Diabetes Prevention and Weight Loss with a Fully Automated Behavioral Intervention by Email, Web, and Mobile Phone: A Randomized Controlled Trial Among Persons with Prediabetes.

BACKGROUND: One-third of US adults, 86 million people, have prediabetes. Two-thirds of adults are overweight or obese and at risk for diabetes. Effective and affordable interventions are needed that can reach these 86 million, and others at high risk, to reduce their progression to diagnosed diabetes. OBJECTIVE: The aim was to evaluate the effectiveness of a fully automated algorithm-driven behavioral intervention for diabetes prevention, Alive-PD, delivered via the Web, Internet, mobile phone, and automated phone calls. METHODS: Alive-PD provided tailored behavioral support for improvements in physical activity, eating habits, and factors such as weight loss, stress, and sleep. Weekly emails suggested small-step goals and linked to an individual Web page with tools for tracking, coaching, social support through virtual teams, competition, and health information. A mobile phone app and automated phone calls provided further support. The trial randomly assigned 339 persons to the Alive-PD intervention (n=163) or a 6-month wait-list usual-care control group (n=176). Participants were eligible if either fasting glucose or glycated hemoglobin A1c (HbA1c) was in the prediabetic range. Primary outcome measures were changes in fasting glucose and HbA1c at 6 months. Secondary outcome measures included clinic-measured changes in body weight, body mass index (BMI), waist circumference, triglyceride/high-density lipoprotein cholesterol (TG/HDL) ratio, and Framingham diabetes risk score. Analysis was by intention-to-treat. RESULTS: Participants' mean age was 55 (SD 8.9) years, mean BMI was 31.2 (SD 4.4) kg/m(2), and 68.7% (233/339) were male. Mean fasting glucose was in the prediabetic range (mean 109.9, SD 8.4 mg/dL), whereas the mean HbA1c was 5.6% (SD 0.3), in the normal range. In intention-to-treat analyses, Alive-PD participants achieved significantly greater reductions than controls in fasting glucose (mean -7.36 mg/dL, 95% CI -7.85 to -6.87 vs mean -2.19, 95% CI -2.64 to -1.73, P<.001), HbA1c (mean -0.26%, 95% CI -0.27 to -0.24 vs mean -0.18%, 95% CI -0.19 to -0.16, P<.001), and body weight (mean -3.26 kg, 95% CI -3.26 to -3.25 vs mean -1.26 kg, 95% CI -1.27 to -1.26, P<.001). Reductions in BMI, waist circumference, and TG/HDL were also significantly greater in Alive-PD participants than in the control group. At 6 months, the Alive-PD group reduced their Framingham 8-year diabetes risk from 16% to 11%, significantly more than the control group (P<.001). Participation and retention was good; intervention participants interacted with the program a median of 17 (IQR 14) of 24 weeks and 71.1% (116/163) were still interacting with the program in month 6. CONCLUSIONS: Alive-PD improved glycemic control, body weight, BMI, waist circumference, TG/HDL ratio, and diabetes risk. As a fully automated system, the program has high potential for scalability and could potentially reach many of the 86 million US adults who have prediabetes as well as other at-risk groups. TRIAL REGISTRATION: Clinicaltrials.gov NCT01479062; https://clinicaltrials.gov/ct2/show/NCT01479062 (Archived by WebCite at http://www.webcitation.org/6bt4V20NR).

Unusual clustering of coefficients of variation in published articles from a medical biochemistry department in India.

A simple statistical method is described to test whether data are consistent with minimum statistical variability expected in a biological experiment. The method is applied to data presented in data tables in a subset of 84 articles among more than 200 published by 3 investigators in a small medical biochemistry department at a major university in India and to 29 "control" articles selected by key word PubMed searches. Major conclusions include: 1) unusual clustering of coefficients of variation (CVs) was observed for data from the majority of articles analyzed that were published by the 3 investigators from 2000-2007; unusual clustering was not observed for data from any of their articles examined that were published between 1992 and 1999; and 2) among a group of 29 control articles retrieved by PubMed key word, title, or title/abstract searches, unusually clustered CVs were observed in 3 articles. Two of these articles were coauthored by 1 of the 3 investigators, and 1 was from the same university but a different department. We are unable to offer a statistical or biological explanation for the unusual clustering observed.

