Alzheimers disease (AD) is a complex and multifactorial disease with the possible involvement of several genes. Complex diseases such as AD have a large affect on the public health. It was estimated in 2007 that over 5 million Americans had AD, and more than $91 billion dollars was spent by medicare on AD and other dementias. Genetics plays a significant role in the etiology of the disease, therefore, it is of public health importance that the genetics of AD be investigated. With the exception of the APOE gene as a susceptibility marker no other genes have been identified for late-onset AD (LOAD). A recent genome wide association study of 17,343 gene-based putative functional single nucleotide polymorphisms (SNPs) found 19 significant variants, including 3 linked to APOE, showing association with LOAD in several population samples. We have set out to replicate the 16 new significant associations in a large case-control cohort of American Whites. Additionally we examined six variants present in positional and/or biological candidate genes for AD. We genotyped the 22 SNPs in up to 1,009 Caucasian Americans with LOAD and up to 1,010 age matched older healthy Caucasian Americans. All variants were genotyped using 5 nuclease assays. We did not observe a statistically significant association between the SNPs with the risk of AD, either individually or stratified by APOE. Our data suggest that the association of the studied variants with LOAD, if it exists, is not statistically significant in our population study.

The risk to develop a substance use disorder (SUD) is a significant public health concern, particularly as it relates to prevention and intervention strategies. Elucidation of the possible precursors to SUD is an objective of this study. The main purpose of this research was to evaluate the relationship between the childs perception of parental behavior and his/her risk for SUD as measured by an index of transmissible liability (TLI). Previous research points to a relationship between parental behavior and behavior problems in the child, which includes substance use disorders. Additionally, much of this research suggests the presence of genetic effects contributing to the individual variation in these traits. Participants were self-selected twin pairs and at least one parent attending the Twins Days Festival (Twinsburg, OH) in 2006 and 2007. Biometrical genetic analysis was applied to the sample of twin pairs on a measure of parental behavior perception (PB) and the TLI. Results of the research indicate that childrens perception of parental behavior is associated with liability for substance use disorders. It was found that the variation in parental behavior perception is due to shared and unique environmental effects, whereas the TLI has a high heritability (h2 = 0.79). The study also validates the liability index as a measure of transmissible risk for substance use disorders as well as provides support for the PB scale as a measure of an aspect of the childs environment.

PURPOSE: The multidimensional health locus of control (MHLC) measures the degree to which an individual feels they are in control of their own health. In order to better tailor interventions to the psychosocial needs of Healthy Black Family Project (HBFP) participants, we explored relationships between MHLC, risk perception, and participation in health behaviors. METHODS: Risk perception analysis was assessed in 87 participants using Fishers exact tests to search for relationships between MHLC scores and risk perception accuracy for diabetes, cardiovascular disease, and cancer (breast, ovarian and colon). Health behavior was assessed in 68 participants. Outcome measures included physical activity level, information seeking behavior and enrollment in the Minority Research Recruitment Database. Change in physical activity was assessed using the Transtheoretical model. Wilsons model was used to assess changes in information seeking behavior. Fishers exact tests were used to test for relationships among MHLC and the outcome measures. RESULTS: Individuals at high risk for diabetes were more likely to underestimate their risk if they scored low on powerful others (p= 0.011). Individuals at moderate risk for cardiovascular disease were more likely to overestimate their risk if they scored high on powerful others (p=0.005). Women at low risk for ovarian cancer were more likely to overestimate their risk if they were externals (p= 0.04). Overall, the majority of individuals maintained or increased their level of physical activity, and information seeking and enrolled in the database regardless of their health locus of control. CONCLUSIONS: These findings highlight diabetes, cardiovascular disease, and ovarian cancer as areas in which participants would benefit from risk education tailored to their locus of control. Maximizing the role of community members, improving patient doctor communication, and the family health history initiative may be appropriate approaches to improve risk awareness. The pattern of behavior change observed in this study may be preliminary evidence that the HBFP is effective at promoting positive health behavior change in individuals regardless of their health locus of control. PUBLIC HEALTH SIGNIFICANCE: Community health outreach programs can use MHLC to explore how to better tailor interventions to their target population. The HBFP may serve as a model for future health promotion efforts.

Women who are found to carry BRCA1 or BRCA2 mutations are given recommendations of management options ranging from surveillance, to chemoprevention, and surgery. Choices regarding management may be influenced by experiences with cancer in a family. Besides management options, young women with a BRCA mutation may be concerned about reproductive choices. This study investigates the reproductive concerns in young women with BRCA mutations and how their choices regarding management are influenced by their family history. A secondary analysis employing a thematic analysis method was performed using interview transcripts. In the initial study open-ended email and telephone interviews were guided by grounded theory methodology. The current study was comprised of 14 women, aged 18-30 who tested positive for a BRCA1 or BRCA2 mutation. Two main themes were identified: 1. Management choices are highly influenced by the cancer histories of family members, 2. Young women who have a BRCA mutation experience a sense of urgency about their reproductive choices. Perceived closeness to family members with cancer appeared to impact decisions for medical management. The results of this study suggest which the participants who elected for prophylactic surgeries had an eminent sense of cancer risks that was largely based on the family history of cancer. A sense of feeling rushed into starting a family and concerns of passing on the BRCA mutation to their children were the reproductive concerns in young women with a BRCA mutation. From these results, health professionals may gain insight into the management choices and concerns of young BRCA mutation carriers. This work also has relevance to public health by being applicable to common diseases and how management choices can be influenced by experiences within a family.

