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BackgroundDocosahexaenoic acid (DHA) is a long chain n-3 polyunsaturated fatty acid that has anticancer activity. Heme oxygenase 1 (HO-1) is a potential therapeutic target due to its cytoprotective activity in cancer cells. We recently reported that DHA induces HO-1 gene transcription in human cancer cells by augmenting the degradation of Bach1 protein, which functions as a negative regulator of HO-1. Since the degradation of Bach1 protein relies on protein phosphorylation, we hypothesized that DHA-induced HO-1 gene transcription could be attenuated by kinase inhibitors, resulting in an enhanced cytotoxicity. Sorafenib, a tyrosine kinase inhibitor, was first applied to test our hypothesis.MethodsHuman cancer cell lines and a xenograft nude mouse model were applied to test our hypothesis. Gene expression was analyzed by western blot analysis and reporter gene assay. Cell viability was analyzed using a colorimetric assay. Isobologram was applied to analyze drug action.ResultsPretreatment of cancer cells with Sorafenib significantly attenuated DHA-induced degradation of Bach1 protein. Consequently, DHA-induced HO-1 gene transcription was reversed by Sorafenib as evidenced by western blot and reporter gene analysis. Sorafenib acted synergistically with DHA to suppress cancer cell viability in various human cancer cell lines and suppressed tumor xenograft growth in mice fed a fish oil enriched diet (high n-3/DHA), as compared to mice fed a corn oil (high n-6) diet. Screening of the NCI-Oncology Drug Set IV identified a group of anticancer compounds, including Sorafenib, which enhanced DHA’s cytotoxicity, as well as a set of compounds that attenuated DHA’s cytotoxicity.ConclusionsWe demonstrate that sorafenib attenuates DHA-induced HO-1 expression and acts in synergy with DHA to suppress cancer cell viability and tumor growth. Considering the known health benefits of DHA and the clinical effectiveness of Sorafenib, their combination is an attractive therapeutic strategy against cancer.

Background In 2010, the Patient Protection and Affordable Care Act instituted dedicated reimbursement for Annual Wellness Visits (AWVs) in primary care, requiring the use of comprehensive health risk assessment (HRA) that covers specific health content. HRAs have been implemented and studied for decades in various settings, but little is known about the effect of introducing HRAs on the dynamics and content of patient-clinician conversations during AWVs and if the effective use of HRAs requires additional training and resources. Methods We used established technology to video-record 40 AWVs conducted by 5 faculty in an academic family medicine residency practice. A comprehensive HRA-Health Planner report was implemented in these practices over a 3-month baseline period without additional training or resources. Subsequently, three of the five clinicians received a brief, low-intensity intervention to use the HRA to support patient behavior change. Patients received a 5-minute orientation on the purpose of the enhanced AWV and advice on how to communicate their needs and preferences more effectively. Twenty-two pre- and post-intervention visit recordings were carefully matched on known covariates and were explored by several evaluators using Conversation Analysis techniques to describe the dynamics and content of conversations. Short exit interviews with patients and clinicians were evaluated by standard content analytic techniques. Results Six overarching themes emerged that described the dynamics of AWV conversations. Patients and clinicians sub-optimally utilized the HRA report and missed many opportunities for promoting behavior change. However, a low-intensity, multi-component intervention significantly decreased the proportion of clinician talk time per visit by 9% (p<0.001), while it increased the proportion of patient talk time by 7% (p<0.001), robustly increased the number and duration of “change talk” by 639% (p= 0.0007), increased the number of patient cut-ins by 237% (p= 0.04) and tended to increase the number and duration of clinician “advice talk” (p=0.065). The total number, duration, and proportions of conversational turn types, “goal setting talk”, “education talk”, and “prescriptive talk” did not change. The majority of patients and clinicians had a positive experience. Patients felt more informed, empowered, and motivated by the HRA-enhanced wellness visit. Clinicians emphasized that the HRA report helped them construct and follow a visit agenda more effectively and that it facilitated the convergence of the patients’ goals with evidence-based recommendations suggested by the HRA report. Conclusions Our study suggests that HRAs introduced without proper framing, education, and additional resources may not allow patients and clinicians to optimally leverage AWVs for health planning and improvement. A low-intensity, multi-component intervention may help patients and clinicians improve the quality of HRA-supported health conversations and realize the potential of AWVs.

Assessing QoL in congenital NGB patients is a complex task. In our cohort, patients who underwent BA and ACE were shown to have decreased SCIM scores. SCIM scores for BA patients were significantly higher in patients who did not receive a BA independent of ACE status. SF-8 and ICIQ scores did not show any statistically significant difference in quality of life survey scores in those who underwent procedures versus those who did not.