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1.  The Association of Whole Grain Consumption with Incident Type 2 Diabetes: The Women's Health Initiative Observational Study 
Annals of epidemiology  2013;23(6):321-327.
PURPOSE
Whole grains may offer protection from diabetes by decreasing energy intake, preventing weight gain, and direct effects on insulin resistance. This study examined associations of whole and refined grains with incident type 2 diabetes (T2D) ascertained by self-reported medication use in a cohort of post-menopausal women.
METHODS
72,215 women free of diabetes at baseline from the Women's Health Initiative Observational Study were included. Whole grain consumption was categorized as 0, <0.5, 0.5-1.0, 1.0-<1.5, 1.5-<2.0, and ≥2.0 servings/day. Proportional hazards regression was performed to estimate hazard ratios (HR) and 95% confidence intervals adjusting for potential confounders.
RESULTS
There were 3,465 cases of incident T2D over median 7.9 years follow-up. Adjusted for age and energy intake/day, successively increasing categories of whole grain consumption were associated with statistically significant reduced risk of incident T2D (HRs= 1.00, 0.83, 0.73, 0.69, 0.61, 0.57, p for trend <0.0001). Results were attenuated after adjustment for confounders and other dietary components. Non-smokers and those who maintained their weight within 5 pounds had a greater reduced risk of T2D with higher consumption of whole grains than smokers and women who gained more weight.
CONCLUSIONS
This large, prospective study found an inverse, dose-response relationship between whole grain consumption and incident T2D in postmenopausal women.
doi:10.1016/j.annepidem.2013.03.010
PMCID: PMC3662533  PMID: 23608304
type 2 diabetes; whole grains; cohort studies
2.  The relationship of area-level sociodemographic characteristics, household composition and individual-level socioeconomic status on walking behavior among adults 
Understanding the contextual factors associated with why adults walk is important for those interested in increasing walking as a mode of transportation and leisure. This paper investigates the relationships between neighborhood-level sociodemographic context, individual level sociodemographic characteristics and walking for leisure and transport. Data from two community-based studies of adults (n=550) were used to determine the association between the area-sociodemographic environment (ASDE), calculated from U.S. Census variables, and individual-level SES as potential correlates of walking behavior. Descriptive statistics, mean comparisons and Pearson’s correlations coefficients were used to assess bivariate relationships. Generalized estimating equations were used to model the relationship between ASDE, as quartiles, and walking behavior. Adjusted models suggest adults engage in more minutes of walking for transportation and less walking for leisure in the most disadvantaged compared to the least disadvantaged neighborhoods but adding individual level demographics and SES eliminated the significant results. However, when models were stratified for free or reduced cost lunch, of those with children who qualified for free or reduced lunch, those who lived in the wealthiest neighborhoods engaged in 10.7 minutes less of total walking per day compared to those living in the most challenged neighborhoods (p<0.001). Strategies to increase walking for transportation or leisure need to take account of individual level socioeconomic factors in addition to area-level measures.
doi:10.1016/j.tra.2013.01.006
PMCID: PMC3667602  PMID: 23729994
Adult; walking; area deprivation; socioeconomic status; active transportation; policy
3.  Severe obesity in children: prevalence, persistence and relation to hypertension 
Background
Newer approaches for classifying gradations of pediatric obesity by level of body mass index (BMI) percentage above the 95th percentile have recently been recommended in the management and tracking of obese children. Examining the prevalence and persistence of severe obesity using such methods along with the associations with other cardiovascular risk factors such as hypertension is important for characterizing the clinical significance of severe obesity classification methods.
Methods
This retrospective study was conducted in an integrated healthcare delivery system to characterize obesity and obesity severity in children and adolescents by level of body mass index (BMI) percentage above the 95th BMI percentile, to examine tracking of obesity status over 2–3 years, and to examine associations with blood pressure. Moderate obesity was defined by BMI 100-119% of the 95th percentile and severe obesity by BMI ≥120% × 95th percentile. Hypertension was defined by 3 consecutive blood pressures ≥95th percentile (for age, sex and height) on separate days and was examined in association with obesity severity.
