As cellular variability and circadian rhythmicity play critical roles in immune and inflammatory responses, we present in this study an agent-based model of human endotoxemia to examine the interplay between circadian controls, cellular variability and stochastic dynamics of inflammatory cytokines. The model is qualitatively validated by its ability to reproduce circadian dynamics of inflammatory mediators and critical inflammatory responses after endotoxin administration in vivo. Novel computational concepts are proposed to characterize the cellular variability and synchronization of inflammatory cytokines in a population of heterogeneous leukocytes. Our results suggest that there is a decrease in cell-to-cell variability of inflammatory cytokines while their synchronization is increased after endotoxin challenge. Model parameters that are responsible for IκB production stimulated by NFκB activation and for the production of anti-inflammatory cytokines have large impacts on system behaviors. Additionally, examining time-dependent systemic responses revealed that the system is least vulnerable to endotoxin in the early morning and most vulnerable around midnight. Although much remains to be explored, proposed computational concepts and the model we have pioneered will provide important insights for future investigations and extensions, especially for single-cell studies to discover how cellular variability contributes to clinical implications.

Introduction

Conventional treatment for young Class III patients involves extraoral devices designed to either protract the maxilla or restrain mandibular growth. The use of skeletal anchorage offers a promising alternative to obtain orthopedic results with fewer dental compensations. Our aim was to evaluate 3-dimensional changes in the mandibles and the glenoid fossae of Class III patients treated with bone-anchored maxillary protraction.

Methods

Twenty-five consecutive skeletal Class III patients between the ages of 9 and 13 years (mean age, 11.10 ± 1.1 year) were treated with Class III intermaxillary elastics and bilateral miniplates (2 in the infrazygomatic crests of the maxilla and 2 in the anterior mandible). The patients had cone-beam computed tomography images taken before initial loading and at the end of active treatment. Three-dimensional models were generated from these images, registered on the anterior cranial base, and analyzed by using color maps.

Results

Posterior displacement of the mandible at the end of treatment was observed in all subjects (posterior ramus: mean, 2.74 ± 1.36 mm; condyles: mean, 2.07 ± 1.16 mm; chin: mean, −0.13 ± 2.89 mm). Remodeling of the glenoid fossa at the anterior eminence (mean, 1.38 ± 1.03 mm) and bone resorption at the posterior wall (mean, −1.34 ± 0.6 mm) were observed in most patients.

Conclusions

This new treatment approach offers a promising alternative to restrain mandibular growth for Class III patients with a component of mandibular prognathism or to compensate for maxillary deficiency in patients with hypoplasia of the midface. Future studies with long-term follow-up and comparisons with facemask and chincup therapies are needed to better understand the treatment effects.

The inflammatory response, and its subsequent resolution, are the result of a very complex cascade of events originating at the site of injury or infection. When the response is severe and persistent, Systemic Inflammatory Response Syndrome can set in, which is associated with a severely debilitating systemic hypercatabolic state. This complex behavior, mediated by cytokines and chemokines, needs to be further explored to better understand its systems properties and potentially identify multiple targets that could be addressed simultaneously. In this context, short term responses of serum cytokines and chemokines were analyzed in two types of insults: rats receiving a “sterile” cutaneous dorsal burn on 20% of the total body surface area (TBSA); rats receiving a cecum ligation and puncture treatment (CLP) to induce infection. Considering the temporal variability observed in the baseline corresponding to the control group, the concept of area under the curve (AUC) was explored to assess the dynamic responses of cytokines and chemokines. MCP-1, GROK/KC, IL-12, IL-18 and IL-10 were observed in both burn and CLP groups. While IL-10 concentration was only increased in the burn group, Eotaxin was only elevated in CLP group. It was also observed that Leptin and IP-1 concentrations were decreased in both CLP and sham-CLP groups. The link between the circulating protein mediators and putative transcription factors regulating the cytokine/chemokine gene expression was explored by searching the promoter regions of cytokine/chemokine genes in order to characterize and differentiate the inflammatory responses based on the dynamic data. Integrating multiple sources together with the bioinformatics tools identified mediators sensitive to type and extent of injury, and provided putative regulatory mechanisms. This is essential to gain a better understanding for the important regulatory points that can be used to modulate the inflammatory state at molecular level.