The utility of routine surveillance blood cultures in asymptomatic hematopoietic stem cell transplant patients.

INTRODUCTION: Surveillance blood cultures (BCs) are often obtained in hematopoietic stem cell transplant (HSCT) patients for earlier detection of blood stream infections (BSI). The major aim of this study was to determine the utility of the current practice of obtaining surveillance blood cultures from asymptomatic transplant patients upon admission for the preparative regimen. METHODS: We conducted an 8-year retrospective study of all patients consecutively admitted to the hospital for a HSCT from 2000 to 2008. RESULTS: In this retrospective analysis, surveillance BCs from 191 eligible patients were analyzed. The incidence of definitive BSIs was 0.52% (1/191) with 6 BCs from other HSCT patients growing probable contaminants. The overall incidence of positive surveillance BCs was 2.9% (7/238) for the BCs taken and 3.7% (7/191) for patients cultured with coagulase negative staphylococcus being isolated from 6 of the 7 patients. The probability of increased BSI after transplantation in patients with initial positive surveillance BCs compared with those having negative BCs, was not significant (P=0.675). No infection-related mortality was observed during the first 60 days posttransplantation in these patients. CONCLUSIONS: The frequency of positive surveillance BCs in asymptomatic HSCT patients at the time of hospital admission for transplant seems to be extremely low. These results, if confirmed by larger studies, show the reduced utility of obtaining surveillance BC in asymptomatic patients before administration of the conditioning regimen and the need for re-evaluation of this practice.

Insulin resistance is improved in overweight African American boys but not in girls following a one-year multidisciplinary community intervention program.

AIM: To assess potential for effectiveness, in a non-randomized pilot study, of a community-based lifestyle intervention program to reduce the risk for type 2 diabetes mellitus in overweight African American (AA) children. RESEARCH DESIGN: Sample of 165 9-11 year-old AA children with body mass index (BMI) >85th percentile were recruited from local recreational sites, schools and churches. Participants self-selected to attend one of two study sites, blinded to the specifics of the intervention administered at each site. The intervention group received a programmatically focused 2-week summer camp with once-a-week community-based exercise, nutrition, and behavioral modification sessions, and their families were invited to monthly nutrition educational sessions. Control group participants received a 2-week conventional YMCA summer camp and their families received nutrition and physical activity education material through the mail. Baseline assessment and 1-year follow-up were conducted in collaboration with the YMCA of the East Bay and Children's Hospital Oakland, CA, with 109 participants (66%) having pre/post data. RESULTS: After one-year of intervention, treatment boys showed a drop in homeostasis model assessment of insulin-resistance (HOMA-IR) (-0.58 vs +0.17; p = 0.003), fasting glucose (Gf, mg/dL) (mean change: -2.9 vs +0.4; p = 0.126) and fasting insulin (If, microU/mL) (-2.2 vs +0.7; p = 0.009) compared to control boys, after accounting for baseline differences and pubertal stage of the child. Treatment girls had similar changes to the control girls in HOMA-IR (-0.02 vs -0.17; p = 0.66), Gr (-0.3 vs +1.4; p = 0.29) and If (+0.03 vs +0.17; p = 0.57). CONCLUSION: After one year, this community-based intervention program effectively improved insulin resistance and thus reduced risk for type 2 diabetes mellitus in overweight AA boys but did not change the risk in girls compared to control children.

Using acupuncture for acute pain in hospitalized children.

