Deep historical borrowing framework to prospectively and simultaneously synthesize control information in confirmatory clinical trials with multiple endpoints.

In current clinical trial development, historical information is receiving more attention as it provides utility beyond sample size calculation. Meta-analytic-predictive (MAP) priors and robust MAP priors have been proposed for prospectively borrowing historical data on a single endpoint. To simultaneously synthesize control information from multiple endpoints in confirmatory clinical trials, we propose to approximate posterior probabilities from a Bayesian hierarchical model and estimate critical values by deep learning to construct pre-specified strategies for hypothesis testing. This feature is important to ensure study integrity by establishing prospective decision functions before the trial conduct. Simulations are performed to show that our method properly controls family-wise error rate and preserves power as compared with a typical practice of choosing constant critical values given a subset of null space. Satisfactory performance under prior-data conflict is also demonstrated. We further illustrate our method using a case study in Immunology.

Depth- and direction-dependent changes in solute transport following cross-linking with riboflavin and UVA light in ex vivo porcine cornea.

Diffusion is an important mechanism of transport for nutrients and drugs throughout the avascular corneal stroma. The purpose of this study was to investigate the depth- and direction-dependent changes in stromal transport properties and their relationship to changes in collagen structure following ultraviolet A (UVA)-riboflavin induced corneal collagen cross-linking (CXL). After cross-linking in ex vivo porcine eyes, fluorescence recovery after photobleaching (FRAP) was performed to measure fluorescein diffusion in the nasal-temporal (NT) and anterior-posterior (AP) directions at corneal depths of 100, 200, and 300 µm. Second harmonic generation (SHG) imaging was also performed at these three corneal depths to quantify fiber alignment. For additional confirmation, an electrical conductivity method was employed to quantify ion permeability in the AP direction in corneal buttons and immunohistochemistry (IHC) was used to image collagen structure. Cross-linked corneas were compared to a control treatment that received the riboflavin solution without UVA light (SHAM). The results of FRAP revealed that fluorescein diffusivity decreased from 23.39 ± 11.60 µm2/s in the SHAM group to 19.87 ± 10.10 µm2/s in the CXL group. This change was dependent on depth and direction: the decrease was more pronounced in the 100 µm depth (P = 0.0005) and AP direction (P = 0.001) when compared to the effect in deeper locations and in the NT direction, respectively. Conductivity experiments confirmed a decrease in solute transport in the AP direction (P < 0.0001). FRAP also detected diffusional anisotropy in the porcine cornea: the fluorescein diffusivity in the NT direction was higher than the diffusivity in the AP direction. This anisotropy was increased following CXL treatment. Both SHG and IHC revealed a qualitative decrease in collagen crimping following CXL. Analysis of SHG images revealed an increase in coherency in the anterior 200 µm of CXL treated corneas when compared to SHAM treated corneas (P < 0.01). In conclusion, CXL results in a decrease in stromal solute transport, and this decrease is concentrated in the most anterior region and AP direction. Solute transport in the porcine cornea is anisotropic, and an increase in anisotropy with CXL may be explained by a decrease in collagen crimping.

Cardiovascular disease risk among rural residents living with diabetes and prediabetes: A cluster randomized trial.

OBJECTIVE: Diabetes is a major health problem that is closely linked with cardiovascular disease (CVD), the leading cause of death in the United States. The purpose of this analysis was to determine the effect of a culturally relevant diabetes health promotion program on diabetes knowledge and self-reported self-care behaviors. DESIGN: A cluster randomized controlled trial was conducted in 12 rural church settings. Seven churches were randomized to the intervention group and five to the control group. SAMPLE: The sample included 146 African American participants diagnosed with diabetes and prediabetes. INTERVENTION: The intervention group participants (n = 75) received the diabetes health program, and those in the control group (n = 71) group received a publicly available diabetes health brochure. MEASURES: Data were collected about diabetes knowledge, self-care activities, fatalism, and social support. RESULTS: Linear mixed model was the statistical test used to analyze group differences. Compared with the control group, the intervention group showed significant changes from pretest to posttest for diabetes knowledge and behaviors associated with diet and blood glucose testing. CONCLUSION: Health promotion programs implemented by public health nurses among rural groups at increased risk for developing CVD can facilitate understanding about strategies to reduce disease risk.

