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Background/Objectives: Obesity polygenic risk scores (PRS) explain substantial variation in body mass index (BMI), yet associations between PRSs and appetitive traits in children remain unclear. To better understand pathways leading to pediatric obesity, this study aimed to assess the association of obesity PRSs and appetitive traits. Subjects/Methods: This study included 248 unrelated children aged 9–12 years. DNA from the children was genotyped (236 met quality control thresholds) and four weighted polygenic risk scores from previous studies were computed and standardized: a 97 SNP PRS, 266 SNP pediatric-specific PRS, 466 SNP adult-specific PRS, and ~2 million SNP PRS. Appetitive traits were assessed using a parent-completed Child Eating Behavior Questionnaire, which evaluated food approach/avoidance traits and a composite obesogenic appetite score. BMI was directly measured and standardized by age and sex. Three associations were evaluated with linear regression: (1) appetitive traits and BMI, (2) PRSs and BMI, and (3) PRSs and appetitive traits, the primary association of interest. Results: Expected positive associations were observed between obesogenic appetitive traits and BMI and all four PRSs and BMI. Examining the association between PRSs and appetitive traits, all PRSs except for the 466 SNP adult PRS were significantly associated with the obesogenic appetite score. Each standard deviation increase in the 266 SNP pediatric PRS was associated with an adjusted 2.1% increase in obesogenic appetite score (95% CI: 0.6%, 3.7%, p = 0.006). Significant partial mediation of the PRS-BMI association by obesogenic appetite score was found for these PRSs; for example, 21.3% of the association between the 266 SNP pediatric PRS and BMI was explained by the obesogenic appetite score. Conclusions: Genetic obesity risk significantly predicted appetitive traits, which partially mediated the association between genetic obesity risk and BMI in children. These findings build

IntroductionWe examined the relationship between current tobacco use and functionally important respiratory symptoms.MethodsLongitudinal cohort study of 16 295 US adults without COPD in Waves 2-3 (W2-3, 2014-2016) of the Population Assessment of Tobacco and Health Study. Exposure-Ten mutually exclusive categories of tobacco use including single product, multiple product, former, and never use (reference). Outcome-Seven questions assessing wheezing/cough were summed to create a respiratory symptom index; cutoffs of ≥2 and ≥3 were associated with functional limitations and poorer health. Multivariable regressions examined both cutoffs cross-sectionally and change over approximately 12 months, adjusting for confounders.ResultsAll tobacco use categories featuring cigarettes (>2/3's of users) were associated with higher risk (vs. never users) for functionally important respiratory symptoms at W2, for example, at symptom severity ≥ 3, risk ratio for exclusive cigarette use was 2.34 [95% CI, 1.92, 2.85] and for worsening symptoms at W3 was 2.80 [2.08, 3.76]. There was largely no increased symptom risk for exclusive use of cigars, smokeless tobacco, hookah, or e-cigarettes (adjustment for pack-years and marijuana attenuated the cross-sectional e-cigarette association from 1.53(95% CI 0.98, 2.40) to 1.05 (0.67, 1.63); RRs for these products were also significantly lower compared to exclusive use of cigarettes. The longitudinal e-cigarette-respiratory symptom association was sensitive to the respiratory index cutoff level; exclusive e-cigarette use was associated with worsening symptoms at an index cutoff ≥ 2 (RR = 1.63 [1.02, 2.59]) and with symptom improvement at an index cutoff of ≥ 3 (RR = 1.64 [1.04, 2.58]).ConclusionsPast and current cigarette smoking drove functionally important respiratory symptoms, while exclusive use of other tobacco products was largely not associated. However, the relationship between e-cigarette use and symptoms was sensitive to adjustment for

The purpose of this study is to validate the seven-item wheezing module from the International Study of Asthma and Allergies in Children (ISAAC) in the nationally representative Population Assessment of Tobacco and Health Study. Adult participants with complete Wave 2-3 data were selected, including those with asthma but excluding those with COPD and other respiratory diseases (n = 16,295). We created a nine-point respiratory symptom index from the ISAAC questions, assessed the reliability of the index, and examined associations with self-reported asthma diagnosis. Threshold values were assessed for association with functional outcomes. The weighted prevalence for one or more respiratory symptom was 18.0% (SE = 0.5) for adults without asthma, 70.1% (SE = 1.3) for those with lifetime asthma, 75.7% (SE = 3.7) for adults with past-year asthma not on medications, and 92.6% (SE = 1.6) for those on medications. Cronbach's alpha for the respiratory symptom index was 0.86. Index scores of ≥2 or ≥3 yielded functionally important respiratory symptom prevalence of 7-10%, adequate sensitivity and specificity for identifying asthma, and consistent independent associations with all functional outcomes and tobacco use variables. Respiratory symptom index scores of ≥2 or ≥3 are indicative of functionally important respiratory symptoms and could be used to assess the relationship between tobacco use and respiratory health.