OBJECTIVE: Clinical study to determine the acceptability and feasibility of acupuncture for acute postoperative pain control in hospitalized children. DESIGN: Nonrandomized clinical trial. SETTING: A single, tertiary referral pediatric intensive care unit. PATIENTS: A total of 20 patients aged 7 months to 18 years. Eleven of the patients had posterior spinal fusion surgery and the remaining nine patients had other surgical diagnoses. INTERVENTIONS: Two 10- to 15-minute sessions of acupuncture 24-48 hours apart. OUTCOME MEASURES AND RESULTS: The treatment was highly accepted (27 patients were approached and 4 patients refused; of the 23 patients enrolled, 20 patients completed the study). Acupuncture was well tolerated by patients without adverse events related to treatment. In follow-up interviews, 70% of both parents and patients believed acupuncture helped the child's pain. Eighty-five percent of the parents said they would pay out of pocket for acupuncture if not covered by insurance. The pain scores, vital signs, and narcotic usage were recorded before and several times after acupuncture. In posterior spinal fusion patients, the mean pain scores (0-10) immediately before and 4 and 24 hours after acupuncture were: 3.7, 1.7, and 3.1, respectively, after the first acupuncture session and 3.7, 2.2, and 3.1, respectively, after the second session. In the other surgical cohort, the mean pain scores immediately before and 4 and 24 hours after the first session of acupuncture were 2.5, 0.3, and 1.6, respectively. CONCLUSIONS: Our results support that acupuncture is highly accepted and feasible in critically ill, postoperative pediatric patients with acute pain. Our findings suggest that acupuncture may be a potentially useful adjunctive tool for acute pediatric postoperative pain management. A randomized, controlled clinical trial is warranted to confirm these findings.

Maternal diet and risk of childhood acute lymphoblastic leukemia.

OBJECTIVE: Intrauterine environmental factors, including maternal diet, may play an etiologic role in acute lymphoblastic leukemia (ALL), a common childhood cancer. Expanding on previous findings from phase 1 of the Northern California Childhood Leukemia Study (NCCLS), a population-based case-control study, we sought to further elucidate and replicate the relationships between maternal diet and ALL risk. METHODS: We matched 282 case-control sets of children (205 pairs and 77 triplets) from phases 1 and 2 of the NCCLS on sex, date of birth, mother's race, Hispanic racial/ethnic status, and county of residence at birth. We used an interviewer-administered food frequency questionnaire to obtain information on maternal dietary intake in the 12 months prior to pregnancy. RESULTS: Risk of ALL was inversely associated with maternal consumption of vegetable (adjusted odds ratio [AOR] = 0.65, 95% confidence interval [CI] 0.50, 0.84); protein sources (AOR = 0.55, 95% CI 0.32, 0.96); fruit (AOR = 0.81, 95% CI 0.65, 1.00); and legume food groups (AOR = 0.75, 95% CI 0.59, 0.95). The risk reduction was strongest for consumption of the protein sources and vegetable food groups, independent of the child's diet up to age 2 years, and consistent across phases 1 and 2 of data collection for vegetable consumption. CONCLUSIONS: These data suggest that it may be prudent for women to consume a diet rich in vegetables and adequate in protein prior to and during pregnancy as a possible means of reducing childhood ALL risk in their offspring.

The effect of vitamins C and E on biomarkers of oxidative stress depends on baseline level.

Oxidative stress is elevated in obesity, and may be a major mechanism for obesity-related diseases. Nonsmokers (n=396) were randomized to 1000 mg/day vitamin C, 800 IU/day vitamin E, or placebo, for 2 months. Treatment effect was examined in multiple regression analyses using an intention-to-treat approach. Vitamin C (P=0.001) and vitamin E (P=0.043) reduced plasma F2-isoprostanes. In the overall sample, changes from baseline were +6.8, -10.6, and -3.9% for placebo, vitamin C, and vitamin E groups, respectively. However, a significant interaction with baseline F2-isoprostane was found. When baseline F2-isoprostane was >50 microg/mL, vitamin C reduced F2-isoprostane by 22% (P=0.01). Vitamin E reduced it by 9.8% (P=0.46). Below that cut point, neither treatment produced further reductions. F2-isoprostane>50 microg/mL was strongly associated with obesity, and was present in 42% of the sample. Change in malondialdehyde concentration was minimal. These findings suggest a role for vitamin C in reducing lipid peroxidation. Future research on effects of vitamins C or E on plasma F2-isoprostane should limit participants to those with baseline levels >50 mug/mL. Further studies are needed to establish whether treatment with vitamins C or E in persons with concentrations above that cut point could slow the development of cardiovascular disease.

