Calorie Restriction Impairs Anti-Tumor Immune Responses in an Immunogenic Preclinical Cancer Model.

(1) Background: Although the important role of dietary energy intake in regulating both cancer progression and host immunity has been widely recognized, it remains unclear whether dietary calorie restriction (CR) has any impact on anti-tumor immune responses. (2) Methods: Using an immunogenic B16 melanoma cell expressing ovalbumin (B16-OVA), we examined the effect of the CR diet on B16-OVA tumor growth and host immune responses. To further test whether the CR diet affects the efficacy of cancer immunotherapy, we examined the effect of CR against anti-PD-1 monoclonal antibody (anti-PD-1 Ab) treatment. (3) Results: The CR diet significantly slowed down the tumor growth of B16-OVA without affecting both CD4+ and CD8+ T cell infiltration into the tumor. Although in vivo depletion of CD8+ T cells facilitated B16-OVA tumor growth in the control diet group, there was no significant change in the tumor growth in the CR diet group with or without CD8+ T cell-depletion. Anti-PD-1 Ab treatment lost its efficacy to suppress tumor growth along with the activation and metabolic shift of CD8+ T cells under CR condition. (4) Conclusions: Our present results suggest that a physical condition restricted in energy intake in cancer patients may impair CD8+ T cell immune surveillance and the efficacy of immunotherapy.

CAMSAP3 negatively regulates lung cancer cell invasion and angiogenesis through nucleolin/HIF-1α mRNA complex stabilization.

AIMS: Cancer metastasis is a major cause of lung cancer-related mortality, so identification of related molecular mechanisms is of interest. Calmodulin-regulated spectrin-associated protein 3 (CAMSAP3) has been implicated in lung cancer malignancies; however, its role in metastatic processes, including invasion and angiogenesis, is largely unknown. MAIN METHOD: The clinical relevance of CAMSAP3 expression in lung cancer was evaluated. The relevance of CAMSAP3 expression to in vitro cell invasion and angiogenesis was assessed in human lung cancer cells and endothelial cells, respectively. The molecular mechanism was identified by qRT-PCR, immunoprecipitation, mass spectrometry, and RNA immunoprecipitation. The in vivo metastatic and angiogenic activities of lung cancer cells were assessed. KEY FINDINGS: Low CAMSAP3 expression was found in malignant lung tissues and strongly correlated with a poor prognosis in lung adenocarcinoma (LUAD). CAMSAP3-knockout NSCLC exhibited high invasive ability, and CAMSAP3 knockout induced HUVEC proliferation and tube formation; these effects were significantly attenuated by reintroduction of exogenous wild-type CAMSAP3. Mechanistically, in the absence of CAMSAP3, the expression of hypoxia-inducible factor-1α (HIF-1α) was upregulated, which increased the levels of downstream HIF-1α targets such as vascular endothelial growth factor A (VEGFA) and matrix metalloproteinases (MMPs) 2 and 9. Proteomic analysis revealed that nucleolin (NCL) bound to CAMSAP3 to regulate HIF-1α mRNA stabilization. In addition, CAMSAP3-knockout lung cancer cells displayed highly aggressive behavior in metastasis and angiogenesis in vivo. SIGNIFICANCE: This study reveals that CAMSAP3 plays a negative regulatory role in lung cancer cell metastatic behavior both in vitro and in vivo through NCL/HIF-1α mRNA complex stabilization.

Low- and moderate- levels of arsenic exposure in young adulthood and incidence of chronic kidney disease: Findings from the CARDIA Trace Element Study.

BACKGROUND: It is unclear whether arsenic exerts adverse health effects on the kidney at low- and moderate- levels of exposure. We prospectively examined toenail arsenic concentrations measured during young adulthood in relation to incidence of chronic kidney disease (CKD) in midlife. METHODS: A total of 3768 participants (53 % female and 48 % blacks) in the Coronary Artery Risk Development in Young Adults (CARDIA) study were included. Arsenic concentration in toenail clippings was assessed by using inductively coupled plasma mass spectrometry at CARDIA exam year 2. Incident CKD was identified if having estimated glomerular filtration rate <60 mL/min per 1.73 m² or albuminuria >30 mg/g. The association between toenail arsenic levels and CKD incidence over a mean of 24 years of follow-up was examined using multivariable-adjusted Cox proportional hazards models. RESULTS: After controlling for potential confounders, including demographics, socioeconomics, lifestyle factors, clinical measurements of blood pressure, lipids, and glucose, and medical history, arsenic exposure measured in toenails was not associated with CKD incidence (quintile 5 versus quintile 1: hazard ratio = 1.04, 95 % confidence interval = 0.78-1.40, P for trend = 0.38). CONCLUSION: This longitudinal study does not support the hypothesis that low- and moderate- levels of arsenic exposure are associated with elevated incidence of CKD in the US general population. Further studies are need to investigate species of arsenic biomarkers in relation to nephrotoxicity.

