Intake of Total and Subgroups of Fat Minimally Affect the Associations between Selected Single Nucleotide Polymorphisms in the PPARγ Pathway and Changes in Anthropometry among European Adults from Cohorts of the DiOGenes Study.

BACKGROUND: Although the peroxisome proliferator-activated receptor γ (PPARγ) pathway is central in adipogenesis, it remains unknown whether it influences change in body weight (BW) and whether dietary fat has a modifying effect on the association. OBJECTIVES: We examined whether 27 single nucleotide polymorphisms (SNPs) within 4 genes in the PPARγ pathway are associated with the OR of being a BW gainer or with annual changes in anthropometry and whether intake of total fat, monounsaturated fat, polyunsaturated fat, or saturated fat has a modifying effect on these associations. METHODS: A case-noncase study included 11,048 men and women from cohorts in the European Diet, Obesity and Genes study; 5552 were cases, defined as individuals with the greatest BW gain during follow-up, and 6548 were randomly selected, including 5496 noncases. We selected 4 genes [CCAAT/enhancer binding protein ß (CEBPB), phosphoenolpyruvate carboxykinase 2, PPARγ gene (PPARG), and sterol regulatory element binding transcription factor 1] according to evidence about biologic plausibility for interactions with dietary fat in weight regulation. Diet was assessed at baseline, and anthropometry was followed for 7 y. RESULTS: The ORs for being a BW gainer for the 27 genetic variants ranged from 0.87 (95% CI: 0.79, 1.03) to 1.12 (95% CI: 0.96, 1.22) per additional minor allele. Uncorrected, CEBPB rs4253449 had a significant interaction with the intake of total fat and subgroups of fat. The OR for being a BW gainer for each additional rs4253449 minor allele per 100 kcal higher total fat intake was 1.07 (95% CI: 1.02, 1.12; P = 0.008), and similar associations were found for subgroups of fat. CONCLUSIONS: Among European men and women, the influence of dietary fat on associations between SNPs in the PPARγ pathway and anthropometry is likely to be absent or marginal. The observed interaction between rs4253449 and dietary fat needs confirmation.

Intervention effects on dietary intake among children by maternal education level: results of the Copenhagen School Child Intervention Study (CoSCIS).

Dietary intake among Danish children, in general, does not comply with the official recommendations. The objectives of the present study were to evaluate the 3-year effect of a multi-component school-based intervention on nutrient intake in children, and to examine whether an intervention effect depended on maternal education level. A total of 307 children (intervention group: n 184; comparison group: n 123) were included in the present study. All had information on dietary intake pre- and post-intervention (mean age 6·8 and 9·5 years for intervention and comparison groups, respectively) assessed by a 7-d food record. Analyses were conducted based on the daily intake of macronutrients (energy percentage (E%)), fatty acids (E%), added sugar (E%) and dietary fibre (g/d and g/MJ). Analyses were stratified by maternal education level into three categories. Changes in nutrient intake were observed in the intervention group, mainly among children of mothers with a short education ( < 10 years). Here, intake of dietary fibre increased (ß = 2·1 g/d, 95 % CI 0·5, 3·6, P= 0·01). Intake of protein tended to increase (ß = 0·6 E%, 95 % CI -0·01, 1·2, P= 0·05), while intake of fat (ß = -1·7 E%, 95 % CI -3·8, 0·3, P= 0·09) and SFA (ß = -0·9, 95 % CI -2·0, 0·2, P= 0·10) tended to decrease. Also, a significant intervention effect was observed on the intake of SFA among children of mothers with a long education (ß = -0·8, 95 % CI -1·5, -0·03, P= 0·04). This multi-component school-based intervention resulted in changes in the dietary intake, particularly among children of mothers with a short education. As the dietary intake of this subgroup generally differs most from the recommendations, the results of the present study are particularly encouraging.

Original article: novelty of Canadian manufacture nasopharyngeal swabs for collection of samples being tested for SARS-CoV-2 in a pandemic setting.

