ORCID Profile
0000-0001-6143-5989
Current Organisations
University of Technology
,
University of Technology Sydney
,
Australian National University
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Public Health and Health Services | Other Language And Culture | Public Health And Health Services Not Elsewhere Classified | Language, Communication and Culture not elsewhere classified | Discourse and Pragmatics | Health and Community Services | Public Health and Health Services not elsewhere classified | Nursing not elsewhere classified
Public health not elsewhere classified | Public Health (excl. Specific Population Health) not elsewhere classified | Health and support services not elsewhere classified | Health not elsewhere classified | Communication not elsewhere classified |
Publisher: Wiley
Date: 03-01-2019
DOI: 10.1002/IJC.32064
Abstract: Despite recent advances in targeted and immune-based therapies, advanced stage melanoma remains a clinical challenge with a poor prognosis. Understanding the genes and cellular processes that drive progression and metastasis is critical for identifying new therapeutic strategies. Here, we found that the GTPase RAB27A was overexpressed in a subset of melanomas, which correlated with poor patient survival. Loss of RAB27A expression in melanoma cell lines inhibited 3D spheroid invasion and cell motility in vitro, and spontaneous metastasis in vivo. The reduced invasion phenotype was rescued by RAB27A-replete exosomes, but not RAB27A-knockdown exosomes, indicating that RAB27A is responsible for the generation of pro-invasive exosomes. Furthermore, while RAB27A loss did not alter the number of exosomes secreted, it did change exosome size and altered the composition and abundance of exosomal proteins, some of which are known to regulate cancer cell movement. Our data suggest that RAB27A promotes the biogenesis of a distinct pro-invasive exosome population. These findings support RAB27A as a key cancer regulator, as well as a potential prognostic marker and therapeutic target in melanoma.
Publisher: Wiley
Date: 27-02-2017
DOI: 10.1002/CBIN.10739
Abstract: Many intracellular pathogens have evolved highly specialized mechanisms to isolate themselves from the host cell's innate immune response while still obtaining the necessary nutrients to survive. Salmonella utilizes type 3 secretion systems (T3SSs) to deliver bacterial proteins called effectors, across the encompassing Salmonella Containing vacuole (SCV) membrane, to subvert the host's membrane trafficking pathways and alter other cellular processes. The Salmonella Pathogenicity Island (SPI)-2 effector SopD2 has recently been demonstrated to modulate multiple members of the Rab GTPase family such as Rab7, Rab8, Rab10, and Rab32 (D'Costa et al., , Cell Reports, 12:1508-18 Spano et al., , Cell Host & Microbe, 19:216-26). Here, we demonstrate the additional capacity of SopD2 to bind Rab34 and modulate its function. Our data indicate that depletion of Rab34 delays maturation of the SCV, and consequently, inhibits intracellular Salmonella enterica serotype typhimurium (S. typhimurium) growth. Interestingly, intracellular growth of the S. typhimurium lacking SopD2 was severely impaired in Rab34-depleted cells, suggesting a compounding virulence effect. Overall this study reveals an additional member of the Rab GTPase family, Rab34, that is modulated by SopD2 and provides insight into its role in Salmonella biology.
Publisher: SAGE Publications
Date: 31-03-2015
Publisher: SAGE Publications
Date: 09-03-2015
Abstract: There is an increasing recognition internationally of the critical impact of communication within healthcare. The link between ineffective communication, patient dissatisfaction and critical incidents is well established. Family Planning New South Wales (FPNSW) has sought to address patient-centred care and communication in its policy platform. This article reports on research conducted within FPNSW, which analysed the discourse features that constituted effective doctor–patient 1 communication in sexual and reproductive health consultations. The principal aim of the research was to understand how effectively messages were conveyed and received and to what degree patients were active participants in their own sexual healthcare. Analysed consultations were characterised by extremely high levels of communicative competence on the part of the doctors who integrated medical expertise with the development of interpersonal relationships with patients, thus positioning patients as active contributors to the consultations and to decisions about their ongoing treatment. The detailed linguistic analysis identified characteristic features of patient-centred communication that are essential to patient-centred care. These interactions demonstrate that communicating care is just as important as delivering care and involves a drawing together of the medical and the interpersonal in consultations. The article details strategies for interweaving medical knowledge and establishing rapport that can inform practitioner communication practices across different healthcare contexts.