Learner-centered nutrition education improves folate intake and food-related behaviors in nonpregnant, low-income women of childbearing age.

BACKGROUND: Recent studies suggest low-income women of childbearing age may be at risk of suboptimal folate intake. OBJECTIVE: To evaluate the effect of learner-centered nutrition education on folate intake and food-related behaviors among nonpregnant, low-income women of childbearing age, compared to education unrelated to nutrition. DESIGN: Participants were randomly assigned by recruitment site to receive either the nutrition lesson or a control lesson about resource management. PARTICIPANTS: Nonpregnant, low-income (< or =185% federal poverty level) women of childbearing age (18 to 45 years, n=155) from five California counties. MAIN OUTCOME VARIABLES: Changes in folate intake and other food-related behaviors. STATISTICAL ANALYSIS: Analysis of covariance, adjusting for baseline responses and potential confounders. RESULTS: Adjusting for baseline, participants who received the nutrition education had greater increases in folate intake and use of the Nutrition Facts label than the control group. Change in intake of specific folate-rich foods differed by ethnicity. Participants in the Special Supplemental Nutrition Program for Women, Infants, and Children who received the nutrition education increased folate intake but had no significant changes in other food-related behaviors. Food stamp recipients who received the nutrition education had no significant changes in folate intake but did increase the frequency of eating more than one kind of vegetable each day, compared to controls. CONCLUSIONS: This study supports the use of learner-centered approaches to nutrition education for low-income audiences, compared to education unrelated to nutrition. Future work is needed to compare learner-centered techniques to traditional pedagogical nutrition education, and to determine whether observed changes from this study persist over the long term.

Folate intake and food-related behaviors in nonpregnant, low-income women of childbearing age.

Information about folate intake among low-income women of childbearing age remains limited. This report presents results from a cross-sectional study of folate intake and food-related behaviors in a sample of low-income, nonpregnant women of childbearing age in California. One hundred fifty-seven nonpregnant, low-income (

Vitamin C in plasma is inversely related to blood pressure and change in blood pressure during the previous year in young Black and White women.

BACKGROUND: The prevalence of hypertension and its contribution to cardiovascular disease risk makes it imperative to identify factors that may help prevent this disorder. Extensive biological and biochemical data suggest that plasma ascorbic acid may be such a factor. In this study we examined the association between plasma ascorbic acid concentration and blood pressure (BP) in young-adult women. METHODS: Participants were 242 Black and White women aged 18-21 yr from the Richmond, CA, cohort of the National Heart, Lung and Blood Institute Growth and Health Study. We examined the associations of plasma ascorbic acid with BP at follow-up year 10, and with change in BP during the previous year. RESULTS: In cross-sectional analysis, plasma ascorbic acid at year 10 was inversely associated with systolic BP and diastolic BP after adjusting for race, body mass index, education, and dietary intake of fat and sodium. Persons in the highest one-fourth of the plasma ascorbic acid distribution had 4.66 mmHg lower systolic BP (95% CI 1.10 to 8.22 mmHg, p = 0.005) and 6.04 mmHg lower diastolic BP (95% CI 2.70 to 9.38 mmHg, p = 0.0002) than those in the lowest one-fourth of the distribution. In analysis of the change in BP, plasma ascorbic acid was also inversely associated with change in systolic BP and diastolic BP during the previous year. While diastolic blood pressure among persons in the lowest quartile of plasma ascorbic acid increased by 5.97 mmHg (95% CI 3.82 to 8.13 mmHg) from year 9 to year 10, those in the highest quartile of plasma vitamin C increased by only 0.23 mmHg (95% CI -1.90 to +2.36 mmHg) (test for linear trend: p < 0.0001). A similar effect was seen for change in systolic BP, p = 0.005. CONCLUSION: Plasma ascorbic acid was found to be inversely associated with BP and change in BP during the prior year. The findings suggest the possibility that vitamin C may influence BP in healthy young adults. Since lower BP in young adulthood may lead to lower BP and decreased incidence of age-associated vascular events in older adults, further investigation of treatment effects of vitamin C on BP regulation in young adults is warranted.