Sickle cell disease (SCD) is associated with significant morbidity, mortality and impaired quality of life. Vaso-occlusive pain crises are the hallmark of sickle cell disease and require frequent visits to the emergency room and admissions to the hospital. Even though national guidelines are available that address the ethical issues of pain management, patients with SCD often receive suboptimal pain control, especially during acute painful episodes. This project planned to determine some methods of improving patient care and satisfaction of pain management in hopes of being able to translate these methods to other health care systems. At the Childrens Hospital of Pittsburgh (CHP) individualized pain plans, which include lists of each patients most recent pain medications, have been in place since 2002. Retrospective data was analyzed to determine whether admission rates have decreased since this time due to improved care and treatment of patients with SCD. Additionally, patient and parent satisfaction with current pain management was evaluated by the use of surveys, with questions regarding overall perceptions of treatment and care. We had also proposed to implement a quality improvement program in the ED to further improve care of patients with sickle cell disease presenting with vaso-occlusive pain crises and then reassess patient and parent satisfaction. However, time restraints did not allow a quality improvement program to be implemented at this time. This study found that admission rates since 2002 had decreased at CHP, since the time that individualized pain plans were designed and put into practice. Baseline measurements of patient and parent satisfaction found that, overall, participants were satisfied with the care and treatment of pain they received in the ED. Future studies should involve developing further methods of improving patient satisfaction with pain management; a possible avenue to pursue may be working on decreasing wait times in the ED. The public health significance of this research is that increasing satisfaction by improved care, treatment, and pain management may lead to improved quality of life for patients with SCD; additionally, similar steps to be taken in other hospitals to increase the level of pain management that sickle cell patients receive.

Sickle cell disease (SCD) is a severe autosomal recessive blood disorder that affects around 1 in 500 African Americans in the United States. Approximately, 1 in 12 African Americans are carriers of sickle cell trait (SCT). The high prevalence of sickle cell trait carriers highlights the importance of having education and trait testing available for individuals, particularly those, who are of childbearing age. Misconceptions and misinformation about sickle cell disease and sickle cell trait can be the reason for an individual to not be motivated to get sickle cell trait testing. This study was created to provide education to the African American community. A pre-post survey research design was used to evaluate 1) knowledge acquisition and retention among study participants who received genetic counseling in the barbershop and beauty salon; and 2) the feasibility of delivering a health education module on sickle cell disease in barbershops and salons in the African American community. As a result of this project, knowledge of sickle cell disease, concern over trait testing, and attitudes toward receiving genetic counseling in a non-clinical setting were evaluated. The data collected suggested that there was significant knowledge gain in 7 of the 9 knowledge questions administered with a p-value <0.05. Concern about trait testing remained low for both the pre and post questionnaires. Attitude about trait testing and genetic counseling remained high for both the pre and post questionnaires as well, resulting in an overall supportive attitude about trait testing and genetic counseling. The mean amount of knowledge gain overall knowledge questions were evaluated using a paired t-test with significance (p<0.05). Overall knowledge gain had a significance of (p<0.001). The public health relevance from the results of this study can inform development of health education materials on genetic disorders common in the African American community. Medical and public health professionals can use the insights gained from this study to provide better education and outreach to the community through non-clinical settings in the community.

PURPOSE: Cleft lip with or without cleft palate (CLP) is a common birth defect, with phenotypes ranging from overt clefts to minimal microforms. Occult defects of the superior orbicularis oris (OO) muscle appear to be a part of this phenotypic spectrum. Analysis of the OO phenotype as a clinical tool is hypothesized to improve recurrence risk estimates in families. METHODS: Upper lip ultrasound images were collected as a component of the Oral-Facial Cleft (OFC) study. Breaks in the continuity of the OO muscle visualized on ultrasound were scored as OO defects. Occurrences of CLP were compared between families with &ge; 1 family member with an OO defect and families without OO defects. Recurrence risks of CLP and of OO muscle defects among siblings and first degree relatives (FDRs) of probands with CLP were calculated using empiric proportions. Similar methods were used to calculate the recurrence risks of CLP and of OO defects among siblings and FDRs of probands with isolated OO defects. RESULTS: The occurrences of CLP in families with and without a history of OO defects are 0.1863 and 0.1165, respectively (p < 0.01, OR = 1.735). The sibling recurrence risk of CLP in this cohort is 9.1%; the FDR risk is 15.7%, which are both significantly different from published CLP recurrence risk data. The likelihoods of one or more siblings or FDRs of a proband with CLP to have an OO defect are 14.7% and 11.4%, respectively. The sibling recurrence of isolated OO muscle defects in this cohort is 17.2%; the FDR recurrence is 16.4%. The chances for one or more siblings or FDRs of a proband with an OO defect to have a CLP are 3.3% and 7.3%, respectively, which are similar to the published recurrence risk estimates of nonsyndromic (NS) CLP. CONCLUSIONS: This study supports OO muscle defects as being part of the CLP spectrum and suggests an improvement in the accuracy of recurrence risk estimates of CLP. Carefully defining the CLP phenotype has considerable public health relevance, as it is a critical component to the enhancement of genetic studies investigating the etiology of CLP.

