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Schmidt-Grimminger D.C.,Avera Cancer Institute | Schmidt-Grimminger D.C.,University of South Dakota | Bell M.C.,University of South Dakota | Bell M.C.,Sanford Burnham Institute for Medical Research | And 4 more authors.
BMC Infectious Diseases | Year: 2011

Background: High-risk strains of human papillomavirus (HPV) cause cervical cancer. American Indian (AI) women in the Northern Plains of the U.S. have significantly higher incidence and mortality rates for cervical cancer than White women in the same geographical area. We compared HPV prevalence, patterns of HPV types, and infection with multiple HPV types in AI and White women living in South Dakota, U.S.Methods: We analyzed the HPV status of cervical samples collected in 2006-2008 from women aged 18-65 years who attended two rural AI reservation clinics (n = 235) or an urban clinic in the same area serving mostly White women (n = 246). Data collection occurred before HPV vaccination was available to study participants. HPV DNA was amplified by using the L1 consensus primer system and an HPV Linear Array detection assay to identify HPV types. We used chi-square tests to compare HPV variables, with percentages standardized by age and lifetime number of sexual partners.Results: Compared to White women, AI women were younger (p = 0.01) and reported more sexual partners (p < 0.001). A lower percentage of AI women tested negative for HPV infection compared to Whites (58% [95% CI = 51-65] vs. 77% [95% CI = 71-82]; p < 0.001), and a higher percentage of AI women were infected by oncogenic types (30% [95% CI = 25-36] vs. 16% [95% CI = 11-21]; p = 0.001). Infections among AI women showed a wider variety and very different pattern of HPV types, including a higher prevalence of mixed HPV infections (19% [95% CI = 26-38] vs. 7% [95% CI = 4-11]; p = 0.001). AI women had a higher percentage of HPV infections that were not preventable by HPV vaccination (32% [95% CI = 26-38] vs. 15% [95% CI = 11-21]; p < 0.001).Conclusions: A higher HPV burden and a different HPV genotyping profile may contribute to the high rate of cervical cancer among AI women. © 2011 Schmidt-Grimminger et al; licensee BioMed Central Ltd.

Whitmore L.S.,Washington State University | Ye P.,Washington State University | Ye P.,Avera Cancer Institute
PLoS ONE | Year: 2015

Metabolic pathways are increasingly postulated to be vital in programming cell fate, including stemness, differentiation, proliferation, and apoptosis. The commitment to meiosis is a critical fate decision for mammalian germ cells, and requires a metabolic derivative of vitamin A, retinoic acid (RA). Recent evidence showed that a pulse of RA is generated in the testis of male mice thereby triggering meiotic commitment. However, enzymes and reactions that regulate this RA pulse have yet to be identified. We developed a mouse germ cellspecific metabolic network with a curated vitamin A pathway. Using this network, we implemented flux balance analysis throughout the initial wave of spermatogenesis to elucidate important reactions and enzymes for the generation and degradation of RA. Our results indicate that primary RA sources in the germ cell include RA import from the extracellular region, release of RA from binding proteins, and metabolism of retinal to RA. Further, in silico knockouts of genes and reactions in the vitamin A pathway predict that deletion of Lipe, hormone-sensitive lipase, disrupts the RA pulse thereby causing spermatogenic defects. Examination of other metabolic pathways reveals that the citric acid cycle is the most active pathway. In addition, we discover that fatty acid synthesis/oxidation are the primary energy sources in the germ cell. In summary, this study predicts enzymes, reactions, and pathways important for germ cell commitment to meiosis. These findings enhance our understanding of the metabolic control of germ cell differentiation and will help guide future experiments to improve reproductive health. Copyright: © 2015 Whitmore, Ye.

