sectionally additionally with lower diastolic blood pressure and higher high-density lipoprotein cholesterol. However, these associations became statistically non-significant after adjustment for body fat. In conclusion, meeting 24 h movement guidelines at baseline increases the odds of meeting them at 2 years follow-up in school-aged children. Furthermore, meeting 24 h movement guidelines is associated with lower levels of cardiometabolic risk factors, but these associations are partly explained by lower body fat. Thus, promoting movement behaviors, especially physical activity, and healthy weight in early childhood is important in supporting cardiometabolic health in children.

Prevalence of Erosive Tooth Wear and Associated Dietary Factors among a Group of Finnish Adolescents.

The aim of this study was to investigate the prevalence and severity of erosive tooth wear (ETW) among Finnish adolescents and to evaluate how frequency as well as amount of the use of erosive products is associated with ETW. The study population consisted of 328 voluntary, >15-year-old secondary school students (males 49.1%, females 50.9%) in three municipalities in Finland. Clinical examination to measure ETW (BEWE index) was carried out by trained and calibrated dentists. Piloted questionnaires included questions on consumption of drinks, fruits and berries, as well as tooth brushing frequency. Means and medians of frequencies and amounts of consumed erosive products were calculated and associations with ETW severity were analysed by logistic regression models. One-third (36.9%) of the participants were in need of at least preventive measures for ETW (BEWE sum score ≥3), but severe ETW (BEWE sum score >9) was rare (2.1%). Boys had severe ETW significantly more frequently than girls (p < 0.001). Habitual consumption of erosive drinks was common especially among boys compared to girls (p = 0.001). ETW was significantly associated with the amount of consumed erosive drinks, fruits, or berries. The prevalence of ETW among adolescences in Finland seems to be at the same level as in other Nordic and European countries. Consumption of erosive products is common and thus, the risk for tooth erosion is high, especially in boys. In addition to erosive drinks, also berries and fruits are associated with ETW and should be included in individual dietary counselling when early signs of ETW are clinically detected.

Integrative analysis of gene expression, DNA methylation, physiological traits, and genetic variation in human skeletal muscle.

We integrate comeasured gene expression and DNA methylation (DNAme) in 265 human skeletal muscle biopsies from the FUSION study with >7 million genetic variants and eight physiological traits: height, waist, weight, waist-hip ratio, body mass index, fasting serum insulin, fasting plasma glucose, and type 2 diabetes. We find hundreds of genes and DNAme sites associated with fasting insulin, waist, and body mass index, as well as thousands of DNAme sites associated with gene expression (eQTM). We find that controlling for heterogeneity in tissue/muscle fiber type reduces the number of physiological trait associations, and that long-range eQTMs (>1 Mb) are reduced when controlling for tissue/muscle fiber type or latent factors. We map genetic regulators (quantitative trait loci; QTLs) of expression (eQTLs) and DNAme (mQTLs). Using Mendelian randomization (MR) and mediation techniques, we leverage these genetic maps to predict 213 causal relationships between expression and DNAme, approximately two-thirds of which predict methylation to causally influence expression. We use MR to integrate FUSION mQTLs, FUSION eQTLs, and GTEx eQTLs for 48 tissues with genetic associations for 534 diseases and quantitative traits. We identify hundreds of genes and thousands of DNAme sites that may drive the reported disease/quantitative trait genetic associations. We identify 300 gene expression MR associations that are present in both FUSION and GTEx skeletal muscle and that show stronger evidence of MR association in skeletal muscle than other tissues, which may partially reflect differences in power across tissues. As one example, we find that increased RXRA muscle expression may decrease lean tissue mass.

Digitally Supported Lifestyle Intervention to Prevent Type 2 Diabetes Through Healthy Habits: Secondary Analysis of Long-Term User Engagement Trajectories in a Randomized Controlled Trial.

BACKGROUND: Digital health interventions may offer a scalable way to prevent type 2 diabetes (T2D) with minimal burden on health care systems by providing early support for healthy behaviors among adults at increased risk for T2D. However, ensuring continued engagement with digital solutions is a challenge impacting the expected effectiveness. OBJECTIVE: We aimed to investigate the longitudinal usage patterns of a digital healthy habit formation intervention, BitHabit, and the associations with changes in T2D risk factors. METHODS: This is a secondary analysis of the StopDia (Stop Diabetes) study, an unblinded parallel 1-year randomized controlled trial evaluating the effectiveness of the BitHabit app alone or together with face-to-face group coaching in comparison with routine care in Finland in 2017-2019 among community-dwelling adults (aged 18 to 74 years) at an increased risk of T2D. We used longitudinal data on usage from 1926 participants randomized to the digital intervention arms. Latent class growth models were applied to identify user engagement trajectories with the app during the study. Predictors for trajectory membership were examined with multinomial logistic regression models. Analysis of covariance was used to investigate the association between trajectories and 12-month changes in T2D risk factors. RESULTS: More than half (1022/1926, 53.1%) of the participants continued to use the app throughout the 12-month intervention. The following 4 user engagement trajectories were identified: terminated usage (904/1926, 46.9%), weekly usage (731/1926, 38.0%), twice weekly usage (208/1926, 10.8%), and daily usage (83/1926, 4.3%). Active app use during the first month, higher net promoter score after the first 1 to 2 months of use, older age, and better quality of diet at baseline increased the odds of belonging to the continued usage trajectories. Compared with other trajectories, daily usage was associated with a higher increase in diet quality and a more pronounced decrease in BMI and waist circumference at 12 months. CONCLUSIONS: Distinct long-term usage trajectories of the BitHabit app were identified, and individual predictors for belonging to different trajectory groups were found. These findings highlight the need for being able to identify individuals likely to disengage from interventions early on, and could be used to inform the development of future adaptive interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03156478; https://clinicaltrials.gov/ct2/show/NCT03156478. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12889-019-6574-y.