Publisher: Hindawi Limited
Date: 18-05-2018
DOI: 10.1111/CMI.12852
Abstract: The intracellular pathogen Legionella pneumophila influences numerous eukaryotic cellular processes through the Dot/Icm-dependent translocation of more than 300 effector proteins into the host cell. Although many translocated effectors localise to the Legionella replicative vacuole, other effectors can affect remote intracellular sites. Following infection, a subset of effector proteins localises to the nucleus where they subvert host cell transcriptional responses to infection. Here, we identified Lpw27461 (Lpp2587), Lpg2519 as a new nuclear-localised effector that we have termed SnpL. Upon ectopic expression or during L. pneumophila infection, SnpL showed strong nuclear localisation by immunofluorescence microscopy but was excluded from nucleoli. Using immunoprecipitation and mass spectrometry, we determined the host-binding partner of SnpL as the eukaryotic transcription elongation factor, Suppressor of Ty5 (SUPT5H)/Spt5. SUPT5H is an evolutionarily conserved component of the DRB sensitivity-inducing factor complex that regulates RNA Polymerase II dependent mRNA processing and transcription elongation. Protein interaction studies showed that SnpL bound to the central Kyprides, Ouzounis, Woese motif region of SUPT5H. Ectopic expression of SnpL led to massive upregulation of host gene expression and macrophage cell death. The activity of SnpL further highlights the ability of L. pneumophila to control fundamental eukaryotic processes such as transcription that, in the case of SnpL, leads to global upregulation of host gene expression.
Publisher: Cold Spring Harbor Laboratory
Date: 11-12-2020
DOI: 10.1101/2020.12.10.420414
Abstract: We present LLAMA, a pipeline for systematic analysis of terabyte scale 4D microscopy datasets. Analysis of in idual biological structures in imaging at this scale requires efficient and robust methods which do not require human micromanagement or editing of outputs. To meet this challenge, we use a machine learning method for semantic segmentation, followed by a robust and configurable object separation and tracking algorithm, and the generation of detailed object level statistics. Advanced visualisation is a key element of LLAMA: we provide a specialised software tool which supports quality control and optimisation as well as visualisation of outputs. LLAMA was used in a quantitative analysis of macrophage surface membrane projections (filopodia, ruffles, tent-pole ruffles) examining the differential effects of two interventions: lipopolysaccharide (LPS) and macrophage colony stimulating factor (CSF-1). Distinct patterns of increased activity were identified. In addition, a continuity of behaviour was found between tent pole ruffling and wave-like ruffling, further defining the role of filopodia in ruffling.
Publisher: Oxford University Press (OUP)
Date: 08-2020
Publisher: Rockefeller University Press
Date: 27-08-2018
Abstract: Pathogen-mediated activation of macrophages arms innate immune responses that include enhanced surface ruffling and macropinocytosis for environmental s ling and receptor internalization and signaling. Activation of macrophages with bacterial lipopolysaccharide (LPS) generates prominent dorsal ruffles, which are precursors for macropinosomes. Very rapid, high-resolution imaging of live macrophages with lattice light sheet microscopy (LLSM) reveals new features and actions of dorsal ruffles, which redefine the process of macropinosome formation and closure. We offer a new model in which ruffles are erected and supported by F-actin tent poles that cross over and twist to constrict the forming macropinosomes. This process allows for formation of large macropinosomes induced by LPS. We further describe the enrichment of active Rab13 on tent pole ruffles and show that CRISPR deletion of Rab13 results in aberrant tent pole ruffles and blocks the formation of large LPS-induced macropinosomes. Based on the exquisite temporal and spatial resolution of LLSM, we can redefine the ruffling and macropinosome processes that underpin innate immune responses.
Publisher: Elsevier BV
Date: 03-2020
Publisher: Wiley
Date: 02-2016
Abstract: Neutrophils express pattern recognition receptors (PRRs) and regulate immune responses via PRR-dependent cytokine production. An emerging theme is that neutrophil PRRs often exhibit cell type-specific adaptations in their signalling pathways. This prompted us to examine inflammasome signalling by the PRR NLRP3 in murine neutrophils, in comparison to well-established NLRP3 signalling pathways in macrophages. Here, we demonstrate that while murine neutrophils can indeed signal via the NLRP3 inflammasome, neutrophil NLRP3 selectively responds to soluble agonists but not to the particulate/crystalline agonists that trigger NLRP3 activation in macrophages via phagolysosomal rupture. In keeping with this, alum did not trigger IL-1β production from human PMN, and the lysosomotropic peptide Leu-Leu-OMe stimulated only weak NLRP3-dependent IL-1β production from murine neutrophils, suggesting that lysosomal rupture is not a strong stimulus for NLRP3 activation in neutrophils. We validated our in vitro findings for poor neutrophil NLRP3 responses to particles in vivo, where we demonstrated that neutrophils do not significantly contribute to alum-induced IL-1β production in mice. In all, our studies highlight that myeloid cell identity and the nature of the danger signal can strongly influence signalling by a single PRR, thus shaping the nature of the resultant immune response.