Influencing cardiovascular health habits in the rural, deep south: results of a cluster randomized trial.

Cardiovascular disease (CVD) is a major cause of death among people living in the United States. Populations, especially minorities, living in the rural South are disproportionately affected by CVD and have greater CVD risk, morbidity and mortality. Culturally relevant cardiovascular health programs implemented in rural community settings can potentially reduce CVD risk and facilitate health behavior modification. The purpose of this study was to examine the effects of a cardiovascular health promotion intervention on the health habits of a group of rural African American adults. The study had a cluster randomized controlled trial design involving 12 rural churches that served as statistical clusters. From the churches (n = 6) randomized to the intervention group, 115 participants were enrolled, received the 6-week health program and completed pretest-posttest measures. The 114 participants from the control group churches (n = 6) did not receive the health program and completed the same pretest-posttest measures. The linear mixed model was used to compare group differences from pretest to posttest. The educational health intervention positively influenced select dietary and confidence factors that may contribute toward CVD risk reduction.

Temporomandibular Joint Condyle-Disc Morphometric Sexual Dimorphisms Independent of Skull Scaling.

PURPOSE: Approximately 2 to 4% of the US population have been estimated to seek treatment for temporomandibular symptoms, predominately women. The study purpose was to determine whether sex-specific differences in temporomandibular morphometry result from scaling with sex differences in skull size and shape or intrinsic sex-specific differences. MATERIALS AND METHODS: A total of 22 (11 male [aged 74.5 ± 9.1 years]; 11 female [aged 73.6 ± 12.8 years]) human cadaveric heads with no history of temporomandibular disc derangement underwent cone beam computed tomography and high-resolution magnetic resonance imaging scanning to determine 3-dimensional cephalometric parameters and temporomandibular morphometric outcomes. Regression models between morphometric outcomes and cephalometric parameters were developed, and intrinsic sex-specific differences in temporomandibular morphometry normalized by cephalometric parameters were determined. Subject-specific finite element (FE) models of the extreme male and extreme female conditions were developed to predict variations in articular disc stress-strain under the same joint loading. RESULTS: In some cases, sex differences in temporomandibular morphometric parameters could be explained by linear scaling with skull size and shape; however, scaling alone could not fully account for some differences between sexes, indicating intrinsic sex-specific differences. The intrinsic sex-specific differences in temporomandibular morphometry included an increased condylar medial length and mediolateral disc lengths in men and a longer anteroposterior disc length in women. Considering the extreme male and female temporomandibular morphometry observed in the present study, subject-specific FE models resulted in sex differences, with the extreme male joint having a broadly distributed stress field and peak stress of 5.28 MPa. The extreme female joint had a concentrated stress field and peak stress of 7.37 MPa. CONCLUSIONS: Intrinsic sex-specific differences independent of scaling with donor skull size were identified in temporomandibular morphometry. Understanding intrinsic sex-specific morphometric differences is critical to determining the temporomandibular biomechanics given the effect of anatomy on joint contact mechanics and stress-strain distributions and requires further study as one potential factor for the increased predisposition of women to temporomandibular disc derangement.

Ordinal Logic Regression: A classifier for discovering combinations of binary markers for ordinal outcomes.

In medicine, it is often useful to stratify patients according to disease risk, severity, or response to therapy. Since many diseases arise from complex gene-gene and gene-environment interactions, patient strata may be defined by combinations of genetic and environmental factors. Traditional statistical methods require specifying interactions a priori making it difficult to identify high order interactions. Alternatively, machine learning methods can model complex interactions, however these models are often difficult to interpret in a clinical setting. Logic regression (LR) enables modeling a binary outcome using logical combinations of binary predictors yielding easily interpretable models. However LR, as currently available, cannot model ordinal responses. This paper extends LR to model an ordinal response and the resulting method is called Ordinal Logic Regression (OLR). Several simulations comparing OLR and Classification and Regression Trees (CART) demonstrate that OLR is superior to CART for identifying variable interactions associated with an ordinal response. OLR is applied to data from a study to determine associations between genetic and health factors with severity of adult periodontitis.

