Strathclyde minor groove binders (S-MGBs) with activity against Acanthamoeba castellanii.

BACKGROUND: Acanthamoeba spp. is the causative agent of Acanthamoeba keratitis and granulomatous amoebic encephalitis. Strathclyde minor groove binders (S-MGBs) are a promising new class of anti-infective agent that have been shown to be effective against many infectious organisms. OBJECTIVES: To synthesize and evaluate the anti-Acanthamoeba activity of a panel of S-MGBs, and therefore determine the potential of this class for further development. METHODS: A panel of 12 S-MGBs was synthesized and anti-Acanthamoeba activity was determined using an alamarBlue™-based trophocidal assay against Acanthamoeba castellanii. Cross-screening against Trypanosoma brucei brucei, Staphylococcus aureus and Escherichia coli was used to investigate selective potency. Cytotoxicity against HEK293 cells allowed for selective toxicity to be measured. DNA binding studies were carried out using native mass spectrometry and DNA thermal shift assays. RESULTS AND DISCUSSION: S-MGB-241 has an IC50 of 6.6 µM against A. castellanii, comparable to the clinically used miltefosine (5.6 µM) and negligible activity against the other organisms. It was also found to have an IC50 > 100 µM against HEK293 cells, demonstrating low cytotoxicity. S-MGB-241 binds to DNA as a dimer, albeit weakly compared to other S-MGBs previously studied. This was confirmed by DNA thermal shift assay with a ΔTm = 1 ±â€Š0.1°C. CONCLUSIONS: Together, these data provide confidence that S-MGBs can be further optimized to generate new, potent treatments for Acanthameoba spp. infections. In particular, S-MGB-241, has been identified as a 'hit' compound that is selectively active against A. castellanii, providing a starting point from which to begin optimization of DNA binding and potency.

Design and Synthesis of Novel Aminoindazole-pyrrolo[2,3-b]pyridine Inhibitors of IKKα That Selectively Perturb Cellular Non-Canonical NF-κB Signalling.

The inhibitory-kappaB kinases (IKKs) IKKα and IKKß play central roles in regulating the non-canonical and canonical NF-κB signalling pathways. Whilst the proteins that transduce the signals of each pathway have been extensively characterised, the clear dissection of the functional roles of IKKα-mediated non-canonical NF-κB signalling versus IKKß-driven canonical signalling remains to be fully elucidated. Progress has relied upon complementary molecular and pharmacological tools; however, the lack of highly potent and selective IKKα inhibitors has limited advances. Herein, we report the development of an aminoindazole-pyrrolo[2,3-b]pyridine scaffold into a novel series of IKKα inhibitors. We demonstrate high potency and selectivity against IKKα over IKKß in vitro and explain the structure-activity relationships using structure-based molecular modelling. We show selective target engagement with IKKα in the non-canonical NF-κB pathway for both U2OS osteosarcoma and PC-3M prostate cancer cells by employing isoform-related pharmacodynamic markers from both pathways. Two compounds (SU1261 [IKKα Ki = 10 nM; IKKß Ki = 680 nM] and SU1349 [IKKα Ki = 16 nM; IKKß Ki = 3352 nM]) represent the first selective and potent pharmacological tools that can be used to interrogate the different signalling functions of IKKα and IKKß in cells. Our understanding of the regulatory role of IKKα in various inflammatory-based conditions will be advanced using these pharmacological agents.

Australian dental school academics' perceptions of gerodontology education in the undergraduate curriculum.

INTRODUCTION: Australia's rapidly growing population of dentate, frail, care-dependent older people require graduates skilled in managing the health needs of this patient group. The perceptions of academics teaching gerodontology may inform future dental curricula recommendations. This study explored the perceptions of gerodontology education amongst Australian dental school academics. MATERIALS AND METHODS: All nine Australian dental schools providing entry-to-practice dentistry programs were invited to participate in semi-structured interviews. Academics from six dentistry programs took part, and the data were analysed using a thematic approach. RESULTS: The three main themes identified from interviews included 'clinical exposure', 'organisational levers', and 'sociological barriers'. The attitudes of students, as well as society and health professionals, were seen as strongly influential in preparing the workforce for managing the oral health of older people. The themes inter-linked with a knock-on effect where societal attitudes and organisational levers impact on the ability to successfully support students' preparation for gerodontology practice. Limited resources were barriers to achieving ideal learning and teaching and continued upon graduation as oral health care for older people was perceived as undervalued and under-resourced. CONCLUSION: There has been a continued cycle of failure in healthcare schemes and advocacy for the improvement of oral health for older people which has contributed to the inadequate preparation of dental graduates for managing frail and care-dependent older people. Organisational, societal, and political change is needed to support the education of dental students in this area to ensure graduate dentists are competent to manage the oral care needs of this growing population.

