Activity-independent targeting of mTOR to lysosomes in primary osteoclasts.

Mammalian target of rapamycin (mTOR) is activated by numerous stimuli, including amino acids and growth factors. This kinase is part of the mTOR complex 1 (mTORC1) which regulates cell proliferation, differentiation, and autophagy. Active mTORC1 is located on lysosomes and has been reported to disassociate from the lysosomal surface in the absence of amino acids. Furthermore, mTORC1 activity has been linked to the vacuolar H+-ATPases (V-ATPases), the proton pumps responsible for lysosomal acidification; however, the exact role of the V-ATPases in mTORC1 signaling is not known. To elucidate the mechanisms involved in mTORC1 regulation by the V-ATPases, we used primary osteoclasts derived from mice carrying a point (R740S) mutation in the a3 subunit of the V-ATPase. In these cells, the mutant protein is expressed but the pump is not functional, resulting in higher lysosomal pH. By analyzing mTOR activation, mTOR/lysosome co-localization, and lysosomal positioning using confocal microscopy, fractionation, and ultrapure lysosomal purification methods, we demonstrate that in primary osteoclasts, mTOR is localized on the lysosomal surface even when mTOR activity is inhibited. Our findings reveal that mTOR targeting to the lysosome in osteoclasts is activity-independent, and that its disassociation from the lysosome during starvation is not universal.

Lysosomal pH Plays a Key Role in Regulation of mTOR Activity in Osteoclasts.

Mammalian target of rapamycin (mTOR) is a serine/threonine kinase involved in the regulation of cell growth. It has been shown to play an important role in osteoclast differentiation, particularly at the earlier stages of osteoclastogenesis. mTOR activation and function, as part of mTORC1 complex, is dependent on lysosomal localization and the vacuolar H(+) -ATPase (V-ATPase) activity; however, the precise mechanism is still not well understood. Using primary mouse osteoclasts that are known to have higher lysosomal pH due to R740S mutation in the V-ATPase a3 subunit, we investigated the role of lysosomal pH in mTORC1 signaling. Our results demonstrated that +/R740S cells had increased basal mTOR protein levels and mTORC1 activity compared to +/+ osteoclasts, while mTOR gene expression was decreased. Treatment with lysosomal inhibitors chloroquine and ammonium chloride, compounds known to raise lysosomal pH, significantly increased mTOR protein levels in +/+ cells, confirming the importance of lysosomal pH in mTOR signaling. These results also suggested that mTOR could be degraded in the lysosome. To test this hypothesis, we cultured osteoclasts with chloroquine or proteasomal inhibitor MG132. Both chloroquine and MG132 increased mTOR and p-mTOR protein levels in +/+ osteoclasts, suggesting that mTOR undergoes both lysosomal and proteasomal degradation. Treatment with cycloheximide, an inhibitor of new protein synthesis, confirmed that mTOR is constitutively expressed and degraded. These results show that, in osteoclasts, the lysosome plays a key role not only in mTOR activation but also in its deactivation through protein degradation, representing a novel molecular mechanism of mTOR regulation.

Restaurant menu labelling: Is it worth adding sodium to the label?

OBJECTIVE: Several provincial and federal bills have recommended various forms of menu labelling that would require information beyond just calories; however, the additional benefit of including sodium information is unknown. The objective of this study was to determine whether sodium information on menus helps consumers make lower-sodium choices and to understand what other factors influence the effect of menu labelling on consumers' meal choices. METHODS: A total of 3,080 Canadian consumers completed an online survey that included a repeated measures experiment in which consumers were asked to select what they would typically order from four mock-restaurant menus. Subsequently, consumers were randomly allocated to see one of three menu-labelling treatments (calories; calories and sodium; or calories, sodium and serving size) and were given the option to change their order. RESULTS: There was a significant difference in the proportion of consumers who changed their order, varying from 17% to 30%, depending on the restaurant type. After participants had seen menu labelling, sodium levels decreased in all treatments (p<0.0001). However, in three of the four restaurant types, consumers who saw calorie and sodium information ordered meals with significantly less sodium than consumers who saw only calorie information (p<0.01). Consumers who saw sodium labelling decreased the sodium level of their meal by an average of 171-384 mg, depending on the restaurant. In the subset of consumers who saw sodium information and chose to change their order, sodium levels decreased by an average of 681-1,360 mg, depending on the restaurant. Sex, intent to lose weight and the amount of calories ordered at baseline were the most important predictors of who used menu labelling. Eighty percent of survey panelists wanted to see nutrition information when dining out. CONCLUSION: Including sodium information alongside calorie information may result in a larger decrease in the amount of sodium ordered by restaurant-goers.