Publisher: Informa UK Limited
Date: 1987
Publisher: SAGE Publications
Date: 03-2015
DOI: 10.1177/102490791502200201
Abstract: This paper reports on research conducted within a Hong Kong (HK) accident and emergency department (AED), which investigated the effectiveness of health care worker-patient communication over the course of patients' journeys from triage to disposition. The research combined qualitative and quantitative ethnographic methods with linguistically-oriented discourse analysis of audiotaped interactions between patients and health care workers. It involved: (1) observations, (2) semi-structured interviews with management and health care workers, (3) surveys with AED staff, (4) audio-recordings of 10 patients' journeys, and (5) follow-up interviews with patients. The paper described the typically complex communication networks involved in AED care. It then exemplified how certain communicative strategies, balancing the communication of medical knowledge with interpersonal communication, could be used to achieve positive healthcare outcomes. This was illustrated by a case study of one patient's journey through the AED, pinpointing health care workers' effective use of communication strategies, their effect on the patient's participation and subsequently the patient's understanding and evaluation of the care he received. The high stress nature of AEDs inevitably poses challenges to communication. The results of this study, however, strongly suggest a correlation between health care workers' use of effective, interpersonally sensitive communication strategies and positive patient outcomes. Health care worker-patient communication that effectively balances interpersonal communication with the communication of medical expertise is integral to ensuring patients' participation in, understanding of, and satisfaction with their healthcare. These communication strategies should be required components in health care worker communication training. (Hong Kong j.emerg.med. 2015 :69-83)
Publisher: Wiley
Date: 04-2016
DOI: 10.1038/CTI.2016.15
Publisher: Wiley
Date: 16-07-2015
DOI: 10.1111/TCT.12423
Abstract: Communication in emergency departments (EDs), often between several health professionals and patients and relatives, is a major cause of patient complaint and error however, communication-skills teaching for medical students largely focuses on in idual clinician-patient interactions. We developed and implemented an evidence-informed online resource, Communication for Health in Emergency Contexts (CHEC www.chec.meu.medicine.unimelb.edu.au/resources) to raise medical students' awareness of the challenges of communication in the ED, and to provide students with communication strategies for addressing these challenges. The foundation of the CHEC resource was the findings and data from a large research project conducted at five emergency departments in Australia over the period 2006-2009. From this, we developed ED scenarios and teaching vignettes using authentic communication data. The project included a nationwide medical curriculum scoping phase, involving interviews with medical students and educators, on ED communication curriculum needs in order to inform the educational activities. The CHEC resource provides students with the opportunity to follow real-life scenarios through all stages of the ED journey, whereas insights from ED medical and nursing staff provide learning opportunities about interprofessional communication for medical students. Evaluation suggests that students find the resource useful, and that the resource has been successfully embedded in medical and junior doctor training on communication and quality and safety. The CHEC resource enhances the capacity of busy clinical educators to raise students' awareness of the communication needs of emergency health care by focusing on communication in high-stress, time-pressured settings using a web format. The CHEC resource provides students with the opportunity to follow real-life scenarios through all stages of the ED journey.
