All exons are not created equal-exon vulnerability determines the effect of exonic mutations on splicing.

It is now widely accepted that aberrant splicing of constitutive exons is often caused by mutations affecting cis-acting splicing regulatory elements (SREs), but there is a misconception that all exons have an equal dependency on SREs and thus a similar vulnerability to aberrant splicing. We demonstrate that some exons are more likely to be affected by exonic splicing mutations (ESMs) due to an inherent vulnerability, which is context dependent and influenced by the strength of exon definition. We have developed VulExMap, a tool which is based on empirical data that can designate whether a constitutive exon is vulnerable. Using VulExMap, we find that only 25% of all exons can be categorized as vulnerable, whereas two-thirds of 359 previously reported ESMs in 75 disease genes are located in vulnerable exons. Because VulExMap analysis is based on empirical data on splicing of exons in their endogenous context, it includes all features important in determining the vulnerability. We believe that VulExMap will be an important tool when assessing the effect of exonic mutations by pinpointing whether they are located in exons vulnerable to ESMs.

Auditory Profile-Based Hearing Aid Fitting: Self-Reported Benefit for First-Time Hearing Aid Users.

Background: Although hearing aids (HAs) can compensate for reduced audibility, functional outcomes and benefits vary widely across individuals. As part of the Danish 'Better hEAring Rehabilitation' (BEAR) project, four distinct auditory profiles differing in terms of audiometric thresholds and supra-threshold hearing abilities were recently identified. Additionally, profile-specific HA-fitting strategies were proposed. The aim of the current study was to evaluate the self-reported benefit of these profile-based HA fittings in a group of new HA users. Methods: A total of 205 hearing-impaired older adults were recruited from two Danish university hospitals. Participants were randomly allocated to one of two treatment groups: (1) NAL-NL2 gain prescription combined with default advanced feature settings ('reference fitting') or (2) auditory profile-based fitting with tailored gain prescription and advanced feature settings ('BEAR fitting'). Two months after treatment, the participants completed the benefit version of the short form of the Speech, Spatial, and Qualities of Hearing Scale (SSQ12-B) and the International Outcome Inventory for Hearing Aids (IOI-HA) questionnaire. Results: Overall, participants reported a clear benefit from HA treatment. However, no significant differences in the SSQ12-B or IOI-HA scores between the reference and BEAR fittings were found. Conclusion: First-time users experience clear benefits from HA treatment. Auditory profile-based HA fitting warrants further investigation.

Experiences of older vulnerable people with ischemic heart disease and their peer mentors: A qualitative process evaluation.

AIM: To understand the content and context of a realized peer mentor intervention, and to explore how mentors and mentees experienced the intervention. DESIGN: The study was designed as a qualitative process evaluation of a 24-week peer mentor intervention. METHODS: Semi-structured individual interviews were conducted from November 2021 to May 2022 in a purposeful sample of older vulnerable people with ischemic heart disease, referred to as mentees (n = 13), and their peer mentors (n = 12). Thematic analysis was used to analyse, categorize and interpret interview data. RESULTS: Five themes captured the content and context of the peer mentor intervention as experienced by mentors and mentees. 'Takes one to know one', stressing the importance of the mentor-mentee matching process; 'Varying demand for mentors', illustrating the difficulties in predicting who has the greatest need for mentoring; 'Varying degree of familiarity', describing the mentor-mentee relationship as a continuum from formal mentor to informal friend; 'Putting the patient first', illustrating how mentors support mentees based on their personal experiences of successful recovery while letting the mentee set the pace and goals; and 'Varying view of success', showing how intervention success is perceived differently by mentors and mentees. CONCLUSIONS: The study provides new knowledge on how and under what contextual circumstances a mentor intervention works. These findings are important for the implementation of future peer mentor interventions to achieve successful peer mentor support. IMPLICATIONS AND IMPACT: Non-attendance and drop-out from the cardiac rehabilitation program are prevalent problems among older vulnerable people with cardiovascular disease. This study describes a low-cost peer mentor intervention that can support this group of patients. REPORTING METHOD: Standards for reporting qualitative research (SRQR) guided our study. PATIENT OR PUBLIC CONTRIBUTION: A board of cardiovascular patients have contributed to the development and implementation of the intervention being evaluated.

