Fruits and vegetables taken can serve as a proxy measure for amounts eaten in a school lunch

This study tests the hypothesis that fruits and vegetables taken on students' lunch trays are usable proxies for fruits and vegetables eaten, and that the proxy is useful with children in the youngest school grade (ie, grade 1; ages 6 to 8 years). A total of 1,168 randomly selected students in grade 1 and grade 3 (ages 8 to 10 years) in 26 schools in the Twin Cities, MN, metropolitan area were observed before and after an intervention that was applied to 13 randomly selected schools. Trained observers recorded food quantities on a child's tray and measured food consumed during the meal. Correlations between amounts of fruits and vegetables taken and eaten ranged from 0.74 to 0.96. The median correlation in grade 1 was the same, 0.82, as in the combined sample. Food taken and food eaten as alternative response variables resulted in the same conclusions about the effects of intervention. The hypothesis is strengthened that food taken can be used as a proxy for consumption in future nutrition education research.     

Development of a polyamine database for assessing dietary intake

Reducing the concentration of polyamines (spermine, spermidine, and putrescine) in the body pool may slow the cancer process. Because dietary spermine, spermidine, and putrescine contribute to the body pool of polyamines, quantifying them in the diet is important. Limited information about polyamine content of food is available, especially for diets in the United States. This brief report describes the development of a polyamine database linked to the Fred Hutchinson Cancer Center food frequency questionnaire (FFQ). Values for spermine, spermidine, and putrescine were calculated and reported per serving size (nmol/serving). Of the foods from the database that were evaluated, fresh and frozen corn contain the highest levels of putrescine (560,000 nmol/serving and 902,880 nmol/serving) and spermidine (137,682 nmol/serving and 221,111 nmol/serving), and green pea soup contains the highest concentration of spermine (36,988 nmol/serving). The polyamine database and FFQ were tested with a convenience sample (n=165). Average daily polyamine intakes from the sample were: 159,133 nmol/day putrescine, 54,697 nmol/day spermidine, and 35,698 nmol/day spermine. Orange and grapefruit juices contributed the greatest amount of putrescine (44,441 nmol/day) to the diet. Green peas contributed the greatest amount of spermidine (3,283 nmol/day) and ground meat contributed the greatest amount of spermine (2,186 nmol/day). Development of this database linked to an FFQ provides a means of estimating polyamine intake and contributes to investigations relating polyamines to cancer.     

Genome-wide analysis of high-risk primary brain cancer pedigrees identifies PDXDC1 as a candidate brain cancer predisposition gene

BackgroundThere is evidence for an inherited contribution to primary brain cancer. Linkage analysis of high-risk brain cancer pedigrees has identified candidate regions of interest in which brain cancer predisposition genes are likely to reside.MethodsGenome-wide linkage analysis was performed in a unique set of 11 informative, extended, high-risk primary brain cancer pedigrees identified in a population genealogy database, which include from 2 to 6 sampled, related primary brain cancer cases. Access to formalin-fixed paraffin embedded tissue samples archived in a biorepository allowed analysis of extended pedigrees.ResultsIndividual high-risk pedigrees were singly informative for linkage at multiple regions. Suggestive evidence for linkage was observed on chromosomes 2, 3, 14, and 16. The chromosome 16 region in particular contains a promising candidate gene, pyridoxal-dependent decarboxylase domain-containing 1 (PDXDC1), with prior evidence for involvement with glioblastoma from other previously reported experimental settings, and contains the lead single nucleotide polymorphism (rs3198697) from the linkage analysis of the chromosome 16 region.ConclusionsPedigrees with a statistical excess of primary brain cancers have been identified in a unique genealogy resource representing the homogeneous Utah population. Genome-wide linkage analysis of these pedigrees has identified a potential candidate predisposition gene, as well as multiple candidate regions that could harbor predisposition loci, and for which further analysis is suggested.     

Newborn screening by tandem mass spectrometry: ethical and social issues

Emerging technologies like Tandem Mass Spectrometry (TMS) enable multiple tests on a single blood sample and allow the expansion of Newborn Screening (NBS) to include various metabolic diseases. Introducing TMS for NBS raises important social and ethical questions: what are the criteria for adding disorders to screening panels? What evidence justifies expansion of screening? How can equity in NBS access and standards be ensured? How can policy standards be set, given the multiplicity of stakeholders? To address emerging issues, policy-makers, patient advocates, clinicians and researchers had a workshop during the 2005 Garrod Symposium. The participants received a summary of the discussion and understood the workshop's goal was to provide a basis for further discussion. This article contributes to this ongoing discussion. Several proposed recommendations assert the centrality of including social and ethical issues in the assessment of whether or not to introduce TMS. The article outlines five key recommendations for advancing the NBS agenda: national public health leadership; transparency; increased national consistency in NBS strategy, including minimum standards; collaboration between the federal and provincial/territorial governments and diverse stakeholders; and supporting research and/or programs based on effectiveness, which integrate ethical and social issues into assessment.     