Bayesian analysis of recurrent event with dependent termination: an application to a heart transplant study.

For a heart transplant patient, the risk of graft rejection and risk of death are likely to be associated. Two fully specified Bayesian models for recurrent events with dependent termination are applied to investigate the potential relationships between these two types of risk as well as association with risk factors. We particularly focus on the choice of priors, selection of the appropriate prediction model, and prediction methods for these two types of risk for an individual patient. Our prediction tools can be easily implemented and helpful to physicians for setting heart transplant patients' biopsy schedule.

Differential expression of mitogen activating protein kinases in periodontitis.

AIM: Following toll-like receptor (TLR) engagement, lipopolysaccharide (LPS) can stimulate the expression of pro-inflammatory cytokines thus activating the innate immune response. The production of inflammatory cytokines results, in part, from the activation of kinase-induced signalling cascades and transcriptional factors. Of the four distinct classes of mitogen-activated protein kinases (MAPK) described in mammals, p38, c-Jun N-terminal activated kinases (JNK1-3) and extracellular activated kinases (ERK1,2) are the best studied. Previous data have established that p38 MAPK signalling is required for inflammation and bone loss in periodontal disease pre-clinical animal models. MATERIALS & METHODS: In this study, we obtained healthy and diseased periodontal tissues along with clinical parameters and microbiological parameters. Excised fixed tissues were immunostained with total and phospho-specific antibodies against p38, JNK and ERK kinases. RESULTS: Intensity scoring from immunostained tissues was correlated with clinical periodontal parameters. Rank correlations with clinical indices were statistically significantly positive (p-value < 0.05) for total p38 (correlations ranging 0.49-0.68), phospho-p38 (range 0.44-0.56), and total ERK (range 0.52-0.59) levels, and correlations with JNK levels also supported association (range 0.42-0.59). Phospho-JNK and phospho-ERK showed no significant positive correlation with clinical parameters of disease. CONCLUSION: These data strongly implicate p38 MAPK as a major MAPK involved in human periodontal inflammation and severity.

Metabolic syndrome and periodontitis in Gullah African Americans with type 2 diabetes mellitus.

AIM: To assess associations of metabolic syndrome, and its individual components, with extent of severe periodontitis among patients with type 2 diabetes mellitus (T2DM). MATERIALS & METHODS: We performed a secondary data analysis (N = 283) using a cross-sectional study population of Gullah African Americans with T2DM. Extent of severe periodontitis was assessed as total diseased tooth-sites/person [evaluated as separate outcomes: 6+mm clinical attachment level (CAL), 5+mm periodontal probing depth (PPD)] using negative binomial regression techniques. Primary independent variables assessed in separate models included metabolic syndrome (yes/no), each metabolic syndrome component (low HDL, hypertension, high triglycerides, large waist circumference) and glycemic control (poor/good). RESULTS: Multivariable CAL-model results showed a significant association for metabolic syndrome status with extent of severe periodontitis (RR = 2.77, p = 0.03). The separate multivariable CAL-model including each metabolic syndrome component showed marginally increased rates among those with large waist circumference (RR = 2.33, p = 0.09) and those with HbA1c ≥ 7% (RR = 1.73, p = 0.06). Multivariable PPD-models showed marginally increased rates among those with metabolic syndrome (RR = 2.18, p = 0.06). CONCLUSION: Metabolic syndrome is associated with the extent of severe periodontitis in this Gullah population with T2DM.

Matrix metalloproteinase-8 expression in periodontal tissues surgically removed from diabetic and non-diabetic patients with periodontal disease.