Satisfaction with and perceived benefits of needs-assessment related to rehabilitation after chemotherapy among patients with breast cancer.

PURPOSE: To investigate satisfaction with and perceived benefits of a model of needs-assessment related to rehabilitation (NARR) in women with early breast cancer after (neo)adjuvant chemotherapy. MATERIALS AND METHODS: Mixed methods were applied using survey (N = 200) along with interviews (N = 20). The survey included measurement of distress and self-assessed need of and satisfaction with the NARR. Type of experienced side/late effects were registered along with numbers of and reasons for referrals to rehabilitation. Individual semi-structured interviews were conducted. Quantitative data were analyzed using descriptive statistics, and qualitative data were analyzed with thematic analysis. RESULTS: Overall, 217 patients participated in a NARR and 200 (92%) accepted participation in the survey. Furthermore, 20/37 (54%) invited patients were interviewed. After the NARR, 39 patients (20%) were referred to rehabilitation. While satisfaction was high, findings regarding distress and need of the NARR were equivocal and indicated a need for talking about experiences throughout the cancer trajectory. CONCLUSIONS: While only 20% had rehabilitation needs, satisfaction with the NARR was high and patients benefitted from being confirmed in normality of their experiences. It is recommended to address patients' side/late effects after chemotherapy for early breast cancer to identify rehabilitation needs, reduce distress, and improve quality of life.

One fifth of patients with early breast cancer were referred to rehabilitation after needs-assessments conducted 2 months after chemotherapy termination.Higher distress and higher self-reported need were significantly associated with not working and experiencing a higher number of side effects/late effects.It is recommended to address patients' side effects/late effects, including psychological distress, after termination of chemotherapy for early breast cancer to identify rehabilitation needs, reduce distress, and ultimately improve quality of life.

Epidermal Acyl-CoA-binding protein is indispensable for systemic energy homeostasis.

OBJECTIVES: The skin is the largest sensory organ of the human body and plays a fundamental role in regulating body temperature. However, adaptive alterations in skin functions and morphology have only vaguely been associated with physiological responses to cold stress or sensation of ambient temperatures. We previously found that loss of acyl-CoA-binding protein (ACBP) in keratinocytes upregulates lipolysis in white adipose tissue and alters hepatic lipid metabolism, suggesting a link between epidermal barrier functions and systemic energy metabolism. METHODS: To assess the physiological responses to loss of ACBP in keratinocytes in detail, we used full-body ACBP-/- and skin-specific ACBP-/- knockout mice to clarify how loss of ACBP affects 1) energy expenditure by indirect calorimetry, 2) response to high-fat feeding and a high oral glucose load, and 3) expression of brown-selective gene programs by quantitative PCR in inguinal WAT (iWAT). To further elucidate the role of the epidermal barrier in systemic energy metabolism, we included mice with defects in skin structural proteins (ma/ma Flgft/ft) in these studies. RESULTS: We show that the ACBP-/- mice and skin-specific ACBP-/- knockout mice exhibited increased energy expenditure, increased food intake, browning of the iWAT, and resistance to diet-induced obesity. The metabolic phenotype, including browning of the iWAT, was reversed by housing the mice at thermoneutrality (30 °C) or pharmacological ß-adrenergic blocking. Interestingly, these findings were phenocopied in flaky tail mice (ma/ma Flgft/ft). Taken together, we demonstrate that a compromised epidermal barrier induces a ß-adrenergic response that increases energy expenditure and browning of the white adipose tissue to maintain a normal body temperature. CONCLUSIONS: Our findings show that the epidermal barrier plays a key role in maintaining systemic metabolic homeostasis. Thus, regulation of epidermal barrier functions warrants further attention to understand the regulation of systemic metabolism in further detail.