Usage patterns, health, and nutritional status of long-term multiple dietary supplement users: a cross-sectional study.

BACKGROUND: Dietary supplement use in the United States is prevalent and represents an important source of nutrition. However, little is known about individuals who routinely consume multiple dietary supplements. This study describes the dietary supplement usage patterns, health, and nutritional status of long-term multiple dietary supplement users, and where possible makes comparisons to non-users and multivitamin/mineral supplement users. METHODS: Using a cross-sectional study design, information was obtained by online questionnaires and physical examination (fasting blood, blood pressure, body weight) from a convenience sample of long-term users of multiple dietary supplements manufactured by Shaklee Corporation (Multiple Supp users, n = 278). Data for non-users (No Supp users, n = 602) and multivitamin/mineral supplement users (Single Supp users, n = 176) were obtained from the National Health and Nutrition Examination Survey (NHANES) 2001-2002 and NHANES III 1988-1994. Logistic regression methods were used to estimate odds ratios with 95% confidence intervals. RESULTS: Dietary supplements consumed on a daily basis by more than 50% of Multiple Supp users included a multivitamin/mineral, B-complex, vitamin C, carotenoids, vitamin E, calcium with vitamin D, omega-3 fatty acids, flavonoids, lecithin, alfalfa, coenzyme Q10 with resveratrol, glucosamine, and a herbal immune supplement. The majority of women also consumed gamma linolenic acid and a probiotic supplement, whereas men also consumed zinc, garlic, saw palmetto, and a soy protein supplement. Serum nutrient concentrations generally increased with increasing dietary supplement use. After adjustment for age, gender, income, education and body mass index, greater degree of supplement use was associated with more favorable concentrations of serum homocysteine, C-reactive protein, high-density lipoprotein cholesterol, and triglycerides, as well as lower risk of prevalent elevated blood pressure and diabetes. CONCLUSION: This group of long-term multiple dietary supplement users consumed a broad array of vitamin/mineral, herbal, and condition-specific dietary supplements on a daily basis. They were more likely to have optimal concentrations of chronic disease-related biomarkers, and less likely to have suboptimal blood nutrient concentrations, elevated blood pressure, and diabetes compared to non-users and multivitamin/mineral users. These findings should be confirmed by studying the dietary supplement usage patterns, health, and nutritional status of other groups of heavy users of dietary supplements.

Impact of California Children's Power Play! Campaign on Fruit and Vegetable Intake and Physical Activity among Fourth- and Fifth-Grade Students.

PURPOSE: Examine the impact of the Children's Power Play! Campaign on fruit and vegetable (FV) intake and physical activity (PA). DESIGN: Study design was a cluster randomized, controlled trial. SETTING: Forty-four low-resource public schools in San Diego County, California, were included in the study. SUBJECTS: Study subjects comprised a total of 3463 fourth/fifth-graders (1571 intervention, 1892 control), with an 86.9% completion rate. INTERVENTION: Throughout 10 weeks, activities were conducted during/after school, including weekly FV/PA lessons and PA breaks; biweekly classroom promotions/taste tests; posters displayed in/around schools; and weekly nutrition materials for parents. MEASURES: Self-reported FV intake (cups/d) and PA (min/d) were collected at baseline and follow-up using a diary-assisted, 24-hour dietary recall and Self-Administered Physical Activity Checklist. ANALYSIS: Multivariate regression models adjusted for demographics and cluster design effects were used, with change as the dependent variable. RESULTS: Intervention children, compared with controls, showed gains in daily FV intake (.26 cups, p < .001) and PA time at recess/lunch (5.1 minutes, p = .003), but not total daily PA minutes. CONCLUSION: Power Play! can help schools and community organizations improve low-income children's FV intake and PA during recess/lunch.

An overview of evidence for a causal relationship between dietary availability of choline during development and cognitive function in offspring.