BACKGROUND: Although it is known that periodontal matrix metalloproteinase-8 (MMP-8) expression is associated with periodontal disease, the information concerning the periodontal MMP-8 expression in diabetic patients with periodontal disease is insufficient. MATERIALS AND METHODS: Periodontal tissue specimens were collected from seven patients without periodontal disease and diabetes (Group 1), 15 patients with periodontal disease alone (Group 2) and 10 patients with both periodontal disease and diabetes (Group 3). The frozen sections were prepared and MMP-8 protein expression was detected using immunohistochemistry and quantified. For in vitro study, human U937 mononuclear cells were pre-exposed to normal or high glucose and then treated with lipopolysaccharide (LPS). RESULTS: The nonparametric Kruskal-Wallis test showed that the difference in MMP-8 protein levels among the three groups were statistically significant (p = 0.003). Nonparametric analysis using Jonckheere-Terpstra test showed a tendency of increase in periodontal MMP-8 levels across Group 1 to Group 2 to Group 3 (p = 0.0002). In vitro studies showed that high glucose and LPS had a synergistic effect on MMP-8 expression. CONCLUSION: Our current study showed an increasing trend in MMP-8 protein expression levels across patients without both periodontal disease and diabetes, patients with periodontal disease alone and patients with both diseases.

Reduction in postoperative high-density lipoprotein cholesterol levels in children undergoing the Fontan operation.

Despite the emerging relevance of high-density lipoprotein (HDL) in the inflammatory cascade and vascular barrier integrity, HDL levels in children undergoing cardiac surgery are unexplored. As a measure of HDL levels, the HDL-cholesterol (HDL-C) in single-ventricle patients was quantified before and after the Fontan operation, and it was determined whether relationships existed between the duration and the type of postoperative pleural effusions. The study prospectively enrolled 12 children undergoing the Fontan operation. Plasma HDL-C levels were measured before and after cardiopulmonary bypass. The outcome variables of interest were the duration and type of chest tube drainage (chylous vs. nonchylous). The Kendall rank correlation coefficient and the Wilcoxon rank sum test were used. There were 11 complete observations. The median preoperative HDL-C level for all the subjects was 30 mg/dl (range, 24-53 mg/dl), and the median postcardiopulmonary bypass level was 21 mg/dl (range, 14-46 mg/dl) (p = 0.004). There was a tendency toward a moderate inverse correlation (-0.42) between the postcardiopulmonary bypass HDL-C level and the duration of chest tube drainage, but the result was not statistically significant (p = 0.07). In the chylous effusion group, the median postcardiopulmonary bypass HDL-C tended to be lower (16 vs. 23 mg/dl; p = 0.09). After the Fontan operation, the plasma HDL-C levels in children are significantly reduced. It is reasonable to conclude that the reduction in HDL-C reflects reduced plasma levels of HDL particles, which may have pertinent implications in postoperative pleural effusions given the antiinflammatory and endothelial barrier functions of HDL.

Consistent Differential Expression Pattern (CDEP) on microarray to identify genes related to metastatic behavior.

BACKGROUND: To utilize the large volume of gene expression information generated from different microarray experiments, several meta-analysis techniques have been developed. Despite these efforts, there remain significant challenges to effectively increasing the statistical power and decreasing the Type I error rate while pooling the heterogeneous datasets from public resources. The objective of this study is to develop a novel meta-analysis approach, Consistent Differential Expression Pattern (CDEP), to identify genes with common differential expression patterns across different datasets. RESULTS: We combined False Discovery Rate (FDR) estimation and the non-parametric RankProd approach to estimate the Type I error rate in each microarray dataset of the meta-analysis. These Type I error rates from all datasets were then used to identify genes with common differential expression patterns. Our simulation study showed that CDEP achieved higher statistical power and maintained low Type I error rate when compared with two recently proposed meta-analysis approaches. We applied CDEP to analyze microarray data from different laboratories that compared transcription profiles between metastatic and primary cancer of different types. Many genes identified as differentially expressed consistently across different cancer types are in pathways related to metastatic behavior, such as ECM-receptor interaction, focal adhesion, and blood vessel development. We also identified novel genes such as AMIGO2, Gem, and CXCL11 that have not been shown to associate with, but may play roles in, metastasis. CONCLUSIONS: CDEP is a flexible approach that borrows information from each dataset in a meta-analysis in order to identify genes being differentially expressed consistently. We have shown that CDEP can gain higher statistical power than other existing approaches under a variety of settings considered in the simulation study, suggesting its robustness and insensitivity to data variation commonly associated with microarray experiments. AVAILABILITY: CDEP is implemented in R and freely available at: http://genomebioinfo.musc.edu/CDEP/. CONTACT: zhengw@musc.edu.

