Exploring Pharmacists' Roles during the 2019-2020 Australian Black Summer Bushfires.

BACKGROUND: Australians are no strangers to sudden natural disasters, such as bushfires. The effects of a natural disaster can devastate local communities and health care services. Currently, limited research has explored the role of the pharmacist during a natural disaster. This study explores the role of the Australian pharmacist during the 2019/2020 Black Summer Bushfires. METHODS: Semi-structured phone interviews were conducted with ten community pharmacists who worked through the Black Summer Bushfires whose daily tasks and work environment were directly affected by the bushfires. Thematic analysis using NVivo®, a qualitative data analysis software was conducted. RESULTS: Analysis of the transcripts generated six main themes: collaboration; trauma and mental health; power and communication; acute presentations; triaging and emergency prescribing. Pharmacists worked in close collaboration with doctors and members of the local community. They provided triaging services, timely health advice about chronic health problems, and managed acute issues, including wound and burn management and mental health support in traumatic conditions, sometimes without power and communication amenities. The challenges presented to pharmacists during the bushfires warranted creative and flexible approaches at times. CONCLUSION: This study highlights the need for mental health support and training for pharmacists, provisional prescribing privileges, and a clearer set of contingency regulations and legislation related to emergencies and natural disasters. Further research is warranted to gain greater insight into the roles undertaken by Australian pharmacists during natural disasters and their autonomy in decision making processes during such times.

A qualitative study of health professions curricula and management of lateral ankle ligament sprain demonstrates inconsistency.

BACKGROUND: Health educators aim to graduate students who are safe, effective and practice evidence-based medicine (EBM). Clinical Practice Guidelines (CPGs) are tools for translating evidence into clinical practice for health professionals and educators who lack time to appraise the evidence. There have been CPGs published for lateral ankle ligament sprains (LALS) for physiotherapists, nurses, and doctors. Clinical decision rules have also been developed for LALS to increase the safety of practice. The Ottawa Ankle Rules (OAR) were developed to screen for the need for an x-ray following an ankle or foot injury. METHODS: Educators from the Australasian College of Sports and Exercise Physicians (ACSEP), St John Ambulance first aiders, pharmacy, nursing, and physiotherapy disciplines were participants in this study. Using purposeful sampling with semi-structured questions and a LALS case study, 19 Australian educators were interviewed. Curricula and textbooks were also collected and analysed. Two researchers independently analysed the data using a deductive method. RESULTS: Analysis found that no educator used a CPG to inform their teaching. There was no common LALS curriculum for the five groups studied. There were two approaches: a triage curriculum (St John Ambulance, pharmacy, nursing) and a reflective curriculum (ASCEP and physiotherapy). Textbooks influenced curriculum for physiotherapy, pharmacy and first aid educators. The triage curricula recommend rest, ice, compression and elevation (RICE) alone, while the reflective curricula uses OAR, RICE, immobilisation if the LALS is severe, functional support (brace), exercises and manual therapy. In addition, ACSEP and physiotherapy do not recommend electrotherapy. All five groups were cautious about the use of non-steroidal anti-inflammatory drugs (NSAIDs). CONCLUSIONS: Physiotherapy and ACSEP educators teach OAR. Despite not using the CPGs to inform curriculum, physiotherapy and ACSEP have unintentionally aligned their curriculum with current LALS CPG recommendations. However, nursing, pharmacy and first aid trainers are not teaching OAR or aligned with LALS CPGs. Educators in pharmacy, nursing and first aid should re-examine their curricula and consider possibly teaching OAR and using CPG. Clinical practice guideline developers should consider pharmacists and first aiders as users of their LALS CPGs.

What is the quality of clinical practice guidelines for the treatment of acute lateral ankle ligament sprains in adults? A systematic review.

