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Background Pesticide use for fruits and vegetable production in Uganda may result in presence of residues on produce which may pose health risks to consumers. Uganda does not have an established system for monitoring pesticide residues in fruits and vegetables and assessing potential health risks. This research aimed to conduct a health risk assessment of presence of pesticide residues in fruits and vegetables in the Kampala Metropolitan Area in Uganda. Method Pesticides were measured in 160 fruits and vegetables samples collected at farms, markets, street vendors, restaurants and homes; and analysed using liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry. Fruit and vegetable consumption information was collected from 2177 people. Pesticide concentrations were compared with European Union maximum residual limits (MRLs). Mean values of pesticide concentration residues found in the sample of fruits and vegetables; and fruits and vegetables intake and body weight were used to calculate the estimated daily intake (EDI) of pesticide residues. EDI values were compared with acceptable daily intakes (ADI) to calculate the hazard quotient by age group, and stage at which consumption happens along the chain. Results Overall, 57 pesticides were detected in fruits and vegetables from farm to fork. Of the 57, 39 pesticides were detected in all the fruits and vegetables studied. Concentrations of fonofos, fenitrothion and fenhexamid were above the European Union MRLs in some samples. Hazard quotients based on dietary ingestion scenarios for 18 pesticides, including dichlorvos (444) alanycarb (314), fonofos (68), fenitrothion (62), dioxacarb (55) and benfuracarb (24) and others, were above 1, indicating the possibility of chronic health risk to consumers. Chronic health risk decreased with age but was stable for stage at which consumption happens along the food chain. The number of pesticides with EDI greater than the ADI decreased with increase in age; with 18, 13, 9, 11, 8, 9, and 9 pesticides for age groups Conclusion Chronic dietary pesticide exposures to Ugandans are likely common, and for some pesticides result in exposure exceeding health-based benchmarks. Risks were highest for younger participants. There is an urgent need to increase monitoring and regulation of pesticides in fruits and vegetables in order to protect consumers, especially the children who are vulnerable to the adverse effects of pesticides.

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YAP1 is a principal component of the Hippo pathway and is considered as one of the critical regulators of tumorigenesis. Recent studies indicate that YAP1 can suppress the antitumor immunity and influence the differentiation of regulatory T cells (Tregs) by inducing TGFβ/SMAD pathway, but the mechanisms of YAP1 regulated modulation of tumor immune microenvironment is still in its infancy. Most importantly no study has been reported in YAP1 associated immune suppression in UCB. Here, we used syngeneic mouse models with three different mouse bladder cancer cells (MB49, UPPL595 and BBN 975) and demonstrated that YAP1 amplification upregulates the expression of IL-6 in tumor cells in vitro and in vivo, which in turn directly induces immunosuppressive tumor microenvironment (TME). YAP1 expression in cancer cells significantly induces the infiltration of MDSCs and attenuates the CD8 T cells in tumor tissue. YAP1 upregulation also induces different CXCR2 associated ligands and influences the polarization of naive macrophages into M2 type or tumor associated macrophages. Additionally, YAP1 expression enhances cancer stemness properties in the cancer cells and induces the intracellular accumulation of lipid droplets, which may also be a major factor in the development of immunosuppressive TME. Our pilot in vivo studies also suggest that YAP1 downregulation in the tumor cells can stimulate antitumor adaptive immunity in the host and improve tumor immunogenicity, leading to tumor regression. Overall, our results demonstrated the key role of YAP1 in modulating the TME and establish a potential rationale for targeting YAP1 in combination with checkpoint inhibitors for treating UCB. Citation Format: Pritam Sadhukhan, Mingxiao Feng, Emily Illingworth, Ido Sloma, M. Talha Ugurlu, Fenna Sille, Woonyoung Choi, David J. McConkey, Mohammad Hoque. YAP1 drives immune suppression in urothelial carcinoma of bladder [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P174.