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1.
J Cell Sci ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005699

RESUMO

Phagocytosis is a dynamic process central to immunity and tissue homeostasis. Current phagocytosis quantitation methods largely rely on indirect or static measurements, such as target clearance or dye uptake, and thus provide limited information about engulfment rates or target processing. Improved kinetic measurements of phagocytosis could provide useful, basic insights in many areas. We present a live-cell, time-lapse, high-content microscopy imaging method based on the detection and quantitation of fluorescent dye "voids" within phagocytes that result from target internalization to quantitate phagocytic events with high temporal resolution. Using this method, we measure target cell densities and antibody concentrations needed for optimal antibody-dependent cellular phagocytosis. We compare void formation and dye uptake methods for phagocytosis detection and examine the connection between target cell engulfment and phagolysosomal processing. We demonstrate how this approach can be used to measure distinct forms of phagocytosis, and changes in macrophage morphology during phagocytosis related to both engulfment and target degradation. Our results provide a high-resolution method for quantitating phagocytosis that provides opportunities to better understand the cellular and molecular regulation of this fundamental biological process.

2.
J Gerontol B Psychol Sci Soc Sci ; 75(3): 674-683, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32059056

RESUMO

OBJECTIVES: While understanding of complex within-person clustering of health behaviors into meaningful profiles of risk is growing, we still know little about whether and how U.S. adults transition from one profile to another as they age. This study assesses patterns of stability and change in profiles of tobacco and alcohol use and body mass index (BMI). METHOD: A nationally representative cohort of U.S. adults 25 years and older was interviewed up to 5 times between 1986 and 2011. Latent transition analysis (LTA) models characterized the most common profiles, patterning of transitions across profiles over follow-up, and assessed whether some were associated with higher mortality risk. RESULTS: We identified 5 profiles: "health promoting" with normal BMI and moderate alcohol consumption; "overweight"; "current smokers"; "obese"; and "nondrinkers". Profile membership was largely stable, with the most common transitions to death or weight gain. "Obese" was the most stable profile, while "smokers" were most likely to transition to another profile. Mortality was most frequent in the "obese" and "nondrinker" profiles. DISCUSSION: Stability was more common than transition, suggesting that adults sort into health behavior profiles relatively early. Women and men were differently distributed across profiles at baseline, but showed broad similarity in transitions.

3.
Menopause ; 27(1): 5-13, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31567864

RESUMO

OBJECTIVE: Although reproductive function is influenced by season, few studies have evaluated seasonal effects on menopausal symptoms. We assessed the impact of season and proximity to the final menstrual period (FMP) on frequency of symptom reporting. METHODS: In all, 955 participants in the Study of Women's Health Across the Nation recorded whether or not they had experienced menopausal symptoms on a monthly menstrual calendar over a 10-year period. We modeled the log-odds of presence of a given symptom each month using a logistic mixed-effects model, assuming a third-order polynomial before the FMP and a different third-order polynomial after the FMP. We assumed sine and cosine functions for month of the year. RESULTS: Five to 10 years before the FMP, ∼20% of women reported hot flashes and night sweats, whereas ∼40% reported trouble sleeping. Prevalence rose ∼4 years before the FMP with a sharp jump in hot flash (∼60%) and night sweats (∼40%) prevalence coincident with the FMP. Peaks in hot flashes and trouble sleeping were observed in July with troughs in January. The peak and trough in night sweats occurred about 1 month earlier. Odds of hot flashes, night sweats, and trouble sleeping were 66%, 50%, and 24% greater, respectively, at the seasonal peak versus the seasonal minimum. CONCLUSION: Menopausal symptoms exhibit seasonal variation associated with the summer and winter equinoxes. Seasonal increases in night sweats precede increases in hot flashes. Prospectively recorded monthly symptom data demonstrate that hot flashes and night sweats increase notably coincident with the FMP. : Video Summary:http://links.lww.com/MENO/A476.