Objectives

To examine how the National Cancer Institute-funded Community Network Program (CNP) operationalized principles of community-based participatory research (CBPR).

Methods

Based on our review of the literature and extant CBPR measurement tools, scientists from nine of 25 CNPs developed a 27-item questionnaire to self-assess CNP operationalization of nine CBPR principles.

Results

Of 25 CNPs, 22 (88%) completed the questionnaire. Most scored well on CBPR principles to recognize community as a unit of identity, build on community strengths, facilitate co-learning, embrace iterative processes in developing community capacity, and achieve a balance between data generation and intervention. CNPs varied in extent to which they employed CBPR principles of addressing determinants of health, sharing power among partners, engaging community in research dissemination, and striving for sustainability.

Conclusions

Although tool development in this field is in its infancy, findings suggest that fidelity to CBPR processes can be assessed in a variety of settings.

Surname lists are increasingly being used to identify Asian study participants. Two Vietnamese surname lists have previously been published: the Vietnamese Community Health Promotion Program (VCHPP) list and the Lauderdale list. This report provides findings from a descriptive analysis of the performance of these lists in identifying Vietnamese. To identify participants for a survey of Vietnamese women, a surname list (that included names that appear on the VCHPP list and/or Lauderdale list) was applied to the Seattle telephone book. We analyzed surname data for all addresses in the survey sample, as well as survey respondents. The VCHPP list identified 4,283 potentially Vietnamese households, and 79% of the households with established ethnicity were Vietnamese; and the Lauderdale list identified 4,068 potentially Viet-namese households, and 80% of the households with established ethnicity were Vietnamese. However, the proportions of contacted households that were Vietnamese varied significantly among commonly occurring surnames. The characteristics of women with surnames on the VCHPP and Lauderdale lists were equivalent. The two lists performed equally well in identifying Vietnamese households. Researchers might consider using different combinations of Vietnamese surnames, depending on whether accuracy or high population coverage is the more important consideration.

Smoking prevalence among Vietnamese American males remains higher than the U.S. general population. This study examined the associations of individual and family factors with quit intention among Vietnamese male smokers in California to guide intervention development to reduce their smoking prevalence. Data for Vietnamese male current smokers (n = 234) in the 2008 California Vietnamese Adult Tobacco Use Survey (N=1,101 males) were analyzed to describe quit intention and previous quit attempts. One-third of Vietnamese male smokers (33%) had no intention to quit at any time, 36% intended to quit soon (in the next 30 days), and 31% intended to quit later (beyond the next 30 days). Half (51.7%) of the sample was in “precontemplation,” indicating no intention to quit within 6 months. Many (71%) had made a serious quit attempt in the past year, but 68% of those who tried to quit used no cessation assistance. Multivariate logistic regression adjusting for age, depression, smoking intensity, nicotine dependence, health knowledge, children in the household and home smoking ban revealed that having smoking-related family conflicts and a quit attempt in the past year with or without assistance were independently associated with an intention to quit either in the next 30 days or later. Higher education was associated with no intention to quit. Findings underscore the importance of designing strategic interventions that meet the needs of smokers at both individual and family levels to promote quit intention and to facilitate successful quitting in this population.

