Use of electronic personal health record systems to encourage HIV screening: an exploratory study of patient and provider perspectives

<p>Abstract</p> <p>Background</p> <p>When detected, HIV can be effectively treated with antiretroviral therapy. Nevertheless in the U.S. approximately 25% of those who are HIV-infected do not know it. Much remains unknown about how to increase HIV testing rates. New Internet outreach methods have the potential to increase disease awareness and screening among patients, especially as electronic personal health records (PHRs) become more widely available. In the US Department of Veterans' Affairs medical care system, 900,000 veterans have indicated an interest in receiving electronic health-related communications through the PHR. Therefore we sought to evaluate the optimal circumstances and conditions for outreach about HIV screening. In an exploratory, qualitative research study we examined patient and provider perceptions of Internet-based outreach to increase HIV screening among veterans who use the Veterans Health Administration (VHA) health care system.</p> <p>Findings</p> <p>We conducted two rounds of focus groups with veterans and healthcare providers at VHA medical centers. The study's first phase elicited general perceptions of an electronic outreach program to increase screening for HIV, diabetes, and high cholesterol. Using phase 1 results, outreach message texts were drafted and then presented to participants in the second phase. Analysis followed modified grounded theory.</p> <p>Patients and providers indicated that electronic outreach through a PHR would provide useful information and would motivate patients to be screened for HIV. Patients believed that electronic information would be more convenient and understandable than information provided verbally. Patients saw little difference between messages about HIV versus about diabetes and cholesterol. Providers, however, felt patients would disapprove of HIV-related messages due to stigma. Providers expected increased workload from the electronic outreach, and thus suggested adding primary care resources and devising methods to smooth the flow of patients getting screened. When provided a choice between unsecured emails versus PHRs as the delivery mechanism for disease screening messages, both patients and providers preferred PHRs.</p> <p>Conclusions</p> <p>There is considerable potential to use PHR systems for electronic outreach and social marketing to communicate to patients about, and increase rates of, disease screening, including for HIV. Planning for direct-to-patient communications through PHRs should include providers and address provider reservations, especially about workload increases.</p

Trademarks, Certification Marks and Technical Standards

The names of many technical standards such as Wi-Fi, Bluetooth and DVD have become household terms known throughout the developed world. This chapter describes different approaches that have been taken with respect to the naming and legal protection of technical standards, ranging from those that are wholly unregulated to those that are administered under strict certification and compliance regimes. It concludes by questioning the need for aggressive protection of marks that exist largely to inform consumers about technical product features rather than the source of standards themselves

Modular engineering and in vivo library selection of tissue-targeting protein nanoparticles

Thesis (Ph.D.)--University of Washington, 2023Targeted delivery remains one of the greatest challenges and opportunities in drug development. In Chapter 1, I review these challenges and opportunities through the lens of the principles of applying self-assembling protein nanomaterials to therapeutic delivery. In Chapter 2, I report an in vivo library selection platform based on protein nanoparticles that encapsulate their own genome. Our selection platform offers a unique tool to optimize protein-based therapeutic performance in a living mammal, a complex physiological environment that cannot yet be comprehensively modeled in silico or in vitro, and to identify targeting ligands of interest. In Chapter 3, I report results towards modularly reprogramming synthetic nucleocapsids for targeted chemotherapeutic delivery by altering both the displayed targeting domains and the encapsulated cargo. I discuss potential future directions in Chapter 4. Together, these results provide new insights and methods for developing self-assembling nanomaterials for in vivo targeted delivery

Site-Directed Mutagenesis to Improve Sensitivity of a Synthetic Two-Component Signaling System

