Determining the Long-Term Effectiveness of a Group-Based Physical Activity Program.

OBJECTIVE: In 2015, only half (48%) of older adults in the United States (≥60 years) reported engaging in any kind of physical activity. Few studies examine the impact of evidence-based programs when adopted in community-based settings. The purpose of this study is to assess the effectiveness of EnhanceFitness (EF) upto 12-months. METHOD: EF was offered to older adults in South Florida. A total of 222 EF classes were offered between October 2008 and December 2014. Program consisted of a 1-hour session held three times a week. Even though participation was required for 4 months, 1,295 participants continued the program for at least 1 year. RESULTS: All participants showed significant improvement in outcome measures. A mean change of 1.5, 1.7, and 1.9 was seen in number of chair stands at 4, 8, and 12 months (p < .001), respectively. The number of arm curls performed improved from 16.8 at baseline to 18.8, 18.8, and 19.2 at 4-, 8-, and 12-months, respectively. Participants improved their up-and-go time by decreasing from 9.1 (baseline) to 8.7 (4 months) to 8.6 (12 months; p = .001). DISCUSSION: Randomized controlled trials are commonly used to determine the efficacy of an intervention. These interventions when disseminated at the population level have the potential to benefit large masses. EF is currently offered at more than 700 locations. This tremendous success of EF brings attention to an important question of continuous monitoring of these programs to ensure program consistency and intended outcomes. The model used by the Healthy Aging Regional Collaborative could be replicated by other communities.

Does Survival Vary for Breast Cancer Patients in the United States? A Study from Six Randomly Selected States.

BACKGROUND: Breast cancer is the most common cancer in women. Disparities in some characteristics of breast cancer patients and their survival data for six randomly selected states in the US were examined. MATERIALS AND METHODS: A probability random sampling method was used to select the records of 2,000 patients from each of six randomly selected states. Demographic and disease characteristics were extracted from the Surveillance Epidemiology and End Results (SEER) database. To evaluate relationships between variables, we employed a Cox Proportional Regression to compare survival times in the different states. RESULTS: Iowa had the highest mean age of diagnosis at 64.14 years (SE = 0.324) and Georgia had the lowest at 57.97 years (SE = 0.313). New Mexico had the longest mean survival time of 189.09 months (SE = 20.414) and Hawaii the shortest at 119.01 (SE = 5.394) months, a 70.08-month difference (5.84 years). Analysis of stage of diagnosis showed that the highest survival times for Whites and American Indians/Alaska Natives were for stage I cancers. The highest survival times for Blacks varied. Stage IV cancer consistently showed the lowest survival times. CONCLUSIONS: Differences in breast cancer characteristics across states highlight the need to understand differences between the states that result in variances in breast cancer survival.

White Matter Deterioration May Foreshadow Impairment of Emotional Valence Determination in Early-Stage Dementia of the Alzheimer Type.

In Alzheimer Disease (AD), non-verbal skills often remain intact for far longer than verbally mediated processes. Four (1 female, 3 males) participants with early-stage Clinically Diagnosed Dementia of the Alzheimer Type (CDDAT) and eight neurotypicals (NTs; 4 females, 4 males) completed the emotional valence determination test (EVDT) while undergoing BOLD functional magnetic resonance imaging (fMRI). We expected CDDAT participants to perform just as well as NTs on the EVDT, and to display increased activity within the bilateral amygdala and right anterior cingulate cortex (r-ACC). We hypothesized that such activity would reflect an increased reliance on these structures to compensate for on-going neuronal loss in frontoparietal regions due to the disease. We used diffusion tensor imaging (DTI) to determine if white matter (WM) damage had occurred in frontoparietal regions as well. CDDAT participants had similar behavioral performance and no differences were observed in brain activity or connectivity patterns within the amygdalae or r-ACC. Decreased fractional anisotropy (FA) values were noted, however, for the bilateral superior longitudinal fasciculi and posterior cingulate cortex (PCC). We interpret these findings to suggest that emotional valence determination and non-verbal skill sets are largely intact at this stage of the disease, but signs foreshadowing future decline were revealed by possible WM deterioration. Understanding how non-verbal skill sets are altered, while remaining largely intact, offers new insights into how non-verbal communication may be more successfully implemented in the care of AD patients and highlights the potential role of DTI as a presymptomatic biomarker.

