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Objective: To examine the association of meat consumption with diabetes risk in the Hawaii component of the Multiethnic Cohort and to assess effect modification by ethnicity.Design: A prospective cohort study. Baseline information on diet and lifestyle was assessed by questionnaire. The cohort was followed up for incident cases of diabetes, which were identified through self-reports, medication questionnaires, or health plan linkages. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals for diabetes associated with quintile of meat consumption.Setting: Hawaii, USA.Subjects: A total of 29,759 Caucasian, 35,244 Japanese-American and 10,509 Native Hawaiian men and women, aged 45-75 years at baseline.Results: During a mean follow-up time of 14 years, 8587 incident diabetes cases were identified. Intake of red meat was positively associated with diabetes risk in men (fifth v. first quintile: HR=1.43; 95% CI 1.29, 1.59) and women (fifth v. first quintile: HR=1.30; 95% CI 1.17, 1.45) in adjusted models. The respective HR for processed red meat intake were 1.57 (95% CI 1.42, 1.75) and 1.45 (95% CI 1.30, 1.62). The association for processed poultry was weaker than for processed red meat, and fresh poultry intake was not associated with diabetes risk. For men only, we observed significant interactions of ethnicity with the red and processed red meat associations, with Caucasians experiencing slightly higher risks than Japanese-Americans.Conclusions: Our findings support the growing evidence that red and processed meat intake increase risk for diabetes irrespective of ethnicity and level of BMI. [ABSTRACT FROM AUTHOR]

Dietary transition in the Arctic is associated with decreased quality of diet, which is of particular concern for women of childbearing age due to the potential impact of maternal nutrition status on the next generation. The study assessed dietary intake and adequacy among Inuit women of childbearing age living in three communities in Nunavut, Canada. A culturally-appropriate quantitative food-frequency questionnaire was administered to 106 Inuit women aged 19-44 years. Sources of key foods, energy and nutrient intakes were determined; dietary adequacy was determined by comparing nutrient intakes with recommendations. The prevalence of overweight/obesity was >70%, and many consumed inadequate dietary fibre, folate, calcium, potassium, magnesium, and vitamin A, D, E, and K. Non-nutrient-dense foods were primary sources of fat, carbohydrate and sugar intakes and contributed >30% of energy. Traditional foods accounted for 21% of energy and >50% of protein and iron intakes. Strategies to improve weight status and nutrient intake are needed among Inuit women in this important life stage. [ABSTRACT FROM AUTHOR]

OBJECTIVE The high diabetes incidence among Japanese Americans and Native Hawaiians cannot be explained by BMI. Therefore, we examined the influence of three dietary patterns of "fat and meat," "vegetables," and "fruit and milk" on diabetes risk in the Hawaii component of the Multiethnic Cohort with 29,759 Caucasians, 35,244 Japanese Americans, and 10,509 Native Hawaiians. RESEARCH DESIGN AND METHODS Subjects aged 45-75 years completed a baseline food frequency questionnaire. After 14 years of follow-up, 8,587 subjects with incident diabetes were identified through self-reports or health plan linkages. Risk was assessed using Cox regression stratified by age and adjusted for ethnicity, BMI, physical activity, education, total energy, smoking, alcohol intake, marital status, and hypertension. RESULTS Fat and meat was significantly associated with diabetes risk in men (hazard ratio 1.40 [95% CI 1.23-1.60], P(trend) < 0.0001) and women (1.22 [1.06-1.40], P(trend) = 0.004) when extreme quintiles were compared. Except in Hawaiian women, the magnitude of the risk was similar across ethnic groups although not always significant. After stratification by BMI, fat and meat remained a predictor of disease primarily among overweight men and among overweight Japanese women. Vegetables lowered diabetes risk in men (0.86 [0.77-0.95], P(trend) = 0.004) but not in women, whereas fruit and milk seemed to be more beneficial in women (0.85 [0.76-0.96], P(trend) = 0.005) than in men (0.92 [0.83-1.02], P(trend) = 0.04). CONCLUSIONS Foods high in meat and fat appear to confer a higher diabetes risk in all ethnic groups, whereas the effects of other dietary patterns vary by sex and ethnicity. [ABSTRACT FROM AUTHOR]