Publisher: Wiley
Date: 17-01-2022
DOI: 10.1111/JAN.15110
Abstract: To increase the quality and safety of patient care, many hospitals have mandated that nursing clinical handover occur at the patient's bedside. This study aims to improve the patient‐centredness of nursing handover by addressing the communication challenges of bedside handover and the organizational and cultural practices that shape handover. Qualitative linguistic ethnographic design combining discourse analysis of actual handover interactions and interviews and focus groups before and after a tailored intervention. Pre‐intervention we conducted interviews with nursing, medical and allied health staff ( n = 14) and focus groups with nurses and students ( n = 13) in one hospital's Rehabilitation ward. We recorded handovers ( n = 16) and multidisciplinary team huddles ( n = 3). An intervention of communication training and recommendations for organizational and cultural change was delivered to staff and ch ioned by ward management. After the intervention we interviewed nurses and recorded and analyzed handovers. Data were collected from February to August 2020. Ward management collected hospital‐acquired complication data. Notable changes post‐intervention included a shift to involve patients in bedside handovers, improved ward‐level communication and culture, and an associated decrease in reported hospital‐acquired complications. Effective change in handover practices is achieved through communication training combined with redesign of local practices inhibiting patient‐centred handovers. Strong leadership to ch ion change, ongoing mentoring and reinforcement of new practices, and collaboration with nurses throughout the change process were critical to success. Ineffective communication during handover jeopardizes patient safety and limits patient involvement. Our targeted, locally designed communication intervention significantly improved handover practices and patient involvement through the use of informational and interactional protocols, and redesigned handover tools and meetings. Our approach promoted a ward culture that prioritizes patient‐centred care and patient safety. This innovative intervention resulted in an associated decrease in hospital‐acquired complications. The intervention has been rolled out to a further five wards across two hospitals.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.NEDT.2019.104212
Abstract: To explore the perceptions and practices of nurses on handovers. At handover, accountability must be transferred to ensure a consistent quality of patient care. Studies highlighted unstructured handovers as a major factor contributing to critical incidents. The design of handover training requires a systematic method for evaluating nurses' practices. An explorative case study, qualitative design that combined ethnography with discourse analysis. A training programme based on these practices was administered to 50 nurses, and a protocol focused on CARE was implemented. The nurses' perceptions and practices were evaluated, and 80 handovers were recorded. Three areas likely to enhance the continuity of care emerged: 1) explicit transfer of responsibility by outgoing nurses 2) responsible engagement of incoming nurses in the handover and 3) adherence to a systematic handover structure. The change in practice from monologic handovers with passive incoming nurses before training to interactive and collaborative handovers, where all nurses appeared to take an active role in clarifying patients' cases, after training was significant.
Publisher: BMJ
Date: 08-2017
DOI: 10.1136/BMJOPEN-2016-015721
Abstract: Despite growing recognition of the importance of speaking up to protect patient safety in critical care, little research has been performed in this area in an intensive care unit (ICU) context. This study explored the communication openness perceptions of Chinese doctors and nurses and identified their perceptions of issues in ICU communication, their reasons for speaking up and the possible factors and strategies involved in promoting the practice of speaking up. A mixed-methods design with quantitative and sequential qualitative components was used. Eighty ICU staff members from a large public hospital in Hong Kong completed a questionnaire regarding their perceptions of communication openness. Ten clinicians whose survey responses indicated support for open communication were then interviewed about their speak-up practices. The participating ICU staff members had similar perceptions of their openness to communication. However, the doctors responded more positively than the nurses to many aspects of communication openness. The two groups also had different perceptions of speaking up. The interviewed ICU staff members who indicated a high level of communication openness reported that their primary reasons for speaking up were to seek and clarify information, which was achieved by asking questions. Other factors perceived to influence the motivation to speak up included seniority, relationships and familiarity with patient cases. Creating an atmosphere of safety and equality in which team members feel confident in expressing their personal views without fear of reprisal or embarrassment is necessary to encourage ICU staff members, regardless of their position, to speak up. Because harmony and saving face is valued in Chinese culture, training nurses and doctors to speak up by focusing on human factors and values rather than simply addressing conflict management is desirable in this context.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.PEC.2014.06.017
Abstract: The human dimensions of healthcare--core values and skilled communication necessary for every healthcare interaction--are fundamental to compassionate, ethical, and safe relationship-centered care. The objectives of this paper are to: describe the development of the International Charter for Human Values in Healthcare which delineates core values, articulate the role of skilled communication in enacting these values, and provide ex les showing translation of the Charter's values into action. We describe development of the Charter using combined qualitative research methods and the international, interprofessional collaboration of institutions and in iduals worldwide. We identified five fundamental categories of human values for every healthcare interaction--Compassion, Respect for Persons, Commitment to Integrity and Ethical Practice, Commitment to Excellence, and Justice in Healthcare--and delineated subvalues within each category. We have disseminated the Charter internationally and incorporated it into education/training. Diverse healthcare partners have joined in this work. We chronicle the development and dissemination of the International Charter for Human Values in Healthcare, the role of skilled communication in demonstrating values, and provide ex les of educational and clinical programs integrating these values. The Charter identifies and promotes core values clinicians and educators can demonstrate through skilled communication and use to advance humanistic educational programs and practice.
