Geometagenomics illuminates the impact of agriculture on the distribution and prevalence of plant viruses at the ecosystem scale

Disease emergence events regularly result from human activities such as agriculture, which frequently brings large populations of genetically uniform hosts into contact with potential pathogens. Although viruses cause nearly 50% of emerging plant diseases, there is little systematic information about virus distribution across agro-ecological interfaces and large gaps in understanding of virus diversity in nature. Here we applied a novel landscape-scale geometagenomics approach to examine relationships between agricultural land use and distributions of plantassociated viruses in two Mediterranean-climate biodiversity hotspots (Western Cape region of South Africa and Rhône river delta region of France). In total, we analysed 1725 geo-referenced plant samples collected over two years from 4.5 × 4.5 km2 grids spanning farmlands and adjacent uncultivated vegetation. We found substantial virus prevalence (25.8–35.7%) in all ecosystems, but prevalence and identified family-level virus diversity were greatest in cultivated areas, with some virus families displaying strong agricultural associations. Our survey revealed 94 previously unknown virus species, primarily from uncultivated plants. This is the first effort to systematically evaluate plant-associated viromes across broad agro-ecological interfaces. Our findings indicate that agriculture substantially influences plant virus distributions and highlight the extent of current ignorance about the diversity and roles of viruses in nature

Outcomes of Intracorporeal Urinary Diversion after Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium

INTRODUCTION AND OBJECTIVE: This study aims to provide an update and compare perioperative outcomes and complications of Intracorporeal urinary diversion (ICUD) and extracorporeal urinary diversion (ECUD) following RARC from a multi-institutional, prospectively maintained database, the International Robotic Cystectomy Consortium (IRCC). METHODS: A retrospective review of 2125 patients from 26 institutions was performed. ICUD was compared with ECUD Multivariate (stepwise variable selection) logistic regression models were fit to evaluate preoperative, operative, and postoperative predictors of receiving ICUD, operative time, high grade complications and 90-days readmissions after RARC. RESULTS: 51% (n=1094) patients underwent ICUD in our cohort. ICUD patients demonstrated shorter operative times (357 vs 400 minutes, p<0.001), less blood loss (300 vs 350 ml, p<0.001), and fewer blood transfusions (4% vs 19%, p<0.001). ICUD patients experienced more high grade complications (13 vs 10%, p=0.02). Utilization of ICUD increased from 9% of all urinary diversions in 2005 to 97% in 2015. Complications after ICUD decreased significantly over time (p<0.001). On multivariable analysis, higher annual cystectomy volume (OR 1.02, 95% CI (1.01-1.03), p<0.002) and year of RARC 2013-2016 (OR 68, 95% CI 44-105, p<0.001) and ASA score <3 (OR 1.75, 95% CI 1.38-2.22, p<0.001) were associated with receiving ICUD. ICUD was associated with shorter operative time (27 minutes, p=0.001). CONCLUSION: Utilization of ICUD has increased over the past decade. Higher annual institutional volume of RARCs was associated with performing ICUD. ICUD was associated with shorter operative times. Although ICUD was associated with higher grade complications compared to ECUD, they decreased over time

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Structure-activity relationship studies on the macrolide exotoxin mycolactone of Mycobacterium ulcerans

BACKGROUND: Mycolactones are a family of polyketide-derived macrolide exotoxins produced by Mycobacterium ulcerans, the causative agent of the chronic necrotizing skin disease Buruli ulcer. The toxin is synthesized by polyketide synthases encoded by the virulence plasmid pMUM. The apoptotic, necrotic and immunosuppressive properties of mycolactones play a central role in the pathogenesis of M. ulcerans. METHODOLOGYPRINCIPAL FINDINGS: We have synthesized and tested a series of mycolactone derivatives to conduct structure-activity relationship studies. Flow cytometry, fluorescence microscopy and Alamar Blue-based metabolic assays were used to assess activities of mycolactones on the murine L929 fibroblast cell line. Modifications of the C-linked upper side chain (comprising C12-C20) caused less pronounced changes in cytotoxicity than modifications in the lower C5-O-linked polyunsaturated acyl side chain. A derivative with a truncated lower side chain was unique in having strong inhibitory effects on fibroblast metabolism and cell proliferation at non-cytotoxic concentrations. We also tested whether mycolactones have antimicrobial activity and found no activity against representatives of Gram-positive (Streptococcus pneumoniae) or Gram-negative bacteria (Neisseria meningitis and Escherichia coli), the fungus Saccharomyces cerevisae or the amoeba Dictyostelium discoideum. CONCLUSION: Highly defined synthetic compounds allowed to unambiguously compare biological activities of mycolactones expressed by different M. ulcerans lineages and may help identifying target structures and triggering pathways