BACKGROUND: Acute lateral ankle ligament sprains (LALS) are a common injury seen by many different clinicians. Knowledge translation advocates that clinicians use Clinical Practice Guidelines (CPGs) to aid clinical decision making and apply evidence-based treatment. The quality and consistency of recommendations from these CPGs are currently unknown. The aims of this systematic review are to find and critically appraise CPGs for the acute treatment of LALS in adults. METHODS: Several medical databases were searched. Two authors independently applied inclusion and exclusion criteria. The content of each CPG was critically appraised independently, by three authors, using the Appraisal of Guidelines for REsearch and Evaluation (AGREE II) instrument online version called My AGREE PLUS. Data related to recommendations for the treatment of acute LALS were abstracted independently by two reviewers. RESULTS: This study found CPGs for physicians and physical therapists (Netherlands), physical therapists, athletic trainers, physicians, and nurses (USA) and nurses (Canada and Australia). Seven CPGs underwent a full AGREE II critical appraisal. None of the CPGs scored highly in all domains. The lowest domain score was for domain 5, applicability (discussion of facilitators and barriers to application, provides advice for practical use, consideration of resource implications, and monitoring/auditing criteria) achieving an exceptionally low joint total score of 9% for all CPGs. The five most recent CPGs scored a zero for applicability. Other areas of weakness were in rigour of development and editorial independence. CONCLUSIONS: The overall quality of the existing LALS CPGs is poor and majority are out of date. The interpretation of the evidence between the CPG development groups is clearly not consistent. Lack of consistent methodology of CPGs is a barrier to implementation. SYSTEMATIC REVIEW: Systematic review registered with PROSPERO ( CRD42015025478 ).

Nuclear transport of cancer extracellular vesicle-derived biomaterials through nuclear envelope invagination-associated late endosomes.

Extracellular membrane vesicles (EVs) function as vehicles of intercellular communication, but how the biomaterials they carry reach the target site in recipient cells is an open question. We report that subdomains of Rab7+ late endosomes and nuclear envelope invaginations come together to create a sub-nuclear compartment, where biomaterials associated with CD9+ EVs are delivered. EV-derived biomaterials were also found in the nuclei of host cells. The inhibition of nuclear import and export pathways abrogated the nuclear localization of EV-derived biomaterials or led to their accumulation therein, respectively, suggesting that their translocation is dependent on nuclear pores. Nuclear envelope invagination-associated late endosomes were observed in ex vivo biopsies in both breast carcinoma and associated stromal cells. The transcriptome of stromal cells exposed to cancer cell-derived CD9+ EVs revealed that the regulation of eleven genes, notably those involved in inflammation, relies on the nuclear translocation of EV-derived biomaterials. Our findings uncover a new cellular pathway used by EVs to reach nuclear compartment.

Analogies Between Cancer-Derived Extracellular Vesicles and Enveloped Viruses with an Emphasis on Human Breast Cancer.

PURPOSE OF REVIEW: Cancer cells utilize extracellular vesicles (EVs) as a means of transferring oncogenic proteins and nucleic acids to other cells to enhance the growth and spread of the tumor. There is an unexpected amount of similarities between these small, membrane-bound particles and enveloped virions, including protein content, physical characteristics (i.e., size and morphology), and mechanisms of entry and exit into target cells. RECENT FINDINGS: This review describes the attributes shared by both cancer-derived EVs, with an emphasis on breast cancer-derived EVs, and enveloped viral particles and discusses the methods by which virions can utilize the EV pathway as a means of transferring viral material and oncogenes to host cells. Additionally, the possible links between human papilloma virus and its influence on the miRNA content of breast cancer-derived EVs are examined. SUMMARY: The rapidly growing field of EVs is allowing investigators from different disciplines to enter uncharted territory. The study of the emerging similarities between cancer-derived EVs and enveloped virions may lead to novel important scientific discoveries.

Breast Cancer-Derived Extracellular Vesicles: Characterization and Contribution to the Metastatic Phenotype.

