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Objectives The authors studied the association of leisure-time physical activity (LTPA) with clustered and individual metabolic risk factors in adolescents taking into account diet and pubertal status. The authors also studied whether screen time was associated with clustered risk. Methods Self-reported LTPA and screen time, lipids, lipoproteins, apolipoproteins, high-sensitivity C reactive protein, blood pressure, body mass index (BMI), pubertal status and diet were assessed in 13-year-old adolescents (n=542) participating in an atherosclerosis prevention study (Special Turku Coronary Risk Factor Intervention Project for Children). Activity groups were formed according to sex-specific LTPA index tertile cut-off points. BMI, high-density lipoprotein cholesterol (HDL-C), triglycerides and blood pressure comprised the cluster. Results An increase in LTPA was associated with a decreased risk for clustered metabolic risk in girls. When sedentary and highly active adolescents were compared, an increase in LTPA decreased clustering of risk factors in boys as well. Little extra benefit on clustered risk was obtained by increasing LTPA from 30 MET h/week (eg, 4-5 h/week bicycling or playing soccer) to 50 MET h/week (eg, 7-8 h/week bicycling or playing soccer). LTPA was beneficially associated with BMI, HDL-C, systolic blood pressure and HDL-C/total cholesterol in girls and HDL-C in boys. Diet and pubertal status were similar in all activity groups. In girls, screen time >2 h/day was associated with an increased risk for clustered risk, independent of LTPA. Conclusion Sedentary adolescents had an increased risk for clustered metabolic risk compared with physically more active peers. Only minor extra benefit was obtained when LTPA increased over 30 MET h/week. Focus in the prevention of clustered risk should especially be on avoiding sedentary lifestyle. [ABSTRACT FROM AUTHOR]

Our aim was to investigate the occurrence of clinical and subclinical autoimmune thyroid disease in 79 patients with celiac disease as reflected in thyroid function, antibodies, and ultrasound. Since subclinical thyroid diseases are common in the population, 184 nonceliac controls were also studied. Normal thyroid function combined with positive antibodies and marked hypoechogenicity was considered subclinical disease. Autoimmune thyroid disease was observed in 13.9% of celiac patients and in 2.1% of controls (P = 0.0005); and subclinical disease in 10.1% and 3.3%, respectively (P = 0.048). The mean thyroid gland volume was 8.3 ml in celiac patients and 10.4 ml in controls (P = 0.007). Hypoechogenicity was found in 73% of celiac patients and in 42% of controls (P < 0.0001). Positive thyroid antibodies were associated with hypoechogenicity in celiac patients but not in controls. In conclusion, the occurrence of both clinical and subclinical autoimmune thyroid disease was increased in celiac disease; subclinical thyroid disease indicates regular surveillance. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Our goal was to study childhood growth patterns and development of overweight in children who were overweight or normal weight at 13 years of age. PARTICIPANTS AND METHODS: This study is part of a prospective atherosclerosis-prevention trial Special Turku Coronary Risk Factor Intervention Project for Children). At 7 months of age, 1062 children were randomly assigned to an intervention group (n = 540) receiving biannual fat-oriented dietary counseling or to a control group (n = 522). Height and weight of the children and their parents were monitored annually. Our study group comprised those children who participated in the 13-year study visit (n = 541). At 13 years of age, the child was classified as overweight (n = 84) if his or her BMI exceeded the international age- and gender-specific overweight criteria. RESULTS: In overweight girls, the annual weight gain increased from 2.8 kg during the third and fourth year of life to 7.5 kg during the 12th year of life, whereas the annual weight gain of the girls who were normal weight ranged from 2.1 to 4.8 kg during the same period. The annual weight gain was similar of overweight boys and in their normal-weight peers until the age of 5 years, but after that it increased from 3.5 to 7.9 kg in overweight and from 2.6 to 5.5 kg in normal-weight boys. The BMI of the girls and boys who were overweight at the age of 13 exceeded the international cutoff point for overweight from the age of 5 and 8 years onward, respectively. The mean BMIs of the mothers and fathers of the overweight children were higher than those of the parents of the normal-weight children. The STRIP intervention had no effect on the examined growth parameters or on parental BMI. CONCLUSIONS: The children who were overweight at 13 years of age gained more weight than their normal-weight peers by the age of 2 or 3 years onward. The girls became overweight by the age of 5 years, whereas the boys only after 8 years of age. Parental BMI and steep weight gain in early childhood indicate markedly increased risk for becoming overweight. [ABSTRACT FROM AUTHOR]

We report here the nearly complete Illumina-sequenced consensus genome sequences of six isolates of echovirus 7 (E7), including oncolytic virotherapy virus RIGVIR and the Wallace prototype. Amino acid identities within the coding region were highly conserved across all isolates, ranging from 95.31% to 99.73%., (Copyright © 2018 Hietanen et al.)