Methods needed to measure predictive accuracy: A study of diabetic patients.

Diabetes is one of the leading causes of morbidity and mortality and it can result in several complications such as kidney failure, heart failure, stroke, and blindness making it a major medical and public health concern in the United States. Statistical methods are important to detect risk factors and identify the best sampling plan to determine predictive bounds for diabetic patients' data. The main objective of this paper is to identify the best fit bootstrapping sampling method and to draw the predictive bound considering diabetes patient data. A random sample was used from the National Health and Nutritional Examination Survey (NHANES) for this study. We found that there were significant relationships between age, marital status, and race/ethnicity with diabetes status (p<0.001) and no relationship was observed between gender and diabetes status. We ran the logistic regression to identify the risk factors from the data. We identified that the significant risk factors are age (p<0.001), total protein (p<0.001), fast food (p<0.0339), and direct HDL (p<0.001). This study provides evidence that the parametric bootstrapping method is the best fit method compared with other methods to estimate the predictive error bounds. These findings will be of great significance for identifying the best sampling methods, which can increase the statistical accuracy of laboratory clinical research of diabetes. This will also allow for the determination of precise risk factors that will best represent the data by detecting mild and extreme outliers from disease observations. Therefore, these results will be useful for researchers and clinicians to select the best sampling methods to study diabetes and other diseases in order to maximize the accuracy of their results. This article is part of a Special Issue entitled: Oxidative Stress and Mitochondrial Quality in Diabetes/Obesity and Critical Illness Spectrum of Diseases - edited by P. Hemachandra Reddy.

Disparities in Cervical Cancer Characteristics and Survival Between White Hispanics and White Non-Hispanic Women.

BACKGROUND: Cervical cancer is the second most common cancer among women resulting in nearly 500,000 cases annually. Screening leads to better treatment and survival time. However, human papillomavirus (HPV) exposure, screening, and treatment vary among races and ethnicities in the United States. The purpose of this study is to examine disparities in characteristics of cervical cancer and survival of cases between White Hispanic (WH) and White non-Hispanic (WNH) women in the United States. METHODS: We used a stratified random sampling method to select cervical cancer patient records from nine states; a simple random sampling method to extract the demographic and disease characteristics data within states from the Surveillance Epidemiology and End Results (SEER) database. We used statistical probability distribution methods for discrete and continuous data. The chi-square test and independent samples t-test were used to evaluate statistically significant differences. Furthermore, the Cox Proportional Regression and the Kaplan-Meier survival estimators were used to compare WH and WNH population survival times in the United States. RESULTS: The samples of WNH and WH women included 4,000 cervical cancer cases from 1973-2009. There were statistically significant differences between ethnicities: marital status (p < 0.001); primary site of cancer (p < 0.001); lymph node involvement (p < 0.001); grading and differentiation (p < 0.0001); and tumor behavior (p < 0.001). The mean age of diagnosis for both groups showed no statistical differences. However, the mean survival time for WNH was 221.7 (standard deviation [SD] = 118.1) months and for WH was 190.3 (SD = 120.3), which differed significantly (p < 0.001). CONCLUSIONS: Clear disparities exist in risk factors, cervical cancer characteristics, and survival time between WH and WNH women.

Type 2 diabetes and its correlates among adults in Bangladesh: a population based study.

