Evidence has supported the association between psychological factors and cancer biology; however, findings are equivocal on the role of psychosocial factors in cancer progression. This study generates a hypothesis of mechanistic variables by examining the clinical effects of psychosocial factors and cortisol dysregulation in patients with metastatic renal cell carcinoma (RCC) and examines associated activation of transcription control pathways. Patients with metastatic RCC (n = 217) were prospectively enrolled in this study. Patients completed questionnaires (Centers for Epidemiologic Studies – Depression; SF-36 Health Status Survey; Duke Social Support Index; Coping Operations Preference Enquiry; organized and non-organized religious activity; and intrinsic religiosity), and provided blood and saliva samples. Cortisol levels and whole genome transcriptional profiling were assessed to identify potential alterations in circadian rhythms and genomic pathways. Separate Cox regression models, controlling for disease risk category, revealed that CES-D scores (p = 0.05, HR = 1.5, 95% CI for HR: 1.00–2.23) and cortisol slope (p = 0.002; HR = 1.9; 95%CI for HR: 1.27–2.97) were significantly associated with decreased survival. Only cortisol slope and risk category remained significant in the complete model. Functional genomic analyses linked depressive symptoms to increased expression of pro-inflammatory and pro-metastatic genes in circulating leukocytes. 116 transcripts were found to be upregulated by an average of 50% or more in high CES-D patients, and 57 transcripts downregulated by at least 50%. These changes were also found in the tumor in a subset of patients. These findings identify depressive symptoms as a key predictor of survival in renal cell carcinoma patients with potential links to dysregulation of cortisol and inflammatory biology.
19 February 2019 in Conservation Science and Practice
Uganda is one of the most species rich countries in Africa because of the presence of several major biomes. However, it is also a country that has lost much of its natural habitat to agriculture. Uganda is a country that has been better surveyed for its biodiversity than many African countries, but despite this, there has not been a comprehensive analysis of the critical sites that contribute to biodiversity conservation at a global, as well as at a national level. We here present such an assessment using mammals, birds, reptiles, amphibians, and plants as surrogate taxa. We identified 36 terrestrial sites that are of sufficient global importance to qualify as Key Biodiversity Areas (KBAs), using the Global Standard for the Identification of KBAs, which complement an additional nine freshwater sites. National red listing of species and ecosystems was used to identify sites of national importance for conservation. We employ a conservation planning approach using Marxan to identify the minimum set of sites needed to conserve all the globally and nationally threatened species and nationally threatened habitats in Uganda. The findings show that most of the remaining natural habitat in Uganda is important for the conservation of globally and nationally threatened species and threatened habitat. Large areas of irreplaceable habitat occur outside protected areas, although more extensive surveys of these areas would likely reduce the area that is irreplaceable.