As new pathogenic viruses continue to emerge, it is paramount to have intervention strategies that target a common denominator in these pathogens. The fusion of viral and cellular membranes during viral entry is one such process that is used by many pathogenic viruses, including chikungunya virus, West Nile virus, and influenza virus. Obatoclax, a small-molecule antagonist of the Bcl-2 family of proteins, was previously determined to have activity against influenza A virus and also Sindbis virus. Here, we report it to be active against alphaviruses, like chikungunya virus (50% effective concentration [EC 50 ] = 0.03 μM) and Semliki Forest virus (SFV; EC 50 = 0.11 μM). Obatoclax inhibited viral entry processes in an SFV temperature-sensitive mutant entry assay. A neutral red retention assay revealed that obatoclax induces the rapid neutralization of the acidic environment of endolysosomal vesicles and thereby most likely inhibits viral fusion. Characterization of escape mutants revealed that the L369I mutation in the SFV E1 fusion protein was sufficient to confer partial resistance against obatoclax. Other inhibitors that target the Bcl-2 family of antiapoptotic proteins inhibited neither viral entry nor endolysosomal acidification, suggesting that the antiviral mechanism of obatoclax does not depend on its anticancer targets. Obatoclax inhibited the growth of flaviviruses, like Zika virus, West Nile virus, and yellow fever virus, which require low pH for fusion, but not that of pH-independent picornaviruses, like coxsackievirus A9, echovirus 6, and echovirus 7. In conclusion, obatoclax is a novel inhibitor of endosomal acidification that prevents viral fusion and that could be pursued as a potential broad-spectrum antiviral candidate., (Copyright © 2017 American Society for Microbiology.)

Background: Coxsackievirus A9 (CV-A9) is a pathogenic enterovirus type within the family Picornaviridae. CV-A9 infects A549 human epithelial lung carcinoma cells by attaching to the αVβ6 integrin receptor through a highly conserved Arg-Gly-Asp (RGD) motif, which is located at the exposed carboxy-terminus of the capsid protein VP1 detected in all studied clinical isolates. However, genetically-modified CV-A9 that lacks the RGD motif (CV-A9-RGDdel) has been shown to be infectious in some cell lines but not in A549, suggesting that RGD-mediated integrin binding is not always essential for efficient entry of CV-A9., Methods: Two cell lines, A549 and SW480, were used in the study. SW480 was the study object for the integrin-independent entry and A549 was used as the control for integrin-dependent entry. Receptor levels were quantitated by cell sorting and quantitative PCR. Antibody blocking assay and siRNA silencing of receptor-encoding genes were used to block virus infection. Peptide phage display library was used to identify peptide binders to CV-A9. Immunofluorescence and confocal microscopy were used to visualize the virus infection in the cells., Results: We investigated the receptor use and early stages of CV-A9 internalization to SW480 human epithelial colon adenocarcinoma cells. Contrary to A549 infection, we showed that both CV-A9 and CV-A9-RGDdel internalized into SW480 cells and that function-blocking anti-αV integrin antibodies had no effect on the binding and entry of CV-A9. Whereas siRNA silencing of β6 integrin subunit had no influence on virus infection in SW480, silencing of β2-microglobulin (β2M) inhibited the virus infection in both cell lines. By using a peptide phage display screening, the virus-binding peptide identical to the N-terminal sequence of HSPA5 protein was identified and shown to block the virus infection in both A549 and SW480 cell lines. HSPA5 was also found to co-localize with CV-A9 at the SW480 cell periphery during the early stages of infection by confocal microscopy., Conclusions: The data suggest that while αVβ6 integrin is essential for CV-A9 in A549 cell line, it is not required in SW480 cell line in which β2M and HSPA5 alone are sufficient for CV-A9 infection. This suggests that the choice of CV-A9 receptor(s) is dependent on the tissue/cellular environment.