The influence of dietary fiber, magnesium (Mg), and glycemic load (GL) on diabetes was examined in the Hawaii component of the Multiethnic Cohort. The 75,512 Caucasian, Japanese American, and Native Hawaiian participants aged 45-75 y at baseline completed a FFQ. After 14 y of follow-up, 8587 incident diabetes cases were identified through self-reports and health plans. We applied Cox regression stratified for age at cohort entry and adjusted for ethnicity, BMI, physical activity, education, and total energy with further stratifications by sex and ethnicity. When comparing extreme quintiles, total fiber intake was associated with reduced diabetes risk among all men [hazard ratio (HR): 0.75; 95% CI: 0.67, 0.84; P-trend < 0.001) and women (HR: 0.95; 95% CI: 0.85, 1.06; P-trend = 0.05). High intake of grain fiber reduced diabetes risk significantly by 10% in men and women. High vegetable fiber intake lowered risk by 22% in all men but not women. Mg intake reduced risk (HR = 0.77 and 0.84 for men and women, respectively) and, due to its strong correlation with fiber (r = 0.83; P < 0.001), may explain the protective effect of fiber. The top GL quintile was associated with a significantly elevated diabetes incidence in Caucasian men and in all women except Japanese Americans. Overall, several associations were more pronounced in Caucasians than in the other groups. These findings suggest that protection against diabetes can be achieved through food choices after taking into account body weight, but, due to differences in commonly consumed foods, risk estimates may differ by ethnic group. [ABSTRACT FROM AUTHOR]

The combination of lithographic methods with two-dimensional DNA origami self-assembly has led, among others, to the development of photonic crystal cavity arrays and the exploration of sensing nanoarrays where molecular devices are patterned on the sub-micrometre scale. Here we extend this concept to the third dimension by mounting three-dimensional DNA origami onto nanopatterned substrates, followed by silicification to provide hybrid DNA-silica structures exhibiting mechanical and chemical stability and achieving feature sizes in the sub-10-nm regime. Our versatile and scalable method relying on self-assembly at ambient temperatures offers the potential to three-dimensionally position any inorganic and organic components compatible with DNA origami nanoarchitecture, demonstrated here with gold nanoparticles. This way of nanotexturing could provide a route for the low-cost production of complex and three-dimensionally patterned surfaces and integrated devices designed on the molecular level and reaching macroscopic dimensions., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Physical inactivity is an established risk factor for diabetes; however, little is known about this association across ethnic groups with different diabetes risk. Therefore, we evaluated the association between physical activity and diabetes and potential effect modification by ethnicity in the Hawaii component of the Multiethnic Cohort., Methods: Participants, aged 45 to 75 years, were enrolled by completing a questionnaire on demographics, diet, and self-reported weekly hours of strenuous sports, vigorous work, and moderate activity. Among the 74,913 participants (39% Caucasian, 14% Native Hawaiian, 47% Japanese American), 8561 incident diabetes cases were identified by self-report, a medication questionnaire, and through health plan linkages. Cox regression was applied to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) while adjusting for known confounders., Results: Engaging in strenuous sports was inversely related to diabetes risk with HRs (4+ hours/week vs. never) of 0.67 (95%CI: 0.57-0.79) in women and 0.80 (95%CI: 0.72-0.88) in men. In stratified analyses, the inverse association was consistent across ethnic groups. The inverse association of vigorous work with diabetes was limited to men, while beneficial effects of moderate activity were observed only in Caucasians., Conclusions: These findings support a role of high-intensity physical activity and ethnic-specific guidelines in diabetes prevention.