This paper describes a new program SnpSift for filtering differential DNA sequence variants between two or more experimental genomes after genotoxic chemical exposure. Here, we illustrate how SnpSift can be used to identify candidate phenotype-relevant variants including single nucleotide polymorphisms, multiple nucleotide polymorphisms, insertions, and deletions (InDels) in mutant strains isolated from genome-wide chemical mutagenesis of Drosophila melanogaster. First, the genomes of two independently isolated mutant fly strains that are allelic for a novel recessive male-sterile locus generated by genotoxic chemical exposure were sequenced using the Illumina next-generation DNA sequencer to obtain 20- to 29-fold coverage of the euchromatic sequences. The sequencing reads were processed and variants were called using standard bioinformatic tools. Next, SnpEff was used to annotate all sequence variants and their potential mutational effects on associated genes. Then, SnpSift was used to filter and select differential variants that potentially disrupt a common gene in the two allelic mutant strains. The potential causative DNA lesions were partially validated by capillary sequencing of polymerase chain reaction-amplified DNA in the genetic interval as defined by meiotic mapping and deletions that remove defined regions of the chromosome. Of the five candidate genes located in the genetic interval, the Pka-like gene CG12069 was found to carry a separate pre-mature stop codon mutation in each of the two allelic mutants whereas the other four candidate genes within the interval have wild-type sequences. The Pka-like gene is therefore a strong candidate gene for the male-sterile locus. These results demonstrate that combining SnpEff and SnpSift can expedite the identification of candidate phenotype-causative mutations in chemically mutagenized Drosophila strains. This technique can also be used to characterize the variety of mutations generated by genotoxic chemicals.

Hypermethylation of the promoter region of tumor-related genes (TRGs) has been shown to silence gene expression during melanoma progression, whereas microRNA-29(miR-29) has been found to downregulate DNA methyltransferases DNMT3A and DNMT3B which were shown as essential to the methylation of TRGs. We hypothesized that the expression level of miR-29 is associated to TRG methylation status and may have prognostic utility in melanoma. AJCC stage I–IV cutaneous melanoma paraffin-embedded archival tissue (PEAT) specimens (n = 149) were assessed. Expression of miR-29 isoforms a, b and c were analyzed by reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR). Expression of DNMT3A and DNMT3B was assessed by immunohistochemistry (IHC) on defined clinically annotated tissue microarrays (TMA) of AJCC stage III melanoma lymph node metastases. Promoter region CpG island methylation status of RASSF1A, TFPI-2, RAR-β, SOCS, GATA4 and genomic sequences MINT17 and MINT31 were previously evaluated in melanoma tissues. miR-29c isoform expression was correlated to advancing AJCC stages in melanoma. miR-29c expression was significantly downregulated in AJCC stage IV melanoma tumors compared to primary melanomas. Hypermethylation status of TRGs and non-coding MINT loci in different stages of melanoma showed an inverse association with miR-29c expression. Overall, an increase in miR-29c expression inversely correlated to both DNMT3A and DNMT3B protein expression in melanomas. Expression of DNMT3B and miR-29c were significantly (p = 0.004 and p = 0.002, respectively) associated with overall survival (OS) in AJCC stage III melanoma patients by multivariate analysis. The studies demonstrated that both miR-29c and DNMT3B have significant roles in melanoma progression and may be useful epigenetic biomarkers for disease outcome.

Foot-and-mouth disease (FMD) outbreaks recently affected 2 countries (Japan and South Korea) in eastern Asia that were free of FMD without vaccination. Analysis of viral protein 1 nucleotide sequences indicated that FMD serotype A and O viruses that caused these outbreaks originated in mainland Southeast Asia to which these viruses are endemic.

Mitigating the unequal burden of cancer often involves conducting community-based trials to develop effective intervention strategies to promote cancer-related health behaviors. However, this is challenging due to the simultaneous influence of numerous factors, at multiple levels in the socio-ecological context, on health behavior. A sound conceptual framework can bring order to this complex environment and provide a roadmap for systematically addressing the multiple determinants of the behavior in question. This paper describes the application of The Health Behavior Framework, an integrative conceptual model, in an ongoing Program Project, “Liver Cancer Control Interventions for Asian-Americans.” The Framework has been integral to shaping all aspects of the three component research trials from selection of the study designs to development of the interventions and data collection instruments. We advocate universal adoption of theory into community-based intervention research as a way to accelerate our ability to develop effective interventions and facilitate synthesis of study results across populations and behavioral outcomes: critical steps in advancing the field of health disparities research.

Objectives

We conducted a trial to evaluate the effectiveness of a cervical cancer control intervention for Vietnamese women.