The purpose of this study is to validate the seven-item wheezing module from the International Study of Asthma and Allergies in Children (ISAAC) in the nationally representative Population Assessment of Tobacco and Health Study. Adult participants with complete Wave 2-3 data were selected, including those with asthma but excluding those with COPD and other respiratory diseases (n = 16,295). We created a nine-point respiratory symptom index from the ISAAC questions, assessed the reliability of the index, and examined associations with self-reported asthma diagnosis. Threshold values were assessed for association with functional outcomes. The weighted prevalence for one or more respiratory symptom was 18.0% (SE = 0.5) for adults without asthma, 70.1% (SE = 1.3) for those with lifetime asthma, 75.7% (SE = 3.7) for adults with past-year asthma not on medications, and 92.6% (SE = 1.6) for those on medications. Cronbach's alpha for the respiratory symptom index was 0.86. Index scores of ≥2 or ≥3 yielded functionally important respiratory symptom prevalence of 7-10%, adequate sensitivity and specificity for identifying asthma, and consistent independent associations with all functional outcomes and tobacco use variables. Respiratory symptom index scores of ≥2 or ≥3 are indicative of functionally important respiratory symptoms and could be used to assess the relationship between tobacco use and respiratory health.

The purpose of this study is to validate the seven-item wheezing module from the International Study of Asthma and Allergies in Children (ISAAC) in the nationally representative Population Assessment of Tobacco and Health Study. Adult participants with complete Wave 2-3 data were selected, including those with asthma but excluding those with COPD and other respiratory diseases (n = 16,295). We created a nine-point respiratory symptom index from the ISAAC questions, assessed the reliability of the index, and examined associations with self-reported asthma diagnosis. Threshold values were assessed for association with functional outcomes. The weighted prevalence for one or more respiratory symptom was 18.0% (SE = 0.5) for adults without asthma, 70.1% (SE = 1.3) for those with lifetime asthma, 75.7% (SE = 3.7) for adults with past-year asthma not on medications, and 92.6% (SE = 1.6) for those on medications. Cronbach's alpha for the respiratory symptom index was 0.86. Index scores of ≥2 or ≥3 yielded functionally important respiratory symptom prevalence of 7-10%, adequate sensitivity and specificity for identifying asthma, and consistent independent associations with all functional outcomes and tobacco use variables. Respiratory symptom index scores of ≥2 or ≥3 are indicative of functionally important respiratory symptoms and could be used to assess the relationship between tobacco use and respiratory health.

BackgroundThe insulin-like growth factor-I (IGFI) receptor is a potential target for breast cancer treatment and may be influenced by dietary intake.MethodsNested, case-control study of 265 postmenopausal breast cancer survivors; primary breast cancer tissue was stained to determine IGFI receptor status. Change in carbohydrate intake from baseline to year 1 of study was estimated from 24-hour dietary recalls. Breast cancer recurrence cases (91) were matched to two controls (n = 174) on disease and study characteristics and counter matched on change in carbohydrate intake. Weighted conditional logistic regression models fit the risk of recurrence on IGFI receptor status and dietary change.ResultsHalf of the tumors were IGFI receptor positive. Increased risk of recurrence was associated with IGFI receptor-positive status [HR 1.7; 95% confidence interval (CI), 1.2-2.5] and, separately, with a stable/increased intake of carbohydrates (HR 2.0; 95% CI, 1.3-5.0). There was a borderline significant interaction between those two variables (P = 0.11). Specifically, carbohydrate intake had no significant impact on risk of recurrence among women who were receptor negative, yet increased the risk of recurrence by more than 5-fold among women who were receptor positive (HR 5.5; 95% CI, 1.8-16.3).ConclusionsAmong women whose tumor tissue is positive for the IGFI receptor, reducing carbohydrate intake after diagnosis could reduce the risk of breast cancer recurrence. These findings need replication in a larger sample.ImpactThis is the first study to suggest that it may be possible to personalize dietary recommendations for breast cancer survivors based on molecular characteristics of their primary tumor tissue. .

