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Wang, Molin

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Molin

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Wang, Molin

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    Optimal dietary patterns for prevention of chronic disease
    (Springer Science and Business Media LLC, 2023-03) Giovannucci, Edward L; Wang, Peilu; Song, Mingyang; Eliassen, A; Wang, Molin; Fung, Teresa; Clinton, Steven K.; Rimm, Eric; Hu, Frank; Willet, Walter C.; Tabung, Fred; Giovannucci, Edward
    Multiple dietary patterns have been associated with different diseases; however, their comparability to improve overall health is yet to be determined. In 205,852 healthcare professionals from three US cohorts followed for up to 32 years, we prospectively assessed two mechanism-based diets and six diets based on dietary recommendations in relation to major chronic disease, defined as a composite outcome of incident major cardiovascular disease, type 2 diabetes, and cancer. We demonstrated that adherence to a healthy diet was generally associated with a lower risk of major chronic disease (hazard ratio [HR] comparing the 90th to 10th percentile of dietary pattern scores: 0.58–0.80). Participants with low insulinemic (HR 0.58, 95% CI 0.57, 0.60), low inflammatory (HR 0.61, 95% CI 0.60, 0.63), or diabetes risk-reducing diet (HR 0.70, 95% CI 0.69, 0.72) had the largest risk reduction for incident major cardiovascular disease, type 2 diabetes, and cancer in composite and individually. Similar findings were observed across sex, and diverse ethnic groups. Our results suggest that dietary patterns that are associated with markers of hyperinsulinemia and inflammation and diabetes development may inform on future dietary guidelines for chronic disease prevention.
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    ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED): a study protocol for a randomized controlled trial
    (BioMed Central, 2017) Drew, David; Chin, Samantha M.; Gilpin, Katherine K.; Parziale, Melanie; Pond, Emily; Schuck, Madeline M.; Stewart, Kathleen; Flagg, Meaghan; Rawlings, Crystal; Backman, Vadim; Carolan, Peter; Chung, Daniel; Colizzo, Francis; Freedman, Matthew; Gala, Manish; Garber, John; Huttenhower, Curtis; Kedrin, Dmitriy; Khalili, Hamed; Kwon, Douglas S.; Markowitz, Sanford D.; Milne, Ginger L.; Nishioka, Norman; Richter, James; Roy, Hemant K.; Staller, Kyle; Wang, Molin; Chan, Andrew
    Background: Although aspirin is recommended for the prevention of colorectal cancer, the specific individuals for whom the benefits outweigh the risks are not clearly defined. Moreover, the precise mechanisms by which aspirin reduces the risk of cancer are unclear. We recently launched the ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED) trial to address these uncertainties. Methods/design ASPIRED is a prospective, double-blind, multidose, placebo-controlled, biomarker clinical trial of aspirin use in individuals previously diagnosed with colorectal adenoma. Individuals (n = 180) will be randomized in a 1:1:1 ratio to low-dose (81 mg/day) or standard-dose (325 mg/day) aspirin or placebo. At two study visits, participants will provide lifestyle, dietary and biometric data in addition to urine, saliva and blood specimens. Stool, grossly normal colorectal mucosal biopsies and cytology brushings will be collected during a flexible sigmoidoscopy without bowel preparation. The study will examine the effect of aspirin on urinary prostaglandin metabolites (PGE-M; primary endpoint), plasma inflammatory markers (macrophage inhibitory cytokine-1 (MIC-1)), colonic expression of transcription factor binding (transcription factor 7-like 2 (TCF7L2)), colonocyte gene expression, including hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD) and those that encode Wnt signaling proteins, colonic cellular nanocytology and oral and gut microbial composition and function. Discussion Aspirin may prevent colorectal cancer through multiple, interrelated mechanisms. The ASPIRED trial will scrutinize these pathways and investigate putative mechanistically based risk-stratification biomarkers. Trial registration This protocol is registered with the U.S. National Institutes of Health trial registry, ClinicalTrials.gov, under the identifier NCT02394769. Registered on 16 March 2015. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1744-z) contains supplementary material, which is available to authorized users.
