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1.  Increasing Hepatitis B Screening for Hmong adults: Results from a randomized controlled community-based study 
Hepatitis B-linked liver cancer disproportionately affects Hmong Americans. With an incidence rate of 18.9/100,000, Hmong Americans experience liver cancer at a rate that is 6–7 times greater than that of non-Hispanic Whites. Serological testing for the hepatitis B virus (HBV) is a principal means to prevent liver cancer deaths through earlier identification of those at risk.
Academic researchers and Hmong leaders collaborated in the design, conduct, and evaluation of a 5-year randomized controlled trial testing a lay health worker (LHW) intervention to promote HBV testing among 260 Hmong adults through in-home education and patient navigation.
Intervention group participants were more likely to report receiving serological testing for HBV (24% vs. 10%, p=0.0056) and showed a greater mean increase in knowledge score (1.3 vs. 0.3 points, p=0.0003) than control group participants. Multivariable modeling indicated that self-reported test receipt was associated with intervention group assignment (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.3–9.2), improvement in knowledge score (OR 1.3 per point, 95% CI 1.02–1.7), female gender (OR 5.3, 95% CI 1.7–16.6), and having seen a doctor in the past year at baseline (OR 4.8, 95% CI 1.3–17.6). The most often cited reason for testing was a doctor’s recommendation.
LHWs were effective in bringing about HBV screening. Doctor visits and adherence to doctors’ recommendations were pivotal. Participation of health care providers is essential to increase HBV testing.
LHWs can significantly increase HBV screening rates for Hmong, but their doctors’ recommendation is highly influential and should be pursued.
PMCID: PMC3650126  PMID: 23613027
Hepatitis B; Hmong; Randomized controlled trial; community-based; liver cancer
2.  Bioinformatics analysis of transcriptional regulation of circadian genes in rat liver 
BMC Bioinformatics  2014;15:83.
The circadian clock is a critical regulator of biological functions controlling behavioral, physiological and biochemical processes. Because the liver is the primary regulator of metabolites within the mammalian body and the disruption of circadian rhythms in liver is associated with severe illness, circadian regulators would play a strong role in maintaining liver function. However, the regulatory structure that governs circadian dynamics within the liver at a transcriptional level remains unknown. To explore this aspect, we analyzed hepatic transcriptional dynamics in Sprague-Dawley rats over a period of 24 hours to assess the genome-wide responses.
Using an unsupervised consensus clustering method, we identified four major gene expression clusters, corresponding to central carbon and nitrogen metabolism, membrane integrity, immune function, and DNA repair, all of which have dynamics which suggest regulation in a circadian manner. With the assumption that transcription factors (TFs) that are differentially expressed and contain CLOCK:BMAL1 binding sites on their proximal promoters are likely to be clock-controlled TFs, we were able to use promoter analysis to putatively identify additional clock-controlled TFs besides PARF and RORA families. These TFs are both functionally and temporally related to the clusters they regulate. Furthermore, we also identified significant sets of clock TFs that are potentially transcriptional regulators of gene clusters.
All together, we were able to propose a regulatory structure for circadian regulation which represents alternative paths for circadian control of different functions within the liver. Our prediction has been affirmed by functional and temporal analyses which are able to extend for similar studies.
PMCID: PMC3987685  PMID: 24666587
Circadian rhythm; Microarray analysis; Gene expression; Consensus clustering; Promoter analysis; Transcription factor; Circadian regulation
3.  Tissue-Specific Gene Expression and Regulation in Liver and Muscle Following Chronic Corticosteroid Administration 
Although corticosteroids (CSs) affect gene expression in multiple tissues, the array of genes that are regulated by these catabolic steroids is diverse, highly tissue specific, and depends on their functions in the tissue. Liver has many important functions in performing and regulating diverse metabolic processes. Muscle, in addition to its mechanical role, is critical in maintaining systemic energy homeostasis and accounts for about 80% of insulin-directed glucose disposal. Consequently, a better understanding of CS pharmacogenomic effects in these tissues would provide valuable information regarding the tissue-specificity of transcriptional dynamics, and would provide insights into the underlying molecular mechanisms of action for both beneficial and detrimental effects.