BackgroundThe insulin-like growth factor-I (IGFI) receptor is a potential target for breast cancer treatment and may be influenced by dietary intake.MethodsNested, case-control study of 265 postmenopausal breast cancer survivors; primary breast cancer tissue was stained to determine IGFI receptor status. Change in carbohydrate intake from baseline to year 1 of study was estimated from 24-hour dietary recalls. Breast cancer recurrence cases (91) were matched to two controls (n = 174) on disease and study characteristics and counter matched on change in carbohydrate intake. Weighted conditional logistic regression models fit the risk of recurrence on IGFI receptor status and dietary change.ResultsHalf of the tumors were IGFI receptor positive. Increased risk of recurrence was associated with IGFI receptor-positive status [HR 1.7; 95% confidence interval (CI), 1.2-2.5] and, separately, with a stable/increased intake of carbohydrates (HR 2.0; 95% CI, 1.3-5.0). There was a borderline significant interaction between those two variables (P = 0.11). Specifically, carbohydrate intake had no significant impact on risk of recurrence among women who were receptor negative, yet increased the risk of recurrence by more than 5-fold among women who were receptor positive (HR 5.5; 95% CI, 1.8-16.3).ConclusionsAmong women whose tumor tissue is positive for the IGFI receptor, reducing carbohydrate intake after diagnosis could reduce the risk of breast cancer recurrence. These findings need replication in a larger sample.ImpactThis is the first study to suggest that it may be possible to personalize dietary recommendations for breast cancer survivors based on molecular characteristics of their primary tumor tissue. .

Background : Converging lines of research suggest that activation of the insulin/insulin-like-growth-factor axis may impact prognosis among breast cancer survivors. Carbohydrate intake can stimulate the insulin/insulin-like -growth-factor axis by elevating blood glucose concentrations, and insulin-like-growth-factor-1 receptor (IGF-1R) activation in breast cancers triggers proliferative signaling. This dissertation examined the influence of carbohydrate intake on breast cancer recurrence and all-cause mortality among postmenopausal breast cancer survivors, and whether the odds of recurrence was modified by IGF-1R expression in the primary cancer. Methods : Secondary analysis of N=2,111 postmenopausal breast cancer survivors enrolled in a dietary intervention trial. Baseline and one-year dietary intake was assessed using 24-hour dietary recalls. One- year change in carbohydrate intake was quantified as tertiles (grams/day) and change in approximately one serving of high or low quality carbohydrate-based foods; quality considered the impact on blood glucose concentrations. Samples of primary breast cancer tissue (N=265) were stained in a nested, case-control, immunohistochemical study to test the interaction between a decreased carbohydrate intake and IGF-1R expression on odds of recurrence. Finally, the impact of carbohydrate quality (high vs. low) on outcomes was assessed among the full cohort. Results : Dietary changes began a median 24 months post-diagnosis. Over a median 7 years, there were N=247 (11.7%) recurrences. Risk of recurrence significantly increased over tertiles of change in carbohydrate intake (p=0.055). A decreased carbohydrate intake (< -26 grams/day) reduced the risk of recurrence by 30% (HR: 0.7; 95%CI:0.5-1.0). Risk reduction significantly differed (p=0.110) by IGF-1R expression in the primary breast cancer: a decreased carbohydrate intake reduced the odds of recurrence by 30% (conditional OR: 0.7;95%CI:0.2- 1.7) among participants who had IGF

