Faculty Bibliography

It has been suggested that neurological problems more frequent in those born preterm are expressed prior to birth, but owing to technical limitations, this has been difficult to test in humans. We applied novel fetal resting-state functional MRI to measure brain function in 32 human fetuses in utero and found that systems-level neural functional connectivity was diminished in fetuses that would subsequently be born preterm. Neural connectivity was reduced in a left-hemisphere pre-language region, and the degree to which connectivity of this left language region extended to right-hemisphere homologs was positively associated with the time elapsed between fMRI assessment and delivery. These results provide the first evidence that altered functional connectivity in the preterm brain is identifiable before birth. They suggest that neurodevelopmental disorders associated with preterm birth may result from neurological insults that begin in utero.

BACKGROUND AND OBJECTIVES:Serum β-trace protein (BTP) and β-2 microglobulin (B2M) are associated with risk of ESRD and death in the general population and in populations at high risk for these outcomes (GP/HR) and those with CKD, but results differ among studies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:) for ESRD (2075 events) and death (7275 events). RESULTS:provided the most consistent improvement in associations and prediction across both outcomes and populations. Assessment of heterogeneity did not yield clinically relevant differences. For ESRD, addition of albuminuria substantially attenuated the improvement in risk prediction and risk classification with novel filtration markers. For mortality, addition of albuminuria did not affect the improvement in risk prediction with the use of novel markers, but lessened improvement in risk classification, especially for the CKD cohort. CONCLUSIONS:is not accurate or albuminuria is not available. Educational efforts to increase measurement of albuminuria in clinical practice may be more cost-effective than measurement of BTP and B2M for improving prognostic information.

BACKGROUND AND OBJECTIVES:Diet soda consumption is common in the United States and is associated with impaired glucose metabolism, diabetes, and metabolic syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:We prospectively analyzed diet soda consumption, assessed by food frequency questionnaire at baseline (1987-1989) and a follow-up examination (1993-1995), and incident ESRD through December 31, 2012 in the Atherosclerosis Risk in Communities study (n=15,368). RESULTS:Baseline mean age of participants was 54 years, 55% were female, and 27% were black. The majority of participants (43.5%) consumed <1 glass/wk of diet soda; 17.8% consumed 1-4 glasses/wk; 25.3% consumed 5-7 glasses/wk; and 13.5% consumed >7 glasses/wk. Over a median follow-up of 23 years, 357 incident ESRD cases were observed. Relative to <1 glass/wk of diet soda, consuming 1-4 glasses/wk, 5-7 glasses/wk, and >7 glasses/wk, respectively, was associated with 1.08-times (95% confidence interval [95% CI], 0.75 to 1.55), 1.33-times (95% CI, 1.01 to 1.75), and 1.83-times (95% CI, 1.01 to 2.52) higher risk of ESRD after adjusting for age, sex, race-center, education level, smoking status, physical activity, total caloric intake, eGFR, body mass index category, diabetes, systolic BP, and serum uric acid (P value for trend <0.001). Results were similar after additional adjustment for dietary acid load, diet quality, dietary sodium, dietary fructose, sugar-sweetened beverages, and dietary phosphorus. Risk estimates were similar by body mass index category (P value for interaction = 0.82), but the association between diet soda and ESRD was only significant for those who were overweight or obese at baseline. Sugar-sweetened beverage consumption was not significantly associated with ESRD in the fully adjusted model. CONCLUSIONS:Diet soda consumption was associated with higher ESRD risk in this general population sample. Further research is necessary to validate these findings in other study populations and to examine potential mechanisms through which diet soda could impact kidney disease.

Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBPMS/GTF2E2) associated with mean corpuscular hemoglobin and mean corpuscular volume. Statistical fine-mapping at this locus pointed to RBPMS at this locus and excluded nearby GTF2E2. Using zebrafish morpholino to evaluate loss of function, we observed a strong in vivo erythropoietic effect for RBPMS but not for GTF2E2, supporting the statistical fine-mapping at this locus and demonstrating that RBPMS is a regulator of erythropoiesis. Our findings show the utility of trans-ethnic GWASs for discovery and characterization of genetic loci influencing hematologic traits.

Importance: The increasing use of cesarean delivery is an emerging global health issue. Prior estimates of China's cesarean rate have been based on surveys with limited geographic coverage. Objective: To provide updated information about cesarean rates and geographic variation in cesarean use in China. Design, Setting, and Data Sources: Descriptive study, covering every county (n = 2865) in mainland China's 31 provinces, using county-level aggregated information on the number of live births, cesarean deliveries, maternal deaths, and perinatal deaths, collected by the Office for National Maternal & Child Health Statistics of China, from 2008 through 2014. Exposures: Live births. Main Outcomes and Measures: Annual rate of cesarean deliveries. Results: Over the study period, there were 100873051 live births, of which 32947229 (32.7%) were by cesarean delivery. In 2008, there were 13160634 live births, of which 3788029 (28.8%) were by cesarean delivery and in 2014 there were 15123276 live births, of which 5280124 (34.9%) were by cesarean delivery. Rates varied markedly by province, from 4.0% to 62.5% in 2014. Despite the overall increase, by 2014 rates of cesarean delieries in 14 of the nation's 17 "super cities" had declined by 4.1 to 17.5 percentage points from their earlier peak values (median, 11.4; interquartile range, 6.3-15.4). In 4 super cities with the largest decreases, there was no increase in maternal or perinatal mortality. Conclusions and Relevance: Between 2008 and 2014, the overall annual rate of cesarean deliveries increased in China, reaching 34.9%. There was major geographic variation in rates and trends over time, with rates declining in some of the largest urban areas.

