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1851. Genome-wide admixture and association study of subclinical atherosclerosis in the Women’s Interagency HIV Study (WIHS)

Title Tesim:
Genome-wide admixture and association study of subclinical atherosclerosis in the Women’s Interagency HIV Study (WIHS)
Creator:
Ofotokun, Ighovwerha, Hanna, David B., Shrestha, Sadeep, Overton, Edgar T., Gange, Stephen J., Shendre, Aditi, Qi, Qibin, Liu, Chenglong, Wiener, Howard W., Floris-Moore, Michelle A., Irvin, Marguerite R., Aouizerat, Bradley E., Zhi, Degui, Kaplan, Robert C., Weber, Kathleen M., Limdi, Nita A., Hodis, Howard N., and Lazar, Jason
Date of publication:
2017
Abstract Tesim:
Cardiovascular disease (CVD) is a major comorbidity among HIV-infected individuals. Common carotid artery intima-media thickness (cCIMT) is a valid and reliable subclinical measure of atherosclerosis and is known to predict CVD. We performed genome-wide association (GWA) and admixture analysis among 682 HIV-positive and 288 HIV-negative Black, non-Hispanic women from the Women’s Interagency HIV study (WIHS) cohort using a combined and stratified analysis approach. We found some suggestive associations but none of the SNPs reached genome-wide statistical significance in our GWAS analysis. The top GWAS SNPs were rs2280828 in the region intergenic to mediator complex subunit 30 and exostosin glycosyltransferase 1 (MED30 | EXT1) among all women, rs2907092 in the catenin delta 2 (CTNND2) gene among HIV-positive women, and rs7529733 in the region intergenic to family with sequence similarity 5, member C and regulator of G-protein signaling 18 (FAM5C | RGS18) genes among HIV-negative women. The most significant local European ancestry associations were in the region intergenic to the zinc finger and SCAN domain containing 5D gene and NADH: ubiquinone oxidoreductase complex assembly factor 1 (ZSCAN5D | NDUF1) pseudogene on chromosome 19 among all women, in the region intergenic to vomeronasal 1 receptor 6 pseudogene and zinc finger protein 845 (VN1R6P | ZNF845) gene on chromosome 19 among HIV-positive women, and in the region intergenic to the SEC23-interacting protein and phosphatidic acid phosphatase type 2 domain containing 1A (SEC23IP | PPAPDC1A) genes located on chromosome 10 among HIV-negative women. A number of previously identified SNP associations with cCIMT were also observed and included rs2572204 in the ryanodine receptor 3 (RYR3) and an admixture region in the secretion-regulating guanine nucleotide exchange factor (SERGEF) gene. We report several SNPs and gene regions in the GWAS and admixture analysis, some of which are common across HIV-positive and HIV-negative women as demonstrated using meta-analysis, and also across the two analytic approaches (i.e., GWA and admixture). These findings suggest that local European ancestry plays an important role in genetic associations of cCIMT among black women from WIHS along with other environmental factors that are related to CVD and may also be triggered by HIV. These findings warrant confirmation in independent samples.
Resource type:
Article
Affiliation Label Tesim:
Department of Medicine
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/fc00-3m12
Identifier:
PMID: 29206233, PMCID: PMC5714351, Publisher DOI: https://doi.org/10.1371/journal.pone.0188725, and Onescience id: dc6f81fad9f54bd04a181cfda7e792fa9f7eceee
ISSN:
1932-6203
Journal Issue:
12
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Female, Genome-Wide Association Study, Cohort Studies, Humans, African Americans, HIV Infections, Atherosclerosis, and Case-Control Studies
Language Label:
English
ORCID:
Other Affiliation:
Department of Medicine/Infectious Diseases; Emory University; Grady Healthcare System, Department of Epidemiology and Population Health; Albert Einstein College of Medicine, Department of Epidemiology; University of Alabama at Birmingham, Division of Infectious Diseases; Department of Medicine; University of Alabama at Birmingham, Department of Epidemiology; Johns Hopkins Bloomberg School of Public Health, Richard M. Fairbanks School of Public Health; Indianapolis University–Purdue University Indianapolis, Department of Medicine; Georgetown University Medical Center, Department of Oral and Maxillofacial Surgery; New York University, Bluestone Center for Clinical Research; New York University, School of Biomedical Informatics; University of Texas Health Science Center at Houston, Department of Biostatistics; University of Alabama at Birmingham, Cook County Health and Hospital System/Hektoen Institute of Medicine, Department of Neurology; University of Alabama at Birmingham, Atherosclerosis Research Unit; University of Southern California, and Department of Medicine; State University of New York; Downstate Medical Center
Page Start:
e0188725
Person:
Ofotokun, Ighovwerha, Hanna, David B., Shrestha, Sadeep, Overton, Edgar T., Gange, Stephen J., Shendre, Aditi, Qi, Qibin, Liu, Chenglong, Wiener, Howard W., Floris-Moore, Michelle A., Irvin, Marguerite R., Aouizerat, Bradley E., Zhi, Degui, Kaplan, Robert C., Weber, Kathleen M., Limdi, Nita A., Hodis, Howard N., and Lazar, Jason
Rights Statement Label:
In Copyright
Source:
47429f84k