Effects of candidates' demographics and evaluation of the virtual Multiple Mini Interview (vMMI) as a tool for selection into paediatric training in Queensland.

INTRODUCTION: The Queensland Basic Paediatric Training Network (QBPTN) is responsible for the selection of candidates into paediatric training in Queensland. The COVID-19 pandemic necessitated interviews to be conducted 'virtually' as virtual Multiple-Mini-Interviews (vMMI). The study aimed to describe the demographic characteristics of candidates applying for selection into paediatric training in Queensland, and to explore their perspectives and experiences with the vMMI selection tool. METHODOLOGY: The demographic characteristics of candidates and their vMMI outcomes were collected and analysed with a mixed methods approach. The qualitative component was comprised of seven semi-structured interviews with consenting candidates. RESULTS: Seventy-one shortlisted candidates took part in vMMI and 41 were offered training positions. The demographic characteristics of candidates at various stages of selection were similar. The mean vMMI scores were not statistically different between candidates from the Modified Monash Model 1 (MMM1) location and others [mean (SD): 43.5 (5.1) versus 41.7 (6.7), respectively, p = 0.26]. However, there was a statistically significant difference (p value 0.03) between being offered and not offered a training position for candidates from MMM2 and above. The analysis of the semi-structured interviews suggested that candidate experiences of the vMMI were influenced by the quality of the management of the technology used. Flexibility, convenience, and reduced stress were the main factors that influenced candidates' acceptance of vMMI. Perceptions of the vMMI process focused on the need to build rapport and facilitate communication with the interviewers. DISCUSSION: vMMI is a viable alternative to face-to-face (FTF) MMI. The vMMI experience can be improved by facilitating enhanced interviewer training, by making provision for adequate candidate preparation and by having contingency plans in place for unexpected technical challenges. Given government priorities in Australia, the impact of candidates' geographical location on the vMMI outcome for candidates from MMM >1 location needs to be further explored.

Using a novel ambulatory monitoring system to support patient safety on an acute infectious disease ward during an unfolding pandemic.

AIM: To gain staff feedback on the implementation and impact of a novel ambulatory monitoring system to support coronavirus patient management on an isolation ward. DESIGN: Qualitative service evaluation. METHODS: Semi-structured interviews were conducted with 15 multidisciplinary isolation ward staff in the United Kingdom between July 2020 and May 2021. Interviews were audio-recorded, transcribed and analysed using thematic analysis. FINDINGS: Adopting Innovation to Assist Patient Safety was identified as the overriding theme. Three interlinked sub-themes represent facets of how the system supported patient safety. Patient Selection was developed throughout the pandemic, as clinical staff became more confident in choosing which patients would benefit most. Trust In the System described how nurses coped with discrepancies between the ambulatory system and ward observation machines. Finally, Resource Management examined how, once trust was built, staff perceived the ambulatory system assisted with caseload management. This supported efficient personal protective equipment resource use by reducing the number of isolation room entries. Despite these reported benefits, face-to-face contact was still highly valued, despite the risk of coronavirus exposure. CONCLUSION: Hospital wards should consider using ambulatory monitoring systems to support caseload management and patient safety. Patients in isolation rooms or at high risk of deterioration may particularly benefit from this additional monitoring. However, these systems should be seen as an adjunct to nursing care, not a replacement. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Nurses valued ambulatory monitoring as a means of ensuring the safety of patients at risk of deterioration and prioritizing their workload. IMPACT: The findings of this research will be useful to all those developing or considering implementation of ambulatory monitoring systems in hospital wards. REPORTING METHOD: This manuscript follows the Consolidated criteria for Reporting Qualitative Research (COREQ) guidelines with inclusion of relevant SQUIRE guidelines for reporting quality improvement. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

A comparative evaluation of quality and depth of learning by trainee doctors in regional, rural, and remote locations.

