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Microbially-derived short-chain fatty acids (SCFAs) in the human gut are tightly coupled to host metabolism, immune regulation, and integrity of the intestinal epithelium. However, the production of SCFAs can vary widely between individuals consuming the same diet, with lower levels often associated with disease. A mechanistic understanding of this heterogeneity is lacking. We present a microbial community-scale metabolic modeling (MCMM) approach to predict individual-specific SCFA production profiles. We assess the quantitative accuracy of our MCMMs usingin vitro,ex vivo, andin vivodata. Next, we identify associations between MCMM SCFA predictions and a panel of blood-based clinical chemistries in a large human cohort. Finally, we demonstrate how MCMMs can be leveraged to design personalized dietary, prebiotic, and probiotic interventions that optimize SCFA production in the gut. Our results represent an important advance in engineering gut microbiome functional outputs for precision health and nutrition.

Research suggests that women's experience of intimate partner violence (IPV) is associated with poor engagement in HIV care and treatment. However, most studies have been cross-sectional and conducted in North America. We examined the association between physical IPV and HIV care outcomes in a prospective cohort study of women living with HIV (WLHIV) in Malawi, South Africa, Uganda, and Zimbabwe. At enrollment, 15% of the 351 participants self-reported physical IPV. IPV experience was not associated with time to first engagement in HIV care or the proportion virally suppressed after 6 months on ART. Women reporting physical IPV were less likely to initiate ART within 6 months of becoming eligible (adjusted RR 0.74, 95% CI 0.53-1.03). IPV screening is critical to identify survivors and link them to appropriate services. However, addressing IPV may not increase engagement in HIV care or viral load suppression among WLHIV in sub-Saharan Africa.

Objective This study aims to assess the product-related, relationship-related, and sex-related factors that act as facilitators and barriers to the acceptability of a vaginal ring (VR) for HIV prevention among adolescent girls. Design Qualitative study. Methods Ninety-six 15 to 17-year-old girls from six urban U.S. sites were enrolled in MTN-023/IPM 030, a 24-week randomized controlled trial assessing the safety and acceptability of a dapivirine VR for HIV prevention. At week 24, 21 girls were randomly selected to participate in in-depth-interviews. Interviews were transcribed verbatim, and data analyzed using a thematic analysis approach. Facilitators and barriers to VR acceptability related to participants' relationships, sexual activity, and characteristics of the VR product were identified. Results Factors related to relationships rarely appeared to act as barriers to VR acceptability; most participants disclosed VR use to sexual partners, and positive reactions from sexual partners, which were common, appeared to facilitate VR acceptability. Emotional and/or physical discomfort surrounding VR use during sex was mentioned occasionally as a barrier to VR acceptability. Product characteristics were most frequently mentioned as barriers to VR acceptability. Many participants reported concerns about the large size of the VR upon first impression. While most found the VR comfortable, some reported pain with VR insertion. Several participants were concerned about VR cleanliness, particularly during menstruation. Conclusion Product considerations, specifically size and use during menstruation, were the most commonly reported barriers to VR acceptability in this study. Adolescent girls may require additional counseling to assuage product concerns regarding a VR for HIV prevention.

Background With antiretroviral (ARV)-based HIV prevention, the hidden epidemic of sexually transmitted infections (STIs) is being uncovered. Most STIs are asymptomatic and not treated by syndromic case management, the standard of care in Africa. There are limited data on STI prevalence among African adolescent girls and young women (AGYW) who are at risk for sequelae from untreated STIs. Methods MTN-034/REACH is a randomized, open label, crossover study assessing the safety of and adherence to the dapivirine vaginal ring and oral emtricitabine-tenofovir in Cape Town and Johannesburg, South Africa, Kampala, Uganda and Harare, Zimbabwe. Sexually active HIV-negative AGYW ages 16–21 years were enrolled and tested for Chlamydia trachomatis/Neisseria gonorrhoeae (CT/GC) by nucleic acid amplification, Trichomonas vaginalis (TV) by rapid test, and syphilis by serology. AGYW with positive test results received treatment. Descriptive statistics were used to summarize STI prevalence at baseline and selected characteristics by STI status. Results Among 247 AGYW enrolled in REACH, 34% were 16–17 years old, 87% single, and the median number of sexual partners in the prior 3 months was 1 (IQR 1–2). At enrollment, 87 (35%) tested positive for any STI with 17 (7%) with >1 STI: 71 (29%) for CT, 21 (8.5%) for GC, 12 (4.9%) for TV and 6 (2.4%) for syphilis. Of AGYW diagnosed with an STI, 90% were asymptomatic. The prevalence of any STI varied by site: 47% in Cape Town, 37% in Johannesburg, 32% in Kampala, and 25% in Harare. STI prevalence was higher among 18–21 year olds versus 16–17 year olds (37% vs 32%). Conclusion STI prevalence among AGYW initiating oral or topical PrEP was alarmingly high and most were asymptomatic, highlighting the limitations of syndromic STI management. There is an urgent need and imperative to provide diagnostic STI testing to AGYW with the delivery of HIV prevention methods.

Plant lignans and their microbial metabolites, e.g., enterolactone (ENL), may affect bile acid (BA) metabolism through interaction with hepatic receptors. We evaluated the effects of a flaxseed lignan extract (50 mg/day secoisolariciresinol diglucoside) compared to a placebo for 60 days each on plasma BA concentrations in 46 healthy men and women (20&ndash, 45 years) using samples from a completed randomized, crossover intervention. Twenty BA species were measured in fasting plasma using LC-MS. ENL was measured in 24-h urines by GC-MS. We tested for a) effects of the intervention on BA concentrations overall and stratified by ENL excretion, and b) cross-sectional associations between plasma BA and ENL. We also explored the overlap in bacterial metabolism at the genus level and conducted in vitro anaerobic incubations of stool with lignan substrate to identify genes that are enriched in response to lignan metabolism. There were no intervention effects, overall or stratified by ENL at FDR &lt, 0.05. In the cross-sectional analysis, irrespective of treatment, five secondary BAs were associated with ENL excretion (FDR &lt, 0.05). In vitro analyses showed positive associations between ENL production and bacterial gene expression of the bile acid-inducible gene cluster and hydroxysteroid dehydrogenases. These data suggest overlap in community bacterial metabolism of secondary BA and ENL.