1852. Genetic architecture of atherosclerosis dissected by QTL analyses in three F2 intercrosses of apolipoprotein E-null mice on C57BL6/J, DBA/2J and 129S6/SvEvTac backgrounds

Title Tesim:
Genetic architecture of atherosclerosis dissected by QTL analyses in three F2 intercrosses of apolipoprotein E-null mice on C57BL6/J, DBA/2J and 129S6/SvEvTac backgrounds
Creator:
Xu, Longquan, Maeda, Nobuyo, Kayashima, Yukako, Zhilicheva, Svetlana, Morgan, Andrew P., Makhanov, Andrei, Makhanova, Natalia, Hiller, Sylvia, and De Villena, Fernando Pardo-Manuel
Date of publication:
2017
Abstract Tesim:
Quantitative trait locus (QTL) analyses of intercross populations between widely used mouse inbred strains provide a powerful approach for uncovering genetic factors that influence susceptibility to atherosclerosis. Epistatic interactions are common in complex phenotypes and depend on genetic backgrounds. To dissect genetic architecture of atherosclerosis, we analyzed F2 progeny from a cross between apolipoprotein E-null mice on DBA/2J (DBA-apoE) and C57BL/6J (B6-apoE) genetic backgrounds and compared the results with those from two previous F2 crosses of apolipoprotein E-null mice on 129S6/SvEvTac (129-apoE) and DBA-apoE backgrounds, and B6-apoE and 129-apoE backgrounds. In these round-robin crosses, in which each parental strain was crossed with two others, large-effect QTLs are expected to be detectable at least in two crosses. On the other hand, observation of QTLs in one cross only may indicate epistasis and/or absence of statistical power. For atherosclerosis at the aortic arch, Aath4 on chromosome (Chr)2:66 cM follows the first pattern, with significant QTL peaks in (DBAx129)F2 and (B6xDBA)F2 mice but not in (B6x129)F2 mice. We conclude that genetic variants unique to DBA/2J at Aath4 confer susceptibility to atherosclerosis at the aortic arch. A similar pattern was observed for Aath5 on chr10:35 cM, verifying that the variants unique to DBA/2J at this locus protect against arch plaque development. However, multiple loci, including Aath1 (Chr1:49 cM), and Aath2 (Chr1:70 cM) follow the second type of pattern, showing significant peaks in only one of the three crosses (B6-apoE x 129-apoE). As for atherosclerosis at aortic root, the majority of QTLs, including Ath29 (Chr9:33 cM), Ath44 (Chr1:68 cM) and Ath45 (Chr2:83 cM), was also inconsistent, being significant in only one of the three crosses. Only the QTL on Chr7:37 cM was consistently suggestive in two of the three crosses. Thus QTL analysis of round-robin crosses revealed the genetic architecture of atherosclerosis.
Resource type:
Article
Affiliation Label Tesim:
Department of Pathology and Laboratory Medicine and Department of Genetics
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/3vg3-3108
Identifier:
Publisher DOI: https://doi.org/10.1371/journal.pone.0182882, PMID: 28837567, PMCID: PMC5570285, and Onescience id: 09c1668c55e45d42710417c81656d250ca43013f
ISSN:
1932-6203
Journal Issue:
8
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Plaque, Atherosclerotic, Chromosome Mapping, Crosses, Genetic, Mice, Transgenic, Animals, Lipids, Mice, Inbred DBA, Mice, Inbred C57BL, Mice, Aorta, Quantitative Trait Loci, Apolipoproteins E, and Atherosclerosis
Language Label:
English
ORCID:
Other Affiliation:
College of Computing; Georgia Institute of Technology
Page Start:
e0182882
Person:
Xu, Longquan, Maeda, Nobuyo, Kayashima, Yukako, Zhilicheva, Svetlana, Morgan, Andrew P., Makhanov, Andrei, Makhanova, Natalia, Hiller, Sylvia, and De Villena, Fernando Pardo-Manuel
Rights Statement Label:
In Copyright
Source:
9306t4964