BACKGROUND: Type 2 diabetes is one of the most prevalent non-communicable diseases in Bangladesh. However, the correlates of type 2 diabetes among adults in Bangladesh remain unknown. We aimed to investigate the correlates of type 2 diabetes among the adults in Bangladesh. METHODS: We conducted a cross-sectional study using data from the nationally representative 2011 Bangladesh Demographic and Health Survey. A random sample of 7,543 (3,823 women and 3,720 men) adults of age 35 years and older from both urban and rural areas, who participated in the survey was included. Diabetes was defined as having a fasting plasma blood glucose level of ≥ 7 mm/L or taking diabetes medication during the survey. Hypothesized factors, e.g., age, sex, education, place of residence, social status, body mass index, and hypertension were considered in the analyses. Multivariable logistic regression models were used to identify the important correlates of type 2 diabetes. RESULTS: Among the respondents, the overall prevalence of diabetes was 11 %, and the prevalence was slightly higher in women (11.2 %) than men (10.6 %). Respondents with the age group of 55-59 years had higher odds of having diabetes (odds ratios (OR) = 2.37, 95 % confidence interval (CI): 1.76-3.21) than the age group of 35-39 years. Moreover, respondents who had higher educational attainment (OR = 1.67, 95 % CI: 1.18-2.36) and higher social status (OR = 2.01, 95 % CI: 1.50-2.70) had higher odds of having diabetes than the respondents with no education and lower social status, respectively. We also found socioeconomic status, place of residence (rural or urban), regions of residence (different divisions), overweight and obesity, and hypertension as significant correlates of type 2 diabetes in Bangladesh. CONCLUSIONS: Our study shows that older age, higher socioeconomic status, higher educational attainment, hypertension, and obesity were found to be significant correlates of type 2 diabetes. Need-based policy program strategies including early diagnosis, awareness via mass media, and health education programs for changing lifestyles should be initiated for older age, wealthy, and/or higher educated individuals in Bangladesh. Moreover, area-specific longitudinal research is necessary to find out the underlying causes of regional variations.

Trends in Outcome and Hospitalization Cost among Adult Patients with Acute Ischemic Stroke in the United States.

INTRODUCTION: New treatments for acute ischemic stroke (AIS) have been introduced and are expected to improve patients' overall outcomes. We assessed the impact of new therapeutic strategies on outcome and cost of hospitalization among adult patients with AIS in the United States. METHODS: Patients with AIS admitted in the United States in 1993-1994 and 2006-2007 were listed using the Nationwide Inpatient Survey database. We determined the rates of occurrence, hospitalization outcomes, and mean hospital charges for all patients. We further analyzed these variables in the ventilated and nonventilated patients. RESULTS: We identified 386,043 patients with AIS admitted in the United States in 1993-1994 and 749,766 patients in 2006-2007. The length of hospitalization was significantly higher in 1993-1994 compared with 2006-2007: 6.9 ± 4.2 days versus 4.66 ± 3 days, respectively. In-hospital mortality rate was 8.9% in 1993-1994 and 5.6% in 2006-2007 (P < 0.0001). There was a significant increase in mean hospital charges in 2006-2007 compared with 1993-1994 ($21,916 ± $14,117 versus $9,646 ± $5,727). The length of hospitalization was significantly shorter in 2006-2007 in nonventilated patients. There was a significant increase in mean hospital charges in 2006-2007 compared with 1993-1994 in both ventilated ($81,528 ± $64,526 versus $25,143 ± $17,172, P<0.0001) and nonventilated patients ($21,085 ± $13,042 versus $10,000 ± $6,300, P<0.0001). The mortality rate was significantly lower in 2006-2007 in both subgroups: 46.5% versus 59.8% in ventilated patients and 4.2% versus 8.2% in nonventilated patients (P < 0.0001). CONCLUSION: Our study suggests that new therapeutic strategies have improved outcomes and increased cost of hospitalization among adult patients with AIS in the United States over a period of 13 years. The hospitalization cost was significantly higher in the ventilated and nonventilated patients in 2006-2007, which may reflect the impact of new therapeutic strategies, the availability of more intensive care units and stroke centers, and the lower mortality rate in this time period.

The Impact of Red Light Cameras on Crashes Within Miami-Dade County, Florida.

