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Delta Omega

2012 Poster Competition Winners

Applied Science:

1st Place - Miranda Jones, PhD Candidate

Title: Secondhand tobacco smoke: an occupational hazard for smoking and non-smoking bar and nightclub employees

Background: Exposure to secondhand tobacco smoke is a major cause of respiratory, cardiovascular and cancer morbidity and mortality around the world. In the absence of comprehensive smoking bans in public places, bars and nightclubs have the highest concentrations of secondhand smoke, posing a serious health risk for employees in these venues.

Objective: To assess exposure of bar and nightclub employees to secondhand smoke, including non-smoking and smoking employees.

Methods: Between 2007 and 2009, we recruited approximately 10 venues per city and up to 5 employees per venue in 24 cities in the Americas, Eastern Europe, Asia and Africa. Air nicotine concentrations were measured for 7 days in 238 venues. To evaluate personal exposure to secondhand smoke, hair nicotine concentrations were also measured for 625 non-smoking and 311 smoking employees (N=936).

Results: Median (interquartile range [IQR]) air nicotine concentrations were 3.5 (1.5, 8.5) ?g/m3 and 0.2 (0.1, 0.7) ?g/m3 in smoking and smoke-free venues, respectively. Median (IQR) hair nicotine concentrations were 6.0 (1.6, 16.0) ng/mg and 1.7 (0.5, 5.5) ng/mg in smoking and non-smoking employees, respectively. After adjustment for age, sex, education, living with a smoker, hair treatment and region, a 2-fold increase in air nicotine concentrations was associated with a 30% (95% confidence interval 23%, 38%) increase in hair nicotine concentrations in non-smoking employees and with a 10% (2%, 19%) increase in smoking employees.

Conclusions: Occupational exposure to secondhand smoke, assessed by air nicotine, resulted in elevated concentrations of hair nicotine among non-smoking and smoking bar and nightclub employees. The high levels of airborne nicotine found in bars and nightclubs and the contribution of this exposure to employee hair nicotine concentrations support the need for legislation measures that ensure complete protection from secondhand smoke in these venues

2nd Place - Yue Guan, ScM Candidate

Title: Parental disclosure of G6PD and its relationship to child health in a Chinese population

Background: Glucose-6-phosphate deficiency (G6PD) is an X-linked enzyme deficiency that commonly manifests as food-induced or drug-induced acute hemolytic anemia but may lead to permanent neurological damage or death if inadequately managed. The challenges of preparing children to independently self-manage their condition are considerable, and health care professionals encourage parents to disclosing age-appropriate illness information to the affected child. Yet, little work has been undertaken to understand parental disclosure regards G6PD that may be related to better physical and psychosocial health of affected children.

Objectives: This study was designed to explore associated factors and patterns of parental disclosure of G6PD to an affected child and its relationship to child health.

Methods: A primary cross-sectional study of individual parents of 94 children affected with G6PD from Taiwan, Hong Kong and the mainland of China was conducted using paper or web-based survey instruments in Chinese. Socio-demographic characteristics, family history, exposure to G6PD health education and attitudes regarding G6PD were assessed along with parent-reported of the child’s age at disclosure and the extent of disclosure discussion for each of 9 key topics. Child health was assessed using the Chinese version of the Child Health Questionnaire-Parent Form (CHQ-PF28) and a 13-item G6PD symptom list.

Results: 44.7% of study children were reported to have experienced at least one clinically significant symptom of acute hemolytic anemia. Children with an anemia symptom history scored significantly lower on measures of physical and psychosocial health. More extensive parental disclosure regarding G6PD was associated with better child health in both physical and psychosocial domains. Parental disclosure was positively associated with child age (r=0.19; p=0.04), sense of control of G6PD (r=0.22; p=0.02), positive emotions related to G6PD (r=0.23; p=0.01), and better quality of parent-reported G6PD education received from providers (r=0.37; p<0.001).

Conclusions: One of the modifiable factors found to be positively related to parental disclosure was the quality of G6PD education reported by parents to have been received from providers. This finding highlights opportunities for educational and behavioral interventions directed toward families and children with G6PD. Developing and testing the feasibility and effectiveness of interventions aimed to construct more accurate and positive illness representations of G6PD, facilitate parental disclosure to children and empower children to self-manage G6PD are important avenues for future research in assuring optimal child health.