Primary hand motor representation areas in healthy children, preadolescents, adolescents, and adults.

The development of the organization of the motor representation areas in children and adolescents is not well-known. This cross-sectional study aimed to provide an understanding for the development of the functional motor areas of the upper extremity muscles by studying healthy right-handed children (6-9 years, n = 10), preadolescents (10-12 years, n = 13), adolescents (15-17 years, n = 12), and adults (22-34 years, n = 12). The optimal representation site and resting motor threshold (rMT) for the abductor pollicis brevis (APB) were assessed in both hemispheres using navigated transcranial magnetic stimulation (nTMS). Motor mapping was performed at 110% of the rMT while recording the EMG of six upper limb muscles in the hand and forearm. The association between the motor map and manual dexterity (box and block test, BBT) was examined. The mapping was well-tolerated and feasible in all but the youngest participant whose rMT exceeded the maximum stimulator output. The centers-of-gravity (CoG) for individual muscles were scattered to the greatest extent in the group of preadolescents and centered and became more focused with age. In preadolescents, the CoGs in the left hemisphere were located more laterally, and they shifted medially with age. The proportion of hand compared to arm representation increased with age (p = 0.001); in the right hemisphere, this was associated with greater fine motor ability. Similarly, there was less overlap between hand and forearm muscles representations in children compared to adults (p<0.001). There was a posterior-anterior shift in the APB hotspot coordinate with age, and the APB coordinate in the left hemisphere exhibited a lateral to medial shift with age from adolescence to adulthood (p = 0.006). Our results contribute to the elucidation of the developmental course in the organization of the motor cortex and its associations with fine motor skills. It was shown that nTMS motor mapping in relaxed muscles is feasible in developmental studies in children older than seven years of age.

Cost-effectiveness of physical activity intervention in children - results based on the Physical Activity and Nutrition in Children (PANIC) study.

BACKGROUND: We assessed the cost-effectiveness of a 2-year physical activity (PA) intervention combining family-based PA counselling and after-school exercise clubs in primary-school children compared to no intervention from an extended service payer's perspective. METHODS: The participants included 506 children (245 girls, 261 boys) allocated to an intervention group (306 children, 60 %) and a control group (200 children, 40 %). The children and their parents in the intervention group had six PA counselling visits, and the children also had the opportunity to participate in after-school exercise clubs. The control group received verbal and written advice on health-improving PA at baseline. A change in total PA over two years was used as the outcome measure. Intervention costs included those related to the family-based PA counselling, the after-school exercise clubs, and the parents' taking time off to travel to and participate in the counselling. The cost-effectiveness analyses were performed using the intention-to-treat principle. The costs per increased PA hour (incremental cost-effectiveness ratio, ICER) were based on net monetary benefit (NMB) regression adjusted for baseline PA and background variables. The results are presented with NMB and cost-effectiveness acceptability curves. RESULTS: Over two years, total PA increased on average by 108 h in the intervention group (95 % confidence interval [CI] from 95 to 121, p < 0.001) and decreased by 65.5 h (95 % CI from 81.7 to 48.3, p < 0.001) in the control group, the difference being 173.7 h. the incremental effectiveness was 87 (173/2) hours. For two years, the intervention costs were €619 without parents' time use costs and €860 with these costs. The costs per increased PA hour were €6.21 without and €8.62 with these costs. The willingness to pay required for 95 % probability of cost-effectiveness was €14 and €19 with these costs. The sensitivity analyses revealed that the ICER without assuming this linear change in PA were €3.10 and €4.31. CONCLUSIONS: The PA intervention would be cost-effective compared to no intervention among children if the service payer's willingness-to-pay for a 1-hour increase in PA is €8.62 with parents' time costs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01803776. Registered 4 March 2013 - Retrospectively registered, https://clinicaltrials.gov/ct2/results?cond=&term=01803776&cntry=&state=&city=&dist= .