Search

Higher omega-3 fatty acid blood levels, as assessed by the Omega-3 Index (O3I, erythrocyte eicosapentaenoic [EPA] + docosahexaenoic [DHA] percentage), have been linked with lower risk for cardiovascular disease and total mortality. Because seafood is an excellent source of EPA and DHA, we reasoned that people living on the coast with direct access to fresh seafood might have higher O3I levels than people living inland. Using O3I data originally collected for other purposes and an observational design, we compared the mean O3I from people in Newport, RI, with that of people living from 5 inland US cities (Indianapolis, IN; Charleston, WV; Lexington, KY; Oklahoma City, OK; and Memphis, TN). The Newport samples were collected at free, industry-sponsored health fairs, whereas the inland city samples were collected at free public health screenings sponsored by the Seafood Nutrition Partnership in 2014 through 2015. The mean (standard deviation) O3I in the Newport sample (n = 226) was 5.13% (1.34%) and the mean of the 5 cities (n = 1109) was 4.48% (1.08%) (P.001). An O3I of ≥8% (considered optimal) was found in 3% of the Newport sample and in 1% of the pooled inland cities (P.05). An O3I of ≤4% (considered low) was found in 22% of the Newport sample and in 41% of the pooled inland cities (P.001). These data support our hypothesis, but because only 3% of those in the Newport sample had an O3I8%, even greater seafood intake (or the use of fortified foods or dietary supplements) is needed to attain optimal omega-3 status.

Background RBC long-chain omega-3 (n–3) fatty acid (FA) percentages (of total fatty acids) are associated with lower risk for total mortality, but it is unknown if a suite of FAs could improve risk prediction. Objectives The objective of this study was to compare a combination of RBC FA levels with standard risk factors for cardiovascular disease (CVD) in predicting risk of all-cause mortality. Methods Framingham Offspring Cohort participants without prevalent CVD having RBC FA measurements and relevant baseline clinical covariates (n = 2240) were evaluated during 11 y of follow-up. A forward, stepwise approach was used to systematically evaluate the association of 8 standard risk factors (age, sex, total cholesterol, HDL cholesterol, hypertension treatment, systolic blood pressure, smoking status, and prevalent diabetes) and 28 FA metrics with all-cause mortality. A 10-fold cross-validation process was used to build and validate models adjusted for age and sex. Results Four of 28 FA metrics [14:0, 16:1n–7, 22:0, and omega-3 index (O3I; 20:5n–3 + 22:6n–3)] appeared in ≥5 of the discovery models as significant predictors of all-cause mortality. In age- and sex-adjusted models, a model with 4 FA metrics was at least as good at predicting all-cause mortality as a model including the remaining 6 standard risk factors (C-statistic: 0.778; 95% CI: 0.759, 0.797; compared with C-statistic: 0.777; 95% CI: 0.753, 0.802). A model with 4 FA metrics plus smoking and diabetes (FA + Sm + D) had a higher C-statistic (0.790; 95% CI: 0.770, 0.811) compared with the FA (P

Aims Free fatty acid receptor 4 (Ffar4) is a G-protein-coupled receptor for endogenous medium-/long-chain fatty acids that attenuates metabolic disease and inflammation. However, the function of Ffar4 in the heart is unclear. Given its putative beneficial role, we hypothesized that Ffar4 would protect the heart from pathologic stress. Methods and results In mice lacking Ffar4 (Ffar4KO), we found that Ffar4 is required for an adaptive response to pressure overload induced by transverse aortic constriction (TAC), identifying a novel cardioprotective function for Ffar4. Following TAC, remodelling was worsened in Ffar4KO hearts, with greater hypertrophy and contractile dysfunction. Transcriptome analysis 3-day post-TAC identified transcriptional deficits in genes associated with cytoplasmic phospholipase A2α signalling and oxylipin synthesis and the reduction of oxidative stress in Ffar4KO myocytes. In cultured adult cardiac myocytes, Ffar4 induced the production of the eicosapentaenoic acid (EPA)-derived, pro-resolving oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE). Furthermore, the activation of Ffar4 attenuated cardiac myocyte death from oxidative stress, while 18-HEPE rescued Ffar4KO myocytes. Systemically, Ffar4 maintained pro-resolving oxylipins and attenuated autoxidation basally, and increased pro-inflammatory and pro-resolving oxylipins, including 18-HEPE, in high-density lipoproteins post-TAC. In humans, Ffar4 expression decreased in heart failure, while the signalling-deficient Ffar4 R270H polymorphism correlated with eccentric remodelling in a large clinical cohort paralleling changes observed in Ffar4KO mice post-TAC. Conclusion Our data indicate that Ffar4 in cardiac myocytes responds to endogenous fatty acids, reducing oxidative injury, and protecting the heart from pathologic stress, with significant translational implications for targeting Ffar4 in cardiovascular disease.

Hopelessness is associated with decreased physical activity (PA) and increased adverse events and death in patients with ischemic heart disease (IHD). Rates of PA in patients with IHD continue to be low in both hospital‐based cardiac rehabilitation and home settings. While researchers have investigated strategies to increase PA among patients with IHD, interventions to promote PA specifically in IHD patients who report hopelessness are lacking. We describe the protocol for a NIH‐funded randomized controlled trial designed to establish the effectiveness of a 6‐week intervention (Heart Up!) to promote increased PA in IHD patients who report hopelessness. Participants (n = 225) are randomized to one of three groups: (1) motivational social support (MSS) from a nurse, (2) MSS from a nurse plus significant other support (SOS), or (3) attention control. Aims are to: (1) test the effectiveness of 6 weeks of MSS and MSS with SOS on increasing mean minutes per day of moderate to vigorous PA; (2) determine the effects of change in moderate to vigorous PA on hopelessness; and (3) determine if perceived social support and motivation (exercise self‐regulation) mediate the effects of the intervention on PA. A total of 69 participants have been enrolled to date. The protocol has been consistently and accurately used by research personnel. We address the protocol challenges presented by the COVID‐19 pandemic and steps taken to maintain fidelity to the intervention. Findings from this study could transform care for IHD patients who report hopelessness by promoting self‐management of important PA goals that can contribute to better health outcomes.

