A wearable cardiac ultrasound imager.

Continuous imaging of cardiac functions is highly desirable for the assessment of long-term cardiovascular health, detection of acute cardiac dysfunction and clinical management of critically ill or surgical patients1-4. However, conventional non-invasive approaches to image the cardiac function cannot provide continuous measurements owing to device bulkiness5-11, and existing wearable cardiac devices can only capture signals on the skin12-16. Here we report a wearable ultrasonic device for continuous, real-time and direct cardiac function assessment. We introduce innovations in device design and material fabrication that improve the mechanical coupling between the device and human skin, allowing the left ventricle to be examined from different views during motion. We also develop a deep learning model that automatically extracts the left ventricular volume from the continuous image recording, yielding waveforms of key cardiac performance indices such as stroke volume, cardiac output and ejection fraction. This technology enables dynamic wearable monitoring of cardiac performance with substantially improved accuracy in various environments.

Effect of Caffeine on Endurance Performance in Athletes May Depend on HTR2A and CYP1A2 Genotypes.

ABSTRACT: Guest, NS, Corey, P, Tyrrell, PN, and El-Sohemy, A. Effect of caffeine on endurance performance in athletes may depend on HTR2A and CYP1A2 genotypes. J Strength Cond Res 36(9): 2486-2492, 2022-This investigation determined whether variation in the HTR2A (serotonin receptor) gene modifies the ergogenic effects of caffeine on endurance and further modifies performance by the CYP1A2 genotype. Male athletes ( n = 100; 25 ± 4 years) completed 10-km cycling time trials under 3 conditions as follows: 0, 2, or 4 mg of caffeine per kg body mass. Using a randomized, double-blinded, placebo-controlled design, data were analyzed using analysis of covariance to compare changes in cycling time between placebo (0 mg·kg -1 ) and each caffeine dose and adjusted for the placebo trial and order of treatment. A significance of ρ ≤ 0.05 was used. Subjects were genotyped for HTR2A (rs6313) and CYP1A2 (rs762551). A significant caffeine- HTR2A interaction ( p = 0.003) was observed; however, after adjustment for placebo trials, the interaction was no longer significant ( p = 0.37). Because of the strong caffeine- CYP1A2 interaction ( p < 0.0001) previously reported in these subjects, where the 4-mg dose resulted in divergent effects (slower and faster) on the 10-km cycling time, we conducted a simplified model to examine these same factors by the HTR2A genotype. The post hoc analysis excluded HTR2A CT heterozygotes and 2-mg·kg -1 caffeine trials. Among CYP1A2 fast metabolizers alone, a significant difference (1.7 minutes; p = 0.006) was observed when comparing (4- vs. 0-mg·kg -1 caffeine trials) between the HTR2A CC ( n = 16; 2.4 minutes) and TT ( n = 7; 0.7 minutes) genotypes. Our results show that 4-mg·kg -1 caffeine improves performance in individuals with the HTR2A CC genotype but only in those who are also CYP1A2 AA fast metabolizers. This study was registered with clinicaltrials.gov (NCT02109783).

Caffeine, CYP1A2 Genotype, and Endurance Performance in Athletes.

PURPOSE: Many studies have examined the effect of caffeine on exercise performance, but findings have not always been consistent. The objective of this study was to determine whether variation in the CYP1A2 gene, which affects caffeine metabolism, modifies the ergogenic effects of caffeine in a 10-km cycling time trial. METHODS: Competitive male athletes (n = 101; age = 25 ± 4 yr) completed the time trial under three conditions: 0, 2, or 4 mg of caffeine per kilogram body mass, using a split-plot randomized, double-blinded, placebo-controlled design. DNA was isolated from saliva and genotyped for the -163A > C polymorphism in the CYP1A2 gene (rs762551). RESULTS: Overall, 4 mg·kg caffeine decreased cycling time by 3% (mean ± SEM) versus placebo (17.6 ± 0.1 vs 18.1 ± 0.1 min, P = 0.01). However, a significant (P <0.0001) caffeine-gene interaction was observed. Among those with the AA genotype, cycling time decreased by 4.8% at 2 mg·kg (17.0 ± 0.3 vs 17.8 ± 0.4 min, P = 0.0005) and by 6.8% at 4 mg·kg (16.6 ± 0.3 vs 17.8 ± 0.4 min, P < 0.0001). In those with the CC genotype, 4 mg·kg increased cycling time by 13.7% versus placebo (20.8 ± 0.8 vs 18.3 ± 0.5 min, P = 0.04). No effects were observed among those with the AC genotype. CONCLUSION: Our findings show that both 2 and 4 mg·kg caffeine improve 10-km cycling time, but only in those with the AA genotype. Caffeine had no effect in those with the AC genotype and diminished performance at 4 mg·kg in those with the CC genotype. CYP1A2 genotype should be considered when deciding whether an athlete should use caffeine for enhancing endurance performance.