The study of extracellular vesicles (EVs) in cancer progression is a complex and rapidly evolving field. Whole categories of cellular interactions in cancer which were originally presumed to be due solely to soluble secreted molecules have now evolved to include membrane-enclosed extracellular vesicles (EVs), which include both exosomes and shed microvesicles (MVs), and can contain many of the same molecules as those secreted in soluble form but many different molecules as well. EVs released by cancer cells can transfer mRNA, miRNA, and proteins to different recipient cells within the tumor microenvironment, in both an autocrine and paracrine manner, causing a significant impact on signaling pathways, mRNA transcription, and protein expression. The transfer of EVs to target cells, in turn, supports cancer growth, immunosuppression, and metastasis formation. This review focuses exclusively on breast cancer EVs with an emphasis on breast cancer-derived exosomes, keeping in mind that breast cancer-derived EVs share some common physical properties with EVs of other cancers.

Tetraspanin CD9 determines invasiveness and tumorigenicity of human breast cancer cells.

Interaction of breast cancer cells (BCCs) with stromal components is critical for tumor growth and metastasis. Here, we assessed the role of CD9 in adhesion, migration and invasiveness of BCCs. We used co-cultures of BCCs and bone marrow-derived multipotent mesenchymal stromal cells (MSCs), and analyzed their behavior and morphology by dynamic total internal reflection fluorescence, confocal and scanning electron microscopy. 83, 16 and 10% of contacts between MDA-MB-231 (MDA), MA-11 or MCF-7 cells and MSCs, respectively, resulted in MSC invasion. MDA cells developed long magnupodia, lamellipodia and dorsal microvilli, whereas long microvilli emerged from MA-11 cells. MCF-7 cells displayed large dorsal ruffles. CD9 knockdown and antibody blockage in MDA cells inhibited MSC invasion by 95 and 70%, respectively, suggesting that CD9 is required for this process. Remarkably, CD9-deficient MDA cells displayed significant alteration of their plasma membrane, harboring numerous peripheral and dorsal membrane ruffles instead of intact magnupodium/lamellipodium and microvillus, respectively. Such modification might explain the delayed adhesion, and hence MSC invasion. In agreement with this hypothesis, CD9-knockdown suppressed the metastatic capacity of MDA cells in mouse xenografts. Our data indicate that CD9 is implicated in BCC invasiveness and metastases by cellular mechanisms that involve specific CD9+ plasma membrane protrusions of BCCs.

The nuclear pool of tetraspanin CD9 contributes to mitotic processes in human breast carcinoma.

UNLABELLED: Tetraspanin-29 (CD9) is an integral membrane protein involved in several fundamental cell processes and in cancer metastasis. Here, characterization of a panel of breast cancer cells revealed a nuclear pool of CD9, not present in normal human mammary epithelial cells. Antibody binding to surface CD9 of breast cancer cells resulted in increased nuclear CD9 fluorescence. CD9 was also found, along with a plasma membrane-associated pool, in the nuclei of all primary ductal breast carcinoma patient specimens analyzed. In all patients, about 40% of the total CD9 cellular fluorescence was nuclear. CD9 colocalized at the nuclear level with CEP97, a protein implicated in centrosome function, and with the IGSF8, an established CD9 partner in the plasma membrane. Co-immunoprecipitation of CEP97 and IGSF8 with CD9 was shown in nuclear extracts from breast cancer cells expressing a CD9-GFP fusion protein. However, by fluorescence resonance energy transfer (FRET) analysis, no direct binding of CD9 with either protein was observed, suggesting that CD9 is part of a larger nuclear protein complex. CD9 depletion or exposure of parental breast cancer cells to anti-CD9 mAb resulted in polynucleation and multipolar mitoses. These data indicate that the nuclear CD9 pool has an important role in the mitotic process. IMPLICATIONS: The discovery of a nuclear pool of CD9 has prognostic and/or therapeutic potential for patients with ductal carcinoma of the breast.