Background De novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D). Methods and findings Seventeen cohorts from 12 countries (7 from Europe, 7 from the United States, 1 from Australia, 1 from Taiwan; baseline years = 1970–1973 to 2006–2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages = 52.3–75.5 years; % women = 20.4%–62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the 4 fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41–1.66; p < 0.001) for 16:0, 1.40 (1.33–1.48; p < 0.001) for 16:1n-7, 1.14 (1.05–1.22; p = 0.001) for 18:0, and 1.16 (1.07–1.25; p < 0.001) for 18:1n9. Heterogeneity was seen across cohorts (I2 = 51.1%–73.1% for each fatty acid) but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0 but were attenuated for 18:1n9 (RR = 1.03, 95% confidence interval (CI) = 0.94–1.13). These findings had limitations in potential reverse causation and residual confounding by imprecisely measured or unmeasured factors. Conclusions Concentrations of fatty acids in the DNL were positively associated with T2D incidence. Our findings support further work to investigate a possible role of DNL and individual fatty acids in the development of T2D., Fumiaki Imamura and colleagues investigate the association between concentrations of fatty acid involved in de-novo lipogensis and incidence of Type 2 diabetes., Author summary Why was this study done? De novo lipogenesis (DNL) is a metabolic pathway involved in the endogenous synthesis of specific fatty acids, such as 16:0, 16:1n7, 18:0, and 18:1n9, and it is linked to the pathophysiology of cardiometabolic diseases, including type 2 diabetes (T2D). Circulating or tissue concentrations of these fatty acids have been investigated for the associations with T2D incidence in epidemiological research. However, published studies reported inconsistent associations inconsistently and were subject to publication bias. Summary evidence is not available to date for the associations between these fatty acids and T2D incidence. An integration of available cohort studies would increase statistical power and allow assessment of generalizability, standardization of analytical strategies, and evidence synthesis with the potential publication bias minimized. What did the researchers do and find? As a part of the Fatty Acids and Outcomes Research Consortium (FORCE), we conducted new individual-participant data analyses of 17 cohort studies of a total of 65,225 adults free of T2D at baseline, among whom 15,383 developed incident T2D over up to 20 years of follow-up. The cohort studies analyzed the associations between fatty acids (16:0, 16:1n7, 18:0, and 18:1n9) and the risk of developing T2D with standardized analytic strategy. In pooled analyses, each of the fatty acids was positively associated with a higher risk of developing T2D. The associations were independent of major risk factors for T2D, such as age, sex, race/ethnicity, socioeconomic characteristics, smoking status, physical activity, and obesity. What do these findings mean? The findings provide the first summary evidence to date for the positive relationships of concentrations of the DNL-related fatty acids with a risk of T2D, indicating the strong relevance of DNL and its determinants to the development of T2D. These fatty acids potentially reflect the status of DNL activity, which may be stimulated or suppressed by a combination of carbohydrate intake, alcohol intake, polyunsaturated fatty acid intake, and other lifestyle and clinical factors. Therefore, the current findings indicate the need for investigation into determinants and consequences of elevated concentrations of these fatty acids. Despite several advantages of our individual-level data analysis in this pooling project, the results cannot establish whether elevated concentrations of these fatty acids caused the development of T2D or whether underlying peripheral or hepatic insulin resistance, for example, may elevate both the fatty acid concentrations and the risk of T2D independently.

Undergraduate research experiences (UREs), whether within the context of a mentor-mentee experience or a classroom framework, represent an excellent opportunity to expose students to the independent scholarship model. The high impact of undergraduate research has received recent attention in the context of STEM disciplines. Reflecting a 2017 survey of statistics faculty, this article examines the perceived benefits of UREs, as well as barriers to the incorporation of UREs, specifically within the field of statistics. Viewpoints of students, faculty mentors, and institutions are investigated. Further, the article offers several strategies for leveraging characteristics unique to the field of statistics to overcome barriers and thereby provide greater opportunity for undergraduate statistics students to gain research experience.

Introduction: Hopelessness and rurality are each associated with increased mortality in adults with ischemic heart disease (IHD), yet there is no known research examining hopelessness in rural adults with IHD. Purpose: This pilot study examined state hopelessness in a primarily rural population of adults with IHD living in West-Northcentral United States. Methods: A longitudinal design was used to collect data from 42 participants during their hospitalization with IHD and at a long-term recovery time point. Rural-Urban Commuting Area (RUCA) codes were used to stratify participants by rurality level, with 64% (n=28) categorized as rural. The relationships between changes in hopelessness and other variables were evaluated with both single- and multi-variable linear models. Results: A moderate to severe level of state hopelessness (>1.8 on the State-Trait Hopelessness Scale) was present in 47.6% (n=20) of participants during their hospitalization and persisted over time, with 57.1% (n=24) of participants reporting hopelessness between 200 to 540 days post-hospital discharge (p=0.42). Changes in state hopelessness levels from baseline to follow-up were not significantly associated with demographics, rurality, prior or current exercise, prior depression, depression score (measured by the Patient Health Questionnaire-8), or time to follow-up (p>0.05). However, participation in home-based exercise (measured by the Cardiac Rehabilitation Exercise Participation Tool) was associated with a significant decrease in state hopelessness among those reporting moderate to severe state hopelessness (n=20) at baseline, with an estimated decrease of 0.72 points in hopelessness levels (SE=0.32; p=0.04). There was no association for hospital-based exercise (p=0.91). Conclusions: Hopelessness symptoms were frequent and persistent in a primarily rural sample of adults with IHD, with a decrease in symptoms observed in the moderately to severely hopeless who participated in home-based exercise. Knowledge of hopelessness in rural IHD patients is important for health care professionals in acute care and outpatient settings so at-risk patients can be identified and interventions employed. Future work should replicate these findings in larger samples.

SummaryThe neutrophil-lymphocyte ratio (NLR) is a biomarker of systemic inflammation and measures innate-adaptive immune system balance. The omega-3-index (O3I) measures the amount of EPA+DHA in blood. Both a low O3I and an elevated NLR are associated with increased risk for chronic disease and mortality, including cardiovascular diseases and cancer. Hypothesizing that low O3I may partly contribute to systemic chronic inflammation, we asked if a relationship existed between O3I and NLR in healthy adults (≥18y, n=28,871, 51% female) without inflammation [C-reactive protein (CRP) 6.6%, suggestive of a quiescent, balanced immune system.

Background Rurality and hopelessness are each associated with increased mortality in adults with ischemic heart disease (IHD), yet there is no known research examining rurality as a risk factor for hopelessness in patients with IHD. This study evaluated rurality as a risk factor for state and trait hopelessness in adults hospitalized with IHD in samples drawn from the Great Lakes and Great Plains regions of the United States. Methods and Results A descriptive cross‐sectional design was used. Data were collected from 628 patients hospitalized for IHD in the Great Lakes (n=516) and Great Plains (n=112). Rural–Urban Commuting Area codes were used to stratify study participants by level of rurality. Levels of state hopelessness (measured by the State‐Trait Hopelessness Scale) were higher in rural patients (58.8% versus 48.8%; odds ratio [OR], 1.50; 95% CI, 1.03–2.18), a difference that remained statistically significant after adjusting for demographics, depression severity (measured by the Patient Health Questionnaire–8), and physical functioning (measured by the Duke Activity Status Index; OR, 1.59; 95% CI, 1.06–2.40; P =0.026). There was evidence of an interaction between marital status and rurality on state hopelessness after accounting for covariates ( P =0.02). Nonmarried individuals had an increased prevalence of state hopelessness (nonmarried 72.0% versus married 52.0%) in rural areas ( P =0.03). Conclusions Rural patients with IHD, particularly those who are nonmarried, may be at higher risk for state hopelessness compared with patients with IHD living in urban settings. Understanding rurality differences is important in identifying subgroups most at risk for hopelessness. Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT04498975.