Results
Among 117,618 children aged 6–17 years with measured blood pressure and BMI at a well-child visit during 2007–2010, the prevalence of obesity was 17.9% overall and was highest among Hispanics (28.9%) and blacks (20.5%) for boys, and blacks (23.3%) and Hispanics (21.5%) for girls. Severe obesity prevalence was 5.6% overall and was highest in 12–17 year old Hispanic boys (10.6%) and black girls (9.5%). Subsequent BMI obtained 2–3 years later also demonstrated strong tracking of severe obesity. Stratification of BMI by percentage above the 95th BMI percentile was associated with a graded increase in the risk of hypertension, with severe obesity contributing to a 2.7-fold greater odds of hypertension compared to moderate obesity.
Conclusion
Severe obesity was found in 5.6% of this community-based pediatric population, varied by gender and race/ethnicity (highest among Hispanics and blacks) and showed strong evidence for persistence over several years. Increasing gradation of obesity was associated with higher risk for hypertension, with a nearly three-fold increased risk when comparing severe to moderate obesity, underscoring the heightened health risk associated with severe obesity in children and adolescents.
doi:10.1186/1687-9856-2014-3
PMCID: PMC3976673  PMID: 24580759
Obesity; Children; Adolescents; Blood pressure
4.  Benefits of Early Hypertension Control on Cardiovascular Outcomes in Patients With Diabetes 
Diabetes Care  2013;36(2):322-327.
OBJECTIVE
To assess the impact of early hypertension (HT) control on occurrence of subsequent major cardiovascular events in those with diabetes and recent-onset HT.
RESEARCH DESIGN AND METHODS
Study subjects were 15,665 adults with diabetes but no diagnosed coronary or cerebrovascular disease at baseline who met standard criteria for new-onset HT. Poisson regression models assessed whether adequate blood pressure control within 1 year of HT onset predicts subsequent occurrence of major cardiovascular events with and without adjustment for baseline Framingham Risk Score (FRS) and other covariates.
RESULTS
Mean age was 51.5 years, and mean blood pressure at HT onset was 136.8/80.8 mmHg. In the year after HT onset, mean blood pressure decreased to 131.4/78.0 mmHg and was <130/80 mmHg in 32.9% of subjects and <140/90 mmHg in 80.2%. Over a mean follow-up of 3.2 years, age-adjusted rates of major cardiovascular events in those with mean 1-year blood pressure measurements of <130/80, 130–139/80–89, and ≥140/90 mmHg were 5.10, 4.27, and 6.94 events/1,000 person-years, respectively (P = 0.004). In FRS-adjusted models, rates of major cardiovascular events were significantly higher in those with mean blood pressure ≥140/90 mmHg in the first year after HT onset (rate ratio 1.30 [95% CI 1.01–1.169]; P = 0.04).
CONCLUSIONS
Failure to adequately control BP within 1 year of HT onset significantly increased the likelihood of major cardiovascular events within 3 years. Prompt control of new-onset HT in patients with diabetes may provide important short-term clinical benefits.
doi:10.2337/dc12-0284
PMCID: PMC3554277  PMID: 22966094
5.  Prehypertension and Hypertension in Community-Based Pediatric Practice 
Pediatrics  2013;131(2):e415-e424.
OBJECTIVE:
To examine the prevalence of prehypertension and hypertension among children receiving well-child care in community-based practices.
METHODS:
Children aged 3 to 17 years with measurements of height, weight, and blood pressure (BP) obtained at an initial (index) well-child visit between July 2007 and December 2009 were included in this retrospective cohort study across 3 large, integrated health care delivery systems. Index BP classification was based on the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents: normal BP, <90th percentile; prehypertension, 90th to 94th percentile; hypertension, 3 BP measurements ≥95th percentile (index and 2 subsequent consecutive visits).
RESULTS:
The cohort included 199 513 children (24.3% aged 3–5 years, 34.5% aged 6–11 years, and 41.2% aged 12–17 years) with substantial racial/ethnic diversity (35.9% white, 7.8% black, 17.6% Hispanic, 11.7% Asian/Pacific Islander, and 27.0% other/unknown race). At the index visit, 81.9% of participants were normotensive, 12.7% had prehypertension, and 5.4% had a BP in the hypertension range (≥95th percentile). Of the 10 848 children with an index hypertensive BP level, 3.8% of those with a follow-up BP measurement had confirmed hypertension (estimated 0.3% prevalence). Increasing age and BMI were significantly associated with prehypertension and confirmed hypertension (P < .001 for trend). Among racial/ethnic groups, blacks and Asians had the highest prevalence of hypertension.