OBJECTIVE: To determine the safety effect of red light camera (RLC) programs, this study attempted to estimate its impact on collisions within Miami-Dade County, Florida Methods: A before-after evaluation using a comparison group along with traffic control correction was employed. Twenty signalized intersections with RLCs that began enforcement on January 1, 2011, were matched to 2 comparison sites located at least 2 miles from camera sites to minimize spillover effect. An empirical Bayes analysis was used to account for potential regression to the mean effects. An index of effectiveness along with 95% confidence intervals were calculated based on the comparison between the estimated and actual number of crashes in the after period. RESULTS: During the first year, RLC sites experienced a marginal decrease in right angle/turn collisions (-3%), a significant increase in rear-end collisions (+40%), and significant decreases in all injury (-19%) and RLR-related injury collisions (-24%). An increase in right angle/turning (+14%) and rear-end (+51%) collisions at the RLC sites was observed after 2 years despite camera enforcement. A significant reduction in RLR-related injury crashes (-17%), however, was still observed after 2 years. A nonsignificant decline in all injury collisions (-12%) was also noted. CONCLUSIONS: RLCs showed a benefit in reducing RLR-related injury collisions at camera sites after enforcement commenced, yet its tradeoff was a large increase in rear-end collisions. There was inconclusive evidence whether RLCs affected right angle/turning and all injury collisions. Statutory changes in crash reporting during the second year of camera enforcement affected the incidence of right angle and rear-end collisions; nevertheless, a "novelty effect" could not be ruled out. Future research should consider events such as low frequencies of severe injury/fatal collisions and changes in crash reporting requirements when conducting RLC analyses.

Inferential statistics from Black Hispanic breast cancer survival data.

In this paper we test the statistical probability models for breast cancer survival data for race and ethnicity. Data was collected from breast cancer patients diagnosed in United States during the years 1973-2009. We selected a stratified random sample of Black Hispanic female patients from the Surveillance Epidemiology and End Results (SEER) database to derive the statistical probability models. We used three common model building criteria which include Akaike Information Criteria (AIC), Bayesian Information Criteria (BIC), and Deviance Information Criteria (DIC) to measure the goodness of fit tests and it was found that Black Hispanic female patients survival data better fit the exponentiated exponential probability model. A novel Bayesian method was used to derive the posterior density function for the model parameters as well as to derive the predictive inference for future response. We specifically focused on Black Hispanic race. Markov Chain Monte Carlo (MCMC) method was used for obtaining the summary results of posterior parameters. Additionally, we reported predictive intervals for future survival times. These findings would be of great significance in treatment planning and healthcare resource allocation.

Trends in outcomes and hospitalization costs for traumatic brain injury in adult patients in the United States.

Several new therapeutic strategies have been introduced for the management of adult traumatic brain injury (TBI) over the last decade, such as the development of management pathways and specialized TBI units and improved treatment of cerebral perfusion. The purpose of this study is to compare TBI-related hospitalization outcomes in the United States between two time periods, 1993-1994 and 2006-2007. We determined the rates of occurrence, in-hospital outcomes, and mean hospital charges for patients hospitalized with adult TBI in 1993-1994 using the nationally representative all-payer Nationwide Inpatient Survey (NIS) database, and compared these outcomes with homologous data from 2006-2007. The incidence of TBI admissions was reduced by 35% in 2006-2007 compared with 1993-1994; (22/100,000 versus 34/100,000 population; p<0.0001). The mean length of hospitalization (mean±SD, in days) was significantly lower in 2006-2007 than in 1993-1994 (2.5±2.4 days versus 2.7±2.6 days; p<0.0001). In-hospital mortality increased significantly in 2006-2007 compared with 1993-1994 (0.8% versus 0.4%, p<0.0001). Average hospitalization charges were significantly higher in 2006-2007 compared with 19993-1994 ($21,460±$21,212 versus $5,142±$4,625; p<0.0001), even after adjusting for inflation. In both time periods, most hospitalized adult TBI patients were graded as mild (98.2% in 1993-1994 versus 98.0% in 2006-2007; p=0.20). There was a significant increase in average hospitalization charges and death rates in all TBI severity subgroups in 2006-2007 compared with 1993-1994. The decline in rate of hospitalization between the two time periods was predominantly related to the decline in the number of admissions of patients with mild TBI. Although the number of TBI admissions was reduced, a significant increase in average hospitalization charges and in-hospital mortality rate was observed in 2006-2007 compared with 1993-1994.

