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OBJECTIVES - To investigate the association between green tea intake and incident stones in two large prospective cohorts.
METHODS - We examined self-reported incident kidney stone risk in the Shanghai Men's Health Study (n = 58 054; baseline age 40-74 years) and the Shanghai Women's Health Study (n = 69 166; baseline age 40-70 years). Information on the stone history and tea intake was collected by in-person surveys. Multivariable Cox proportional hazards models were adjusted for baseline demographic variables, medical history and dietary intakes including non-tea oxalate from a validated food frequency questionnaire.
RESULTS - During 319 211 and 696 950 person-years of follow up, respectively, 1202 men and 1451 women reported incident stones. Approximately two-thirds of men and one-quarter of women were tea drinkers at baseline, of whom green tea was the primary type consumed (95% in men, 88% in women). Tea drinkers (men: hazard ratio 0.78, 95% confidence interval 0.69-0.88; women: hazard ratio 0.8, 95% confidence interval 0.77-0.98) and specifically green tea drinkers (men: hazard ratio 0.78, 95% confidence interval 0.69-0.88; women: hazard ratio 0.84, 95% confidence interval 0.74-0.95) had lower incident risk than never/former drinkers. Compared with never/former drinkers, a stronger dose-response trend was observed for the amount of dried tea leaf consumed/month by men (hazard ratio 0.67, 95% confidence interval 0.56-0.80, P  < 0.001) than by women (hazard ratio 0.87, 95% confidence interval 0.70-1.08, P  = 0.041).
CONCLUSIONS - Green tea intake is associated with a lower risk of incident kidney stones, and the benefit is observed more strongly among men.
© 2018 The Japanese Urological Association.

RATIONALE - Sex differences in the dopaminergic response to psychostimulants could have implications for drug abuse risk and other psychopathology involving the dopamine system, but human data are limited and mixed.
OBJECTIVES - Here, we sought to investigate sex differences in dopamine release after oral D-amphetamine administration.
METHODS - We used [F]fallypride positron emission tomography (PET) to measure the change in dopamine D2/3 receptor availability (%ΔBP, an index of dopamine release) between placebo and D-amphetamine sessions in two independent datasets containing a total of 39 females (on either hormonal birth control n = 18, postmenopausal n = 10, or studied in the first 10 days of their menstrual cycle n = 11) and 37 males.
RESULTS - Using both a priori anatomical regions of interest based on previous findings and voxelwise analyses, we failed to consistently detect broad sex differences in D-amphetamine-induced dopamine release. Nevertheless, there was limited evidence for greater right ventral striatal dopamine release in young adult males relative to similarly aged females, but this was not consistently observed across samples. Plasma estradiol did not correlate with dopamine release and this measure did not differ in females on and off hormonal birth control.
CONCLUSIONS - While our finding in young adults from one dataset of greater %ΔBP in males is partially consistent with a previously published study on sex differences in D-amphetamine-induced dopamine release, our data do not support the presence of consistent widespread sex differences in this measure of dopamine release.

RATIONALE & OBJECTIVE - Inflammation, cardiac remodeling, and fibrosis may explain in part the excess risk for cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Growth differentiation factor 15 (GDF-15), galectin 3 (Gal-3), and soluble ST2 (sST2) are possible biomarkers of these pathways in patients with CKD.
STUDY DESIGN - Observational cohort study.
SETTING & PARTICIPANTS - Individuals with CKD enrolled in either of 2 multicenter CKD cohort studies: the Seattle Kidney Study or C-PROBE (Clinical Phenotyping and Resource Biobank Study).
EXPOSURES - Circulating GDF-15, Gal-3, and sST2 measured at baseline.
OUTCOMES - Primary outcome was all-cause mortality. Secondary outcomes included hospitalization for physician-adjudicated heart failure and the atherosclerotic CVD events of myocardial infarction and cerebrovascular accident.
ANALYTIC APPROACH - Cox proportional hazards models used to test the association of each biomarker with each outcome, adjusting for demographics, CVD risk factors, and kidney function.
RESULTS - Among 883 participants, mean estimated glomerular filtration rate was 49±19mL/min/1.73m. Higher GDF-15 (adjusted HR [aHR] per 1-SD higher, 1.87; 95% CI, 1.53-2.29), Gal-3 (aHR per 1-SD higher, 1.51; 95% CI, 1.36-1.78), and sST2 (aHR per 1-SD higher, 1.36; 95% CI, 1.17-1.58) concentrations were significantly associated with mortality. Only GDF-15 level was also associated with heart failure events (HR per 1-SD higher, 1.56; 95% CI, 1.12-2.16). There were no detectable associations between GDF-15, Gal-3, or sST2 concentrations and atherosclerotic CVD events.
LIMITATIONS - Event rates for heart failure and atherosclerotic CVD were low.
CONCLUSIONS - Adults with CKD and higher circulating GDF-15, Gal-3, and sST2 concentrations experienced greater mortality. Elevated GDF-15 concentration was also associated with an increased rate of heart failure. Further work is needed to elucidate the mechanisms linking these circulating biomarkers with CVD in patients with CKD.
Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