OBJECTIVES: Health benefits of high-fiber foods may be attributed, in part, to microbial metabolites of plant compounds. Lignans and their microbial metabolites, the enterolignans [enterolactone (ENL) and enterodiol (END)], reduce serum lipids through a variety of mechanisms, including regulation of bile acid (BA) synthesis. BA, released into the gut lumen in response to dietary fat, undergo microbial metabolism to secondary (2°) BA, which have been positively associated with chronic disease, e.g., liver disease and colorectal cancer. Our aims were to evaluate the effects of a flaxseed lignan supplement on circulating BA and examine associations between enterolignans and 2° BA. METHODS: We conducted a randomized, crossover trial of a flaxseed lignan supplement (50 mg/d secoisolariciresinol diglucoside) compared to placebo in 46 healthy men and women (20-45 y). Each period lasted 60 days, separated by a 60-day washout period. Six primary and fourteen 2° BA species were measured in fasting plasma using LC-MS. ENL and END were measured in 24-h urines by GC-MS. Low- and high-ENL excreters were defined as below and above the median 24-h ENL excretion at the end of the flaxseed lignan intervention (23.4 µmol/24 h). Linear mixed models were used to a) test the effects of the intervention on individual BA concentrations, overall and stratified by low and high ENL excreters; and b) to cross-sectionally determine the association between plasma 2(o) BA and ENL and END. RESULTS: There was no significant effect of the flaxseed lignan intervention compared to placebo on BA concentrations overall, or by ENL-excreter status, after FDR adjustment. In the cross-sectional analysis, irrespective of treatment, six 2° BA were statistically significantly associated with ENL (FDR

Two phase 3 clinical trials showed that use of a monthly vaginal ring containing 25 mg dapivirine was well tolerated and reduced HIV-1 incidence in women by approximately 30% compared with placebo. We aimed to evaluate use and safety of the dapivirine vaginal ring (DVR) in open-label settings with high background rates of HIV-1 infection, an important step for future implementation.We did a phase 3B open-label extension trial of the DVR (MTN-025/HIV Open-label Prevention Extension [HOPE]). Women who were HIV-1-negative and had participated in the MTN-020/ASPIRE phase 3 trial were offered 12 months of access to the DVR at 14 clinical research centres in Malawi, South Africa, Uganda, and Zimbabwe. At each visit (monthly for 3 months, then once every 3 months), women chose whether or not to accept the offer of the ring. Used, returned rings were tested for residual amounts of dapivirine as a surrogate marker for adherence. HIV-1 serological testing was done at each visit. Dapivirine amounts in returned rings and HIV-1 incidence were compared with data from the ASPIRE trial, and safety was assessed. This study is registered with ClinicalTrials.gov, NCT02858037.Between July 16, 2016, and Oct 10, 2018, of 1756 women assessed for eligibility, 1456 were enrolled and participated in the study. Median age was 31 years (IQR 27-37). At baseline, 1342 (92·2%) women chose to take the DVR; ring acceptance was more than 79% at each visit up until 12 months and 936 (73·2%) of 1279 chose to take the ring at all visits. 12 530 (89·3%) of 14 034 returned rings had residual dapivirine amounts consistent with some use during the previous month (0·9 mg released) and the mean dapivirine amount released was greater than in the ASPIRE trial (by 0·21 mg; p0·0001). HIV-1 incidence was 2·7 per 100 person-years (95% CI 1·9-3·8, 35 infections), compared with an expected incidence of 4·4 per 100 person-years (3·2-5·8) among a population matched on age, site, and presence of a sexually transmitted infection from the placebo group of ASPIRE. No serious adverse events or grade 3 or higher adverse events observed were assessed as related to the DVR.High uptake and persistent use in this open-label extension study support the DVR as an HIV-1 prevention option for women. With an increasing number of HIV-1 prophylaxis choices on the horizon, these results suggest that the DVR will be an acceptable and practical option for women in Africa.The Microbicide Trials Network and the National Institute of Allergy and Infectious Diseases, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health, all components of the US National Institutes of Health.

BACKGROUND: Young women aged 15–24 years are disproportionately affected by the HIV epidemic. Two phase III trials of a vaginal ring containing 25-mg dapivirine demonstrated HIV-1 risk reduction in adult women older than 21 years but not in those aged 18–21 years. Lack of protection was correlated with low adherence. METHODS: In this phase-IIa, randomized, double-blind, placebo-controlled, US, multicenter trial of the dapivirine ring in sexually active females, aged 15–17 years, participants were randomized 3:1 to a dapivirine or placebo ring to be inserted monthly for 6 months (NCT02028338). Primary safety end points included grade 2 product related adverse events and any grade 3 and higher adverse events. Adherence to ring use was assessed by plasma dapivirine concentrations, residual levels in used rings, and self-report. A plasma dapivirine concentration of >95 pg/mL was used to define short-term adherence; a residual ring level of

Glucosamine and chondroitin (G&amp, C), typically taken for joint pain, are among the most frequently used specialty supplements by US adults. More recently, G&amp, C have been associated with lower incidence of colorectal cancer in human observational studies and reduced severity of experimentally-induced ulcerative colitis in rodents. However, little is known about their effects on colon-related physiology. G&amp, C are poorly absorbed and therefore metabolized by gut microbiota. G&amp, C have been associated with changes in microbial structure, which may alter host response. We conducted a randomized, double-blind, placebo-controlled crossover trial in ten healthy adults to evaluate the effects of a common dose of G&amp, C compared to placebo for 14 days on gut microbial community structure, measured by 16S rRNA gene sequencing. Linear mixed models were used to evaluate the effect of G&amp, C compared to placebo on fecal microbial alpha and beta diversity, seven phyla, and 137 genera. Nine genera were significantly different between interventions (False Discovery Rate &lt, 0.05). Abundances of four Lachnospiraceae genera, two Prevotellaceae genera, and Desulfovibrio were increased after G&amp, C compared to placebo, while Bifidobacterium and a member of the Christensenellaceae family were decreased. Our results suggest that G&amp, C affect the composition of the gut microbiome which may have implications for therapeutic efficacy.

BACKGROUND: Microbial metabolism of lignans from high-fiber plant foods produces bioactive enterolignans, such as enterolactone (ENL) and enterodiol (END). Enterolignan exposure influences cellular pathways important to cancer risk and is associated with reduced colon tumorigenesis in animal models and lower colorectal cancer risk in humans. OBJECTIVES: The aim of this study was to test the effects of a flaxseed lignan supplement (50 mg secoisolariciresinol diglucoside/d) compared with placebo on host gene expression in colon biopsies and exfoliated colonocyte RNA in feces and fecal microbial community composition, and to compare responses in relation to ENL excretion. METHODS: We conducted a 2-period randomized, crossover intervention in 42 healthy men and women (20–45 y). We used RNA-seq to measure differentially expressed (DE) genes in colonic mucosa and fecal exfoliated cells through the use of edgeR and functional analysis with Ingenuity Pathway Analysis. We used 16S ribosomal RNA gene (V1–V3) analysis to characterize the fecal microbiome, and measured END and ENL in 24-h urine samples by gas chromatography–mass spectrometry. RESULTS: We detected 32 DE genes (false discovery rate