CONCLUSIONS:
The prevalence of hypertension in this community-based study is lower than previously reported from school-based studies. With the size and diversity of this cohort, these results suggest the prevalence of hypertension in children may actually be lower than previously reported.
doi:10.1542/peds.2012-1292
PMCID: PMC3557407  PMID: 23359583
hypertension; prehypertension; pediatrics; blood pressure; databases; health information technology; electronic health records
6.  Deletion and Gene Expression Analyses Define the Paxilline Biosynthetic Gene Cluster in Penicillium paxilli 
Toxins  2013;5(8):1422-1446.
The indole-diterpene paxilline is an abundant secondary metabolite synthesized by Penicillium paxilli. In total, 21 genes have been identified at the PAX locus of which six have been previously confirmed to have a functional role in paxilline biosynthesis. A combination of bioinformatics, gene expression and targeted gene replacement analyses were used to define the boundaries of the PAX gene cluster. Targeted gene replacement identified seven genes, paxG, paxA, paxM, paxB, paxC, paxP and paxQ that were all required for paxilline production, with one additional gene, paxD, required for regular prenylation of the indole ring post paxilline synthesis. The two putative transcription factors, PP104 and PP105, were not co-regulated with the pax genes and based on targeted gene replacement, including the double knockout, did not have a role in paxilline production. The relationship of indole dimethylallyl transferases involved in prenylation of indole-diterpenes such as paxilline or lolitrem B, can be found as two disparate clades, not supported by prenylation type (e.g., regular or reverse). This paper provides insight into the P. paxilli indole-diterpene locus and reviews the recent advances identified in paxilline biosynthesis.
doi:10.3390/toxins5081422
PMCID: PMC3760044  PMID: 23949005
indole-diterpene; paxilline; prenylation
7.  Obesogenic Family Types Identified through Latent Profile Analysis 
Background
Obesity may cluster in families due to shared physical and social environments.
Purpose
This study aims to identify family typologies of obesity risk based on family environments.
Methods
Using 2007–2008 data from 706 parent/youth dyads in Minnesota, we applied latent profile analysis and general linear models to evaluate associations between family typologies and body mass index (BMI) of youth and parents.
Results
Three typologies described most families with 18.8% “Unenriched/Obesogenic,” 16.9% “Risky Consumer,” and 64.3% “Healthy Consumer/Salutogenic.” After adjustment for demographic and socioeconomic factors, parent BMI and youth BMI Z-scores were higher in unenriched/obesogenic families (BMI difference=2.7, p<0.01 and BMI Z-score difference=0.51, p<0.01, respectively) relative to the healthy consumer/salutogenic typology. In contrast, parent BMI and youth BMI Z-scores were similar in the risky consumer families relative to those in healthy consumer/salutogenic type.
Conclusions
We can identify family types differing in obesity risks with implications for public health interventions.
doi:10.1007/s12160-011-9286-9
PMCID: PMC3184384  PMID: 21638195
Latent profile analysis; Family types; Youth; Obesogenic environment
8.  Accuracy of Heart Disease Prevalence Estimated from Claims Data Compared With an Electronic Health Record 
Introduction
We developed a decision support tool that can guide the development of heart disease prevention programs to focus on the interventions that have the most potential to benefit populations. To use it, however, users need to know the prevalence of heart disease in the population that they wish to help. We sought to determine the accuracy with which the prevalence of heart disease can be estimated from health care claims data.
Methods
We compared estimates of disease prevalence based on insurance claims to estimates derived from manual health records in a stratified random sample of 480 patients aged 30 years or older who were enrolled at any time from August 1, 2007, through July 31, 2008 (N = 474,089) in HealthPartners insurance and had a HealthPartners Medical Group electronic record. We compared randomly selected development and validation samples to a subsample that was also enrolled on August 1, 2005 (n = 272,348). We also compared the records of patients who had a gap in enrollment of more than 31 days with those who did not, and compared patients who had no visits, only 1 visit, or 2 or more visits more than 31 days apart for heart disease.
Results
Agreement between claims data and manual review was best in both the development and the validation samples (Cohen’s κ, 0.92, 95% confidence interval [CI], 0.87–0.97; and Cohen’s κ, 0.94, 95% CI, 0.89–0.98, respectively) when patients with only 1 visit were considered to have heart disease.