Vitamin D-related genes and cardiometabolic markers in healthy children: a Mendelian randomisation study.

Observational studies show associations between low serum 25-hydroxyvitamin D (25(OH)D) and cardiometabolic risk markers. This Mendelian randomisation study examined associations between cardiometabolic markers in children and SNP in genes related to vitamin D metabolism (DHCR7; group-specific complement (GC); cytochrome P450 subfamily IIR1 (CYP2R1); and CYP24A1) and action (CYP27B1 and VDR). In 699 healthy 8-11-year-old children, we genotyped eleven SNP. We generated a genetic risk score based on SNP associated with low 25(OH)D and investigated associations between this and blood pressure, plasma lipids and insulin. Furthermore, we examined whether SNP related to vitamin D actions modified associations between 25(OH)D and the cardiometabolic markers. All GC and CYP2R1 SNP influenced serum 25(OH)D. A risk score based on four of the six SNP was associated with 3·4 (95 % CI 2·6, 4·2) mmol/l lower 25(OH)D per risk allele (P < 0·001), but was not associated with the cardiometabolic markers. However, interactions were indicated for the three VDR SNP (Pinteraction < 0·081) on associations between 25(OH)D and TAG, systolic blood pressure and insulin, which all decreased with increasing 25(OH)D only in major allele homozygotes (ß -0·02 (95 % CI -0·04, -0·01) mmol/l; ß -0·5 (95 % CI -0·9, -0·1) mmHg; and ß -0·5 (95 % CI -1·4, 0·3) pmol/l, respectively). In conclusion, genetic variation affected 25(OH)D substantially, but the genetic score was not associated with cardiometabolic markers in children. However, VDR polymorphisms modified associations with vitamin D, which warrants further investigation of VDR's role in the relationship between vitamin D and cardiometabolic risk.

[Dercum's disease].

Dercum's disease is a rare disease, which mainly affects women and has an unknown prevalence and aetiology. The disease is characterised by generalised obesity and more than three-month painful subcutaneous adipose tissue not responding to usual pain treatment. A suggested classi-fication of the disease includes four types: generalised diffuse, generalised nodular, localised nodular and juxta-articular. Diagnosis is one of exclusion, and treatment includes medical and surgical options with the aim of pain palliation and increased mobility and function.

PET/DW-MRI for evaluating treatment in chronic hepatitis C patients.

This feasibility study set out to investigate the use of FDG-PET/DW-MRI in chronic hepatitis C patients to examine changes in local liver inflammation after treatment with direct-acting antivirals (DAA). Twelve patients with chronic hepatitis C were prospectively enrolled, performing FDG-PET/DW-MRI prior to and after DAA treatment. PET/DW-MRI included PET acquisition 60 and 90 min after FDG-injection, DIXON, for attenuation correction, T2- and DW-MRI with 10 b-values between 0-700 s/mm2. The following parameters were measured from fusion of 3 volumes of interest (VOIs) placed in the liver parenchyma: Mean standard uptake value after 60 and 90 minutes (SUVmean60 and SUVmean90), total Apparent Diffusion Coefficient (ADC), perfusion fraction (PF), pseudo-diffusion (D*) and perfusion-free diffusion (D). We found PET/DW-MRI of chronic hepatitis C patients to be feasible. Patients were cooperative, tolerated the scans well and the image quality was acceptable. A total of 10 patients were available for final analysis. All patients achieved sustained virologic response and normalized alanine-aminotransferase (ALAT) levels after treatment with DAA. Perfusion fraction measured by DW-MRI changed significantly after treatment, from mean 0.21 (± 0.04) to 0.26 (± 0.06), P=0.005 and D* from 0.50 (± 0.13) × 10-3 s/mm2 to 0.62 (± 0.15) × 10-3 s/mm2, P=0.028. All other parameters, including FDG-uptake, was unchanged. These results suggest that liver perfusion is changed shortly after DAA treatment, with no significant change in inflammation. The study concludes that PET/DW-MR is feasible in quantifying perfusion and possibly inflammation in chronic hepatitis C patients and may be used to follow treatment.