BACKGROUND: Ecstasy (MDMA) use has regained popularity in the United States, particularly in the form of "Molly," which is often marketed as pure MDMA. Surveys have generally not included "Molly" in the definition of ecstasy, so rates of use may be underestimated. As popularity of ecstasy increases, research is needed to examine use among those at highest risk for use-nightlife attendees. METHODS: We surveyed 679 young adults (age 18-25) entering nightclubs and festivals holding electronic dance music (EDM) parties in New York City in 2015. A variation of time-space sampling was utilized. We examined prevalence and correlates of self-reported lifetime ecstasy use. RESULTS: Self-reported lifetime ecstasy use was common (42.8%, 95% CI: 32.8, 52.7). Use was most common among older participants, frequent party attendees, and those reporting higher levels of exposure to users. Those surveyed outside of festivals were less likely to report use compared to those surveyed outside of nightclubs (AOR = 0.37, p = .015). Over a third of ecstasy users (36.8%)reported use in pill, powder, and crystal form. Ecstasy users were also more likely to report use of other drugs, including novel psychoactive substances (e.g., 2C series drugs, synthetic cathinones ["bath salts"]). Half (50.4%) reported suspecting (21.9%) or finding out (28.5%) that their ecstasy had ever contained a drug other than MDMA. CONCLUSION: A large percentage of nightlife attendees in NYC report lifetime ecstasy use. Findings should inform prevention and harm reduction programming. Further research is needed as ecstasy continues to change (e.g., in form, purity, and name).

Study Objectives:Mounting evidence implicates disturbed sleep or lack of sleep as one of the risk factors for Alzheimer's disease (AD), but the extent of the risk is uncertain. We conducted a broad systematic review and meta-analysis to quantify the effect of sleep problems/disorders on cognitive impairment and AD. Methods:Original published literature assessing any association of sleep problems or disorders with cognitive impairment or AD was identified by searching PubMed, Embase, Web of Science, and the Cochrane library. Effect estimates of individual studies were pooled and relative risks (RR) and 95% confidence intervals (CI) were calculated using random effects models. We also estimated the population attributable risk. Results:Twenty-seven observational studies (n = 69216 participants) that provided 52 RR estimates were included in the meta-analysis. Individuals with sleep problems had a 1.55 (95% CI: 1.25-1.93), 1.65 (95% CI: 1.45-1.86), and 3.78 (95% CI: 2.27-6.30) times higher risk of AD, cognitive impairment, and preclinical AD than individuals without sleep problems, respectively. The overall meta-analysis revealed that individuals with sleep problems had a 1.68 (95% CI: 1.51-1.87) times higher risk for the combined outcome of cognitive impairment and/or AD. Approximately 15% of AD in the population may be attributed to sleep problems. Conclusion:This meta-analysis confirmed the association between sleep and cognitive impairment or AD and, for the first time, consolidated the evidence to provide an "average" magnitude of effect. As sleep problems are of a growing concern in the population, these findings are of interest for potential prevention of AD.

OBJECTIVE:This study compared trends in racial-ethnic disparities in mental health care access among whites, blacks, Hispanics, and Asians by using the Institute of Medicine definition of disparities as all differences except those due to clinical appropriateness, clinical need, and patient preferences. METHODS:Racial-ethnic disparities in mental health care access were examined by using data from a nationally representative sample of 214,597 adults from the 2004-2012 Medical Expenditure Panel Surveys. The main outcome measures included three mental health care access measures (use of any mental health care, any outpatient care, and any psychotropic medication in the past year). RESULTS:Significant disparities were found in 2004-2005 and in 2011-2012 for all three racial-ethnic minority groups compared with whites in all three measures of access. Between 2004 and 2012, black-white disparities in any mental health care and any psychotropic medication use increased, respectively, from 8.2% to 10.8% and from 7.6% to 10.0%. Similarly, Hispanic-white disparities in any mental health care and any psychotropic medication use increased, respectively, from 8.4% to 10.9% and 7.3% to 10.3%. CONCLUSIONS:No reductions in racial-ethnic disparities in access to mental health care were identified between 2004 and 2012. For blacks and Hispanics, disparities were exacerbated over this period. Clinical interventions that improve identification of symptoms of mental illness, expansion of health insurance, and other policy interventions that remove financial barriers to access may help to reduce these disparities.

SETTING:Four regions in Kazakhstan where participants were recruited from June 2012 to May 2014. OBJECTIVE:To examine associations between incarceration history and tobacco, alcohol, and drug consumption, and human immunodeficiency virus (HIV) infection and diabetes mellitus (DM) with TB. DESIGN:This matched case-control study included 1600 participants who completed a survey on sociodemographics, history of incarceration, tobacco, alcohol and drug use, and HIV and DM diagnosis. Conditional logistic regression analysis was used to examine associations between a TB diagnosis and risk factors. RESULTS:Participants who had ever smoked tobacco (aOR 1.73, 95%CI 1.23-2.43, P  0.01), ever drank alcohol (aOR 1.41, 95%CI 1.03-1.93, P  0.05), were HIV-positive (aOR 36.37, 95%CI 2.05-646.13, P  0.05) or had DM (aOR 13.96, 95%CI 6.37-30.56, P  0.01) were more likely to have TB. CONCLUSIONS:The association between TB and tobacco use, alcohol use, HIV and DM in Kazakhstan suggests a need for comprehensive intervention and prevention approaches that also address tobacco and alcohol use, DM and HIV.