Research Grants Program Office

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BACKGROUND: In California, all four-year public colleges have adopted 100% smoke-/tobacco-free policies (TFP) whereas community colleges (CCs), particularly rural CCs, are less likely to have tobacco-free environments. This raises concerns about health equity, particularly because smoking prevalence is higher in rural areas compared to urban. We examined policy adoption barriers and facilitators for rural California CCs with the aim of providing lessons learned to support TFP adoption by rural CCs and improve conditions for student health and well-being. METHODS: A multiple case study of four CCs in California with (n = 2) and without (n = 2) TFPs was conducted. Semi-structured interviews with 12 campus and community stakeholders, school administrative data, and policy-relevant documents were analyzed at the case level with comparison across cases to identify key barriers, facilitators and campus-specific experiences. RESULTS: All four CCs shared similar barriers to policy adoption including concerns about wildfires, individual rights, and fear of marginalizing people who smoke on campus. These CCs have experienced serious wildfires in the last ten years, have high community smoking prevalence, and fewer school resources for student health. For the two tobacco-free CCs, long-term wildfire mitigation efforts along with leadership support, campus/community partnerships and a collective approach involving diverse campus sectors were essential facilitators in successful TFP adoption. CONCLUSION: Study results underscore contextual pressures and campus dynamics that impact tobacco control efforts at colleges in rural communities. Strategies to advance college TFP adoption and implementation should recognize rural cultural and community priorities.

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Although numerous editorials claim the COVID-19 pandemic has disproportionately impacted vulnerable populations, particularly those affected by HIV, these claims have received limited empirical evaluation. We analyzed posts to Reddit's r/HIVAIDS from January 3, 2012 through April 30, 2022 to (a) assess changes in the volume of posts during the pandemic and (b) determine the needs of HIV affected communities. There were cumulatively 100% (95%CI: 75-126) more posts than expected since the US declared a pandemic emergency. The most prevalent themes in these posts were for obtaining an HIV + diagnosis (representing 34% (95%CI:29-40) of all posts), seeking HIV treatment (20%; 95%CI:16-25), finding psychosocial support (16%; 95%CI:12-20), and tracking disease progression (8%; 95%CI:5-11). Discussions about PrEP and PEP were the least common, representing less than 6% of all posts each. Social media has increasingly become an important health resource for vulnerable populations seeking information, advice, and support. Public health organizations should recognize how the lay public uses social media and collaborate with social media companies to ensure that the needs of help-seekers on these platforms are met.

Abstract: Glioblastoma multiforme (GBM) is the most aggressive primary malignant brain tumor in adults, with a poor prognosis that highlights a dire clinical need for innovative therapeutic interventions. Despite significant advances in diagnoses and multimodality therapies, the overall prognosis for patients with GBM remains poor, with a median survival time of 15-18 months. Therefore, there is an unmet medical need to develop alternative treatment strategies to improve clinical outcomes. Dysregulation of post-transcriptional control and translational machinery have been implicated in malignant tumor development. Cytoplasmic polyadenylation element binding proteins (CPEB1-CPEB4) are RNA-binding proteins that regulate poly(A) tail elongation of target mRNAs and subsequently contribute to phenotypic changes in cancer cells. Notably, a self-cleaving ribozyme was identified in the CPEB3 gene, but its role in cancer is wholly unexplored. Considering the role of CPEB3 as a tumor suppressor gene and the promotion of cancer progression through the downregulation of CPEB3, our hypothesis is that the CPEB3 ribozyme regulates CPEB3 expression, and its activity contributes to the progression of tumors. Using antisense oligonucleotides (ASOs) as an approach, we demonstrated that inhibition of CPEB3 ribozyme resulted in an increase of CPEB3 mRNA and protein expression. Blocking the CPEB3 ribozyme led to a significant reduction in cell proliferation, migration, and invasion in GBM cell lines. Gene set enrichment analysis (GSEA) revealed the downregulation of epithelial-mesenchymal transition (EMT), angiogenesis, and hypoxia gene sets in GBM cells treated with ASO compared to Ctrl-ASO. We further measured VEGFA mRNA and protein expression and found that ASO-treated GBM cells secreted significantly less VEGF in conditioned media. Inhibition of the CPEB3 ribozyme also mitigated the EMT process in GBM cells. Subsequently, ASO strategies were applied to patient-derived glioma stem cells (GSCs), representing a clinically relevant model for pre-clinical therapeutic intervention. We found that treatment of CPEB3 ribozyme ASO up-regulated CPEB3 mRNA and inhibited cell proliferation in GSCs. Furthermore, the combination of ASO and temozolomide chemotherapy exhibited a more pronounced decrease in GSCs proliferation compared to individual treatment alone. Collectively, this study highlights the significance of the CPEB3 ribozyme in GBM and explores therapeutic approaches focused on targeting CPEB3 in cancer. Citation Format: Claire Chen, Eric Wang, Lily Tong, Mehran Nikan, Daniela A. Bota, Claudia Benavente, Andrej Luptak. Suppression of the CPEB3 ribozyme modulates the progression of glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3180.

