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Open Access Publications from the University of California

Scholarly Works (2 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2015)

Little is understood about the genesis of autoimmune diseases caused by deficiencies in TAM receptors (Tyro3, Axl, Mer). One of the causes of autoimmunity could be defective thymic education. Our goal was to elucidate the localization and role of TAM receptors and their ligands within the thymus. We show that Axl and Mer, but not Tyro3, are expressed within the thymus. Through immunohistochemistry, we identify Axl and Mer expression primarily on macrophages in both the medulla and cortex. Using knockout mice, we show that Axl and Mer perform necessary but redundant roles in the elimination of basally accumulated apoptotic thymocytes. The absence of both receptors leads to immense apoptotic cell accumulation within thymic cortex and medulla.These changes result in minor morphological defects as the weight but not the ratio of medulla to cortex was affected in the Axl-/-Mertk-/- mice. We further use this model to instigate Axl dependence on Gas6 as a ligand in thymus. Additionally, we show that during acute thymocyte apoptosis, Mer but not Axl is critical in cellular clearance.

    Cover page: The Role and Location of TAM Receptors in the Thymus
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2019)

    Introduction

    Geographic and transportation barriers are associated with poorer HIV-related health outcomes in sub-Saharan Africa, but data on the impact of these barriers on prevention interventions are limited. We estimated the association between distance to clinic and other transportation-related barriers on pre-exposure prophylaxis (PrEP) uptake and initial clinic visit attendance in a rural community in southwestern Uganda enrolled in the ongoing SEARCH study (NCT01864603).

    Methods

    Community-wide HIV testing was conducted and offered to adult (≥15 years) participants in Ruhoko. Participants were eligible for PrEP based on an empiric risk score, having an HIV-discordant partner, or self-referral at either the community health campaign or during home-based testing from March to April 2017. We collected data from PrEP-eligible households on GPS-measured distance to clinic, walking time to clinic and road difficulty. A sample of participants was also asked to identify their primary barriers to PrEP use with a semi-quantitative questionnaire. We used multivariable logistic regression to evaluate the association between transportation barriers and (1) PrEP uptake among PrEP-eligible individuals and (2) four-week clinic visit attendance among PrEP initiators.

    Results

    Of the 701 PrEP-eligible participants, 272 (39%) started PrEP within four weeks; of these, 45 (17%) were retained at four weeks. Participants with a distance to clinic of ≥2 km were less likely to start PrEP (aOR 0.34; 95% CI 0.15 to 0.79, p = 0.012) and less likely to be retained on PrEP once initiated (aOR 0.29; 95% CI 0.10 to 0.84; p = 0.024). Participants who were deemed eligible during home-based testing and did not have the option of same-day PrEP start were also substantially less likely to initiate PrEP (aOR 0.16, 95% CI 0.07 to 0.37, p < 0.001). Of participants asked to name barriers to PrEP use (N = 98), the most frequently cited were "needing to take PrEP every day" (N = 18) and "low/no risk of getting HIV" (N = 18). Transportation-related barriers, including "clinic is too far away" (N = 6) and "travel away from home" (N = 4) were also reported.

    Conclusions

    Distance to clinic is a significant predictor of PrEP uptake and four-week follow-up visit attendance in a community in rural Uganda. Interventions that address geographic and transportation barriers may improve PrEP uptake and retention in sub-Saharan Africa.
      Cover page: Distance to clinic is a barrier to PrEP uptake and visit attendance in a community in rural Uganda.
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