Objectives: The COVID-19 pandemic caused a global shortage of nasopharyngeal (NP) swabs, required for RT-PCR testing. Canadian manufacturers were contacted to share NP swab innovations. The primary objective was to determine whether novel NP test swabs were comparable to commercially available swabs regarding user characteristics, ability to collect a specimen, and diagnostic performance using RT-PCR testing. Methods: Participants were randomized by swab (test/control) and nostril (left/right). A calculated positive percent agreement ≥90% was considered successful. Mean Ct values of viral genes and housekeeping gene (RNase P) were considered similar if a Ct difference ≤ 2 between control and test group was obtained. There also was a qualitative assessment of swabs usability. Results: 647 participants were enrolled from Huaycan Hospital in Lima, Peru, distributed over 8 NP swabs brands. Seven brands agreed to share their results. There were no statistically significant differences between the test swabs of these 7 brands and control swabs. Conclusion: All the seven brands are comparable to the commercially available flocked swabs used for SARS-CoV-2 regarding test results agreement, ability to collect a specimen, and user characteristics.

Dietary arginine and linear growth: the Copenhagen School Child Intervention Study.

The amino acid arginine is a well-known growth hormone (GH) stimulator and GH is an important modulator of linear growth. The aim of the present study was to investigate the effect of dietary arginine on growth velocity in children between 7 and 13 years of age. Data from the Copenhagen School Child Intervention Study during 2001-2 (baseline), and at 3-year and 7-year follow-up, were used. Arginine intake was estimated via a 7 d precoded food diary at baseline and 3-year follow-up. Data were analysed in a multilevel structure in which children were embedded within schools. Random intercept and slopes were defined to estimate the association between arginine intake and growth velocity, including the following covariates: sex; age; baseline height; energy intake; puberty stage at 7-year follow-up and intervention/control group. The association between arginine intake and growth velocity was significant for the third and fourth quintile of arginine intake (2.5-2.8 and 2.8-3.2 g/d, respectively) compared with the first quintile ( < 2.2 g/d) (P for trend = 0.04). Protein intake (excluding arginine) was significantly associated with growth velocity; however, the association was weaker than the association between arginine intake and growth velocity (P for trend = 0.14). The results of the present study suggest a dose-dependent physiological role of habitual protein intake, and specifically arginine intake, on linear growth in normally growing children. However, since the study was designed in healthy children, we cannot firmly conclude whether arginine supplementation represents a relevant clinical strategy. Further research is needed to investigate whether dietary arginine may represent a nutritional strategy potentially advantageous for the prevention and treatment of short stature.

A cross-sectional study on trans-fatty acids and risk markers of CHD among middle-aged men representing a broad range of BMI.

Intake of trans-fatty acids (TFA), especially industrially produced TFA (I-TFA), has been associated with the risk of CHD through influence on serum lipid levels. Other causal pathways remain less investigated. In the present cross-sectional study of middle-aged men representing a broad range of BMI, the association between intake of TFA, I-TFA and ruminant TFA (R-TFA) and obesity-associated risk markers of CHD was assessed. The study comprised 393 Danish men (median age 49 years) with a median BMI of 28·4 kg/m(2). Intake of TFA was estimated based on 7 d dietary records, whereas outcomes of interest (waist circumference, sagittal abdominal diameter, percentage of truncal fat, C-reactive protein, IL-6, blood lipids, blood pressure, HbA1c and insulin sensitivity index) were obtained through clinical examination. The associations were assessed by linear regression analysis. The median intake of total TFA among the 393 men was 1·3 g/d, covering a daily I-TFA intake of 0·4 g (10-90th percentile 0·0-1·0) and R-TFA intake of 0·9 g (10-90th percentile 0·4-1·8). Intake of these amounts of TFA showed no significant associations with abdominal fatness, inflammatory markers, blood lipids, blood pressure and insulin homeostasis. Among middle-aged men with a generally low intake of TFA, neither I-TFA nor R-TFA was significantly related to obesity-associated risk markers of CHD. The decreased average intake of I-TFA in Denmark since 1995 is suggested to effectively prevent occurrence of the adverse metabolic changes and health consequences, which have formerly been observed in relation to, especially, I-TFA intake.