Common genetic variants are associated with lower serum 25-hydroxyvitamin D concentrations across the year among children at northern latitudes.

In a longitudinal study including 642 healthy 8-11-year-old Danish children, we investigated associations between vitamin D dependent SNP and serum 25-hydroxyvitamin D (25(OH)D) concentrations across a school year (August-June). Serum 25(OH)D was measured three times for every child, which approximated measurements in three seasons (autumn, winter, spring). Dietary and supplement intake, physical activity, BMI and parathyroid hormone were likewise measured at each time point. In all, eleven SNP in four vitamin D-related genes: Cytochrome P450 subfamily IIR1 (CYP2R1); 7-dehydrocholesterol reductase/nicotinamide adenine dinucleotide synthetase-1(DHCR7/NADSYN1); group-specific complement (GC); and vitamin D receptor were genotyped. We found minor alleles of CYP2R1 rs10500804, and of GC rs4588 and rs7041 to be associated with lower serum 25(OH)D concentrations across the three seasons (all P<0·01), with estimated 25(OH)D differences of -5·8 to -10·6 nmol/l from major to minor alleles homozygosity. In contrast, minor alleles homozygosity of rs10741657 and rs1562902 in CYP2R1 was associated with higher serum 25(OH)D concentrations compared with major alleles homozygosity (all P<0·001). Interestingly, the association between season and serum 25(OH)D concentrations was modified by GC rs7041 (P interaction=0·044), observed as absence of increase in serum 25(OH)D from winter to spring among children with minor alleles homozygous genotypes compared with the two other genotypes of rs7041 (P<0·001). Our results suggest that common genetic variants are associated with lower serum 25(OH)D concentrations across a school year. Potentially due to modified serum 25(OH)D response to UVB sunlight exposure. Further confirmation and paediatric studies investigating vitamin D-related health outcomes of these genotypic differences are needed.

The Effect of Game-Based Interventions in Rehabilitation of Diabetics: A Systematic Review and Meta-Analysis.

INTRODUCTION: Game-based interventions have been proposed as a way to improve both patient adherence to physical activity (PA) and disease-related knowledge to achieve better self-management of blood glucose levels (HbA1c). The objective of this study was to systematically review the literature on the effect of game-based interventions on HbA1c, diabetes-related knowledge, and physical outcomes in rehabilitation of diabetes patients. METHODS: We conducted a systematic literature search in MEDLINE, EMBASE, PEDro, Scopus, Cochrane Central Register of Controlled Trials, CINAHL, and Psych INFO in October 2014 based on a priori defined inclusion criteria: patients with diabetes (type 1 or type 2), game-based interventions, and randomized controlled trials. RESULTS: The database search identified 1,101 potential articles for screening, four of which were eligible for the present systematic review. Game-based interventions show no effect on HbA1c (three studies) standardized mean difference = -0.10, 95% confidence interval = [-0.33, 0.14] compared to usual care or waiting lists. Game-based interventions were superior to controls in improving health-related quality of life, muscle strength, and balance (one study). No difference was found between game-based interventions and usual care or waiting lists in terms of diabetes-related knowledge (one study). DISCUSSION: PA is important for diabetes management. The present review indicates that game-based interventions are not superior to ordinary PA in controlling HbA1c. Due to the weak methodological quality of the included studies and the very low body of evidence, the likelihood that the real effect of game-based interventions will be substantially different (i.e., large enough difference to possibly affect decision-making) is high.

Vitamin D status and its determinants during autumn in children at northern latitudes: a cross-sectional analysis from the optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study.