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    Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta-analysis
    (BMJ Publishing Group Ltd., 2013) Haider, Batool A; Olofin, Ibironke; Wang, Molin; Spiegelman, Donna; Ezzati, Majid; Fawzi, Wafaie
    Objectives: To summarise evidence on the associations of maternal anaemia and prenatal iron use with maternal haematological and adverse pregnancy outcomes; and to evaluate potential exposure-response relations of dose of iron, duration of use, and haemoglobin concentration in prenatal period with pregnancy outcomes. Design: Systematic review and meta-analysis Data sources Searches of PubMed and Embase for studies published up to May 2012 and references of review articles. Study selection criteria Randomised trials of prenatal iron use and prospective cohort studies of prenatal anaemia; cross sectional and case-control studies were excluded. Results: 48 randomised trials (17 793 women) and 44 cohort studies (1 851 682 women) were included. Iron use increased maternal mean haemoglobin concentration by 4.59 (95% confidence interval 3.72 to 5.46) g/L compared with controls and significantly reduced the risk of anaemia (relative risk 0.50, 0.42 to 0.59), iron deficiency (0.59, 0.46 to 0.79), iron deficiency anaemia (0.40, 0.26 to 0.60), and low birth weight (0.81, 0.71 to 0.93). The effect of iron on preterm birth was not significant (relative risk 0.84, 0.68 to 1.03). Analysis of cohort studies showed a significantly higher risk of low birth weight (adjusted odds ratio 1.29, 1.09 to 1.53) and preterm birth (1.21, 1.13 to 1.30) with anaemia in the first or second trimester. Exposure-response analysis indicated that for every 10 mg increase in iron dose/day, up to 66 mg/day, the relative risk of maternal anaemia was 0.88 (0.84 to 0.92) (P for linear trend<0.001). Birth weight increased by 15.1 (6.0 to 24.2) g (P for linear trend=0.005) and risk of low birth weight decreased by 3% (relative risk 0.97, 0.95 to 0.98) for every 10 mg increase in dose/day (P for linear trend<0.001). Duration of use was not significantly associated with the outcomes after adjustment for dose. Furthermore, for each 1 g/L increase in mean haemoglobin, birth weight increased by 14.0 (6.8 to 21.8) g (P for linear trend=0.002); however, mean haemoglobin was not associated with the risk of low birth weight and preterm birth. No evidence of a significant effect on duration of gestation, small for gestational age births, and birth length was noted. Conclusions: Daily prenatal use of iron substantially improved birth weight in a linear dose-response fashion, probably leading to a reduction in risk of low birth weight. An improvement in prenatal mean haemoglobin concentration linearly increased birth weight.
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    Inflammatory and Angiogenic Factors at Mid-Pregnancy Are Associated with Spontaneous Preterm Birth in a Cohort of Tanzanian Women
    (Public Library of Science, 2015) McDonald, Chloe R.; Darling, Anne M.; Conroy, Andrea L.; Tran, Vanessa; Cabrera, Ana; Liles, W. Conrad; Wang, Molin; Aboud, Said; Urassa, Willy; Fawzi, Wafaie; Kain, Kevin C.
    Research Question Preterm birth (PTB) is the leading cause of perinatal mortality worldwide, with the greatest burden occurring in resource-constrained settings. Based on the hypothesis that altered placental angiogenesis and inflammation early in pregnancy lead to PTB, we examined whether levels of inflammatory and angiogenic mediators, measured early in pregnancy, were predictive of spontaneous PTB (sPTB). Study Design Plasma samples were collected from a prospective cohort of primigravid Tanzanian women between 12–27 weeks gestation. A panel of 18 markers was screened on a training cohort of 426 women. Markers associated with sPTB in the training cohort were repeated in a test cohort of 628 women. All markers were measured by ELISA. Findings: In both the training and test cohorts plasma levels of IL-18BP, sICAM-1, sEndoglin and CHI3L1 were elevated and Leptin was lower at enrollment in women who subsequently experienced sPTB. In multivariate analysis women with plasma levels of CHI3L1, C5a, sICAM-1, AngptL3, sEndgolin, sFlt-1 and IL-18BP in the highest quartile had an increased risk of sPTB compared with those in the lowest quartile. Women with Leptin and Ang2 in the highest quartile had a reduced risk of sPTB compared with women in the lowest quartile. Implications Levels of angiogenic and inflammatory mediators measured at mid-pregnancy were associated with subsequent sPTB. These findings provide insight into mechanisms underlying sPTB and suggest biomarkers that may have clinical utility in risk-stratifying pregnancies.