BACKGROUND: An equitable supply and distribution of medical practitioners for all the population is an important issue, especially in Australia where 28% of the population live in rural and remote areas. Research identified that training in rural/remote locations is a predictor for the uptake of rural practice, but training must provide comparable learning and clinical experiences, irrespective of location. Evidence shows GPs in rural and remote areas are more likely to be engaged in complex care. However, the quality of GP registrar education has not been systematically evaluated. This timely study evaluates GP registrar learning and clinical training experiences in regional, rural, and remote locations in Australia using assessment items and independent evaluation. METHODS: The research team retrospectively analysed GP trainee formative clinical assessment reports compiled by experienced medical educators during real-time patient consultations. Written reports were assessed using Bloom's taxonomy classified into low and high cognitive level thinking. Regional, rural, and remotely located trainees were compared using Pearson chi-squared test and Fisher's exact test (for 2 × 2 comparisons) to calculate associations between categorical proportions of learning setting and 'complexity'. RESULTS: 1650 reports (57% regional, 15% rural and 29% remote) were analysed, revealing a statistically significant association between learner setting and complexity of clinical reasoning. Remote trainees were required to use a high level of clinical reasoning in managing a higher proportion of their patient visits. Remotely trained GPs managed significantly more cases with high clinical complexity and saw a higher proportion of chronic and complex cases and fewer simple cases. CONCLUSIONS: This retrospective study showed GP trainees in all locations experienced comparable learning experiences and depth of training. However, learning in rural and remote locations had equal or more opportunities for seeing higher complexity patients and the necessity to apply greater levels of clinical reasoning to manage each case. This evidence supports learning in rural and remote locations is of a similar standard of learning as for regional trainees and in several areas required a superior level of thinking. Training needs to seriously consider utilising rural and remote clinical placements as exceptional locations for developing and honing medical expertise.

The Use of Wearable Pulse Oximeters in the Prompt Detection of Hypoxemia and During Movement: Diagnostic Accuracy Study.

BACKGROUND: Commercially available wearable (ambulatory) pulse oximeters have been recommended as a method for managing patients at risk of physiological deterioration, such as active patients with COVID-19 disease receiving care in hospital isolation rooms; however, their reliability in usual hospital settings is not known. OBJECTIVE: We report the performance of wearable pulse oximeters in a simulated clinical setting when challenged by motion and low levels of arterial blood oxygen saturation (SaO2). METHODS: The performance of 1 wrist-worn (Wavelet) and 3 finger-worn (CheckMe O2+, AP-20, and WristOx2 3150) wearable, wireless transmission-mode pulse oximeters was evaluated. For this, 7 motion tasks were performed: at rest, sit-to-stand, tapping, rubbing, drinking, turning pages, and using a tablet. Hypoxia exposure followed, in which inspired gases were adjusted to achieve decreasing SaO2 levels at 100%, 95%, 90%, 87%, 85%, 83%, and 80%. Peripheral oxygen saturation (SpO2) estimates were compared with simultaneous SaO2 samples to calculate the root-mean-square error (RMSE). The area under the receiver operating characteristic curve was used to analyze the detection of hypoxemia (ie, SaO2<90%). RESULTS: SpO2 estimates matching 215 SaO2 samples in both study phases, from 33 participants, were analyzed. Tapping, rubbing, turning pages, and using a tablet degraded SpO2 estimation (RMSE>4% for at least 1 device). All finger-worn pulse oximeters detected hypoxemia, with an overall sensitivity of ≥0.87 and specificity of ≥0.80, comparable to that of the Philips MX450 pulse oximeter. CONCLUSIONS: The SpO2 accuracy of wearable finger-worn pulse oximeters was within that required by the International Organization for Standardization guidelines. Performance was degraded by motion, but all pulse oximeters could detect hypoxemia. Our findings support the use of wearable, wireless transmission-mode pulse oximeters to detect the onset of clinical deterioration in hospital settings. TRIAL REGISTRATION: ISRCTN Registry 61535692; http://www.isrctn.com/ISRCTN61535692. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-034404.

Experiences of current vital signs monitoring practices and views of wearable monitoring: A qualitative study in patients and nurses.