Publisher: Public Library of Science (PLoS)
Date: 26-01-2016
Publisher: Springer Science and Business Media LLC
Date: 18-01-2017
DOI: 10.1038/NCOMMS14133
Abstract: Danger signals activate Toll-like receptors (TLRs), thereby initiating inflammatory responses. Canonical TLR signalling, via Toll/Interleukin-1 receptor domain (TIR)-containing adaptors and proinflammatory transcription factors such as NF-κB, occurs in many cell types however, additional mechanisms are required for specificity of inflammatory responses in innate immune cells. Here we show that SCIMP, an immune-restricted, transmembrane adaptor protein (TRAP), promotes selective proinflammatory cytokine responses by direct modulation of TLR4. SCIMP is a non-TIR-containing adaptor, binding directly to the TLR4-TIR domain in response to lipopolysaccharide. In macrophages, SCIMP is constitutively associated with the Lyn tyrosine kinase, is required for tyrosine phosphorylation of TLR4, and facilitates TLR-inducible production of the proinflammatory cytokines IL-6 and IL-12p40. Point mutations in SCIMP abrogating TLR4 binding also prevent SCIMP-mediated cytokine production. SCIMP is, therefore, an immune-specific TLR adaptor that shapes host defence and inflammation.
Publisher: Wiley
Date: 14-03-2017
DOI: 10.1038/ICB.2017.10
Abstract: Protein tyrosine phosphorylation guides many molecular interactions for cellular functions. SCIMP is a transmembrane adaptor protein (TRAP) family member that mediates selective proinflammatory cytokine responses generated by pathogen-activated Toll-like receptor (TLR) pathways in macrophages. TLR activation triggers SCIMP phosphorylation and selective phosphorylation of distinct tyrosine residues on this adaptor offers the potential for regulating or biasing inflammatory responses. To analyze site-specific phosphorylation events, we developed three probes based on the SH2 domains of known SCIMP effectors, and used them for pull-downs from macrophage extracts. CRISPR-mediated SCIMP-deficient RAW264.7 macrophage-like cells were reconstituted with various phosphorylation-deficient (Y58F, Y96F, Y120F) SCIMPs, and used to demonstrate the specificity of LPS/TLR4-induced, site-specific phosphorylation of SCIMP for the temporal recruitment of the effectors Grb2, Csk and SLP65. Our findings reveal potential for differential SCIMP phosphorylation and specific effectors to influence TLR signaling and inflammatory programs. Furthermore, the use of Csk-SH2 pull-downs to identify additional known and new Csk targets in LPS-activated macrophages reveals the wider utility of our SH2 probes.
Publisher: SAGE Publications Ltd
Date: 2017
Publisher: Informa UK Limited
Date: 07-03-2019
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.CELREP.2018.07.027
Abstract: IL-1β requires processing by caspase-1 to generate the active, pro-inflammatory cytokine. Acute IL-1β secretion from inflammasome-activated macrophages requires caspase-1-dependent GSDMD cleavage, which also induces pyroptosis. Mechanisms of IL-1β secretion by pyroptotic and non-pyroptotic cells, and the precise functions of caspase-1 and GSDMD therein, are unresolved. Here, we show that, while efficient early secretion of endogenous IL-1β from primary non-pyroptotic myeloid cells in vitro requires GSDMD, later IL-1β release in vitro and in vivo proceeds independently of GSDMD. IL-1β maturation is sufficient for slow, caspase-1/GSDMD-independent secretion of ectopic IL-1β from resting, non-pyroptotic macrophages, but the speed of IL-1β release is boosted by inflammasome activation, via caspase-1 and GSDMD. IL-1β cleavage induces IL-1β enrichment at PIP2-enriched plasma membrane ruffles, and this is a prerequisite for IL-1β secretion and is mediated by a polybasic motif within the cytokine. We thus reveal a mechanism in which maturation-induced IL-1β trafficking facilitates its unconventional secretion.