Magnesium levels in relation to rates of preterm birth: a systematic review and meta-analysis of ecological, observational, and interventional studies.

CONTEXT: Experimental studies suggest that magnesium levels in pregnant women may affect the length of gestation, as magnesium affects the activity of smooth muscle in the uterus. Little is known about the association between magnesium levels or supplementation and the rate of preterm birth. OBJECTIVE: The aim of this systematic review was to summarize the data on magnesium soil levels and preterm birth rates from ecological, observational, and interventional studies. DATA SOURCES: Soil magnesium levels were obtained from US Geological Survey data, and preterm birth rates were acquired from the March of Dimes Foundation. Relevant epidemiological and clinical studies published until April 2019 in peer-reviewed journals were retrieved from PubMed, Google Scholar, and related reference lists. STUDY SELECTION: Original studies published in English, conducted in humans, and in which magnesium (dietary/supplemental intake or biomarkers) was an exposure and preterm birth was an outcome were included. DATA EXTRACTION: Eleven studies were included in the systematic review. Meta-analysis was performed on 6 studies. Overall relative risk (RR) and corresponding 95%CIs for risk of preterm birth in relation to magnesium supplementation were estimated by a random-effects model. RESULTS: The ecological study revealed an inverse correlation between magnesium content in soil and rates of preterm birth across the United States (r = -0.68; P < 0.001). Findings from 11 observational studies generally support an inverse association between serum magnesium levels and rates of preterm birth. Of the 6 eligible randomized controlled trials, which included 3068 pregnant women aged 20 to 35 years and 352 preterm infants, the pooled RR was 0.58 (95%CI, 0.35-0.96) for women in the magnesium supplementation group compared with women in the control group. CONCLUSIONS: Accumulated evidence from ecological, observational, and interventional studies consistently indicates that adequate magnesium intake during pregnancy may help reduce the incidence of preterm birth.

Serum magnesium concentration and incident cognitive impairment: the reasons for geographic and racial differences in stroke study.

PURPOSE: To examine the prospective association between serum Mg level and the incidence of cognitive impairment. METHODS: A random sub-cohort (n = 2063) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort was included in this study. Baseline serum Mg concentration was measured using inductively coupled plasma mass spectrometry. According to the current reference interval of serum magnesium (0.75-0.95 mmol/L), we classified participants below the interval as Level 1 and used it as the referent. The rest of the study population were equally divided into three groups, named Level 2 to 4. Incident cognitive impairment was identified using the Six-Item Screener. Multivariable-adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using logistic regression models. RESULTS: After adjustment for potential confounders, an inverse threshold association between serum Mg level and incident cognitive impairment was observed. Compared to those with hypomagnesemia (Level 1: < 0.75 mmol/L), the relative odds of incident cognitive impairment was reduced by 41% in the second level [OR (95% CI) = 0.59 (0.37, 0.94)]; higher serum Mg level did not provide further benefits [Level 3 and 4 versus Level 1: OR (95% CI) = 0.54 (0.34, 0.88) and 0.59 (0.36, 0.96), P for linear trend = 0.08]. CONCLUSIONS: Findings from this prospective study suggest that sufficient Mg status within the normal range may be beneficial to cognitive health in the US general population.

Walking pace and the risk of stroke: A meta-analysis of prospective cohort studies.