Background : Converging lines of research suggest that activation of the insulin/insulin-like-growth-factor axis may impact prognosis among breast cancer survivors. Carbohydrate intake can stimulate the insulin/insulin-like -growth-factor axis by elevating blood glucose concentrations, and insulin-like-growth-factor-1 receptor (IGF-1R) activation in breast cancers triggers proliferative signaling. This dissertation examined the influence of carbohydrate intake on breast cancer recurrence and all-cause mortality among postmenopausal breast cancer survivors, and whether the odds of recurrence was modified by IGF-1R expression in the primary cancer. Methods : Secondary analysis of N=2,111 postmenopausal breast cancer survivors enrolled in a dietary intervention trial. Baseline and one-year dietary intake was assessed using 24-hour dietary recalls. One- year change in carbohydrate intake was quantified as tertiles (grams/day) and change in approximately one serving of high or low quality carbohydrate-based foods; quality considered the impact on blood glucose concentrations. Samples of primary breast cancer tissue (N=265) were stained in a nested, case-control, immunohistochemical study to test the interaction between a decreased carbohydrate intake and IGF-1R expression on odds of recurrence. Finally, the impact of carbohydrate quality (high vs. low) on outcomes was assessed among the full cohort. Results : Dietary changes began a median 24 months post-diagnosis. Over a median 7 years, there were N=247 (11.7%) recurrences. Risk of recurrence significantly increased over tertiles of change in carbohydrate intake (p=0.055). A decreased carbohydrate intake (< -26 grams/day) reduced the risk of recurrence by 30% (HR: 0.7; 95%CI:0.5-1.0). Risk reduction significantly differed (p=0.110) by IGF-1R expression in the primary breast cancer: a decreased carbohydrate intake reduced the odds of recurrence by 30% (conditional OR: 0.7;95%CI:0.2- 1.7) among participants who had IGF

available at publisher's website.

IntroductionPrevalence of walking and cycling for transport is low and varies greatly across countries. Few studies have examined neighborhood perceptions related to walking and cycling for transport in different countries. Therefore, it is challenging to prioritize appropriate built-environment interventions.ObjectivesThe aim of this study was to examine the strength and shape of the relationship between adults' neighborhood perceptions and walking and cycling for transport across diverse environments.MethodsAs part of the International Physical activity and Environment Network (IPEN) adult project, self-reported data were taken from 13,745 adults (18-65 years) living in physically and socially diverse neighborhoods in 17 cities across 12 countries. Neighborhood perceptions were measured using the Neighborhood Environment Walkability Scale, and walking and cycling for transport were measured using the International Physical Activity Questionnaire-Long Form. Generalized additive mixed models were used to model walking or cycling for transport during the last seven days with neighborhood perceptions. Interactions by city were explored.ResultsWalking-for-transport outcomes were significantly associated with perceived residential density, land use mix-access, street connectivity, aesthetics, and safety. Any cycling for transport was significantly related to perceived land use mix-access, street connectivity, infrastructure, aesthetics, safety, and perceived distance to destinations. Between-city differences existed for some attributes in relation to walking or cycling for transport.ConclusionsMany perceived environmental attributes supported both cycling and walking; however, highly walkable environments may not support cycling for transport. People appear to walk for transport despite safety concerns. These findings can guide the implementation of global health strategies.

INTRODUCTION: Prevalence of walking and cycling for transport is low and varies greatly across countries. Few studies have examined neighborhood perceptions related to walking and cycling for transport in different countries. Therefore, it is challenging to prioritize appropriate built-environment interventions. OBJECTIVES: The aim of this study was to examine the strength and shape of the relationship between adults' neighborhood perceptions and walking and cycling for transport across diverse environments. METHODS: As part of the International Physical activity and Environment Network (IPEN) adult project, self-reported data were taken from 13,745 adults (18-65 years) living in physically and socially diverse neighborhoods in 17 cities across 12 countries. Neighborhood perceptions were measured using the Neighborhood Environment Walkability Scale, and walking and cycling for transport were measured using the International Physical Activity Questionnaire-Long Form. Generalized additive mixed models were used to model walking or cycling for transport during the last seven days with neighborhood perceptions. Interactions by city were explored. RESULTS: Walking-for-transport outcomes were significantly associated with perceived residential density, land use mix-access, street connectivity, aesthetics, and safety. Any cycling for transport was significantly related to perceived land use mix-access, street connectivity, infrastructure, aesthetics, safety, and perceived distance to destinations. Between-city differences existed for some attributes in relation to walking or cycling for transport. CONCLUSIONS: Many perceived environmental attributes supported both cycling and walking; however, highly walkable environments may not support cycling for transport. People appear to walk for transport despite safety concerns. These findings can guide the implementation of global health strategies.