Logic Forest: an ensemble classifier for discovering logical combinations of binary markers.

MOTIVATION: Highly sensitive and specific screening tools may reduce disease -related mortality by enabling physicians to diagnose diseases in asymptomatic patients or at-risk individuals. Diagnostic tests based on multiple biomarkers may achieve the needed sensitivity and specificity to realize this clinical gain. RESULTS: Logic regression, a multivariable regression method predicting an outcome using logical combinations of binary predictors, yields interpretable models of the complex interactions in biologic systems. However, its performance degrades in noisy data. We extend logic regression for classification to an ensemble of logic trees (Logic Forest, LF). We conduct simulation studies comparing the ability of logic regression and LF to identify variable interactions predictive of disease status. Our findings indicate LF is superior to logic regression for identifying important predictors. We apply our method to single nucleotide polymorphism data to determine associations of genetic and health factors with periodontal disease. AVAILABILITY: LF code is publicly available on CRAN, http://cran.r-project.org/.

Health insurance status is associated with periodontal disease progression among Gullah African-Americans with type 2 diabetes mellitus.

OBJECTIVES: Assess periodontal disease progression among GullahAfrican Americans with type 2 diabetes mellitus (T2DM) according to health insurance coverage. METHODS: From an ongoing clinical trial among T2DM Gullah, we extracted a cohort that was previously enrolled in a cross-sectional study (N=93). Comparing prior exam to trial initiation, total tooth sites/person with periodontal disease progression events [evaluated separately: 2+ mm of clinical attachment loss (CAL), 2+ mm increased periodontal probing depths (PPD), bleeding on probing (BOP) emergence] were evaluated according to health insurance coverage using regression techniques appropriate for data with different counts of potential events per subject (varying tooth sites available). We used negative binomial regression techniques to account for overdispersion and fit multivariable models that also included baseline glycemic control (poor: glycated hemoglobin > OR =7 percent, well: glycated hemoglobin <7 percent), history of established periodontitis, age, gender, body mass index, annual income, and oral hygiene behaviors. Final models included health insurance status, other significant predictors, and any observed confounders. RESULTS: Privately insured were most prevalent (41.94 percent), followed by uninsured (23.66 percent), Medicare (19.35 percent), and Medicaid (15.05 percent). Those with poor glycemic control (65.59 percent) were more prevalent than well-controlled (34.41 percent). CAL events ranged from 0 to 58.8 percent tooth sites/ person (11.83 +/- 12.44 percent), while PPD events ranged from 0 to 44.2 percent (8.66 +/- 10.97 percent) and BOP events ranged from 0 to 95.8 percent (23.65 +/- 17.21 percent). Rates of CAL events were increased among those who were uninsured [rate ratio (RR) = 1.75, P = 0.02], Medicare-insured (RR = 1.90, P = 0.03), and Medicaid-insured (RR = 1.89, P = 0.06). CONCLUSIONS: Increased access to health care, including dental services, may achieve reduction in chronic periodontal disease progression (as determined by CAL) for this study population. These results are very timely given the March 2010 passing of the US healthcare reform bills.

Acculturation and Health Beliefs: Interactions Between Host and Heritage Culture Underlie Latina/o Caregivers' Beliefs About HPV Vaccination.