1853. Genetic and pharmacological inhibition of TTK impairs pancreatic cancer cell line growth by inducing lethal chromosomal instability

Title Tesim:
Genetic and pharmacological inhibition of TTK impairs pancreatic cancer cell line growth by inducing lethal chromosomal instability
Creator:
Major, Michael B., Stratford, Jeran K., Hill, Rebecca A., Yeh, Jen Jen, Yan, Feng, Der, Channing J., and Graves, Lee M.
Date of publication:
2017
Abstract Tesim:
Pancreatic ductal adenocarcinoma, which accounts for the majority of pancreatic cancers, is a lethal disease with few therapeutic options. Genomic profiling of pancreatic ductal adenocarcinoma has identified a complex and heterogeneous landscape. Understanding the molecular characteristics of pancreatic ductal adenocarcinoma will facilitate the identification of potential therapeutic strategies. We analyzed the gene expression profiles of primary tumors from patients compared to normal pancreas and identified high co-overexpression of core components of the spindle assembly checkpoint, including the protein kinase TTK (also known as MPS-1). We found overexpression of TTK protein in a subset of pancreatic ductal adenocarcinoma primary tumors and cell lines. siRNA-mediated depletion or catalytic inhibition of TTK resulted in an aberrant cell cycle profile, multi- and micro-nucleation, induction of apoptosis, and decreased cell proliferation and transformed growth. Selective catalytic inhibition of TTK caused override of the spindle assembly checkpoint-induced cell cycle arrest. Interestingly, we identified ubiquitin specific peptidase 16 (Usp16), an ubiquitin hydrolase, as a phosphorylation substrate of TTK. Usp16 regulates chromosomal condensation and G2/M progression by deubiquitinating histone H2A and polo-like kinase 1. Phosphomimetic mutants of Usp16 show enhanced proteosomal degradation and may prolong the G2/M transition allowing for correction of replication errors. Taken together, our results suggest a critical role for TTK in preventing aneuploidy-induced cell death in pancreatic cancer.
Resource type:
Article
Affiliation Label Tesim:
University of North Carolina at Chapel Hill and Department of Pharmacology
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/395k-pt97
Identifier:
PMID: 28380042, Onescience id: 1daf7ff5191dbcc13b8509dcfef2c8e526306e12, Publisher DOI: https://doi.org/10.1371/journal.pone.0174863, and PMCID: PMC5381904
ISSN:
1932-6203
Journal Issue:
4
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Flow Cytometry, M Phase Cell Cycle Checkpoints, Gene Expression Profiling, Humans, Cell Cycle Proteins, Immunoblotting, Carcinoma, Pancreatic Ductal, Apoptosis, Cell Cycle, Oligonucleotide Array Sequence Analysis, Chromosomal Instability, Cell Line, Tumor, Immunoprecipitation, and Aneuploidy
Language Label:
English
ORCID:
Other Affiliation:
Department of Computer Science, University of North Carolina at Chapel Hill, and Department of Surgery
Page Start:
e0174863
Person:
Major, Michael B., Stratford, Jeran K., Hill, Rebecca A., Yeh, Jen Jen, Yan, Feng, Der, Channing J., and Graves, Lee M.
Rights Statement Label:
In Copyright
Source:
6108vh28g