Purpose: Approximately 20% of young adults in the United States are obese, and most of them gain weight between young and middle adulthood. Few studies have examined the association between elevated body mass index (BMI) in early adulthood and mortality or have examined that such effects are independent of changes in weight. To our knowledge, no such study has been conducted in African-American samples., Methods: We used data from 13,941 African-American and white adults who self-reported their weight at the age of 25, and had weight and height measured when they were 45-64 years of age (1987-1989). Date of death was ascertained between 1987 and 2005. Hazard ratios and hazard differences for the effects of BMI at age 25 on all-cause mortality were determined using Cox proportional hazard and additive hazard models, respectively., Results: In the combined ethnic-gender groups, the hazard ratio associated with a 5 kg/m(2) increase in BMI at age 25 was 1.28 (95% confidence interval [CI]: 1.22-1.35), and the hazard difference was 2.75 (2.01-3.50) deaths/1,000 person-years. Associations were observed in all four ethnic-gender groups. Models including weight change from age 25 to age in 1987-1989 resulted in null estimates for BMI in African-American men, whereas associations were maintained or only mildly attenuated in other ethnic-gender groups., Conclusions: Excess weight during young adulthood should be avoided because it contributes to increases in death rates that may be independent of changes in weight experienced in later life. Further study is needed to better understand these associations in African-American men., (Copyright © 2012 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Mammographic density is a strong risk factor for breast cancer, yet the underlying histopathologic correlates are not clear. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play important roles in multiple stages of tumorigenesis. This study examined the association between mammographic density and expression of MMPs 1, 3, 9, and 12 and TIMP3 in benign and malignant breast tissue of 277 women with mainly Caucasian and Japanese ancestry. Tissue microarrays with up to 4 benign and 4 malignant cores per woman were stained immunohistochemically and evaluated. Digitized prediagnostic mammograms were assessed for densities using a computer-assisted method. General linear models adjusted for known confounders were applied to estimate mean densities by staining category. Strong expression of all MMPs was about twice as frequent in malignant as in benign tissue, while TIMP3 expression in stromal tissue was higher in benign than malignant cores. For MMP3 and 9, less than 10% of cores stained positive; thus, they were not further analyzed. None of the markers showed a statistically significant association with breast density in the entire study population and ethnic-specific results were conflicting and difficult to explain. Although not statistically significant, mean density was consistently lower with more extensive TIMP3 expression in stromal and epithelial tissue. These findings indicate that the higher breast cancer risk in women with dense breasts may be influenced by lower TIMP3 expression. However, future investigations into activities and ratios of additional proteases and their inhibitors as well as other pathways, such as inflammation, are needed.

Severe immune dysfunction is an established risk factor of lymphoma, but the role of moderate alterations of immunity is not clear and prospective investigations are needed. We examined several immune-related disorders and medications in relation to non-Hodgkin lymphoma (NHL) in the Multiethnic Cohort. Over 215,000 subjects of African American, Caucasian, Japanese American, Latino and Native Hawaiian ancestry aged 45-75 years completed a questionnaire, including information on medical history, in 1993-1996. After exclusions, we performed Cox regression among 193,050 cohort members including 939 incident NHL cases while adjusting for sex, age, ethnicity, education, body mass index and alcohol intake. Self-reported diabetes was not associated with NHL overall, but was positively associated with risk among Japanese Americans [hazard ratio (HR) = 1.55; 95% confidence interval (CI): 1.10-2.17]. Participants with a history of blood transfusion were at increased risk with HR = 1.39 (95% CI: 1.06-1.84) in men and HR = 1.22 (95% CI: 0.94-1.58) in women, especially for the diffuse large B-cell lymphoma subtype. History of asthma or other allergies was associated with elevated risk only among Latinos (HR = 1.46; 95% CI: 1.07-2.00) who also showed a significant relation between current use of antihistamines and NHL (HR = 1.80; 95% CI: 1.09-2.97). Use of nonsteroidal anti-inflammatory drugs was not associated with NHL. Our findings from this large prospective study support a moderate risk for NHL related to blood transfusions, current long-term antihistamine use and diabetes, but the associations were limited to certain ethnic groups and require further replications., (2009 UICC)

We examined dietary patterns and the risk of non-Hodgkin lymphoma (NHL) in the Multiethnic Cohort, which includes more than 215,000 Caucasians, African-Americans, Japanese-Americans, Native Hawaiians, and Latinos aged 45-75 at baseline. All subjects completed a validated food-frequency questionnaire. After a median follow-up time of 10 years, we identified 939 incident NHL cases through linkages with tumor registries. Three patterns, "Vegetables,""Fruit and Milk," and "Fat and Meat," were analyzed using Cox regression. None of the patterns was significantly associated with the risk of NHL in the total population. However, the Vegetables pattern was inversely related to risk in Caucasian women with a hazard ratio of 0.56 (P(trend) = 0.04), and the Fat and Meat pattern was associated with a fivefold higher risk of follicular lymphoma in men (P(trend) = 0.03). The lack of significant results in men and women indicates a limited role of diet in NHL etiology, but dietary patterns might have ethnic- and subgroup-specific effects on NHL.