Background: Obesity, sedentary lifestyle and poor cardiorespiratory fitness in childhood may increase the risk of health problems later in life., Purpose: The authors studied the association of early childhood weight status with cardiorespiratory fitness and leisure-time physical activity (LTPA) in adolescence. The stability and associations of LTPA and fitness from childhood through adolescence were also studied., Methods: Body mass index (BMI) was assessed annually since birth in a prospective, longitudinal study. The mean BMI between ages 2 and 7 years indicated weight status at preschool age. Fitness was studied with a shuttle run test at age 9 and with a maximal cycle ergometer test at age 17. The same questionnaire was used to assess LTPA at age 9, 13 and 17. Complete data on preschool BMI, LTPA at ages 13 and 17 and fitness at age 17 years was provided by 351 children, while fitness and LTPA data were available for 74 children at ages 9 and 17., Results: Preschool BMI was inversely associated with fitness in adolescence independently of adolescent LTPA (p=0.0001). Children who had a high preschool BMI but whose weight status was reduced in adolescence had similar fitness in adolescence as the children with a persistently low BMI. Regardless of the fitness level in childhood, the children whose LTPA increased between age 9 and 17 had a similar adolescent fitness level as persistently active subjects., Conclusions: It is important to maintain a healthy body weight and a physically active lifestyle from very childhood through adolescence to improve fitness during adolescence.

Background: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268)., Methods and Findings: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction)  = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio  = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio  = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents., Conclusions: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.

Objective: To examine the effects of child-oriented dietary intervention on parental eating attitudes and dietary behaviour., Design: In the prospective, randomized Special Turku Coronary Risk Factor Intervention Project for Children (the STRIP study), a cohort of Finnish families took part in a nutritional intervention trial focused on the quality of their children's fat intake since the age of 8 months. Health-related and hedonic eating attitudes of the parents were measured after 10 years of dietary intervention using a validated Health and Taste Attitude Scales (HTAS) questionnaire (n 660). Parents' eating behaviour was studied using a 1 d food record (n 491)., Setting: Finland., Subjects: Mothers and fathers (n 660) of the STRIP children., Results: The parents of the intervention families had a higher level of interest in healthy eating compared with control parents. The interest in natural products or hedonic eating attitudes did not differ between the groups. The parents' general health interest was associated with low saturated fat intake, fruit and vegetable consumption, fibre intake and seeking pleasure in eating, but it was not associated with BMI. The intervention also improved the quality of dietary fat among parents with the lowest level of interest in healthy eating., Conclusions: Parents' general health interest was associated with regular dietary counselling as well as with healthier food choice behaviour. However, the dietary intervention that focused especially on the quality of the child's fat intake also enhanced specific changes in the family's fat consumption without a high level of interest in healthy eating.

Background: Dietary fiber has health benefits, but fiber recommendations for children are controversial because fiber may displace energy., Objective: The objective was to longitudinally evaluate dietary fiber intake in children and to study associations between growth variables, serum cholesterol concentrations, and intakes of fiber, energy, and nutrients., Design: Altogether, 543 children from a prospective randomized atherosclerosis prevention trial (the Special Turku Coronary Risk factor Intervention Project; STRIP) participated in this study between the ages of 8 mo and 9 y. The intervention children (n = 264) were counseled to replace part of saturated fat with unsaturated fat. Nutrient intakes, weight, height, and serum total, HDL-, and LDL-cholesterol and triglyceride concentrations were analyzed. Children were divided into 3 groups according to mean dietary fiber intake in foods: low (lowest 10%), high (highest 10%), and average (middle 80%) fiber intakes., Results: Fiber intake associated positively with energy intake and inversely with fat intake. Children with a high fiber intake received more vitamins and minerals than did children in other groups. In longitudinal growth analyses, weights and heights were similar in all 3 fiber intake groups, and fiber intake (g/d) associated positively with weight gain between 8 mo and 2 y. Serum cholesterol concentrations decreased with increasing fiber intakes. Children in the intervention group had a higher fiber intake than did the control children during the entire follow-up period., Conclusion: Fiber intake did not displace energy or disturb growth between 13 mo and 9 y of age. Serum cholesterol values correlated inversely with fiber intake, which indicated that part of the cholesterol-lowering intervention effect in the STRIP project may have been explained by dietary fiber.