1854. Further Development of the Assessment of Military Multitasking Performance: Iterative Reliability Testing

Title Tesim:
Further Development of the Assessment of Military Multitasking Performance: Iterative Reliability Testing
Creator:
Finkelstein, Marsha, Smith, Laurel B., McCulloch, Karen L., Davidson, Leslie F., Scherer, Matthew R., Radomski, Mary V., Weightman, Margaret M., Heaton, Kristin J., and Cecchini, Amy S.
Date of publication:
2017
Abstract Tesim:
The Assessment of Military Multitasking Performance (AMMP) is a battery of functional dual-tasks and multitasks based on military activities that target known sensorimotor, cognitive, and exertional vulnerabilities after concussion/mild traumatic brain injury (mTBI). The AMMP was developed to help address known limitations in post concussive return to duty assessment and decision making. Once validated, the AMMP is intended for use in combination with other metrics to inform duty-readiness decisions in Active Duty Service Members following concussion. This study used an iterative process of repeated interrater reliability testing and feasibility feedback to drive modifications to the 9 tasks of the original AMMP which resulted in a final version of 6 tasks with metrics that demonstrated clinically acceptable ICCs of > 0.92 (range of 0.92–1.0) for the 3 dual tasks and > 0.87 (range 0.87–1.0) for the metrics of the 3 multitasks. Three metrics involved in recording subject errors across 2 tasks did not achieve ICCs above 0.85 set apriori for multitasks (0.64) and above 0.90 set for dual-tasks (0.77 and 0.86) and were not used for further analysis. This iterative process involved 3 phases of testing with between 13 and 26 subjects, ages 18–42 years, tested in each phase from a combined cohort of healthy controls and Service Members with mTBI. Study findings support continued validation of this assessment tool to provide rehabilitation clinicians further return to duty assessment methods robust to ceiling effects with strong face validity to injured Warriors and their leaders.
Resource type:
Article
Affiliation Label Tesim:
Division of Physical Therapy
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/q7hc-h847
Identifier:
Onescience id: 38c216b39af2201e4c54f3f96caa4831061ff7f0, PMCID: PMC5215871, PMID: 28056045, and Publisher DOI: https://doi.org/10.1371/journal.pone.0169104
ISSN:
1932-6203
Journal Issue:
1
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Neuropsychological Tests, Humans, Adult, Brain Injuries, Male, Female, Task Performance and Analysis, Brain Concussion, Young Adult, Reproducibility of Results, and Military Personnel
Language Label:
English
ORCID:
Other Affiliation:
Courage Kenny Research Center; Abbott Northwestern Hospital, United States Army Research Institute of Environmental Medicine, Department of Clinical Research and Leadership; George Washington School of Medicine and Health Sciences, Clinical and Rehabilitative Medicine Research Program; Medical Research Materiel Command, Boston University School of Public Health; Department of Environmental Health, and Defense and Veterans Brain Injury Center
Page Start:
e0169104
Person:
Finkelstein, Marsha, Smith, Laurel B., McCulloch, Karen L., Davidson, Leslie F., Scherer, Matthew R., Radomski, Mary V., Weightman, Margaret M., Heaton, Kristin J., and Cecchini, Amy S.
Rights Statement Label:
In Copyright
Source:
ng451p65v

1855. Flat and complex temperate reefs provide similar support for fish: Evidence for a unimodal species-habitat relationship

