Xpf and Not the Fanconi Anaemia Proteins or Rev3 Accounts for the Extreme Resistance to Cisplatin in Dictyostelium discoideum

Organisms like Dictyostelium discoideum, often referred to as DNA damage “extremophiles”, can survive exposure to extremely high doses of radiation and DNA crosslinking agents. These agents form highly toxic DNA crosslinks that cause extensive DNA damage. However, little is known about how Dictyostelium and the other “extremophiles” can tolerate and repair such large numbers of DNA crosslinks. Here we describe a comprehensive genetic analysis of crosslink repair in Dictyostelium discoideum. We analyse three gene groups that are crucial for a replication-coupled repair process that removes DNA crosslinks in higher eukarya: The Fanconi anaemia pathway (FA), translesion synthesis (TLS), and nucleotide excision repair. Gene disruption studies unexpectedly reveal that the FA genes and the TLS enzyme Rev3 play minor roles in tolerance to crosslinks in Dictyostelium. However, disruption of the Xpf nuclease subcomponent results in striking hypersensitivity to crosslinks. Genetic interaction studies reveal that although Xpf functions with FA and TLS gene products, most Xpf mediated repair is independent of these two gene groups. These results suggest that Dictyostelium utilises a distinct Xpf nuclease-mediated repair process to remove crosslinked DNA. Other DNA damage–resistant organisms and chemoresistant cancer cells might adopt a similar strategy to develop resistance to DNA crosslinking agents

Smoke rings:towards a comprehensive tobacco free policy for the Olympic Games

Background The tobacco industry has long sought affiliation with major sporting events, including the Olympic Games, for marketing, advertising and promotion purposes. Since 1988, each Olympic Games has adopted a tobacco-free policy. Limited study of the effectiveness of the smoke-free policy has been undertaken to date, with none examining the tobacco industry's involvement with the Olympics or use of the Olympic brand. Methods and Findings A comparison of the contents of Olympic tobacco-free policies from 1988 to 2014 was carried out by searching the websites of the IOC and host NOCs. The specific tobacco control measures adopted for each Games were compiled and compared with measures recommended by the WHO Tobacco Free Sports Initiative and Article 13 of the Framework Convention on Tobacco Control (FCTC). This was supported by semi-structured interviews of key informants involved with the adoption of tobacco-free policies for selected games. To understand the industry's interests in the Olympics, the Legacy Tobacco Documents Library (http://legacy.library.ucsf.edu) was systematically searched between June 2013 and August 2014. Company websites, secondary sources and media reports were also searched to triangulate the above data sources. This paper finds that, while most direct associations between tobacco and the Olympics have been prohibited since 1988, a variety of indirect associations undermine the Olympic tobacco-free policy. This is due to variation in the scope of tobacco-free policies, limited jurisdiction and continued efforts by the industry to be associated with Olympic ideals. Conclusions The paper concludes that, compatible with the IOC's commitment to promoting healthy lifestyles, a comprehensive tobacco-free policy with standardized and binding measures should be adopted by the International Olympic Committee and all national Olympic committees

An online network tool for quality information to answer questions about occupational safety and health: usability and applicability

<p>Abstract</p> <p>Background</p> <p>Common information facilities do not always provide the quality information needed to answer questions on health or health-related issues, such as Occupational Safety and Health (OSH) matters. Barriers may be the accessibility, quantity and readability of information. Online Question & Answer (Q&A) network tools, which link questioners directly to experts can overcome some of these barriers. When designing and testing online tools, assessing the usability and applicability is essential. Therefore, the purpose of this study is to assess the usability and applicability of a new online Q&A network tool for answers on OSH questions.</p> <p>Methods</p> <p>We applied a cross-sectional usability test design. Eight occupational health experts and twelve potential questioners from the working population (workers) were purposively selected to include a variety of computer- and internet-experiences. During the test, participants were first observed while executing eight tasks that entailed important features of the tool. In addition, they were interviewed. Through task observations and interviews we assessed applicability, usability (effectiveness, efficiency and satisfaction) and facilitators and barriers in use.</p> <p>Results</p> <p>Most features were usable, though several could be improved. Most tasks were executed effectively. Some tasks, for example searching stored questions in categories, were not executed efficiently and participants were less satisfied with the corresponding features. Participants' recommendations led to improvements. The tool was found mostly applicable for additional information, to observe new OSH trends and to improve contact between OSH experts and workers. Hosting and support by a trustworthy professional organization, effective implementation campaigns, timely answering and anonymity were seen as important use requirements.</p> <p>Conclusions</p> <p>This network tool is a promising new strategy for offering company workers high quality information to answer OSH questions. Q&A network tools can be an addition to existing information facilities in the field of OSH, but also to other healthcare fields struggling with how to answer questions from people in practice with high quality information. In the near future, we will focus on the use of the tool and its effects on information and knowledge dissemination.</p

Current quality of life and its determinants among opiate-dependent individuals five years after starting methadone treatment

This study explores the current QoL of opiate-dependent individuals who started outpatient methadone treatment at least 5 years ago and assesses the influence of demographic, psychosocial, drug and health-related variables on individuals' QoL. Participants (n = 159) were interviewed about their current QoL, psychological distress and severity of drug-related problems, using the Lancashire Quality of Life Profile, the Brief Symptom Inventory and the Addiction Severity Index. Potential determinants of QoL were assessed in a multiple linear regression analysis. Five years after the start of methadone treatment, opiate-dependent individuals report low QoL scores on various domains. No association was found between drug-related variables and QoL, but a significant negative impact of psychological distress was identified. Severity of psychological distress, taking medication for psychological problems and the inability to change one's living situation were associated with lower QoL. Having at least one good friend and a structured daily activity had a significant, positive impact on QoL. Opiate-dependent individuals' QoL is mainly determined by their psychological well-being and a number of psychosocial variables. These findings highlight the importance of a holistic approach to treatment and support in methadone maintenance treatment, which goes beyond fixing the negative physical consequences of opiate dependence