Objective: Using the Hawaii component of the Multiethnic Cohort (MEC), we estimated diabetes incidence among Caucasians, Japanese Americans, and Native Hawaiians., Research Design and Methods: After excluding subjects who reported diabetes at baseline or had missing values, 93,860 cohort members were part of this analysis. New case subjects were identified through a follow-up questionnaire (1999-2000), a medication questionnaire (2003-2006), and linkage with two major health plans (2007). We computed age-standardized incidence rates and estimated hazard ratios (HRs) for ethnicity, BMI, education, and combined effects of these variables using Cox regression analysis., Results: After a total follow-up time of 1,119,224 person-years, 11,838 incident diabetic case subjects were identified with an annual incidence rate of 10.4 per 1,000 person-years. Native Hawaiians had the highest rate with 15.5, followed by Japanese Americans with 12.5, and Caucasians with 5.8 per 1,000 person-years; the adjusted HRs were 2.65 for Japanese Americans and 1.93 for Native Hawaiians. BMI was positively related to incidence in all ethnic groups. Compared with the lowest category, the respective HRs for BMIs of 22.0-24.9, 25.0-29.9, and > or =30.0 kg/m(2) were 2.10, 4.12, and 9.48. However, the risk was highest for Japanese Americans and intermediate for Native Hawaiians in each BMI category. Educational achievement showed an inverse association with diabetes risk, but the protective effect was limited to Caucasians., Conclusions: Within this multiethnic population, diabetes incidence was twofold higher in Japanese Americans and Native Hawaiians than in Caucasians. The significant interaction of ethnicity with BMI and education suggests ethnic differences in diabetes etiology.

Background: We explored the association of mammographic density, a breast cancer risk factor, with hormonal and proliferation markers in benign tissue from tumor blocks of pre-and postmenopausal breast cancer cases., Methods: Breast cancer cases were recruited from a case-control study on breast density. Mammographic density was assessed on digitized prediagnostic mammograms using a computer-assisted method. For 279 participants of the original study, we obtained tumor blocks and prepared tissue microarrays (TMA), but benign tissue cores were only available for 159 women. The TMAs were immunostained for estrogen receptor alpha (ERalpha) and beta (ERbeta), progesterone receptor (PR), HER2/neu, Ki-67, and Proliferating Cell Nuclear Antigen (PCNA). We applied general linear models to compute breast density according to marker expression., Results: A substantial proportion of the samples were in the low or no staining categories. None of the results was statistically significant, but women with PR and ERbeta staining had 3.4% and 2.4% higher percent density. The respective values for Caucasians were 5.7% and 11.6% but less in Japanese women (3.5% and -1.1%). Percent density was 3.4% higher in women with any Ki-67 staining and 2.2% in those with positive PCNA staining., Conclusion: This study detected little evidence for an association between mammographic density and expression of steroid receptors and proliferation markers in breast tissue, but it illustrated the problems of locating tumor blocks and benign breast tissue samples for epidemiologic research. Given the suggestive findings, future studies examining estrogen effects in tissue, cell proliferation, and density in the breast may be informative.

This study examined the relation of soy intake with hormonal and proliferation markers in benign and malignant breast tissue using tissue microarrays (TMAs). TMAs with up to 4 malignant and 4 benign tissue samples for 268 breast cancer cases were constructed. Soy intake in early life and in adulthood was assessed by questionnaire. The TMAs were stained for estrogen receptor (ER) alpha, ERbeta, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2/neu), proliferating cell nuclear antigen (PCNA), and Ki-67 using standard immunohistochemical methods. Logistic regression was applied for statistical analysis. A higher percentage of women showed positive marker expression in malignant than in benign tissue. With one exception, HER2/neu, no significant associations between soy intake and pathologic markers were observed. Early life soy intake was associated with lower HER2/neu and PCNA staining of malignant tissue. In benign tissue, early life soy intake showed higher ER and PR expression, but no difference in proliferation markers. The results of this investigation provide some assurance that soy intake does not adversely affect markers of proliferation. TMAs were shown to be a useful tool for epidemiologic research.

Background: Experimental and epidemiologic studies suggest that soy may promote weight loss., Aim of the Study: The goal of this study was to examine the relation of soy intake with body weight over the lifespan of women with Caucasian, Japanese, and Native Hawaiian ancestry., Methods: We assessed the relation between lifetime soy consumption and body mass index (BMI) among 1,418 women in Hawaii. All subjects reported anthropometric measures, regular diet, and soy intake throughout life. The lifetime soy questionnaire was completed again by a subset of 356 women 5 years after study entry and the kappa values indicated moderate agreement. We regressed soy intake on BMI at study entry and at age 21 while controlling for confounding variables, computed least square means, and performed trend tests., Results: Higher soy consumption in adulthood was related to a lower BMI (P=0.02). This association was only significant for Caucasian women and for postmenopausal subjects. The women in the highest category also experienced a smaller annual weight change since age 21 (by 0.05 kg/year) than the low soy intake group (P=0.02). We observed no association between early life soy intake and BMI. High vegetable consumption was significantly associated with a higher soy intake among Caucasian women., Conclusions: In this study, women consuming more soy during adulthood had a lower BMI, but the relation was primarily observed for Caucasian and postmenopausal subjects. This indicates that the association may be due to other nutritional factors and behaviors common in women with high soy intake.