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.

The influence of measurement error on calibration, discrimination, and overall estimation of a risk prediction model.

BACKGROUND: Self-reported height and weight are commonly collected at the population level; however, they can be subject to measurement error. The impact of this error on predicted risk, discrimination, and calibration of a model that uses body mass index (BMI) to predict risk of diabetes incidence is not known. The objective of this study is to use simulation to quantify and describe the effect of random and systematic error in self-reported height and weight on the performance of a model for predicting diabetes. METHODS: Two general categories of error were examined: random (nondirectional) error and systematic (directional) error on an algorithm relating BMI in kg/m2 to probability of developing diabetes. The cohort used to develop the risk algorithm was derived from 23,403 Ontario residents that responded to the 1996/1997 National Population Health Survey linked to a population-based diabetes registry. The data and algorithm were then simulated to allow for estimation of the impact of these errors on predicted risk using the Hosmer-Lemeshow goodness-of-fit χ2 and C-statistic. Simulations were done 500 times with sample sizes of 9,177 for males and 10,618 for females. RESULTS: Simulation data successfully reproduced discrimination and calibration generated from population data. Increasing levels of random error in height and weight reduced the calibration and discrimination of the model. Random error biased the predicted risk upwards whereas systematic error biased predicted risk in the direction of the bias and reduced calibration; however, it did not affect discrimination. CONCLUSION: This study demonstrates that random and systematic errors in self-reported health data have the potential to influence the performance of risk algorithms. Further research that quantifies the amount and direction of error can improve model performance by allowing for adjustments in exposure measurements.

A comparison of micronutrient inadequacy and risk of high micronutrient intakes among vitamin and mineral supplement users and nonusers in Canada.

Although supplement use is prevalent in North America, there is little information on how supplements affect the prevalence of nutrient adequacy or risk of intakes greater than the tolerable upper intake level (UL). The objectives of this study were to compare the prevalence of nutrient adequacy and percent of intakes greater than the UL from diet alone between supplement users and nonusers and determine the contribution of supplements to nutrient intakes. Dietary intakes (24-h recall) and supplement use (previous 30 d) from respondents ≥1 y in the Canadian Community Health Survey 2.2 (n = 34,381) were used to estimate the prevalence of nutrient adequacy and intakes greater than the UL. Software for Intake Distribution Evaluation was used to estimate usual intakes. The prevalence of nutrient adequacy from diet alone was not significantly higher among supplement users than nonusers for any nutrient. Based on diet alone, children 1-13 y had a low prevalence of nutrient adequacy (<30%) except for vitamin D and calcium. Among respondents ≥14 y, inadequacies of vitamins A and D, calcium, and magnesium were >30%. For other nutrients, there was a low prevalence of nutrient adequacy. There were no nutrient intakes greater than the UL from diet alone, except zinc in children. When supplements were included, ≥10% of users in some age/sex groups had intakes of vitamins A and C, niacin, folic acid, iron, zinc, and magnesium greater than the UL, reaching >80% for vitamin A and niacin in children. In conclusion, from diet alone, the prevalence of nutrient adequacy was low for most nutrients except for calcium, magnesium, and vitamins A and D. For most nutrients, supplement users were not at greater risk of inadequacy than nonusers; supplement use sometimes led to intakes greater than the UL.

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.

The role of ethnicity in predicting diabetes risk at the population level.

BACKGROUND: The current form of the diabetes population risk tool (DPoRT) includes a non-specific category of ethnicity in concordance with publicly data available. Given the importance of ethnicity in influencing diabetes risk and its significance in a multi-ethnic population, it is prudent to determine its influence on a population-based risk prediction tool. OBJECTIVE: To apply and compare the DPoRT with a modified version that includes detailed ethnic information in Canada's largest and most ethnically diverse province. METHODS: Two additional diabetes prediction models were created: a model that contained predictors specific to the following ethnic groups--White, Black, Asian, south Asian, and First Nation; and a reference model which did not include a term for ethnicity. In addition to discrimination and calibration, 10-year diabetes incidence was compared. The algorithms were developed in Ontario using the 1996-1997 National Population Health Survey (N=19,861) and validated in the 2000/2001 Canadian community health survey (N=26,465). RESULTS: All non-white ethnicities were associated with higher risk for developing diabetes with south Asians having the highest risk. Discrimination was similar (0.75-0.77) and sufficient calibration was maintained for all models except the detailed ethnicity models for males. DPoRT produced the lowest overall ratio between observed and predicted diabetes risk. DPoRT identified more high risk cases than the other algorithms in males, whereas in females both DPoRT and the full ethnicity model identified more high risk cases. Overall DPoRT and full ethnicity algorithms were very similar in terms of predictive accuracy and population risk. CONCLUSION: Although from the individual risk perspective, incorporating information on ethnicity is important, when predicting new cases of diabetes at the population level and accounting for other risk factors, detailed ethnic information did not improve the discrimination and accuracy of the model or identify significantly more diabetes cases in the population.