Sufficient summer/autumn vitamin D status appears important to mitigate winter nadirs at northern latitudes. We conducted a cross-sectional study to evaluate autumn vitamin D status and its determinants in 782 Danish 8-11-year-old children (55°N) using baseline data from the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study, a large randomised controlled trial. Blood samples and demographic and behavioural data, including 7-d dietary recordings, objectively measured physical activity, and time spent outdoors during school hours, were collected during September-November. Mean serum 25-hydroxyvitamin D (25(OH)D) was 60·8 (sd 18·7) nmol/l. Serum 25(OH)D levels ≤50 nmol/l were found in 28·4 % of the children and 2·4 % had concentrations <25 nmol/l. Upon multivariate adjustment, increasing age (per year) (ß -2·9; 95 % CI -5·1, -0·7 nmol/l), female sex (ß -3·3; 95 % CI -5·9, -0·7 nmol/l), sampling in October (ß -5·2; 95 % CI -10·1, -0·4 nmol/l) and November (ß -13·3; 95 % CI -17·7, -9·1), and non-white ethnicity (ß -5·7; 95 % CI -11·1, -0·3 nmol/l) were negatively associated with 25(OH)D (all P<0·05). Likewise, immigrant/descendant background was negatively associated with 25(OH)D, particularly in females (ß -16·3; 95 % CI -21·9, -10·7) (P<0·001) (P interaction=0·003). Moderate-to-vigorous physical activity (MVPA) (min/d) (ß 0·06; 95 % CI 0·01, 0·12), outdoor walking during school hours (min/week) (ß 0·4; 95 % CI 0·1, 0·6) and intake of vitamin D-containing supplements ≥3 d/week (ß 8·7; 95 % CI 6·4, 11·0) were positively associated with 25(OH)D (all P<0·05). The high proportion of children with vitamin D status below the recommended sufficiency level of 50 nmol/l raises concern as levels expectedly drop further during winter months. Frequent intake of vitamin D supplements was strongly associated with status. MVPA and outdoor activity during school hours should be investigated further in interventions to improve autumn vitamin D status in children at northern latitudes.

Seasonal variations in growth and body composition of 8-11-y-old Danish children.

BACKGROUND: Earlier studies on seasonality in growth reported the largest height gains during spring and largest body weight gains during autumn. We examined seasonality in height, body weight, BMI, fat mass index (FMI), and fat-free mass index (FFMI) among contemporary Danish 8-11-y olds. METHODS: A total of 760 children from the OPUS School Meal Study provided >2,200 measurements on height, body weight, and composition between September and June. Average velocities were calculated using change-score analyses based on 3-mo intervals. As a complementary analysis, point velocities derived from estimated growth curves were fitted using semiparametric regression that included covariate adjustment and allowed flexible modeling of the time trend. RESULTS: Average velocities showed the following trends: height was higher than the average (6.10 cm/y) in January-April. Body weight was below the average (4.02 kg/y) in August-January and above in January-May; BMI (average: 0.49 kg/ m(2)/y) and FFMI (average: 0.17 kg/m(2)/y) showed similar trends. In contrast, FMI was above the average (0.38 kg/m(2)/y) in November-March. Similar trends were seen for point velocities. CONCLUSION: Our findings suggest seasonality in growth and body composition of Danish children. We recovered the well-known height velocity peak during spring time, but unlike earlier studies, we found coincident peaks in body weight, BMI, and FFMI velocities.

Effects of school meals with weekly fish servings on vitamin D status in Danish children: secondary outcomes from the OPUS (Optimal well-being, development and health for Danish children through a healthy New Nordic Diet) School Meal Study.