AIMS: To understand current experiences of vital signs monitoring of patients and clinical staff on a surgical ward, and views on the introduction of wearable ambulatory monitoring into the general ward environment. DESIGN: Qualitative study. METHODS: Semi-structured interviews using topic guides were conducted with 15 patients and 15 nurses on a surgical ward between July 2018 and August 2019. The concept of ambulatory wearable devices for clinical monitoring was introduced at the end of the interview. RESULTS: Three interconnected themes were identified. Vital sign data as evidence for escalation, examined nurses' use of data to support escalation of care and the implications for patients perceived to be deteriorating who have not reached the threshold for escalation. The second theme, Trustworthiness of vital sign data, described nurses' practice of using manual measurements to recheck or confirm automated vital signs readings when concerned. The final theme, finding a balance between continuous and intermittent monitoring, both patients and nurses agreed that although continuous monitoring may improve safety and reassurance, these needed to be balanced with multiple limitations. Factors to be considered included noise pollution, comfort, and impact on patient mobility and independence. Introduction of the concept of ambulatory wearable devices was viewed positively by both groups as offering solutions to some of the issues identified with traditional monitoring. However, most agreed that this would not be suitable for all patients and should not replace direct nurse/patient contact. CONCLUSION: Both patients and staff identified the benefits of continuous monitoring to improve patient safety but, due to limitations, use should be carefully considered and patient-centred. IMPACT: Feedback from nurses and patients suggests there is scope for ambulatory monitoring systems to be integrated into the hospital environment; however, both groups emphasized these should not add more noise to the ward nor replace direct nursing contact.

Readiness to enter the workforce: perceptions of health professions students at a regional Australian university.

BACKGROUND: Perceived readiness for practice can help mitigate the stress and uncertainty associated with transitioning from university into the workforce. This study aimed to identify factors influencing the readiness for clinical practice among final-year medical, dental, and pharmacy students at an Australian regional university. METHODS: The study utilised a sequential explanatory mixed-methods approach with surveys administered for the quantitative phase and interviews/focus groups for the qualitative phase. Descriptive statistics and inductive thematic analysis were utilised for the quantitative and qualitative data, respectively. Triangulation of findings from both phases facilitated in-depth understanding of the factors that influenced participants' self-perceived readiness for clinical practice. RESULTS: From the three disciplines, 132 students completed the survey and 14 participated in the focus groups and interviews. Students felt most prepared in their patient-centred capabilities, core skills, and advanced consultation skills, and least prepared in their system-related capabilities and clinical care skills. Themes identified as essential enablers and confidence builders in relation to workforce readiness in all three disciplines were: gained knowledge and skills, value of clinical placement experiences, support from peers, family and staff. However, students felt their work-readiness was impaired by heavy academic workloads and poor knowledge of health care systems, which affected skills development. Participants suggested additional support in health care system and clinical governance, mental healthcare, and induction to placement sites to further improve their work readiness. CONCLUSIONS: The findings of this study suggest that improving work-readiness of healthcare students requires alignment of learning needs to real-world practice opportunities, ensuring support systems are appropriate, and early familiarisation with the healthcare system.

A Chest Patch for Continuous Vital Sign Monitoring: Clinical Validation Study During Movement and Controlled Hypoxia.

BACKGROUND: The standard of care in general wards includes periodic manual measurements, with the data entered into track-and-trigger charts, either on paper or electronically. Wearable devices may support health care staff, improve patient safety, and promote early deterioration detection in the interval between periodic measurements. However, regulatory standards for ambulatory cardiac monitors estimating heart rate (HR) and respiratory rate (RR) do not specify performance criteria during patient movement or clinical conditions in which the patient's oxygen saturation varies. Therefore, further validation is required before clinical implementation and deployment of any wearable system that provides continuous vital sign measurements. OBJECTIVE: The objective of this study is to determine the agreement between a chest-worn patch (VitalPatch) and a gold standard reference device for HR and RR measurements during movement and gradual desaturation (modeling a hypoxic episode) in a controlled environment. METHODS: After the VitalPatch and gold standard devices (Philips MX450) were applied, participants performed different movements in seven consecutive stages: at rest, sit-to-stand, tapping, rubbing, drinking, turning pages, and using a tablet. Hypoxia was then induced, and the participants' oxygen saturation gradually reduced to 80% in a controlled environment. The primary outcome measure was accuracy, defined as the mean absolute error (MAE) of the VitalPatch estimates when compared with HR and RR gold standards (3-lead electrocardiography and capnography, respectively). We defined these as clinically acceptable if the rates were within 5 beats per minute for HR and 3 respirations per minute (rpm) for RR. RESULTS: Complete data sets were acquired for 29 participants. In the movement phase, the HR estimates were within prespecified limits for all movements. For RR, estimates were also within the acceptable range, with the exception of the sit-to-stand and turning page movements, showing an MAE of 3.05 (95% CI 2.48-3.58) rpm and 3.45 (95% CI 2.71-4.11) rpm, respectively. For the hypoxia phase, both HR and RR estimates were within limits, with an overall MAE of 0.72 (95% CI 0.66-0.78) beats per minute and 1.89 (95% CI 1.75-2.03) rpm, respectively. There were no significant differences in the accuracy of HR and RR estimations between normoxia (≥90%), mild (89.9%-85%), and severe hypoxia (<85%). CONCLUSIONS: The VitalPatch was highly accurate throughout both the movement and hypoxia phases of the study, except for RR estimation during the two types of movements. This study demonstrated that VitalPatch can be safely tested in clinical environments to support earlier detection of cardiorespiratory deterioration. TRIAL REGISTRATION: ISRCTN Registry ISRCTN61535692; https://www.isrctn.com/ISRCTN61535692.