PURPOSE: The extent to which walking pace is associated with a reduced risk for stroke remains unclear. This study examined the association between walking pace and stroke risk based on prospective cohort studies. METHODS: Databases of PubMed, EMBASE, Web of Science, Scopus, and China National Knowledge Internet were searched from the inception dates to January 31, 2019, for prospective cohort studies focusing on walking pace and risk of stroke in adults. Two reviewers independently extracted data and assessed the quality of the studies. The dependent measure was stroke incidence. Using random-effects models, a meta-analysis was performed to estimate the overall relative risks (RR) of stroke incidence and 95% confidence intervals (CIs) for the individuals with the fastest walking paces vs. individuals with the slowest walking paces. A dose-response relationship was also examined. RESULTS: After screening 1294 titles/abstracts and 14 full-text studies identified in the search, 7 studies (from 8 cohorts) were included in the meta-analysis. The 7 studies included a total of 135,645 participants (95.2% women; mean age 63.6 years) and 2229 stroke events (median follow-up time = 8.0 years). Compared to individuals in the slowest walking-pace category (median = 1.6 km/h), individuals in the fastest walking-pace category (median = 5.6 km/h) had a 44% lower risk of stroke (pooled RR = 0.56, 95%CI: 0.48-0.65). There was also a linear dose-response relationship (RR = 0.87; 95%CI: 0.83-0.91), with the risk of stroke decreased by 13% for every 1 km/h increment in baseline walking pace. We observed similar results across walking-pace assessment, type of stroke ascertainment, stroke subtypes, sex, sample size, and duration of follow-up. CONCLUSION: Findings from this meta-analysis indicate that walking pace is inversely associated with the risk of stroke.

Association Between Gestational Weight Gain and Autism Spectrum Disorder in Offspring: A Meta-Analysis.

OBJECTIVE: This study aimed to quantitatively examine the association between gestational weight gain (GWG) and risk of autism spectrum disorder (ASD) in offspring. METHODS: Electronic databases were searched for studies of excessive or inadequate GWG, as compared with recommended GWG, in relation to the risk of ASD in offspring. Measures of the association from primary studies were pooled using a meta-analytic approach and expressed as weighted odds ratios (ORs) with 95% CIs. RESULTS: Nine studies were identified, including 323,253 participants with 4,135 cases of ASD from five cohort studies and 1,462 cases and 3,265 controls from four case-control studies. Evidence from cohort studies indicates that both excessive and inadequate GWG was significantly associated with a higher risk for ASD in offspring. The pooled OR of ASD was 1.10 (95% CI: 1.02-1.18) for excessive GWG and 1.13 (95% CI: 1.04-1.24) for inadequate GWG using recommended GWG as the reference. Evidence from case-control studies suggests that excessive GWG (1.38 [95% CI: 1.19-1.62]) but not inadequate GWG (0.87 [95% CI: 0.72-1.04]) was significantly associated with a higher risk for ASD. CONCLUSIONS: The accumulated evidence has supported that gaining weight outside the recommended GWG is associated with a higher risk for ASD in offspring.

Intakes of Folate, Vitamin B6, and Vitamin B12 in Relation to Diabetes Incidence Among American Young Adults: A 30-Year Follow-up Study.

OBJECTIVE: To prospectively examine intakes of folate, vitamin B6, and vitamin B12 in relation to diabetes incidence in a large U.S. cohort. RESEARCH DESIGN AND METHODS: A total of 4,704 American adults aged 18-30 years and without diabetes were enrolled in 1985-1986 and monitored until 2015-2016 in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Dietary assessment was conducted by a validated dietary history questionnaire at baseline, in 1992-1993, and in 2005-2006. The cumulative average intakes of folate, vitamin B6, and vitamin B12 were used in the analyses. Incident diabetes was ascertained by plasma glucose levels, oral glucose tolerance tests, hemoglobin A1c concentrations, and/or antidiabetic medications. RESULTS: During 30 years (mean 20.5 ± 8.9) of follow-up, 655 incident cases of diabetes occurred. Intake of folate, but not vitamin B6 or vitamin B12, was inversely associated with diabetes incidence after adjustment for potential confounders. Compared with the lowest quintile of total folate intake, the multivariable-adjusted hazard ratios (95% CI) in quintiles 2-5 were 0.85 (0.67-1.08), 0.78 (0.60-1.02), 0.82 (0.62-1.09), and 0.70 (0.51-0.97; P trend = 0.02). Higher folate intake was also associated with lower plasma homocysteine (P trend < 0.01) and insulin (P trend < 0.01). Among supplement users, folate intake was inversely associated with serum C-reactive protein levels (P trend < 0.01). CONCLUSIONS: Intake of folate in young adulthood was inversely associated with diabetes incidence in midlife among Americans. The observed association may be partially explained by mechanisms related to homocysteine level, insulin sensitivity, and systemic inflammation.