Methods

The study group included 234 women who had not received a Pap test in the last three years. Experimental group participants received a lay health worker home visit. Our trial end-point was Pap smear receipt within six months of randomization. Pap testing completion was ascertained through women's self-reports and medical record reviews. We examined intervention effects among women who had ever received a Pap smear (prior to randomization) and women who had never received a Pap smear.

Results

Three-quarters of the experimental group women completed a home visit. Ever screened experimental group women were significantly more likely to report Pap testing (p<0.02) and have records verified Pap testing (p<0.04) than ever screened control group women. There were no significant differences between the trial arms for women who had never been screened.

Conclusions

Our findings indicate that lay health worker interventions for Vietnamese women are feasible to implement and can positively impact levels of Pap testing use among ever screened women (but not never screened women).

A 51-year-old female undergoing an outpatient stress echocardiogram to evaluate atypical chest pain developed acute ST elevation in the anterior precordial leads on electrocardiogram following exercise. Echocardiography revealed a severe rise in pulmonary artery systolic pressure (PASP) with marked right ventricular (RV) enlargement and interventricular septum flattening. Subsequently, cardiac catherization confirmed an exercise-induced elevation in PASP and diagnosed pulmonary arterial hypertension without evidence of coronary artery disease. This case suggests that an acute elevation in pulmonary artery pressure with RV dilation may be a potential cause of acute ST elevation during stress testing.

Background

Research in genetics has developed rapidly recently due to the aid of next generation sequencing (NGS). However, massively-parallel NGS produces enormous amounts of data, which leads to storage, compatibility, scalability, and performance issues. The Cloud Computing and MapReduce framework, which utilizes hundreds or thousands of shared computers to map sequencing reads quickly and efficiently to reference genome sequences, appears to be a very promising solution for these issues. Consequently, it has been adopted by many organizations recently, and the initial results are very promising. However, since these are only initial steps toward this trend, the developed software does not provide adequate primary functions like bisulfite, pair-end mapping, etc., in on-site software such as RMAP or BS Seeker. In addition, existing MapReduce-based applications were not designed to process the long reads produced by the most recent second-generation and third-generation NGS instruments and, therefore, are inefficient. Last, it is difficult for a majority of biologists untrained in programming skills to use these tools because most were developed on Linux with a command line interface.

Results

To urge the trend of using Cloud technologies in genomics and prepare for advances in second- and third-generation DNA sequencing, we have built a Hadoop MapReduce-based application, CloudAligner, which achieves higher performance, covers most primary features, is more accurate, and has a user-friendly interface. It was also designed to be able to deal with long sequences. The performance gain of CloudAligner over Cloud-based counterparts (35 to 80%) mainly comes from the omission of the reduce phase. In comparison to local-based approaches, the performance gain of CloudAligner is from the partition and parallel processing of the huge reference genome as well as the reads. The source code of CloudAligner is available at http://cloudaligner.sourceforge.net/ and its web version is at http://mine.cs.wayne.edu:8080/CloudAligner/.

Conclusions

Our results show that CloudAligner is faster than CloudBurst, provides more accurate results than RMAP, and supports various input as well as output formats. In addition, with the web-based interface, it is easier to use than its counterparts.

One of the great challenges in the post-genomic era is to decipher the underlying principles governing the dynamics of biological responses. As modulating gene expression levels is among the key regulatory responses of an organism to changes in its environment, identifying biologically relevant transcriptional regulators and their putative regulatory interactions with target genes is an essential step towards studying the complex dynamics of transcriptional regulation. We present an analysis that integrates various computational and biological aspects to explore the transcriptional regulation of systemic inflammatory responses through a human endotoxemia model. Given a high-dimensional transcriptional profiling dataset from human blood leukocytes, an elementary set of temporal dynamic responses which capture the essence of a pro-inflammatory phase, a counter-regulatory response and a dysregulation in leukocyte bioenergetics has been extracted. Upon identification of these expression patterns, fourteen inflammation-specific gene batteries that represent groups of hypothetically ‘coregulated’ genes are proposed. Subsequently, statistically significant cis-regulatory modules (CRMs) are identified and decomposed into a list of critical transcription factors (34) that are validated largely on primary literature. Finally, our analysis further allows for the construction of a dynamic representation of the temporal transcriptional regulatory program across the host, deciphering possible combinatorial interactions among factors under which they might be active. Although much remains to be explored, this study has computationally identified key transcription factors and proposed a putative time-dependent transcriptional regulatory program associated with critical transcriptional inflammatory responses. These results provide a solid foundation for future investigations to elucidate the underlying transcriptional regulatory mechanisms under the host inflammatory response. Also, the assumption that coexpressed genes that are functionally relevant are more likely to share some common transcriptional regulatory mechanism seems to be promising, making the proposed framework become essential in unravelling context-specific transcriptional regulatory interactions underlying diverse mammalian biological processes.

Differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes requires extensive changes in gene expression, which are partly mediated by post-translational modifications of nucleosomal histones. An essential modification for oligodendrocyte differentiation is the removal of acetyl groups from lysine residues which is catalyzed by histone deacetylases (HDACs). The transcriptional targets of HDAC activity within OPCs however, have remained elusive and have been identified in this study by interrogating the oligodendrocyte transcriptome. Using a novel algorithm that allows clustering of gene transcripts according to expression kinetics and expression levels, we defined major waves of co-regulated genes. The initial overall decrease in gene expression was followed by the up-regulation of genes involved in lipid metabolism and myelination. Functional annotation of the down-regulated gene clusters identified transcripts involved in cell cycle regulation, transcription, and RNA processing. To define whether these genes were the targets of HDAC activity, we cultured rat OPCs in the presence of trichostatin A (TSA), an HDAC inhibitor previously shown to inhibit oligodendrocyte differentiation. By overlaying the defined oligodendrocyte transcriptome with the list of ‘TSA sensitive’ genes, we determined that a high percentage of ‘TSA sensitive’ genes are part of a normal program of oligodendrocyte differentiation. TSA treatment increased the expression of genes whose down-regulation occurs very early after induction of OPC differentiation, but did not affect the expression of genes with a slower kinetic. Among the increased ‘TSA sensitive’ genes we detected several transcription factors including Id2, Egr1, and Sox11, whose down-regulation is critical for OPC differentiation. Thus, HDAC target genes include clusters of co-regulated genes involved in transcriptional repression. These results support a de-repression model of oligodendrocyte lineage progression that relies on the concurrent down-regulation of several inhibitors of differentiation.

Hypermethylation of the promoter region of tumor-related genes (TRGs) has been shown to silence gene expression during melanoma progression, whereas microRNA-29(miR-29) has been found to downregulate DNA methyltransferases DNMT3A and DNMT3B which were shown as essential to the methylation of TRGs. We hypothesized that the expression level of miR-29 is associated to TRG methylation status and may have prognostic utility in melanoma. AJCC stage I–IV cutaneous melanoma paraffin-embedded archival tissue (PEAT) specimens (n = 149) were assessed. Expression of miR-29 isoforms a, b and c were analyzed by reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR). Expression of DNMT3A and DNMT3B was assessed by immunohistochemistry (IHC) on defined clinically annotated tissue microarrays (TMA) of AJCC stage III melanoma lymph node metastases. Promoter region CpG island methylation status of RASSF1A, TFPI-2, RAR-β, SOCS, GATA4 and genomic sequences MINT17 and MINT31 were previously evaluated in melanoma tissues. miR-29c isoform expression was correlated to advancing AJCC stages in melanoma. miR-29c expression was significantly downregulated in AJCC stage IV melanoma tumors compared to primary melanomas. Hypermethylation status of TRGs and non-coding MINT loci in different stages of melanoma showed an inverse association with miR-29c expression. Overall, an increase in miR-29c expression inversely correlated to both DNMT3A and DNMT3B protein expression in melanomas. Expression of DNMT3B and miR-29c were significantly (p = 0.004 and p = 0.002, respectively) associated with overall survival (OS) in AJCC stage III melanoma patients by multivariate analysis. The studies demonstrated that both miR-29c and DNMT3B have significant roles in melanoma progression and may be useful epigenetic biomarkers for disease outcome.