Conclusion
In this population, prevalence of heart disease can be estimated from claims data with acceptable accuracy.
doi:10.5888/pcd9.120009
PMCID: PMC3475521  PMID: 22916996
9.  Expression, Purification, and Characterisation of Dehydroquinate Synthase from Pyrococcus furiosus 
Enzyme Research  2011;2011:134893.
Dehydroquinate synthase (DHQS) catalyses the second step of the shikimate pathway to aromatic compounds. DHQS from the archaeal hyperthermophile Pyrococcus furiosus was insoluble when expressed in Escherichia coli but was partially solubilised when KCl was included in the cell lysis buffer. A purification procedure was developed, involving lysis by sonication at 30°C followed by a heat treatment at 70°C and anion exchange chromatography. Purified recombinant P. furiosus DHQS is a dimer with a subunit Mr of 37,397 (determined by electrospray ionisation mass spectrometry) and is active over broad pH and temperature ranges. The kinetic parameters are KM (3-deoxy-D-arabino-heptulosonate 7-phosphate) 3.7 μM and kcat 3.0 sec−1 at 60°C and pH 6.8. EDTA inactivates the enzyme, and enzyme activity is restored by several divalent metal ions including (in order of decreasing effectiveness) Cd2+, Co2+, Zn2+, and Mn2+. High activity of a DHQS in the presence of Cd2+ has not been reported for enzymes from other sources, and may be related to the bioavailability of Cd2+ for P. furiosus. This study is the first biochemical characterisation of a DHQS from a thermophilic source. Furthermore, the characterisation of this hyperthermophilic enzyme was carried out at elevated temperatures using an enzyme-coupled assay.
doi:10.4061/2011/134893
PMCID: PMC3092513  PMID: 21603259
10.  Authors' response 
doi:10.3399/bjgp09X420987
PMCID: PMC2688050
11.  Association of Hip Circumference With Incident Diabetes and Coronary Heart Disease 
American Journal of Epidemiology  2009;169(7):837-847.
When waist circumference is taken into account, larger hip circumference is associated with reduced risk factors for diabetes and cardiovascular disease. The authors investigated the prospective association of hip circumference with type 2 diabetes and coronary heart disease (CHD) incidence in a biracial cohort of men and women in 4 US communities. A total of 10,767 participants from the Atherosclerosis Risk in Communities (ARIC) study were followed from 1987 to 1998. Hip and waist circumferences and body mass index (BMI) were modeled separately and mutually in association with incident diabetes and CHD by using proportional hazards regression. After adjustment for age, race, sex, and clinical center, hip circumference was positively associated with incident diabetes. However, after further controlling for waist circumference, BMI, and confounding variables, successive quintiles of hip circumference were associated with a statistically significant reduced hazard of incident diabetes (hazard ratios = 1.00, 0.79, 0.60, 0.44, 0.41). Similarly, successive quintiles of hip circumference were associated with a statistically significant reduced hazard of CHD after controlling for waist circumference, BMI, and confounding variables (hazard ratios = 1.00, 0.92, 0.75, 0.63, 0.50). Although excess adiposity is a general risk factor for diabetes and CHD, for a given BMI and waist circumference, greater hip circumference appears to lessen the risk of diabetes and CHD.
doi:10.1093/aje/kwn395
PMCID: PMC2727216  PMID: 19224980
adiposity; anthropometry; coronary disease; diabetes mellitus
12.  Use of evidence in hypertension guidelines: should we measure in both arms? 
For at least 25 years, hypertension guidelines have suggested measuring blood pressure in both arms, but GPs' acceptance of this is low. Current and past versions of major guidelines were identified to review and assess the degree to which they provided justification, evidence, and a description of dual-arm measurement techniques. It is suggested that if guidelines better justified recommendations and cited primary literature to support claims, a greater percentage of practitioners might accept and adhere to such guidance.
doi:10.3399/bjgp09X395012
PMCID: PMC2648937  PMID: 19275828
blood pressure; guidelines; hypertension
13.  The association of hip circumference with incident hip fracture in a cohort of postmenopausal women: The Iowa Women's Health Study 
Annals of epidemiology  2008;18(11):836-841.