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    The effect of standard dose multivitamin supplementation on disease progression in HIV-infected adults initiating HAART: a randomized double blind placebo-controlled trial in Uganda
    (BioMed Central, 2015) Guwatudde, David; Wang, Molin; Ezeamama, Amara E.; Bagenda, Danstan; Kyeyune, Rachel; Wamani, Henry; Manabe, Yukari C.; Fawzi, Wafaie
    Background: Efficacy trials investigating the effect of multivitamin (MV) supplementations among patients on Highly Active Antiretroviral Therapy (HAART) have so far been inconclusive. We conducted a randomized, double blind, placebo controlled trial to determine the effect of one recommended daily allowance (RDA) of MV supplementation on disease progression in patients initiating HAART. Methods: Eligible subjects were randomized to receive placebo or MV supplementation including vitamins B-complex, C and E. Participants were followed for up to 18 months. Primary endpoints were: change in CD4 cell count, weight and quality of life (QoL). Secondary endpoints were: i) development of a new or recurrent HIV disease progression event, including all-cause mortality; ii) switching from first- to second-line antiretroviral therapy (ART); and iii) occurrence of an adverse event. Intent-to-treat analysis, using linear regression mixed effects models were used to compare changes over time in the primary endpoints between the study arms. Kaplan-Meier time-to-event analysis and the log-rank test was used to compare HIV disease progression events and all-cause mortality. Results: Four hundred participants were randomized, 200 onto MV and 200 onto placebo. By month 18, the average change in CD4 cell count in the MV arm was 141 cells/uL compared to 147 cells/uL in the placebo arm, a mean difference of −6 · 17 [95 % CI −29 · 3, 16 · 9]. The average change in weight in the MV arm was 3 · 9 kg compared to 3 · 3 kg in the placebo arm, a mean difference of 0 · 54 [95 % CI −0 · 40, 1 · 48]; whereas average change in QoL scores in the MV arm was 6 · 8 compared to 8 · 8 in the placebo arm, a mean difference of −2.16 [95 % CI −4 · 59,0 · 27]. No significant differences were observed in these primary endpoints, or in occurrence of adverse events between the trial arms. Conclusions: One RDA of MV supplementation was safe but did not have an effect on indicators of disease progression among HIV infected adults initiating HAART. Trial registration Clinical trials NCT01228578, registered on 15th October 2010.
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    Particulate Matter Air Pollution Exposure, Distance to Road, and Incident Lung Cancer in the Nurses’ Health Study Cohort
    (NLM-Export, 2014) Puett, Robin C.; Hart, Jaime; Yanosky, Jeff D.; Spiegelman, Donna; Wang, Molin; Fisher, Jared A.; Hong, Biling; Laden, Francine
    Background: A body of literature has suggested an elevated risk of lung cancer associated with particulate matter and traffic-related pollutants. Objective: We examined the relation of lung cancer incidence with long-term residential exposures to ambient particulate matter and residential distance to roadway, as a proxy for traffic-related exposures. Methods: For participants in the Nurses’ Health Study, a nationwide prospective cohort of women, we estimated 72-month average exposures to PM2.5, PM2.5–10, and PM10 and residential distance to road. Follow-up for incident cases of lung cancer occurred from 1994 through 2010. Cox proportional hazards models were adjusted for potential confounders. Effect modification by smoking status was examined. Results: During 1,510,027 person-years, 2,155 incident cases of lung cancer were observed among 103,650 participants. In fully adjusted models, a 10-μg/m3 increase in 72-month average PM10 [hazard ratio (HR) = 1.04; 95% CI: 0.95, 1.14], PM2.5 (HR = 1.06; 95% CI: 0.91, 1.25), or PM2.5–10 (HR = 1.05; 95% CI: 0.92, 1.20) was positively associated with lung cancer. When the cohort was restricted to never-smokers and to former smokers who had quit at least 10 years before, the associations appeared to increase and were strongest for PM2.5 (PM10: HR = 1.15; 95% CI: 1.00, 1.32; PM2.5: HR = 1.37; 95% CI: 1.06, 1.77; PM2.5–10: HR = 1.11; 95% CI: 0.90, 1.37). Results were most elevated when restricted to the most prevalent subtype, adenocarcinomas. Risks with roadway proximity were less consistent. Conclusions: Our findings support those from other studies indicating increased risk of incident lung cancer associated with ambient PM exposures, especially among never- and long-term former smokers. Citation: Puett RC, Hart JE, Yanosky JD, Spiegelman D, Wang M, Fisher JA, Hong B, Laden F. 2014. Particulate matter air pollution exposure, distance to road, and incident lung cancer in the Nurses’ Health Study Cohort. Environ Health Perspect 122:926–932; http://dx.doi.org/10.1289/ehp.1307490
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    Plasma Phospholipid Long-Chain Omega-3 Fatty Acids and Total and Cause-Specific Mortality in Older Adults
    (American College of Physicians, 2013) Mozaffarian, Dariush; Lemaitre, Rozenn N.; King, Irena B.; Song, Xiaoling; Huang, Hongyan; Sacks, Frank; Rimm, Eric; Wang, Molin; Siscovick, David S.