Increased statistical power with combined independent randomization tests used with multiple-baseline design.

OBJECTIVES: Physicians often assess the effectiveness of treatments on a small number of patients. Multiple-baseline designs (MBDs), based on the Wampold-Worsham (WW) method of randomization and applied to four subjects, have relatively low power. Our objective was to propose another approach with greater power that does not suffer from the time requirements of the WW method applied to a greater number of subjects. STUDY DESIGN AND SETTING: The power of a design that involves the combination of two four-subject MBDs was estimated using computer simulation and compared with the four- and eight-subject designs. The effect of a delayed linear response to treatment on the power of the test was also investigated. RESULTS: Power was found to be adequate (>80%) for a standardized mean difference (SMD) greater than 0.8. The effect size associated with 80% power from combined tests was smaller than that of the single four-subject MBD (SMD=1.3) and comparable with the eight-subject MBD (SMD=0.6). A delayed linear response to the treatment resulted in important reductions in power (20-35%). CONCLUSIONS: By combining two four-subject MBD tests, an investigator can detect better effect sizes (SMD=0.8) and be able to complete a comparatively timelier and feasible study.

Effects of vitamin E on bone turnover markers among US postmenopausal women.

Increased oxidative stress and inflammation resulting from aging and declining estrogen levels can lead to increased bone loss in postmenopausal women. Alpha-tocopherol and gamma-tocopherol, the two predominant isomers of vitamin E, have antioxidant and anti-inflammatory properties, but their effects on bone metabolism have not been well studied in humans. We examined the associations between dietary and total (diet and supplements) alpha-tocopherol intake, serum alpha-tocopherol and gamma-tocopherol levels and their ratio, and bone turnover markers (BTMs) among postmenopausal women aged ≥45 years. We used cross-sectional data from the National Health and Nutrition Examination Survey 1999­2002. Multiple regression models with adjustments for relevant confounders were used to examine the associations between intake and serum levels of tocopherols, and serum bone-specific alkaline phosphatase (BAP), a biomarker of bone formation, and urinary N-telopeptides/creatinine (uNTx/Cr), a biomarker of bone resorption. The study sample included 497 postmenopausal women who were not taking estrogen, steroids, or osteoporosis medications, were free from kidney and liver disease, cancer, and rheumatoid arthritis, and were fasting >9 hours prior to examination. Participants had a mean age of 65.5 ± 0.6 years and over 45% used vitamin E (alpha-tocopherol) supplements in the past month. Vitamin E supplement users had significantly lower serum gamma-tocopherol, higher serum alpha-tocopherol levels, and higher ratio of serum alpha-tocopherol to gamma-tocopherol than nonusers. High serum gamma-tocopherol levels and low ratio of serum alpha-tocopherol to gamma-tocopherol were associated with increased BAP levels (p < 0.01 for both). There were no associations between any of the vitamin E variables and uNTx/Cr. In conclusion, we hypothesize that gamma-tocopherol may uncouple bone turnover, resulting in more bone formation than resorption. Vitamin E supplements in the form of alpha-tocopherol suppress serum gamma-tocopherol levels and may have negative effects on bone formation. Further research is needed to investigate the potential anabolic effect of gamma-tocopherol from food sources on bone.

Divergent body mass index trajectories between Aboriginal and non-Aboriginal Canadians 1994-2009--an exploration of age, period, and cohort effects.

