Electronic health record reveals community-level cardiometabolic health benefits associated with 10 years of community-based participatory research.

BACKGROUND: While a major goal of community-based participatory research (CBPR) is to improve community health; it is unclear how to measure longstanding success of CBPR. OBJECTIVE: We sought to determine the impact of ongoing CBPR on cardiometabolic health of participating communities, including in people not directly participating in research. METHODS: We used linear mixed-effects modelling with electronic medical records from 2002 to 2012 from the Yukon-Kuskokwim Health Corporation, which provides health care to all Alaska Native people in southwestern Alaska, to compare rates of change in cardiometabolic risk factors between communities that did and did not participate in ongoing CBPR beginning in 2003. RESULTS: We analysed 1,262,035 medical records from 12,402 individuals from 10 study and 38 control communities. Blood pressure declined faster in study than in control communities: systolic blood pressure (0.04 mmHg/year; 95% confidence interval [CI]: 0.01, 0.08); diastolic blood pressure (DBP) (0.07 mmHg/year; 95% CI: 0.04, 0.09). Body mass index increased 0.04 units/year faster in study communities than in control communities (95% CI: 0.03, 0.05). More study visits were associated with faster reduction of DBP and triglyceride levels in study communities. CONCLUSIONS: Ongoing CBPR may improve overall cardiometabolic health in communities, perhaps by increasing engagement in health and advocacy.

Sex differences in obesity prevalence and cardiometabolic factors among Western Alaska Native people.

BACKGROUND AND AIMS: Obesity is associated with increased risks of cardiovascular disease, type 2 diabetes, and other chronic diseases. Prevalence estimates for metabolic disorders are well documented in many populations, but Alaska Native groups are understudied. The Western Alaska Tribal Collaborative for Health Study combines data from three Alaska Native study cohorts to assess differences in obesity prevalence and associations with cardiometabolic risk factors by sex. METHODS AND RESULTS: Analyses were based upon a sample of 3985 adult Yup'ik and Inupiat participants with a mean age of 40 years. Prevalence of obesity and metabolic risk factors was assessed according to nationally recognized guidelines. Regression analysis was used to evaluate the association between obesity and cardiometabolic risk factors, including lipids, blood pressure and glucose. The prevalence of obesity (BMI ≥ 30) was significantly higher in women (40%) than men (20%). Only 18.6% of men had a waist circumference (WC) > 102 cm, while 58% of women had a WC > 88 cm (p < 0.001). Women had higher mean HDL-C and triglyceride levels compared to men, while systolic and diastolic blood pressure, LDL-C, and glucose means were higher in men than in women. In multivariate analyses, BMI and WC were significantly associated with all of the cardiometabolic risk factors, although these associations were more pronounced in men than women. CONCLUSION: The high prevalence of obesity and central adiposity among AN women is an important public health concern. Differences in associations between obesity and cardiometabolic risk factors by sex warrants further investigation to develop effective intervention programs.

Isotopic estimates of sugar intake are related to chronic disease risk factors but not obesity in an Alaska native (Yup'ik) study population.

BACKGROUND/OBJECTIVES: Sugar intake may be causally associated with chronic disease risk, either directly or by contributing to obesity. However, evidence from observational studies is mixed, in part due to the error and bias inherent in self-reported measures of sugar intake. Objective biomarkers may clarify the relationship between sugar intake and chronic disease risk. We have recently validated a biomarker of sugar intake in an Alaska Native (Yup'ik) study population that incorporates red blood cell carbon and nitrogen isotope ratios in a predictive model. This study tested associations of isotopic estimates of sugar intake with body mass index (BMI), waist circumference (WC) and a broad array of other physiological and biochemical measures of chronic disease risk in Yup'ik people. SUBJECTS/METHODS: In a cross-sectional sample of 1076 Yup'ik people, multiple linear regression was used to examine associations of sugar intake with BMI, WC and other chronic disease risk factors. RESULTS: Isotopic estimates of sugar intake were not associated with BMI (P=0.50) or WC (P=0.85). They were positively associated with blood pressure, triglycerides (TG) and leptin, and are inversely associated with total-, high-density lipoprotein- and low-density lipoprotein-cholesterol and adiponectin. CONCLUSIONS: Isotopic estimates of sugar intake were not associated with obesity, but were adversely associated with other chronic disease risk factors in this Yup'ik study population. This first use of stable isotope markers of sugar intake may influence recommendations for sugar intake by Yup'ik people; however, longitudinal studies are required to understand associations with chronic disease incidence.