IntroductionPrevalence of walking and cycling for transport is low and varies greatly across countries. Few studies have examined neighborhood perceptions related to walking and cycling for transport in different countries. Therefore, it is challenging to prioritize appropriate built-environment interventions.ObjectivesThe aim of this study was to examine the strength and shape of the relationship between adults' neighborhood perceptions and walking and cycling for transport across diverse environments.MethodsAs part of the International Physical activity and Environment Network (IPEN) adult project, self-reported data were taken from 13,745 adults (18-65 years) living in physically and socially diverse neighborhoods in 17 cities across 12 countries. Neighborhood perceptions were measured using the Neighborhood Environment Walkability Scale, and walking and cycling for transport were measured using the International Physical Activity Questionnaire-Long Form. Generalized additive mixed models were used to model walking or cycling for transport during the last seven days with neighborhood perceptions. Interactions by city were explored.ResultsWalking-for-transport outcomes were significantly associated with perceived residential density, land use mix-access, street connectivity, aesthetics, and safety. Any cycling for transport was significantly related to perceived land use mix-access, street connectivity, infrastructure, aesthetics, safety, and perceived distance to destinations. Between-city differences existed for some attributes in relation to walking or cycling for transport.ConclusionsMany perceived environmental attributes supported both cycling and walking; however, highly walkable environments may not support cycling for transport. People appear to walk for transport despite safety concerns. These findings can guide the implementation of global health strategies.

Habitual short sleep duration appears to increase the risk of obesity. The objective of this paper is to investigate the association of habitual sleep duration with objective measures of energy balance. One hundred twelve African-American and 111 non-Hispanic whites aged 21-69 y participated in a cross-sectional study of dietary assessment and biomarkers. Participants reported the mean number of hours per day spent sleeping over the past year. Short sleep duration was defined as ≤6 h/d of sleep. Energy intake (kilocalories) was objectively assessed using the 2-point doubly labeled water technique to determine total energy expenditure, which is approximately equal to energy intake. Physical activity energy expenditure (kilocalories) was estimated as total energy expenditure minus each participant's calculated basal metabolic rate and the thermogenic effect of food. Compared with participants who slept ≤6 h, individuals who slept 8 h were significantly less likely to be obese (OR: 0.33; 95% CI: 0.14, 0.79). However, this association was not linear across 6-9 h of sleep (P-trend = 0.16). There was an inverse association between sleep and energy intake (P-trend = 0.07): compared with ≤6 h/d, adults who reported ≥9 h sleep consumed 178 fewer kcal/d. There was also an inverse association between sleep and physical activity (P-trend = 0.05): compared with ≤6 h/d of sleep, adults who reported 9 h of usual sleep expended 113 fewer kcal/d in physical activity. These data indicate that, compared with longer sleep duration, adults who report habitual short sleep duration have somewhat higher physical activity energy expenditure but considerably higher energy intake. Habitual short sleep duration appears to be 1 of the facets of modern life leading to a mismatch between energy intake and physical activity.

Habitual short sleep duration appears to increase the risk of obesity. The objective of this paper is to investigate the association of habitual sleep duration with objective measures of energy balance. One hundred twelve African-American and 111 non-Hispanic whites aged 21-69 y participated in a cross-sectional study of dietary assessment and biomarkers. Participants reported the mean number of hours per day spent sleeping over the past year. Short sleep duration was defined as ≤6 h/d of sleep. Energy intake (kilocalories) was objectively assessed using the 2-point doubly labeled water technique to determine total energy expenditure, which is approximately equal to energy intake. Physical activity energy expenditure (kilocalories) was estimated as total energy expenditure minus each participant's calculated basal metabolic rate and the thermogenic effect of food. Compared with participants who slept ≤6 h, individuals who slept 8 h were significantly less likely to be obese (OR: 0.33; 95% CI: 0.14, 0.79). However, this association was not linear across 6-9 h of sleep (P-trend = 0.16). There was an inverse association between sleep and energy intake (P-trend = 0.07): compared with ≤6 h/d, adults who reported ≥9 h sleep consumed 178 fewer kcal/d. There was also an inverse association between sleep and physical activity (P-trend = 0.05): compared with ≤6 h/d of sleep, adults who reported 9 h of usual sleep expended 113 fewer kcal/d in physical activity. These data indicate that, compared with longer sleep duration, adults who report habitual short sleep duration have somewhat higher physical activity energy expenditure but considerably higher energy intake. Habitual short sleep duration appears to be 1 of the facets of modern life leading to a mismatch between energy intake and physical activity.

