A Three Delays theoretical framework to describe social determinants as barriers to dental care.

OBJECTIVES: The Three Delays model is a well-established global public health framework for the utilization of obstetric services where each delay represents a series of factors affecting utilization: (1) Delay #1-Deciding to seek care, (2) Delay #2-Reaching an appropriate facility and (3) Delay #3-Receiving adequate care. The aim of this qualitative study was to explore the application of the Three Delays model to dental service utilization and describe factors attributed to delayed utilization within this framework. METHODS: This study utilized a framework analysis, underpinned by the Three Delays model, to examine delays in dental care utilization. A criterion purposive sample of English-speaking adults (18+ years) in Massachusetts and Florida, USA with limited dental care access was recruited. Data were collected via semi-structured interviews conducted in two phases: 17 individual interviews, followed by interviews with a subset of five participants over 3 months (a total of 18 interviews). The analysis involved inductive thematic coding and systematic organization within the framework. RESULTS: Major themes and subthemes were constructed from the participants' narratives, identified and categorized as factors in the Three Delays framework. Each of the delays was interrelated to the other two, and Delay #1 was the most common delay based on the participants' interviews. The themes and subthemes contributing to one or more delays included interpersonal communication, prior dental experience, financial considerations, childcare costs, social connection, technology literacy, time constraints, competing priorities, stressors such as eviction and immigration status and microaggressions including racism and stigma. CONCLUSION: The Three Delays model was applicable to the study of dental care utilization and factors that impact the decision to seek dental care, reaching an appropriate dental facility and receiving adequate dental care in this study context.

Androgen blockade primes NLRP3 in macrophages to induce tumor phagocytosis.

Immune-based therapies induce durable remissions in subsets of patients across multiple malignancies. However, there is limited efficacy of immunotherapy in metastatic castrate-resistant prostate cancer (mCRPC), manifested by an enrichment of immunosuppressive (M2) tumor- associated macrophages (TAM) in the tumor immune microenvironment (TME). Therefore, therapeutic strategies to overcome TAM-mediated immunosuppression are critically needed in mCRPC. Here we discovered that NLR family pyrin domain containing 3 (NLRP3), an innate immune sensing protein, is highly expressed in TAM from metastatic PC patients treated with standard-of-care androgen deprivation therapy (ADT). Importantly, ex vivo studies revealed that androgen receptor (AR) blockade in TAM upregulates NLRP3 expression, but not inflammasome activity, and concurrent AR blockade/NLRP3 agonist (NLRP3a) treatment promotes cancer cell phagocytosis by immunosuppressive M2 TAM. In contrast, NLRP3a monotherapy was sufficient to enhance phagocytosis of cancer cells in anti-tumor (M1) TAM, which exhibit high de novo NLRP3 expression. Critically, combinatorial treatment with ADT/NLRP3a in a murine model of advanced PC resulted in significant tumor control, with tumor clearance in 55% of mice via TAM phagocytosis. Collectively, our results demonstrate NLRP3 as an AR-regulated "macrophage phagocytic checkpoint", inducibly expressed in TAM by ADT and activated by NLRP3a treatment, the combination resulting in TAM-mediated phagocytosis and tumor control.