Association between selenium intake and breast cancer risk: results from the Women's Health Initiative.

PURPOSE: It has been hypothesized that selenium (Se) can prevent cancer, and that Se deficiency may be associated with an increased risk of breast cancer. However, findings from epidemiological studies have been inconsistent. The objective of this study was to assess the association between Se intake and risk of breast cancer in the Women's Health Initiative (WHI). METHODS: This study included 145,033 postmenopausal women 50-79 years who completed baseline questionnaires between October 1993 and December 1998, which addressed dietary and supplemental Se intake and breast cancer risk factors. The association between baseline Se intake and incident breast cancer was examined in Cox proportional hazards analysis. RESULTS: During a mean follow-up of 15.5 years, 9487 cases of invasive breast cancer were identified. Total Se (highest versus lowest quartile: HR 1.00, 95% CI 0.92-1.09, Ptrend = 0.66), dietary Se (highest versus lowest quartile: HR 0.99, 95% CI 0.89-1.08, Ptrend = 0.61), and supplemental Se (yes versus no: HR 0.99, 95% CI 0.95-1.03) were not associated with breast cancer incidence. CONCLUSIONS: This study indicates that Se intake is not associated with incident breast cancer among postmenopausal women in the United States. Further studies are needed to confirm our findings by using biomarkers such as toenail Se to reduce the potential for misclassification of Se status.

Erythrocyte omega-3 index, ambient fine particle exposure, and brain aging.

OBJECTIVE: To examine whether long-chain omega-3 polyunsaturated fatty acid (LCn3PUFA) levels modify the potential neurotoxic effects of particle matter with diameters <2.5 µm (PM2.5) exposure on normal-appearing brain volumes among dementia-free elderly women. METHODS: A total of 1,315 women (age 65-80 years) free of dementia were enrolled in an observational study between 1996 and 1999 and underwent structural brain MRI in 2005 to 2006. According to prospectively collected and geocoded participant addresses, we used a spatiotemporal model to estimate the 3-year average PM2.5 exposure before the MRI. We examined the joint associations of baseline LCn3PUFAs in red blood cells (RBCs) and PM2.5 exposure with brain volumes in generalized linear models. RESULTS: After adjustment for potential confounders, participants with higher levels of RBC LCn3PUFA had significantly greater volumes of white matter and hippocampus. For each interquartile increment (2.02%) in omega-3 index, the average volume was 5.03 cm3 (p < 0.01) greater in the white matter and 0.08 cm3 (p = 0.03) greater in the hippocampus. The associations with RBC docosahexaenoic acid and eicosapentaenoic acid levels were similar. Higher LCn3PUFA attenuated the inverse associations between PM2.5 exposure and white matter volumes in the total brain and multimodal association areas (frontal, parietal, and temporal; all p for interaction <0.05), while the associations with other brain regions were not modified. Consistent results were found for dietary intakes of LCn3PUFAs and nonfried fish. CONCLUSIONS: Findings from this prospective cohort study among elderly women suggest that the benefits of LCn3PUFAs on brain aging may include the protection against potential adverse effects of air pollution on white matter volumes.

Physical activity and risk of bladder cancer among postmenopausal women.

Physical activity is associated with decreased risk for many cancers. Studies on the association between physical activity and risk of bladder cancer are limited, and findings are inconsistent. Postmenopausal women (mean age = 63.3) were recruited into the Women's Health Initiative from 1993 to 1998. Self-reported baseline information on physical activity and other covariates were available in 141 288 participants. Incident bladder cancer cases were collected through 2018 and centrally adjudicated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined by Cox proportional hazard regression models. Effect modification due to smoking was assessed. During an average of 18.5 years of follow-up, 817 bladder cancer cases were identified. Compared to physically inactive women, those who engaged in ≥15 MET-hours/week of total physical activity, ≥8.75 MET-hours/week of walking or ≥11.25 MET-hours/week of moderate to vigorous physical activity had lower risk of bladder cancer (HR = 0.74, 95% CI: 0.59-0.94, P for linear trend = .02; HR = 0.79, 95% CI: 0.63-0.98, P for linear trend = .03; and HR = 0.76, 95% CI: 0.61-0.94, P for linear trend = .02, respectively). No effect modification was found by smoking status (P for interaction = .06, 0.91 and 0.27, respectively). We found that total physical activity, walking and moderate to vigorous physical activity were inversely associated with bladder cancer incidence among postmenopausal women in a dose-response manner. Physical activity may play a potential role in the primary prevention of bladder cancer. Further studies with objective measurements of physical activity are needed to confirm these findings.