Publisher: The Royal Society
Date: 17-12-2019
Abstract: Macropinocytosis is a prevalent and essential pathway in macrophages where it contributes to anti-microbial responses and innate immune cell functions. Cell surface ruffles give rise to phagosomes and to macropinosomes as multi-functional compartments that contribute to environmental s ling, pathogen entry, plasma membrane turnover and receptor signalling. Rapid, high resolution, lattice light sheet imaging demonstrates the dynamic nature of macrophage ruffling. Pathogen-mediated activation of surface and endosomal Toll-like receptors (TLRs) in macrophages upregulates macropinocytosis. Here, using multiple forms of imaging and microscopy, we track membrane-associated, fluorescently-tagged Rab8a expressed in live macrophages, using a variety of cell markers to demonstrate Rab8a localization and its enrichment on early macropinosomes. Production of a novel biosensor and its use for quantitative FRET analysis in live cells, pinpoints macropinosomes as the site for TLR-induced activation of Rab8a. We have previously shown that TLR signalling, cytokine outputs and macrophage programming are regulated by the GTPase Rab8a with PI3 Kγ as its effector. Finally, we highlight another effector, the phosphatase OCRL, which is located on macropinosomes and interacts with Rab8a, suggesting that Rab8a may operate on multiple levels to modulate phosphoinositides in macropinosomes. These findings extend our understanding of macropinosomes as regulatory compartments for innate immune function in macrophages. This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.
Publisher: SAGE Publications
Date: 08-2008
Abstract: Effective communication and interpersonal skills have long been recognized as fundamental to the delivery of quality health care. However, there is mounting evidence that the pressures of communication in high stress work areas such as hospital emergency departments (EDs) present particular challenges to the delivery of quality care. A recent report on incident management in the Australian health care system (NSW Health, 2005a) cites the main cause of critical incidents (that is, adverse events such as an incorrect procedure leading to patient harm), as being poor and inadequate communication between clinicians and patients. This article presents research that describes and analyses spoken interactions between health care practitioners and patients in one ED of a large, public teaching hospital in Sydney, Australia. The research aimed to address the challenges and critical incidents caused by breakdowns in communication that occur between health practitioners and patients and by refining and extending knowledge of discourse structures, to identify ways in which health care practitioners can enhance their communicative practices thereby improving the quality of the patient journey through the ED. The research used a qualitative ethnographic approach combined with discourse analysis of audio-recorded interactions. Some key findings from the analysis of data are outlined including how the absence of information about processes, the pressure of time within the ED, ergent goals of clinicians and patients, the delivery of diagnoses and professional roles impact on patient experiences. Finally, the article presents an in-depth linguistic analysis on interpersonal and experiential patterns in the discursive practices of patients, nurses and doctors.
Publisher: The Company of Biologists
Date: 30-12-2019
DOI: 10.1242/JCS.239194
Abstract: Toll-like receptors (TLRs) are danger-sensing receptors that typically propagate self-limiting inflammatory responses, but can unleash uncontrolled inflammation in non-homeostatic or disease settings. Activation of TLRs by pathogen- and/or host-derived stimuli triggers a range of signalling and transcriptional pathways to programme inflammatory and anti-microbial responses, including the production of a suite of inflammatory cytokines and other mediators. Multiple sorting and signalling adaptors are recruited to receptor complexes on the plasma membrane or endosomes where they act as scaffolds for downstream signalling kinases and effectors at these sites. So far, seven proximal TLR adaptors have been identified: MyD88, MAL, TRIF (also known as TICAM1), TRAM (TICAM2), SARM (SARM1), BCAP (PIK3AP1) and SCIMP. Most adaptors tether directly to TLRs through homotypic Toll/interleukin-1 receptor domain (TIR)–TIR interactions, whereas SCIMP binds to TLRs through an atypical TIR–non-TIR interaction. In this Review, we highlight the key roles for these adaptors in TLR signalling, scaffolding and receptor sorting and discuss how the adaptors thereby direct the differential outcomes of TLR-mediated responses. We further summarise TLR adaptor regulation and function, and make note of human diseases that might be associated with mutations in these adaptors.