OBJECTIVE - To investigate race-sex associations with risk among whites and blacks in the southeastern United States. The relationship between race, sex, and kidney stone risk is poorly understood.
METHODS - Participants were 42,136 black and white adults enrolled in the Southern Community Cohort Study between 2002 and 2009, with no history of kidney stones and receiving Medicare or Medicaid services. Incident kidney stone diagnoses through December 2014 were determined via linkage with Centers for Medicare and Medicaid Services research files. Hazard ratios (HRs) for associations with race and sex were computed from multivariable Cox proportional hazards models adjusting for baseline characteristics, comorbid diseases, and dietary intakes.
RESULTS - During 116,931 and 270,917 person-years of follow-up for whites and blacks, respectively, age-adjusted incidence rates (95% confidence interval [CI]) were 5.98 (4.73-7.23) and 4.50 (3.86-5.14) per 1000 person-years for white men and women, respectively, while corresponding rates among blacks were 2.19 (1.71-2.67) and 2.47 (2.19-2.75) per 1000 person-years. Risk was higher among whites compared to blacks (HR = 2.23, 95% CI 1.97-2.53). Male sex was significantly associated with risk among whites (HR = 1.45, 95% CI 1.20-1.75), but not among blacks (HR = 0.90, 95% CI 0.75-1.07). Formal tests of interaction by race and sex were statistically significant for all models (P = .01 for fully adjusted model).
CONCLUSION - The association of incident kidney stones with sex differs between whites and blacks. White men have the highest risk, while no difference in risk is observed between black men and women.
Copyright © 2018 Elsevier Inc. All rights reserved.

BACKGROUND - Late-life depression (LLD) is associated with a fragile antidepressant response and high recurrence risk. This study examined what measures predict recurrence in remitted LLD.
METHODS - Individuals of age 60 years or older with a Diagnostic and Statistical Manual - IV (DSM-IV) diagnosis of major depressive disorder were enrolled in the neurocognitive outcomes of depression in the elderly study. Participants received manualized antidepressant treatment and were followed longitudinally for an average of 5 years. Study analyses included participants who remitted. Measures included demographic and clinical measures, medical comorbidity, disability, life stress, social support, and neuropsychological testing. A subset underwent structural magnetic resonance imaging (MRI).
RESULTS - Of 241 remitted elders, approximately over 4 years, 137 (56.8%) experienced recurrence and 104 (43.2%) maintained remission. In the final model, greater recurrence risk was associated with female sex (hazard ratio [HR] = 1.536; confidence interval [CI] = 1.027-2.297), younger age of onset (HR = 0.990; CI = 0.981-0.999), higher perceived stress (HR = 1.121; CI = 1.022-1.229), disability (HR = 1.060; CI = 1.005-1.119), and less support with activities (HR = 0.885; CI = 0.812-0.963). Recurrence risk was also associated with higher Montgomery-Asberg Depression Rating Scale (MADRS) scores prior to censoring (HR = 1.081; CI = 1.033-1.131) and baseline symptoms of suicidal thoughts by MADRS (HR = 1.175; CI = 1.002-1.377) and sadness by Center for Epidemiologic Studies-Depression (HR = 1.302; CI, 1.080-1.569). Sex, age of onset, and suicidal thoughts were no longer associated with recurrence in a model incorporating report of multiple prior episodes (HR = 2.107; CI = 1.252-3.548). Neither neuropsychological test performance nor MRI measures of aging pathology were associated with recurrence.
CONCLUSIONS - Over half of the depressed elders who remitted experienced recurrence, mostly within 2 years. Multiple clinical and environmental measures predict recurrence risk. Work is needed to develop instruments that stratify risk.
© 2018 Wiley Periodicals, Inc.