Title Tesim:
Flat and complex temperate reefs provide similar support for fish: Evidence for a unimodal species-habitat relationship
Creator:
Pickering, Emily A., Paxton, Avery B., Peterson, Charles H., Taylor, J. Christopher, and Adler, Alyssa M.
Date of publication:
2017
Abstract Tesim:
Structural complexity, a form of habitat heterogeneity, influences the structure and function of ecological communities, generally supporting increased species density, richness, and diversity. Recent research, however, suggests the most complex habitats may not harbor the highest density of individuals and number of species, especially in areas with elevated human influence. Understanding nuances in relationships between habitat heterogeneity and ecological communities is warranted to guide habitat-focused conservation and management efforts. We conducted fish and structural habitat surveys of thirty warm-temperate reefs on the southeastern US continental shelf to quantify how structural complexity influences fish communities. We found that intermediate complexity maximizes fish abundance on natural and artificial reefs, as well as species richness on natural reefs, challenging the current paradigm that abundance and other fish community metrics increase with increasing complexity. Naturally occurring rocky reefs of flat and complex morphologies supported equivalent abundance, biomass, species richness, and community composition of fishes. For flat and complex morphologies of rocky reefs to receive equal consideration as essential fish habitat (EFH), special attention should be given to detecting pavement type rocky reefs because their ephemeral nature makes them difficult to detect with typical seafloor mapping methods. Artificial reefs of intermediate complexity also maximized fish abundance, but human-made structures composed of low-lying concrete and metal ships differed in community types, with less complex, concrete structures supporting lower numbers of fishes classified largely as demersal species and metal ships protruding into the water column harboring higher numbers of fishes, including more pelagic species. Results of this study are essential to the process of evaluating habitat function provided by different types and shapes of reefs on the seafloor so that all EFH across a wide range of habitat complexity may be accurately identified and properly managed.
Resource type:
Article
Affiliation Label Tesim:
University of North Carolina at Chapel Hill
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/vaj2-bz64
Identifier:
PMCID: PMC5584758, PMID: 28873447, Publisher DOI: https://doi.org/10.1371/journal.pone.0183906, and Onescience id: dde5e1326acc25ee0a4bc8e89f22bb451268b52c
ISSN:
1932-6203
Journal Issue:
9
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Ecology, Community Structure, Animals, Organisms, Temperature, Biomass, Geography, Q, Ecological Metrics, Geology, Engineering and Technology, Coral Reefs, Sedimentary Geology, Seawater, Community Ecology, Reefs, Marine and Aquatic Sciences, Ships, Medicine, Surveys and Questionnaires, Marine Biology, Vertebrates, R, Habitats, Sediment, Seasons, Biology and Life Sciences, Biodiversity, Science, Earth Sciences, Species Diversity, Transportation, Fishes, Petrology, Research Article, Metals, and Ecology and Environmental Sciences
Language Label:
English
ORCID:
Other Affiliation:
Department of Biology and National Ocean Service; National Centers for Coastal Ocean Science; National Oceanic and Atmospheric Administration
Page Start:
e0183906
Person:
Pickering, Emily A., Paxton, Avery B., Peterson, Charles H., Taylor, J. Christopher, and Adler, Alyssa M.
Rights Statement Label:
In Copyright
Source:
c534fv02j