4.
Infect Immun ; 88(2)2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31611280

RESUMO

The pulmonary immune response protects healthy individuals against Pneumocystis pneumonia (PcP). However, the immune response also drives immunopathogenesis in patients who develop severe PcP, and it is generally accepted that optimal treatment requires combination strategies that promote fungal killing and also provide effective immunomodulation. The anti-inflammatory drug sulfasalazine programs macrophages for enhanced Pneumocystis phagocytosis and also suppresses PcP-related immunopathogenesis. Anti-Pneumocystis antibody opsonizes Pneumocystis organisms for greater phagocytosis and may also mask antigens that drive immunopathogenesis. Thus, we hypothesized that combining antibody and sulfasalazine would have the dual benefit of enhancing fungal clearance while dampening immunopathogenesis and allow the rescue of severe PcP. To model a clinically relevant treatment scenario in mice, therapeutic interventions were withheld until clear symptoms of pneumonia were evident. When administered individually, both passive antibody and sulfasalazine improved pulmonary function and enhanced Pneumocystis clearance to similar degrees. However, combination treatment with antibody and sulfasalazine produced a more rapid improvement, with recovery of body weight, a dramatic improvement in pulmonary function, reduced lung inflammation, and the rapid clearance of the Pneumocystis organisms. Accelerated fungal clearance in the combination treatment group was associated with a significant increase in macrophage phagocytosis of Pneumocystis Both passive antibody and sulfasalazine resulted in the suppression of Th1 cytokines and a marked increase in lung macrophages displaying an alternatively activated phenotype, which were enhanced by combination treatment. Our data support the concept that passive antibody and sulfasalazine could be an effective and specific adjunctive therapy for PcP, with the potential to accelerate fungal clearance while attenuating PcP-associated immunopathogenesis.

5.
Methods Mol Biol ; 2041: 345-349, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646502

RESUMO

Extracellular nucleotides are potent damage-associated molecular patterns that shape the immune response to cell stress and tissue damage. These nucleotides are sensed by purinergic receptors and mediate a wide range of cellular effects. Among the best characterized of these effects is cellular migration. While the motility responses of leukocytes to nucleotides can be achieved by microscopic live-cell imaging approaches, such systems are time-consuming and require costly equipment and analysis tools not readily available to all researchers. Transwell migration chambers are a widely used alternative to microscopy due to their relatively low cost and moderate through-put capacity. However, extracellular nucleotides are labile and rapidly degraded in serum-containing cell cultures due to the presence of phosphohydrolases. Thus, evaluating leukocyte migration to nucleotides presents a number of challenges not seen with more stable classes of chemoattractants like proteins and lipids. Here we describe a method to measure leukocyte migration to nucleotides that is cost-effective, rapid and produces robust and reproducible migration of leukocytes using transwell migration chambers.

6.
J Neuroinflammation ; 16(1): 261, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31822279

RESUMO

BACKGROUND: Neuroinflammation is thought to contribute to the pathogenesis of Alzheimer's disease (AD), yet numerous studies have demonstrated a beneficial role for neuroinflammation in amyloid plaque clearance. We have previously shown that sustained expression of IL-1ß in the hippocampus of APP/PS1 mice decreases amyloid plaque burden independent of recruited CCR2+ myeloid cells, suggesting resident microglia as the main phagocytic effectors of IL-1ß-induced plaque clearance. To date, however, the mechanisms of IL-1ß-induced plaque clearance remain poorly understood. METHODS: To determine whether microglia are involved in IL-1ß-induced plaque clearance, APP/PS1 mice induced to express mature human IL-1ß in the hippocampus via adenoviral transduction were treated with the Aß fluorescent probe methoxy-X04 (MX04) and microglial internalization of fibrillar Aß (fAß) was analyzed by flow cytometry and immunohistochemistry. To assess microglial proliferation, APP/PS1 mice transduced with IL-1ß or control were injected intraperitoneally with BrdU and hippocampal tissue was analyzed by flow cytometry. RNAseq analysis was conducted on microglia FACS sorted from the hippocampus of control or IL-1ß-treated APP/PS1 mice. These microglia were also sorted based on MX04 labeling (MX04+ and MX04- microglia). RESULTS: Resident microglia (CD45loCD11b+) constituted > 70% of the MX04+ cells in both Phe- and IL-1ß-treated conditions, and < 15% of MX04+ cells were recruited myeloid cells (CD45hiCD11b+). However, IL-1ß treatment did not augment the percentage of MX04+ microglia nor the quantity of fAß internalized by individual microglia. Instead, IL-1ß increased the total number of MX04+ microglia in the hippocampus due to IL-1ß-induced proliferation. In addition, transcriptomic analyses revealed that IL-1ß treatment was associated with large-scale changes in the expression of genes related to immune responses, proliferation, and cytokine signaling. CONCLUSIONS: These studies show that IL-1ß overexpression early in amyloid pathogenesis induces a change in the microglial gene expression profile and an expansion of microglial cells that facilitates Aß plaque clearance.