We performed an integrated analysis of transcriptional data from liver and muscle in response to methylprednisolone (MPL) infusion, which included clustering and functional annotation of clustered gene groups, promoter extraction and putative transcription factor (TF) identification, and finally, regulatory closeness (RC) identification.
This analysis allowed the identification of critical transcriptional responses and CS-responsive functions in liver and muscle during chronic MPL administration, the prediction of putative transcriptional regulators relevant to transcriptional responses of CS-affected genes which are also potential secondary bio-signals altering expression levels of target-genes, and the exploration of the tissue-specificity and biological significance of gene expression patterns, CS-responsive functions, and transcriptional regulation.
The analysis provided an integrated description of the genomic and functional effects of chronic MPL infusion in liver and muscle.
PMCID: PMC3956809  PMID: 24653645
liver; muscle; glucocorticoids; corticosteroids; gene expression; gene regulation; promoter analysis
4.  Population-environment drivers of H5N1 avian influenza molecular change in Vietnam 
Health & place  2012;18(5):1122-1131.
This study identifies population and environment drivers of genetic change in H5N1 avian influenza viruses (AIV) in Vietnam using a landscape genetics approach. While prior work has examined how combinations of local-level environmental variables influence H5N1 occurrence, this research expands the analysis to the complex genetic characteristics of H5N1 viruses. A dataset of 125 highly pathogenic H5N1 AIV isolated in Vietnam from 2003–2007 is used to explore which population and environment variables are correlated with increased genetic change among viruses. Results from non-parametric multidimensional scaling and regression analyses indicate that variables relating to both the environmental and social ecology of humans and birds in Vietnam interact to affect the genetic character of viruses. These findings suggest that it is a combination of suitable environments for species mixing, the presence of high numbers of potential hosts, and in particular the temporal characteristics of viral occurrence, that drive genetic change among H5N1 AIV in Vietnam.
PMCID: PMC3904498  PMID: 22652510
landscape genetics; H5N1 avian influenza; Vietnam; disease ecology
5.  Understanding and Use of Nicotine Replacement Therapy and Nonpharmacologic Smoking Cessation Strategies Among Chinese and Vietnamese Smokers and Their Families 
Population-based studies have reported high rates of smoking prevalence among Chinese and Vietnamese American men. Although nicotine replacement therapy (NRT) is effective, recommended, and accessible without prescription, these populations underuse NRT for smoking cessation. The aim of this study was to assess understanding and use of NRT and nonpharmacologic treatments among Chinese and Vietnamese American male smokers and their families.
In-depth qualitative interviews were conducted with 13 smoker–family pairs, followed by individual interviews with each participant. A total of 39 interviews were conducted in Vietnamese or Chinese, recorded, translated, and transcribed into English for analysis.
Four themes were identified: use and understanding of NRT, nonpharmacologic strategies, familial and religious approaches, and willpower. Both smokers and their family members believed strongly in willpower and a sense of personal responsibility as the primary drivers for stopping smoking. Lack of these 2 qualities keeps many Chinese and Vietnamese men from using NRT to quit smoking. Those who do use NRT often use it incorrectly, following their own preferences rather than product instructions.
Our findings indicate the importance of culturally appropriate patient education about NRT. It may be necessary to teach smokers and their families at an individual level about NRT as a complementary approach that can strengthen their resolve to quit smoking. At a community level, public health education on the indication and appropriate use of evidence-based smoking cessation resources, such as NRT, would be an important component of effective tobacco control.
PMCID: PMC3938957  PMID: 24556252
6.  Developing Theoretically Based and Culturally Appropriate Interventions to Promote Hepatitis B Testing in 4 Asian American Populations, 2006–2011 
Hepatitis B infection is 5 to 12 times more common among Asian Americans than in the general US population and is the leading cause of liver disease and liver cancer among Asians. The purpose of this article is to describe the step-by-step approach that we followed in community-based participatory research projects in 4 Asian American groups, conducted from 2006 through 2011 in California and Washington state to develop theoretically based and culturally appropriate interventions to promote hepatitis B testing. We provide examples to illustrate how intervention messages addressing identical theoretical constructs of the Health Behavior Framework were modified to be culturally appropriate for each community.