Children's vitamin D intake and status can be optimised to meet recommendations. We investigated if nutritionally balanced school meals with weekly fish servings affected serum 25-hydroxyvitamin D (25(OH)D) and markers related to bone in 8- to 11-year-old Danish children. We conducted an explorative secondary outcome analysis on data from 784 children from the OPUS School Meal Study, a cluster-randomised cross-over trial where children received school meals for 3 months and habitual lunch for 3 months. At baseline, and at the end of each dietary period, 25(OH)D, parathyroid hormone (PTH), osteocalcin (OC), insulin-like growth factor-1 (IGF-1), bone mineral content (BMC), bone area (BA), bone mineral density (BMD), dietary intake and physical activity were assessed. School meals increased vitamin D intake by 0·9 (95 % CI 0·7, 1·1) µg/d. No consistent effects were found on 25(OH)D, BMC, BA, BMD, IGF-1 or OC. However, season-modified effects were observed with 25(OH)D, i.e. children completing the school meal period in January/February had higher 25(OH)D status (5·5 (95 % CI 1·8, 9·2) nmol/l; P = 0·004) than children completing the control period in these months. A similar tendency was indicated in November/December (4·1 (95 % CI -0·12, 8·3) nmol/l; P = 0·057). However, the effect was opposite in March/April (-4·0 (95 % CI -7·0, -0·9) nmol/l; P = 0·010), and no difference was found in May/June (P = 0·214). Unexpectedly, the school meals slightly increased PTH (0·18 (95 % CI 0·07, 0·29) pmol/l) compared with habitual lunch. Small increases in dietary vitamin D might hold potential to mitigate the winter nadir in Danish children's 25(OH)D status while higher increases appear necessary to affect status throughout the year. More trials on effects of vitamin D intake from natural foods are needed.

What do Danish children eat, and does the diet meet the recommendations? Baseline data from the OPUS School Meal Study.

A child's diet is an important determinant for later health, growth and development. In Denmark, most children in primary school bring their own packed lunch from home and attend an after-school care institution. The aim of the present study was to evaluate the food, energy and nutrient intake of Danish school children in relation to dietary guidelines and nutrient recommendations, and to assess the food intake during and outside school hours. In total, 834 children from nine public schools located in the eastern part of Denmark were included in this cross-sectional study and 798 children (95·7 %) completed the dietary assessment sufficiently (August-November 2011). The whole diet was recorded during seven consecutive days using the Web-based Dietary Assessment Software for Children (WebDASC). Compared with the food-based dietary guidelines and nutrient recommendations, 85 % of the children consumed excess amounts of red meat, 89 % consumed too much saturated fat, and 56 % consumed too much added sugar. Additionally 35 or 91 % of the children (depending on age group) consumed insufficient amounts of fruits and vegetables, 85 % consumed insufficient amounts of fish, 86 % consumed insufficient amounts of dietary fibre, 60 or 84 % had an insufficient Fe intake (depending on age group), and 96 % had an insufficient vitamin D intake. The study also showed that there is a higher intake of fruits and bread during school hours than outside school hours; this is not the case with, for example, fish and vegetables, and future studies should investigate strategies to increase fish and vegetable intake during school hours.

Diet-induced changes in iron and n-3 fatty acid status and associations with cognitive performance in 8-11-year-old Danish children: secondary analyses of the Optimal Well-Being, Development and Health for Danish Children through a Healthy New Nordic Diet School Meal Study.

Fe and n-3 long-chain PUFA (n-3 LCPUFA) have both been associated with cognition, but evidence remains inconclusive in well-nourished school-aged children. In the Optimal Well-Being, Development and Health for Danish Children through a Healthy New Nordic Diet (OPUS) School Meal Study, the 3-month intervention increased reading performance, inattention, impulsivity and dietary intake of fish and Fe. This study investigated whether the intervention influenced n-3 LCPUFA and Fe status and, if so, explored how these changes correlated with the changes in cognitive performance. The study was a cluster-randomised cross-over trial comparing school meals with packed lunch (control). At baseline and after each treatment, we measured serum ferritin, whole-blood n-3 LCPUFA and Hb, and performance in reading, mathematics and d2-test of attention. Data were analysed using mixed models (n 726) and principal component analysis of test performances (n 644), which showed two main patterns: 'school performance' and 'reading comprehension'. The latter indicated that children with good reading comprehension were also more inattentive and impulsive (i.e. higher d2-test error%). The intervention improved 'school performance' (P=0·015), 'reading comprehension' (P=0·043) and EPA+DHA status 0·21 (95% CI 0·15, 0·27) w/w % (P<0·001), but it did not affect serum ferritin or Hb. At baseline, having small Fe stores was associated with poorer 'school performance' in girls, but with better 'reading comprehension' in both boys and girls. Both baseline EPA+DHA status and the intervention-induced increase in EPA+DHA status was positively associated with 'school performance', suggesting that n-3 LCPUFA could potentially explain approximately 20 % of the intervention effect. These exploratory associations indicate that increased fish intake might explain some of the increase in reading performance and inattention in the study.

