No Incidence of BRAF Mutations in Salivary Gland Carcinomas—Implications for Anti-EGFR Therapies

BRAF is the main effector of KRAS in the RAS-RAF-MAPK axis, a signaling pathway downstream of EGFR. The activation of this cascade is an important pathway in cancer development and is considered a key pathway for therapeutic molecules. Recent studies in metastatic colorectal cancer found that an oncogenic activation of BRAF by a point mutation in exon 15 (V600E) could bypass the EGFR-initiated signaling cascade with the effect that patients bearing the mutant BRAF allele are not likely to benefit from EGFR-targeted therapies. We designed an allele-specific PCR and screened 65 salivary gland carcinoma (SGC) of the main histopathological types for the BRAF V600E mutation. All 65 SGC in this cohort (100%) presented the BRAF wildtype. In a previous study, we found a KRAS wildtype in 98.5% of SGC. These findings imply that SGC rarely acquires mutations that result in a constitutive activation of the signaling cascade downstream of EGFR and this pleads in favor of further therapeutic trials with EGFR-targeting monoclonal antibodies

Frequency of secondary dyslipidemia in obese children

Ulrike Korsten-Reck1, Katrin Kromeyer-Hauschild2, Katrin Korsten1, Manfred W Baumstark1, Hans-H Dickhuth1, Aloys Berg11Department of Rehabilitative and Preventive Sports Medicine, University Medical Center, University of Freiburg, 79106 Freiburg, Germany; 2Institute of Human Genetics and Anthropology, Friedrich-Schiller-University Jena, 07740 Jena, GermanyObjective: This paper reports the frequency, type, and degree of dyslipidemia in obese children before therapeutic intervention. The relationships between lipid values and weight status, as well as lipid values and physical fitness, of these children were also investigated.Design and methods: The initial examination of the Freiburg Intervention Trial for Obese Children (FITOC) measured the values of triglycerides (TG), total cholesterol (C), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in 546 obese children aged 7–12 (body mass index [BMI] > 97th percentile), and compared these values with those of the age- and sex-specific reference group in the Lipid Research Clinics Population Studies Data Book (LRC). Four groups were selected according to the following scheme: A, Normolipidemia; B, Hyper-LDL-cholesterolemia alone; C, Hypo-HDL-C + hypertriglyceridemia; D, Combined hyperlipidemia = Hyper-LDL-C + hypertriglyceridemia. Body mass index, BMI-SDS (corrected BMI), and physical performance in watt/kg body weight were measured.Results: A total of 45.8% of the overweight children showed an abnormal lipid profile. Ten percent of the children had high LDL-C levels (group B), while 15% had increased LDL-C and increased TG (group D) (higher prevalence in boys). In 18.9% we found increased TG, combined with decreased HDL-C values (group C).Conclusion: Obese children are at risk of dyslipoproteinemia and related diseases. Children with the highest BMI-SDS and lowest physical fitness have the lowest HDL-C values and increased TG, indicating a higher risk for the metabolic syndrome.Keywords: atherosclerotic risk, childhood, dyslipidemia, obesit

BMI at Age 8 Years Is Influenced by the Type 2 Diabetes Susceptibility Genes HHEX-IDE and CDKAL1

OBJECTIVE: To determine whether HHEX-IDE and CDKAL1 genes, which are associated with birth weight and susceptibility to type 2 diabetes, continue to influence growth during childhood. RESEARCH DESIGN AND METHODS: BMI, weight, and height at age 8 years expressed as age- and sex-corrected standard deviation scores (SDS) against national reference data and single-nucleotide polymorphism genotyping of HHEX-IDE and CDKAL1 loci were analyzed in 646 prospectively followed children in the German BABYDIAB cohort. All children were singleton full-term births; 386 had mothers with type 1 diabetes, and 260 had fathers with type 1 diabetes and a nondiabetic mother. RESULTS: Type 2 diabetes risk alleles at the HHEX-IDE locus were associated with reduced BMI-SDS at age 8 years (0.17 SDS per allele; P = 0.004). After stratification for birth weight, both HHEX-IDE and CDKAL1 risk alleles were associated with reduced BMI-SDS (0.45 SDS, P = 0.0002; 0.52 SDS, P = 0.0001) and weight-SDS (0.22 SDS, P = 0.04; 0.56 SDS, P = 0.0002) in children born large for gestational age (>90th percentile) but not children born small or appropriate for gestational age. Within children born large for gestational age, BMI and weight decreased with each additional type 2 diabetes risk allele ( approximately -2 kg per allele; >8 kg overall). Findings were consistent in children of mothers with type 1 diabetes (P < 0.0001) and children of nondiabetic mothers (P = 0.008). CONCLUSIONS: The type 2 diabetes susceptibility alleles at HHEX-IDE and CDKAL1 loci are associated with low BMI at age 8 years in children who were born large for gestational age

The Biological Standard of Living in the two Germanies.