Hu Y.,Avera Institute for Human Genetics | Ehli E.A.,Avera Institute for Human Genetics | Ehli E.A.,University of South Dakota | Nelson K.,Avera Institute for Human Genetics | And 9 more authors.
PLoS ONE | Year: 2012

The Affymetrix Drug Metabolism Enzymes and Transporters (DMET) microarray is the first assay to offer a large representation of SNPs conferring genetic diversity across known pharmacokinetic markers. As a convenient and painless alternative to blood, saliva samples have been reported to work well for genotyping on the high density SNP arrays, but no reports to date have examined this application for saliva-derived DNA on the DMET platform. Genomic DNA extractions from saliva samples produced an ample quantity of genomic DNA for DMET arrays, however when human amplifiable DNA was measured, it was determined that a large percentage of this DNA was from bacteria or fungi. A mean of 37.3% human amplifiable DNA was determined for saliva-derived DNAs, which results in a significant decrease in the genotyping call rate (88.8%) when compared with blood-derived DNAs (99.1%). More interestingly, the percentage of human amplifiable DNA correlated with a higher genotyping call rate, and almost all samples with more than 31.3% human DNA produced a genotyping call rate of at least 96%. SNP genotyping results for saliva derived DNA (n = 39) illustrated a 98.7% concordance when compared with blood DNA. In conclusion, when compared with blood DNA and tested on the DMET array, saliva-derived DNA provided adequate genotyping quality with a significant lower number of SNP calls. Saliva-derived DNA does perform very well if it contains greater than 31.3% human amplifiable DNA. © 2012 Hu et al.

Schmidt-Grimminger D.,Avera Cancer Institute | Schmidt-Grimminger D.,University of South Dakota | Frerichs L.,University of Nebraska Medical Center | Workman K.,Great Plains Tribal Epidemiology Center | And 2 more authors.
Journal of Cancer Education | Year: 2013

Native American women in the Northern Plains have a high prevalence of human papillomavirus (HPV) and high incidence of cervical disease and cervical cancer. HPV vaccination coverage is shown to be lower among nonwhite populations and disparity populations. We assessed HPV knowledge, attitudes, and beliefs towards HPV and HPV vaccination during a community-based participatory research project among tribal youth, young adults, parents, and health professionals. In 2009, we recruited a total of 73 individuals to participate in four tribal focus groups: tribal health providers, (n = 10), Indian Health Service providers (n = 7), young adult women ages 19-26 (n = 22), girls (14-18) (n = 18), and parents (n = 16). Of these, 62 (84.93 %) completed a survey, which included 10 healthcare providers, 22 young adults, 14 teens, and 16 parents. We employed a qualitative thematic analysis of focus group transcript data and conducted frequency analysis of survey data, which were both reviewed and triangulated by a Community Advisory Board. Based on the results of this study, the tribal community advisory board identified local tribal settings for interventions to increase HPV vaccination coverage through health education classes and a school-based vaccination clinic. In addition to tribal community-wide education events to increase awareness of HPV disease, the HPV vaccine, provider-specific training was identified as a potential intervention. These community-based focus group findings underscore the importance of locally and cultural tailored educational interventions to further increase HPV knowledge and HPV vaccination among disparate populations like American Indian adolescent and young adult women. © 2013 Springer Science+Business Media New York.

Buchwald D.,University of Washington | Muller C.,University of Washington | Bell M.,University of South Dakota | Schmidt-Grimminger D.,University of South Dakota | Schmidt-Grimminger D.,Avera Cancer Institute
Health Education and Behavior | Year: 2013

Background. American Indian women in the Northern Plains have a high incidence of cervical cancer. We assessed attitudes on vaccination against human papillomavirus (HPV) in this population. Method. In partnership with two tribal communities, from 2007 to 2009, we surveyed women 18 to 65 years old attending two reservation clinics (n = 118 and n = 76) and an urban clinic in the same region serving primarily White women (n = 158) on HPV knowledge, vaccine familiarity, and willingness to vaccinate children against HPV. We used chi-square tests and binary logistic regression to compare groups and identify correlates of willingness to vaccinate. Results. American Indian women were less knowledgeable about HPV than White women (p <.001), especially its role in cervical cancer. Willingness to vaccinate children was differentially distributed across the three clinic samples (p <.001), but this association did not persist after adjusting for demographics and HPV knowledge. Among all samples, more correct answers to HPV knowledge questions was the only factor positively correlated with willingness to vaccinate (odds ratios = 1.2-1.5; p <.00-.05). Conclusions. These findings underscore the importance of locally relevant educational interventions to increase HPV vaccination rates among American Indian women. © 2013 Society for Public Health Education.

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