Supplemental Digital Content is available in the text., Background: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the CHREBP locus have separately been linked to HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations. We hypothesized that SSB consumption would modify the association between genetic variants in the CHREBP locus and dyslipidemia. Methods: Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near CHREBP were considered. SSB consumption was estimated from validated questionnaires, and participants were grouped by their estimated intake. Results: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers (β, 2.12 [95% CI, 1.16–3.07] mg/dL per allele; P

Background To develop and evaluate a strategy for reducing the prevalence and impact of waterborne disease, a water quality intervention was developed for Fiji by Give Clean Water, Inc. in partnership with the Fiji Ministry of Health. Residents were provided and trained on how to use a Sawyer® PointONE™ filter, while also being taught proper handwashing techniques. At the time of the filter installation, all households were surveyed inquiring about the prior 2- to 4-week period. Households were measured a second time between 19 and 225 days later (mean = 66 days). Results To date, five economic and health outcomes have been tracked on 503 households to evaluate the efficacy of the intervention. When comparing baseline to follow-up among the 503 households, the 2-week diarrhea prevalence decreased in households from 17.5% at baseline to 1.8% at follow-up. Also, the 2-week prevalence of severe diarrhea decreased per household from 9.7% at baseline to 0.6% at follow-up. Finally, monthly diarrhea-related medical costs reduced by an average of Fijian (FJ) $3.54 per person, and monthly water expenses reduced by FJ $0.63 per person. All estimated values are obtained from general linear and logistic mixed-effect models, which adjusted for location, season, time to follow-up, household size, water source, and respondent changing. Changes in economic and health outcomes from installation to follow-up were statistically significant (p

Importance: Limited empirical research has examined the extent to which cohort-level prevalence of substance use is associated with the onset of drug use and transitioning into greater involvement with drug use. Objective: To use cross-national data to examine time-space variation in cohort-level drug use to assess its associations with onset and transitions across stages of drug use, abuse, dependence, and remission. Design, setting, and participants: The World Health Organization World Mental Health Surveys carried out cross-sectional general population surveys in 25 countries using a consistent research protocol and assessment instrument. Adults from representative household samples were interviewed face-to-face in the community in relation to drug use disorders. The surveys were conducted between 2001 and 2015. Data analysis was performed from July 2017 to July 2018. Main outcomes and measures: Data on timing of onset of lifetime drug use, DSM-IV drug use disorders, and remission from these disorders was assessed using the Composite International Diagnostic Interview. Associations of cohort-level alcohol prevalence and drug use prevalence were examined as factors associated with these transitions. Results: Among the 90 027 respondents (48.1% [SE, 0.2%] men; mean [SE] age, 42.1 [0.1] years), 1 in 4 (24.8% [SE, 0.2%]) reported either illicit drug use or extramedical use of prescription drugs at some point in their lifetime, but with substantial time-space variation in this prevalence. Among users, 9.1% (SE, 0.2%) met lifetime criteria for abuse, and 5.0% (SE, 0.2%) met criteria for dependence. Individuals who used 2 or more drugs had an increased risk of both abuse (odds ratio, 5.17 [95% CI, 4.66-5.73]; P < .001) and dependence (odds ratio, 5.99 [95% CI, 5.02-7.16]; P < .001) and reduced probability of remission from abuse (odds ratio, 0.86 [95% CI, 0.76-0.98]; P = .02). Birth cohort prevalence of drug use was also significantly associated with both initiation and illicit drug use transitions; for example, after controlling for individuals' experience of substance use and demographics, for each additional 10% of an individual's cohort using alcohol, a person's odds of initiating drug use increased by 28% (odds ratio, 1.28 [95% CI, 1.26-1.31]). Each 10% increase in a cohort's use of drug increased individual risk by 12% (1.12 [95% CI, 1.11-1.14]). Conclusions and relevance: Birth cohort substance use is associated with drug use involvement beyond the outcomes of individual histories of alcohol and other drug use. This has important implications for understanding pathways into and out of problematic drug use. The World Health Organization World Mental Health (WMH) Survey Initiative is supported by the United States National Institute of Mental Health (NIMH; R01 MH070884), the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the United States Public Health Service (R13-MH066849, R01-MH069864, and R01 DA016558), the Fogarty International Center (FIRCA R03-TW006481), the Pan American Health Organization, Eli Lilly and Company, Ortho-McNeil Pharmaceutical Inc., GlaxoSmithKline, and Bristol-Myers Squibb. This work was supported by an Australian National Health and Medical Research Council (NHMRC) project grant (no. 1081984). Dr Degenhardt is supported by a NHMRC Senior Principal Research Fellowship (no. 1135991) and NIDA NIH grant R01 DA044170–02. We thank the staff of the WMH Data Collection and Data Analysis Coordination Centres for assistance with instrumentation, fieldwork, and consultation on data analysis. None of the funders had any role in the design, analysis, interpretation of results, or preparation of this paper. The views and opinions expressed in this report are those of the authors and should not be construed to represent the views of the World Health Organization, other sponsoring organizations, agencies, or governments. The 2007 Australian National Survey of Mental Health and Wellbeing is funded by the Australian Government Department of Health and Ageing. The Argentina survey -- Estudio Argentino de Epidemiología en Salud Mental (EASM) -- was supported by a grant from the Argentinian Ministry of Health (Ministerio de Salud de la Nación). The São Paulo Megacity Mental Health Survey is supported by the State of São Paulo Research Foundation (FAPESP) Thematic Project Grant 03/00204–3. The Bulgarian Epidemiological Study of common mental disorders EPIBUL is supported by the Ministry of Health and the National Center for Public Health Protection. The Chinese World Mental Health Survey Initiative is supported by the Pfizer Foundation. The Colombian National Study of Mental Health (NSMH) is supported by the Ministry of Social Protection. The Mental Health Study Medellín – Colombia was carried out and supported jointly by the Center for Excellence on Research in Mental Health (CES University) and the Secretary of Health of Medellín. The ESEMeD project is funded by the European Commission (Contracts QLG5–1999-01042; SANCO 2004123, and EAHC 20081308), (the Piedmont Region (Italy)), Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spain (FIS 00/0028), Ministerio de Ciencia y Tecnología, Spain (SAF 2000–158-CE), Departament de Salut, Generalitat de Catalunya, Spain, DIUE de la Generalitat de Catalunya (2017 SGR 452; 2014 SGR 748), Instituto de Salud Carlos III (CIBER CB06/02/0046, RETICS Degenhardt et al. Page 12 JAMA Psychiatry. Author manuscript; available in PMC 2019 August 05. Author Manuscript Author Manuscript Author Manuscript Author Manuscript RD06/0011 REM-TAP), and other local agencies and by an unrestricted educational grant from GlaxoSmithKline. Implementation of the Iraq Mental Health Survey (IMHS) and data entry were carried out by the staff of the Iraqi MOH and MOP with direct support from the Iraqi IMHS team with funding from both the Japanese and European Funds through United Nations Development Group Iraq Trust Fund (UNDG ITF). The Israel National Health Health Services Research and the National Insurance Institute of Israel. The World Mental Health Japan (WMHJ) Survey is supported by the Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H13- SHOGAI-023, H14-TOKUBETSU-026, H16-KOKORO-013, H25-SEISHIN-IPPAN-006) from the Japan Ministry of Health, Labour and Welfare. The Lebanese Evaluation of the Burden of Ailments and Needs Of the Nation (L.E.B.A.N.O.N.) is supported by the Lebanese Ministry of Public Health, the WHO (Lebanon), National Institute of Health / Fogarty International Center (R03 TW006481–01), anonymous private donations to IDRAAC, Lebanon, and unrestricted grants from, Algorithm, AstraZeneca, Benta, Bella Pharma, Eli Lilly, Glaxo Smith Kline, Lundbeck, Novartis, OmniPharma, Pfizer, Phenicia, Servier, UPO. The Mexican National Comorbidity Survey (MNCS) is supported by The National Institute of Psychiatry Ramon de la Fuente (INPRFMDIES 4280) and by the National Council on Science and Technology (CONACyT-G30544- H), with supplemental support from the Pan American Health Organization (PAHO). Te Rau Hinengaro: The New Zealand Mental Health Survey (NZMHS) is supported by the New Zealand Ministry of Health, Alcohol Advisory Council, and the Health Research Council. The Nigerian Survey of Mental Health and Wellbeing (NSMHW) is supported by the WHO (Geneva), the WHO (Nigeria), and the Federal Ministry of Health, Abuja, Nigeria. The Northern Ireland Study of Mental Health was funded by the Health & Social Care Research & Development Division of the Public Health Agency. The Peruvian World Mental Health Study was funded by the National Institute of Health of the Ministry of Health of Peru. The Polish project Epidemiology of Mental Health and Access to Care –EZOP Project (PL 0256) was supported by Iceland, Liechtenstein and Norway through funding from the EEA Financial Mechanism and the Norwegian Financial Mechanism. EZOP project was co-financed by the Polish Ministry of Health. The South Africa Stress and Health Study (SASH) is supported by the US National Institute of Mental Health (R01-MH059575) and National Institute of Drug Abuse with supplemental funding from the South African Department of Health and the University of Michigan. The Psychiatric Enquiry to General Population in Southeast Spain – Murcia (PEGASUSMurcia) Project has been financed by the Regional Health Authorities of Murcia (Servicio Murciano de Salud and Consejería de Sanidad y Política Social) and Fundación para la Formación e Investigación Sanitarias (FFIS) of Murcia. The Ukraine Comorbid Mental Disorders during Periods of Social Disruption (CMDPSD) study is funded by the US National Institute of Mental Health (RO1-MH61905). The US National Comorbidity Survey Replication (NCS-R) is supported by the National Institute of Mental Health (NIMH; U01-MH60220) with supplemental support from the National Institute of Drug Abuse (NIDA), the Substance Abuse and Mental Health Services Administration (SAMHSA), the Robert Wood Johnson Foundation (RWJF; Grant 044708), and the John W. Alden Trust. Dr Andrade is supported by the Brazilian Council for Scientific and Technological Development (CNPq Grant # 307784/2016–9). Dr Stein is supported by the Medical Research Council of South Africa (MRC). In the past three years, Dr Degenhardt has received investigator-initiated untied educational grants for studies of opioid medications in Australia from Indivior, Mundipharma and Seqirus. Dr Kessler received support for his epidemiological studies from Sanofi Aventis; was a consultant for Johnson & Johnson Wellness and Prevention, Sage Pharmaceuticals, Shire, Takeda; served on an advisory board for the Johnson & Johnson Services Inc. Lake Nona Life Project; and being a co-owner of DataStat, Inc., a market research firm that carries out healthcare research. Dr Demyttenaere has served on advisory boards for Boehringer Ingelheim, Eli Lilly, Lundbeck, Johnson&Johnson, Livanova, Servier, and has research grants from Eli Lilly, foundation ‘ga voor geluk’, Fonds voor Wetenschappelijk Onderzoek Vlaanderen. Dr Stein has received research grants and/or consultancy honoraria from AMBRF, Biocodex, Cipla, Lundbeck, National Responsible Gambling Foundation, Novartis, Servier, and Sun. The views expressed in this report are those of the authors and should not be construed to represent the views or policies of the WHO, other sponsoring organisations, agencies, or governments, and do not necessarily represent the views, official policy, or position of the US. Department of Health and Human Services or any of its affiliated institutions or agencies. Dr Glantz’s role on this study is through his involvement as a Science Officer on U01- MH60220. He had no involvement in the other cited grants.