Gerodontology in the dental school curriculum: A scoping review.

OBJECTIVE: To explore the current status of gerodontology in the undergraduate dental curriculum. BACKGROUND: Internationally, there is recognition for the need to include gerodontology in dental education due to accelerating numbers of older dentate people. There is wide variation in the content and method of delivery of gerodontology in undergraduate curricula of dental schools. METHODS: A scoping review framework was chosen to identify existing gaps and key concepts in the research on current undergraduate gerodontology education. Arksey and O'Malley's framework was used with the qualitative data analysis software NVivo to identify comparable information on geriatric dental education. RESULTS: Five themes were highlighted in the studies including (1) gerodontology curriculum content, (2) attitudes, skills and knowledge of undergraduate dental students, (3) didactic teaching, (4) elective and compulsory teaching, and (5) extra-mural learning. The review found large variations in methodologies, presentation of data and findings. All studies emphasised a need for greater inclusion of gerodontology content in the undergraduate dental curriculum. CONCLUSION: The review found limited research reporting on the educational outcomes of gerodontology in dental curricula with a lack of comprehensive information to inform gerodontology content in dental schools. This review has highlighted the need for national and international guidelines to ensure mandatory inclusion of sufficient and specific gerodontology training to prepare graduates for a growing dentate frail and care-dependent population.

Differential MHC class II synthesis and ubiquitination confers distinct antigen-presenting properties on conventional and plasmacytoid dendritic cells.

The importance of conventional dendritic cells (cDCs) in the processing and presentation of antigen is well established, but the contribution of plasmacytoid dendritic cells (pDCs) to these processes, and hence to T cell immunity, remains unclear. Here we showed that unlike cDCs, pDCs continued to synthesize major histocompatibility complex (MHC) class II molecules and the MHC class II ubiquitin ligase MARCH1 long after activation. Sustained MHC class II-peptide complex formation, ubiquitination and turnover rendered pDCs inefficient in the presentation of exogenous antigens but enabled pDCs to continuously present endogenous viral antigens in their activated state. As the antigen-presenting abilities of cDCs and pDCs are fundamentally distinct, these two cell types may activate largely nonoverlapping repertoires of CD4(+) T cells.

Niosome-encapsulated balanocarpol: compound isolation, characterisation, and cytotoxicity evaluation against human breast and ovarian cancer cell lines.

Natural products have been successfully used to treat various ailments since ancient times and currently several anticancer agents based on natural products are used as the main therapy to treat cancer patients, or as a complimentary treatment to chemotherapy or radiation. Balanocarpol, which is a promising natural product that has been isolated from Hopea dryobalanoides, has been studied as a potential anticancer agent but its application is limited due to its high toxicity, low water solubility, and poor bioavailability. Therefore, the aim of this study is to improve the characteristics of balanocarpol and increase its anticancer activity through its encapsulation in a bilayer structure of a lipid-based nanoparticle drug delivery system where the application of nanotechnology can help improve the limitations of balanocarpol. The compound was first extracted and isolated from H. dryobalanoides. Niosome nanoparticles composed of Span 80 (SP80) and cholesterol were formulated through an innovative microfluidic mixing method for the encapsulation and delivery of balanocarpol. The prepared particles were spherical, small, and uniform with an average particles size and polydispersity index ∼175 nm and 0.088, respectively. The encapsulation of balanocarpol into the SP80 niosomes resulted in an encapsulation efficiency of ∼40%. The niosomes formulation loaded with balanocarpol showed a superior anticancer effect over the free compound when tested in vitro on human ovarian carcinoma (A2780) and human breast carcinoma (ZR-75-1). This is the first study to report the use of SP80 niosomes for the successful encapsulation and delivery of balanocarpol into cancer cells.