7.
Epidemiology ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31809338

RESUMO

Latent class models have become a popular means of summarizing survey questionnaires and other large sets of categorical variables. Often these classes are of primary interest to better understand complex patterns in data. Increasingly, these latent classes are reified into predictors of other outcomes of interests, treating the most likely class as the true class to which an individual belongs even though there is uncertainty in class membership. This uncertainty can be viewed as a form of measurement error in predictors, leading to bias in the estimates of the regression parameters associated with the latent classes. Despite this fact, there is very limited literature treating latent class predictors as measurement error models. Most applications ignore this issue and fit a two-stage model that treats the modal class prediction as truth. Here, we develop two approaches-one likelihood-based, the other Bayesian-to implement a joint model for latent class analysis and outcome prediction. We apply these methods to an analysis of how acculturation behaviors predict depression in South Asian immigrants to the United States. A simulation study gives guidance for when a two-stage model can be safely implemented and when the joint model may be required.

8.
Adv Exp Med Biol ; 1185: 169-173, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31884607

RESUMO

Although the retina resides within the immune-protected ocular environment, inflammatory processes mounted in the eye can lead to retinal damage. Unchecked chronic ocular inflammation leads to retinal damage. Thus, retinal degenerative diseases that result in chronic inflammation accelerate retinal tissue destruction and vision loss. Treatments for chronic retinal inflammation involve corticosteroid administration, which has been associated with glaucoma and cataract formation. Therefore, we must consider novel, alternative treatments. Here, we provide a brief review of our current understanding of chronic innate inflammatory processes in retinal degeneration and the complex role of a putative inflammatory regulator, Caveolin-1 (Cav1). Furthermore, we suggest that the complex role of Cav1 in retinal inflammatory modulation is likely dictated by cell type-specific subcellular localization.


Assuntos
Caveolina 1/metabolismo , Inflamação/patologia , Retina/patologia , Humanos , Degeneração Retiniana/patologia
9.
Am J Prev Med ; 57(6): e203-e210, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31753273

RESUMO

INTRODUCTION: This study sought to empirically evaluate whether the Medicaid expansion under the Affordable Care Act increased smoking cessation among low-income childless adult smokers. METHODS: The effects of the Medicaid expansion on smoking quit attempts and the probability of 30- and 90-day smoking cessation were evaluated using logistic regression and data from the 2010-2011 and 2014-2015 waves of the Tobacco Use Supplement to the Current Population Survey. Using boosted logistic regression, the Tobacco Use Supplement was restricted to an analytic sample composed of childless adults with high probability of being <138% of the federal poverty level. Propensity score weighting was used to compare changes in smoking cessation among a sample of current and past smokers in states that expanded Medicaid with a control sample of current and past smokers in states that did not expand Medicaid with similar sociodemographic characteristics and smoking histories. This study additionally controlled for state socioeconomic trends, welfare policies, and tobacco control policies. Analysis was conducted between January 2018 and June 2019. RESULTS: After weighting by propensity score and adjusting for state socioeconomic trends, welfare policies, and tobacco control policies, the Medicaid expansion was not associated with increases in smoking quit attempts or smoking cessation. CONCLUSIONS: The Medicaid expansion did not appear to improve smoking cessation, despite extending health insurance eligibility to 2.3 million low-income smokers. Greater commitments to reducing barriers to cessation benefits and increasing smoking cessation in state Medicaid programs are needed to reduce smoking in low-income populations.