Objective

Measurement tools such as surveys assessing knowledge, attitudes and behaviors need to be theoretically consistent with interventions. The purpose of this paper is to describe the first steps in the process of constructing a theoretically-based set of measures that is currently used in three trials to reduce liver cancer disparities.

Methods

Guided by a common theoretical formulation - the Health Behavior Framework - we identified constructs relevant for liver cancer control research, compiled items from previous studies and constructed new items, and translated and pilot tested items in collaboration with members of the Vietnamese, Korean, and Hmong communities.

Results

We constructed three questionnaires in Vietnamese, Hmong and Korean language that are slightly different due to cultural and language nuances, but contain a core set of measures assessing identical constructs of the Health Behavior Framework. Initial research demonstrates that items are easily understood and that they are generally related to hepatitis B screening as expected.

Conclusions

Researchers are encouraged to follow a similar process for creating theory-based assessment tools. Measuring common theoretical constructs can advance liver cancer control and other health research by facilitating a more systematic comparison of findings across different populations and intervention strategies.

Objective

Recent US data indicate that women of Vietnamese descent have higher cervical cancer incidence rates than women of any other race/ethnicity, and lower levels of Pap testing than white, black, and Latina women. Our objective was to provide information about Pap testing barriers and facilitators that could be used to develop cervical cancer control intervention programs for Vietnamese American women.

Design

We conducted a cross-sectional, community-based survey of Vietnamese immigrants. Our study was conducted in metropolitan Seattle, Washington. A total of 1,532 Vietnamese American women participated in the study. Demographic, health care, and knowledge/belief items associated with previous cervical cancer screening participation (ever screened and screened according to interval screening guidelines) were examined.

Results

Eighty-one percent of the respondents had been screened for cervical cancer in the previous three years. Recent Pap testing was strongly associated (p<0.001) with having a regular doctor, having a physical in the last year, previous physician recommendation for testing, and having asked a physician for testing. Women whose regular doctor was a Vietnamese man were no more likely to have received a recent Pap smear than those with no regular doctor.

Conclusion

Our findings indicate that cervical cancer screening disparities between Vietnamese and other racial/ethnic groups are decreasing. Efforts to further increase Pap smear receipt in Vietnamese American communities should enable women without a source of health care to find a regular provider. Additionally, intervention programs should improve patient-provider communication by encouraging health care providers (especially male Vietnamese physicians serving women living in ethnic enclaves) to recommend Pap testing, as well as by empowering Vietnamese women to specifically ask their physicians for Pap testing.

Background

Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is a transmembrane protein with multiple functions in different cell types. CEACAM1 expression is frequently mis-regulated in cancer, with down-regulation reported in several tumors of epithelial origin and de novo expression of CEACAM1 in lung cancer and malignant melanoma. In this report we analyzed the regulation of CEACAM1 expression in three breast cancer cell lines that varied in CEACAM1 expression from none (MCF7) to moderate (MDA-MB-468) to high (MCF10A, comparable to normal breast).

Results

Using in vivo footprinting and chromatin immunoprecipitation experiments we show that the CEACAM1 proximal promoter in breast cells is bound in its active state by SP1, USF1/USF2, and IRF1/2. When down-regulated the CEACAM1 promoter remains accessible to USF2 and partially accessible to USF1. Interferon-γ up-regulates CEACAM1 mRNA by a mechanism involving further induction of IRF-1 and USF1 binding at the promoter. As predicted by this analysis, silencing of IRF1 and USF1 but not USF2 by RNAi resulted in a significant decrease in CEACAM1 protein expression in MDA-MB-468 cells. The inactive CEACAM1 promoter in MCF7 cells exhibits decreased histone acetylation at the promoter region, with no evidence of H3K9 or H3K27 trimethylation, histone modifications often linked to condensed chromatin structure.

Conclusions

Our data suggest that transcription activators USF1 and IRF1 interact to modulate CEACAM1 expression and that the chromatin structure of the promoter is likely maintained in a poised state that can promote rapid induction under appropriate conditions.