Telephone counseling helps maintain long-term adherence to a high-vegetable dietary pattern

Achieving long-term adherence to a dietary pattern is a challenge in many studies investigating the relationship between diet and disease. The Women's Healthy Eating and Living Study was a multi-institutional randomized trial in 3088 women at risk for breast cancer recurrence. At baseline, the average participant followed a healthy dietary pattern of 7 vegetable and fruit servings, 21 g/d of fiber, and 28.7% energy from fat, although fat intake increased over the enrollment period. Using primarily telephone counseling, the intervention group was encouraged to substantially increase intakes of vegetables, fruits, and fiber while decreasing fat intake. Sets of 24-h dietary recalls were completed on 90% of eligible participants at 1 y and 86% at 4 y. Using a conservative imputation analysis, at 1 y, the intervention group consumed 38% more vegetable servings (100% when including juice) than the comparison group, 20% more fruit, 38% more fiber, 50% more legumes, and 30% more whole grain foods, with a 20% lower intake of energy from fat. At 4 y, the between-group differences were 65% for vegetables (including juice), 25% fruit, 30% fiber, 40% legumes, 30% whole grain foods, and 13% lower intake of energy from fat. The intervention effect on fat intake was similar for early vs. late enrollees. Plasma carotenoid concentrations on a random 28% sample validated self-reported vegetable and fruit intake, with a between-group difference of 66% at 1 y and over 40% at 4 y. This large change will allow testing of hypotheses on the role of dietary change in preventing additional breast cancer events.     

Elevated blood-lead levels among children living in the rural Philippines

OBJECTIVE: Generally, lead poisoning is not considered a significant environmental hazard for children in rural areas of developing countries. With a prospectively designed policy experiment, the research community and the government are conducting a broad-based investigation to introduce and evaluate the impact of health policy reforms on children in a rural area of the Philippines - the Quality Improvement Demonstration Study (QIDS). As part of this study, we researched lead exposure in children under the age of five. METHODS: We sampled a population of children from the Visayas region in the central Philippines, covering approximately one third of the country's geographical area. From December 2003 to September 2004, the survey collected blood lead levels (BLL) together with demographic, socioeconomic and child health data points. Supplemental field-testing among a sub-sample of the most exposed children assessed the sources of environmental lead exposure. FINDINGS: Among children in this study, 21% (601 of 2861 children) had BLL greater than 10 microg/dl. BLL were associated independently with age, haemoglobin concentration, water source, roofing material, expenditures and history of breastfeeding. A follow-up assessment of possible environmental exposures among the sub-sample of children with elevated BLL revealed no single or predominant exposure source. Instead, there appear to be multiple potential sources, such as fossil-fuel combustion, lead paint (in or around 38% of homes) and household items. CONCLUSION: Elevated BLL are common among children in the Visayas, and may signify an under-recognized threat to children living in rural areas of other developing nations. This setting has varied environmental sources of lead. Observed correlates of BLL may be of clinical, environmental and public health utility to identify and mitigate the consequences of lead toxicity.     

RAS Amplification as a Negative Predictor of Benefit from Anti-EGFR–Containing Therapy Regimens in Metastatic Colorectal Cancer