This review is part of a series intended for non-specialists that will provide an overview of evidence for causal relationships between micronutrient deficiencies and brain function. Here, we review 34 studies in rodents linking the availability of choline during gestation and perinatal development to neurological function or performance of offspring in cognitive and behavioral tests. Experimental designs, major results, and statistical criteria are summarized in Tables 1-4. Based on our reading of the literature, the evidence suggests that choline supplementation during development results in improved performance of offspring in cognitive or behavioral tests, and in changes in a variety of neurological functional indicators: (1) enhanced performance was observed, particularly on more difficult tasks; (2) increases (choline supplementation) or decreases (choline deficiency) were observed in electrophysiological responsiveness and size of neurons in offspring; and (3) supplementation resulted in some protection against adverse effects of several neurotoxic agents (including alcohol) in offspring. Discussion topics include methodological issues, such as the importance of independent replication, causal criteria, and uncertainties in interpreting test results.

Relations of glycemic index and glycemic load with plasma oxidative stress markers.

BACKGROUND: Recent data suggest that acute hyperglycemia may increase in vivo free radical production. This increased production has been implicated in many disease processes. OBJECTIVE: The objective was to investigate whether a diet with a high glycemic index (GI) or glycemic load (GL) is associated with greater oxidative stress as measured by 2 lipid peroxidation markers, malondialdehyde (MDA) and F2-isoprostanes (IsoPs). DESIGN: Plasma MDA and IsoP concentrations were measured in 292 healthy adults, and dietary GI and GL were assessed by using a validated food-frequency questionnaire. Cross-sectional associations between GI, GL, and the 2 markers were examined by using multiple regression techniques with adjustment for potential confounding variables. RESULTS: Dietary GI was positively associated with both plasma MDA and IsoPs. The mean multivariate-adjusted MDA concentrations increased from 0.55 to 0.73 micromol/L as GI increased from the lowest to the highest quartile (P for trend = 0.02); the corresponding IsoP concentrations increased from 0.034 to 0.040 ng/mL (P for trend = 0.03). GL was positively associated with both MDA and IsoPs, but the linear relation was significant only for MDA. In addition, a marginally significant interaction between overall GI and body mass index (BMI; in kg/m2) for plasma MDA was observed (P = 0.09). The positive association between overall GI and MDA was stronger in those with a BMI < 26.5 than for those with a BMI > or = 26.5. CONCLUSIONS: Chronic consumption of high-GI foods may lead to chronically high oxidative stress. A low-GI diet, not a low-carbohydrate diet, appears to be beneficial in reducing oxidative stress.

Variability in hepatic iron concentration in percutaneous needle biopsy specimens from patients with transfusional hemosiderosis.

In patients with sickle cell disease or beta-thalassemia receiving RBC transfusions for a long period, a precise knowledge of the liver iron concentration (LIC) is essential for treatment. Patients underwent LIC and liver pathology assessment by duplicate biopsies in 2 passes from the same local liver site. Fresh tissue cores in trace element-free containers and tissues from dissolved paraffin-embedded cores were analyzed. LIC measurements in each of 2 paraffin-embedded cores did not differ significantly (median, 12,455 vs 12,153 microg/g dry weight; n = 29). A significant difference was observed when 1 fresh tissue sample and 1 paraffin-embedded core were analyzed (median, 11,716 vs 12,864 microg/g dry weight; n = 16; P < .001) with a median disagreement between LIC measurements of 23.0%. We found high agreement in LICs between liver biopsy specimens processed by the paraffin-embedding technique but overestimation of LICs in comparison with desiccated fresh tissue samples.

Associations between apolipoprotein E genotype and circulating F2-isoprostane levels in humans.