OBJECTIVE - Hepatocyte deletion of estrogen receptor alpha (LKO-ERα) worsens fatty liver, dyslipidemia, and insulin resistance in high-fat diet fed female mice. However, whether or not hepatocyte ERα regulates reverse cholesterol transport (RCT) in mice has not yet been reported.
METHODS AND RESULTS - Using LKO-ERα mice and wild-type (WT) littermates fed a Western-type diet, we found that deletion of hepatocyte ERα impaired in vivo RCT measured by the removal of H-cholesterol from macrophages to the liver, and subsequently to feces, in female mice but not in male mice. Deletion of hepatocyte ERα decreased the capacity of isolated HDL to efflux cholesterol from macrophages and reduced the ability of isolated hepatocytes to accept cholesterol from HDL ex vivo in both sexes. However, only in female mice, LKO-ERα increased serum cholesterol levels and increased HDL particle sizes. Deletion of hepatocyte ERα increased adiposity and worsened insulin resistance to a greater degree in female than male mice. All of the changes lead to a 5.6-fold increase in the size of early atherosclerotic lesions in female LKO-ERα mice compared to WT controls.
CONCLUSIONS - Estrogen signaling through hepatocyte ERα plays an important role in RCT and is protective against lipid retention in the artery wall during early stages of atherosclerosis in female mice fed a Western-type diet.
Published by Elsevier GmbH.

BACKGROUND AND AIMS - Most familial hypercholesterolemia (FH) patients remain undertreated, and it is unclear what role health disparities may play for FH patients in the US. We sought to describe sex and racial/ethnic disparities in a national registry of US FH patients.
METHODS - We analyzed data from 3167 adults enrolled in the CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia (CASCADE-FH) registry. Logistic regression was used to evaluate for disparities in LDL-C goals and statin use, with adjustments for covariates including age, cardiovascular risk factors, and statin intolerance.
RESULTS - In adjusted analyses, women were less likely than men to achieve treated LDL-C of <100 mg/dL (OR 0.68, 95% CI, 0.57-0.82) or ≥50% reduction from pretreatment LDL-C (OR 0.79, 95% CI, 0.65-0.96). Women were less likely than men to receive statin therapy (OR, 0.60, 95% CI, 0.50-0.73) and less likely to receive a high-intensity statin (OR, 0.60, 95% CI, 0.49-0.72). LDL-C goal achievement also varied by race/ethnicity: compared with whites, Asians and blacks were less likely to achieve LDL-C levels <100 mg/dL (Asians, OR, 0.47, 95% CI, 0.24-0.94; blacks, OR, 0.49, 95% CI, 0.32-0.74) or ≥50% reduction from pretreatment LDL-C (Asians, OR 0.56, 95% CI, 0.32-0.98; blacks, OR 0.62, 95% CI, 0.43-0.90).
CONCLUSIONS - In a contemporary US population of FH patients, we identified differences in LDL-C goal attainment and statin usage after stratifying the population by either sex or race/ethnicity. Our findings suggest that health disparities contribute to the undertreatment of US FH patients. Increased efforts are warranted to raise awareness of these disparities.
Copyright © 2017 Elsevier B.V. All rights reserved.

INTRODUCTION - Kidney stone risk factors are understudied among Asians. Our study objective was to investigate associations of obesity and other chronic diseases with incident kidney stones among the urban Chinese.
PATIENTS AND METHODS - Included in this study are two prospective cohorts: the Shanghai Women's Health Study (N = 69,166) and Shanghai Men's Health Study (N = 58,054). Incident kidney stones were determined by self-report in 2004 and 2008. Cox regression models were used to evaluate the associations of study variables with stone risk with adjustment of demographics, medical history, and dietary intakes.
RESULTS - There were 2653 incident stones over 1,007,958 person-years of follow-up. Overall incidence rates (per 1000 person-years, 95% confidence interval [CI]) were 2.10 (1.99, 2.21) among women and 3.80 (3.59, 4.02) among men. Higher body mass index (BMI) was associated with risk (BMI ≥25 vs 18.5-24.9 kg/m, women: hazard ratio [HR] = 1.14 [95% CI 1.01, 1.28]; men: HR = 1.17 [1.03, 1.32]). High waist-hip ratio (≥0.80 and ≥0.90 for women and men, respectively) was associated with risk (HR 1.13, 95% CI 1.01, 1.27 for women; HR 1.19, 95% CI 1.05, 1.35 for men). Coronary heart disease or stroke history was associated with risk in women only (HR 1.31, 95% CI 1.10, 1.56). Hypertension history was associated with risk in men only (HR 1.27, 95% CI 1.11, 1.45). No significant association with diabetes mellitus was observed.
CONCLUSIONS - Among the Chinese, kidney stone incidence in men is almost twice that of women. Obesity is a shared risk factor. Hypertension history is associated with risk in men, whereas history of coronary heart disease or stroke is associated with risk in women.