Serum low-density lipoprotein (LDL) particle composition varies according to lifestyle and age. To analyze its long-term tracking, we studied LDL particle size consecutively in 100 children at the ages of 7, 9 and 11 years using a high-resolution 3% polyacrylamide gel tube, electrophoresis method, searching also for long-term determinants of the particle size. The mean LDL particle sizes at 7 and 9 years, and at 7 and 11 years correlated directly (r=0.72 and 0.39, respectively). The probability that children would remain in the same LDL particle size tertile between 7 and 11 years of age was 48% (p=0.008). Longitudinally, total, high-density lipoprotein (HDL) and LDL cholesterol concentrations and body mass index (BMI) associated directly with mean LDL particle size, and triglyceride concentration and triglyceride/HDL cholesterol ratio correlated inversely. A shift from pre-puberty to puberty was associated with an increase in LDL particle size. Sex, serum insulin concentration, or energy nutrient intakes did not associate with LDL particle size. In conclusion, although mean LDL particle size tracks in 7- to 11-year-old healthy children, changes in serum triglycerides, HDL, LDL, and total cholesterol concentration, BMI, and pubertal status all modify LDL particle size.

Context: A common variant in the FTO gene, rs9939609, associates with body mass index (BMI) in adults and in children aged 7 yr or older., Objective: Our aim was to examine the associations of the FTO genotype with BMI, cardiovascular risk factors, energy intake, and leisure-time physical activity in children followed up since infancy., Methods: Healthy participants of the STRIP Study, genotyped for rs9939609, were followed from age 7 months (n = 640) to 15 yr (n = 438). The children were randomly assigned to lifestyle intervention and control groups. Height, weight, blood pressure, and serum lipids were measured annually. Food records and physical activity index were obtained at age 15 yr., Results: The FTO genotype did not associate with BMI in children younger than 7 yr of age. From age 7 yr onward, the children homozygous for the A allele had progressively higher BMI than the children with one or two T alleles (P = 0.029 for FTO by age interaction). Furthermore, in longitudinal, BMI Z-score-adjusted analysis, the AA genotype associated with higher systolic and diastolic blood pressure and with elevated serum total and low-density lipoprotein-cholesterol (P = 0.01, P < 0.001, P = 0.05, and P = 0.04 for main effect, respectively). The FTO genotype did not associate with energy intake or physical activity index at age 15. The FTO *Study group interactions were not significant., Conclusions: Our results suggest that the effect of the FTO genotype on BMI becomes evident only after age 7 yr. These results further suggest that the FTO gene is not directly associated with energy intake or physical activity.

Background: Previous studies have suggested that interventions to lower dietary fat content and improved fat quality lead to a compensatory increase in sucrose content., Objective: The purpose of this work was to determine what associations exist between sucrose intake and intake of nutrients, intake of specific foods, and growth in children aged 13 months to 9 years of age in the prospective, randomized Special Turku Coronary Risk Factor Intervention Project., Subjects and Methods: Nutrient intake and food consumption were evaluated annually at ages 13 months through 9 years by using food records. Altogether, 543 children were divided into 3 groups according to mean sucrose intake: constantly high sucrose intake (highest 10%), constantly low sucrose intake (lowest 10%), and average sucrose intake (80%). Absolute and relative weights and heights were recorded at 7, 13, and 24 months of age and annually thereafter until 9 years old., Results: The high sucrose-intake group exceeded the recommended sucrose intake (<10% of energy intake, World Health Organization) already at the age of 2 years. Energy and total fat intake did not differ between the sucrose-intake groups. Children with low and average sucrose intake consumed more protein and had a better dietary fat quality than children with high sucrose intake. They also tended to receive more vitamin E, niacin, calcium, iron, zinc, and dietary fiber than children who consumed a high sucrose diet. Children in the low sucrose-intake group consumed more grains, vegetables, and dairy products than the other children. Sugar intake had no direct association with obesity, but weight, height, and BMI of children differed between the sucrose-intake groups between 7 months and 9 years of age., Conclusions: In children aged 13 months to 9 years, long-term low sucrose intake is associated with better nutrient intake and growth than high sucrose intake.