    BACKGROUND: Long-chain ω-3 polyunsaturated fatty acids (ω3-PUFAs), including eicosapentaenoic acid (EPA) (20:5ω-3), docosapentaenoic acid (DPA) (22:5ω-3), and docosahexaenoic acid (DHA) (22:6ω-3), have been shown to reduce cardiovascular risk, but effects on cause-specific and total mortality and potential dose-responses remain controversial. Most observational studies have assessed self-reported dietary intake and most randomized trials have tested effects of adding supplements to dietary intake and evaluated secondary prevention, thus limiting inference for dietary ω3-PUFAs or primary prevention. OBJECTIVE: To investigate associations of plasma phospholipid EPA, DPA, DHA, and total ω3-PUFA levels with total and cause-specific mortality among healthy older adults not receiving supplements. DESIGN: Prospective cohort study. SETTING: 4 U.S. communities. PARTICIPANTS: 2692 U.S. adults aged 74 years (±5 years) without prevalent coronary heart disease (CHD), stroke, or heart failure at baseline. MEASUREMENTS: Phospholipid fatty acid levels and cardiovascular risk factors were measured in 1992. Relationships with total and cause-specific mortality and incident fatal or nonfatal CHD and stroke through 2008 were assessed. RESULTS: During 30 829 person-years, 1625 deaths (including 570 cardiovascular deaths), 359 fatal and 371 nonfatal CHD events, and 130 fatal and 276 nonfatal strokes occurred. After adjustment, higher plasma levels of ω3-PUFA biomarkers were associated with lower total mortality, with extreme-quintile hazard ratios of 0.83 for EPA (95% CI, 0.71 to 0.98; P for trend = 0.005), 0.77 for DPA (CI, 0.66 to 0.90; P for trend = 0.008), 0.80 for DHA (CI, 0.67 to 0.94; P for trend = 0.006), and 0.73 for total ω3-PUFAs (CI, 0.61 to 0.86; P for trend < 0.001). Lower risk was largely attributable to fewer cardiovascular than noncardiovascular deaths. Individuals in the highest quintile of phospholipid ω3-PUFA level lived an average of 2.22 more years (CI, 0.75 to 3.13 years) after age 65 years than did those in the lowest quintile. LIMITATION: Temporal changes in fatty acid levels and misclassification of causes of death may have resulted in underestimated associations, and unmeasured or imperfectly measured covariates may have caused residual confounding. CONCLUSION: Higher circulating individual and total ω3-PUFA levels are associated with lower total mortality, especially CHD death, in older adults. PRIMARY FUNDING SOURCE: National Institutes of Health.
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    Plasma Phospholipid Trans‐Fatty Acids Levels, Cardiovascular Diseases, and Total Mortality: The Cardiovascular Health Study
    (Blackwell Publishing Ltd, 2014) Wang, Qianyi; Imamura, Fumiaki; Lemaitre, Rozenn N.; Rimm, Eric; Wang, Molin; King, Irena B.; Song, Xiaoling; Siscovick, David; Mozaffarian, Dariush
    Background: While self‐reported trans–fatty acid (TFA) consumption is linked to coronary heart disease (CHD), relationships between objective biomarkers of TFA subtypes (t‐16:1n9, total t‐18:1, and cis/trans‐(c/t‐), t/c‐ and t/t‐18:2) and cardiovascular disease (CVD) or total mortality are not well established. Methods and Results: We evaluated 2742 adults in the Cardiovascular Health Study, aged 74±5 years and free of prevalent CVD, with plasma phospholipid TFA measures in 1992. Incident fatal and nonfatal CHD events, CVD and non‐CVD mortality, and total mortality were centrally adjudicated through 2010. Risks were assessed using Cox proportional hazards. During 31 494 person‐years, 1735 total deaths and 639 total CHD events occurred. In the multivariate model including mutual adjustment for the 5 TFA subtypes, circulating t/t‐18:2 was associated with higher total mortality (extreme quintile hazard ratio (HR)=1.23, 95% CI=1.04 to 1.44, P‐trend=0.01), CVD mortality (HR=1.40, 95% CI=1.05 to 1.86, P‐trend=0.02), and total CHD (HR=1.39, 95% CI=1.06 to 1.83, P‐trend=0.01). t/c‐18:2 was positively related to total mortality (HR=1.19, P‐trend=0.05), total CHD (HR=1.67, P‐trend=0.002), and nonfatal CHD (HR=2.06, P‐trend=0.002) after mutual adjustment; these associations were insignificant without mutual adjustment. Neither t‐16:1n9 nor t‐18:1 was significantly associated with total mortality or CVD, nor was c/t‐18:2 if we excluded early cases. Conclusions: Among circulating TFAs, t/t‐18:2 was most adversely associated with total mortality, mainly due to the increased risk of CVD. t/c‐18:2 was also positively associated with total mortality and CHD, but only after adjustment for other TFAs. These results highlight the need for further investigation of dietary sources, nondietary determinants, and health effects of specific TFA subtypes, especially t‐18:2 isomers.