Secondary lymphedema is the accumulation of protein-rich fluid in the interstitial spaces of the extremities. It typically occurs as a result of a trauma or infection in the lymphatic system. This is a significant public health issue because lymphedema has emerged as one of the most debilitating consequences of breast cancer treatment and currently no model exists to predict who will be affected. The aim of this study was to examine genes that may increase the susceptibility to developing secondary lymphedema following breast cancer surgery and/or radiation. Perometry and bioelectrical impedance spectrometry (BIS) were also used to examine clinical and subclinical swelling in individuals. This is a case-control study that sequenced connexin genes of 70 women with secondary lymphedema and over 100 control participants without lymphedema. Connexins form gap junction channels that facilitate communication between cells. The connexins that were sequenced include connexin 47 (GJA12), connexin 37 (GJA4), connexin 40 (GJA5), and exon 2 of connexin 43 (GJA1). Four missense mutations and one synonymous substitution were identified in connexin 47. The mutations were not found to be polymorphic in control individuals. The identification of connexin 47 mutations is compelling and warrants further research to determine if and how this gene increases the risk of secondary lymphedema after breast cancer treatment. These findings could have implications for prevention, management, and early diagnosis of breast cancer-associated secondary lymphedema.

Duchenne muscular dystrophy (DMD) is a progressive, degenerative muscle disease. It is caused by a large variety of mutations in the dystrophin gene. Studies of new therapies that are based on specific genotypes are generating a high level of interest among both researchers and patients. This investigation examines the mutations reported in patients with DMD by the large international academic research group, the Cooperative International Neuromuscular Research Group (CINRG). It also compares the types of mutations reported in two large mutation databases, Leiden DMD mutation database and the French Universal Mutation Database-Duchenne Muscular Dystrophy (UMD-DMD), to those reported in DMD patients from three CINRG studies. Diagnostic, strength, and medical history data were reviewed retrospectively for 374 DMD patients from 20 CINRG centers worldwide. The frequency of each type of mutation found in the CINRG data was compared with similar information abstracted from the Leiden and UMD-DMD mutation databases. On an exploratory basis, the distribution of DMD-causing lesions in the CINRG data was also compared to data from the patient registry, DuchenneConnect. The distribution of dystrophin mutations within the CINRG database is similar to the two large published databases and the patient registry data collection. The immediate results improve understanding of the many mutations in the dystrophin gene. These results suggest the need for more rigorous and harmonized genetic screening as well as the continued collection of global data in easily accessed, searchable databases. The results of this work have a public health importance because DMD is the most common form of muscular dystrophy. Furthermore, the creation and improvements to existing disease databases can advance the standard of care for all patients and families with muscular dystrophy over diverse geographies and cultures. Harmonization of mutation data collection for DMD studies will benefit clinical trials and ultimately enhance pairing of eligible patients to specific molecular-based treatments.

OBJECTIVES: The Tuskegee Syphilis Study and HIV conspiracy beliefs have continuing effects on perceptions of medical research in the African American community. This study was designed to explore how knowledge and beliefs concerning the Tuskegee Study and HIV impact African Americans willingness to partake in medical research, how research incentives may influence that willingness and what level of importance they believe medical research has in their lives. METHODS: Responses to medical research questionnaires were assessed for 100 participants. Outcome measures included accuracy of Tuskegee study knowledge, likelihood of participation in research based on incentives, level of importance of research and enrollment into a recruitment database. Data concerning knowledge and beliefs of the Tuskegee Study and HIV, likelihood of participation and level of importance were analyzed via two-way correlation tables and chi-square analysis. RESULTS: Analysis revealed a relatively high level of inaccuracy of Tuskegee study knowledge and HIV. Influences of these topics in relation to willingness to participate in research and overall perceptions of medical research were minimal. However, there were associations indicating that individuals with moderate or greater knowledge of the Tuskegee Study were less likely to participate in research if free medical care was offered when compared to individuals who knew little or nothing regarding the study. CONCLUSIONS: In order to improve the likelihood of minority participation, the medical research community should tailor their recruitment efforts to take into account common beliefs in the African American community concerning medical research. PUBLIC HEALTH SIGNIFICANCE: The data have implications related to the ability to garner trust between the African American and medical research communities, with the ultimate goal to improve likelihood of minority participation in medical research. With a significant degree of misconceptions concerning both the Tuskegee Study and HIV being prevalent in the community, it is vital to take into account these beliefs in order to more effectively recruit African Americans. Outwardly dismissing these beliefs could result in further distrust between the scientific and African American community.