OBJECTIVES: Aboriginal Canadians have a high burden of obesity and obesity-related chronic conditions. Body mass index (BMI) trajectories from 1994 to 2009 were estimated for Aboriginal and non-Aboriginal Canadians using self-reported height and weight data from the National Population Health Survey to explore age, period, and cohort effects of BMI change. METHODS: Linear growth curve models were estimated for 311 Aboriginal and 10,967 non-Aboriginal respondents divided into five birth cohorts born in the 1940s, 50s, 60s, 70s, and 80s. RESULTS: Overall, Aboriginal Canadians experienced higher rates of BMI increase over the 14-year period. Rate of BMI increase was specifically higher for Aboriginal adults born in the 1960s and 1970s when compared with non-Aboriginal adults. At ages 25, 35, and 45, recent-born cohorts had consistently higher BMIs compared with earlier-born cohorts with magnitudes of differences typically larger in the Aboriginal population. Recent-born cohorts also exhibited steeper BMI trajectories. CONCLUSIONS: Cohort effects may be responsible for the divergent BMI trajectories between Aboriginal and non-Aboriginal Canadians born in the 1960s and 1970s. Aboriginal Canadians, particularly of more recent-born cohorts, experienced faster increases in BMI from 1994 to 2009 than non-Aboriginal Canadians, suggesting that prevalence of obesity will continue to rise in this population without intervention.

Socio-economic patterns of obesity among aboriginal and non-Aboriginal Canadians.

OBJECTIVES: Large disparities exist between Aboriginal and non-Aboriginal Canadians in both obesity and socio-economic status (SES). The purpose of this paper was to assess associations between obesity and three indicators of SES - employment, education and income - in conjunction with demographic and lifestyle factors. METHODS: Using the nationally-representative Canadian Community Health Survey (CCHS) cycle 2.2 (2004), among 334 off-reserve Aboriginal and 6,259 non-Aboriginal Canadians aged 25-64 years in the 10 provinces, obesity status was determined by body mass index derived from measured height and weight. Logistic regression was used to assess the relationships between socio-demographic variables and obesity status. RESULTS: Controlling for other socio-economic and lifestyle factors, odds for obesity were lower by 80% among Aboriginal men and 64% among Aboriginal women who were employed during the 12 months prior to the survey compared to Aboriginal men and women who were not employed. Employment was not significantly associated with obesity among non-Aboriginal adults. Probability for obesity increased as household income increased among Aboriginal men, but a negative association between income and obesity was observed among Aboriginal women. These associations persisted after adjustment for physical activity level, fruit and vegetable consumption, smoking, and marital status in the models. CONCLUSION: Unemployment among obese Aboriginal Canadians warrants attention. The knowledge that both high and low SES Aboriginal Canadians, of varying socio-demographic characteristics and lifestyle, experience high rates of obesity can lead to new hypotheses of how obesity develops in this population and influence how interventions are planned.

Genetic variation in TAS1R2 (Ile191Val) is associated with consumption of sugars in overweight and obese individuals in 2 distinct populations.

BACKGROUND: Taste is an important determinant of food consumption, and genetic variations in the sweet taste receptor subunit TAS1R2 may contribute to interindividual variations in sugar consumption. OBJECTIVE: We determined whether Ser9Cys and Ile191Val variations in TAS1R2 were associated with differences in the consumption of sugars in 2 populations. DESIGN: Population 1 included 1037 diabetes-free young adults in whom we assessed dietary intake by using a 1-mo, 196-item food-frequency questionnaire. Population 2 consisted of 100 individuals with type 2 diabetes with dietary intakes assessed by using 2 sets of 3-d food records administered 2 wk apart. Dietary counseling was provided between food records 1 and 2. Dietary intakes between genotypes were compared by using analysis of covariance adjusted for potential confounders. RESULTS: In population 1, a significant Ile191Val × body mass index (BMI; in kg/m²) interaction was detected for the consumption of sugars, and the effect of genotype was significant only in individuals with a BMI ≥ 25 (n = 205). In comparison with individuals homozygous for the Ile allele, Val carriers consumed fewer sugars (122 ± 6 compared with 103 ± 6 g sugar/d, respectively; P = 0.01). Regression estimates that associated BMI with total sugar consumption by Ile/Ile and Val-carrier genotype intersected at a BMI of 23.5. In population 2, Val carriers also consumed less sugar than did individuals with the Ile/Ile genotype (99 ± 6 compared with 83 ± 6 g sugar/d, respectively; P = 0.04) on food record 2, and sugar was the only macronutrient that decreased significantly (-9 ± 4 g sugar/d, P = 0.02) in Val carriers who received dietary counseling. CONCLUSION: Our findings show that a genetic variation in TAS1R2 affects habitual consumption of sugars and may contribute to interindividual differences in changing behaviors in response to dietary counseling.