As the effect of biomedical prevention interventions on the natural history of HIV-1 infection in participants who seroconvert is unknown, the Microbicide Trials Network (MTN) established a longitudinal study (MTN-015) to monitor virologic, immunological, and clinical outcomes, as well as behavioral changes among women who become HIV-infected during MTN trials. We describe the rationale, study design, implementation, and enrollment of the initial group of participants in the MTN seroconverter cohort.Initiated in 2008, MTN-015 is an ongoing observational cohort study enrolling participants who acquire HIV-1 infection during effectiveness studies of candidate microbicides. Eligible participants from recently completed and ongoing MTN trials are enrolled after seroconversion and return for regular follow-up visits with clinical and behavioral data collection. Biologic samples including blood and genital fluids are stored for future testing.MTN-015 was implemented initially at six African sites and enrolled 100/139 (72%) of eligible women who seroconverted in HIV Prevention Trials Network protocol 035 (HPTN 035, conducted by the MTN). The median time from seroconversion in HPTN 035 to enrollment in MTN-015 was 18 months. Retention was good with70% of visits completed. Implementation challenges included regulatory reviews, translation, and testing of questionnaires, and site readiness.Enrollment of HIV-seroconverters into a longitudinal observational follow-up study is feasible and acceptable to participants. Data and samples collected in this protocol will be used to assess safety of investigational HIV microbicides and answer other important public health questions for HIV infected women.

Background Evidence is lacking regarding whether vaginal pre-exposure prophylaxis with topical tenofovir (TFV) reduces the risk of rectal HIV acquisition. Setting Bronx, NY. Methods MTN-014 was a phase 1, cross-over, randomized sequence trial comparing the cross-compartment pharmacokinetics and pharmacodynamics of daily TFV reduced-glycerin 1% gel after 14 days each of rectal and vaginal application, with directly observed dosing and a 6-week washout period between phases. Results Fourteen HIV-uninfected women enrolled; 91% of doses were observed and 13 women completed all study procedures. TFV and TFV diphosphate (TFV-DP) were detected in most samples collected from the dosing compartment. After vaginal dosing, TFV was detected in 10/14 samples of rectal fluid (RF) (median 4.4 ng/sponge) and 1/13 rectal tissue samples (0.2 ng/mg); TFV-DP was detected in 2/13 rectal tissue samples at 59.8 and 76.5 fmol/mg. After rectal dosing, TFV was detected in 9/14 samples of vaginal fluid (median 1.1 ng/swab) and in 6/14 vaginal tissue samples (median below limit of quantification); TFV-DP was detected in 3/14 vaginal tissue samples at 17.3, 87.6, and 77.1 fmol/mg. Neither cervicovaginal lavage fluid nor RF collected 24 hours after rectal or vaginal dosing resulted in a statistically significant suppression of viral replication. Conclusions In this study of 14 days each of vaginal and rectal application of TFV reduced-glycerin 1% gel, we found only a small degree of cross-compartment distribution of TFV in RF and vaginal fluids and no pharmacodynamic activity in ex vivo testing. Although high TFV concentrations in the dosing compartment may be protective, low cross-compartment tissue concentrations are not likely to be protective.

Accurate estimates of study product use are critical to understanding and addressing adherence challenges in HIV prevention trials. The VOICE trial exposed a significant gap between self-reported adherence and drug detection. The VOICE-D qualitative study was designed to better understand non-adherence during VOICE, and was conducted in 2 stages: before (stage 1) and after (stage 2) drug detection results were provided to participants. Transcripts from 44 women who participated in both stages were analysed to understand the effect of presenting drug detection data on narratives of product use. Thirty-six women reported high adherence in stage 1, yet admitted non-use in stage 2, three reported high adherence in both stages (contrary to their drug detection results) and five had consistent responses across both stages and drug results. Presenting objective measures of use may facilitate more accurate product use reporting and should be evaluated in future prevention trials.

Background: Mexican immigrants are disproportionally affected by diet-related risk of metabolic dysfunction. Whether adhering to a traditional Mexican diet or adopting a US diet contributes to metabolic changes associated with future risk of type 2 diabetes and other chronic diseases has not been investigated. Objective: The purpose of this study was to test in a randomized crossover feeding trial the metabolic responses to a Mexican diet compared with a commonly consumed US diet. Design: First- and second-generation healthy women of Mexican descent (n = 53) were randomly assigned in a crossover design to consume a Mexican or US diet for 24 d each, separated by a 28-d washout period. Diets were eucaloric and similar in macronutrient composition. The metabolic responses to diets were assessed by measuring fasting serum concentrations of glucose, insulin, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), adiponectin, C-reactive protein (CRP), and interleukin 6 (IL-6), as well as the homeostasis model assessment of insulin resistance (HOMA-IR) at the beginning and end of each period. Linear mixed models tested the intervention effect on the biomarkers, while adjusting for diet sequence, feeding period, baseline and washout biomarker concentrations, age, acculturation, and BMI. Results: Compared with the US diet, the Mexican diet reduced insulin by 14% [geometric means (95% CIs): 9.3 (8.3, 10.3) compared with 8.0 (7.2, 8.9) μU/mL; P = 0.02], HOMA-IR by 15% [2.0 (1.8, 2.3) compared with 1.7 (1.6, 2.0); P = 0.02], and IGFBP-3 by 6% (mean ± SEM: 2420 ± 29 compared with 2299 ± 29 ng/mL; P < 0.01) and tended to reduce circulating concentrations of IGF-1 by 4% (149 ± 2.6 compared with 144 ± 2.5 ng/mL; P = 0.06). There was no significant intervention effect on serum concentrations of glucose, adiponectin, CRP, or IL-6 in the US compared with the Mexican diet. Conclusion: Compared with the commonly consumed US diet, the traditional Mexican diet modestly improved insulin sensitivity under conditions of weight stability in healthy women of Mexican descent, while having no impact on biomarkers of inflammation. This trial was registered at clinicaltrials.gov as {"type":"clinical-trial","attrs":{"text":"NCT01369173","term_id":"NCT01369173"}}NCT01369173.