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.

The impact of stressful life events on unprotected anal intercourse among gay and bisexual men.

We investigated the hypothesis that gay and bisexual men experiencing stressful life events are more likely to engage in risky sexual behavior. Data were from a cohort study of 155 HIV-positive and 207 HIV-negative men in Ontario, Canada (1998-2007). We quantified the relation between stressful life events and unprotected anal intercourse with a non-regular partner. In the past 6 months, 19% reported unprotected intercourse (HIV+: 28%; HIV-: 13%) and 58% reported one or more stressful life events (HIV+: 64%; HIV-: 55%). Among HIV-negative men, the odds of unprotected intercourse increased by 1.15 for each additional event (95%CI 1.06, 1.24). Among HIV-positive men, those who reported the event "problems due to alcohol or drugs" were 1.80 (95%CI 1.27, 2.56) times more likely to report unprotected intercourse. Interventions to assist men to cope with stress may help to prevent population spread of HIV and improve overall health.

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.

Association between the Healthy Eating Index and bone turnover markers in US postmenopausal women aged ≥45 y.

BACKGROUND: Some studies have reported that overall diet quality affects bone status in postmenopausal women; however, the findings are inconsistent. OBJECTIVES: Our primary objective was to examine the association between overall diet quality and bone turnover markers (BTMs) in postmenopausal women aged ≥45 y by using the Healthy Eating Index 2005 (HEI-2005)-a diet quality-assessment tool-developed by the US Department of Agriculture. Our secondary objective was to explore the associations between the components of the HEI-2005 and the MyPyramid food groups and BTMs. DESIGN: We used cross-sectional data from NHANES 1999-2002. Multiple regression models with adjustments for relevant confounders were used to examine the relation between the total HEI-2005 score and its components and food groups and serum bone-specific alkaline phosphatase (BAP), a biomarker of bone formation, and urinary N-telopeptides/creatinine (uNTx/Cr), a biomarker of bone resorption. RESULTS: No association was found between the total HEI-2005 score and BTMs. The milk group component of HEI-2005 had a significant negative linear relation with uNTx/Cr. Women in the lowest tertile of the MyPyramid milk group had the highest uNTx/Cr. Those in the highest tertile of energy-adjusted added sugar intake had the highest BAP. CONCLUSIONS: Our results support the ability of a healthy diet with adequate dairy intake to promote bone health in aging women. However, we found that the HEI-2005 is not a good measure of healthy eating for optimal bone health. Further research is needed to develop an overall dietary assessment tool in relation to bone health for postmenopausal women.

Flaxseed cotyledon fraction reduces tumour growth and sensitises tamoxifen treatment of human breast cancer xenograft (MCF-7) in athymic mice.

Dietary flaxseed (FS) inhibited the growth of human breast tumours and enhanced the effectiveness of tamoxifen (TAM) in athymic mice with low oestradiol (E2) levels. The present study determined whether the n-3 fatty acid-rich cotyledon fraction of FS (FC), alone or in combination with TAM, has a similar effect and thus can substitute for FS. In a 2 × 2 factorial design, ovariectomised mice with established oestrogen receptor (ER)-positive breast tumours (MCF-7) were treated as follows: groups 1 and 2 were fed the basal diet (BD, control) and FC diet (82 g FC/kg), respectively. Groups 3 and 4 with TAM implants (5 mg) were fed the BD and FC diet, respectively. At 8 weeks post-treatment, mice were euthanised, and tumours were analysed by immunohistochemistry and real-time PCR. BD, FC and FC/TAM groups significantly decreased tumour area, but the TAM group did not. Tumour regression in the FC/TAM group was greater compared to the TAM group. FC lowered cell proliferation but had no effect on apoptosis; the opposite was observed with TAM. FC suppressed mRNA expressions of pS2 and insulin-like growth factor 1 receptor (IGF-1R) and protein expressions of ERα, phosphospecific ERα, human epidermal growth factor receptor 2 (HER2), phosphospecific HER2 (pHER2) and amplified in breast 1 (AIB1), while TAM up-regulated mRNA expressions of Bcl2, progesterone receptor and IGF-1R and protein expression of pHER2, and down-regulated ERß mRNA. FC modulated the effect of TAM on tumour growth biomarkers. In conclusion, FC reduced the growth of ER+ human breast tumours at low circulating E2, alone and combined with TAM, in part through modulation of ER- and growth factor-mediated signalling pathways; it may substitute for FS in increasing the effectiveness of TAM.