PURPOSE
As the mean age of the US population increases, the public health burden of osteoporotic fractures is expected to increase. This study prospectively examined the independent association of hip circumference with hip fracture.
METHODS
The prospective association of hip circumference and hip fracture was examined in a cohort of 30,652 postmenopausal women.
RESULTS
Compared to the lowest quintile, successive quintiles of hip circumference were associated with a reduced hazard of hip fracture over 18 years of follow-up (HRs = 1.00, 0.78, 0.74, 0.76, 0.69, p for trend = 0.0015) after adjusting for age. Controlling for waist, this association persisted (HRs = 1.00, 0.78, 0.73, 0.72, 0.54, p for trend = 0.0006). Additionally controlling for BMI, the association of hip fracture with hip circumference was attenuated to the null while the association with successive quintiles of BMI remained significant and inverse (HRs = 1.00, 0.55, 0.45, 0.40, 0.35, p for trend <0.0001).
CONCLUSIONS
Although hip circumference has a strong inverse association with risk of hip fracture, this association was not independent of BMI. These results suggest that in the prediction of hip fracture risk, overall body size may be more important than body composition of the femoral-gluteal region.
doi:10.1016/j.annepidem.2008.07.007
PMCID: PMC2577069  PMID: 18940632
anthropometry; hip fractures; cohort studies
14.  Degree of Concordance with DASH Diet Guidelines and Incidence of Hypertension and Fatal Cardiovascular Disease 
American journal of hypertension  2007;20(3):225-232.
Background
Guidelines to prevent and treat hypertension advocate the Dietary Approaches to Stop Hypertension (DASH) diet.
Methods
We studied whether a greater concordance with the DASH diet is associated with reduced incidence of hypertension (self-reported) and mortality from cardiovascular disease in 20,993 women initially aged 55–69. We created a DASH diet concordance score using food frequency data in 1986 and followed the women for events through 2002.
Results
No woman had perfect concordance with the DASH diet. Adjusted for age and energy intake, incidence of hypertension was inversely associated with the degree of concordance with the DASH diet, with hazard ratios across quintiles of 1.0, 0.91, 0.95, 0.99, and 0.87 (p trend = 0.02). There also were inverse, but not monotonic, associations between better DASH diet concordance and mortality from coronary heart disease, stroke, and all CVD. However, after adjustment for other risk factors, there was little evidence that any endpoint was associated with the DASH diet score.
Conclusions
Our results suggest that greater concordance with DASH guidelines did not have an independent long-term association with hypertension or cardiovascular mortality in this cohort. This implies that very high concordance, as achieved in the DASH trials, may be necessary to achieve the benefits of the DASH diet.
doi:10.1016/j.amjhyper.2006.09.003
PMCID: PMC2020811  PMID: 17324731
Diet; hypertension; coronary disease; cerebrovascular accident
15.  Crystallization and preliminary X-ray crystallographic analysis of 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase from Mycobacterium tuberculosis  
Crystals of 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase from M. tuberculosis have been grown and a native data set has been collected to a maximum resolution of 2.5 Å.
The enzymes of the shikimate pathway are attractive targets for new-generation antimicrobial agents. The first step of this pathway is catalysed by 3-deoxy-d-­arabino-heptulosonate-7-phosphate (DAH7P) synthase and involves the condensation of phosphoenolpyruvate (PEP) and erythrose 4-phosphate (E4P) to form DAH7P. DAH7P synthases have been classified into two apparently evolutionarily unrelated types and whereas structural data have been obtained for the type I DAH7P synthases, no structural information is available for their type II counterparts. The type II DAH7P synthase from Mycobacterium tuberculosis was co-expressed as native and selenomethionine-substituted protein with the Escherichia coli chaperonins GroEL and GroES in E. coli, purified and crystallized. Native crystals of M. tuberculosis DAH7P synthase belong to space group P3121 or P3221 and diffract to 2.5 Å, with unit-cell parameters a = b = 203.61, c = 66.39 Å. There are either two or three molecules in the asymmetric unit. Multiwavelength anomalous diffraction (MAD) phasing using selenomethionine-substituted protein is currently under way.
doi:10.1107/S1744309105007931
PMCID: PMC1952427  PMID: 16511053
Mycobacterium tuberculosis; shikimate pathway; chorismate biosynthesis; 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase

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