An Omega-3 Index (O3I; EPA+DHA as a % of erythrocyte total fatty acids) in the desirable range (8%-12%) has been associated with improved heart and brain health.To determine the combination of fish intake and supplement use that is associated with an O3I of8%.Two cross-sectional studies comparing the O3I to EPA+DHA/fish intake.The first study included 28 individuals and assessed their fish and EPA+DHA intake using both a validated triple-pass 24-hr recall dietary survey and a single fish-intake question. The second study used de-identified data from 3,458 adults (84% from US) who self-tested their O3I and answered questions about their fish intake and supplement use.Study 1, chi-squared, one-way ANOVA, and Pearson correlations were computed. In Study 2, multi-variable regression models were used to predict O3I levels from reported fish/supplement intakes.The mean ± SD O3I was 4.87 ± 1.32%, and 5.99 ± 2.29% in the first and second studies, respectively. Both studies showed that for every increase in fish intake category the O3I increased by 0.50-0.65% (p 0.0001). In the second study, about half of the population was taking omega-3 supplements, 32% reported no fish intake and 17% reported eating fish2 times per week. Taking an EPA+DHA supplement increased the O3I by 2.2% (p 0.0001). The odds of having an O3I of ≥8% were 44% in the highest intake group (≥3 servings/week and supplementation) and 2% in the lowest intake group (no fish intake or supplementation); and in those consuming 2 fish meals per week but not taking supplements (as per recommendations), 10%.Current AHA recommendations are unlikely to produce a desirable O3I. Consuming at least 3 fish servings per week plus taking an EPA+DHA supplement markedly increases the likelihood of achieving this target level.

While the promise of electronic medical record and biobank data is large, major questions remain about patient privacy, computational hurdles, and data access. One promising area of recent development is pre-computing non-individually identifiable summary statistics to be made publicly available for exploration and downstream analysis. In this manuscript we demonstrate how to utilize pre-computed linear association statistics between individual genetic variants and phenotypes to infer genetic relationships between products of phenotypes (e.g., ratios; logical combinations of binary phenotypes using ‘and’ and ‘or’) with customized covariate choices. We propose a method to approximate covariate adjusted linear models for products and logical combinations of phenotypes using only pre-computed summary statistics. We evaluate our method’s accuracy through several simulation studies and an application modeling various fatty acid ratios using data from the Framingham Heart Study. These studies show consistent ability to recapitulate analysis results performed on individual level data including maintenance of the Type I error rate, power, and effect size estimates. An implementation of this proposed method is available in the publicly available R package pcsstools.