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    Effect of Multivitamin Supplementation on Measles Vaccine Response among HIV-Exposed Uninfected Tanzanian Infants
    (American Society for Microbiology, 2013) Sudfeld, Christopher; Duggan, Christopher; Histed, A.; Manji, K. P.; Meydani, S. N.; Aboud, S.; Wang, Molin; Giovannucci, Edward; Fawzi, Wafaie
    Immunization and nutritional interventions are mainstays of child health programs in sub-Saharan Africa, yet few published data exist on their interactions. HIV-exposed (but uninfected) infants enrolled in a randomized placebo-controlled trial of multivitamin supplements (vitamins B complex, C, and E) conducted in Tanzania were sampled for an assessment of measles IgG quantity and avidity at 15 to 18 months. Infants were vaccinated between 8.5 and 12 months of age, and all mothers received high-dose multivitamins as the standard of care. Of 201 HIV-exposed infants who were enrolled, 138 (68.7%) were seropositive for measles. There were no effects of infant multivitamin supplementation on measles seroconversion proportions, IgG concentrations, or IgG avidity (P > 0.05). The measles seroconversion proportion was greater for HIV-exposed infants vaccinated at 10 to 11 months of age than for those vaccinated at 8.5 to 10 months (P = 0.032) and greater for infants whose mothers had a CD4 T-cell count of <200 cells/μl than for infants whose mothers had a CD4 T-cell count of >350 cells/μl (P = 0.039). Stunted infants had a significantly decreased IgG quantity compared to nonstunted infants (P = 0.012). As for measles avidity, HIV-exposed infants vaccinated at 10 to 11 months had increased antibody avidity compared to those vaccinated at 8.5 to 10 months (P = 0.031). Maternal CD4 T-cell counts of <200 cells/μl were associated with decreased avidity compared to counts of >350 cells/μl (P = 0.047), as were lower infant height-for-age z-scores (P = 0.016). Supplementation with multivitamins containing B complex, C, and E does not appear to improve measles vaccine responses for HIV-exposed infants. Studies are needed to better characterize the impact of maternal HIV disease severity on the immune system development of HIV-exposed infants and the effect of malnutrition interventions on vaccine responses. (This study has been registered at ClinicalTrials.gov under registration no. NCT00197730.)
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    Angiogenic and inflammatory biomarkers in midpregnancy and small-for-gestational-age outcomes in Tanzania
    (Elsevier BV, 2014) Darling, Anne Marie; McDonald, Chloe; Conroy, Andrea L.; Hayford, Kyla T.; Liles, W. Conrad; Wang, Molin; Aboud, Said; Urassa, Willy S.; Kain, Kevin C.; Fawzi, Wafaie
    OBJECTIVE To investigate the relationship between a panel of angiogenic and inflammatory biomarkers measured in mid-pregnancy and small-for-gestational age (SGA) outcomes in sub-Saharan Africa. STUDY DESIGN Concentrations of 18 angiogenic and inflammatory biomarkers were determined in 432 pregnant women in Dar es Salaam, Tanzania who participated in a trial examining the effect of multivitamins on pregnancy outcomes. Infants falling below the 10th percentile of birth weight for gestational age relative to the applied growth standards were considered SGA. Multivariate binomial regression models with the log link function were used to determine the relative risk of SGA associated with increasing quartiles of each biomarker. Stepwise cubic restricted splines were used to test for non-linearity of these associations. Receiver operating curves obtained from multivariate logistic regression models were used to assess the discriminatory capability of selected biomarkers. RESULTS A total of 60 participants (13.9%) gave birth to SGA infants. Compared to those in the first quartile, the risk of SGA was reduced among those in the fourth quartiles of VEGF-A (adjusted risk ratio (RR) 0.38, 95% Confidence Interval (CI), 0.19-0.74), PGF (adjusted RR 0.28, 95% CI, 0.12-0.61), sFlt-1 (adjusted RR 0.48, 95% CI, 0.23-1.01), MCP-1 (adjusted RR 0.48, 95% CI, 0.25-0.92), and Leptin (adjusted RR 0.46, 95% CI, 0.22-0.96) CONCLUSION Our findings provide evidence of altered angiogenic and inflammatory mediators, at mid-pregnancy, in women who went on to deliver small for gestational age infants.