Associations of television viewing, physical activity and dietary behaviours with obesity in aboriginal and non-aboriginal Canadian youth.

OBJECTIVE: To determine associations of diet, physical activity and television (TV) viewing time with obesity among aboriginal and non-aboriginal youth in conjunction with socio-economic variables. DESIGN: Cross-sectional study of differences between aboriginal and non-aboriginal groups and associations between lifestyle and socio-economic factors with obesity were examined. SETTING: Population data from the Canadian Community Health Survey Cycle 2.2 conducted in 2004 in the ten provinces of Canada. SUBJECTS: A total of 198 aboriginal and 4448 non-aboriginal Canadian youth aged 12-17 years. RESULTS: Compared to non-aboriginal youth, physical activity participation among aboriginal youth was higher, but consumption of vegetables and dairy products was lower, and more aboriginal youth were 'high' TV watchers. Low income adequacy was associated with decreased odds for obesity among aboriginal youth in contrast to higher odds among non-aboriginal youth. Non-aboriginal 'high' TV watchers consumed more soft drinks and non-whole-grain products than did 'low' TV watchers. Physical activity participation did not differ between 'high' and 'low' TV watchers for both groups, and was associated with lowered odds for obesity only among aboriginal youth. CONCLUSIONS: Sociodemographic and lifestyle risk factors associated with obesity differ between aboriginal and non-aboriginal youth. These findings may be useful for guiding intervention efforts.

A pure likelihood approach to the analysis of genetic association data: an alternative to Bayesian and frequentist analysis.

Investigators performing genetic association studies grapple with how to measure strength of association evidence, choose sample size, and adjust for multiple testing. We apply the evidential paradigm (EP) to genetic association studies, highlighting its strengths. The EP uses likelihood ratios (LRs), as opposed to P-values or Bayes' factors, to measure strength of association evidence. We derive EP methodology to estimate sample size, adjust for multiple testing, and provide informative graphics for drawing inferences, as illustrated with a Rolandic Epilepsy (RE) fine-mapping study. We focus on controlling the probability of observing weak evidence for or against association (W) rather than type I errors (M). For example, for LR> or =32 representing strong evidence, at one locus with n=200 cases, n=200 controls, W=0.134, whereas M=0.005. For n=300 cases and controls, W=0.039 and M=0.004. These calculations are based on detecting an OR=1.5. Despite the common misconception, one is not tied to this planning value for analysis; rather one calculates the likelihood at all possible values to assess evidence for association. We provide methodology to adjust for multiple tests across m loci, which adjusts M and W for m. We do so for (a) single-stage designs, (b) two-stage designs, and (c) simultaneously controlling family-wise error rate (FWER) and W. Method (c) chooses larger sample sizes than (a) or (b), whereas (b) has smaller bounds on the FWER than (a). The EP, using our innovative graphical display, identifies important SNPs in elongator protein complex 4 (ELP4) associated with RE that may not have been identified using standard approaches.

Vitamin C deficiency in a population of young Canadian adults.

A cross-sectional study of the 979 nonsmoking women and men aged 20-29 years who participated in the Toronto Nutrigenomics and Health Study from 2004 to 2008 was conducted to determine the prevalence of serum ascorbic acid (vitamin C) deficiency and its association with markers of chronic disease in a population of young Canadian adults. High performance liquid chromatography was used to determine serum ascorbic acid concentrations from overnight fasting blood samples. A 1-month, 196-item food frequency questionnaire was used to assess dietary intakes. Results showed that 53% of subjects had adequate, 33% had suboptimal, and 14% had deficient levels of serum ascorbic acid. Subjects with deficiency had significantly higher measurements of mean C-reactive protein, waist circumference, body mass index, and blood pressure than did subjects with adequate levels of serum ascorbic acid. The odds ratio for serum ascorbic acid deficiency was 3.43 (95% confidence interval: 2.14, 5.50) for subjects who reported not meeting the recommended daily intake of vitamin C compared with those who did. Results suggest that 1 of 7 young adults has serum ascorbic acid deficiency, in part, because of unmet recommended dietary intakes. Furthermore, serum ascorbic acid deficiency is associated with elevated markers of chronic disease in this population of young adults, which may have long-term adverse health consequences.