OBJECTIVE Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis. RESEARCH DESIGN AND METHODS For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed in each cohort following a prespecified protocol, and cohort-specific associations were pooled using inverse variance–weighted meta-analysis. RESULTS A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per interquintile range (difference between the 90th and 10th percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% CIs of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89), and 0.81 (0.75, 0.88), respectively (all P < 0.001). ALA was not associated with T2D (HR 0.97 [95% CI 0.92, 1.02]) per interquintile range. Associations were robust across prespecified subgroups as well as in sensitivity analyses. CONCLUSIONS Higher circulating biomarkers of seafood-derived n-3 fatty acids, including EPA, DPA, DHA, and their sum, were associated with lower risk of T2D in a global consortium of prospective studies. The biomarker of plant-derived ALA was not significantly associated with T2D risk.

HIGHLIGHTS • Nutrition-based interventions to reduce COVID-19 morbidity/mortality are needed. • The Omega-3 Index (O3I) was measured in banked blood from 100 COVID-19 patients. • Risk for death was analyzed as a function of quartiles (Q) of the O3I. • Patients in Q4 (O3I ≥ 5.7%) vs. Q1-3 were 75% less likely to die (p=0.07). • These pilot data suggest that a higher O3I may lower risk for death from COVID-19., Very-long chain omega-3 fatty acids (EPA and DHA) have anti-inflammatory properties that may help reduce morbidity and mortality from COVID-19 infection. We conducted a pilot study in 100 patients to test the hypothesis that RBC EPA+DHA levels (the Omega-3 Index, O3I) would be inversely associated with risk for death by analyzing the O3I in banked blood samples drawn at hospital admission. Fourteen patients died, one of 25 in quartile 4 (Q4) (O3I ≥5.7%) and 13 of 75 in Q1-3. After adjusting for age and sex, the odds ratio for death in patients with an O3I in Q4 vs Q1-3 was 0.25, p=0.07. Although not meeting the classical criteria for statistical significance, this strong trend suggests that a relationship may indeed exist, but more well-powered studies are clearly needed.

Background Lack of sustainable access to clean drinking water continues to be an issue of paramount global importance, leading to millions of preventable deaths annually. Best practices for providing sustainable access to clean drinking water, however, remain unclear. Widespread installation of low-cost, in-home, point of use water filtration systems is a promising strategy. Methods We conducted a prospective, randomized, controlled trial whereby 16 villages were selected and randomly assigned to one of four treatment arms based on the installation location of Sawyer® PointONE™ filters (filter in both home and school; filter in home only; filter in school only; control group). Water samples and self-reported information on diarrhea were collected at multiple times throughout the study. Results Self-reported household prevalence of diarrhea decreased from 25.6 to 9.76% from installation to follow-up (at least 7 days, and up to 200 days post-filter installation). These declines were also observed in diarrhea with economic or educational consequences (diarrhea which led to medical treatment and/or missing school or work) with baseline prevalence of 9.64% declining to 1.57%. Decreases in diarrhea prevalence were observed across age groups. There was no evidence of a loss of efficacy of filters up to 200 days post-filter installation. Installation of filters in schools was not associated with decreases in diarrhea prevalence in school-aged children or family members. Unfiltered water samples both at schools and homes contained potential waterborne bacterial pathogens, dissolved heavy metals and metals associated with particulates. All dissolved metals were detected at levels below World Health Organization action guidelines. Conclusions This controlled trial provides strong evidence of the effectiveness of point-of-use, hollow fiber membrane filters at reducing diarrhea from bacterial sources up to 200 days post-installation when installed in homes. No statistically significant reduction in diarrhea was found when filters were installed in schools. Further research is needed in order to explore filter efficacy and utilization after 200 days post-installation. Trial registration ClinicalTrials.gov, NCT03972618. Registered 3 June 2019—retrospectively registered.

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15–18%, at least p, Associations between of omega-3 fatty acids and mortality are not clear. Here the authors report that, based on a pooled analysis of 17 prospective cohort studies, higher blood omega-3 fatty acid levels correlate with lower risk of all-cause mortality.

Background: The association between long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) and prostate cancer (PC) remains unclear. Methods: We compared incident PC rates as a function of the Omega-3 Index [O3I, erythrocyte eicosapentaenoic and docosahexaenoic acids (EPA + DHA)] in 5607 men (40&ndash, 80 years of age) seen at the Cooper Clinic who were free of PC at baseline. The average follow-up was 5.1 &plusmn, 2.8 years until censoring or reporting a new PC diagnosis. Proportional hazards regression was used to model the linear association between baseline O3I and the age-adjusted time to diagnosis. A meta-analysis of n-3 PUFA biomarker-based studies and incident PC was updated with the present findings. Results: A total of 116 cases of incident PC were identified. When O3I was examined as a continuous variable, the age-adjusted hazard ratio (HR) (95% CI) was 0.98 (0.89, 1.07, p = 0.25) for each 1% increment in the O3I. The updated meta-analysis with 10 biomarker-based studies found no significant relationship between EPA or DHA levels and risk for PC. Conclusions: We find no evidence in this study nor in a meta-analysis of similar studies that consuming n-3 PUFA-rich fish or using fish oil supplements affects the risk of PC.

Gene-based tests of association (e.g., variance components and burden tests) are now common practice for analyses attempting to elucidate the contribution of rare genetic variants on common disease. As sequencing datasets continue to grow in size, the number of variants within each set (e.g., gene) being tested is also continuing to grow. Pathway-based methods have been used to allow for the initial aggregation of gene-based statistical evidence and then the subsequent aggregation of evidence across the pathway. This "multi-set" approach (first gene-based test, followed by pathway-based) lacks thorough exploration in regard to evaluating genotype-phenotype associations in the age of large, sequenced datasets. In particular, we wonder whether there are statistical and biological characteristics that make the multi-set approach optimal vs. simply doing all gene-based tests? In this paper, we provide an intuitive framework for evaluating these questions and use simulated data to affirm us this intuition. A real data application is provided demonstrating how our insights manifest themselves in practice. Ultimately, we find that when initial subsets are biologically informative (e.g., tending to aggregate causal genetic variants within one or more subsets, often genes), multi-set strategies can improve statistical power, with particular gains in cases where causal variants are aggregated in subsets with less variants overall (high proportion of causal variants in the subset). However, we find that there is little advantage when the sets are non-informative (similar proportion of causal variants in the subsets). Our application to real data further demonstrates this intuition. In practice, we recommend wider use of pathway-based methods and further exploration of optimal ways of aggregating variants into subsets based on emerging biological evidence of the genetic architecture of complex disease.