Intervention approaches included mass media in the Vietnamese community, small-group educational sessions at churches in the Korean community, and home visits by lay health workers in the Hmong and Cambodian communities.
Use of the Health Behavior Framework allowed a systematic approach to intervention development across populations, resulting in 4 different culturally appropriate interventions that addressed the same set of theoretical constructs.
The development of theory-based health promotion interventions for different populations will advance our understanding of which constructs are critical to modify specific health behaviors.
PMCID: PMC4008952  PMID: 24784908
7.  Antiviral Susceptibility of Highly Pathogenic Avian Influenza A(H5N1) Viruses Isolated from Poultry, Vietnam, 2009–2011 
Emerging Infectious Diseases  2013;19(12):1963-1971.
We assessed drug susceptibilities of 125 avian influenza A(H5N1) viruses isolated from poultry in Vietnam during 2009–2011. Of 25 clade 1.1 viruses, all possessed a marker of resistance to M2 blockers amantadine and rimantadine; 24 were inhibited by neuraminidase inhibitors. One clade 1.1 virus contained the R430W neuraminidase gene and reduced inhibition by oseltamivir, zanamivir, and laninamivir 12-, 73-, and 29-fold, respectively. Three of 30 clade 2.3.4 viruses contained a I223T mutation and showed 7-fold reduced inhibition by oseltamivir. One of 70 clade viruses had the H275Y marker of oseltamivir resistance and exhibited highly reduced inhibition by oseltamivir and peramivir; antiviral agents DAS181 and favipiravir inhibited H275Y mutant virus replication in MDCK-SIAT1 cells. Replicative fitness of the H275Y mutant virus was comparable to that of wildtype virus. These findings highlight the role of drug susceptibility monitoring of H5N1 subtype viruses circulating among birds to inform antiviral stockpiling decisions for pandemic preparedness.
PMCID: PMC3840871  PMID: 24274711
Influenza; viruses; H5N1; Oseltamivir; H275Y; antiviral; zoonoses
Avian diseases  2011;55(4):659-666.
Domestic poultry act as a reservoir for persistent H5N1 endemicity in Vietnam, and the circulation of poultry flocks across farms and to market is thought to drive the spatial movement and evolution of avian influenza viruses. Using a dataset of complete or nearly full genomic sequences from highly pathogenic H5N1 avian influenza viruses collected in domestic poultry in Vietnam from 2003 to 2007, we explore potential differences in genetic characteristics according to species of isolation and the spatio-temporal characteristics of the viruses. Clustering algorithms and analysis of variance indicate that H5N1 viruses in Vietnam show differences in the amount of genetic change that chicken viruses experience as compared to duck viruses, with duck viruses showing higher rates of molecular evolution on all eight of influenza's gene segments. There also exist distinct patterns of genetic differentiation according to the year in which they were isolated. These findings suggest that genetic evolution of avian influenza viruses is continuous through time but could also be mediated by the species in which the viruses occur, information which has implications for prevention efforts.
PMCID: PMC3841065  PMID: 22312987
H5N1 avian influenza; genetic differentiation; poultry; ecology; cluster analysis; analysis of variance
9.  Highly Pathogenic H5N1 Avian Influenza Viruses Exhibit Few Barriers to Gene Flow in Vietnam 
EcoHealth  2012;9(1):60-69.
Locating areas where genetic change is inhibited can illuminate underlying processes that drive evolution of pathogens. The persistence of highly pathogenic H5N1 avian influenza in Vietnam since 2003, and the continuous molecular evolution of Vietnamese avian influenza viruses, indicates that local environmental factors are supportive not only of incidence but also of viral adaptation. This article explores whether gene flow is constant across Vietnam, or whether there exist boundary areas where gene flow exhibits discontinuity. Using a dataset of 125 highly pathogenic H5N1 avian influenza viruses, principal components analysis and wombling analysis are used to indicate the location, magnitude, and statistical significance of genetic boundaries. Results show that a small number of geographically minor boundaries to gene flow in highly pathogenic H5N1 avian influenza viruses exist in Vietnam, but that overall there is little division in genetic exchange. This suggests that differences in genetic characteristics of viruses from one region to another are not the result of barriers to H5N1 viral exchange in Vietnam, and that H5N1 avian influenza is able to spread relatively unimpeded across the country.