NF-kappaB -94Ins/Del ATTG polymorphism modifies the association between dietary polyunsaturated fatty acids and HDL-cholesterol in two distinct populations.

We previously showed that polymorphisms in the tumor necrosis factor (TNF)-alpha gene, which is regulated by nuclear factor kappa B (NF-kappaB), modify the association between dietary polyunsaturated fatty acid (PUFA) intake and circulating HDL-cholesterol. Our objective was to determine whether a common polymorphism in the NFKB1 gene (-94Ins/Del ATTG) interacts with PUFA intake to affect HDL-cholesterol in two distinct populations. Participants were diabetes-free young adults (n=593) and older individuals with diet-treated type 2 diabetes (n=103). The NF-kappaB polymorphism modified the association between dietary PUFA intake and HDL-cholesterol in both populations (p=0.02 and 0.005 for interaction). Among individuals with the Ins/Ins genotype, each 1% increase in energy from PUFA was associated with a 0.03+/-0.01 mmol/L (p for slope=0.009) and 0.06+/-0.02 mmol/L (p=0.02) increase in HDL-cholesterol among participants from the diabetes-free and diabetic populations. An inverse relationship was observed among those with the Del/Del genotype, which was significantly different from that of the Ins/Ins groups in both populations (p=0.02 and 0.006). No effects were observed for the Ins/Del genotype in either population (p>0.05). These findings show that this functional polymorphism in the NF-kB gene modifies the association between PUFA intake and plasma HDL-cholesterol in two distinct populations.

Dopamine D2 receptor genotype (C957T) and habitual consumption of sugars in a free-living population of men and women.

BACKGROUND/AIMS: The dopamine D2 receptor (DRD2) has been implicated in modulating the rewarding effects of foods high in sugar. The purpose of this study was to determine whether a variation in the DRD2 gene affects habitual consumption of sugars in a free-living population. METHODS: Caucasian men (n = 96) and women (n = 217) 20-29 years of age completed a 1-month food frequency questionnaire and were genotyped for the C957T polymorphism in the DRD2 gene. Analyses of covariance with post-hoc Tukey tests were used to compare nutrient intakes between genotypes adjusting for potential confounders. RESULTS: Among men, consumption of sucrose was 60 +/- 6, 48 +/- 4, and 39 +/- 5 g/day for those with the CC, CT and TT genotypes, respectively, with a significant difference between the homozygotes (p = 0.03), suggesting an additive mode of inheritance. Among women, sucrose consumption was 42 +/- 4, 53 +/- 2, and 44 +/- 4 g/day for the CC, CT and TT genotypes, respectively, with CC and CT differing significantly (p = 0.02), suggesting a partial heterosis mode of inheritance. No differences were observed for protein or fat. CONCLUSIONS: These findings suggest that genetic variation in DRD2 influences food selection and may explain some of the interindividual differences in sugar consumption.

Genetic polymorphisms of tumor necrosis factor-alpha modify the association between dietary polyunsaturated fatty acids and fasting HDL-cholesterol and apo A-I concentrations.

