The ability to acquire iron from the extracellular environment is a key determinant of pathogenicity in mycobacteria. Mycobacterium tuberculosis acquires iron exclusively via the siderophore mycobactin T, the biosynthesis of which depends on the production of salicylate from chorismate. Salicylate production in other bacteria is either a two-step process involving an isochorismate synthase (chorismate isomerase) and a pyruvate lyase, as observed for Pseudomonas aeruginosa, or a single-step conversion catalyzed by a salicylate synthase, as with Yersinia enterocolitica. Here we present the structure of the enzyme MbtI (Rv2386c) from M. tuberculosis, solved by multiwavelength anomalous diffraction at a resolution of 1.8 Å, and biochemical evidence that it is the salicylate synthase necessary for mycobactin biosynthesis. The enzyme is critically dependent on Mg 2؉ for activity and produces salicylate via an isochorismate intermediate. MbtI is structurally similar to salicylate synthase (Irp9) from Y. enterocolitica and the large subunit of anthranilate synthase (TrpE) and shares the overall architecture of other chorismate-utilizing enzymes, such as the related aminodeoxychorismate synthase PabB. Like Irp9, but unlike TrpE or PabB, MbtI is neither regulated by nor structurally stabilized by bound tryptophan. The structure of MbtI is the starting point for the design of inhibitors of siderophore biosynthesis, which may make useful lead compounds for the production of new antituberculosis drugs, given the strong dependence of pathogenesis on iron acquisition in M. tuberculosis.
Recent policy initiatives within the United Kingdom have recognized that effective care for older people can only be achieved if health care staff are willing and skilled enough to address patient needs in a holistic way. The preliminary stages of the action research project described here focused on the perceptions of nursing staff regarding the factors that impacted on their ability to address mental health needs within a general hospital ward. A phenomenological approach allowed us to identify the experience of addressing mental health needs in this setting from the perspective of the research participants. A focus group was facilitated with nursing staff whose primary professional focus was the provision of physical health care within an older adult unit. Thematic content analysis was used to analyse the focus group data, and four key themes emerged, namely 'disruption', 'role conflict', 'professional resources' and 'professional distress'. These themes provide a focus for the ongoing development of the action research methods and will embed future work in the experience of those charged with ensuring that mental health care is a key element of their practice. This study highlights the urgent need for further work in this area, as we contend that it is only by addressing the professional needs of the staff concerned, that effective patient-centred care can be ensured.
Ultrasonically activated irrigation for 1 min with 1% NaOCl after canal preparation in straight root canals is potentially an effective supplementary step in microbial control.
This study explored the views of mental health service users regarding the concept of nurse prescribing, an area that to date has not been examined in any significant way. A qualitative approach was used to gather data from a series of focus groups made up of service users within the Avon and Wiltshire Mental Health Partnership NHS Trust area. Content analysis was used to analyse data from each focus group and four major themes were identified from the relevant component categories. This study identifies that service users have a number of concerns regarding the adoption of nurse prescribing within the mental health context, in particular the need for nurses taking on a prescribing role to be adequately educated and supported in this function. Participants were concerned that in developing a prescribing role, nurses did not neglect other core nursing activities and that the issues of role profile, skill mix and collaborative working were not undermined. The study provides useful information regarding the development of this role within mental health nursing, and offers constructs that could be explored further among service user and patient groups using quantitative methodologies.
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