How does GP training impact rural and remote underserved communities? Exploring community and professional perceptions.

BACKGROUND: Substantial government funding has been invested to support the training of General Practitioners (GPs) in Australia to serve rural communities. However, there is little data on the impact of this expanded training on smaller communities, particularly for smaller rural and more remote communities. Improved understanding of the impact of training on underserved communities will assist in addressing this gap and inform ongoing investment by governments and communities. METHOD: A purposive sample of GP supervisors, GP registrars, practice managers and health services staff, and community members (n = 40) from previously identified areas of workforce need in rural and remote North-West Queensland were recruited for this qualitative study. Participants had lived in their communities for periods ranging from a few months to 63 years (Median = 12 years). Semi-structured interviews and a focus group were conducted to explore how establishing GP training placements impacts underserved communities from a health workforce, health outcomes, economic and social perspective. The data were then analysed using thematic analysis. RESULTS: Participants reported they perceived GP training to improve communities' health services and health status (accessibility, continuity of care, GP workforce, health status, quality of health care and sustainable health care), some social factors (community connectedness and relationships), cultural factors (values and identity), financial factors (economy and employment) and education (rural pathway). Further, benefits to the registrars (breadth of training, community-specific knowledge, quality of training, and relationships with the community) were reported that also contributed to community development. CONCLUSION: GP training and supervision is possible in smaller and more remote underserved communities and is perceived positively. Training GP registrars in smaller, more remote communities, matches their training more closely with the comprehensive primary care services needed by these communities.

The impact of localised general practice training on Queensland's rural and remote general practice workforce.

BACKGROUND: The diverse rural medical education initiatives that have been developed in Australia to address the medical workforce maldistribution have been less successful in many smaller and remote communities. This study explored the factors that attract and retain GP registrars and supervisors and the impact that localised training (i.e., rural and remote workplace-based training and support) has on both GP registrars and supervisors, and the GP workforce in rural and remote underserved areas. METHODS: A purposive sample of 79 GP registrars, supervisors, practice managers, health services staff and community representatives living and working in areas of low GP workforce in rural and remote Australia were invited to participate in semi-structured interviews and one focus group divided over two phases. Thematic analysis was used to explore themes within the data. FINDINGS: Attractors and barriers to rural and remote practice were identified as the main themes. Attractors include family and community lifestyle factors, individual intrinsic motivators, and remote medicine experiences. In contrast, barriers include work related, location, or family factors. Further, localised GP training was reported to specifically influence GP registrars and supervisors through education, social and financial factors. CONCLUSION: The current study has provided a contemporary overview of the issues encountered in expanding GP training capacity in rural and remote communities to improve the alignment of training opportunities with community and workforce needs. Strategies including matching scope of practice to registrar interests have been implemented to promote the attractors and lessen the barriers associated with rural and remote practice.

Building general practice training capacity in rural and remote Australia with underserved primary care services: a qualitative investigation.

BACKGROUND: Australians living in rural and remote areas have access to considerably fewer doctors compared with populations in major cities. Despite plentiful, descriptive data about what attracts and retains doctors to rural practice, more evidence is needed which informs actions to address these issues, particularly in remote areas. This study aimed to explore the factors influencing General Practitioners (GPs), primary care doctors, and those training to become GPs (registrars) to work and train in remote underserved towns to inform the building of primary care training capacity in areas needing more primary care services (and GP training opportunities) to support their population's health needs. METHODS: A qualitative approach was adopted involving a series of 39 semi-structured interviews of a purposeful sample of 14 registrars, 12 supervisors, and 13 practice managers. Fifteen Australian Medical Graduates (AMG) and eleven International Medical Graduates (IMG), who did their basic medical training in another country, were among the interviewees. Data underwent thematic analysis. RESULTS: Four main themes were identified including 1) supervised learning in underserved communities, 2) impact of working in small, remote contexts, 3) work-life balance, and 4) fostering sustainable remote practice. Overall, the findings suggested that remote GP training provides extensive and safe registrar learning opportunities and supervision is generally of high quality. Supervisors also expressed a desire for more upskilling and professional development to support their retention in the community as they reach mid-career. Registrars enjoyed the challenge of remote medical practice with opportunities to work at the top of their scope of practice with excellent clinical role models, and in a setting where they can make a difference. Remote underserved communities contribute to attracting and retaining their GP workforce by integrating registrars and supervisors into the local community and ensuring sustainable work-life practice models for their doctors. CONCLUSIONS: This study provides important new evidence to support development of high-quality GP training and supervision in remote contexts where there is a need for more GPs to provide primary care services for the population.

