Publications
Department of Medicine faculty members published more than 3,600 peer-reviewed articles in 2024.
2014
2014
2014
The association between the host immune environment and the size of the HIV reservoir during effective antiretroviral therapy is not clear. Progress has also been limited by the lack of a well-accepted assay for quantifying HIV during therapy. We examined the association between multiple measurements of HIV and T cell activation (as defined by markers including CD38, HLA-DR, CCR5 and PD-1) in 30 antiretroviral-treated HIV-infected adults. We found a consistent association between the frequency of CD4+ and CD8+ T cells expressing HLA-DR and the frequency of resting CD4+ T cells containing HIV DNA. This study highlights the need to further examine this relationship and to better characterize the biology of markers commonly used in HIV studies. These results may also have implications for reactivation strategies.
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In addition to their protein coding function, exons can also serve as transcriptional enhancers. Mutations in these exonic-enhancers (eExons) could alter both protein function and transcription. However, the functional consequence of eExon mutations is not well known. Here, using massively parallel reporter assays, we dissect the enhancer activity of three liver eExons (SORL1 exon 17, TRAF3IP2 exon 2, PPARG exon 6) at single nucleotide resolution in the mouse liver. We find that both synonymous and non-synonymous mutations have similar effects on enhancer activity and many of the deleterious mutation clusters overlap known liver-associated transcription factor binding sites. Carrying a similar massively parallel reporter assay in HeLa cells with these three eExons found differences in their mutation profiles compared to the liver, suggesting that enhancers could have distinct operating profiles in different tissues. Our results demonstrate that eExon mutations could lead to multiple phenotypes by disrupting both the protein sequence and enhancer activity and that enhancers can have distinct mutation profiles in different cell types.
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The transcriptional activation of one out of ?2800 olfactory receptor (OR) alleles is a poorly understood process. Here, we identify a plethora of putative OR enhancers and study their in vivo activity in olfactory neurons. Distinguished by an unusual epigenetic signature, candidate OR enhancers are characterized by extensive interchromosomal interactions associated with OR transcription and share a similar pattern of transcription factor footprints. In particular, we establish the role of the transcription factor Bptf as a facilitator of both enhancer interactions and OR transcription. Our observations agree with the model whereby OR transcription occurs in the context of multiple interacting enhancers. Disruption of these interchromosomal interactions results in weak and multigenic OR expression, suggesting that the rare coincidence of numerous enhancers over a stochastically chosen OR may account for the singularity and robustness in OR transcription.
View on PubMed2014
OBJECTIVE
Unintended pregnancy is common and disproportionately occurs among low-income women. We conducted a qualitative study with low-income women to better typologize pregnancy intention, understand the relationship between pregnancy intention and contraceptive use, and identify the contextual factors that shape pregnancy intention and contraceptive behavior.
STUDY DESIGN
Semistructured interviews were conducted with low-income, African-American and white women aged 18-45 recruited from reproductive health clinics in Pittsburgh, PA, to explore factors that influence women's pregnancy-related behaviors. Narratives were analyzed using content analysis and the constant comparison method.
RESULTS
Among the 66 participants (36 African-American and 30 white), we identified several factors that may impede our public health goal of increasing the proportion of pregnancies that are consciously desired and planned. First, women do not always perceive that they have reproductive control and therefore do not necessarily formulate clear pregnancy intentions. Second, the benefits of a planned pregnancy may not be evident. Third, because preconception intention and planning do not necessarily occur, decisions about the acceptability of a pregnancy are often determined after the pregnancy has already occurred. Finally, even when women express a desire to avoid pregnancy, their contraceptive behaviors are not necessarily congruent with their desires. We also identified several clinically relevant and potentially modifiable factors that help to explain this intention-behavior discrepancy, including women's perceptions of low fecundity and their experiences with male partner contraceptive sabotage.
CONCLUSION
Our findings suggest that the current conceptual framework that views pregnancy-related behaviors from a strict planned behavior perspective may be limited, particularly among low-income populations.
IMPLICATIONS
This study identified several cognitive and interpersonal pathways to unintended pregnancy among low-income women in Pittsburgh, PA, including perceptions of low reproductive control, perceptions of low fecundity and male partner reproductive coercion.
View on PubMed2014
2014
2014
2014
OBJECTIVE
The goal of this study was to summarise the websites of electronic cigarette (e-cigarette) manufacturers in China and describe how they market their products.
METHODS
From March to April 2013, we used two search keywords 'electronic cigarette' (Dian Zi Xiang Yan in Chinese) and 'manufacturer' (Sheng Chan Chang Jia in Chinese) to search e-cigarette manufacturers in China on Alibaba, an internet-based e-commerce business that covers business-to-business online marketplaces, retail and payment platforms, shopping search engine and data-centric cloud computing services. A total of 18 websites of 12 e-cigarette manufacturers in China were analysed by using a coding guide which includes 14 marketing claims.
RESULTS
Health-related benefits were claimed most frequently (89%), followed by the claims of no secondhand smoke (SHS) exposure (78%), and utility for smoking cessation (67%). A wide variety of flavours, celebrity endorsements and e-cigarettes specifically for women were presented. None of the websites had any age restriction on access, references to government regulation or lawsuits. Instruction on how to use e-cigarettes was on 17% of the websites.
CONCLUSIONS
Better regulation of e-cigarette marketing messages on manufacturers' websites is needed in China. The frequent claims of health benefits, smoking cessation, strategies appealing to youth and women are concerning, especially targeting women. Regulators should prohibit marketing claims of health benefits, no SHS exposure and value for smoking cessation in China until health-related, quality and safety issues have been adequately addressed. To avoid e-cigarette use for initiation to nicotine addiction, messages targeting youth and women should be prohibited.
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