52 research outputs found

    Work related musculoskeletal injuries sustained by Australian osteopaths: Qualitative analysis of effects on practitioner health, clinical practice, and patient care

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    Background: There is limited literature that explores the experiences of osteopaths injured while engaging in clinical practice. Evidence from other similar health professions has described the numerous effects of work-related musculoskeletal injuries (WRMI). Work-related musculoskeletal injury refers to trauma to joints, ligaments, muscles and tendons resulting from injury sustained while undertaking work duties. This research aimed to gain a contextualised understanding of the experiences of osteopaths who have sustained a work-related musculoskeletal injury while performing clinical practice. Method: This research used a descriptive qualitative design. Participants were recruited as part of a larger cross-sectional study. Thirteen Australian osteopaths who had sustained a work-related musculoskeletal injury consented to participate in semi-structured interviews during May and June 2016. Thematic analysis was used to elicit important themes from the interview transcripts that had been recorded and transcribed verbatim. The qualitative accounts provided by the participants were coded for the impacts of their injuries on work, home life and leisure activities. Results: The participants provided detailed, contextual information about their injuries, including the contributing factors and the experience of living with a WRMI. The findings indicate that injured osteopaths often continue working because of financial commitments and their dedication to patient care. The participants offered insights into the challenges they faced due to the injury and the management strategies they used to deal with the impact on their work and personal life. The injuries were mostly unreported, the burden being carried by the participants and their families. Conclusion: This is the first research that explores the experiences of osteopaths who have sustained a WRMI. We anticipate that this research will encourage a broad and constructive discussion within the profession of the issues associated with WRMIs, including risk minimisation and injury prevention. Further research is warranted to understand the relationship between osteopaths training in ergonomics and injury prevention. This would lead to the development of guidelines and educational curricula addressing safe work for osteopaths. © 2017 The Author(s)

    Work related musculoskeletal injuries sustained by Australian osteopaths: qualitative analysis of effects on practitioner health, clinical practice, and patient care.

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    BACKGROUND: There is limited literature that explores the experiences of osteopaths injured while engaging in clinical practice. Evidence from other similar health professions has described the numerous effects of work-related musculoskeletal injuries (WRMI). Work-related musculoskeletal injury refers to trauma to joints, ligaments, muscles and tendons resulting from injury sustained while undertaking work duties. This research aimed to gain a contextualised understanding of the experiences of osteopaths who have sustained a work-related musculoskeletal injury while performing clinical practice. METHOD: This research used a descriptive qualitative design. Participants were recruited as part of a larger cross-sectional study. Thirteen Australian osteopaths who had sustained a work-related musculoskeletal injury consented to participate in semi-structured interviews during May and June 2016. Thematic analysis was used to elicit important themes from the interview transcripts that had been recorded and transcribed verbatim. The qualitative accounts provided by the participants were coded for the impacts of their injuries on work, home life and leisure activities. RESULTS: The participants provided detailed, contextual information about their injuries, including the contributing factors and the experience of living with a WRMI. The findings indicate that injured osteopaths often continue working because of financial commitments and their dedication to patient care. The participants offered insights into the challenges they faced due to the injury and the management strategies they used to deal with the impact on their work and personal life. The injuries were mostly unreported, the burden being carried by the participants and their families. CONCLUSION: This is the first research that explores the experiences of osteopaths who have sustained a WRMI. We anticipate that this research will encourage a broad and constructive discussion within the profession of the issues associated with WRMIs, including risk minimisation and injury prevention. Further research is warranted to understand the relationship between osteopaths training in ergonomics and injury prevention. This would lead to the development of guidelines and educational curricula addressing safe work for osteopaths

    A comprehensive review of the current and future role of the microbiome in pancreatic ductal adenocarcinoma

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    Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second most common cause of cancer death in the USA by 2030, yet progress continues to lag behind that of other cancers, with only 9% of patients surviving beyond 5 years. Long-term survivorship of PDAC and improving survival has, until recently, escaped our understanding. One recent frontier in the cancer field is the microbiome. The microbiome collectively refers to the extensive community of bacteria and fungi that colonise us. It is estimated that there is one to ten prokaryotic cells for each human somatic cell, yet, the significance of this community in health and disease has, until recently, been overlooked. This review examines the role of the microbiome in PDAC and how it may alter survival outcomes. We evaluate the possibility of employing microbiomic signatures as biomarkers of PDAC. Ultimately this review analyses whether the microbiome may be amenable to targeting and consequently altering the natural history of PDAC

    B-RAF Mutant Alleles Associated with Langerhans Cell Histiocytosis, a Granulomatous Pediatric Disease

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    Langerhans cell histiocytosis (LCH) features inflammatory granuloma characterised by the presence of CD1a+ dendritic cells or 'LCH cells'. Badalian-Very et al. recently reported the presence of a canonical (V600E)B-RAF mutation in 57% of paraffin-embedded biopsies from LCH granuloma. Here we confirm their findings and report the identification of two novel B-RAF mutations detected in LCH patients.Mutations of B-RAF were observed in granuloma samples from 11 out of 16 patients using 'next generation' pyrosequencing. In 9 cases the mutation identified was (V600E)B-RAF. In 2 cases novel polymorphisms were identified. A somatic (600DLAT)B-RAF insertion mimicked the structural and functional consequences of the (V600E)B-RAF mutant. It destabilized the inactive conformation of the B-RAF kinase and resulted in increased ERK activation in 293 T cells. The (600DLAT)B-RAF and (V600E)B-RAF mutations were found enriched in DNA and mRNA from the CD1a+ fraction of granuloma. They were absent from the blood and monocytes of 58 LCH patients, with a lower threshold of sequencing sensitivity of 1%-2% relative mutation abundance. A novel germ line (T599A)B-RAF mutant allele was detected in one patient, at a relative mutation abundance close to 50% in the LCH granuloma, blood monocytes and lymphocytes. However, (T599A)B-RAF did not destabilize the inactive conformation of the B-RAF kinase, and did not induce increased ERK phosphorylation or C-RAF transactivation.Our data confirmed presence of the (V600E)B-RAF mutation in LCH granuloma of some patients, and identify two novel B-RAF mutations. They indicate that (V600E)B-RAF and (600DLAT)B-RAF mutations are somatic mutants enriched in LCH CD1a(+) cells and absent from the patient blood. Further studies are needed to assess the functional consequences of the germ-line (T599A)B-RAF allele