Metabolomic-Guided Isolation of Bioactive Natural Products from Curvularia sp., an Endophytic Fungus of Terminalia laxiflora.

Endophytic fungi associated with medicinal plants are a potential source of novel chemistry and biology. Metabolomic tools were successfully employed to compare the metabolite fingerprints of solid and liquid culture extracts of endophyte Curvularia sp. isolated from the leaves of Terminalia laxiflora. Natural product databases were used to dereplicate metabolites in order to determine known compounds and the presence of new natural products. Multivariate analysis highlighted the putative metabolites responsible for the bioactivity of the fungal extract and its fractions on NF-κB and the myelogenous leukemia cell line K562. Metabolomic tools and dereplication studies using high-resolution electrospray ionization mass spectrometry directed the fractionation and isolation of the bioactive components from the fungal extracts. This resulted in the isolation of N-acetylphenylalanine (1: ) and two linear peptide congeners of 1: : dipeptide N-acetylphenylalanyl-L-phenylalanine (2: ) and tripeptide N-acetylphenylalanyl-L-phenylalanyl-L-leucine (3: ).

Shaping medical student's understanding of and approach to rural practice through the undergraduate years: a longitudinal study.

BACKGROUND: Over the last two decades medical schools have increased rural practice learning opportunities for students in an effort to improve recruitment to the rural workforce. James Cook University's (JCU) medical school was established in northern Australia in 2000 with a specific focus on meeting the health needs of people in rural and remote areas. As part of a longitudinal study this paper explores the situational and motivational learning factors contributing to the development of JCU's medical students' understanding of and approaches to rural medical practice. METHODS: After completing each consecutive, compulsory rural clinical placement in Year Two, Four and Six of their MBBS program, JCU medical students were asked to complete a survey about their rural learning experiences. The survey consisted of a combination of single choice, Guttman and Likert scales and open response questions. Data from two open response questions were coded and thematically analysed. Content analysis enabled the predominant value of each theme to be calculated. RESULTS: Collation of the survey data revealed 680 answers to both questions resulting in 1322 comments for analysis. Nine themes were categorized into clinical practice issues and person issues. The evolution of scope of practice across the years, the importance of inspirational mentors, access to urban areas and a sense of community were key findings. Positive rural clinical placement experiences inclusive of supportive ongoing learning opportunities and rural community living contribute positively to medical students' interest in future rural medical practice. However, the ability to work for periods of time in both rural and urban settings suggested a possible need for a new additional model of practice. CONCLUSION: Clear links between a sense of community and belonging both professionally and socially as well as combined rural-urban practice options were important factors in the education and development of future rural practitioners. Ways to establish and support practice models incorporating both rural and urban locations needs to be investigated.

Enhancing health professional education capacity in the Western Pacific region.

In the past 5 years there has been a rapid rise in numbers of foreign-trained medical graduates returning to their countries to work as interns across the Western Pacific. These graduates were found to have a varied and different level of clinical knowledge and skill from that previously experienced in the region. This change in workforce profile led to an urgent need for upskilling clinicians as educators and supervisors. A team of clinical education facilitators were invited to design and deliver context-specific professional education workshops to address this need. These workshops were designed to equip clinical staff with education and supervision skills to optimise teaching and learning opportunities in clinical settings for these new graduates of foreign medical programs. Embracing a collaborative approach and addressing learning needs in local contexts has enabled the team to enhance medical education capacity in the Western Pacific region. This article presents the context of the need for and development of clinical education workshops for intern supervisors in the Western Pacific.