Publisher: Unpublished
Date: 2013
Publisher: Elsevier BV
Date: 2019
Publisher: Elsevier BV
Date: 08-2020
Publisher: Bio-Protocol, LLC
Date: 2020
Publisher: Springer New York
Date: 05-11-2017
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: Informa UK Limited
Date: 02-01-2016
Publisher: Asian Pacific Journal of Tropical Medicine Press
Date: 08-2015
Publisher: Wiley
Date: 03-03-2017
DOI: 10.1111/JOCN.13699
Abstract: To understand the challenges that clinicians face in communicating with patients and other clinicians within a Hong Kong trilingual emergency department. Effective communication has long been recognised as fundamental to the delivery of quality health care, especially in high-risk and time-constrained environments such as emergency departments. The issue of effective communication is particularly relevant in Hong Kong emergency departments, due to the high volume of patients and the linguistic complexity of this healthcare context. In Hong Kong, emergency department clinicians are native speakers of Chinese, but have received their medical training in English. The clinicians read and record virtually all of their medical documentation in English, yet they communicate verbally with patients in Cantonese and Mandarin. In addition, communication between clinicians occurs in spoken Cantonese, mixed with medical English. Thus, medical information is translated numerous times within one patient journey. This complex linguistic environment creates the potential for miscommunication. A mixed-methods design consisting of a quantitative survey with a sequential qualitative interview. Data were collected in a survey from a purposive s le of 58 clinicians and analysed through descriptive statistics. Eighteen of the clinicians were then invited to take part in semi-structured interviews, the data from which were then subjected to a manifest content analysis. Nearly half of the clinicians surveyed believed that medical information may be omitted or altered through repeated translation in a trilingual emergency department. Eighty-three per cent of clinicians stated that there are communication problems at triage. Over 40% said that they have difficulties in documenting medical information. Around 50% believed that long work hours reduced their ability to communicate effectively with patients. In addition, 34% admitted that they rarely or never listen to patients during a consultation. The findings reveal that the quality of communication in this Hong Kong emergency department is compromised by specific factors inherent in the linguistic complexity of Hong Kong emergency departments. These factors include the constant translation of medical information, inadequate documentation of medical information and significant professional and cultural pressures. Each of these issues increases the likelihood that healthcare communication will be difficult, incomplete or incorrect. This research provides empirical evidence for, and justifies the development of, an effective framework to enable clinicians to overcome communication challenges. The findings of this study may shed light on the unique conditions faced by clinicians, particularly in relation to communication, in the complex trilingual healthcare context of an emergency department similar to those in Hong Kong, and provide potential policy solutions for barriers to improve communication in such settings.
Publisher: Informa UK Limited
Date: 02-01-2016
Publisher: Unpublished
Date: 2012
Publisher: Wiley
Date: 23-06-2016
DOI: 10.1111/TRA.12415
Abstract: Macrophages are activated by contact with pathogens to mount innate immune defenses against infection. Toll-like receptor 4 (TLR4) at the macrophage surface recognizes and binds bacterial lipopolysaccharide (LPS), setting off signaling and transcriptional events that lead to the secretion of pro- and anti-inflammatory cytokines these in turn control inflammatory and antimicrobial responses. Although the complex regulatory pathways downstream of TLR4 have been extensively studied, further molecules critical for modulating the resulting cytokine outputs remain to be characterized. Here we establish potential roles for APPL1 and 2 signaling adaptors as regulators of LPS/TLR4-induced signaling, transcription, and cytokine secretion. APPL1 and 2 are differentially localized to distinct signaling-competent membrane domains on the surface and in endocytic compartments of LPS-activated macrophages. By depleting cells of each adaptor respectively we show separate and opposing functions for APPL1 and 2 in Akt and MAPK signaling. Specifically, APPL2 has a dominant role in nuclear translocation of NF-KB p65 and it serves to constrain the secretion of pro- and anti-inflammatory cytokines. The APPLs, and in particular APPL2, are thus revealed as adaptors with important capacity to modulate inflammatory responses mounted by LPS/TLR4 during infection.