Background RAS short variant (SV) mutations in colorectal cancer (CRC) are associated with lack of benefit from epidermal growth factor receptor (EGFR) monoclonal antibody (EGFRmAb). However, the clinical implications for RAS amplification (RASa) as a biomarker for anti‐EGFR therapy in CRC remain ill defined.MethodsGenomic analysis was performed using the Foundation Medicine (FM) comprehensive genomic profiling database of 37,233 CRC cases. Clinical outcomes were assessed using two independent cohorts: the City of Hope (COH) cohort of 338 patients with metastatic CRC (mCRC) and the Flatiron Health–FM real‐world clinicogenomic database (CGDB) of 3,904 patients with mCRC.Results RASa was detected in 1.6% (614/37,233) of primarily mCRC. RASa 6–9 (n = 241, 39%), 10–19 (n = 165, 27%), and ≥ 20 (n = 209, 34%) copy number subsets had co‐RAS SV/BRAF V600E in 63%/3%, 31%/0.6%, and 4.8%/0% of cases, respectively. In the COH cohort, six patients with RASa (13–54 copies) received EGFRmAb, four of six had progressive disease, two had stable disease, and median time to treatment discontinuation (TTD) was 2.5 months. Of the CGDB EGFRmAb‐treated patients, those with RASa (n = 9) had median TTD of 4.7 months and overall survival (OS) of 11.4 months, those with RAS SV (n = 101) had median TTD and OS of 5.3 and 9.4 months, and those with RAS/BRAF wild‐type (n = 608) had median TTD and OS of 7.6 and 13.7 months.ConclusionPatients with RASa without RAS mutations (1.1% of mCRC) may have poor outcomes on EGFRmAb, although numbers herein were small, and interpretation is confounded by combination chemotherapy. Larger independent studies are warranted to determine if RASa, including degree of amplification, may act similarly to RAS mutation as a resistance mechanism to EGFRmAb therapies.Implications for PracticeGenomic data suggest that RAS amplification occurs as the sole RAS/RAF alteration in >1% of colorectal cancer cases and that degree of amplification inversely correlates with co‐occurring MAPK pathway alterations. Preliminary clinical evidence suggests that RAS amplification may function similarly to RAS mutation as a negative predictor of benefit from anti‐epidermal growth factor receptor therapies in colorectal cancer. More clinical data are needed, and comprehensive genomic profiling, including detection of RAS amplification, should be used in trial design to inform therapy selection.     

Perinatal bisphenol A exposure increases estrogen sensitivity of the mammary gland in diverse mouse strains

BACKGROUND: Studies of low-dose effects of xenoestrogens have yielded conflicting results that may be attributed to differences in estrogen sensitivity between the rodent strains examined. Perinatal exposure of CD-1 mice to low doses of the xenoestrogen bisphenol A (BPA) alters peripubertal mammary gland development. Future studies to assess the role of estrogen receptors as mediators of BPA action require estrogen receptor knock-out mice that were generated on a C57Bl6 background. The sensitivity of the C57Bl6 strain to estradiol and BPA is unknown. OBJECTIVES: In the present study we examined whether the mammary glands of CD-1 and C57Bl6 mice exhibited similar responses to 17beta-estradiol (E(2)) and whether perinatal exposure to BPA equally enhanced sensitivity of the mammary glands to E(2) at puberty. METHODS: Immature mice were ovariectomized and treated for 10 days with one of eight doses of E(2). Morphological mammary gland parameters were examined to identify doses producing half-maximal effects. Mice were exposed perinatally to 0 or 250 ng BPA/kg body weight (bw)/day from gestational day 8 until postnatal day (PND) 2. On PND25, female offspring were ovariectomized and given an estrogen challenge of 0, 0.5, or 1 microg E(2)/kg bw/day for 10 days. Morphometric parameters of the mammary gland were compared between strains. RESULTS: Both strains exhibited similar responses to E(2). Perinatal BPA exposure altered responses to E(2) at puberty for several parameters in both strains, although the effect in CD-1 was slightly more pronounced. CONCLUSION: Both mouse strains provide adequate models for the study of perinatal exposure to xenoestrogens.     

Drinking water with uranium below the U.S. EPA water standard causes estrogen receptor-dependent responses in female mice

BACKGROUND: The deleterious impact of uranium on human health has been linked to its radioactive and heavy metal-chemical properties. Decades of research has defined the causal relationship between uranium mining/milling and onset of kidney and respiratory diseases 25 years later. OBJECTIVE: We investigated the hypothesis that uranium, similar to other heavy metals such as cadmium, acts like estrogen. METHODS: In several experiments, we exposed intact, ovariectomized, or pregnant mice to depleted uranium in drinking water [ranging from 0.5 microg/L (0.001 microM) to 28 mg/L (120 microM). RESULTS: Mice that drank uranium-containing water exhibited estrogenic responses including selective reduction of primary follicles, increased uterine weight, greater uterine luminal epithelial cell height, accelerated vaginal opening, and persistent presence of cornified vaginal cells. Coincident treatment with the antiestrogen ICI 182,780 blocked these responses to uranium or the synthetic estrogen diethylstilbestrol. In addition, mouse dams that drank uranium-containing water delivered grossly normal pups, but they had significantly fewer primordial follicles than pups whose dams drank control tap water. CONCLUSIONS: Because of the decades of uranium mining/milling in the Colorado plateau in the Four Corners region of the American Southwest, the uranium concentration and the route of exposure used in these studies are environmentally relevant. Our data support the conclusion that uranium is an endocrine-disrupting chemical and populations exposed to environmental uranium should be followed for increased risk of fertility problems and reproductive cancers.