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.

Folic acid fortification above mandated levels results in a low prevalence of folate inadequacy among Canadians.

BACKGROUND: Understanding folate intakes after folic acid fortification of the food supply will help to establish dietary and supplement recommendations that balance health benefits and risks. OBJECTIVES: The objectives were to estimate the prevalence of folate inadequacy (POFI) and intakes above the Tolerable Upper Intake Level (UL) among Canadians and to estimate the supplemental dose that, with diet, provides reproductive-aged women with 400 µg folic acid/d to prevent neural tube defects. DESIGN: Twenty-four-hour recall and supplement (prior 30 d) data from the 2004 Canadian Community Health Survey (n = 35,107) were used to calculate the POFI and intakes above the UL with and without adjustment for fortification overages. POFI was also estimated by risk factors thought to be related to low folate intake. The Software for Intake Distribution Evaluation (SIDE program; Department of Statistics and Center for Agricultural and Rural Development, Iowa State University) was used to estimate usual dietary intakes in all analyses. RESULTS: Except for women aged >70 y, POFI was <20% after adjustment for fortification overages. For children aged <14 y, POFI approached zero, even when supplement use was excluded. POFI among adults was unaffected by supplement use, except for women aged >70 y. Only 18% of reproductive-aged women consumed 400 µg folic acid/d from diet and supplements. Modeling showed that supplements containing 325-700 µg folic acid would provide adult women with 400 µg/d but not more than the UL. Diabetes was associated with POFI. CONCLUSIONS: Innovative strategies are needed to ensure that the subgroups of Canadians who could still benefit from improved folate intake are targeted. Consideration should be given to removing folic acid from supplements designed for young children and men.

Stress and increased HIV infection risk among gay and bisexual men.

OBJECTIVE: Our principal objective was to determine whether psychosocial stress raises the risk of HIV infection among gay and bisexual men. If so, we also aimed to evaluate the evidence for the underlying mechanism, specifically whether stress has an intermediate effect on sexual risk behaviour or an independent, cofactor effect. METHODS: Participants were recruited through the provincial HIV diagnostic laboratory, physicians and community organizations in Ontario, Canada, 1998-2006. Confirmed recent seroconverters (n = 123 cases) were asked about stressful life events and behaviour during the likely period of infection (median 8, range 3-33 months). HIV-negative controls (n = 240) were asked about an equivalent time period. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Cases reported more stressful life events (median = 3, 33% 5 or more) than controls (median = 2, 20% 5 or more). Compared to men who reported no events, risk of HIV infection increased with the number of events, to a 2.5-fold increase in risk among men reporting 5 or more (95% CI 1.3, 4.7). The association weakened when adjusted for sexual risk behaviour (OR = 1.7, 95% CI 0.82, 3.6) and when restricted to men who engaged in unprotected receptive anal sex with an HIV-positive or status unknown partner (OR = 1.3, 95% CI 0.50, 3.6). CONCLUSIONS: Gay and bisexual men experiencing stressful life events were at increased risk of HIV infection. This effect was mediated by sexual risk behaviour. We recommend that coping strategies in response to stress be considered in prevention research and health policy.

The effect of secoisolariciresinol diglucoside and flaxseed oil, alone and in combination, on MCF-7 tumor growth and signaling pathways.

Flaxseed (FS), an oilseed containing high amounts of the phytoestrogen lignan, secoisolariciresinol diglucoside (SDG), and n-3 fatty acid, alpha-linolenic acid-rich oil (FO), has been shown to inhibit the growth of established human breast tumors (MCF-7) in ovariectomized (OVX) athymic mice. However, the major FS component responsible for this effect and the mechanism(s) of its action are unclear. Hence, this study determined, in a 2 x 2 factorial design, the effect of SDG and FO, alone or in combination, on the growth of established human estrogen receptor positive (ER+) breast tumors and the potential mechanism(s) of its action. OVX mice with established ER+ human breast tumors (MCF-7) were treated for 8 wk with basal diet (BD, control) or BD supplemented with SDG (1 g/kg), FO (38.5 g/kg), or SDG + FO. All treatments reduced the tumor growth, but SDG had the greatest effect primarily through reducing tumor cell proliferation rather than increasing apoptosis. SDG had a main effect in the reduction of PS2, BCL2, and IGF-1R mRNA expression, whereas FO had a main effect only in PAKT reduction. SDG alone also lowered the ERalpha, ERbeta, EGFR, BCL2 mRNA, and PMAPK protein, indicating that its effect involves the modulation of the ER- and growth factor receptor-mediated signaling pathways.