Associations of obesity with triglycerides and C-reactive protein are attenuated in adults with high red blood cell eicosapentaenoic and docosahexaenoic acids.

BACKGROUND: N-3 fatty acids are associated with favorable, and obesity with unfavorable, concentrations of chronic disease risk biomarkers. OBJECTIVE: We examined whether high eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid intakes, measured as percentages of total red blood cell (RBC) fatty acids, modify associations of obesity with chronic disease risk biomarkers. METHODS: In a cross-sectional study of 330 Yup'ik Eskimos, generalized additive models (GAM) and linear and quadratic regression models were used to examine associations of BMI with biomarkers across RBC EPA and DHA categories. RESULTS: Median (5th-95th percentile) RBC EPA and DHA were 2.6% (0.5-5.9%) and 7.3% (3.3-8.9%), respectively. In regression models, associations of BMI with triglycerides, glucose, insulin, C-reactive protein (CRP) and leptin differed significantly by RBC EPA and DHA. The GAM confirmed regression results for triglycerides and CRP: at low RBC EPA and RBC DHA, the predicted increases in triglycerides and CRP concentrations associated with a BMI increase from 25 to 35 were 99.5±45.3 mg/dl (106%) and 137.8±71.0 mg/dl (156%), respectively, for triglycerides and 1.2±0.7 mg/l (61%) and 0.8±1.0 mg/l (35%), respectively, for CRP. At high RBC EPA and RBC DHA, these predicted increases were 13.9±8.1 mg/dl (23%) and 12.0±12.3 mg/dl (18%), respectively, for triglycerides and 0.5±0.5 mg/l (50%) and -0.5±0.6 mg/l (-34%), respectively, for CRP. CONCLUSIONS: In this population, high RBC EPA and DHA were associated with attenuated dyslipidemia and low-grade systemic inflammation among overweight and obese persons. This may help inform recommendations for n-3 fatty acid intakes in the reduction of obesity-related disease risk.

Isolation and characterization of new polymorphic microsatellite loci in the mixotrophic orchid Limodorum abortivum L. Swartz (Orchidaceae).

Here, we report the isolation and characterization of 11 polymorphic microsatellites in Limodorum abortivum. Allele variability has been characterized in three populations from Southern Italy and France. The number of alleles ranged from one to six per locus with an average of 3.8 alleles per locus. Observed and expected heterozygosity values ranged from 0.000 to 1.000 and from 0.492 to 0.806, respectively, with striking differences among populations. These microsatellites should be valuable tools for studying fine-scale genetic structure of scattered Limodorum abortivum populations, patterns of relationship with closely related taxa and the evolutionary ecology of its mycorrhizal interactions.

Sources of variability in birth defects prevalence rates.

BACKGROUND: The characteristics and methodologies of state-based birth defect surveillance systems might influence reported prevalence rates, making comparisons among states difficult. Standardizing methods to minimize variability beyond true differences in prevalence will aid national surveillance efforts and birth defects prevention programs. METHODS: Using data provided in the January 2000 Congenital Malformations Surveillance Report from the National Birth Defects Prevention Network, we characterized the surveillance methodologies among all sites. We then identified prevalence rates that are highly varied among systems that use each of our specified methodologies. We also examined the standards used by other collective health registries that exist across geographical boundaries. RESULTS: Large differences in prevalence rates across case ascertainment methods (active, passive, or combination of both) were observed for some conditions, but not for others. We identified additional factors which may influence prevalence rates, including case ascertainment sources, case inclusion criteria, and inclusion of elective terminations and stillbirths. The impact of each of these factors on prevalence rates may be defect-specific. CONCLUSIONS: We conclude that while some variability is expected due to differences in the true prevalence of birth defects, extreme differences among states are more likely due to differences in surveillance practices. The Birth Defects Prevention Act prompted new initiatives to develop birth defect surveillance systems, but there are no nationally agreed upon standards in existence to guide the process. This study was performed in support of developing standards that will influence new and existing state surveillance systems.

Statistical models to predict the need for postoperative intensive care and hospitalization in pediatric surgical patients.