The association between type 2 diabetes mellitus and bladder cancer risk among postmenopausal women.

INTRODUCTION: Evidence on the association between diabetes and risk of bladder cancer has been controversial. In addition, findings on the associations between duration of diabetes, diabetes treatment, and risk of bladder cancer have been inconsistent. METHODS: A total of 148,208 participants in Women's Health Initiative study were included. Information on diabetes status, diabetes duration, and treatment was collected both at baseline and during follow-up. Information on potential confounders including age, race/ethnicity, education, occupation, family history of cancer, smoking status, alcohol consumption, total physical activity, body mass index, and daily dietary intake were collected at baseline. Bladder cancer cases were collected and confirmed by a centralized review of pathology reports. Cox proportional hazard models with time-varying covariates were used to examine associations of diabetes status, duration of diabetes, and diabetes treatment with bladder cancer risk. RESULTS: During a median follow-up of 18.5 years, 865 bladder cancer cases were identified. There were no significant associations of diabetes, duration of diabetes, or diabetes treatment with risk of bladder cancer. Participants with prevalent diabetes did not have significantly higher risk of bladder cancer compared with those without diabetes. CONCLUSION: Diabetes was not significantly associated with risk of bladder cancer among postmenopausal women.

Magnesium intake is inversely associated with risk of obesity in a 30-year prospective follow-up study among American young adults.

PURPOSE: Although laboratory studies suggest a potential role of magnesium (Mg) in weight regulation, human studies relating Mg intake to body weight are limited. This study sought to prospectively examine the association between Mg intake and incidence of obesity and related anthropometric and biochemical indicators. METHODS: The Coronary Artery Risk Development in Young Adults (CARDIA) study recruited 5115 American young adults, aged 18-30 years, at baseline in 1985-6, and re-examined them in eight follow-ups. Incident obesity was defined as body mass index (BMI) ≥ 30 kg/m2. Dietary Mg intake was collected using the CARDIA Diet History at baseline and exam years 7 and 20. RESULTS: During the 30-year follow-up, 1675 incident cases of obesity were identified. After adjustment for potential confounders, Mg intake was inversely associated with incidence of obesity. The multivariable-adjusted hazard ratios (95% confidence interval) from quintile 1 (Q1) (lowest intake group) to quintile 5 (Q5) (highest intake group) were 1 (referent), 0.86 (0.74, 1.00), 0.83 (0.71, 0.97), 0.55 (0.46, 0.66), and 0.49 (0.40, 0.60); P for trend < 0.01. Consistently, Mg intake was inversely associated with the levels of BMI, triceps skinfold, suprailiac skinfold, subscapular skinfold, fasting insulin, and C-reactive protein. The observed associations were not materially modified by age, sex, race, or BMI at baseline. In addition, the intakes of foods rich in Mg, including whole grains, nuts and seeds, legumes, and dark-green vegetables, were associated with lower incidence of obesity. CONCLUSIONS: This longitudinal study suggests that Mg intake is inversely associated with incidence of obesity.

Intakes of long-chain omega-3 polyunsaturated fatty acids and non-fried fish in relation to incidence of chronic kidney disease in young adults: a 25-year follow-up.

PURPOSE: The prevalence of chronic kidney disease (CKD) is increasing rapidly in many countries and has become a major public health concern. Although intakes of long-chain omega-3 polyunsaturated fatty acids (LCω3PUFA) and its food source-fish-may have renal protective effects, little is known about the longitudinal association between these dietary factors and CKD incidence. METHODS: A total of 4133 healthy individuals of black and white race aged 18-30 at baseline (1985-1986) from the Coronary Artery Risk Development in Young Adults study were enrolled and followed up over 25 years. LCω3PUFA and fish intake were assessed by an interview-based dietary history questionnaire at baseline, year 7 (1992-1993) and 20 (2005-2006). RESULTS: Four hundred and eighty-nine incident cases of CKD were identified. After adjustment for potential confounders, LCω3PUFA intake was inversely associated with CKD incidence [HR = 0.73 (95% CI 0.60-0.89), P = 0.002, with one standard division (0.19 g/day) increment in LCω3PUFA]. This inverse association was persisted among females [0.64 (95% CI 0.48, 0.84; P = 0.002], but not males (Pinteraction = 0.070). A marginal significant inverse association was also found between non-fried fish consumption and CKD incidence (HR = 0.86, 95% CI 0.73, 1.01; P = 0.073). CONCLUSIONS: Dietary LCω3PUFA intake was inversely associated with incidence of CKD among American young adults over 25 years of follow-up. The suggestive evidence of the inverse association between non-fried fish consumption with CKD incidence needs further confirmation.