Apolipoprotein E (apoE), an important determinant of plasma lipoprotein metabolism, has three common alleles (epsilon2, epsilon3, and epsilon4). Population studies have shown that the risk of diseases characterized by oxidative damage, such as coronary heart disease and Alzheimer's disease, is significantly higher in epsilon4 carriers. We evaluated the association between apoE genotypes and plasma F2-isoprostane levels, an index of lipid peroxidation, in humans. Two hundred seventy-four healthy subjects (104 males, 170 females; 46.9 +/- 13.0 yr; 200 whites, 74 blacks; 81 nonsmokers, 64 passive smokers, and 129 active smokers) recruited for a randomized clinical antioxidant intervention trial were included in this analysis. ApoE genotype was determined by PCR and restriction enzyme digestion. Free plasma F2-isoprostane was measured by GC-MS. Genotype groups were compared using multiple regression analysis with adjustment for sex, age, race, smoking status, body mass index, plasma ascorbic acid, and beta-carotene. Subjects with epsilon3/epsilon4 and epsilon4/epsilon4 genotype (epsilon4-carriers) and with epsilon2/epsilon3 and epsilon3/epsilon3 (non-epsilon4-carriers) were pooled for analysis. In subjects with high cholesterol levels (total cholesterol above 200 mg/dl), plasma F2-isoprostane levels were 29% higher in epsilon4 carriers than in non-epsilon4-carriers (P= 0.0056). High-cholesterol subjects that are epsilon4 carriers have significantly higher levels of lipid peroxidation as assessed by circulating F2-isoprostane levels.

Exposure to Bovine Leukemia Virus Is Associated with Breast Cancer: A Case-Control Study.

BACKGROUND: Age, reproductive history, hormones, genetics, and lifestyle are known risk factors for breast cancer, but the agents that initiate cellular changes from normal to malignant are not understood. We previously detected bovine leukemia virus (BLV), a common oncogenic virus of cattle, in the breast epithelium of humans. The objective of this study was to determine whether the presence of BLV DNA in human mammary epithelium is associated with breast cancer. METHODS: This was a case-control study of archival formalin fixed paraffin embedded breast tissues from 239 donors, received 2002-2008 from the Cooperative Human Tissue Network. Case definition as breast cancer versus normal (women with no history of breast cancer) was established through medical records and examination of tissues by an anatomical pathologist. Breast exposure to BLV was determined by in situ-PCR detection of a biomarker, BLV DNA, localized within mammary epithelium. RESULTS: The frequency of BLV DNA in mammary epithelium from women with breast cancer (59%) was significantly higher than in normal controls (29%) (multiply- adjusted odds ratio = 3.07, confidence interval = 1.66-5.69, p = .0004, attributable risk = 37%). In women with premalignant breast changes the frequency of BLV DNA was intermediate (38%) between that of women with breast cancer and normal controls (p for trend < .001). CONCLUSIONS: Among the specimens in this study, the presence of amplified BLV DNA was significantly associated with breast cancer. The odds ratio magnitude was comparable to those of well-established breast cancer risk factors related to reproductive history, hormones, and lifestyle and was exceeded only by risk factors related to genetics (familial breast cancer), high dose ionizing radiation, and age. These findings have the potential for primary and secondary prevention of breast cancer.

Diet in midpuberty and sedentary activity in prepuberty predict peak bone mass.

BACKGROUND: An average daily calcium intake of 1300 mg is recommended for North American adolescents aged 9-18 y. However, questions remain about these recommendations. OBJECTIVE: We assessed whether there is a stage of puberty when dietary calcium is more strongly related to peak bone mass, as indicated by young adult bone mass (YABM); whether dietary calcium intake > 1000 mg/d in adolescence is associated with higher YABM; and whether race affects any of these associations between dietary calcium and YABM. Secondarily, we evaluated relations between sedentariness and YABM. DESIGN: In a retrospective cohort study, we recruited 693 black and white women aged 21-24 y who had participated in the 10-y National Heart, Lung, and Blood Institute Growth and Health Study and measured YABM with the use of dual-energy X-ray absorptiometry. Dietary calcium and sedentary activity data, gathered through 3-d food records and self-reports of television-video viewing at 8 annual examinations, were averaged over 3 pubertal stages. Complete data were available from 161 black and 180 white females. Multiple regression, controlling for race, weight, and height, was applied to assess diet and activity relations with YABM. RESULTS: Dietary calcium was most strongly associated with YABM in midpuberty. Calcium intake > 1000 mg/d was associated with higher YABM, but this association was not significant at all skeletal sites. Race did not affect the observed relations between calcium and YABM. Sedentary activity in prepuberty was inversely associated with YABM. CONCLUSIONS: Interventions should focus on ensuring adequate calcium intake in midpuberty and on minimizing sedentariness in prepuberty.