This study examined the interactive effects of acculturation (host culture acquisition) and enculturation (heritage culture retention) on Latina/o caregivers' beliefs about their child completing the human papillomavirus vaccine series. Participants were 161 caregiver-child dyads from Florida. Using multiple regression, caregiver knowledge and health beliefs (perceived threat, benefits, barriers, subjective norms, and self-efficacy) about series completion were predicted from caregivers' scores on acculturation, enculturation, and their interaction, controlling for sociodemographics. Acculturation and enculturation interacted to predict knowledge, benefits, barriers, and self-efficacy. Caregivers with high acculturation scores generally supported series completion, regardless of their enculturation score. However, when acculturation was low, caregivers who retained more (vs. less) of their heritage culture were more knowledgeable and held more favorable beliefs about series completion. Findings highlight the importance of independently assessing acculturation and enculturation in Latina/o immigrant populations. Overlooking enculturation may lead to incomplete conclusions about acculturation and health.

Sexual dimorphisms in three-dimensional masticatory muscle attachment morphometry regulates temporomandibular joint mechanics.

Temporomandibular joint (TMJ) disorders disproportionally affect females, with female to male prevalence varying from 3:1 to 8:1. Sexual dimorphisms in masticatory muscle attachment morphometry and association with craniofacial size, critical for understanding sex-differences in TMJ function, have not been reported. The objective of this study was to determine sex-specific differences in three-dimensional (3D) TMJ muscle attachment morphometry and craniofacial sizes and their impact on TMJ mechanics. Human cadaveric TMJ muscle attachment morphometry and craniofacial anthropometry (10Males; 11Females) were determined by previously developed 3D digitization and imaging-based methods. Sex-differences in muscle attachment morphometry and craniofacial anthropometry, and their correlation were determined, respectively using multivariate general linear and linear regression statistical models. Subject-specific musculoskeletal models of the mandible were developed to determine effects of sexual dimorphisms in mandibular size and TMJ muscle attachment morphometry on joint loading during static biting. There were significant sex-differences in craniofacial size (p = 0.024) and TMJ muscle attachment morphometry (p < 0.001). TMJ muscle attachment morphometry was significantly correlated with craniofacial size. TMJ contact forces estimated from biomechanical models were significantly, 23% on average (p < 0.001), greater for females compared to those for males when generating the same bite forces. There were significant linear correlations between TMJ contact force and both 3D mandibular length (R2 = 0.48, p < 0.001) and muscle force moment arm ratio (R2 = 0.68, p < 0.001). Sexual dimorphisms in masticatory muscle morphology and craniofacial sizes play critical roles in subject-specific TMJ biomechanics. Sex-specific differences in the TMJ mechanical environment should be further investigated concerning mechanical fatigue of TMJ discs associated with TMJ disorders.

An investigation of the MC-SIMEX method with application to measurement error in periodontal outcomes.

Measurement error is pervasive in medical research. In periodontal research studies, one measure of disease status is the probed pocket depth (PPD), the depth of the space between a tooth and the surrounding gum. In larger studies, these assessments are made by multiple examiners, each having distinct measurement error characteristics. Because PPD is recorded in whole millimeters, it may be regarded as discrete and its associated error as misclassification error. This study investigates the impact of this measurement error when evaluating the effect of periodontal disease status on levels of inflammatory markers in gingival crevicular fluid (GCF). The marker readings are either left or right censored, due to quantities that are either too small to be reliably quantified or so large that they saturate the detector. Additionally, marker readings from multiple periodontal sites within a subject's mouth are correlated. These considerations give rise to a clustered survival model for the marker readings in which the discrete predictor of interest is misclassified. Associations between the GCF markers and periodontal assessments are corrected for misclassification error using the MC-SIMEX method. Simulation studies reveal the impact of varying degrees of misclassification error on associations of interest. Analysis of pilot data from a periodontal study, for which examiner misclassification rates are estimated from calibration studies, further illustrates the approach.