Physical stature is used as a proxy for the biological standard of living in the two Germanies before and after unification in an analysis of a cross-sectional sample (1998) of adult heights, as well as among military recruits of the 1990s. West Germans tended to be taller than East Germans throughout the period under consideration. Contrary to official proclamations of a classless society, there were substantial social differences in physical stature in East-Germany. Social differences in height were greater in the East among females, and less among males than in the West. The difficulties experienced by the East-German population after 1961 is evident in the increase in social inequality of physical stature thereafter, as well as in the increasing gap relative to the height of the West-German population. After unification, however, there is a tendency for East-German males, but not of females, to catch up with their West-German counterparts

Comparison of major dish item and food group consumption between normal and obese Korean children: application to development of a brief food frequency questionnaire for obesity-related eating behaviors

This study sought to compare intake levels of major dish items and food groups between normal and obese Korean children in order to understand obesity-related eating behaviors. The study was also conducted to apply the information on the differences in major dish items and food groups found in this study to development of a brief food frequency questionnaire (FFQ) for children's obesity-related eating behaviors. Finally, the developed FFQ was evaluated for reliability. A total of 290, 24-hour dietary recall data from 9-11 year-old normal or obese participants in the 2001 Korean National Health and Nutrition Examination Survey (KNHANES) were reviewed to identify dish items and food groups showing outstanding differences between the normal and obese groups. Based on the level of intake amount between the two groups, a total of 7 items, including ddeokbokggi, spaghetti, ham roast, pork cutlet, dairy products & ices, kimchi, and fruits, were selected to be included in the FFQ. The former 5 items were seen to be consumed more in the obese group, while the latter 2 items were so in the normal group. The questionnaire was formatted into a frequency response section of a seven-category option and reference period of the last 7 days. Test-retest reliability of the developed FFQ was examined by administering it to 153, 9-11 year-old children at a public elementary school in Seoul twice at a month interval. The level of reliability was found to be reasonably high. In conclusion, this study suggests that high consumption of several high-calorie dish items and low consumption of kimchi and fruits may be important eating behaviors in relation to obesity risk among 9-11 year-old children who need nutrition educators' attention. The current study also implies that a simple FFQ can be utilized to reliably assess 9-11 year-old children's diets

Current Guidelines for Obesity Prevention in Childhood and Adolescence

Objective: Current guidelines for prevention of obesity in childhood and adolescence are discussed. Methods: A literature search was performed in Medline via PubMed, and appropriate studies were analyzed. Results: Programs to prevent childhood obesity have so far remained mainly school-based and effects have been limited. Analyses by age group show that prevention programs have the best results in younger children (Conclusion: Behavior-oriented prevention programs showed only limited long-term effects. Certain groups at risk for the development of obesity are not reached effectively by current programs. Although universally valid conclusions cannot be drawn given the heterogeneity of available studies, clearly combining behavior-based programs with community-based prevention to counteract an ‘obesogenic environment' is crucial for sustainable success of future obesity prevention programs

Relation of obesity-related attitudes, knowledge, and eating behaviors with body weight and body shape satisfaction in 5th-grade Korean children

Obesity is a worldwide epidemic problem. The downward trend of an obesity onset age calls for research efforts on how to develop useful nutrition educational programs for children to maintain adequate body weight. Understanding the roles of objective and subjective body status in obesity-related attitudes, knowledge, and behaviors can provide important information. The current study aimed to examine obesity-related attitudes and knowledge and practices of eating behavior guidelines in relation to obesity and body shape satisfaction among children. The gender effect in the relations was also investigated. A self-administered survey was conducted with 260 fifth grade children at 2 public elementary schools in the suburbs of Seoul. Information on demographics, body size, body satisfaction, obesity-related attitudes and knowledge, and eating behaviors was collected. Study findings from one-way analysis of variance tests indicated no differences in mean scores of the attitudes, knowledge, and eating behaviors across the levels of obesity for both gender. The levels of body shape satisfaction was, however, found to be significantly related with the attitudes and eating behaviors in girls, while no such relation was seen in boys. Girls with lower body shape dissatisfaction had significantly more negative attitudes toward obesity which was not translated into practice of healthy eating behaviors. That is, contrary to general expectation, the level of practicing the eating behavior guidelines was significantly lower in those girls. While underlying reasons for this observation is not fully answered, gender-specific, body satisfaction-stratified, and behavior-focused approach in designing obesity prevention programs for elementary school girls is suggested efficient and useful