Structures of type IV pilins from Thermus thermophilus demonstrate similarities with type II secretion system pseudopilins

AbstractType IV pilins are proteins which form polymers that extend from the surface of the bacterial cell; they are involved in mediating a wide variety of functions, including adhesion, motility and natural competence. Here we describe the determination of the crystal structures of three type IVa pilins proteins from the thermophile Thermus thermophilus. They form part of a cluster of pilus-like proteins within the genome; our results show that one, Tt1222, is very closely related to the main structural type IV pilin, PilA4. The other two, Tt1218 and Tt1219, also adopt canonical pilin-like folds but, interestingly, are most closely related to the structures of the type II secretion system pseudopilins, EpsI/GspI and XcpW/GspJ. GspI and GspJ have been shown to form a complex with another pseudopilin, GspK, and this heterotrimeric complex is known to play a key role in initiating assembly of a pseudopilus which is thought to drive the secretion process. The structural similarity of Tt1218 and Tt1219 to GspI and GspJ suggests that they might work in a similar way, to deliver functions associated with type IV pili in T. thermophilus, such as natural competence

Osteoporosis management in Australian general practice: an analysis of current osteoporosis treatment patterns and gaps in practice.

BACKGROUND:Among Australians aged 50 and over, an estimated 1 in 4 men and 2 in 5 women will experience a minimal trauma fracture during their remaining lifetime. Effective fracture prevention is hindered by substantial undertreatment, even of patients who clearly warrant pharmacological therapy. Poor adherence to osteoporosis treatment is also a leading cause of repeat fractures and hospitalisation. The aim of this study was to identify current osteoporosis treatment patterns and gaps in practice in Australia, using general practice data, and to explore general practitioners' (GPs') attitudes to osteoporosis treatment and their views on patient factors affecting osteoporosis management. METHODS:The study was conducted in two phases. Phase 1 was a longitudinal retrospective cohort study which utilised data from MedicineInsight - a national general practice data program that extracts longitudinal, de-identified patient data from clinical information systems (CISs) of participating general practices. Phase 2 included semi-structured, in-depth telephone interviews with a sample of MedicineInsight practice GPs. Data were analysed using an inductive thematic analysis method informed by the theory of planned behaviour. RESULTS:A diagnosis of osteoporosis was recorded in 12.4% of patients over the age of 50 years seen in general practice. Of those diagnosed with osteoporosis, almost a quarter were not prescribed osteoporosis medicines. From 2012 to 17, there was a progressive increase in the number of denosumab prescriptions, while prescriptions for bisphosphonates and other osteoporosis medicines decreased. More than 80% of patients who ceased denosumab treatment had no subsequent bisphosphonate prescription recorded. Interviews with GPs revealed beliefs and attitudes that may have influenced their intentions towards prescribing and osteoporosis management. CONCLUSIONS:This study suggests that within the Australian general practice setting, osteoporosis is underdiagnosed and undertreated. In addition, it appears that most patients who ceased denosumab treatment had no record of subsequent antiresorptive therapy, which would place them at risk of further fractures. The study supports the need for the development of clinical education programs addressing GP knowledge gaps and attitudes, and the implementation of specific interventions such as good reminder/recall systems to avoid delays in reviewing and treating patients with osteoporosis

Chronic Thromboembolic Pulmonary Hypertension

The pulmonary hypertension (PH) and right heart dysfunction that results from chronic thromboembolic involvement of the pulmonary vascular bed is potentially curable with surgical endarterectomy. Over the past several decades, growing clinical experience has brought about increased recognition of this treatable form of PH. Moreover, advances in cardiothoracic surgical techniques have given an increasing number of patients with chronic thromboembolic PH (CTEPH) a surgical remedy with decreasing perioperative morbidity and mortality risks. The availability of pulmonary hypertensive—specific medical therapy for CTEPH patients with surgically inaccessible disease also has been a positive therapeutic advance over the past several years. However, despite this progress, chronic thromboembolic disease as a sequela of acute pulmonary emboli continues to be underappreciated. Furthermore, even if CTEPH has been appropriately diagnosed, misinterpretation of diagnostic information may lead to the inappropriate exclusion of patients from surgical consideration. This may result in the prescription of pulmonary hypertensive medical therapy in CTEPH patients with potentially surgically correctable disease. This difficulty arises from a lack of objective criteria as to what constitutes surgical chronic thromboembolic disease, which primarily is a result of the variability in surgical experience in specialty centers in the United States. Consequently, clinicians must be wary about using pulmonary hypertensive medications in CTEPH patients. Before prescription, it is important to exclude patients from surgical consideration by consulting a specialized center with expertise in this discipline

Interprofessional training for final year healthcare students: a mixed methods evaluation of the impact on ward staff and students of a two-week placement and of factors affecting sustainability

BACKGROUND: Multiple care failings in hospitals have led to calls for increased interprofessional training in medical education to improve multi-disciplinary teamwork. Providing practical interprofessional training has many challenges and remains uncommon in medical schools in the UK. Unlike most previous research, this evaluation of an interprofessional training placement takes a multi-faceted approach focusing not only on the impact on students, but also on clinical staff delivering the training and on outcomes for patients. METHODS: We used mixed methods to examine the impact of a two-week interprofessional training placement undertaken on a medical rehabilitation ward by three cohorts of final year medical, nursing and therapy students. We determined the effects on staff, ward functioning and participating students. Impact on staff was evaluated using the Questionnaire for Psychological and Social factors at work (QPSNordic) and focus groups. Ward functioning was inferred from standard measures of care including length of stay, complaints, and adverse events. Impact on students was evaluated using the Readiness for Interprofessional Learning Survey (RIPLS) among all students plus a placement survey among medical students. RESULTS: Between 2007 and 2010, 362 medical students and 26 nursing and therapy students completed placements working alongside the ward staff to deliver patient care. Staff identified benefits including skills recognition and expertise sharing. Ward functioning was stable. Students showed significant improvements in the RIPLS measures of Teamwork, Professional Identity and Patient-Centred Care. Despite small numbers of students from other professions, medical students’ rated the placement highly. Increasing student numbers and budgetary constraints led to the cessation of the placement after three years. CONCLUSIONS: Interprofessional training placements can be delivered in a clinical setting without detriment to care and with benefits for all participants. While financial support is a necessity, it appears that having students from multiple professions is not critical for a valuable training experience; staff from different professions and students from a single profession can work successfully together. Difficulty in aligning the schedules of different student professions is commonly cited as a barrier to interprofessional training. Our experience challenges this and should encourage provision of authentic interprofessional training experience

Incorporating patient partner scores into high stakes assessment : an observational study into opinions and attitudes

Peer reviewedPublisher PD

Professionalization of a nonstate actor

Can nonstate militants professionalize? That is the core question of this piece. Discussions of professionalism have spread to the state military from civilian professions such as education, medicine, and law. This piece examines whether nonstate actors exhibit the same fundamental processes found within these state-based organizations. These fundamentals are the creation of a recognized internal ethos, which acts as a collective standard for those involved. A commitment to expertise and the punishment of those who do not reach these collective expectations reinforce this ethos. To answer this question, this piece examines the development of the Provisional Irish Republican Army (PIRA) during the Troubles. It highlights consistencies and inconsistencies with traditional forces and argues that groups like the PIRA can professionalize and increase their effectiveness in doing so. This widens the field of professionalism studies and provides an additional lens through which to examine nonstate groups