Obesity may increase the risk for non-Hodgkin's lymphoma (NHL) through an inflammatory pathway. We explored the relation of NHL with body size at different times in life within the Multiethnic Cohort that includes African Americans, Caucasians, Japanese, Latinos, and Native Hawaiians. Participants were 45 to 75 years old at recruitment in 1993 to 1996. This analysis included 87,079 men and 105,972 women with 461 male and 378 female NHL cases. We used Cox regression to model NHL risk with age as the time metric while adjusting for age at baseline, ethnicity, education, alcohol intake, and age at first live birth. Body weight and body mass index at age 21 were stronger predictors of NHL risk than anthropometric characteristics at baseline. For men, being in the highest quartile of body mass index and body weight at age 21 conferred a nonsignificant 86% and 41% higher NHL risk, respectively, whereas there was no association at baseline. For women, the risk associated with the highest quartile of weight at age 21 was 1.6 (P(trend) = 0.04), whereas women in the highest quartile at baseline had a nonsignificant risk of 27%. Height was positively related to NHL in men and women. Despite the small numbers, there was some consistency for risk estimates across ethnic groups and weak evidence for an association with NHL subtypes. These findings indicate that weight at age 21 may represent lifetime adiposity better than body weight at cohort entry. Alternatively, weight at age 21 may be more relevant for the etiology of NHL.

We investigate mechanisms of regression of liver hyperplasia which occurs after induction of growth by hepatomitogens and their subsequent withdrawal. We hypothesized that transforming growth factor beta 1 (TGF-beta 1) might be involved in the control of regression. Therefore we studied the effect of this agent on DNA synthesis and death of hepatocytes cultured in vitro. Both the low basal rate of DNA synthesis of untreated cells and its increase by epidermal growth factor (10 ng/ml) were suppressed by TGF-beta 1 at concentrations higher than 0.01-0.1 ng/ml. At the same range of concentrations of TGF-beta 1, the DNA content of the cultures declined significantly and numerous dead cells could be seen in the monolayer. Time course studies showed that TGF-beta 1 (1 ng/ml) decreased DNA content in the cultures linearly to 41 +/- 7% of controls during a period of 48 h. A similar decrease occurred with vital hepatocytes in hematoxylin and eosin stained monolayers. These changes were accompanied by an extensive release of lactate dehydrogenase which began at 20 h and was 70% of the total lactate dehydrogenase content of the cultures at 40-48 h. Little formation of guanidine hydrochloride resistant bodies and no fragmentation of DNA, indicators of apoptotic cell death, were detected after TGF-beta 1 (1 ng/ml) treatment. Time lapse cinematography revealed an active detachment of the cells from the underlying collagen gel. These studies show that inhibition of DNA synthesis by TGF-beta 1 is associated with enhanced cell death in cultured hepatocytes.

Parenchymal liver cells were isolated from human liver pieces of surgical waste as well as from rat livers. DNA synthetic activity was measured after different times in primary culture by [3H]thymidine incorporation and autoradiography. Labeling of control cultures of human hepatocytes at densities between 8,000 and 15,000 cells/cm2 was very low (0.4 to 1.3%). Human recombinant epidermal growth factor increased labeling 2- to 4-fold (P less than 0.01). Treatment with known inducers of liver growth in rats, namely, cyproterone acetate, alpha-hexachlorocyclohexane, nafenopin, phenobarbital, and rifampicin did not increase the number of labeled human liver cells. In some of the experiments, a 24-h exposure to the chemicals of rat or human hepatocytes was followed by a 24-h treatment with epidermal growth factor (EGF). In rat hepatocytes, incorporation rates were significantly increased. Cyproterone acetate and EGF acted in an additive manner, alpha-hexachlorocyclohexane and EGF were clearly overadditive, and phenobarbital had little effect. In human hepatocytes, little alteration in labeling indices was found; in some cases labeling was, rather, found to be lower than in cultures treated with EGF alone. These results show that human hepatocytes cultured in vitro are sensitive to stimulation of DNA synthesis by EGF; they differ from rat hepatocytes in their response to some drugs which show liver growth-promoting activity in rodents.