PMCID: PMC3771539  PMID: 22350419
H5N1 avian influenza; gene flow; wombling; Vietnam
10.  Three-dimensional assessment of maxillary changes associated with bone anchored maxillary protraction 
Bone-anchored maxillary protraction has been shown to be an effective treatment modality for the correction of Class III malocclusions. The purpose of this study was to evaluate 3-dimensional changes in the maxilla, the surrounding hard and soft tissues, and the circummaxillary sutures after bone-anchored maxillary protraction treatment.
Twenty-five consecutive skeletal Class III patients between the ages of 9 and 13 years (mean, 11.10 ± 1.1 years) were treated with Class III intermaxillary elastics and bilateral miniplates (2 in the infrazygomatic crests of the maxilla and 2 in the anterior mandible). Cone-beam computed tomographs were taken before initial loading and 1 year out. Three-dimensional models were generated from the tomographs, registered on the anterior cranial base, superimposed, and analyzed by using color maps.
The maxilla showed a mean forward displacement of 3.7 mm, and the zygomas and the maxillary incisors came forward 3.7 and 4.3 mm, respectively.
This treatment approach produced significant orthopedic changes in the maxilla and the zygomas in growing Class III patients.
PMCID: PMC3734342  PMID: 22133943
11.  Dynamics of hepatic gene expression profile in a rat cecal ligation and puncture model 
The Journal of Surgical Research  2011;176(2):583-600.
Sepsis remains a major clinical challenge in intensive care units. The difficulty in developing new and more effective treatments for sepsis exemplifies our incomplete understanding of the underlying pathophysiology of it. One of the more widely used rodent models for studying polymicrobial sepsis is cecal ligation and puncture (CLP). While a number of CLP studies investigated the ensuing systemic inflammatory response, they usually focus on a single time point post CLP and therefore fail to describe the dynamics of the response. Furthermore, previous studies mostly use surgery without infection (herein referred to as Sham CLP, SCLP) as a control for the CLP model, however SCLP represents an aseptic injurious event that also stimulates a systemic inflammatory response. Thus, there is a need to better understand the dynamics and expression patterns of both injury- and sepsis- induced gene expression alterations to identify potential regulatory targets. In this direction, we characterized the response of the liver within the first 24 h in a rat model of SCLP and CLP using a time series of microarray gene expression data.
Rats were randomly divided into three groups, sham, SCLP and CLP. Rats in SCLP group are subjected to laparotomy, cecal ligation and puncture while those in CLP group are subjected to the similar procedures without cecal ligation and puncture. Animals were saline resuscitated and sacrificed at defined time points (0, 2, 4, 8, 16, and 24 h). Liver tissues were explanted and analyzed for their gene expression profiles using microarray technology. Unoperated animals (Sham) serve as negative controls. After identifying differentially expressed probesets between sham and SCLP or CLP conditions over time, the concatenated data sets corresponding to these differentially expressed probesets in sham and SCLP or CLP groups were combined and analyzed using a “consensus clustering” approach. Promoters of genes that share common characteristics were extracted, and compared with gene batteries comprised of co expressed genes in order to identify putatative transcription factors which could be responsible for the co regulation of those genes.
The SCLP/CLP genes whose expression patterns significantly changed compared to sham over time were identified, clustered, and finally analyzed for pathway enrichment. Our results indicate that both CLP and SCLP triggered the activation of a pro-inflammatory response, enhanced synthesis of acute-phase proteins, increased metabolism and tissue damage markers. Genes triggered by CLP which can be directly linked to bacteria removal functions were absent in SCLP injury. In addition, genes relevant to oxidative stress induced damage were unique to CLP injury, which may be due to the increased severity of CLP injury vs. SCLP injury. Pathway enrichment identified pathways with similar functionality but different dynamics in the two injury models, indicating that the functions controlled by those pathways are under the influence of different transcription factors and regulatory mechanisms. Putatively identified transcription factors, notably including CREB, NF-KB and STAT, were obtained through analysis of the promoter regions in the SCLP/CLP genes. Our results show that while transcription factors such as NF-KB, HOMF, and GATA were common in both injuries for the IL-6 signaling pathway, there were many other transcription factors associated with that pathway which were unique to CLP, including FKHD, HESF and IRFF. There were 17 transcription factors that were identified as important in at least 2 pathways in the CLP injury, but only 7 transcription factors with that property in the SCLP injury. This also supports the hypothesis of unique regulatory modules that govern the pathways present in both the CLP and SCLP response.