Background

Physician patterns of screening for hepatitis B (HBV) and hepatocellular carcinoma (HCC) among Asian Americans are not well described.

Aims

To describe HBV and HCC screening practices among providers with large Asian American populations.

Methods

Providers within San Francisco’s safety net system were surveyed with respect to HBV and HCC screening practices as well as knowledge, attitudes, and barriers to HCC screening.

Results

Among the 109 respondents (response rate = 72%), 62% were aged >40, 65% female, 24% Asian, 87% primary care providers, and 48% had >25% Asian patients. Only 76% had screened >50% of their Asian patients for HBV and 43% had vaccinated >50% of eligible patients against HBV. Although 94% knew Asians were disproportionately affected by HCC, only 79% had screened for HCC in >50% of their Asian patients with chronic hepatitis B (CHB). A majority believed that HCC screening in CHB reduces HCC mortality (70%) and is cost-effective (57%). The most common HCC screening modality was AFP with abdominal ultrasound every 6–12 months (63%). Factors associated with HBV screening were familiarity with AASLD guidelines (OR 6.4, 95% CI 1.3–30.1, p = 0.02) and having vaccinated >50% of eligible patients against HBV (OR 2.2, 95% CI 1.1–4.5, p = 0.03). Factors associated with HCC screening using abdominal ultrasound every 6–12 months were having >25% Asian patients (OR = 4.5, 95% CI 1.3–15.3, p = 0.02) and higher HCC knowledge score (OR = 1.9 per item, 95% CI 1.01–3.6, p = 0.045).

Conclusions

HBV and HCC screening rates and HBV vaccination among Asians from physician report is suboptimal. HCC screening is associated with having more Asian patients and higher provider knowledge. Provider education is essential in increasing rates of HBV and HCC screening among Asian Americans.

Background

Comprehensively understanding corticosteroid pharmacogenomic effects is an essential step towards an insight into the underlying molecular mechanisms for both beneficial and detrimental clinical effects. Nevertheless, even in a single tissue different methods of corticosteroid administration can induce different patterns of expression and regulatory control structures. Therefore, rich in vivo datasets of pharmacological time-series with two dosing regimens sampled from rat liver are examined for temporal patterns of changes in gene expression and their regulatory commonalities.

Results

The study addresses two issues, including (1) identifying significant transcriptional modules coupled with dynamic expression patterns and (2) predicting relevant common transcriptional controls to better understand the underlying mechanisms of corticosteroid adverse effects. Following the orientation of meta-analysis, an extended computational approach that explores the concept of agreement matrix from consensus clustering has been proposed with the aims of identifying gene clusters that share common expression patterns across multiple dosing regimens as well as handling challenges in the analysis of microarray data from heterogeneous sources, e.g. different platforms and time-grids in this study. Six significant transcriptional modules coupled with typical patterns of expression have been identified. Functional analysis reveals that virtually all enriched functions (gene ontologies, pathways) in these modules are shown to be related to metabolic processes, implying the importance of these modules in adverse effects under the administration of corticosteroids. Relevant putative transcriptional regulators (e.g. RXRF, FKHD, SP1F) are also predicted to provide another source of information towards better understanding the complexities of expression patterns and the underlying regulatory mechanisms of those modules.

Conclusions

We have proposed a framework to identify significant coexpressed clusters of genes across multiple conditions experimented from different microarray platforms, time-grids, and also tissues if applicable. Analysis on rich in vivo datasets of corticosteroid time-series yielded significant insights into the pharmacogenomic effects of corticosteroids, especially the relevance to metabolic side-effects. This has been illustrated through enriched metabolic functions in those transcriptional modules and the presence of GRE binding motifs in those enriched pathways, providing significant modules for further analysis on pharmacogenomic corticosteroid effects.

Background

The rate of H. pylori infection in Vietnam is reportedly high, but the spectrum of H. pylori-associated gastroduodenal diseases has not been systematically investigated. Moreover, despite the similarities of ethnicity and diet, the age-standardized incidence rate of gastric cancer in the northern city of Hanoi is higher than that in the southern city of Ho Chi Minh, but the reason for this phenomenon is unknown. The virulence of Vietnamese H. pylori has also not been investigated in detail.