Smoking and exposure to environmental tobacco smoke decrease some plasma antioxidants and increase gamma-tocopherol in vivo after adjustment for dietary antioxidant intakes.

BACKGROUND: Free radicals in cigarette smoke may cause oxidative damage to macromolecules, contributing to cardiovascular diseases and cancer. Decreased plasma antioxidant concentrations may indicate cigarette smoke-related oxidative stress. OBJECTIVE: We compared the effects on plasma antioxidant concentrations in cotinine-confirmed active and passive smokers with those in nonsmokers, independent of differences in dietary intakes and other covariates. DESIGN: Plasma samples from 83 smokers, 40 passive smokers, and 36 nonsmokers were analyzed for total ascorbic acid, alpha- and gamma-tocopherols, 5 carotenoids, retinol, and cotinine. Groups were compared by using analysis of variance with adjustment for sex, age, race, body mass index, alcohol intake, triacylglycerol concentration, fruit and vegetable intakes, and dietary antioxidants. RESULTS: After adjustment for dietary antioxidant intakes and other covariates, smokers and passive smokers had significantly lower plasma beta-carotene concentrations than did nonsmokers (0.15, 0.17, and 0.24 micro mol/L, respectively) and significantly higher gamma-tocopherol concentrations (7.8, 7.8, and 6.5 micro mol/L, respectively). Smokers had significantly lower plasma ascorbic acid and beta-cryptoxanthin concentrations than did nonsmokers and passive smokers (ascorbic acid: 43.6, 54.5, and 54.6 micro mol/L, respectively; beta-cryptoxanthin: 0.12, 0.16, and 0.16 micro mol/L, respectively) and significantly lower concentrations of lutein and zeaxanthin than did nonsmokers (0.33 compared with 0.41 micro mol/L). The P values for all the differences described above were < 0.05. No significant differences in plasma concentrations of alpha-tocopherol, alpha-carotene, total carotenoids, lycopene, or retinol were observed. CONCLUSIONS: These results indicate that cigarette smokers and nonsmokers exposed to cigarette smoke have a significantly lower plasma antioxidant status than do unexposed nonsmokers, independent of differences in dietary antioxidant intakes. Further research is required to explain why plasma gamma-tocopherol concentrations were significantly higher in smokers and passive smokers than in nonsmokers.

Antioxidant supplementation decreases lipid peroxidation biomarker F(2)-isoprostanes in plasma of smokers.

Free radicals in cigarette smoke (CS) cause oxidative damage to proteins, DNA, and lipids, contributing to the pathobiology of atherosclerosis, heart disease, and cancer. In vitro studies have shown that antioxidants quench free radicals and ameliorate certain aspects of biomolecular damage caused by CS. It is hypothesized that a combination of antioxidants is more effective than a single antioxidant, due to their interactions. To investigate whether supplemental antioxidants reduce CS-related lipid peroxidation in vivo and whether they are more effective in combination, we conducted an intervention study in smokers. In a randomized double-blind placebo-controlled trial, we investigated whether vitamin C or an antioxidant mixture containing vitamin C, alpha-lipoic acid, and vitamin E decreases plasma F(2)-isoprostane levels, an index of oxidant stress, in smokers. Plasma of 126 smokers (mean age, 46 years; age range, 20-78 years) was analyzed for F(2)-isoprostanes at baseline and after intervention with antioxidants and placebo. In smokers with a body mass index (BMI) above the median, 2 months of daily supplementation with 500 mg of vitamin C decreased plasma F(2)-isoprostane levels by 28.8 pmol/liter when compared with the placebo group (P = 0.001); levels in the mixture group were 7.45 pmol/liter lower after treatment, but this difference was not statistically significant (P = 0.14). There was no treatment effect in smokers with a low BMI. BMI was significantly positively associated with plasma F(2)-isoprostane levels (trend P = 0.001). Antioxidants decrease smoking-related lipid peroxidation markers of oxidative stress in humans with high BMI. Our results do not indicate that an antioxidant combination is more effective than vitamin C alone. The intake of antioxidants may help prevent smoking-related diseases. Smoking cessation should still be considered the most effective way to prevent smoking-related diseases.