OBJECTIVES In VOICE, a phase IIB trial of daily oral and vaginal tenofovir for HIV prevention, at least 50% of women receiving active products had undetectable tenofovir in all plasma samples tested. MTN-003D, an ancillary study using in-depth interviews (IDIs) and focus group discussions (FGDs), together with retrospective disclosure of plasma tenofovir pharmacokinetic results, explored adherence challenges during VOICE. METHODS We systematically recruited participants with pharmacokinetic data (median six plasma samples), categorized as low (0%, N = 79), inconsistent (1-74%, N = 28) or high (≥75%; N = 20) on the basis of frequency of tenofovir detection. Following disclosure of pharmacokinetic results, reactions were captured and adherence challenges systematically elicited; IDIs and FGDs were audio-recorded, transcribed, coded and thematically analysed. RESULTS We interviewed 127 participants from South Africa, Uganda and Zimbabwe. The most common reactions to pharmacokinetic results included surprise (41%; low pharmacokinetic), acceptance (39%; inconsistent pharmacokinetic) and happiness (65%; high pharmacokinetic). On the basis of participants' explanations, we developed a typology of adherence patterns: noninitiation, discontinuation, misimplementation (resulting from visit-driven use, variable taking, modified dosing or regimen) and adherence. Fear of product side effects/harm was a frequent concern, fuelled by stories shared among participants. Although women with high pharmacokinetic levels reported similar concerns, several described strategies to overcome challenges. Women at all pharmacokinetic levels suggested real-time drug monitoring and feedback to improve adherence and reporting. CONCLUSION Retrospective provision of pharmacokinetic results seemingly promoted candid discussions around nonadherence and study participation. The effect of real-time drug monitoring and feedback on adherence and accuracy of reporting should be evaluated in trials.

Background Little is known regarding HIV disease outcomes among individuals who become infected with HIV while receiving antiretroviral medications for prevention. We compared HIV disease parameters among women who seroconverted while receiving tenofovir-containing oral or vaginal pre-exposure prophylaxis (PrEP) to placebo. Methods Participants with HIV seroconversion in a randomized placebo-controlled trial of oral tenofovir, oral tenofovir/emtricitabine, and vaginal tenofovir gel (MTN-003) were followed in a longitudinal cohort study (MTN-015). The effect of oral and vaginal tenofovir-containing PrEP on HIV disease progression was compared to placebo using linear mixed effects and Cox proportional hazard models, as appropriate. Additional analyses were performed to compare the outcomes among participants with detectable tenofovir or emtricitabine in plasma at the first quarterly visit in MTN-003. Results A total of 224 participants were included in the analysis; 93% from South Africa and 94% clade C virus. No differences in HIV RNA at steady state or the trajectory over 12 months were observed for each active arm compared to placebo; tenofovir gel recipients had higher CD4+ T cell counts (722 vs 596 cells/mm3; p = 0.02) at 90 days after estimated HIV seroconversion and higher average rates of change over 12 months compared to placebo (-181 vs -92 cells/mm3 per year; p = 0.08). With a median follow-up of 31 months, no significant differences were observed for time to CD4+ T cell count ≤350 cells/mm3, or the composite endpoint of CD4+ T cells ≤350 cells/mm3, initiation of antiretroviral therapy or death for each active arm compared to placebo. Additionally, there were no significant differences in the HIV RNA or CD4+ T cell counts at baseline, the change to month 12, or any disease progression outcomes among participants with oral drug detected and no oral drug detected compared to placebo. Conclusions No clinically significant differences in HIV seroconversion outcomes were observed among women randomized to tenofovir-containing oral or vaginal PrEP regimens, however low overall adherence limits the generalizability of these findings.

Long-term use of aspirin is associated with lower risk of colorectal cancer and other cancers; however, the mechanism of chemopreventive effect of aspirin is not fully understood. Animal studies suggest that COX-2, NFκB signaling and Wnt/β-catenin pathways may play a role, but no clinical trials have systematically evaluated the biological response to aspirin in healthy humans. Using a high-density antibody array, we assessed the difference in plasma protein levels after 60 days of regular dose aspirin (325 mg/day) compared to placebo in a randomized double-blinded crossover trial of 44 healthy non-smoking men and women, aged 21-45 years. The plasma proteome was analyzed on an antibody microarray with ~3,300 full-length antibodies, printed in triplicate. Moderated paired t-tests were performed on individual antibodies, and gene-set analyses were performed based on KEGG and GO pathways. Among the 3,000 antibodies analyzed, statistically significant differences in plasma protein levels were observed for nine antibodies after adjusting for false discoveries (FDR adjusted p-value

Background/objectivesCertain populations with a large proportion of indigenous American (IA) genetic ancestry may be evolutionarily adapted to traditional diets high in legumes and complex carbohydrates, and may have a detrimental metabolic response to US diets high in refined carbohydrates and added sugars. We tested whether IA ancestry modified the metabolic response to a US versus traditional Mexican diet in a controlled dietary intervention.Subjects/methodsFirst and second generation Mexican immigrant women (n=53) completed a randomized crossover feeding trial testing the effects of a US versus traditional Mexican diet. The metabolic response to the diets was measured by fasting serum concentrations of glucose, insulin, insulin-like growth factor-1 (IGF-1), IGF-binding protein-3 (IGFBP-3), adiponectin, C-reactive protein, interleukin-6 and computed homeostasis model assessment for insulin resistance (HOMAIR). Blood collected at baseline was used for genotyping, and estimation of African, European and IA ancestries with the use of 214 ancestry informative markers.ResultsThe genetic ancestral background was 56% IA, 38% European and 6% African. Women in the highest IA ancestry tertile (>62%) were shorter in height, less educated and less acculturated to the US lifestyle, and tended to have higher waist-to-hip ratio compared with women in the middle and lowest IA ancestry tertiles, respectively. Compared with the US diet, the traditional Mexican diet tended to reduce glucose, insulin, IGF-1, IGFBP-3 and HOMAIR among women in the middle IA ancestry group (IA ancestry ⩽45-62%), whereas having no effect on biomarkers related to inflammation.ConclusionsWe observed modest interactions between IA ancestry and the metabolic response to a US versus traditional Mexican diet among Mexican immigrant women.

Face à une crise de la planification avérée depuis plusieurs décennies, l’aménagement peine à relever le défi de l’agir dans un monde incertain. Toutefois, impulsés par des formes de gouvernance inédites, des objets territoriaux non identifiés apparaissent, ouvrant la voie à de nouvelles modalités d’action. En suivant, pendant quatre ans, les projets d’aménagement conduits par un Conseil général, nous avons mis en évidence le rôle central qu’y tiennent les interactions et les échanges entre acteurs. Ceux-ci dessinent une dynamique proche de celle de l’improvisation. Souvent considérée péjorativement, l’improvisation pourrait représenter un modèle d’action efficace pour construire des identités partagées et garantir la coordination de leurs actions. L’analyse des pratiques des chefs de projet a conduit à accorder une attention particulière à des qualités et valeurs telles que l’écoute, la confiance, l’engagement, dans une logique de don et de croyance, au coeur des échanges avec les partenaires et de l’engagement réciproque au service du projet., Exposed to increasing levels of uncertainty, the planning model is facing a crisis that affects its theories as well as its methods and tools. In relation with varying structures of governance, some unidentified forms of territories appear, which support new methods of action. By working four years at a French General council, I could approach the planning projects that he managed from within and develop a perspective in which interactions and process of sharing appear to play a central role. Patterns and themes designed by these interactions can be associated to an improvisational action model. Generally considered in a pejorative way, I propose to see improvisation as an efficient way of building common identities and goals and coordinate action between actors. Observing the project managers practices drives to underline a capacity to listen, to build trust, and to foster a special commitment within a logic of giving and belief, which guarantee mutual exchange and active contribution to the project.