BACKGROUND: Heterogeneity in circulating lipid concentrations in response to dietary polyunsaturated fatty acids (PUFAs) may be due, in part, to genetic variations. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that can induce hyperlipidemia and is known to be modulated by dietary PUFAs. OBJECTIVE: The objective was to determine whether TNF-alpha genotypes modify the association between dietary PUFA intake and serum lipid concentrations. DESIGN: The study involved 53 men and 56 women aged 42-75 y with type 2 diabetes. Dietary intakes were assessed with the use of a 3-d food record, and blood samples were collected to determine fasting serum lipids. DNA was isolated from blood for genotyping by polymerase chain reaction-restriction fragment length polymorphism for the TNF-alpha -238G-->A and -308G-->A polymorphisms. RESULTS: PUFA intake was positively associated with serum HDL cholesterol in carriers of the -238A allele (beta = 0.06 +/- 0.03 mmol/L per 1% of energy from PUFAs; P = 0.03), but negatively associated in those with the -238GG genotype (beta = -0.03 +/- 0.01, P = 0.03) (P = 0.004 for interaction). PUFA intake was inversely associated with HDL cholesterol in carriers of the -308A allele (beta = -0.07 +/- 0.02, P = 0.002), but not in those with the -308GG genotype (beta = 0.02 +/- 0.02, P = 0.13) (P = 0.001 for interaction). A stronger gene x diet interaction was observed when the polymorphisms at the 2 positions (-238/-308) were combined (P = 0.0003). Similar effects were observed for apolipoprotein A-I, but not with other dietary fatty acids and serum lipids. CONCLUSION: TNF-alpha genotypes modify the relation between dietary PUFA intake and HDL-cholesterol concentrations. These findings suggest that genetic variations affecting inflammation may explain some of the inconsistencies between previous studies relating PUFA intake and circulating HDL.

Pesticide exposures in professional turf applicators, job titles, and tasks performed: implications of exposure measurement error for epidemiologic study design and interpretation of results.

BACKGROUND: Little information on the validity of job title and task classifications, for the prediction of pesticide use or exposure, is available. METHODS: Job titles and task classifications were evaluated in relation to the absorbed dose of herbicides in 98 professional turf applicators. Self-reported use over a 1-week period and other proxies of pesticide use were compared with employer records. RESULTS: Job titles and tasks performed explained (R(2)) 11% and 16% of the variation in dose, respectively. Individuals who sprayed pesticides only, had the highest average doses in the study followed by those spraying and mixing, and those mixing only. The use of 2,4-D products by individual workers over a work season was not related to standardized measures of the amount purchased or used at the company. CONCLUSIONS: These findings suggest that job titles and tasks performed are poor proxies of pesticide use and exposures in professional turf applicators.

Risk of stroke in women exposed to low-dose oral contraceptives: a critical evaluation of the evidence.

BACKGROUND: Use of the oral contraceptive pill (OCP) has been reported to be associated with stroke. With current OCPs containing less than 50 micro g of ethinyl estradiol, and many earlier studies reporting the association between OCPs and stroke, subjected to biases, we determined whether such an association exists and, if so, the magnitude of the risk. METHODS: Two independent searches were conducted to obtain relevant articles from MEDLINE, EMBASE, and Science Citation (1970 to June 2000). Eligible articles published in English describing OCP use and stroke outcomes were retrieved, and relevant data were abstracted. Pooling of results from these studies was performed using odds ratios (ORs) provided, and heterogeneity was calculated using chi(2) analysis. RESULTS: From 779 potential articles, 36 eligible studies describing 20 distinct populations were retrieved (4 cohort and 16 case-control studies). The pooled OR from the cohort studies demonstrated no increased stroke risk with OCP use (0.95; 95% confidence interval [CI], 0.51-1.78; P =.01); the pooled OR from the case-control studies showed a significant association (2.13; 95% CI, 1.59-2.86; P<.001). The risk of stroke with OCP use, however, was significant only with thrombotic stroke (2.74; 95% CI, 2.24-3.35; P =.009) and not with hemorrhagic stroke or stroke death. There was statistically significant heterogeneity among these studies, and potential biases and confounders were not adequately addressed. CONCLUSIONS: These results cast doubt on a true association between low-dose OCPs and stroke because of the low absolute magnitude of the ORs, the severe methodological limitations, and the ORs of less than 1.0 in the cohort studies. The association is tenuous at best and perhaps nonexistent.

A cohort study of dietary fibre intake and menarche.