Television viewing, food preferences, and food habits among children: a prospective epidemiological study.

BACKGROUND: Obesity has increased since the early 1980s, and despite numerous attempts, effective strategies to counter this worldwide epidemic are lacking. Food preferences are established early in life and are difficult to change later. There is therefore a need to identify factors that influence the development of food preferences. Our aim was therefore, to investigate cross-sectional and prospective associations between TV viewing habits and food preferences and habits, respectively. We hypothesized that more TV viewing was associated with less healthy concomitant and future food preferences and food habits. METHODS: Data are from the Danish part of European Youth Heart Study (EYHS) I and II, a prospective cohort study conducted among 8-10-year-old and 14-16-year-old Danes in 1997-98. Six years later 2003-04 the 8-10-year-olds were followed up at age 14-16 years, and a new group of 8-10-year olds were included. Data were analysed using mixed linear regression analysis. Cross-sectional analyses included 697 8-10-year-olds and 495 14-16-year-olds. Prospective analyses included 232 pupils with complete data at baseline and follow-up. Associations between TV viewing habits and the sum of healthy food preferences (ΣHFP), and the sum of healthy food habits (ΣHFH), respectively, were examined. RESULTS: Inverse cross-sectional associations between TV viewing (h/day) and both ΣHFP and ΣHFH were present for both the 8-10-year-old and the 14-16-year-old boys and girls. The frequency of meals in front of the TV (times/week) was also inversely associated with ΣHFP among 8-10-year-old boys, and with ΣHFH in all sex- and age groups. Among girls, baseline TV viewing (h/day) was directly associated with adverse development in the ΣHFP during follow-up. The concomitant 6-year changes in ΣHFH and TV viewing (h/day) were inversely associated in boys. CONCLUSIONS: Long time spent on TV viewing, and possibly to a lesser degree, frequent consumption of meals during TV viewing, seem to be associated with generally having unhealthy food preferences and food habits among school-aged children. These associations, however, were not generally persistent after 6 years of follow-up.

Three-Year Intervention Effects on Food and Beverage Intake-Results from the Quasi-Experimental Copenhagen School Child Intervention Study (CoSCIS).

The diet of Danish children is often not in accordance with dietary guidelines. We aimed to evaluate changes in the intake of selected foods and beverages during a multi-component school-based physical activity intervention, and to investigate if changes were modified by socioeconomic status (SES). The study included 307 children (intervention group: 184; comparison group: 123) with information on dietary intake pre- and post-intervention as well as on SES. Linear regression models were conducted to assess the effect of the intervention on changes in dietary factors. Children from the intervention group increased their intake of whole-grain bread during the intervention (group means: 6.1 g/d (95% CI: 2.2 to 10.0) vs. 0.3 g/d (95% CI: -3.1 to 3.7) in the comparison group, p = 0.04). A significant interaction between SES and group allocation was observed to change in fruit intake (p = 0.01). Among children from low SES families, only those from the comparison group decreased their fruit intake (group means: -40.0 g/d (95% CI: -56.0 to -23.9) vs. 9.3 g/d (95% CI: -16.1 to 94) in the intervention group, p = 0.006). The present study found no convincing effect of introducing a multi-component intervention on dietary intake except a small beneficial effect on whole-grain bread consumption. However, beneficial intervention effects in fruit intake were found particularly among children from low SES families.

Lactobacillus acidophilus induces virus immune defence genes in murine dendritic cells by a Toll-like receptor-2-dependent mechanism.