Metabolomic profiles were used to characterise the effects of consuming a high-phytochemical diet compared with a diet devoid of fruits and vegetables (F&V) in a randomised trial and cross-sectional study. In the trial, 8 h fasting urine from healthy men (n 5) and women (n 5) was collected after a 2-week randomised, controlled trial of two diet periods: a diet rich in cruciferous vegetables, citrus and soya (F&V), and a fruit- and vegetable-free (basal) diet. Among the ions found to differentiate the diets, 176 were putatively annotated with compound identifications, with forty-six supported by MS/MS fragment evidence. Metabolites more abundant in the F&V diet included markers of the dietary intervention (e.g. crucifers, citrus and soya), fatty acids and niacin metabolites. Ions more abundant in the basal diet included riboflavin, several acylcarnitines and amino acid metabolites. In the cross-sectional study, we compared the participants based on the tertiles of crucifers, citrus and soya from 3 d food records (n 36) and FFQ (n 57); intake was separately divided into the tertiles of total fruit and vegetable intake for FFQ. As a group, ions individually differential between the experimental diets differentiated the observational study participants. However, only four ions were significant individually, differentiating the third v. first tertile of crucifer, citrus and soya intake based on 3 d food records. One of these ions was putatively annotated: proline betaine, a marker of citrus consumption. There were no ions significantly distinguishing tertiles by FFQ. The metabolomic assessment of controlled dietary interventions provides a more accurate and stronger characterisation of the diet than observational data.

Sulforaphane (SFN), is an effective in vitro antagonist of ligand activation of the human pregnane and xenobiotic receptor (PXR). PXR mediated CYP3A4 up-regulation is implicated in adverse drug-drug interactions making identification of small molecule antagonists a desirable therapeutic goal. SFN is not an antagonist to mouse or rat PXR in vitro; thus, normal rodent species are not suitable as in vivo models for human response. To evaluate whether SFN can effectively antagonize ligand activation of human PXR in vivo, a three-armed, randomized, crossover trial was conducted with 24 healthy adults. The potent PXR ligand – rifampicin (300 mg/d) was given alone for 7 days in arm 1, or in daily combination with 450 µmoles SFN (Broccoli Sprout extract) in arm 2; SFN was given alone in arm 3. Midazolam as an in vivo phenotype marker of CYP3A was administered before and after each treatment arm. Rifampicin alone decreased midazolam AUC by 70%, indicative of the expected increase in CYP3A4 activity. Co-treatment with SFN did not reduce CYP3A4 induction. Treatment with SFN alone also did not affect CYP3A4 activity in the cohort as a whole, although in the subset with the highest basal CYP3A4 activity there was a statistically significant increase in midazolam AUC (i.e., decrease in CYP3A4 activity). A parallel study in humanized PXR mice yielded similar results. The parallel effects of SFN between humanized PXR mice and human subjects demonstrate the predictive value of humanized mouse models in situations where species differences in ligand-receptor interactions preclude the use of a native mouse model for studying human ligand-receptor pharmacology.

BACKGROUND: Hispanics in the United States are less likely than other groups to receive screening services for colorectal cancer. METHODS: The authors conducted a clinic-based individual randomized trial that enrolled Hispanic patients ages 50 to 79 years who had been seen in the Seattle-based community clinic in the past 5 years. A total of 501 patients met the eligibility criteria and were randomized to 1 of 3 conditions: 1) usual care; 2) mailed fecal occult blood test (FOBT) card and instructions on how to complete the test (mailed FOBT only); and 3) mailed FOBT card and instructions on how to complete the test, telephone reminders, and home visits (mailed FOBT and outreach). The authors assessed postintervention differences in rates of FOBT screening in intervention and usual care groups using computerized medical records reviewed from June 2007 to March 2008. RESULTS: Data analysis occurred between November 2008 and September 2009. Nine-month postintervention screening rates were 26% among patients who received the mailed packet only intervention (P < .001 compared with usual care) and 31% in the group that received the mailed packet and outreach intervention (P < .001 compared with usual care). This compared with 2% in the group that received usual care. Screening rates in the mailed FOBT only group and in the mailed FOBT and outreach group were not significantly different (P = .28). CONCLUSIONS: Culturally appropriate clinic-based interventions may increase colorectal cancer screening among underserved Hispanics. Cancer 2011. © 2010 American Cancer Society.

The strength of associations between various exposures (e.g., diet, tobacco, chemopreventive agents) and colorectal cancer risk may partially depend on the complex interaction between epithelium and stroma across anatomic subsites. Currently, baseline data describing genome-wide coding and long noncoding gene expression profiles in the healthy colon specific to tissue type and location are lacking. Therefore, colonic mucosal biopsies from 10 healthy participants who were enrolled in a clinical study to evaluate effects of lignan supplementation on gut resiliency were used to characterize the site-specific global gene expression signatures associated with stromal vs. epithelial cells in the sigmoid colon and rectum. Using RNA-seq, we demonstrate that tissue type and location patterns of gene expression and upstream regulatory pathways are distinct. For example, consistent with a key role of stroma in the crypt niche, mRNAs associated with immunoregulatory and inflammatory processes (i.e., CXCL14, ANTXR1), smooth muscle contraction (CALD1), proliferation and apoptosis (GLP2R, IGFBP3), and modulation of extracellular matrix (MMP2, COL3A1, MFAP4) were all highly expressed in the stroma. In comparison, HOX genes (HOXA3, HOXD9, HOXD10, HOXD11, and HOXD-AS2, a HOXD cluster antisense RNA 2), and WNT5B expression were also significantly higher in sigmoid colon compared with the rectum. These findings provide strong impetus for considering colorectal tissue subtypes and location in future observational studies and clinical trials designed to evaluate the effects of exposures on colonic health.

Contains fulltext : 159332.pdf (Publisher’s version ) (Open Access) Across Europe, citizens are increasingly expected to participate in the implementation of flood risk management (FRM), by engaging in voluntary-based activities to enhance preparedness, implementing property-level measures, and so forth. Although citizen participation in FRM decision making is widely addressed in academic literature, citizens’ involvement in the delivery of FRM measures is comparatively understudied. Drawing from public administration literature, we adopted the notion of “coproduction” as an analytical framework for studying the interaction between citizens and public authorities, from the decision-making process through to the implementation of FRM in practice. We considered to what extent coproduction is evident in selected European Union (EU) member states, drawing from research conducted within the EU project STAR-FLOOD (Strengthening and Redesigning European Flood Risk Practices towards Appropriate and Resilient Flood Risk Governance Arrangements). On the basis of a cross-country comparison between Flanders (Belgium), England (United Kingdom), France, the Netherlands, and Poland, we have highlighted the varied forms of coproduction and reflected on how these have been established within divergent settings. Coproduction is most prominent in discourse and practice in England and is emergent in France and Flanders. By contrast, FRM in the Netherlands and Poland remains almost exclusively reliant on governmental protection measures and thereby consultation-based forms of coproduction. Analysis revealed how these actions are motivated by different underlying rationales, which in turn shape the type of approaches and degree of institutionalization of coproduction. In the Netherlands, coproduction is primarily encouraged to increase societal resilience, whereas public authorities in the other countries also use it to improve cost-efficiency and redistribute responsibilities to its beneficiaries. 14 p.