1856. First year physical activity findings from turn up the HEAT (Healthy Eating and Activity Time) in summer day camps

Title Tesim:
First year physical activity findings from turn up the HEAT (Healthy Eating and Activity Time) in summer day camps
Creator:
Chandler, Jessica L., Turner-Mcgrievy, Gabrielle M., Beets, Michael W., Moore, Justin B., Ward, Dianne S., Weaver, R. Glenn, Brazendale, Keith, and Huberty, Jennifer L.
Date of publication:
2017
Abstract Tesim:
Summer day camps (SDCs) serve 14 million children yearly in the U.S. and aim to provide participating children with 60 minutes of moderate-to-vigorous physical activity (MVPA). This study evaluated an intervention designed to increase the percent of children meeting this MVPA guideline.
Resource type:
Article
Affiliation Label Tesim:
Department of Nutrition
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/91ab-mw89
Identifier:
PMCID: PMC5369693, Publisher DOI: https://doi.org/10.1371/journal.pone.0173791, Onescience id: 259d3c29de7a7e6be4e33ab450e1e7999d393bd1, and PMID: 28350830
ISSN:
1932-6203
Journal Issue:
3
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Humans, Seasons, Time Factors, Accelerometry, Child, Preschool, Male, Health Promotion, Child, Camping, Healthy Diet, Female, Logistic Models, Exercise, Outcome Assessment (Health Care), and United States
Language Label:
English
ORCID:
Other Affiliation:
Department of Exercise Science; University of South Carolina, Department of Health Promotion; Education; and Behavior; University of South Carolina, Department of Family and Community Medicine; Wake Forest School of Medicine, and School of Nutrition and Health Promotion; Arizona State University
Page Start:
e0173791
Person:
Chandler, Jessica L., Turner-Mcgrievy, Gabrielle M., Beets, Michael W., Moore, Justin B., Ward, Dianne S., Weaver, R. Glenn, Brazendale, Keith, and Huberty, Jennifer L.
Rights Statement Label:
In Copyright
Source:
sn00b3615

1857. Factors influencing postnatal Option B+ participation and breastfeeding duration among HIV-positive women in Lilongwe District, Malawi: A qualitative study

Title Tesim:
Factors influencing postnatal Option B+ participation and breastfeeding duration among HIV-positive women in Lilongwe District, Malawi: A qualitative study
Creator:
Flax, Valerie L., Hoffman, Irving F., Mofolo, Innocent, Maman, Suzanne, Hosseinipour, Mina C., and Hamela, Gloria
Date of publication:
2017
Abstract Tesim:
To ensure the health of mothers and children, prevention of mother-to-child HIV transmission (PMTCT) programs test women for HIV, engage HIV-positive women in care, and promote recommended breastfeeding practices. Under Malawi’s Option B+ PMTCT program, ~20% of women are lost-to-follow-up (LTFU) and little is known about their breastfeeding practices. The purpose of this study is to describe facilitators and barriers to Option B+ participation and how participation influences breastfeeding duration. We conducted in-depth interviews with HIV-positive women in Option B+ (n = 32) or LTFU from Option B+ (n = 32). They were recruited from four government clinics in Lilongwe District and had a child aged 0–23 months. Women in Option B+ had better disclosure experiences and more social support than LTFU women. The most common reasons for LTFU were fear of HIV disclosure, anticipated or experienced stigma, and insufficient social support. Other reasons included: non-acceptance of HIV status, antiretroviral therapy (ART) side effects, lack of funds for transport, and negative experiences with clinic staff. Worries about possible transmission, even while on ART, influenced timing of weaning for some women in Option B+. Despite their knowledge of the risk of HIV transmission to the child, most LTFU women continued to breastfeed after stopping ART because they considered breastmilk to be an important source of nutrients for the child. Given that HIV-positive Malawian women LTFU from Option B+ breastfeed in the absence of ART, efforts are needed to use evidence-based strategies to address the barriers to Option B+ participation and avert preventable transmission through breastmilk.
Resource type:
Article
Affiliation Label Tesim:
Department of Nutrition, UNC Project-Malawi, and Department of Health Behavior
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/14at-fj07
Identifier:
PMCID: PMC5391929, Publisher DOI: https://doi.org/10.1371/journal.pone.0175590, PMID: 28410374, and Onescience id: 88752315e252eb150b1fbb347d7ec6265641968b
ISSN:
1932-6203
Journal Issue:
4
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Adult, Infectious Disease Transmission, Vertical, HIV Infections, Pregnancy, Social Stigma, Infant, Newborn, Social Support, Female, Anti-Retroviral Agents, Infant, Young Adult, Humans, Program Evaluation, Mothers, Interviews as Topic, Breast Feeding, and Malawi
Language Label:
English
ORCID:
Other Affiliation:
RTI International and Department of Medicine
Page Start:
e0175590
Person:
Flax, Valerie L., Hoffman, Irving F., Mofolo, Innocent, Maman, Suzanne, Hosseinipour, Mina C., and Hamela, Gloria
Rights Statement Label:
In Copyright
Source:
z890s0436