10.
J Nutr ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31687759

RESUMO

BACKGROUND: The menopause has adverse effects on cardiometabolic profiles that are linked to an increased risk of atherosclerosis in women. A healthy diet during the menopausal transition may counteract the menopause-induced atherosclerotic risk. OBJECTIVE: This prospective cohort study aimed to examine the associations between empirically derived dietary patterns and subclinical carotid atherosclerosis in midlife women. METHODS: A total of 1246 midlife women (average age at baseline: 46.3 y) from the Study of Women's Health Across the Nation who completed dietary assessments and had a carotid ultrasound scan were included. Dietary data were collected at 3 time points, during 1996-1997, 2001-2003, and 2005-2007. Measures of carotid atherosclerosis included common carotid artery intima-media thickness (CCA-IMT), adventitial diameter (AD), and carotid plaque index collected during 2009-2013. Three statistical methods, including principal component analysis (PCA), reduced rank regression (RRR), and partial least squares regression (PLS), were used to identify dietary patterns. RESULTS: A Western dietary pattern was identified from each method and a Prudent dietary pattern from PCA. High adherence to the Western pattern was associated with higher CCA-IMT. Women in the fourth quartile of the Western pattern identified by PCA, RRR, and PLS had 0.042 mm (95% CI: 0.011, 0.073), 0.033 mm (95% CI: 0.0086, 0.057), and 0.049 mm (95% CI: 0.025, 0.074), respectively, larger CCA-IMT than women in the first quartile; these differences correspond to 30%, 24%, and 35% of the sample SD, respectively. The Prudent pattern was not significantly associated with CCA-IMT. No significant associations were found between the identified dietary patterns and AD or carotid plaque. CONCLUSIONS: The positive association between the Western diet and CCA-IMT was robust under different dietary pattern derivation methods. The adoption of a diet low in red meat, processed meat, deep-fried products, and sugar-sweetened beverages among midlife women is associated with a lower future risk of atherosclerosis.

11.
Stroke ; 50(11): 3191-3197, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31526122

RESUMO

Background and Purpose- Stroke is the leading cause of serious, long-term disability in the United States, and the number of stroke survivors is projected to rise. Physical functioning status may be compromised in survivors living in low socioeconomic status environments in comparison to higher socioeconomic status environments. Higher socioeconomic status environments may include benefits in the built environment such as sidewalks, accessible transit, or low traffic volume. Investigation is needed to understand the effects of the socioenvironmental context on trajectories of stroke survivors' physical health-related quality of life (PH-QOL) over time. Methods- Participants from the REGARDS (REasons for Geographic and Racial Differences in Stroke) study enrolled in the ancillary Caring for Adults Recovering from the Effects of Stroke project completed the SF-12 around 6 to 12, 18, 27, and 36 months poststroke. Measures of area-level income, wealth, education, and employment at the census tract level were combined to represent participants' neighborhood socioeconomic status. Linear mixed models were used to predict trajectories of PH-QOL over time, controlling for individual characteristics. Results- The average trajectory of PH-QOL was flat over time. However, women and younger stroke survivors had better trajectories over time than men and older stroke survivors. Higher neighborhood socioeconomic status was significantly associated with better PH-QOL across all time points (ß=1.73; 95% CI, 0.17-3.30), after controlling for demographic variables and severity of stroke. Conclusions- Our findings demonstrate that neighborhood socioeconomic status, sex, and age are associated with the poststroke recovery process. The results of this study suggest the importance of evaluating the environment surrounding stroke survivors when they return to their home communities. Future research should identify specific features of the environment within different socioeconomic status neighborhoods to better understand how they contribute to PH-QOL among stroke survivors.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31480698