BACKGROUND Tenofovir (TFV) gel partially protected against human immunodeficiency virus (HIV) in one but not subsequent trials. The disappointing results were attributed largely to poor adherence. However, timing of gel application relative to sex may impact pharmacokinetics and contribute to outcomes. Thus, we conducted a single-dose pharmacokinetic study of TFV gel applied 1 or 24 hours before or 1 hour before and 1 hour after (BAT) sex and compared results with dosing without sex. METHODS Twenty-four couples were enrolled; cervicovaginal lavage (CVL) and tissue were collected 2 hours after sex with matching timed collections at no sex visits and assayed for drug concentrations and CVL anti-HIV activity. RESULTS Compared with dosing without sex, median TFV concentrations after sex decreased 72% and 78% (P < .001) in CVL, 75% and 71% (P < .001) in vaginal tissue, and 75% (P = .06) and 55% (P < .001) in cervical tissue with -1 hour and -24 hour dosing, respectively. Median concentration of TFV-diphosphate also decreased significantly in cervical tissue with -1 hour, dosing. BAT dosing resulted in drug levels at least as great as those in the absence of sex. Percent inhibition of HIV infection by post-coital CVL increased significantly from median (interquartile range) of 55% (54%) in the absence of gel to 99% (7%), 77% (57%), and 100% (0.4%) with -1 hour, -24 hour, or BAT dosing, respectively, and correlated significantly with drug concentration. CONCLUSIONS Timing of TFV gel application relative to sex significantly impacts drug levels. BAT dosing or sustained delivery may be optimal for preexposure prophylaxis.

OBJECTIVES: This study compared use of food labels before and after implementation of new Food and Drug Administration regulations in 1994. METHODS: Data were obtained by random-digit-dial surveys of Washington State residents in 1993 (n = 1001) and 1996 (n = 1450). RESULTS: After implementation of the new regulations, usual label use increased significantly, by 8.5 percentage points in women and 11.3 percentage points in men. More respondents looked for information on fat content and fewer failed to use labels because they "take too much time" or "are too hard to understand. CONCLUSIONS: Use of food labels and satisfaction with their content have increased, but 70% of adults still want labels to be easier to understand.

Dapivirine (DPV) is a nonnucleoside reverse transcriptase inhibitor with a favorable safety profile following vaginal application. A penile tolerance study was conducted prior to further development of DPV as a candidate vaginal microbicide. Twenty-four circumcised and 24 uncircumcised (N=48) healthy HIV-negative male participants aged 18 years or older were randomized 2:1:1 to apply DPV 0.05% gel, matched placebo gel, or universal placebo gel, respectively, to their penis once daily for 7 sequential days. The safety, acceptability, and pharmacokinetic profile of DPV 0.05% gel were assessed by the presence of Grade 2 or higher genitourinary adverse events (AEs) and systemic AEs, a behavioral questionnaire, and pharmacokinetic plasma blood draw, respectively, at the final clinic visit (FCV). There were no Grade 2 genitourinary AEs in 47 participants completing the FCV. One participant in the DPV arm failed to attend the FCV. There were 13 AEs reported; all were Grade 1 except one Grade 2 corneal laceration unrelated to study product. Participants liked the gel to a moderate extent, yet 72% reported they would be "very likely" to use a gel like the one they used in the study every time they have intercourse. DPV was detectable in plasma in all 23 DPV arm study participants at the FCV. On average, the circumcised participants' DPV concentrations were 54% of those in uncircumcised participants (p=0.07). Topical seven-day penile application of DPV 0.05% gel was locally and systemically safe, was acceptable to male participants, and resulted in systemic exposure to the drug.

Background: Long-term use of aspirin is associated with lower colorectal cancer (CRC) incidence; however, the mechanism of the chemopreventive effect of aspirin is not fully understood. Animal studies suggest that COX-2, NFκB signaling and Wnt/β-catenin pathways may play a role, but no clinical trials have systematically evaluated the biological response to aspirin in healthy humans. Methods: We assessed the difference in plasma protein levels after 60 days of regular dose aspirin (325 mg/day) compared to placebo in a randomized, double-blinded, placebo-controlled, cross-over trial of 44 healthy non-smoking men and women, aged 21-45 years. Plasma proteomics was analyzed on an antibody microarray with ∼3,000 full-length antibodies, printed in triplicate. Moderated paired t-test was performed on individual antibodies, and gene set analyses were performed for KEGG and GO pathways. Results: Among the 3,387 antibodies, significant differences in plasma protein levels were observed for 267 antibodies (p Citation Format: Xiaoliang Wang, Yuzheng Zhang, Ali Shojaie, Paul D. Lampe, Lisa Levy, Ulrike Peters, John D. Potter, Emily White, Johanna W. Lampe. Exploratory plasma proteomic analysis in a randomized cross-over trial of aspirin among healthy individuals. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4284.