Bayesian modeling of multivariate spatial binary data with applications to dental caries.

Dental research gives rise to data with potentially complex correlation structure. Assessments of dental caries yield a binary outcome indicating the presence or absence of caries experience for each surface of each tooth in a subject's mouth. In addition to this nesting, caries outcome exhibit spatial structure among neighboring teeth. We develop a Bayesian multivariate model for spatial binary data using random effects autologistic regression that controls for the correlation within tooth surfaces and spatial correlation among neighboring teeth. Using a sample from a clinical study conducted at the Medical University of South Carolina, we compare this autologistic model with covariates to alternative models to demonstrate the improvement in predictions and also to assess the effects of covariates on caries experience.

Simvastatin suppresses LPS-induced MMP-1 expression in U937 mononuclear cells by inhibiting protein isoprenylation-mediated ERK activation.

Matrix metalloproteinase (MMP) plays a crucial role in periodontal disease and is up-regulated by oral Gram-negative, pathogen-derived LPS. In this study, we reported that simvastatin, a 3-hydroxyl-3-methylglutaryl-CoA reductase inhibitor, effectively inhibited LPS-stimulated MMP-1 as well as MMP-8 and MMP-9 expression by U937 mononuclear cells. Our studies showed that the geranylgeranyl transferase inhibitor inhibited LPS-stimulated MMP-1 expression, and addition of isoprenoid intermediate geranylgeranyl pyrophosphate (GGPP) reduced the inhibitory effect of simvastatin on LPS-stimulated MMP-1 expression. We also demonstrated that simvastatin inhibited the activation of Ras and Rac, and the inhibition was abolished by addition of GGPP. The above results indicate that protein isoprenylation is involved in the regulation of MMP-1 expression by LPS and simvastatin. Moreover, we showed that simvastatin inhibited LPS-stimulated nuclear AP-1, but not NF-kappaB activity, and the inhibition was reversed by addition of GGPP. Simvastatin also inhibited LPS-stimulated ERK but not p38 MAPK and JNK. Finally, we showed that the inhibition of LPS-stimulated ERK activation by simvastatin was reversed by GGPP. Taken together, this study showed that simvastatin suppresses LPS-induced MMP-1 expression in U937 mononuclear cells by targeting protein isoprenylation-mediated ERK activation.

Periodontal disease status in gullah african americans with type 2 diabetes living in South Carolina.

BACKGROUND: African Americans have a disproportionate burden of diabetes. Gullah African Americans are the most genetically homogeneous population of African descent in the United States, with an estimated European admixture of only 3.5%. This study assessed the previously unknown prevalence of periodontal disease among a sample of Gullah African Americans with diabetes and investigated the association between diabetes control and the presence of periodontal disease. METHODS: Two hundred thirty-five Gullah African Americans with type 2 diabetes were included. Diabetes control was assessed by percentage of glycosylated hemoglobin (HbA1c) and divided into three categories: well controlled, <7%; moderately controlled, 7% to 8.5%; and poorly controlled, >8.5%. Participants were categorized as healthy (no clinical attachment loss [AL] or bleeding on probing) or as having early periodontitis (clinical AL > or =1 mm in at least two teeth), moderate periodontitis (three sites with clinical AL > or =4 mm and at least two sites with probing depth [PD] > or =3 mm), or severe periodontitis (clinical AL > or =6 mm in at least two teeth and PD > or =5 mm in at least one site). Observed prevalences of periodontitis were compared to rates reported for the National Health and Nutrition Examination Survey (NHANES) studies. RESULTS: All subjects had evidence of periodontal disease: 70.6% had moderate periodontitis and 28.5% had severe disease. Diabetes control was not associated with periodontal disease. The periodontal disease proportions were significantly higher than the reported national prevalence of 10.6% among African Americans without diabetes. CONCLUSION: Our sample of Gullah African Americans with type 2 diabetes exhibited a higher prevalence of periodontal disease compared to African Americans, with and without diabetes, as reported in NHANES III and NHANES 1999-2000.