By using microarrays to assess multiple genes in a high throughput manner, we demonstrate that an inflammatory response involving different dynamics and different genes is triggered by SCLP and CLP. From our analysis of the CLP data, the key characteristics of sepsis are a pro inflammatory response which drives hypermetabolism, immune cell activation, and damage from oxidative stress. This contrasts with SCLP, which triggers a modified inflammatory response leading to no immune cell activation, decreased detoxification potential, and hyper metabolism. Many of the identified transcription factors that drive the CLP-induced response are not found in the SCLP group, suggesting that SCLP and CLP induce different types of inflammatory responses via different regulatory pathways.
PMCID: PMC3368040  PMID: 22381171
sepsis; trauma; gene expression; transcription factor; microarray; inflammation; liver
12.  Hepatocellular Carcinoma Screening Practices and Impact on Survival among Hepatitis B-Infected Asian Americans 
Journal of Viral Hepatitis  2012;19(8):594-600.
Asians Americans have a high burden of hepatitis B (HBV) associated hepatocellular carcinoma (HCC). HCC screening practices in this population are unknown. We aimed to investigate predictors and patterns of HCC screening and its impact on survival in HBV-infected Asian Americans. Clinical data were obtained from a retrospective cohort of 1870 HBsAg-positive Asians in San Francisco’s safety net clinics. In 824 patients at-risk for HCC, screening (≥1 imaging and/or AFP per year) decreased from 67% to 47% to 24% from the first to second to tenth year after HBV diagnosis, respectively. AFP, imaging, and imaging plus AFP were used in 37%, 14%, and 49% during the first year after diagnosis, and imaging plus AFP increased to 64% by the tenth year. Among 1431 patients followed in 2007, age 40-64 years, female gender, cirrhosis, hepatologist evaluation, HBV diagnosis after 2003, and testing for HBeAg were associated with HCC screening. Of the 51 patients with HCC, more cirrhotics received screening and were diagnosed with early stage disease. Median survival following HCC diagnosis was higher in screened patients (1624 vs.111 days, p=0.02). MELD score at HCC diagnosis (HR 1.2, 95%CI: 1.1-1.3) and receipt of curative therapy (HR 0.3, 95%CI: 0.08-0.94) were associated with survival. Screening rates in at-risk Asian Americans, particularly among non-cirrhotics, were suboptimal and decreased over time. Among patients with HCC, receipt of prior screening improved survival, and this survival benefit was related to better liver function at HCC diagnosis and receipt of curative therapy.
PMCID: PMC3390753  PMID: 22762144
liver cancer; hepatitis B; safety net healthcare system; cirrhosis; mortality
13.  A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff 
Fly  2012;6(2):80-92.
We describe a new computer program, SnpEff, for rapidly categorizing the effects of variants in genome sequences. Once a genome is sequenced, SnpEff annotates variants based on their genomic locations and predicts coding effects. Annotated genomic locations include intronic, untranslated region, upstream, downstream, splice site, or intergenic regions. Coding effects such as synonymous or non-synonymous amino acid replacement, start codon gains or losses, stop codon gains or losses, or frame shifts can be predicted.
Here the use of SnpEff is illustrated by annotating ~356,660 candidate SNPs in ~117 Mb unique sequences, representing a substitution rate of ~1/305 nucleotides, between the Drosophila melanogaster w1118; iso-2; iso-3 strain and the reference y1; cn1 bw1 sp1 strain. We show that ~15,842 SNPs are synonymous and ~4,467 SNPs are non-synonymous (N/S ~0.28). The remaining SNPs are in other categories, such as stop codon gains (38 SNPs), stop codon losses (8 SNPs), and start codon gains (297 SNPs) in the 5′UTR. We found, as expected, that the SNP frequency is proportional to the recombination frequency (i.e., highest in the middle of chromosome arms). We also found that start-gain or stop-lost SNPs in Drosophila melanogaster often result in additions of N-terminal or C-terminal amino acids that are conserved in other Drosophila species. It appears that the 5′ and 3′ UTRs are reservoirs for genetic variations that changes the termini of proteins during evolution of the Drosophila genus.