Objective: We studied whether the serum leptin concentration at age 2 years predicts changes in relative body weight by age 8 and whether the serum leptin concentration is associated with intake of energy and nutrients at age 5., Methods: A total of 156 8-year-old participants of the Special Turku Coronary Risk Factor Intervention Project were chosen to represent children whose relative weight decreased, was stable, or increased during the preceding 6 years. Their serum leptin concentrations were measured in samples collected when they were 2 years. Serum leptin was also measured in 100 5-year-old children in the Special Turku Coronary Risk Factor Intervention Project whose energy and nutrient intakes were analyzed using 4-day food records., Results: The boys whose relative weight decreased (n = 25), was stable (n = 28), or increased (n = 26) between 2 and 8 years of age had similar serum leptin concentrations at the age of 2 years. The girls whose relative weight decreased (n = 27) had higher serum leptin concentrations at 2 years than the girls whose relative weight remained stable (n = 26) but only when the leptin values were not adjusted for body mass index. The serum leptin concentration was higher in 5-year-old girls than in 5-year-old boys even when adjusted for body mass index. Serum leptin correlated with relative weight in girls and boys (r = 0.65 and r = 0.45, respectively). Serum leptin concentration adjusted for relative weight correlated poorly with intakes of energy, fat, saturated fat, carbohydrates, sucrose, and protein., Conclusions: Serum leptin concentrations at age 2 poorly predicted changes in relative body weight during the following 6 years and poorly reflected the intake of energy or major nutrients at age 5.

Objective: Elevated serum concentration of C-reactive protein (CRP) predicts cardiovascular events in adults. Because atherosclerosis begins in childhood, we undertook a study to determine whether changes in brachial artery endothelial function and the thickness of the carotid intima-media complex, 2 markers of early atherosclerosis, are related to CRP levels in healthy children., Methods and Results: Brachial artery flow-mediated dilatation (FMD) and carotid artery intima-media thickness (IMT) were measured with ultrasound in 79 children (aged 10.5+/-1.1 years). Compared with the children with CRP levels under the detection limit (<0.1 mg/L, n=40, group 1), the children with higher CRP (0.1 mg/L< or =CRP< or =0.7 mg/L, n=20, group 2; CRP >0.7 mg/L, n=19, group 3) had lower FMD (9.0+/-4.4% versus 7.8+/-3.3% versus 6.5+/-2.6%, respectively; P=0.015 for trend) and greater carotid IMT (0.45+/-0.03 versus 0.46+/-0.04 versus 0.49+/-0.06 mm, respectively, P=0.002 for trend). CRP level remained a statistically significant independent predictor for brachial FMD and carotid IMT in multivariate analyses., Conclusions: These data suggest that CRP affects the arteries of healthy children by disturbing endothelial function and promoting intima-media thickening. The findings support the hypothesis that CRP plays a role in the pathogenesis of early atherosclerosis.

Objectives: To evaluate the effects of diet, serum cholesterol concentrations, and apolipoprotein E phenotype on neurodevelopment of 5-year-old children., Study Design: Prospective, 4.4-year cohort study in 496 children. Fat-modified diet was introduced to intervention families of 7-month-old infants. Control children consumed an unrestricted diet. Nutrient intakes, serum cholesterol, and neurodevelopment were studied. The groups were combined in univariate and stepwise multivariate logistic regression analyses., Results: In 13-month-old boys (girls), energy intake was 996 (938) kcal, fat intake 26.6 (26.4) percent of energy (E%), and protein intake 17.2 (17.4) E%. In 5-year-old boys (girls), the intakes were 1484 (1364) kcal, 32.1 (31.9) E%, and 15.5 (15.9) E%, respectively. The intakes of total fat and saturated fat and serum cholesterol were not associated with neurodevelopment. In boys, high intake of protein at 5 years, high intakes of protein at 4 years and cholesterol at 2 years, and high intake of polyunsaturated fatty acids at 3 years predicted favorable outcomes in the tests of speech and language skills, gross motor function and perception, and visual motor skills, respectively. Apolipoprotein E phenotype did not influence the test performance., Conclusions: Moderate restriction of dietary fat has no unfavorable effects on neurodevelopment in early childhood. However, the quality of fat and the relative intake of protein may influence neurodevelopment of the boys.

Between May and August 1995, 5 patients in a bone marrow transplantation (BMT) ward developed bacteremia caused by Pseudomonas aeruginosa resistant to tobramycin (TRPA). Previously, isolates of TRPA had been limited to patients who were treated in 1 intensive care unit (ICU) of this tertiary care teaching hospital in Helsinki, Finland. To study whether the outbreak was caused by a single or multiple strains of P. aeruginosa, 102 isolates of TRPA from clinical samples obtained from different hospital units and 22 isolates obtained from the hospital environment were characterized by pulsed-field gel electrophoresis. All isolates from hematological patients produced 1 unique fragment pattern, which was also isolated from 3 ICU patients before the BMT ward outbreak began as well as from 5 shower heads in the BMT ward. The outbreak in the BMT ward was successfully controlled by eradicating the probable environmental source--contaminated hand showers--but the endemic infections continued in the ICU.