Lactobacilli are probiotics that, among other health-promoting effects, have been ascribed immunostimulating and virus-preventive properties. Certain Lactobacillus spp. have been shown to possess strong interleukin-12 (IL-12) -inducing properties. As IL-12 production depends on the up-regulation of type I interferons (IFNs), we hypothesized that the strong IL-12-inducing capacity of Lactobacillus acidophilus NCFM in murine bone-marrow-derived dendritic cells (DCs) is caused by an up-regulation of IFN-ß, which subsequently induces IL-12 and the double-stranded RNA binding Toll-like receptor-3 (TLR-3). The expression of the genes encoding IFN-ß, TLR-3, IL-12 and IL-10 in DCs upon stimulation with L. acidophilus NCFM was determined. Lactobacillus acidophilus NCFM induced a much stronger expression of Ifn-ß, Il-12 and Il-10 compared with the synthetic double-stranded RNA ligand Poly I:C, whereas the levels of expressed Tlr-3 were similar. Whole genome microarray gene expression analysis revealed that other genes related to viral defence were significantly up-regulated and among the strongest induced genes in DCs stimulated with L. acidophilus NCFM. The ability to induce IFN-ß was also detected in another L. acidophilus strain (X37), but was not a property of other probiotic strains tested, i.e. Bifidobacterium bifidum Z9 and Escherichia coli Nissle 1917. The IFN-ß expression was markedly reduced in TLR-2(-/-) DCs, dependent on endocytosis, and the major cause of the induction of Il-12 and Tlr-3 in DCs stimulated with L. acidophilus NCFM. Collectively, our results reveal that certain lactobacilli trigger the expression of viral defence genes in DCs in a TLR-2 manner dependent on IFN-ß.

Past and current body size affect validity of reported energy intake among middle-aged Danish men.

Our objectives were to estimate the degree of misreporting energy intake (EI) and analyze associations with previous BMI, current BMI, or both. The study was part of the Adiposity and Genetics Study follow-up study including 309 Danish men (age 40-65 y) originally sampled from the obligatory draft board examination. Height and weight were measured at the mean ages of 20 (draft board), 33, 44, and 49 y (current age). Obesity was categorized as BMI >or= 31 kg/m(2). Dietary intake for 7 d and physical activity (PA) level (PAL) were self-reported. Resting metabolic rate (RMR) was measured in a ventilated hood system. By comparing EI with energy expenditure and assuming energy balance, reporting accuracy (RA) was estimated as EI/(RMR.PAL). A plausibility interval was calculated to encompass specific variation components of EI, RMR, and PAL; the specific 95% plausibility interval was 1.00 +/- 0.35. Participants were categorized as underreporters (RA 1.35) of EI. The relation between RA and BMI was studied through linear regression analysis. Overall, the RA was (mean +/- SE) 0.76 +/- 0.01. Of 309 participants, 35% underreported and 7% overreported. Whether stratified for current BMI or draft board BMI, the obese men were more likely to underreport than those who were not obese. Among those currently not obese, underreporting was more prevalent among those who were obese at the draft board examination (44%) than among those who were not (21%). Regression analysis showed that both previous and current BMI and their combination were significantly associated with RA. Thus, underreporting of dietary intake seems to be associated with not only current BMI but also with current BMI in combination with previous BMI.

PNA-mediated modulation and redirection of Her-2 pre-mRNA splicing: specific skipping of erbB-2 exon 19 coding for the ATP catalytic domain.

The Her-2 receptor coded for by the proto-oncogenic erbB-2 gene is a clinically validated target for treatment of a significant genetic subclass of breast cancers, and Her-2 is also overexpressed or mutated in a range of other cancers. In an approach to exploit antisense mediated splicing interference as a means of manipulating erbB-2 expression in a therapeutically relevant fashion, we have studied the effect on mRNA splicing of a series of peptide nucleic acid (PNA) oligomers targeting specific intron-exon junctions in the erbB-2 pre-mRNA. In particular, we are interested in identifying PNA oligomers that specifically induce skipping of exon 19 as this exon is coding for the ATP catalytic domain of Her-2, and if expressed such truncated version of the Her-2 protein should be functionally inactive in a dominant negative fashion. Therefore, antisense compounds having efficient erbB-2 exon 19 skipping activity could be very interesting in terms of drug discovery. In the present study we identified PNA oligomers having such activity in SK-BR-3 and HeLa cancer cells in culture.

Bifidobacterium bifidum actively changes the gene expression profile induced by Lactobacillus acidophilus in murine dendritic cells.