    Genetic and Structural Basis for Selection of a Ubiquitous T Cell Receptor Deployed in Epstein-Barr Virus Infection

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    Despite the ∼1018 αβ T cell receptor (TCR) structures that can be randomly manufactured by the human thymus, some surface more frequently than others. The pinnacles of this distortion are public TCRs, which exhibit amino acid-identical structures across different individuals. Public TCRs are thought to result from both recombinatorial bias and antigen-driven selection, but the mechanisms that underlie inter-individual TCR sharing are still largely theoretical. To examine this phenomenon at the atomic level, we solved the co-complex structure of one of the most widespread and numerically frequent public TCRs in the human population. The archetypal AS01 public TCR recognizes an immunodominant BMLF1 peptide, derived from the ubiquitous Epstein-Barr virus, bound to HLA-A*0201. The AS01 TCR was observed to dock in a diagonal fashion, grasping the solvent exposed peptide crest with two sets of complementarity-determining region (CDR) loops, and was fastened to the peptide and HLA-A*0201 platform with residue sets found only within TCR genes biased in the public response. Computer simulations of a random V(D)J recombination process demonstrated that both TCRα and TCRβ amino acid sequences could be manufactured easily, thereby explaining the prevalence of this receptor across different individuals. Interestingly, the AS01 TCR was encoded largely by germline DNA, indicating that the TCR loci already comprise gene segments that specifically recognize this ancient pathogen. Such pattern recognition receptor-like traits within the αβ TCR system further blur the boundaries between the adaptive and innate immune systems

    Engrailed-2 (EN2) - a novel biomarker in epithelial ovarian cancer

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    YesBackground: Epithelial ovarian cancer is a common malignancy, with no clinically approved diagnostic biomarker. Engrailed-2 (EN2) is a homeodomain-containing transcription factor, essential during embryological neural development, which is dysregulated in several cancer types. We evaluated the expression of EN2 in Epithelial ovarian cancer, and reviewed its role as a biomarker. Methods: We evaluated 8 Epithelial ovarian cancer cell lines, along with > 100 surgical specimens from the Royal Surrey County Hospital (2009–2014). In total, 108 tumours and 5 normal tissue specimens were collected. En2 mRNA was evaluated by semi-quantitative RT-PCR. Histological sub-type, and platinum-sensitive/−resistant status were compared. Protein expression was assessed in cell lines (immunofluorescence), and in > 150 tumours (immunohistochemistry). Results: En2 mRNA expression was elevated in serous ovarian tumours compared with normal ovary (p < 0.001), particularly in high-grade serous ovarian cancer (p < 0.0001) and in platinum-resistant tumours (p = 0.0232). Median Overall Survival and Progression-free Survival were reduced with high En2 expression (OS = 28 vs 42 months, p = 0.0329; PFS = 8 vs 27 months; p = 0.0004). Positive cytoplasmic EN2 staining was demonstrated in 78% of Epithelial ovarian cancers, with absence in normal ovary. EN2 positive high-grade serous ovarian cancer patients had a shorter PFS (10 vs 17.5 months; p = 0.0103). Conclusion: The EN2 transcription factor is a novel ovarian cancer biomarker. It demonstrates prognostic value, correlating with worse Overall Survival and Progression-free Survival. It is hoped that further work will validate its use as a biomarker, and provide insight into the role of EN2 in the development, progression and spread of ovarian cancer.Oncology Research and Development Departments at the Royal Surrey County Hospital and the University of Surre

    Intravesical Mycobacterium brumae triggers both local and systemic immunotherapeutic responses against bladder cancer in mice

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    The standard treatment for high-risk non-muscle invasive bladder cancer (BC) is the intravesical administration of live Mycobacterium bovis BCG. Previous studies suggest improving this therapy by implementing non-pathogenic mycobacteria, such as Mycobacterium brumae, and/or different vehicles for mycobacteria delivery, such as an olive oil (OO)-in-water emulsion. While it has been established that BCG treatment activates the immune system, the immune effects of altering the mycobacterium and/or the preparation remain unknown. In an orthotopic murine BC model, local immune responses were assessed by measuring immune cells into the bladder and macromolecules in the urine by flow cytometry and multiplexing, respectively. Systemic immune responses were analyzed by quantifying sera anti-mycobacteria antibody levels and recall responses of ex vivo splenocytes cultured with mycobacteria antigens. In both BCG- and M. brumae-treated mice, T, NK, and NKT cell infiltration in the bladder was significantly increased. Notably, T cell infiltration was enhanced in OO-in-water emulsified mycobacteria-treated mice, and urine IL-6 and KC concentrations were elevated. Furthermore, mycobacteria treatment augmented IgG antibody production and splenocyte proliferation, especially in mice receiving OO-in-water emulsified mycobacteria. Our data demonstrate that intravesical mycobacterial treatment triggers local and systemic immune responses, which are most significant when OO-in-water emulsified mycobacteria are used
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