OBJECTIVE: To develop statistical models for predicting postoperative hospital and ICU stay in pediatric surgical patients based on preoperative clinical characteristics and operative factors related to the degree of surgical stress. We hypothesized that preoperative and operative factors will predict the need for ICU admission and may be used to forecast the length of ICU stay or postoperative hospital stay. DESIGN: Prospective data collection from 1,763 patients. SETTING: Tertiary care children's hospital. PATIENTS AND PARTICIPANTS: All pediatric surgical patients, including those undergoing day surgery. Patients undergoing dental or ophthalmologic surgical procedures were excluded. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: A logistic regression model predicting ICU admission was developed from all patients. Poissonregression models were developed from 1,161 randomly selected patients and validated from the remaining 602 patients. The logistic regression model for ICU admission was highlypredictive (area under the receiver operating characteristics (ROC) curve = 0.981). In the data set used for development of Poisson regression models, significant correlations occurred between the observed and predicted ICU stay (Pearson r = 0.468, p < 0.0001, n = 131) and between the observed and predicted hospital stay for patients undergoing general (r = 0.695, p < 0.0001), orthopedic (r = 0.717, p < 0.0001), cardiothoracic (r = 0.746, p < 0.0001), urologic (r = 0.458, p < 0.0001), otorhinolaryngologic (r = 0.962, p < 0.0001), neurosurgical (r = 0.7084, p < 0.0001) and plastic surgical (r = 0.854, p < 0.0001) procedures. In the validation data set, correlations between predicted and observed hospital stay were significant for general (p < 0.0001), orthopedic (p < 0.0001), cardiothoracic (p = 0.0321) and urologic surgery (p = 0.0383). The Poisson models for length of ICU stay, otorhinolaryngology, neurosurgery or plastic surgery could not be validated because of small numbers of patients. CONCLUSIONS: Preoperative and operative factors may be used to develop statistical models predicting the need for ICU admission in pediatric surgical patients, and hospital stay following general surgical, orthopedic, cardiothoracic and urologic procedures. These statistical models need to be refined and validatedfurther, perhaps using data collection from multiple institutions.

Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome.

Down syndrome is a complex genetic and metabolic disorder attributed to the presence of three copies of chromosome 21. The extra chromosome derives from the mother in 93% of cases and is due to abnormal chromosome segregation during meiosis (nondisjunction). Except for advanced age at conception, maternal risk factors for meiotic nondisjunction are not well established. A recent preliminary study suggested that abnormal folate metabolism and the 677C-->T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene may be maternal risk factors for Down syndrome. The present study was undertaken with a larger sample size to determine whether the MTHFR 677C-->T polymorphism was associated with increased risk of having a child with Down syndrome. Methionine synthase reductase (MTRR) is another enzyme essential for normal folate metabolism. A common polymorphism in this gene was recently associated with increased risk of neural tube defects and might also contribute to increased risk for Down syndrome. The frequencies of the MTHFR 677C-->T and MTRR 66A-->G mutations were evaluated in DNA samples from 157 mothers of children with Down syndrome and 144 control mothers. Odds ratios were calculated for each genotype separately and for potential gene-gene interactions. The results are consistent with the preliminary observation that the MTHFR 677C-->T polymorphism is more prevalent among mothers of children with Down syndrome than among control mothers, with an odds ratio of 1.91 (95% confidence interval [CI] 1.19-3.05). In addition, the homozygous MTRR 66A-->G polymorphism was independently associated with a 2. 57-fold increase in estimated risk (95% CI 1.33-4.99). The combined presence of both polymorphisms was associated with a greater risk of Down syndrome than was the presence of either alone, with an odds ratio of 4.08 (95% CI 1.94-8.56). The two polymorphisms appear to act without a multiplicative interaction.

Biochemical analysis of human immunodeficiency virus-1 reverse transcriptase containing a mutation at position lysine 263.

Site-directed mutagenesis has been used to assess the importance of lysine 263 in substrate binding of human immunodeficiency virus-1 (HIV-1) reverse transcriptase. Previous studies have indicated that lysine 263 functions in the binding of 2'-deoxynucleoside 5'-triphosphate (dNTP) substrates (Basu, A., Tirumalai, R. S., and Modak, M. J. (1989) J. Biol. Chem. 264, 8746-8752). We studied this interaction directly by using site-specific mutagenesis to change lysine 263 to a serine. Highly purified mutant enzyme K263S bound natural dNTP substrates and primed polynucleic acid substrates with equal affinity when compared to the wild type reverse transcriptase. No difference was observed in the binding of 3'-azido-2',3'-dideoxythymidine 5'-triphosphate to the mutant reverse transcriptase on the basis of Km and Ki determinations. The serine substitution had no effect on RNase H activity. These results indicate that lysine 263 is not essential in the binding of substrates to HIV-1 reverse transcriptase.