Strengths of the Study: 1st study exploring health status of children with G6PD; 1st study exploring parents’ role in caring children with G6PD; Implications for children’s role in G6PD self-care.

Limitations of the Study: Conclusions cannot be drawn about causal pathways; Lack of documented clinical data and reliance on parental report of symptoms.

3rd Place - Megan Tschudy, MD Candidate

Title: Newborn Home Visitation: Teaching pediatric residents to extend the medical home into the community

Background: The scope of primary care has broadened with pediatricians addressing an increasing range of social and environmental issues. In vulnerable populations, home visits by have improved many child health indicators. No previous studies have examined pediatric resident change in knowledge, attitudes or behaviors after a home visit with a patient whom they have a longitudinal relationship.

Methods: A prospective cohort study was conducted between September 2009 and June 2010 in two outpatient clinics at an urban academic pediatric residency program in Baltimore, Maryland. The participants were residents who serve as primary care providers (n=32). Infants who received care in these clinics were recruited for a newborn home visit intervention. Residents completed an educational module about home visits and the community prior to the visit. They also completed a pre and post visit survey assessing knowledge of community, attitudes, and practice behaviors. Comparison of pre and post intervention likert scores was made using a nonparametric Wilcoxon sign rank test.

Results: Post intervention residents had improved knowledge of the community, positively changed attitudes towards their patients, and clinical behaviors tailored better toward the patients and families they serve. There was a significant positive change (p < 0.05) in: adequacy of medical knowledge, not being concerned about safety, understanding of home and community, excitement about home visits, understanding that the home situation affects how one prescribes medicine and refers to subspecialists, and likelihood of making a future home visit. 39% percent reported a change in their views of how they should treat patients and 87% indicated home visits should be part of the permanent curriculum.

Conclusions: Conducting home visits was associated with residents’ improved understanding of the community, and home situation of their patients. Residents felt home visits provided an important educational experience. Next steps will examine the impact of resident home visitation on family trust and healthcare utilization.

Basic/Lab Science:

1st Place - Wen-Hsuan Lin, PhD Candidate

Title: Viral Control and Immune Evasion in Measles Virus Infection: from Animal Experiments to Within-host Modeling

Measles virus (MeV) infection is a leading cause of vaccine-preventable childhood mortality worldwide. Infection with MeV induces both immune activation and immune suppression. The host immune response to MeV has been used as a paradigm for other acute or chronic viral infections. However, recent lines of evidence have suggested that the clearance of MeV is a prolonged and complicated process. We have investigated the in vivo process of MeV clearance by experimentally infecting 8 rhesus macaques with wild-type MeV and analyzing the virological and immunologic changes for 4 months. We found that MeV RNA persisted in the blood, respiratory tract or lymph nodes 4-5 times longer than infectious virus and was cleared in three phases. To identify host immune correlates to MeV clearance, we measured parameters related to immune suppression, MeV-specific T-cell and humoral activation using multiple assays. From these data, we identified an inverse correlation of viral load, foxp3 gene expression and the magnitude of MV-specific T cell response. To further examine the effect of individual host immune factors to the MeV load dynamics, we developed mathematical models for the process of within-host clearance of MeV RNA. More specifically, we fit the virus-load dynamics observed in these animals with models, which express viral replication and elimination in terms of the strength of MeV-specific IFNg-producing T-cell responses, antibody responses, target cell limitations and the immunosuppressive activity of regulatory T cells. Based on the model, we found that both MeV-specific T-cell and humoral responses contribute to controlling MeV replication in naïve animals and that suppression of the immune system might substantially slows viral clearance, and thereby contributes to the secondary peaks in virus load. These results have profound consequences for our understanding of acute viral infections, the development of prolonged immunity and, potentially, viral transmission. Here, we also provide a successful example for the study of in-host viral clearance that integrates biological measurements and mathematical modeling.