Vitamin D status is associated with cardiometabolic markers in 8-11-year-old children, independently of body fat and physical activity.

Vitamin D status has been associated with cardiometabolic markers even in children, but the associations may be confounded by fat mass and physical activity behaviour. This study investigated associations between vitamin D status and cardiometabolic risk profile, as well as the impact of fat mass and physical activity in Danish 8-11-year-old children, using baseline data from 782 children participating in the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study. We assessed vitamin D status as serum 25-hydroxyvitamin D (25(OH)D) and measured blood pressure, fasting plasma glucose, homoeostasis model of assessment-insulin resistance, plasma lipids, inflammatory markers, anthropometry and fat mass by dual-energy X-ray absorptiometry, and physical activity by 7 d accelerometry during August-November. Mean serum 25(OH)D was 60·8 (sd 18·7) nmol/l. Each 10 mmol/l 25(OH)D increase was associated with lower diastolic blood pressure (-0·3 mmHg, 95 % CI -0·6, -0·0) (P=0·02), total cholesterol (-0·07 mmol/l, 95 % CI -0·10, -0·05), LDL-cholesterol (-0·05 mmol/l, 95 % CI -0·08, -0·03), TAG (-0·02 mmol/l, 95 % CI -0·03, -0·01) (P≤0·001 for all lipids) and lower metabolic syndrome (MetS) score (P=0·01). Adjustment for fat mass index did not change the associations, but the association with blood pressure became borderline significant after adjustment for physical activity (P=0·06). In conclusion, vitamin D status was negatively associated with blood pressure, plasma lipids and a MetS score in Danish school children with low prevalence of vitamin D deficiency, and apart from blood pressure the associations were independent of body fat and physical activity. The potential underlying cause-effect relationship and possible long-term implications should be investigated in randomised controlled trials.

The effects of Nordic school meals on concentration and school performance in 8- to 11-year-old children in the OPUS School Meal Study: a cluster-randomised, controlled, cross-over trial.

It is widely assumed that nutrition can improve school performance in children; however, evidence remains limited and inconclusive. In the present study, we investigated whether serving healthy school meals influenced concentration and school performance of 8- to 11-year-old Danish children. The OPUS (Optimal well-being, development and health for Danish children through a healthy New Nordic Diet) School Meal Study was a cluster-randomised, controlled, cross-over trial comparing a healthy school meal programme with the usual packed lunch from home (control) each for 3 months (NCT 01457794). The d2 test of attention, the Learning Rating Scale (LRS) and standard tests on reading and mathematics proficiency were administered at baseline and at the end of each study period. Intervention effects were evaluated using hierarchical mixed models. The school meal intervention did not influence concentration performance (CP; primary outcome, n 693) or processing speed; however, the decrease in error percentage was 0·18 points smaller (P<0·001) in the intervention period than in the control period (medians: baseline 2·03%; intervention 1·46%; control 1·37%). In contrast, the intervention increased reading speed (0·7 sentence, P=0·009) and the number of correct sentences (1·8 sentences, P<0·001), which corresponded to 11 and 25%, respectively, of the effect of one school year. The percentage of correct sentences also improved (P<0·001), indicating that the number correct improved relatively more than reading speed. There was no effect on overall math performance or outcomes from the LRS. In conclusion, school meals did not affect CP, but improved reading performance, which is a complex cognitive activity that involves inference, and increased errors related to impulsivity and inattention. These findings are worth examining in future trials.