Two-component signaling (2CS) systems enable bacterial cells to respond to changes in their local environment, often using a membrane-bound sensor protein and a cytoplasmic responder protein to regulate gene expression. Previous work has shown that Escherichia coli’s natural EnvZ/OmpR 2CS could be modified to construct a light-sensing bacterial photography system. The resulting bacterial photographs, or “coliroids,” rely on a phosphotransfer reaction between Cph8, a synthetic version of EnvZ that senses red light, and OmpR. Gene expression changes can be visualized through upregulation of a LacZ reporter gene by phosphorylated OmpR. Unfortunately, basal LacZ expression leads to a detectable reporter signal even when cells are grown in the light, diminishing the contrast of the coliroids. We performed site-directed mutagenesis near the phosphotransfer site of Cph8 to isolate mutants with potentially improved image contrast. Five mutants were examined, but only one of the mutants, T541S, increased the ratio of dark/light gene expression, as measured by β-galactosidase activity. The ratio changed from 2.57 fold in the starting strain to 5.59 in the T541S mutant. The ratio decreased in the four other mutant strains we examined. The phenotype observed in the T541S mutant strain may arise because the serine sidechain is chemically similar but physically smaller than the threonine sidechain. This may minimally change the protein’s local structure, but may be less sterically constrained when compared to threonine, resulting in a higher probability of a phosphotransfer event. Our initial success pairing synthetic biology and site-directed mutagenesis to optimize the bacterial photography system’s performance encourages us to imagine further improvements to the performance of this and other synthetic systems, especially those based on 2CS signaling

MAF1 is a predictive biomarker in HER2 positive breast cancer.

RNA polymerase III transcription is pivotal in regulating cellular growth and frequently deregulated in various cancers. MAF1 negatively regulates RNA polymerase III transcription. Currently, it is unclear if MAF1 is universally deregulated in human cancers. Recently, MAF1 expression has been demonstrated to be altered in colorectal and liver carcinomas and Luminal B breast cancers. In this study, we analyzed clinical breast cancer datasets to determine if MAF1 alterations correlate with clinical outcomes in HER2-positive breast cancer. Using various bioinformatics tools, we screened breast cancer datasets for alterations in MAF1 expression. We report that MAF1 is amplified in 39% of all breast cancer sub-types, and the observed amplification co-occurs with MYC. MAF1 amplification correlated with increased methylation of the MAF1 promoter and MAF1 protein expression is significantly decreased in luminal, HER2-positive, and TNBC breast cancer subtypes. MAF1 protein expression is also significantly reduced in stage 2 and 3 breast cancer compared to normal and significantly decreased in all breast cancer patients, regardless of race and age. In SKBR3 and BT474 breast cancer cell lines treated with anti-HER2 therapies, MAF1 mRNA expression is significantly increased. In HER2-positive breast cancer patients, MAF1 expression significantly increases and correlates with five years of relapse-free survival in response to trastuzumab treatment, suggesting MAF1 is a predictive biomarker in breast cancer. These data suggest a role for MAF1 alterations in HER2-positive breast cancer. More extensive studies are warranted to determine if MAF1 serves as a predictive and prognostic biomarker in breast cancer

BDP1 as a biomarker in serous ovarian cancer

Abstract Background TFIIIB, an RNA polymerase III specific transcription factor has been found to be deregulated in human cancers with much of the research focused on the TBP, BRF1, and BRF2 subunits. To date, the TFIIIB specific subunit BDP1 has not been investigated in ovarian cancer but has previously been shown to be deregulated in neuroblastoma, breast cancer, and Non‐Hodgkins lymphoma. Results Using in silico analysis of clinically derived platforms, we report a decreased BDP1 expression as a result of deletion in serous ovarian cancer and a correlation with higher and advanced ovarian stages. Further analysis in the context of TP53 mutations, a major contributor to ovarian tumorigenesis, suggests that high BDP1 expression is unfavorable for overall survival and high BDP1 expression occurs in stages 2, 3 and 4 serous ovarian cancer. Additionally, high BDP1 expression is disadvantageous and unfavorable for progression‐free survival. Lastly, BDP1 expression significantly decreased in patients treated with first‐line chemotherapy, platin and taxane, at twelve‐month relapse‐free survival. Conclusions Taken together with a ROC analysis, the data suggest BDP1 could be of clinical relevance as a predictive biomarker in serous ovarian cancer. Lastly, this study further demonstrates that both the over‐ and under expression of BDP1 warrants further investigation and suggests BDP1 may exhibit dual function in the context of tumorigenesis