As genome sequencing is becoming inexpensive and routine, SnpEff enables rapid analyses of whole-genome sequencing data to be performed by an individual laboratory.
PMCID: PMC3679285  PMID: 22728672
Drosophila melanogaster; Personal Genomes; next generation DNA sequencing; whole-genome SNP analysis
14.  An Agent-Based Model of Cellular Dynamics and Circadian Variability in Human Endotoxemia 
PLoS ONE  2013;8(1):e55550.
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.
PMCID: PMC3559552  PMID: 23383223
15.  Three-dimensional assessment of mandibular and glenoid fossa changes after bone-anchored Class III intermaxillary traction 
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.
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.
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.
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.
PMCID: PMC3553657  PMID: 22748987
16.  Comparison of the Cytokine and Chemokine Dynamics of the Early Inflammatory Response in Models of Burn Injury and Infection 
Cytokine  2011;55(3):362-371.
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.
PMCID: PMC3148335  PMID: 21652218
Cytokines; Chemokines; Burn injury; Cecum ligation and puncture
17.  Operationalization of community-based participatory research principles across the National Cancer Institute’s Community Network Programs 
American Journal of Public Health  2011;102(6):1195-1203.
To examine how the National Cancer Institute-funded Community Network Program (CNP) operationalized principles of community-based participatory research (CBPR).
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.
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.
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.
PMCID: PMC3292685  PMID: 22095340
Cancer disparities; community health; empowerment; health status disparities; indigenous populations; minority health; partnerships; training
18.  Lessons Learned from the Application of a Vietnamese Surname List for Survey Research 
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.
PMCID: PMC2891931  PMID: 19798578
Vietnamese; Surname lists
19.  Individual and Family Factors Associated with Intention to Quit among Male Vietnamese American Smokers: Implications for Intervention Development 
Addictive behaviors  2010;36(4):294-301.
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.
PMCID: PMC3056150  PMID: 21177041
tobacco use; smoking cessation; intention to quit; Asian Americans; Vietnamese Americans
20.  Using Drosophila melanogaster as a Model for Genotoxic Chemical Mutational Studies with a New Program, SnpSift 
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.
PMCID: PMC3304048  PMID: 22435069
personal genomes; Drosophila melanogaster; whole-genome SNP analysis; next-generation DNA sequencing
21.  Downregulation of microRNA-29c is associated with hypermethylation of tumor-related genes and disease outcome in cutaneous melanoma 
Epigenetics  2011;6(3):388-394.
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.
PMCID: PMC3063331  PMID: 21081840
DNMT3; melanoma; metastasis; methylation; miR-29
22.  Southeast Asian Foot-and-Mouth Disease Viruses in Eastern Asia 
Emerging Infectious Diseases  2012;18(3):499-501.
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.
PMCID: PMC3309575  PMID: 22377196
foot-and-mouth disease; foot-and-mouth disease viruses; viruses; epidemiology; nucleotide sequences; serotypes; viral protein 1; eastern Asia; Japan; South Korea
23.  Integrating Theory into Community Interventions to Reduce Liver Cancer Disparities: The Health Behavior Framework 
Preventive medicine  2009;50(1-2):63-67.
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.
PMCID: PMC3243444  PMID: 19716379
Hepatitis B virus; Liver cancer; Cancer prevention; Theory; Community-based Intervention; Health behavior; Disparities; Asians; Ethnic minorities; Cancer screening; Conceptual model
American journal of public health  2010;100(10):1924-1929.
We conducted a trial to evaluate the effectiveness of a cervical cancer control intervention for Vietnamese women.
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.
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.
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).
PMCID: PMC2936992  PMID: 20724673
Asian Americans; Cancer; Screening
25.  Acute ST segment elevation during exercise stress echocardiography due to severe pulmonary hypertension 
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.
PMCID: PMC3118137  PMID: 21645399

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