Background: Greater acculturation to the U.S. dietary habits has been suggested to contribute to the high rates of obesity, insulin resistance, and therefore, potential risk of type 2 diabetes (T2D) and breast cancer. Mexican immigrants may be evolutionary adapted to traditional diets high in legumes and complex carbohydrates. When consuming an inexpensive, readily available U.S. diet high in refined carbohydrates and added sugars they may experience a detrimental metabolic and/or inflammatory response, placing them at a disproportionately higher risk of certain cancers. To better understand these biological mechanisms that may underlie immigrant-related health disparities, we tested whether genetic ancestry modified the metabolic response to a traditional Mexican versus U.S. diet in a controlled feeding trial. Methods: First and second generation, female, Mexican immigrants (n=53) completed a randomized, crossover feeding trial testing the response to a Mexican versus U.S. diet for 24 days each, separated by a 28-day washout period. The trial diets were designed to provide energy content for weight maintenance and were similar in macronutrient composition. Participants were instructed to consume only study provided foods. The traditional Mexican diet was high in corn tortillas, beans, Mexican soups, fruits, vegetables, animal fats, full-fat milk, and Mexican cheeses; in contrast, the U.S. diet was high in refined carbohydrates, vegetable oils, nonfat or low-fat milk, processed foods, processed meats and sugar-sweetened beverages. The metabolic response to the diets was measured by fasting serum concentrations of glucose, insulin, insulin-like growth factor (IGF)-1, IGF binding protein (IGFBP)-3, adiponectin, C-reactive protein (CRP), interleukin-6 (IL-6), and the calculated homeostasis model assessment of insulin resistance (HOMA-IR) at the beginning and end of each feeding period. DNA was extracted from baseline blood for genotyping and estimation of each participant's proportion of genetic ancestry from four populations – Indigenous American (IA), European, African, and Asian – with the use of 218 Informative Ancestry Markers. Linear mixed models were adjusted for diet sequence, feeding period, baseline and washout biomarker concentrations, age, body weight, and acculturation. Results: The overall genetic ancestral background of the study sample was 53% IA and 36% European ancestry. In general, genetic ancestry did not modify the metabolic responses to the Mexican versus U.S. diet. However, genetic ancestry was associated with some baseline participant's characteristics and measures. Greater IA ancestry trended toward a positive association with waist-to-hip ratio (P=0.08) and was inversely associated with both education and acculturation (P Conclusions: Genetic ancestry suggested differences in baseline measures of several biomarkers that have been identified as cancer susceptibility biomarkers. Although, we found a significant metabolic response to the traditional Mexican versus U.S. diet, overall, we did not observe correlations between genetic ancestry and this response. Nonetheless, the results from the study may inform our understanding of variation in cancer susceptibility biomarkers in vulnerable populations. Additional research is needed to further investigate whether genetic ancestry modifies the associations of other lifestyle exposures, such as physical activity or smoking, with cancer susceptibility biomarkers in Mexican immigrants and other minority groups. Citation Format: Margarita Santiago-Torres, Jean De Dieu Tapsoba, Mario Kratz, Johanna W. Lampe, Kara L. Breymeyer, Lisa Levy, Xiaoling Song, Adriana Villaseñor, Ching-Yun Wang, Christopher Carlson, Marian L. Neuhouser. Does genetic ancestry influence the metabolic response to a traditional Mexican versus U.S. diet? A randomized crossover feeding trial among first and second generation women of Mexican descent. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr A68.

Background/Aims: Interindividual variation in aspirin (ASA) metabolism is attributed to concomitant use of drugs or alcohol, urine pH, ethnicity, sex, and genetic variants in UDP-glucuronosyltransferases (UGT). Little is known about the effects of diet. Methods: We evaluated cross-sectionally whether urinary excretion of ASA and its metabolites [salicylic acid (SA), salicyluric acid (SUA) phenolic glucuronide (SUAPG), salicylic acid acyl glucuronide (SAAG) and salicylic acid phenolic glucuronide (SAPG)] differed by UGT1A6 genotype and dietary factors shown to induce UGT. Following oral treatment with 650 mg ASA, urine was collected over 8 h in 264 men and 264 women (21–45 years old). Results: There were statistically significant differences in metabolites excreted between sexes and ethnicities. Men excreted more SUA; women more ASA (p = 0.03), SA, SAAG and SAPG (p ≤ 0.001 for all). Compared to Caucasians, Asians excreted more ASA, SA and SAAG, and less SUA and SUAPG (p ≤ 0.03 for all); African-Americans excreted more SAAG and SAPG and less SUA (p ≤ 0.04). There was no effect of UGT1A6 genotypes. Increased ASA and decreased SUAPG excretion was observed with increased servings of vegetables (p = 0.008), specifically crucifers (p = 0.05). Conclusion: Diet may influence the pharmacokinetics of ASA, but effects may be through modulation of glycine conjugation rather than glucuronidation.

Background: Obesity increases risk for breast and other cancers. This is of concern among Hispanics who have higher rates of obesity when compared to non-Hispanic Whites. More versus less acculturated Hispanics often have diets high in simple sugars and low in fiber, which is proposed to contribute to adiposity. Therefore, we aimed to examine the associations between obesity, acculturation, and dietary intake among healthy, Mexican-descent women. Methods: A cross-sectional analysis was conducted among 1st and 2nd generation healthy Mexican-descent women (n=58) who were screened for participation in a controlled feeding study in Seattle, WA. Women were pre-menopausal, non-smoking, ages 18 to 45 years, with a body mass index (BMI) between 18.5 and 40.0 kg/m2. Additional exclusion criteria addressed a mix of medical and practical issues and included impaired glucose tolerance (fasting glucose ≥100mg/dL), current pregnancy or lactation, and heavy alcohol use, defined as ≥ 2 drinks/day. Analyses included demographics, acculturation measures, self-reported dietary intake (3-day food records) and measured anthropometrics. Dietary intake is reported as percentage of total energy. Comparisons across BMI categories were tested using general linear models for continuous dietary intake variables, while adjusting for age. Adjusted logistic regression models were used to calculate the odds ratio (OR) for overweight and obesity (BMI ≥25.0), as compared to normal weight (BMI Results: Women in the study had lived in the US for 13.8 ± 6.4 years, 60% were born in Mexico, 64% self-identified as Mexican versus Mexican-American and 53% were overweight or obese. Overweight and obese women significantly (P Conclusions: These results are consistent with the hypothesis that more acculturated women consume less dietary fiber and more simple sugars, which may contribute to overweight and obesity. Prevention efforts for obesity-related breast and other cancers should include dietary recommendations that encourage diets high in dietary fiber, while reducing the consumption of added sugars in this highly-at risk population. Citation Format: Margarita Santiago-Torres, Kara L. Breymeyer, Mario Kratz, Johanna W. Lampe, Lisa Levy, Marian L. Neuhouser. Dietary intake in the relation between acculturation and obesity among healthy, Mexican-descent women. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B06.

Objective Test the hypothesis that soy isoflavone supplementation preserves bone mineral density (BMD) in men and women. Methods We conducted a controlled, parallel-arm, double-blinded trial with 145 participants, 50–80 years, with random assignment to soy beverage daily for 12 months. Active treatment (+ISO) received soy protein containing 83 mg isoflavones (45.6 mg genistein, 31.7 mg daidzein), aglycone units; the comparison group (−ISO) received soy protein containing 3 mg isoflavones. We measured BMD using dual-energy X-ray absorptiometry at the total hip and posterior–anterior spine (L1–L4) at baseline in 22 women and 123 men, and at 12 months in 13 women and 98 men. We used linear mixed models to test for an isoflavone effect on percentage BMD change from baseline in spine and hip. Results Among all participants, mean percent change in spine BMD (±S.E.) was 0.16 ± 0.44 in −ISO ( P = 0.10) at 12 months. Treatment effects on spine BMD were significantly greater in women than men ( P = 0.01). At 12 months, in women, mean percent change was 0.58 ± 0.70 in +ISO and −1.84 ± 0.86 in −ISO ( P = 0.05); among men it was 1.32 ± 0.53 in +ISO and 0.31 ± 0.48 in −ISO ( P = 0.16). By comparison, percent change in hip BMD was similar in the treatment groups, and was not different between men and women. Mean percent change in hip BMD from baseline to 12 months was 0.54 ± 0.38 in +ISO and −0.13 ± 0.36 in −ISO ( P = 0.20) among all participants. Conclusions Soy protein containing isoflavones showed a modest benefit in preserving spine, but not hip BMD in older women.