1858. Extreme low dose of 5-fluorouracil reverses MDR in cancer by sensitizing cancer associated fibroblasts and down-regulating P-gp

Title Tesim:
Extreme low dose of 5-fluorouracil reverses MDR in cancer by sensitizing cancer associated fibroblasts and down-regulating P-gp
Creator:
Ma, Yan, Fallon, John K., Wang, Yuhua, Wang, Yongjun, Liu, Feng, and Xu, Zhenghong
Date of publication:
2017
Abstract Tesim:
We conducted a prospective, meaningful study of extreme low dose of 5-fluorouracil (5FU) as a metronomic agent targeting cancer associated fibroblasts (CAFs) to reverse Multidrug resistance (MDR) by sensitizing cancer associated fibroblasts and down-regulating P-glycoprotein (P-gp). The combination of 5FU and Taxol inhibited resistant KB-8-5 tumor growth by 79% and H460/Tax-R tumor growth by 55%. The inhibition was significant for both tumor types compared with Taxol treatment alone (p<0.001 and p = 0.0067, respectively). Nevertheless, the low-dose 5FU (2.2 mg/kg compared to the therapeutic dose of 50–150 mg/kg) showed negligible tumor inhibitory effect. The tumor growth inhibition study on resistant tumors demonstrated that the continuous administration of low dose 5FU with Taxol significantly inhibited the tumor growth. The treatment overcomes drug resistance in tumors by down-regulating multi-drug resistance transporter protein (P-gp), and more importantly, by eliminating CAFs recruited by resistant tumors. Compared with traditional metronomic chemotherapy, 5FU as metronomic agent targeting CAFs can avoid the disadvantages resulted from the concomitant administration of antiangiogenetic drug. The approach has good translational potential for clinical trials when treating stroma-rich drug resistant tumors.
Resource type:
Article
Affiliation Label Tesim:
Division of Molecular Pharmaceutics
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/q160-xp20
Identifier:
Onescience id: 7b0ff8e6492a9b063e5be041d591b447da34062e, Publisher DOI: https://doi.org/10.1371/journal.pone.0180023, PMID: 28662182, and PMCID: PMC5491115
ISSN:
1932-6203
Journal Issue:
6
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Dose-Response Relationship, Drug, Fluorouracil, Down-Regulation, Fibroblasts, Drug Resistance, Neoplasm, Humans, Paclitaxel, Neoplasms, Animals, Cell Line, Tumor, ATP-Binding Cassette, Sub-Family B, Member 1, Mice, Antineoplastic Combined Chemotherapy Protocols, and Mice, Nude
Language Label:
English
ORCID:
Other Affiliation:
School of Chinese Materia Medica; Guangzhou University of Chinese Medicine and School of Pharmacy; Shenyang Pharmaceutical University
Page Start:
e0180023
Person:
Ma, Yan, Fallon, John K., Wang, Yuhua, Wang, Yongjun, Liu, Feng, and Xu, Zhenghong
Rights Statement Label:
In Copyright
Source:
qr46r5875

1859. Exploring the HIV continuum of care among young black MSM

Title Tesim:
Exploring the HIV continuum of care among young black MSM
Creator:
LeGrand, Sara, Choi, Seul Ki, Hurt, Christopher B., Hightow-Weidman, Lisa, Muessig, Kathryn E., and Egger, Joseph
Date of publication:
2017
Abstract Tesim:
HIV disproportionately impacts young, black men who have sex with men (YBMSM) who experience disparities across the HIV care continuum. A more nuanced understanding of facilitators and barriers to engagement in care, missed visits, antiretroviral uptake, adherence and viral suppression could improve care and intervention design.
Resource type:
Article
Affiliation Label Tesim:
Department of Health Behavior and Institute for Global Health and Infectious Diseases
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/fb9h-m167
Identifier:
Onescience id: 5252b17db0d0d283c7a4660bcf68b5ab2537ec54, Publisher DOI: https://doi.org/10.1371/journal.pone.0179688, PMID: 28662170, and PMCID: PMC5491033
ISSN:
1932-6203
Journal Issue:
6
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Adult, African Continental Ancestry Group, Humans, Young Adult, Continuity of Patient Care, Homosexuality, Male, Male, Insurance Coverage, HIV Infections, and Anti-HIV Agents
Language Label:
English
ORCID:
Other Affiliation:
Duke Global Health Institute; Duke University and
Page Start:
e0179688
Person:
LeGrand, Sara, Choi, Seul Ki, Hurt, Christopher B., Hightow-Weidman, Lisa, Muessig, Kathryn E., and Egger, Joseph
Rights Statement Label:
In Copyright
Source:
qj72pd496