OBJECTIVES: To assess associations between individual and total circulating n-3 fatty acids (FAs) with self-reported sleep duration and difficulty sleeping in the Fatty Acids and Outcome Research Consortium (FORCE). METHODS: De novo harmonized individual-level analyses were performed and pooled in 10 prospective studies (N = 22,717) with data on sleep duration and 7 studies (N = 9997) with data on difficulty initiating sleeping (DIS). Participant ages ranged from 35 to 96 years from 5 countries (Finland, Iceland, Sweden, Singapore, and the United States). Measured circulating FAs included alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), and the sum of EPA, DPA and DHA. FAs were expressed as a % of total FAs. Self-reported sleep duration was categorized as short (8 hrs). DIS was categorized as yes or no (reference). Cross-sectional associations were assessed by multinomial logistic regression in each study with a standardized protocol including definitions for exposures, outcomes and covariates (demographics, health factors and dietary habits). Cohort-specific odds ratios (OR) per quintile (reference: Q1) of FAs were pooled with inverse-variance weighted meta-analysis. RESULTS: In pooled multivariate analysis, we found that participants with higher circulating n-3 FAs (Q5) had a lower risk of short and long sleep duration. For short sleep ORs (95% confidence intervals, CI) for Q5 were 0.87 (0.78–0.98) for EPA, 0.87 (0.77–0.97) for DPA, 0.83 (0.73–0.93) for DHA and 0.83 (0.74–0.93) for the sum of EPA, DPA and DHA, respectively. For long sleep ORs (95% CI) were 0.79 (0.64–0.97) for DHA, and 0.80 (0.65–0.98) for the sum of EPA, DPA and DHA. The only significant association observed for DIS was for Q3 of DHA, OR = 0.77, 95% CI = 0.63–0.96. CONCLUSIONS: In pooled de novo analyses across multiple cohorts, higher levels of n-3 FAs are associated with lower risk of suboptimal sleep (i.e., too little or too much sleep); These novel findings support the need for additional investigation of the temporal nature and causality of these relationships. FUNDING SOURCES: International Life Sciences Institute, North America.

Background: Biomarker levels of very long-chain saturated fatty acids (VLCSFAs) have been found to be favorably associated with cardiovascular risk factors including lower risk of diabetes and reduced triglycerides. Few studies have examined the association between VLCSFAs and coronary heart disease (CHD). Aims: To assess the association of circulating arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) with incident total, fatal, and nonfatal CHD. Methods: We used data from the Fatty Acids and Outcomes Research Consortium consisting of 15 prospective cohorts worldwide which included adults (age≥18 years) who were free of cardiovascular disease and had blood measurements of 20:0, 22:0, and 24:0 at baseline. A study protocol with standardized definitions of exposures, disease outcomes, and covariates was developed, for which each cohort conducted individual participant-level analysis. Cohort-specific associations were pooled using inverse variance-weighted meta-analysis to calculate the overall relative risk (RR) per interquintile range (difference between the 90 th and 10 th percentiles) and 95% confidence interval (CI). Results: Among 33,083 participants, 6,165 cases of total CHD were ascertained. The overall pooled RR and 95% CI were 0.96 (0.89, 1.02) for 20:0, 1.01 (0.92, 1.11) for 22:0, 0.94 (0.86, 1.02) for 24:0, and 0.96 (0.89, 1.04) for 20:0 + 22:0 + 24:0 ( Figure 1 ). However, we noted heterogeneity by lipid compartments, with significant inverse associations for higher 22:0 [0.77 (0.62, 0.96)], 24:0 [0.61 (0.49, 0.77)], and 20:0 + 22:0 + 24:0 [0.73 (0.60, 0.89)] in the total plasma/serum compartment but not in the phospholipid compartment. Similar associations were observed for fatal and nonfatal CHD and when using a random-effects model. Conclusion: Higher circulating VLCSFAs were not associated with total CHD in a global consortium of prospective studies. The finding of an inverse association with total CHD for VLCSFAs in the total plasma/serum compartment warrants further research.

Background: Several recent studies have linked higher blood levels of the long-chain omega-3 polyunsaturated fatty acids (PUFAs) with lower risk of certain disease outcomes, in particular cardiovascular disease (CVD). Limited studies have evaluated associations between n-3 PUFA levels and total and cause-specific mortality. Methods: We meta-analyzed the association of circulating omega-3 PUFAs with total and cause-specific mortality from 15 distinct cohorts in 10 countries following a total of 36,840 individuals (baseline average age 66 yrs; 47% female; median follow-up 13.7 yrs), with 11,635 deaths. Total mortality, and 3 cause-specific mortalities (CVD, cancer or other), were separately predicted by levels of the long chain omega-3 PUFAs eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA) and the Omega-3 index (EPA+DHA), as well as levels of alpha-linolenic acid (ALA, an intermediate chain n-3 PUFA). Using cohort-specific fatty acid levels (range from 10 th to 90 th percentiles), each cohort fit a Cox regression model adjusting for demographics, health related covariates, and n-6 PUFA levels. Cohort-specific estimates were pooled with inverse-variance weighted meta-analysis. Results: Higher levels of EPA, DPA, DHA and the Omega-3 index were all associated with lower all-cause mortality [EPA meta-analysis Hazard Ratio (HR)=0.90 (95% CI: 0.85, 0.95), DPA HR=0.84 (95% CI: 0.77, 0.91), DHA HR=0.84 (95% CI: 0.75, 0.93), Omega-3 index HR = 0.84 (95% CI 0.77, 0.92) (Figure)], as well as for each cause-specific mortality (CVD, cancer and other; HRs from 0.85 to 0.92). ALA showed no association with total-mortality or cause-specific mortality [HRs from 0.97 to 1.00)]. Conclusions: We have found strong evidence of inverse associations between long-chain omega-3 PUFA levels and all-cause and cause-specific mortality. Further controlled studies are needed in order to determine the extent to which these observations represent a causal or coincidental relationships.

International audience; Background: Prevalences of Alcohol Use Disorders (AUDs) and Mental Health Disorders (MHDs) in many individual countries have been reported but there are few cross-national studies. The WHO World Mental Health (WMH) Survey Initiative standardizes methodological factors facilitating comparison of the prevalences and associated factors of AUDs in a large number of countries to identify differences and commonalities.Methods: Lifetime and 12-month prevalence estimates of DSM-IV AUDs, MHDs, and associations were assessed in the 29 WMH surveys using the WHO CIDI 3.0.Results: Prevalence estimates of alcohol use and AUD across countries and WHO regions varied widely. Mean lifetime prevalence of alcohol use in all countries combined was 80%, ranging from 3.8% to 97.1%. Combined average population lifetime and 12-month prevalence of AUDs were 8.6% and 2.2% respectively and 10.7% and 4.4% among non-abstainers. Of individuals with a lifetime AUD, 43.9% had at least one lifetime MHD and 17.9% of respondents with a lifetime MHD had a lifetime AUD. For most comorbidity combinations, the MHD preceded the onset of the AUD. AUD prevalence was much higher for men than women. 15% of all lifetime AUD cases developed before age 18. Higher household income and being older at time of interview, married, and more educated, were associated with a lower risk for lifetime AUD and AUD persistence.Conclusions: Prevalence of alcohol use and AUD is high overall, with large variation worldwide. The WMH surveys corroborate the wide geographic consistency of a number of well-documented clinical and epidemiological findings and patterns.