Dendritic cells (DC) play a pivotal regulatory role in activation of both the innate as well as the adaptive immune system by responding to environmental microorganisms. We have previously shown that Lactobacillus acidophilus induces a strong production of the pro-inflammatory and Th1 polarizing cytokine IL-12 in DC, whereas bifidobacteria do not induce IL-12 but inhibit the IL-12 production induced by lactobacilli. In the present study, genome-wide microarrays were used to investigate the gene expression pattern of murine DC stimulated with Lactobacillus acidophilus NCFM and Bifidobacterium bifidum Z9. L. acidophilus NCFM strongly induced expression of interferon (IFN)-beta, other virus defence genes, and cytokine and chemokine genes related to the innate and the adaptive immune response. By contrast, B. bifidum Z9 up-regulated genes encoding cytokines and chemokines related to the innate immune response. Moreover, B. bifidum Z9 inhibited the expression of the Th1-promoting genes induced by L. acidophilus NCFM and had an additive effect on genes of the innate immune response and Th2 skewing genes. The gene encoding Jun dimerization protein 2 (JDP2), a transcription factor regulating the activation of JNK, was one of the few genes only induced by B. bifidum Z9. Neutralization of IFN-beta abrogated L. acidophilus NCFM-induced expression of Th1-skewing genes, and blocking of the JNK pathway completely inhibited the expression of IFN-beta. Our results indicate that B. bifidum Z9 actively inhibits the expression of genes related to the adaptive immune system in murine dendritic cells and that JPD2 via blocking of IFN-beta plays a central role in this regulatory mechanism.

Should glycemic index and glycemic load be considered in dietary recommendations?

High glycemic index (GI) and glycemic load (GL) have been proposed to be associated with increased risk of lifestyle diseases. Since protein intake varies little in humans, adherence to the common recommendation to reduce fat intake probably leads to increases in carbohydrate intake, which emphasizes the need to investigate the effects of carbohydrate on diet-related conditions and diseases. This review examines the epidemiological literature linking GI and GL to heart disease, insulin sensitivity, type 2 diabetes, dyslipidemia, and obesity among initially healthy people. The evidence for associations between GI and particularly GL and health among free-living populations is mixed. Only the positive association between GI and development of type 2 diabetes was consistent across cross-sectional and longitudinal studies for both sexes. Low GI/GL may protect against heart disease in women, and cross-sectional studies indicate low GI/GL may reduce high-density-lipoprotein cholesterol and triacylglycerol levels in both sexes. Based on the evidence found in this review, it seems premature to include GI/GL in dietary recommendations.

Dietary glycaemic index and glycaemic load in Danish children in relation to body fatness.

The aim of this study was to describe dietary glycaemic index (GI) and glycaemic load (GL) values in the diets of Danish children, and to examine the associations between dietary GI, GL and body fatness. Data were collected during 1997-8 as part of the European Youth Heart Study. The study population comprised 485 children aged 10 years and 364 children aged 16 years from Odense County, Denmark. Dietary GI and GL were estimated using international food tables, and the associations between energy-adjusted dietary GI, GL and body fatness were analysed by multiple linear regression. The mean daily dietary GI value was 85 (SD 6.9) with a range of 62-111. No significant differences were found between age groups and gender. The daily dietary GL was higher among boys aged 16, with a GL of 330 (sd 95) (P<0.05), compared with girls or younger boys. Dietary GL was higher among 10-year-old boys than girls (250 (sd 81) v. 230 (sd 66) P<0.05), whereas dietary GL among 16-year-old girls was 230 (sd 56). Neither dietary GI nor GL was associated with the sum of four skinfolds (SigmaSF) among girls or among 10-year-old boys. Among 16-year-old boys, significant associations were observed between dietary GI and SigmaSF (beta=0.60, SE=0.21, P=0.006), and between dietary GL and SigmaSF (beta=0.15, SE=0.06, P=0.009). In conclusion, dietary GI and GL were positively associated with body fatness among Danish boys aged 16 years, whereas no associations were found among girls or younger boys.