Impact of Postnatal Antibiotics and Parenteral Nutrition on the Gut Microbiota in Preterm Infants During Early Life.

BACKGROUND: The early-life gut microbiota, which is critically important for the long-term health of infants, is normally sensitive to perturbations, especially in preterm infants. However, how the gut microbiota develops and what key factors affect the preterm gut microbiota remain largely unknown. We hypothesized that preterm microbial dysbiosis exists from the beginning after birth, and microbial alteration is associated with parenteral nutrition and antibiotic therapy interventions. METHODS: Fecal samples were collected from fifty-one preterm and fifty full-term vaginally delivered (FTVD) infants at 7 time points for 90 days after birth. The microbial profiles of 558 fecal DNA samples were analyzed by sequencing their 16S ribosomal RNA amplicons. A random-effects generalized least square regression was used to identify factors that influence the bacterial composition over time. RESULTS: The altered gut microbiota in preterm infants existed from the meconium, having significantly lower levels of Escherichia-Shigella than those in FTVD infants. The developmental trajectories of 7 predominant bacterial groups successfully fitted with exponential/linear function curves (R2 , 0.921-0.993) in both groups. By day 90, depleted levels of Bacteroides and Parabacteroides and an overabundance of Peptoclostridium were characteristic of the preterm group. The prolonged use of antibiotics and parenteral nutrition had significant adverse effects on the Lactobacillus and Bifidobacterium levels in preterm infants. Moreover, gestational age, sex, and birth weight were factors impacting specific genera in preterm infants. CONCLUSION: The early-life microbial composition and functions were markedly different in preterm infants, being associated with the prolonged use of postnatal antibiotics and parenteral nutrition.

The association between parental weight status and risk of hypertension in children aged 6 to 12 years.

BACKGROUND AND OBJECTIVES: Parents may play important roles in the regulation of children's weight status and consequently the development of childhood hypertension. Thus, this study aimed to examine parental weight status, as a marker of parents' diet and lifestyle, in relation to risk of hypertension in their children. METHODS AND STUDY DESIGN: A total of 1,949 children aged 6 to 12 years (1,012 girls, 52%) and their parents were included. Information on demographics, anthropometrics, lifestyle, diet, and medical history were obtained from the participants and their parents through self-administered questionnaires. Childhood hypertension and elevated blood pressure were defined as SBP and/or DBP ≥95th and ≥90th age- and gender-specific percentile, respectively. Parental overweight was defined as BMI ≥24.0 kg/m2. RESULTS: The prevalence of childhood hypertension was 8.4%, with no significant gender difference (p=0.36). Parents' weight status, especially maternal, was associated with childhood hypertension. After adjustment for potential confounders, children with two parents being overweight were two times more likely to have hypertension as compared with children who had both parents being of normal weight [multivariable-adjusted odds ratio=2.09; 95% confidence interval: (1.26, 3.46)]. After further adjustment for children's body mass index, the observed association was substantially attenuated and became statistically non-significant. CONCLUSIONS: Findings from this study suggest that parental weight status is associated with the prevalence of hypertension in children presumably through influencing children's weight. Further studies are needed to establish causal inference. This study highlights the importance of parental lifestyle in children's health.

Calcium Intake and Serum Calcium Level in Relation to the Risk of Ischemic Stroke: Findings from the REGARDS Study.