1860. Exploring factors associated with ART adherence and retention in care under Option B+ strategy in Malawi: A qualitative study

Title Tesim:
Exploring factors associated with ART adherence and retention in care under Option B+ strategy in Malawi: A qualitative study
Creator:
Sikwese, Pascal, O’Malley, Gabrielle, Gugsa, Salem, Phiri, Sam, Chikonda, Janet, Sande, Odala, Potter, Katy, and Tweya, Hannock
Date of publication:
2017
Abstract Tesim:
Although several studies have documented challenges related to inadequate adherence to antiretroviral therapy (ART) and high loss to follow-up (LTFU) among Option B+ women, there is limited understanding of why these challenges occur and how to address them. This qualitative study examines women’s experiences with ART adherence and retention in care. Between July and October 2015, in-depth interviews were conducted with 39 pregnant and lactating women who initiated ART at Bwaila Hospital in Lilongwe, Malawi. Study participants included 14 in care and 25 out of care women, according to facility records. Data were analyzed using an inductive, open-coding approach to thematic analysis. Ten of the respondents (7 out of care, 3 in-care) had stopped and re-started treatment before the interview date. One of the most important factors influencing adherence and retention was the strength of women’s support systems. In contrast to women in-care, most out-of-care women lacked emotional and financial support from male partners, received minimal counseling from providers at initiation, lacked designated guardians to assist with medication refills or clinic appointments, and were highly mobile. Mobility led to difficulties in accessing treatment in new settings. The most common reasons women re-started treatment following interruptions were due to providers’ counseling and encouragement and the mother’s desire to be healthy. Improved counseling at initiation, active follow-up counseling, women’s economic empowerment interventions, promotion of peer counseling schemes and meaningful engagement of male partners can help in addressing the identified barriers and promoting sustained retention of Option B+ women.
Resource type:
Article
Affiliation Label Tesim:
Department of Medicine
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/e2/82/bb/5c/e282bb5c-ecfc-4dd2-8603-2a46b5cc8e4b
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/gx7k-3v95
Identifier:
Publisher DOI: https://doi.org/10.1371/journal.pone.0179838, PMCID: PMC5479573, PMID: 28636669, and Onescience id: bcc40d3b9570405ff414938ce15ae22d93a4d422
ISSN:
1932-6203
Journal Issue:
6
Journal Title:
PloS One
Journal Volume:
12
Keyword:
Qualitative Research, Adult, Malawi, Breast Feeding, Interviews as Topic, HIV Infections, Medication Adherence, Young Adult, Counseling, Anti-Retroviral Agents, Program Development, Humans, and Female
Language Label:
English
ORCID:
Other Affiliation:
Lighthouse Trust, International Training and Education Center for Health (I-TECH); University of Washington; Department of Global Health, University of Malawi; College of Medicine; School of Public Health and Family Medicine; Department of Public Health, Ministry of Health; District Health Office, and International Union Against Tuberculosis and Lung Disease
Page Start:
e0179838
Person:
Sikwese, Pascal, O’Malley, Gabrielle, Gugsa, Salem, Phiri, Sam, Chikonda, Janet, Sande, Odala, Potter, Katy, and Tweya, Hannock
Rights Statement Label:
In Copyright
Source:
73666956n