Methods

Individuals undergoing esophagogastroduodenoscopy were randomly recruited. H. pylori infection status was determined based on the combined results of culture, histology, immunohistochemistry, rapid urine test and serum ELISA. Peptic ulcer (PU) and gastroesophageal reflux disease was diagnosed by endoscopy, and chronic gastritis was determined histologically. H. pylori virulence factors were investigated by PCR and sequencing.

Results

Among the examined patients, 65.6% were infected with H. pylori. The prevalence of infection was significantly higher in those over 40 years of age than in those aged ≤40. Chronic gastritis was present in all H. pylori-infected individuals, 83.1% of whom had active gastritis, and 85.3% and 14.7% had atrophy and intestinal metaplasia, respectively. PU was present in 21% of infected patients, whereas its incidence was very low in non-infected individuals. The prevalence of PU was significantly higher in Hanoi than in Ho Chi Minh. The prevalence of vacA m1, which has been identified as an independent risk factor for PU in Vietnam, was significantly higher among H. pylori isolates from Hanoi than among those from Ho Chi Minh.

Conclusions

H. pylori infection is common in Vietnam and is strongly associated with PU, active gastritis, atrophy and intestinal metaplasia. vacA m1 is associated with an increased risk for PU and might contribute to the difference in the prevalence of PU and gastric cancer between Hanoi and Ho Chi Minh.

Background

Microarray technology is a powerful and widely accepted experimental technique in molecular biology that allows studying genome wide transcriptional responses. However, experimental data usually contain potential sources of uncertainty and thus many experiments are now designed with repeated measurements to better assess such inherent variability. Many computational methods have been proposed to account for the variability in replicates. As yet, there is no model to output expression profiles accounting for replicate information so that a variety of computational models that take the expression profiles as the input data can explore this information without any modification.

Results

We propose a methodology which integrates replicate variability into expression profiles, to generate so-called 'true' expression profiles. The study addresses two issues: (i) develop a statistical model that can estimate 'true' expression profiles which are more robust than the average profile, and (ii) extend our previous micro-clustering which was designed specifically for clustering time-series expression data. The model utilizes a previously proposed error model and the concept of 'relative difference'. The clustering effectiveness is demonstrated through synthetic data where several methods are compared. We subsequently analyze in vivo rat data to elucidate circadian transcriptional dynamics as well as liver-specific corticosteroid induced changes in gene expression.

Conclusions

We have proposed a model which integrates the error information from repeated measurements into the expression profiles. Through numerous synthetic and real time-series data, we demonstrated the ability of the approach to improve the clustering performance and assist in the identification and selection of informative expression motifs.

CEACAM1-4S (carcinoembryonic antigen-related cell adhesion molecule 1) is a type I membrane protein with a short (12 amino acid) cytoplasmic tail. Wild type CEACAM1-4S transfected MCF7 cells form glands with lumena when grown in 3D culture, while null mutations of two putative phosphorylation sites (T457A and S459A) in the cytoplasmic domain fail to undergo lumen formation. When gene chip analysis was performed on mRNA isolated from both wild type and T457A,S459A mutated CEACAM1-4S transfected MCF7 cells grown in 3D culture, calpain-9 (CAPN9) was identified out of over 400 genes with a >2 log 2 difference as a potential inducer of lumen formation. Inhibition of CAPN9 expression in MCF7/CEACAM1-4S cells by RNAi or by calpeptin or PD150606 inhibited lumen formation. Transfection of CAPN9 into wild type MCF7 cells restores lumen formation demonstrating that calpain-9 may plays a critical role in lumen formation. Additionally, we demonstrate that the apoptosis related kinase, PKC-δ is activated by proteolytic cleavage during lumen formation exclusively in wild type CEACAM1-4S transfected MCF7 cells grown in 3D culture, and that lumen formation is inhibited by either RNAi to PKC-δ or by the PKC-δ inhibitor rottlerin.