Renal AAV2-Mediated Overexpression of Long Non-Coding RNA H19 Attenuates Ischemic Acute Kidney Injury Through Sponging of microRNA-30a-5p

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Anwendung von „High-flow“-Sauerstoff-Therapie im Rettungsdienst: Welche Gefahren ergeben sich für Anwender aus der Perspektive des Arbeits- und Brandschutzes?

Die Anaesthesiologie - Die Anwendung von hohen Sauerstoffkonzentration birgt Gefahren für Patienten und Anwender. Hohe Umgebungskonzentrationen an Sauerstoff bergen die Gefahr von...     

Application of the adverse outcome pathway framework to genotoxic modes of action

In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity pathways using five example case studies. Each of these genetic toxicology AOPs proposed for further development includes the relevant molecular initiating events, key events, and adverse outcomes (AOs), identification and/or further development of the appropriate assays to link an agent to these events, and discussion regarding the biological plausibility of the proposed AOP. A key difference between these proposed genetic toxicology AOPs versus traditional AOPs is that the AO is a genetic toxicology endpoint of potential significance in risk characterization, in contrast to an adverse state of an organism or a population. The first two detailed case studies describe provisional AOPs for aurora kinase inhibition and tubulin binding, leading to the common AO of aneuploidy. The remaining three case studies highlight provisional AOPs that lead to chromosome breakage or mutation via indirect DNA interaction (inhibition of topoisomerase II, production of cellular reactive oxygen species, and inhibition of DNA synthesis). These case studies serve as starting points for genotoxicity AOPs that could ultimately be published and utilized by the broader toxicology community and illustrate the practical considerations and evidence required to formalize such AOPs so that they may be applied to genetic toxicity evaluation schemes. Environ. Mol. Mutagen. 61:114–134, 2020. © 2019 Wiley Periodicals, Inc.     

The role of multidisciplinary decision making in oropharyngeal cancer: do we follow guidelines and are treatment decisions being implemented?

European Archives of Oto-Rhino-Laryngology - A multidisciplinary team (MDT) approach to cancer management is gold-standard. With an increasing disease incidence and growing research into human...     

Pancreatic cancer and thromboembolic disease, 150 years after Trousseau

The connection between pancreatic cancer and venous thrombosis has been discussed for almost 150 years. The exact pathophysiological mechanisms are still partly understood, but it is known that pancreatic cancer induces a prothrombotic and hypercoagulable state and genetic events involved in neoplastic transformation (e.g., KRAS, c-MET, p53), procoagulant factors [e.g., tissue factor (TF), platelet factor 4 (PF4), plasminogen activator inhibitor type 1 (PAI-1)], mucin production (e.g., through activation of P- and L-selectin) and pro-inflammatory factors [e.g., cytokines, cyclooxygenase-2 (COX-2)] may be implicated. Also pancreatitis, both acute and chronic, is associated with increased risk of venous thrombosis, but in this circumstance a direct inflammatory process may be more important. This article discusses the incidence, treatment and outcome of venous thromboembolism (VTE) complicating pancreatic disease, with special emphasis on new knowledge obtained during the last fifteen years.     

Patterns and Predictors of Reincarceration among Prisoners with Serious Mental Illness: A Cohort Study: Modèles et prédicteurs de réincarcération chez les prisonniers souffrant de maladie mentale grave : Une étude de cohorte

Background:A small proportion of people who have serious mental illness and rapid and frequent incarcerations account for a disproportionate amount of overall service use and cost. It is important to describe such individuals, so that services can respond more effectively.Methods:We investigated a cohort of 4,704 incarcerated men and women who were discharged from a correctional mental health service and followed for a median of 535 days. We investigated social, clinical, demographic, and offense characteristics as predictors of return to the service using Cox survival analyses. Secondly, we characterized individuals as high-frequency service users as those who had 3 or more incarcerations during a 1-year period and investigated their characteristics.Results:We found that a higher rate of return to custody was associated with schizophrenia spectrum/bipolar affective disorder (BPAD), personality disorder traits, crack cocaine and methamphetamine use, and unstable housing. Charges of theft/robbery and breach of probation were also positively associated, and sex assault was negatively associated with return to custody. Within a 1-year time period, we found 7.2% of individuals were high-frequency service users, which accounted for 19.5% of all reincarcerations.Conclusion:Identification of the characteristics of those with mental illness in custody, especially those who have high-frequency returns to custody, may provide opportunity to target resources more effectively. The primary targets of intervention would be to treat those with schizophrenia/BPAD and substance use problems, particularly those using stimulants, and addressing homelessness. This could reduce the problem of repeated criminalization of the mentally ill and reduce the overall incarceration rate.     

Mutational Signature Analysis Reveals NTHL1 Deficiency to Cause a Multi-tumor Phenotype

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