Guillain-Barré syndrome after influenza vaccination in the United States, a report from the CDC/FDA vaccine adverse event reporting system (1990-2009).

OBJECTIVES: To determine the rate of Guillain-Barré syndrome (GBS) after administration of influenza vaccine in the United States and to provide further information about the characteristics and temporal profile of these incidents. METHODS: Data were acquired from the Vaccine Adverse Event Reporting System, supplemented by data from the Center for Biologics and Research under the Freedom of Information Act between 1990 and 2009. RESULTS: There were 802 cases (mean age, 54.72 ± 18.4 years) of GBS reported after influenza vaccination in the United States between 1990 and 2009. Among the 802 vaccinated patients with available data, 624 (77.8%) developed GBS within 6 weeks and 78 (9.7%) after 6 weeks, whereas these data were unavailable for the remaining 100 patients (13%). The reporting rate of post-influenza vaccine GBS was within the range expected in the general population or approximately 0.46 cases per million vaccinations. A non-Gaussian distribution of GBS within the first 6 weeks post-vaccination was noted, given that the peak incidence occurred in the second week. CONCLUSIONS: The incidence of post-influenza vaccine GBS is similar to the incidence of idiopathic GBS in the general population. Although the nonnormal distribution of post-vaccination GBS suggests that some cases may be triggered by vaccination, the greater risk of complications from influenza virus infections makes vaccination the first-line strategy for infection prevention and support the current guidelines on vaccination.

Analysis of data from the CDC/FDA vaccine adverse event reporting system (1990-2009) on Guillain-Barre syndrome after hepatitis vaccination in the USA.

We used data from the Vaccine Adverse Event Reporting System, supplemented by additional data provided by the Center for Biologics Evaluation and Research, to identify 189 patients with Guillain-Barré syndrome (GBS) reported after hepatitis vaccination with a mean age of 30.65 years, affecting men and women equally. Among vaccinated patients, 133 (70%) developed GBS within six weeks, 30 (15.9%) after six weeks, and for the remaining 26 (13.7%), the time between GBS occurrence and vaccination was not specified. The reporting rate of post-hepatitis vaccine GBS is approximately 3.4 cases per one million vaccinations, which is in the range expected in the general population. The unbalanced distribution of reports in the first six weeks after vaccination suggests that some cases of GBS may be triggered by vaccination. Nonetheless, the low incidence of hepatitis vaccine-associated GBS, and the dramatic incidence reduction of hepatitis and its complications after vaccination, support the current guidelines for vaccination.

Guillain-Barré syndrome after H1N1 vaccination in the United States: a report using the CDC/FDA Vaccine Adverse Event Reporting System (2009).

BACKGROUND: Although the Guillain-Barré syndrome (GBS) can be associated with the seasonal influenza vaccine, there is no definite evidence that GBS is associated with H1N1 influenza vaccination. The objective of this report is to study the occurrence and characteristics of GBS after H1N1 vaccine administration in the United States in 2009. METHODS: Data were acquired from the Vaccine Adverse Event Reporting System and supplemented by additional information obtained from the Center for Biologics Evaluation and Research, under the Federal Freedom of Information Act. RESULTS: A total of 62 individuals (mean age 46.51 ± 22.41 years), 33 of whom were men, developed GBS associated with the H1N1 influenza vaccination in 2009. Sixty GBS cases were reported within 6 weeks after vaccination, with 31 cases (50.0%) reported in the first 2 weeks. The estimated rate of occurrence of GBS was 6.2 cases per 10 million vaccinations, which is comparable to the rate of GBS in the general population. CONCLUSION: The higher rate of GBS reports in the first 6 weeks after H1N1 vaccination suggests that some GBS cases may be triggered by H1N1 vaccination. This warrants early recognition, treatment, and active surveillance in the postvaccination setting.

Trends in outcome and hospitalization charges of adult patients admitted with botulism in the United States.