RESUMO

(1) Background: Smoking restrictions have been shown to be associated with reduced smoking, but there are a number of gaps in the literature surrounding the relationship between smoke-free policies and cessation, including the extent to which this association may be modified by sociodemographic characteristics. (2) Methods: We analyzed data from the Tobacco Use Supplement to the Current Population Survey, 2003-2015, to explore whether multiple measures of smoking restrictions were associated with cessation across population subgroups. We examined area-based measures of exposure to smoke-free laws, as well as self-reported exposure to workplace smoke-free policies. We used age-stratified, fixed effects logistic regression models to assess the impact of each smoke-free measure on 90-day cessation. Effect modification by gender, education, family income, and race/ethnicity was examined using interaction terms. (3) Results: Coverage by workplace smoke-free laws and self-reported workplace smoke-free policies was associated with higher odds of cessation among respondents ages 40-54. Family income modified the association between smoke-free workplace laws and cessation for women ages 25-39 (the change in the probability of cessation associated with coverage was most pronounced among lower-income women). (4) Conclusions: Heterogeneous associations between policies and cessation suggest that smoke-free policies may have important implications for health equity.


Assuntos
Política Antifumo , Abandono do Hábito de Fumar/legislação & jurisprudência , Adulto , Idoso , Grupos Étnicos , Feminino , Humanos , Renda , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pobreza , Autorrelato , Estados Unidos , Local de Trabalho/legislação & jurisprudência , Adulto Jovem
13.
Muscle Nerve ; 60(5): 513-519, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31397910

RESUMO

BACKGROUND: Our pilot study tested the feasibility and performance of an eye-controlled power wheelchair for amyotrophic lateral sclerosis (ALS) patients. METHODS: In this prospective pilot study, participants drove the wheelchair three times around an indoor course. We assessed the time to complete the course; starting and stopping on command; turning 90, 135, and 180 degrees; time to backup; and obstacle negotiation. Following their use of the wheelchair, subjects were given a questionnaire to assess user experience. RESULTS: Twelve patients participated, and all were able to complete three trials without difficulty. Eight participants completed all of the individual tasks (eg, turning, stopping, etc.) without any errors. Overall performance ratings were high across all participants (4.6/5-excellent). CONCLUSIONS: Our eye-controlled power wheelchair prototype is feasible and has a very favorable user experience. This system has the potential to improve the mobility and independence of ALS patients, and other groups with motor impairments.


Assuntos
Esclerose Amiotrófica Lateral/reabilitação , Desenho de Equipamento , Movimentos Oculares , Satisfação do Paciente , Cadeiras de Rodas , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos
15.
16.
ANZ J Surg ; 89(7-8): 795, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31379079
17.
PLoS One ; 14(7): e0219301, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31291324

RESUMO

BACKGROUND: The potential impacts of beverage intake during the midlife on future subclinical atherosclerosis among women are unclear. The aim of this study was to evaluate the prospective associations between the intakes of eight beverage groups and subclinical carotid atherosclerosis in midlife women. METHODS: Data came from the Study of Women's Health Across the Nation, a multicenter, multiethnic, and prospective cohort study. A total of 1,235 midlife women had measures of subclinical carotid atherosclerosis and repeatedly beverage intake data collected using a validated food frequency questionnaire. Beverages were aggregated into eight groups, including coffee, tea, sugar-sweetened beverages, artificially sweetened beverages, fruit juices, whole milk, milk with lower fat content, and alcoholic beverages. The associations of beverage intake with common carotid artery intima-media thickness (CCA-IMT) and adventitial diameter (CCA-AD) were estimated using linear models; the associations with carotid plaque were estimated using log-binomial models. RESULTS: Coffee intake was associated with CCA-IMT in an inverted J-shaped pattern. After adjusting for covariates, women with >0 to <1 cup/day and 1 to <2 cups/day of coffee intake had a 0.031 mm (95% CI: 0.012, 0.051) and a 0.027 mm (95% CI: 0.005, 0.049) larger CCA-IMT, respectively, than coffee non-drinkers. Women who consumed ≥2 cups/day of coffee did not have significantly different CCA-IMT than non-drinkers. There was an inverse linear association between moderate alcoholic beverages intake and CCA-IMT (P-trend = 0.014). Whole milk intake had inverted U-shaped associations with CCA-IMT and carotid plaque. No significant associations were found between other beverage groups and subclinical atherosclerosis. CONCLUSIONS: In midlife women, occasional coffee intake may be associated with more subclinical atherosclerosis while moderate alcoholic beverages intake may be associated with less subclinical atherosclerosis. Future work should focus on the determination of the optimal beverage intake profile for maximum cardiovascular benefits in midlife women.