The neutrophil-lymphocyte ratio (NLR) is a biomarker of systemic inflammation and measures innate-adaptive immune system balance. The omega-3-index (O3I) measures the amount of EPA+DHA in blood. Both a low O3I and an elevated NLR are associated with increased risk for chronic disease and mortality, including cardiovascular diseases and cancer. Hypothesizing that low O3I may partly contribute to systemic chronic inflammation, we asked if a relationship existed between O3I and NLR in healthy adults (≥18 y, n = 28,871, 51% female) without inflammation [C-reactive protein (CRP)3 mg/mL)] who underwent a routine clinical assessment. NLR was inversely associated with O3I before (p 0.0001) and after adjusting for age, sex, BMI, and CRP (p 0.0001). Pearson correlations of other variables with NLR were r = 0.06 (CRP), r = 0.14 (age), and r = 0.01(BMI). In this healthy population, an O3I 6.6% was associated with increasing NLR whereas NLR remained relatively constant (low) when O3I 6.6%, suggestive of a quiescent, balanced immune system.

The popularization of biobanks provides an unprecedented amount of genetic and phenotypic information that can be used to research the relationship between genetics and human health. Despite the opportunities these datasets provide, they also pose many problems associated with computational time and costs, data size and transfer, and privacy and security. The publishing of summary statistics from these biobanks, and the use of them in a variety of downstream statistical analyses, alleviates many of these logistical problems. However, major questions remain about how to use summary statistics in all but the simplest downstream applications. Here, we present a novel approach to utilize basic summary statistics (estimates from single marker regressions on single phenotypes) to evaluate more complex phenotypes using multivariate methods. In particular, we present a covariate-adjusted method for conducting principal component analysis (PCA) utilizing only biobank summary statistics. We validate exact formulas for this method, as well as provide a framework of estimation when specific summary statistics are not available, through simulation. We apply our method to a real data set of fatty acid and genomic data.

Author(s): Arkin, Adam P; Cottingham, Robert W; Henry, Christopher S; Harris, Nomi L; Stevens, Rick L; Maslov, Sergei; Dehal, Paramvir; Ware, Doreen; Perez, Fernando; Canon, Shane; Sneddon, Michael W; Henderson, Matthew L; Riehl, William J; Murphy-Olson, Dan; Chan, Stephen Y; Kamimura, Roy T; Kumari, Sunita; Drake, Meghan M; Brettin, Thomas S; Glass, Elizabeth M; Chivian, Dylan; Gunter, Dan; Weston, David J; Allen, Benjamin H; Baumohl, Jason; Best, Aaron A; Bowen, Ben; Brenner, Steven E; Bun, Christopher C; Chandonia, John-Marc; Chia, Jer-Ming; Colasanti, Ric; Conrad, Neal; Davis, James J; Davison, Brian H; DeJongh, Matthew; Devoid, Scott; Dietrich, Emily; Dubchak, Inna; Edirisinghe, Janaka N; Fang, Gang; Faria, Jose P; Frybarger, Paul M; Gerlach, Wolfgang; Gerstein, Mark; Greiner, Annette; Gurtowski, James; Haun, Holly L; He, Fei; Jain, Rashmi; Joachimiak, Marcin P; Keegan, Kevin P; Kondo, Shinnosuke; Kumar, Vivek; Land, Miriam L; Meyer, Folker; Mills, Marissa; Novichkov, Pavel S; Oh, Taeyun; Olsen, Gary J; Olson, Robert; Parrello, Bruce; Pasternak, Shiran; Pearson, Erik; Poon, Sarah S; Price, Gavin A; Ramakrishnan, Srividya; Ranjan, Priya; Ronald, Pamela C; Schatz, Michael C; Seaver, Samuel MD; Shukla, Maulik; Sutormin, Roman A; Syed, Mustafa H; Thomason, James; Tintle, Nathan L; Wang, Daifeng; Xia, Fangfang; Yoo, Hyunseung; Yoo, Shinjae; Yu, Dantong

The recent simulation-based inference (SBI) movement in algebra-based introductory statistics courses (Stat 101) has provided preliminary evidence of improved student conceptual understanding and retention. However, little is known about whether these positive effects are preferentially distributed across types of students entering the course. We consider how two metrics of Stat 101 student preparation (precourse performance on concept inventory and math ACT score) may or may not be associated with end of course student performance on conceptual inventories. Students across all preparation levels tended to show improvement in Stat 101, but more improvement was observed across all student preparation levels in early versions of a SBI course. Furthermore, students' gains tended to be similar regardless of whether students entered the course with more preparation or less. Recent data on a sample of students using a current version of an SBI course showed similar results, though direct comparison with non-SBI students was not possible. Overall, our analysis provides additional evidence that SBI curricula are effective at improving students' conceptual understanding of statistical ideas postcourse regardless student preparation. Further work is needed to better understand nuances of student improvement based on other student demographics, prior coursework as well as instructor and institutional variables.

OBJECTIVES: Higher omega-3 fatty acid blood levels, as assessed by the Omega-3 Index (O3I, erythrocyte EPA + DHA expressed as a % of total fatty acids), have been linked with lower risk for cardiovascular disease and total mortality. Seafood is an excellent source of EPA and DHA. The purpose of this study was to determine if individuals living in a coastal US city (Newport, RI) with direct access to fresh seafood have higher O3I levels than people living in inland cities. METHODS: Dried blood spot samples were collected from a convenience sample of people attending a sponsored health fair on the boardwalk in Newport, RI between July and August 2019. Attendees interested in obtaining their O3I signed a consent form before testing and then provided a drop of blood for testing. As a comparator inland group, we used published data (Harris et al. PLEFA 2019;148:30–34) from 7 US cities in the “stroke belt” (note, only one of the 7 cities was coastal, Jacksonville, FL). Dried blood samples were analyzed for the O3I by gas chromatography in both settings. RESULTS: The Newport sample included 234 individuals, 50/50 male/female, with a mean (SD) age of 46 (16) years. The 7 cities comparator cohort contained 2177 subjects, with a mean age of 48 (16) years and of those reporting gender, 78% were female. The mean (SD) O3I in Newport was 5.15% (1.37%), whereas in the 7 cities study it was 4.42% (1.12%; P 8% (considered optimal) was found in 3% of the Newport sample compared to 1.2% in the 7 cities study (P = 0.19). CONCLUSIONS: These data support our hypothesis that the O3I is higher in populations living in a coastal city than those living inland. Still, only 3% of individuals with immediate access to fresh seafood had O3I levels in the optimal zone. Given the documented health benefits of having an optimal O3I, increased intakes of EPA and DHA from fish and other dietary sources or supplementation should be recommended. FUNDING SOURCES: RB Health (US) LLC.