BACKGROUND: To assess the impact of new therapeutic strategies on outcomes and hospitalization charges among adult patients with botulism in the United States. METHODS: We determined in-hospital outcomes and charges for patients with botulism hospitalized in 1993-1994 and compared them with those observed among patients hospitalized in 2006-2007. Mortality, length of stay, and hospitalization charges were calculated. Age, sex, race, ethnicity, and discharge status were also reported. RESULTS: There were 66 and 132 admissions of adult patients with botulism in 1993-1994 and 2006-2007, respectively. Men predominance was observed in 2006-2007 compared to women predominance during the 1993-1994 time period. There was no significant difference in the average length of stay and in-hospital mortality rate between the two groups studied. However, in the 2006-2007 group, there was a significant increase in the mean hospitalization charges (USD 126,092 ± 120,535 vs. USD 83,623 ± 82,084; p = 0.0107) and in the proportion of patients requiring mechanical ventilation when compared to 1993-1994 (34 vs. 13.6%; p < 0.0001). CONCLUSION: Botulism continues to be an infrequent cause of hospitalization, with a significant increase in the average hospitalization charges in 2006-2007 when compared to 1993-1994, despite a nonsignificant change in the mortality rate and average length of hospitalization.

The safety profile of home infusion of intravenous immunoglobulin in patients with neuroimmunologic disorders.

OBJECTIVES: To assess the overall safety of high-dose intravenous immunoglobulin (IG) products used to treat patients with neuroimmunological disorders in a supervised home-based setting. METHODS: The incidence of adverse reactions was assessed in a retrospective chart review of 420 patients who consecutively received 4076, home-based, individual, intravenous immunoglobulin (IVIG) infusions between January 2009 and December 2009. RESULTS: A total of 90 patients (21.4%) developed adverse reactions related to IVIG administration (2.6% per individual infusion). A total of 95.5% of adverse reactions were mild, and no serious side effects were observed. The incidence of adverse reactions was significantly lower in the subgroup of patients with neuroimmunological disorders who received premedication (18.2% compared with 29.3%, P = 0.02). There was no significant statistical difference in the incidence of side effects among the different brands of IVIG used in this study. CONCLUSIONS: The combination of premedication and well-defined clinical, IVIG infusion policies may reduce the incidence of high-dose IVIG adverse reactions administered in a home-based setting in patients with neuroimmunological disorders.

Metabolic syndrome in aboriginal Canadians: prevalence and genetic associations.

OBJECTIVES: The prevalence rates of type 2 diabetes (T2DM) and coronary heart disease (CHD) in Ontario Oji-Cree are among the world's highest. Since metabolic syndrome (MetS) increases risk of T2DM and CHD, we characterized prevalence and putative genetic determinants of MetS in Oji-Cree. METHODS AND RESULTS: In 515 adult (> or = 18 years old) and 115 adolescent (< 18 years old) Oji-Cree subjects, using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, we determined that 29.9% of Oji-Cree adults, and 43.4% of adults > or = 35 years of age, had MetS. Furthermore, 33.9 and 8.7% of female Oji-Cree adults and adolescents, respectively, had MetS. Increased waist girth and depressed HDL cholesterol were the most prevalent individual MetS components, while increased blood pressure was least prevalent. AGT T174M, GNB3 825C>T, and APOC3 -455T>C genotypes were significantly associated with MetS (P = 0.018, 0.0056, and 0.029, respectively) for female adults, whereas FABP2 A54T genotype was associated with MetS (P = 0.040) for female adolescents. CONCLUSIONS: The high MetS prevalence in Oji-Cree adults, especially women, is consistent with their high risk of T2DM and CHD. Functional polymorphisms in three candidate genes for plasma lipoproteins and blood pressure were associated with MetS in adult Oji-Cree. Furthermore, several female adolescents met the adult MetS criteria, suggesting that the genesis of MetS begins in youth, especially among aboriginal females.

Differences between carotid wall morphological phenotypes measured by ultrasound in one, two and three dimensions.