18.
J Epidemiol Glob Health ; 9(2): 103-106, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31241867

RESUMO

Depression is a leading cause of disability worldwide and can be diagnosed and treated in primary care clinics. No studies to date have demonstrated the prevalence of depression in rural, primary care settings in Mexico. The objective of this study is to describe the prevalence of visits for depression in primary care settings in one group of rural communities within Chiapas, Mexico. We performed a cross-sectional, retrospective study of depression prevalence in primary care clinics in the Sierra region of Chiapas, Mexico during the calendar year of 2014. We determined the average depression prevalence is 7.9% (6 community clinics, n = 4555). The prevalence of depression in rural Chiapas, Mexico is much higher than the Mexican national average of 4.0-4.5% found in a home-based survey. Further efforts to understand the causes, develop improved mental health services in primary care, and reduce the higher burden of depression in rural communities in Mexico are urgently needed.

19.
Epidemiology ; 30(4): 597-608, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31045611

RESUMO

BACKGROUND: The All of Us Research Program is building a national longitudinal cohort and collecting data from multiple information sources (e.g., biospecimens, electronic health records, and mobile/wearable technologies) to advance precision medicine. Participant-provided information, collected via surveys, will complement and augment these information sources. We report the process used to develop and refine the initial three surveys for this program. METHODS: The All of Us survey development process included: (1) prioritization of domains for scientific needs, (2) examination of existing validated instruments, (3) content creation, (4) evaluation and refinement via cognitive interviews and online testing, (5) content review by key stakeholders, and (6) launch in the All of Us electronic participant portal. All content was translated into Spanish. RESULTS: We conducted cognitive interviews in English and Spanish with 169 participants, and 573 individuals completed online testing. Feedback led to over 40 item content changes. Lessons learned included: (1) validated survey instruments performed well in diverse populations reflective of All of Us; (2) parallel evaluation of multiple languages can ensure optimal survey deployment; (3) recruitment challenges in diverse populations required multiple strategies; and (4) key stakeholders improved integration of surveys into larger Program context. CONCLUSIONS: This efficient, iterative process led to successful testing, refinement, and launch of three All of Us surveys. Reuse of All of Us surveys, available at http://researchallofus.org, may facilitate large consortia targeting diverse populations in English and Spanish to capture participant-provided information to supplement other data, such as genetic, physical measurements, or data from electronic health records.

20.
Diabetes Care ; 42(7): 1290-1296, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31010876

RESUMO

OBJECTIVE: To determine the prevalence and prognostic significance of unrecognized myocardial infarction (MI) by delayed-enhancement MRI (DE-MRI) in asymptomatic patients with diabetes. RESEARCH DESIGN AND METHODS: In this prospective, two-center study of asymptomatic patients without known cardiac disease (n = 120), two prespecified cohorts underwent a research MRI: 1) a high-risk group with type 1 diabetes and chronic renal insufficiency (n = 50) and 2) an average-risk group with type 2 diabetes (n = 70). The primary end point was a composite of all-cause mortality and clinical MI. RESULTS: Overall, the prevalence of unrecognized MI was 19% by DE-MRI (28% high-risk group and 13% average-risk group) and 5% by electrocardiography. During up to 5 years of follow-up with a total of 460 patient-years of follow-up, the rate of death/MI was markedly higher in patients with diabetes with (vs. without) unrecognized MI (all 44% vs. 7%, high-risk group 43% vs. 6%, and average-risk group 44% vs. 8%; all P < 0.01). After adjustment for Framingham risk score, left ventricular ejection fraction, and diabetes type, the presence of unrecognized MI by DE-MRI conferred an eightfold increase in risk of death/MI (95% CI 3.0-21.1, P < 0.0001). Addition of unrecognized MI to clinical indices significantly improved model discrimination for adverse events (integrated discrimination improvement = 0.156, P = 0.001). CONCLUSIONS: Unrecognized MI is prevalent in asymptomatic patients with diabetes without a history of cardiac disease and confers a markedly increased risk of death and clinical MI.

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