BACKGROUND: The roles of omega-3 (n3) fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and low-dose aspirin in the primary prevention of ischemic cardiovascular disease (CVD) are controversial. Since omega-3 (n3) fatty acids and aspirin affect cyclooxygenase activity in platelets, there could be a clinically-relevant effect of aspirin combined with a particular n3 fatty acid level present in each individual. METHODS: RBC EPA+DHA, arachidonic acid (AA) and docosapentaenoic acid (DPA) were measured in 2500 participants without known CVD in the Framingham Heart Study. We then tested for interactions with reported aspirin use (1004 reported use and 1494 did not) on CVD outcomes. The median follow-up was 7.2 years. RESULTS: Having RBC EPA+DHA in the second quintile (4.2–4.9% of total fatty acids) was associated with significantly reduced risk for future CVD events (relative to the first quintile

BackgroundNon-­resolving activation of immune responses is central to the pathogenesis of heart failure (HF). Free fatty acid receptor 4 (Ffar4) is a G-protein coupled receptor (GPR) for medium-and long-chain fatty acids (FA) that regulates metabolism and attenuates inflammation in diabetes and obesity. Here, we tested the hypothesis that Ffar4 functions as a cardioprotective nutrient sensor that resolves inflammation to maintain cardiac homeostasis.MethodsMice with systemic deletion of Ffar4 (Ffar4KO) were subjected to pressure overload by transverse aortic constriction (TAC). Transcriptome analysis of cardiac myocytes was performed three days post-TAC. Additionally, Ffar4-mediated effects on inflammatory oxylipin production in cardiac myocytes and oxylipin composition in plasma lipoproteins were evaluated.ResultsIn Ffar4KO mice, TAC induced more severe remodeling, identifying an entirely novel cardioprotective role for Ffar4 in the heart. Transcriptome analysis 3-days post-TAC indicated a failure to induce cell death and inflammatory genes in Ffar4KO cardiac myocytes, as well as a specific failure to induce cytoplasmic phospholipase A2α (cPLA2α) signaling genes. In cardiac myocytes, Ffar4 signaling through cPLA2α-cytochrome p450 ω/ω-1 hydroxylase induced production of the EPA-derived anti-inflammatory oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE). Systemically, loss of Ffar4 altered oxylipin content in circulating plasma lipoproteins consistent with a loss of anti-inflammatory oxylipins at baseline, and inability to produce both pro-inflammatory and pro-resolving oxylipins following TAC. Finally, we confirmed that Ffar4 is expressed in human heart and down-regulated in HF.ConclusionsOur results identify a novel function for Ffar4 in the heart as a FA nutrient sensor that resolves inflammation to maintain cardiac homeostasis.

OBJECTIVES: To assess prospective association between circulating biomarkers of individual trans fatty acids (TFAs) and incident type 2 diabetes (T2D) in diverse populations. METHODS: A harmonized analysis of individual level data was conducted for TFA biomarkers and incident T2D by pooling ten prospective cohort or nested-case-control studies from five countries (Australia, Germany, Iceland, UK, and USA). Fatty acids (FAs) were measured in plasma phospholipid, red blood cell membrane phospholipid, or total plasma collected between 1990–2008 from 22,711 participants aged ≥18 years without prevalent diabetes. Evaluated TFAs included trans-16:1n-9, sum of trans-18:1 isomers (trans-18:1n6 to trans-18:1n12), sum of trans-18:2 isomers (cis/trans-18:2, trans/cis-18:2, trans/trans-18:2), and individual trans-18:2 isomers. The multivariable-adjusted relative risk or odds ratio was estimated in each cohort by lipid compartments using a pre-specified protocol for definitions of exposures, covariates, and outcomes for statistical analysis. Association estimates were pooled using fixed-effects inverse-variance weighted meta-analysis. RESULTS: During an average maximum of 14 years of follow-up, 2244 cases of incident T2D were identified. Median levels of TFAs across cohorts were 0.05–0.18% total FAs for trans-16:1n-9, 0.09–2.05% for total trans-18:1, 0.10–0.73% for total trans-18:2, and 0.01–0.36% for individual trans-18:2 isomers. In overall pooled analysis, TFAs evaluated per inter-quintile range were not significantly associated with risk of T2D (Figure 1). Findings were consistent when TFAs were assessed categorically in study specific-quintiles, and when associations were pooled within lipid compartment (i.e., phospholipids vs. total plasma). CONCLUSIONS: Overall, biomarker levels of TFAs were not significantly associated with risk of incident T2D in this international pooling project. Findings may be due to mixed TFA sources (industrial vs. ruminant), a general decline in TFA exposure during this period, or no effect of circulating TFA on diabetes. Associations of TFA biomarkers with T2D at higher exposures should be investigated. FUNDING SOURCES: See Table 1. SUPPORTING TABLES, IMAGES AND/OR GRAPHS

Background: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies. Methods: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance–weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available). Results: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88–0.99), 0.78 (0.70–0.85), and 0.88 (0.79–0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88–1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86–0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships. Conclusions: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.

International audience; BACKGROUND:Saturated fatty acids (SFAs) of different chain lengths have unique metabolic and biological effects, and a small number of recent studies suggest that higher circulating concentrations of the very-long-chain SFAs (VLSFAs) arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) are associated with a lower risk of diabetes. Confirmation of these findings in a large and diverse population is needed.OBJECTIVE:We investigated the associations of circulating VLSFAs 20:0, 22:0, and 24:0 with incident type 2 diabetes in prospective studies.METHODS:Twelve studies that are part of the Fatty Acids and Outcomes Research Consortium participated in the analysis. Using Cox or logistic regression within studies and an inverse-variance-weighted meta-analysis across studies, we examined the associations of VLSFAs 20:0, 22:0, and 24:0 with incident diabetes among 51,431 participants.RESULTS:There were 14,276 cases of incident diabetes across participating studies. Higher circulating concentrations of 20:0, 22:0, and 24:0 were each associated with a lower risk of incident diabetes. Pooling across cohorts, the RR (95% CI) for incident diabetes comparing the 90th percentile to the 10th percentile was 0.78 (0.70, 0.87) for 20:0, 0.84 (0.77, 0.91) for 22:0, and 0.75 (0.69, 0.83) for 24:0 after adjustment for demographic, lifestyle, adiposity, and other health factors. Results were fully attenuated in exploratory models that adjusted for circulating 16:0 and triglycerides.CONCLUSIONS:Results from this pooled analysis indicate that higher concentrations of circulating VLSFAs 20:0, 22:0, and 24:0 are each associated with a lower risk of diabetes.

Background: Effects of omega-3 fatty acids on the prevention of type 2 diabetes (T2D) are unclear. Relatively few prospective studies have utilized objective omega-3 biomarkers to assess risk. Aims: To assess the prospective relationship between circulating and tissue levels of alpha linoleic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), with respect to risk of T2D. Methods: A global consortium of 20 prospective cohort studies from 14 nations with assessments of ALA, EPA, DPA, or DHA in adults (age > 18 years) were identified through July 2017 and included in this investigation. A pre-specified analytic protocol, including definitions for exposures, covariate list, disease outcome definitions, and subgroup analyses was developed and followed in new participant-level cohort analysis. Associations were pooled using inverse variance-weighted meta-analysis. Results: Among 65,147 participants, 16,693 incident cases of T2D occurred during follow-up (median follow-up in the cohorts ranged from 2.5 to 21.2 years). In pooled multivariate analysis, per interquintile range (difference between the midpoints of the first and fifth quintile for each fatty acid), EPA, DPA, DHA, and their sum ( Figure 1 ) were associated with 8%, 21%, 18%, and 19% lower risk of T2D, respectively (all P Conclusion: Higher circulating and tissue biomarkers of seafood-derived omega-3 fatty acids, EPA, DPA, and DHA, were associated with lower risk of T2D in a global consortium of prospective studies. Plant-derived ALA was not significantly associated with risk.