The Paleozoic Origin of Enzymatic Lignin Decomposition Reconstructed from 31 Fungal Genomes

Wood is a major pool of organic carbon that is highly resistant to decay, owing largely to the presence of lignin. The only organisms capable of substantial lignin decay are white rot fungi in the Agaricomycetes, which also contains non–lignin-degrading brown rot and ectomycorrhizal species. Comparative analyses of 31 fungal genomes (12 generated for this study) suggest that lignin-degrading peroxidases expanded in the lineage leading to the ancestor of the Agaricomycetes, which is reconstructed as a white rot species, and then contracted in parallel lineages leading to brown rot and mycorrhizal species. Molecular clock analyses suggest that the origin of lignin degradation might have coincided with the sharp decrease in the rate of organic carbon burial around the end of the Carboniferous period

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Opinions of the Dutch public on palliative sedation: a mixed-methods approach

Background Palliative sedation is defined as deliberately lowering a patient&apos;s consciousness, to relieve intolerable suffering from refractory symptoms at the end of life. Palliative sedation is considered a last resort intervention in end-of-life care that should not be confused with euthanasia. Aim To inform healthcare professionals about attitudes of the general public regarding palliative sedation. Design and setting A cross-sectional survey among members of the Dutch general public followed by qualitative interviews. Method One thousand nine hundred and sixty members of the general public completed the questionnaire, which included a vignette describing palliative sedation (response rate 78%); 16 participants were interviewed. Results In total, 22% of the responders indicated knowing the term &apos;palliative sedation&apos;. Qualitative data showed a variety of interpretations of the term. Eighty-one per cent of the responders agreed with the provision of sedatives as described in a vignette of a patient with untreatable pain and a life expectancy of &lt;1 week who received sedatives to alleviate his suffering. This percentage was somewhat lower for a patient with a life expectancy of &lt;1 month (74%, P = 0.007) and comparable in the case w Conclusion Most of the general public accept the use of palliative sedation at the end of life, regardless of a potential life-shortening effect. However, confusion exists about what palliative sedation represents. This should be taken into account by healthcare professionals when communicating with patients and their relatives on end-of-life care options

Opinions of the Dutch public on palliative sedation: a mixed-methods approach

Background Palliative sedation is defined as deliberately lowering a patient's consciousness, to relieve intolerable suffering from refractory symptoms at the end of life. Palliative sedation is considered a last resort intervention in end-of-life care that should not be confused with euthanasia. Aim To inform healthcare professionals about attitudes of the general public regarding palliative sedation. Design and setting A cross-sectional survey among members of the Dutch general public followed by qualitative interviews. Method One thousand nine hundred and sixty members of the general public completed the questionnaire, which included a vignette describing palliative sedation (response rate 78%); 16 participants were interviewed. Results In total, 22% of the responders indicated knowing the term 'palliative sedation'. Qualitative data showed a variety of interpretations of the term. Eighty-one per cent of the responders agreed with the provision of sedatives as described in a vignette of a patient with untreatable pain and a life expectancy of <1 week who received sedatives to alleviate his suffering. This percentage was somewhat lower for a patient with a life expectancy of <1 month (74%, P = 0.007) and comparable in the case w Conclusion Most of the general public accept the use of palliative sedation at the end of life, regardless of a potential life-shortening effect. However, confusion exists about what palliative sedation represents. This should be taken into account by healthcare professionals when communicating with patients and their relatives on end-of-life care options

Opinions of the Dutch public on palliative sedation: A mixed-methods approach

Background: Palliative sedation is defined as deliberately lowering a patient's consciousness, to relieve intolerable suffering from refractory symptoms at the end of life. Palliative sedation is considered a last resort intervention in endof-life care that should not be confused with euthanasia. Aim: To inform healthcare professionals about attitudes of the general public regarding palliative sedation. Design and setting: A cross-sectional survey among members of the Dutch general public followed by qualitative interviews. Method: One thousand nine hundred and sixty members of the general public completed the question

Candida auris in Healthcare Facilities, New York, USA, 2013–2017

Candida auris is an emerging yeast that causes healthcare-associated infections. It can be misidentified by laboratories and often is resistant to antifungal medications. We describe an outbreak of C. auris infections in healthcare facilities in New York City, New York, USA. The investigation included laboratory surveillance, record reviews, site visits, contact tracing with cultures, and environmental sampling. We identified 51 clinical case-patients and 61 screening case-patients. Epidemiologic links indicated a large, interconnected web of affected healthcare facilities throughout New York City. Of the 51 clinical case-patients, 23 (45%) died within 90 days and isolates were resistant to fluconazole for 50 (98%). Of screening cultures performed for 572 persons (1,136 total cultures), results were C. auris positive for 61 (11%) persons. Environmental cultures were positive for samples from 15 of 20 facilities. Colonization was frequently identified during contact investigations; environmental contamination was also common