OBJECTIVE: To evaluate the influence of dietary fibre on menarche in a cohort of pre-menarcheal girls. DESIGN: Prospective cohort study. SETTING: Ontario, Canada. SUBJECTS: Free-living pre-menarcheal girls (n = 637), 6 to 14 years of age. METHODOLOGY: Information on dietary intake, physical activity and date of menarche was collected at baseline and was updated annually by self-administered questionnaires for three years. Cox proportional hazards models were used to evaluate the association between dietary fibre and menarche, adjusting for age at entry to the study and potential confounders. RESULTS: A higher intake of energy-adjusted dietary fibre was associated with a lower risk of (i.e. a later age at) menarche (relative hazard 0.54, 95% confidence interval (CI) 0.31-0.94 for highest vs. lowest quartile, P for trend = 0.027). At the fibre component level, a higher intake of energy-adjusted cellulose was associated with a lower risk of menarche (relative hazard 0.45, 95% CI 0.26-0.76, P for trend = 0.009). CONCLUSIONS: The findings are consistent with the hypothesis that pre-menarcheal dietary intake can influence menarche.

Soluble fiber intake at a dose approved by the US Food and Drug Administration for a claim of health benefits: serum lipid risk factors for cardiovascular disease assessed in a randomized controlled crossover trial.

BACKGROUND: The US Food and Drug Administration (FDA) approved health claims for 2 dietary fibers, beta-glucan (0.75 g/serving) and psyllium (1.78 g/serving), on the assumption that 4 servings/d would reduce cardiovascular disease risk. OBJECTIVE: We assessed the efficacy of this dose of fibers in reducing serum lipid risk factors for cardiovascular disease. DESIGN: Sixty-eight hyperlipidemic adults consumed a test (high-fiber) and a control low-fat (25% of energy), low-cholesterol (<150 mg/d) diet for 1 mo each in a randomized crossover study. The high-fiber diet included 4 servings/d of foods containing beta-glucan or psyllium that delivered 8 g/d more soluble fiber than did similar, unsupplemented foods in the control diet. Fasting blood samples and blood pressure readings were obtained at baseline and weeks 2 and 4, and the subjects' weight was monitored weekly. RESULTS: Compared with the control diet, the high-fiber diet reduced total cholesterol (2.1 +/- 0.7%; P = 0.003), total:HDL cholesterol (2.9 +/- 0.8%; P = 0.001), LDL:HDL cholesterol (2.4 +/- 1.0%; P = 0.015), and apolipoprotein B:A-I (1.4 +/- 0.8%; P = 0.076). Applying the Framingham cardiovascular disease risk equation to the data confirmed a reduction in risk of 4.2 +/- 1.4% (P = 0.003). Small reductions in blood pressure were found after both diets. The subjects reported no significant differences in palatability or gastrointestinal symptoms between the diets. CONCLUSIONS: The reduction in serum lipid risk factors for cardiovascular disease supports the FDA's approval of a health claim for a dietary fiber intake of 4 servings/d. Although relatively small in terms of patient treatment, the reduction in cardiovascular disease risk is likely to be significant on a population basis.

Development of models to predict dose of pesticides in professional turf applicators.

Epidemiologic studies designed to assess the chronic effects of pesticides are limited by inadequate measurements of exposures. Although cohort studies have been initiated to evaluate the effects of 2,4-dichlorophenoxyacetic acid (2,4-D) and other pesticides in professional turf applicators, they may have limited power to detect significant health risks and may be subject to bias from exposure measurement error. In this study, the doses of 2,4-D, mecoprop [2-(4-chloro-2 methylphenoxy) propionic acid, MCPP] and dicamba (3,6-dichloro-o-anisic acid) were evaluated in a group of 98 professional turf applicators from 20 companies across southwestern Ontario. During a 1-week period (Saturday to Thursday), the volume of pesticide (active ingredient) applied was only weakly related to the total dose of 2,4-D absorbed (R(2)=0.21). Two additional factors explained a large proportion of variation in dose: the type of spray nozzle used and the use of gloves while spraying. Individuals who used a fan-type nozzle had significantly higher doses than those who used a gun-type nozzle. Glove use was associated with significantly lower doses. Job satisfaction and current smoking influenced the dose but were not highly predictive. In the final multiple regression models predicting total absorbed dose of 2,4-D and mecoprop, approximately 63-68% of the variation was explained. The future application of these models for epidemiologic research will depend on the availability of information and records from employers, the feasibility of contacting study subjects and cost.