The role of leptin and other hormones related to bone metabolism and appetite regulation as determinants of gain in body fat and fat-free mass in 8-11-year-old children.

BACKGROUND: Regulation of body composition during childhood is complex. Numerous hormones are potentially involved. Leptin has been proposed to restrain weight gain, but results are inconsistent. OBJECTIVE: We examined whether baseline fasting levels of ghrelin, adiponectin, leptin, insulin, IGF-I, osteocalcin, and intact parathyroid hormone (iPTH) were associated with body composition cross sectionally and longitudinally in 633 8-11-year-olds. DESIGN: Data on hormones and body composition by dual-energy x-ray absorptiometry from the OPUS School Meal Study were used. We looked at baseline hormones as predictors of baseline fat mass index (FMI) or fat-free mass index (FFMI), and also subsequent changes (3 and 6 months) in FMI or FFMI using models with hormones individually or combined. RESULTS: Cross-sectionally, baseline leptin was positively associated with FMI in girls (0.211 kg/m(2) pr. µg/mL; 97.5% confidence interval [CI],0.186-0.236; P < .001) and boys (0.231 kg/m(2) pr. µg/mL; 97.5% CI, 0.200-0.261; P < .001). IGF-I in both sexes and iPTH in boys were positively associated with FMI. An inverse association between adiponectin and FFMI in boys and a positive association between IGF-I and FFMI were found in girls. In longitudinal models, baseline leptin was inversely associated with subsequent changes in FMI (-0.018 kg/m(2) pr. µg/mL; 97.5% CI, -0.034 - -0.002; P = .028) and FFMI (-0.014 kg/m(2) pr. µg/mL; 97.5% CI, -0.024 - -0.003; P = .006) in girls. CONCLUSIONS: Cross-sectional findings support that leptin is produced in proportion to body fat mass, but the longitudinal observations support that leptin inhibits gains in FMI and FFMI in girls, a finding that may reflect preserved leptin sensitivity in this predominantly normal weight population.

Provision of healthy school meals does not affect the metabolic syndrome score in 8-11-year-old children, but reduces cardiometabolic risk markers despite increasing waist circumference.

An increasing number of children are exhibiting features of the metabolic syndrome (MetS) including abdominal fatness, hypertension, adverse lipid profile and insulin resistance. Healthy eating practices during school hours may improve the cardiometabolic profile, but there is a lack of evidence. In the present study, the effect of provision of school meals rich in fish, vegetables and fibre on a MetS score (primary outcome) and on individual cardiometabolic markers and body composition (secondary outcomes) was investigated in 834 Danish school children. The study was carried out as a cluster-randomised, controlled, non-blinded, cross-over trial at nine schools. Children aged 8-11 years received freshly prepared school lunch and snacks or usual packed lunch from home (control) each for 3 months. Dietary intake, physical activity, cardiometabolic markers and body composition were measured at baseline and after each dietary period. The school meals did not affect the MetS score (P= 1.00). However, it was found that mean arterial pressure was reduced by 0.4 (95% CI 0.0, 0.8) mmHg (P= 0.04), fasting total cholesterol concentrations by 0.05 (95% CI 0.02, 0.08) mmol/l (P= 0.001), HDL-cholesterol concentrations by 0.02 (95% CI 0.00, 0.03) mmol/l, TAG concentrations by 0.02 (95% CI 0.00, 0.04) mmol/l (both P< 0.05), and homeostasis model of assessment-insulin resistance by 0.10 (95% CI 0.04, 0.16) points (P= 0.001) compared with the control diet in the intention-to-treat analyses. Waist circumference increased 0.5 (95% CI 0.3, 0.7) cm (P< 0.001), but BMI z-score remained unaffected. Complete-case analyses and analyses adjusted for household educational level, pubertal status and physical activity confirmed the results. In conclusion, the school meals did not affect the MetS score in 8-11-year-olds, as small improvements in blood pressure, TAG concentrations and insulin resistance were counterbalanced by slight undesired effects on waist circumference and HDL-cholesterol concentrations.