Context Evidence is lacking that a dietary pattern high in vegetables, fruit, and fiber and low in total fat can influence breast cancer recurrence or survival. Objective To assess whether a major increase in vegetable, fruit, and fiber intake and a decrease in dietary fat intake reduces the risk of recurrent and new primary breast cancer and all-cause mortality among women with previously treated early stage breast cancer. Design, Setting, and Participants Multi-institutional randomized controlled trial of dietary change in 3088 women previously treated for early stage breast cancer who were 18 to 70 years old at diagnosis. Women were enrolled between 1995 and 2000 and followed up through June 1, 2006. Intervention The intervention group (n=1537) was randomly assigned to receive a telephone counseling program supplemented with cooking classes and newsletters that promoted daily targets of 5 vegetable servings plus 16 oz of vegetable juice; 3 fruit servings; 30 g of fiber; and 15% to 20% of energy intake from fat. The comparison group (n=1551) was provided with print materials describing the “5-A-Day” dietary guidelines. Main Outcome Measures Invasive breast cancer event (recurrence or new primary) or death from any cause. Results From comparable dietary patterns at baseline, a conservative imputation analysis showed that the intervention group achieved and maintained the following statistically significant differences vs the comparison group through 4 years: servings of vegetables, 65%; fruit,25%; fiber,30%, and energy intake from fat, −13%. Plasma carotenoid concentrations validated changes in fruit and vegetable intake. Throughout the study, women in both groups received similar clinical care. Over the mean 7.3-year follow-up, 256 women in the intervention group (16.7%) vs 262 in the comparison group (16.9%) experienced an invasive breast cancer event (adjusted hazard ratio, 0.96; 95% confidence interval, 0.80-1.14; P=.63), and 155 intervention group women (10.1%

To examine whether weight gain after diagnosis of breast cancer affects the risk of breast cancer recurrence. Patients included 3215 women diagnosed with early stage breast cancer (Stage I > 1 cm., II, and IIIA) who were enrolled either in an observational cohort of breast cancer survivors or were part of the comparison group of a dietary intervention trial to prevent breast cancer recurrence. We computed weight change from 1 year prior to diagnosis to study enrollment. Delayed entry Cox proportional hazards models were used to evaluate associations of categories of weight change with time to recurrence, controlling for known prognostic factors. Neither moderate (5-10%) nor large (> 10%) weight gain (HR 0.8, 95% CI, 0.6-1.1; HR 0.9, 95% CI, 0.7-1.2, respectively) after breast cancer diagnosis was associated with an increased risk of breast cancer recurrence in the early years post-diagnosis (median time of 73.7 months from diagnosis). Our research provides evidence that weight gain commonly seen in the first several years following a breast cancer diagnosis does not increase a woman's risk for breast cancer recurrence in the first 5-7 years post-diagnosis. However, this research does not address the effects of weight gain on overall survival or on the risk of other new cancers, other prognostic outcomes of concern to the breast cancer survivor.

To examine whether weight gain after diagnosis of breast cancer affects the risk of breast cancer recurrence. Patients included 3215 women diagnosed with early stage breast cancer (Stage I > 1 cm., II, and IIIA) who were enrolled either in an observational cohort of breast cancer survivors or were part of the comparison group of a dietary intervention trial to prevent breast cancer recurrence. We computed weight change from 1 year prior to diagnosis to study enrollment. Delayed entry Cox proportional hazards models were used to evaluate associations of categories of weight change with time to recurrence, controlling for known prognostic factors. Neither moderate (5-10%) nor large (> 10%) weight gain (HR 0.8, 95% CI, 0.6-1.1; HR 0.9, 95% CI, 0.7-1.2, respectively) after breast cancer diagnosis was associated with an increased risk of breast cancer recurrence in the early years post-diagnosis (median time of 73.7 months from diagnosis). Our research provides evidence that weight gain commonly seen in the first several years following a breast cancer diagnosis does not increase a woman's risk for breast cancer recurrence in the first 5-7 years post-diagnosis. However, this research does not address the effects of weight gain on overall survival or on the risk of other new cancers, other prognostic outcomes of concern to the breast cancer survivor.