2nd Place - Mindy Graham

Title: Targeting the Human Androgen Receptor Gene with Platinum-Conjugated Triplex-Forming Oligonucleotides

Androgen receptor (AR) gene expression is required to maintain prostrate tumor cell growth, and inhibition of this gene would be expected to prevent prostate tumor cell proliferation. The human AR gene contains numerous homopurine tracts that can serve as binding sites for triplex-forming oligonucleotides (TFOs), a class of oligonucleotides that have significant potential as antigene agents. We have developed a novel type of TFO that is comprised of 2'-O-methylribonucleotides and contains a N7-trans-diamminechloroplatinumdeoxyguanosine residue at either its 5'- (Pt-mrTFO) or 3'-end (mrTFO-Pt). When bound to a homopurine tract in double-stranded DNA, the platinum group of the Pt-mrTFO can cross-link with suitably positioned guanine residues adjacent to the TFO binding site, a reaction that irreversibly anchors the TFO to its DNA target. Such cross-link formation would be expected to interfere with transcription and/or replication of the target DNA. We have identified 27 different homopurine tracts in the transcribed region of the human AR gene whose sequences are compatible with cross-link formation by Pt-mrTFOs or mrTFO-Pt. In preliminary studies, we have synthesized a mrTFO-Pt whose sequence (mr-TTTCTTCTTTTCTCTCTTGPt; T = 2'-O-methylribothymine; C = 2'-O-methylribo-5-methylcytosine; GPt = N7-trans-diamminechloroplatinumdeoxyguanosine) targets a 19 nucleotide homopurine sequence located on the transcribed strand in the 2nd intron of the human AR gene. At physiological pH and temperature, the mrTFO containing deoxyguanosine derivatized with a non-reactive platinum group, diethylenetriamineplatinum(II), mr-TFO-Pt-i, forms a stable triplex (melting temperature = 69?C) with a 31 bp DNA duplex containing the target homopurine sequence found within the AR gene. The reactive mrTFO-Pt cross-links to this duplex to the extent of 80% under physiological conditions as shown by gel electrophoretic mobility shift assays. To test its ability to inhibit transcription, the mrTFO-Pt was cross-linked to a firefly luciferase reporter plasmid that contained a single copy of the AR target gene sequence placed in the transcribed region between the plasmid's CMV promoter and luciferase reporter gene. The cross-linked plasmid was co-transfected with a Renilla luciferase reporter plasmid (to monitor transfection efficiency) into AA8 cells in culture and luciferase activity was determined 24 hrs after transfection using a dual luciferase assay (Promega Inc.). Luciferase expression decreased 96% compared to that from a non-cross-linked control plasmid. The mrTFO-Pt was found to be resistant to degradation when incubated at 37?C for a period of 24 hrs with cell culture medium containing 10% fetal calf serum.  Transfection of a human prostate cancer cell line (LAPC4) with a Lipofectamine complex of the 5'-fluorescein-labeled mrTFO-Pt-i resulted in nuclear localization of the label in 69% of the cells as revealed by fluorescence microscopy of the live cells.  The ability of the mrTFO-Pt to cross-link effectively with its target, and inhibit DNA transcription suggests that these compounds may have potential as therapeutic agents to disrupt AR signaling in androgen-resistant prostate cancer.

3rd Place - Andrew Jaffe

Title: Bump Hunting in Genomics Data from Large Epidemiological Studies

During the last five years, high-throughput technologies have been successfully used by epidemiology studies, but almost all have focused on sequence variation through genome-wide association studies [GWAS]. Today, the study of other genomic events is becoming more common in large-scale epidemiological studies. Many of these, unlike the single nucleotide polymorphism studied in GWAS, are continuous outcomes. In this context, the exercise of searching for regions of interest is akin to the problems described in the statistical “bump hunting” literature. New statistical challenges arise when the measurements are continuous rather than categorical, when they are measured with uncertainty, and when both biological signal, and measurement error are characterized by spatial correlation along the genome. But perhaps the most challenging complication is that data from large studies are collected through-out long periods making it susceptible to “batch effects”. An example that combines all three characteristics is genome-wide DNA methylation measurements. Here, we present a data analysis pipeline that effectively models measurement error, removes batch effects, detects regions of interest, and attaches statistical uncertainty to reported regions. We illustrate the usefulness of our approach by detecting genomic regions of DNA methylation associated with a continuous trait in a well-characterized population of newborns. Our framework offers a comprehensive yet flexible approach for identifying general regions of biological interest in large epidemiological studies.