Publisher: Elsevier BV
Date: 04-2022
Publisher: Springer Berlin Heidelberg
Date: 2015
Publisher: Oxford University Press (OUP)
Date: 30-03-2018
Abstract: Transmembrane adaptor proteins (TRAPs) are protein scaffolds and signaling regulators with established roles in signal-induced activation of lymphocytes. A subset of the TRAP family, the palmitoylated TRAPs (pTRAPs), are increasingly emerging with additional roles in innate immune cells. Targeted to lipid rafts, tetraspannin-enriched microdomains, and protein microclusters in membranes, pTRAP scaffolds exert spatiotemporal regulation by recruiting signaling kinases, particularly Src and Syk family members, as well as Csk, and other effectors. In this way, pTRAPs modulate signaling and influence resulting cell responses, including the selective output of inflammatory cytokines and other mediators. Here, we review studies revealing that different pTRAPs work together, often with overlapping or redundant roles, for positive and negative regulation of key innate immune pathways, including Fc receptor and pattern recognition receptor signaling. Recent findings show that pTRAPs can bind directly to innate immune receptors, in addition to other transmembrane binding partners. Thus, pTRAPs are important, multifunctional scaffolds in pathways that are fundamental to erse innate immune responses.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.PEC.2018.01.018
Abstract: To provide an integrative review of literature on health communication in East Asia and detail culturally-specific influences. Using PRISMA model, search of PubMed, PsychInfo, Web of Knowledge, ERIC and CINAHL databases were conducted for studies between January 2000 and March 2017, using the terms 'clinician/health professional-patient', 'nurse/doctor-patient, 'communication' and 'Asia'. 38 studies were included: Mainland China, Hong Kong, Japan, South Korea, and Taiwan. The existing body of research on clinician patient communication in East Asia can be classified: 1) understanding the roles and expectations of the nurse, clinician, patient, and family in clinician-patient consultations: a) nurse-patient communication b) doctor-patient communication c) the role of family member and 2) factors affecting quality of care: d) cultural attitudes towards death and terminal illnesses e) communication preferences affecting trust, decision-making and patient satisfaction f) the extent to which patient centred care is being implemented in practice and g) communication practices in multilingual/multi-disciplinary environments. The review detailed the complexity and heterogeneity of clinician-patient communication across East Asia. The studies reviewed indicate that research in East Asia is starting to move beyond a preference for Western-based communication practices. There is a need to consider local culture in understanding and interpreting medical encounters in East Asia. The paper highlights the need for a specific culturally-appropriate model of health communication in East Asia which may significantly improve relationships between clinicians and patients.
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.CELREP.2018.08.028
Abstract: The multi-ligand endocytic receptor, low-density lipoprotein-receptor-related protein 1 (LRP1), has anti-inflammatory roles in disease. Here, we reveal that pathogen-activated Toll-like receptors (TLRs) activate LRP1 in human and mouse primary macrophages, resulting in phosphorylation of LRP1 at Y4507. In turn, this allows LRP1 to activate and recruit the guanosine triphosphatase (GTPase), Rab8a, with p110γ 101 as its phosphatidylinositol 3-kinase (PI3K) effector complex. PI3Kγ is a known regulator of TLR signaling and macrophage reprogramming. LRP1 coincides with Rab8a at signaling sites on macropinosomal membranes. In LRP1-deficient cells, TLR-induced Rab8 activation is abolished. CRISPR-mediated knockout of LRP1 in macrophages alters Akt/mTOR signaling and produces a pro-inflammatory bias in cytokine outputs, mimicking the Rab8a knockout and PI3Kγ-null phenotype. Thus, TLR-LRP1 crosstalk activates the Rab8a/PI3Kγ complex for reprogramming macrophages, revealing this as a key mechanism through which LRP1 helps to suppress inflammation.
Publisher: Elsevier BV
Date: 03-2017
Publisher: Unpublished
Date: 2011
Publisher: SAGE Publications
Date: 17-11-2015
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.JCRC.2017.10.044
Abstract: Ineffective communication during mechanical ventilation (MV) and critical illness is distressing to many patients. This study aimed to describe the scope of communication content of ventilated critically ill patients. We performed a prospective qualitative interview study in a multidisciplinary intensive care unit. Ten alert, orientated adult patients who previously underwent MV for at least 24h and were able to speak at the time of interview were recruited. Semi-structured interviews with stimulated recall technique were conducted. A descriptive thematic analysis was performed of the patient-generated content using a free coding technique, where recurrent themes and subthemes were noted, coded and analyzed. Patients' communication content included medical discussions with clinicians communication with family to provide advice or comfort, make requests and plans, express feelings and convey personal perspectives on medical care and expression of their own psychoemotional needs. The scope of communication content of ventilated ICU patients was broad, extending far beyond task-focused subject matter. Content ranged from conveying symptom-related messages to active participation in medical discussions, to conversing with family about a range of complex multi-dimensional issues, to sharing their own psychoemotional experiences. These patient-centered needs should be recognized and addressed in communication strategies.
Publisher: SAGE Publications Ltd
Date: 2011
Location: Australia
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 05-2011
End Date: 05-2014
Amount: $718,245.00
Funder: Australian Research Council
View Funded ActivityStart Date: 07-2009
End Date: 12-2012
Amount: $250,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 01-2007
End Date: 12-2009
Amount: $416,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 08-2014
End Date: 12-2018
Amount: $480,000.00
Funder: Australian Research Council
View Funded Activity