Background - Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The extent to which these associations are present in other study populations is unknown.
Methods - Within 20 prospective cohorts from the National Cancer Institute Cohort Consortium, a nested case-control study was designed including 5364 incident lung cancer case patients and 5364 control subjects who were individually matched to case patients by age, sex, cohort, and smoking status. Centralized biochemical analyses were performed to measure circulating concentrations of vitamin B6, folate, and methionine, as well as cotinine as an indicator of recent tobacco exposure. The association between these biomarkers and lung cancer risk was evaluated using conditional logistic regression models.
Results - Participants with higher circulating concentrations of vitamin B6 and folate had a modestly decreased risk of lung cancer risk overall, the odds ratios when comparing the top and bottom fourths (OR 4vs1 ) being 0.88 (95% confidence interval [CI] = 0.78 to 1.00) and 0.86 (95% CI = 0.74 to 0.99), respectively. We found stronger associations among men (vitamin B6: OR 4vs1 = 0.74, 95% CI = 0.62 to 0.89; folate: OR 4vs1 = 0.75, 95% CI = 0.61 to 0.93) and ever smokers (vitamin B6: OR 4vs1 = 0.78, 95% CI = 0.67 to 0.91; folate: OR 4vs1 = 0.87, 95% CI = 0.73 to 1.03). We further noted that the association of folate was restricted to Europe/Australia and Asia, whereas no clear association was observed for the United States. Circulating concentrations of methionine were not associated with lung cancer risk overall or in important subgroups.
Conclusions - Although confounding by tobacco exposure or reverse causation cannot be ruled out, these study results are compatible with a small decrease in lung cancer risk in ever smokers who avoid low concentrations of circulating folate and vitamin B6.
© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

AIMS - To investigate the association between health literacy and cognition and nursing and patient-reported incontinence in a geriatric inpatient population transitioning to skilled nursing facilities (SNF).
METHODS - Health literacy, depression, and cognition were assessed via the Brief Health Literacy Screen (BHLS), Geriatric Depression Scale 5-item (GDS) and Brief Interview for Mental Status (BIMS), respectively. Multivariable logistic regression assessed the association between BHLS score and incontinence by: (1) nursing-reported urinary incontinence during hospitalization; and (2) patient self-reported "bladder accidents" in the post-enrollment study interview.
RESULTS - A total of 1556 hospitalized patients aged 65 and older met inclusion criteria, of whom 922 (59.3%) were women and 1480 had available BHLS scores. A total of 464 (29.8%) and 515 (33.1%) patients had nursing-reported and self-reported urinary incontinence, respectively. Nursing-reported incontinence was significantly associated with lower BHLS (ie, poorer health literacy) (aOR 0.93, 95%CI 0.89-0.99) and BIMS (ie, poorer cognition) (aOR 0.90, 95%CI 0.83-0.97) scores and need for assistance with toileting (aOR 7.08, 95%CI 2.16-23.21). Patient-reported incontinence was significantly associated with female sex (aOR 1.62, 95%CI 1.19-2.21), increased GDS score (ie, greater likelihood of depression) (aOR 1.22, 95%CI 1.10-1.36) and need for assistance with toileting (aOR 2.46, 95%CI 1.26-4.79).
CONCLUSIONS - Poorer health literacy and cognition are independently associated with an increased likelihood of nursing-reported urinary incontinence among geriatric inpatients transitioning to SNF. Practitioners should consider assessment of health literacy and cognition in frail patients at risk for urinary incontinence and that patient and nursing assessment may be required to capture the diagnosis.
© 2017 Wiley Periodicals, Inc.