Ultrasound measurements are both surrogate markers and risk factors for atherosclerosis end points. Carotid intima-media thickness (IMT) is most commonly used, but ultrasound can also define structures in higher spatial dimensions, such as total plaque area (TPA) and total plaque volume (TPV). Because there are minimal data regarding the relationship between IMT, TPA and TPV, we measured these variables in 272 Oji-Cree subjects. We found pairwise correlations for IMT:TPA, IMT:TPV and TPA:TPV of 0.507, 0.588 and 0.846, respectively (transformed variables, all P <0.0001). In a subset of 168 subjects with complete cardiovascular risk factor data, we performed multivariate regression analysis to identify sources of variation for IMT, TPA and TPV. We found that the ultrasound traits showed different correlations with individual cardiovascular risk factors. In particular, IMT was significantly associated with hypertension, TPA with smoking and plasma cholesterol, and TPV with diabetes. Therefore, these ultrasound measures of carotid artery morphology, while somewhat correlated, likely represent distinctive quantitative traits with different biological determinants, as underscored by different risk factor associations in the multivariate regression analysis. Because the measurements have different implications and determinants, investigators might need to be selective about the particular measurements they choose for specific applications.

Venn analysis as part of a bioinformatic approach to prioritize expressed sequence tags from cardiac libraries.

OBJECTIVES: We needed to sort expressed sequence tags (ESTs) from human cardiac expression libraries. DESIGN AND METHODS: We annotated DNA sequence text files of 35,152 cardiac ESTs using our search and annotation tool called Multiblast.pl. We generated lists of the most prevalent ESTs in each library, and using a novel Venn tool, we grouped ESTs that were common to all or exclusive to particular libraries. RESULTS: Hypothetical protein KIAA0553 was expressed 120 times among 917 ESTs from an adult cardiac library (13.1%) compared only once among 8075 ESTs from fetal cardiac libraries (P < 10(-114)), this was confirmed using Northern analysis. We collated biochemical features of KIAA0553 and determined DNA polymorphism frequencies. We also used the Venn tool to specify genes that were uniquely expressed in hypertrophic cardiomyocytes. CONCLUSIONS: Annotating ESTs and sorting them using Venn analysis can help specify new candidate disease genes from the current lists of "hypothetical proteins".

Optimizing RNA extraction yield from whole blood for microarray gene expression analysis.

OBJECTIVES: Microarray analysis of gene expression profiles of blood leukocytes has many potential clinical and research applications. DESIGN AND METHODS: We used the PAXgene Blood RNA System to prepare RNA from the whole blood of normal volunteers using two incubation times followed by gene expression profiling using the Affymetrix HU133A GeneChip. CONCLUSIONS: Longer incubation gave a significantly higher RNA yield and samples that were satisfactory for microarray analysis, with excellent pairwise correlations between replicates.

Genetic variation in PPARG encoding peroxisome proliferator-activated receptor gamma associated with carotid atherosclerosis.

BACKGROUND AND PURPOSE: Peroxisome proliferator-activated receptor gamma is a crucial molecule in atherogenesis because it is associated with metabolic risk factors such as obesity and diabetes and also plays a key role in subcellular metabolism of arterial wall macrophage foam cells. Genetic variation in PPARG has been associated with metabolic and cardiovascular end points. METHODS: We investigated the relationship between 2 common PPARG polymorphisms, namely P12A and c.1431C>T, and carotid atherosclerosis in a sample of 161 Canadian aboriginal people. Dependent variables were carotid intima media thickness (IMT), assessed using B-mode ultrasonography, and total carotid plaque volume (TPV), assessed using 3D ultrasound. RESULTS: Using multivariate analysis, we found that subjects with > or =1 PPARG A12 allele had less carotid IMT than others (0.72+/-0.03 versus 0.80+/-0.02 mm; P=0.0045), with no between-genotype difference in TPV. In contrast, subjects with the PPARG c.1431T allele had greater TPV than others (124+/-18.4 versus 65.1+/-23.7 mm3; P=0.0079), with no between-genotype difference in IMT. CONCLUSIONS: The findings show an association between PPARG genotypes and carotid arterial phenotypes, and further reflect the prevailing view that the PPARG A12 allele protects against deleterious phenotypes. Also, whereas IMT and TPV are somewhat correlated with each other, they might also represent distinct traits with discrete determinants representing different stages of atherogenesis.