Mammalian polynucleotide kinase 3'-phosphatase (PNKP), a DNA end-processing enzyme with 3'-phosphatase and 5'-kinase activities, is involved in multiple DNA repair pathways, including base excision (BER), single-strand break (SSBR), and double-strand break repair (DSBR). However, little is known as to how PNKP functions in such diverse repair processes. Here we report that PNKP is acetylated at K142 (AcK142) by p300 constitutively but at K226 (AcK226) by CBP, only after DSB induction. Co-immunoprecipitation analysis using AcK142 or AcK226 PNKP-specific antibodies showed that AcK142-PNKP associates only with BER/SSBR, and AcK226 PNKP with DSBR proteins. Despite the modest effect of acetylation on PNKP's enzymatic activity in vitro, cells expressing non-acetylable PNKP (K142R or K226R) accumulated DNA damage in transcribed genes. Intriguingly, in striatal neuronal cells of a Huntington's Disease (HD)-based mouse model, K142, but not K226, was acetylated. This is consistent with the reported degradation of CBP, but not p300, in HD cells. Moreover, transcribed genomes of HD cells progressively accumulated DSBs. Chromatin-immunoprecipitation analysis demonstrated the association of Ac-PNKP with the transcribed genes, consistent with PNKP's role in transcription-coupled repair. Thus, our findings demonstrate that acetylation at two lysine residues, located in different domains of PNKP, regulates its distinct role in BER/SSBR versus DSBR.

Objectives: The objectives of this retrospective study were to analyze telehealth utilization for two specialty care practices: oral medicine (OM) and oral and maxillofacial surgery (OMFS) during the first 2 years of the pandemic, its impact as a new treatment modality and on participating providers, as well as identify the type of patient visit that most readily adopted telehealth. Methods: Retrospective study of patients who sought specialty services, OM and OMFS, at an outpatient clinic in a university health system setting between March 1, 2019, and February 28, 2022. Source data were obtained from Epic, an electronic medical record application. Data were graphed using Tableau and Microsoft Excel software. Statistical analysis was performed utilizing chi-squared test and analysis of variance (ANOVA). Results: OMFS utilized telehealth 12% of the time, and OM 8% of the time. The majority (87%) of telehealth visits were for return patients (RPs). Compared with the first year of the pandemic, there was a decrease in the number of telehealth visits in the second year (p = 0.0001). As of August 2022, new patient (NP) telehealth encounters have largely returned to prepandemic levels (0-1.5%), whereas RP telehealth visits remained at an average level of 11.4% (9.4-12.4%). Surveyed providers consider telehealth as an effective complement to in-person care and will continue its use (4.2/5 Likert scale). Conclusions: Telehealth has become a viable pathway of care for OM and OMFS who previously did not utilize the remote platform to deliver healthcare. As a new treatment modality, telehealth is perceived as impactful in increasing access to specialty care by participating providers. NP visits are now almost completely in person, but telehealth continues for RPs. Ongoing demand for telehealth highlights urgency to develop appropriate standards and effective remote diagnostic/monitoring tools to maximize telehealth's capability to leverage finite health care resources and increase access to specialty care.