Several characteristics of aberrant crypt foci (ACF) suggest that they are precursors of colorectal cancer, but the factors that promote or inhibit their growth are largely unknown. We conducted a pilot study to explore whether factors associated with risk of colorectal cancer are also associated with number or size of rectal ACF. Thirty-two U.S. veterans, ages 50 to 80 years, were recruited to undergo magnifying chromoendoscopy for imaging of rectal ACF and colonoscopy for identification of polyps or cancer. Participants completed a questionnaire on cigarette smoking, use of nonsteroidal anti-inflammatory drugs (NSAIDs), and family history of colorectal cancer. Fisher's exact test was used to assess the statistical significance of associations between colorectal cancer risk factors and characteristics of ACF. Cochran-Mantel-Haenszel statistics and polytomous regression were used to test the significance of associations adjusted for age. Participants with a history of adenoma had more ACF than those without (age-adjusted P = 0.02), but the numbers in the two groups overlapped markedly. Older participants had more (P = 0.06) and larger (P = 0.009) ACF than younger participants. No associations were identified between either ACF number or size and cigarette smoking, use of NSAIDs, or family history of colorectal cancer. These findings suggest that persons with adenomas have somewhat more rectal ACF than persons without, and that older age is a risk factor for ACF growth. Future research should be directed toward developing techniques to identify ACF that are likely to progress to cancer and the modifiable factors that promote or inhibit such progression.

One hundred four adults completed a multiple choice food label comprehension questionnaire and a food frequency questionnaire. Most respondents were able to accurately rate the fat content of five different foods using only the food label information. However, some underestimated food content for some foods. Also, only 29% correctly selected the definition of % daily value for fat (%DV), as "percent of the maximum daily recommended amount of fat."

ObjectiveTo evaluate the accuracy of a simplified inventory procedure for assessing nutrient intake from vitamin and mineral supplements.DesignParticipants brought their supplements to a clinic. An interviewer conducted the supplement inventory procedure, which consisted of recording data on the type of multiple vitamin and single supplements used. For the multiple vitamins, the interviewer recorded the exact dose for a subset of nutrients (vitamin C, calcium, selenium). For other nutrients, we imputed the dose in multiple vitamins. The dose of all single supplements was recorded. Labels of the supplements were photocopied and we transcribed the exact nutrient label data for the criterion measure. Spearman correlation coefficients were used to assess precision of nutrient intakes from the simplified inventory compared to the criterion measure.Setting/subjectsData are from 104 adult vitamin supplement users in Washington state.ResultsCorrelation coefficients between nutrient intake estimated from the simplified inventory compared to the criterion measure were high (0.8–1.0) for those nutrients (vitamin C, calcium, selenium) for which the interviewer recorded the exact dose contained in multiple vitamins. However, for nutrients for which imputations were made regarding dose in multiple vitamins, correlation coefficients ranged from good (0.8 for vitamin E) to poor (0.3 for iron).ConclusionsThe simplified inventory is rapid (4–5 min) and practical for large-scale studies. The precision of nutrient estimates using this procedure was variable, although excellent for the subset of nutrients for which the dose was recorded exactly. This study illustrates many of the challenges of collecting high quality supplement data.

Regular use of aspirin is associated with lower colon cancer risk. High inter-individual variation in aspirin metabolism has been attributed to several factors, including sex, concomitant use of other drugs or alcohol, urine pH, ethnicity, and variants in metabolizing enzymes involved in glucuronidation of aspirin metabolites [i.e., UDP glucuronosyltransferases (UGT)]. However, little is known about the impact of other exposures, including dietary factors. Dietary constituents of citrus fruits, cruciferous vegetables and soy have been shown to induce UGT. Higher intakes may alter UGT activity and affect the ratio of aspirin metabolites excreted. We evaluated, cross-sectionally, whether urinary excretion of aspirin [ASA] and its metabolites (salicylic acid [SA], salicyluric acid [SUA], salicyluric phonolic glucuronide [SUPG], salicyl acyl and phenolic acid glucuronides [SAG/SPG]) differed by UGT1A6 genotype and dietary factors. Following an oral dose of 650 mg aspirin, healthy men (N=264) and women (N=264), 20–40 years, collected urine over an 8-h period. Participant exclusion criteria included medical history of gastrointestinal, hepatic or renal disorders, and exposure to non-dietary factors known to influence biotransformation enzymes, e.g., medications, excessive alcohol, and smoking. FFQ data were available for 481 participants. Multiple linear regression was used to determine whether there were differences in aspirin metabolism by UGT1A6 genotype, or daily intake of protein, total fruit or vegetable intake, and soy, citrus and cruciferous vegetable intake, adjusted for body mass index (BMI), age, sex, ethnicity, urine volume and pH, and energy intake. There were statistically significant differences in the ratios of metabolites excreted, (specific metabolite/sum of metabolites), between sexes and between ethnic groups. Men excreted more SUA (P Of the factors evaluated, ethnicity and sex were the greatest, albeit modest, contributors to variability in aspirin metabolism (R2=2−13%), whereas UGT1A6 had no effect. Our results also suggest that diet may influence aspirin metabolism, but the effects do not appear to be via glucuronidation. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B99.

Assessing vitamin and mineral supplement use is important because supplement use per se is an exposure of interest for the risk of several chronic diseases and because supplements contribute a large proportion of total (diet plus supplement) micronutrient intake, another important exposure in epidemiologic research. Unfortunately, little is known about methods for obtaining valid information about supplement use. The authors conducted a validation study in 1996 comparing supplement data collected in a telephone interview and from a self-administered questionnaire with data derived from a detailed, in-person interview and transcription of the labels of supplement bottles (i.e., a gold standard) among adult supplement users in Washington State (n = 104). Spearman correlation coefficients comparing average daily supplemental vitamin and mineral intake from the interview or questionnaire with the gold standard ranged from 0.76 (95% confidence interval 0.66-0.83) for vitamin C to 0.08 (95% confidence interval -0.14 to 0.29) for iron, with a mean of about 0.5. The principal sources of error were inaccurate assumptions about the micronutrient composition of multiple vitamins and respondent confusion regarding the distinction between multiple vitamins and single supplements. These results suggest that commonly used epidemiologic methods of assessing supplement use may incorporate significant amounts of error in estimates of some nutrients.