BACKGROUND AND PURPOSE: Data on the association between calcium (Ca) and ischemic stroke are sparse and inconsistent. This study aimed to examine Ca intake and serum Ca levels in relation to risk of ischemic stroke. METHODS: The primary analysis included 19,553 participants from the Reasons for Geographic And Racial Differences in Stroke (REGARDS) study. A subcohort was randomly selected to create a case-cohort study (n=3,016), in which serum Ca levels were measured. Ischemic stroke cases were centrally adjudicated by physicians based on medical records. Cox proportional hazards regression for the cohort and weighted Cox proportional hazard regression with robust sandwich estimation method for the case-cohort analysis with adjustment for potential confounders were performed. RESULTS: During a mean 8.3-year follow-up, 808 incident cases of ischemic stroke were documented. Comparing the highest quintile to the lowest, a statistically significant inverse association was observed between total Ca intake and risk of ischemic stroke (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.55 to 0.95; Plinear-trend=0.183); a restricted cubic spline analysis indicated a threshold effect like non-linear association of total Ca intake with ischemic stroke (Pnon-linear=0.006). In the case-cohort, serum Ca was inversely associated with the risk of ischemic stroke. Compared to the lowest, the highest quintile of serum Ca had a 27% lower risk of ischemic stroke (HR, 0.73; 95% CI, 0.53 to 0.99; Plinear-trend=0.013). Observed associations were mainly mediated by type 2 diabetes, hypertension, and cholesterol. CONCLUSION: s These findings suggest that serum Ca has inverse and Ca intake has threshold effect like association with risk of ischemic stroke.

Intake of Vegetables and Fruits Through Young Adulthood Is Associated with Better Cognitive Function in Midlife in the US General Population.

BACKGROUND: Vegetables and fruits (VF) may differentially affect cognitive functions, presumably due to their various nutrient contents, but evidence from epidemiologic studies is limited. OBJECTIVES: The aim of this study was to examine the long-term association between VF intakes, including VF subgroups, in young adulthood and cognitive function in midlife. METHODS: A biracial cohort of 3231 men and women aged 18-30 y at baseline in 1985-1986 were followed up for 25 y in the Coronary Artery Risk Development in Young Adults Study. Diet was measured at baseline, and in examination years 7 and 20. Cognitive function was assessed at examination year 25 through the use of 3 tests: the Rey Auditory Verbal Learning Test (RAVLT), the Digit Symbol Substitution Test (DSST), and the Stroop test. The mean differences (MDs) with 95% CIs in cognitive scores across intake categories were estimated through the use of the multivariable-adjusted general linear regression model. RESULTS: Excluding potatoes, intake of whole vegetables was significantly associated with a better cognitive performance after adjustment for potential confounders in all 3 cognitive tests (quintile 5 compared with quintile 1-RAVLT, MD: 0.33; 95% CI: 0.01, 0.64; P-trend = 0.08; DSST, MD: 2.84; 95% CI: 0.93, 4.75; P-trend < 0.01; Stroop test, MD: -2.87; 95% CI: -4.24, -1.50; P-trend < 0.01]. Similarly, intake of fruits, except fruit juices, was significantly related to a better cognitive performance (quintile 5 compared with quintile 1-DSST, MD: 2.41; 95% CI: 0.70, 4.12; P-trend = 0.03). CONCLUSIONS: This study supports the long-term benefits of VF consumption on cognitive performance, except those VF with relatively low fiber content such as potatoes and fruit juices, among the middle-aged US general population.

Smoking Cessation and the Risk of Bladder Cancer among Postmenopausal Women.

Smoking is the strongest established risk factor for bladder cancer. Former smokers have a lower risk of bladder cancer compared with current smokers, but findings on the dose-response relationship between years after quitting and the risk of bladder cancer are inconsistent. A total of 143,279 postmenopausal women from the Women's Health Initiative Study were included. Cox proportional hazards regression models were applied for estimating age- and multivariable-adjusted HRs and their 95% confidence intervals (CI). There were 870 bladder cancer cases identified over an average of 14.8 years of follow-up. After adjusting for pack-years of smoking, bladder cancer risk among former smokers declined by 25% within the first 10 years of cessation and continued to decrease as cessation time increased but remained higher than never smokers after 30 years of quitting (HR, 1.92; 95% CI, 1.43-2.58). Smokers who quit smoking had a lower risk of bladder cancer compared with current smokers (HR, 0.61; 95% CI, 0.40-0.94). We conclude that among postmenopausal women, there is a significant reduction in the risk of bladder cancer after quitting smoking. In addition to primary prevention, smoking cessation is critical to prevent the incidence of bladder cancer in older women.