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  • eness of ****. ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.BACKGROUND Critically sized bone defects represent a significant challenge to orthopaedic surgeons worldwide. These defects generally result from severe trauma or resection of a whole large tumour. Autologous bone grafts are the current gold standard for the reconstruction of such defects. However, due to increased patient morbidity and the need for a second operative site, other lines of treatment should be introduced. To find alternative unconventional therapies to manage such defects, bone tissue engineering using a combination of suitable bioactive factors, cells, and biocompatible scaffolds offers a promising new approach for bone regeneration. AIM To evaluate the healing capacity of platelet-rich fibrin (PRF) membranes seeded with allogeneic mesenchymal bone marrow-derived stem cells (BMSCs) on critically sized mandibular defects in a rat model. METHODS Sixty-three Sprague Dawley rats were subjected to bilateral bone defects of critical size in the mandibles created by a 5-mm diameter trephine ***. Ratssized mandibular bone defects in rats was better promoted by PRF membranes seeded with BMSCs than with PRF membranes alone. ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. https://www.selleckchem.com/products/c-176-sting-inhibitor.html All rights reserved.BACKGROUND Keratoconus is a degenerative corneal disease characterised by aberrant cell behaviour and loss of matrix that can result in vision loss. Cells extracted from peripheral corneas can form stem cell-enriched spheres, which have shown the potential to repopulate the normal peripheral corneal stroma in vitro upon sphere implantation but have not been previously studied in keratoconic tissue. AIM To investigate the therapeutic potential of stem cell-enriched spheres formed from extracted peripheral human corneal cells when introduced to keratoconic tissue. METHODS Stem cell-enriched spheres were formed from extracts of normal cadaveric human peripheral corneal cells. These spheres were implanted into incisions created in full thickness and onto the surface of 10 µm thin sections of keratoconic and normal stromal tissues in vitro. Tissue sections were used to maximise use of limited keratoconic tissue available for research. Living cells were stained with Calcein-AM and visualised with stereo and fluores ABCB5, ∆Np63 and p63α were detectable by droplet digital PCR up to D14. Double immunolabelling revealed absence of ABCB5 staining in migrated cells but positive staining of alpha smooth muscle actin (myofibroblast marker) in some migrated cells. Droplet digital PCR showed similar expression patterns of differentiation markers but a reduction in stem cell markers between normal and keratoconic tissue with an increase in stromal cell markers and a reduction in epithelial cell markers, indicating an appropriate response to repopulating diseased tissue. CONCLUSION Cells from implanted stem cell-enriched spheres can repopulate a keratoconic corneal stromal surface in a directed manner and exhibit migratory stromal cell phenotypes. ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.Human induced pluripotent stem cells (hiPSCs) are invaluable resources for producing high-quality differentiated cells in unlimited quantities for both basic research and clinical use. They are particularly useful for studying human disease mechanisms in vitro by making it possible to circumvent the ethical issues of human embryonic stem cell research. However, significant limitations exist when using conventional flat culturing methods especially concerning cell expansion, differentiation efficiency, stability maintenance and multicellular 3D structure establishment, differentiation prediction. Embryoid bodies (EBs), the multicellular aggregates spontaneously generated from iPSCs in the suspension system, might help to address these issues. Due to the unique microenvironment and cell communication in EB structure that a 2D culture system cannot achieve, EBs have been widely applied in hiPSC-derived differentiation and show significant advantages especially in scaling up culturing, differentiation efficiency enhancement, ex vivo simulation, and organoid establishment. EBs can potentially also be used in early prediction of iPSC differentiation capability. To improve the stability and feasibility of EB-mediated differentiation and generate high quality EBs, critical factors including iPSC pluripotency maintenance, generation of uniform morphology using micro-pattern 3D culture systems, proper cellular density inoculation, and EB size control are discussed on the basis of both published data and our own laboratory experiences. Collectively, the production of a large quantity of homogeneous EBs with high quality is important for the stability and feasibility of many PSCs related studies. ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.Poor recovery of neuronal functions is one of the most common healthcare challenges for patients with different types of brain injuries and/or neurodegenerative diseases. Therapeutic interventions face two major challenges (1) How to generate neurons de novo to replenish the neuronal loss caused by injuries or neurodegeneration (restorative neurogenesis) and (2) How to prevent or limit the secondary tissue damage caused by long-term accumulation of glial cells, including microglia, at injury site (glial scar). In contrast to mammals, zebrafish have extensive regenerative capacity in numerous vital organs, including the brain, thus making them a valuable model to improve the existing therapeutic approaches for human brain repair. In response to injuries to the central nervous system (CNS), zebrafish have developed specific mechanisms to promote the recovery of the lost tissue architecture and functionality of the damaged CNS. These mechanisms include the activation of a restorative neurogenic program in a specific set of glial cells (ependymoglia) and the resolution of both the glial scar and inflammation, thus enabling proper neuronal specification and survival. In this review, we discuss the cellular and molecular mechanisms underlying the regenerative ability in the adult zebrafish brain and conclude with the potential applicability of these mechanisms in repair of the mammalian CNS. ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
    eness of MSCs. ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.BACKGROUND Critically sized bone defects represent a significant challenge to orthopaedic surgeons worldwide. These defects generally result from severe trauma or resection of a whole large tumour. Autologous bone grafts are the current gold standard for the reconstruction of such defects. However, due to increased patient morbidity and the need for a second operative site, other lines of treatment should be introduced. To find alternative unconventional therapies to manage such defects, bone tissue engineering using a combination of suitable bioactive factors, cells, and biocompatible scaffolds offers a promising new approach for bone regeneration. AIM To evaluate the healing capacity of platelet-rich fibrin (PRF) membranes seeded with allogeneic mesenchymal bone marrow-derived stem cells (BMSCs) on critically sized mandibular defects in a rat model. METHODS Sixty-three Sprague Dawley rats were subjected to bilateral bone defects of critical size in the mandibles created by a 5-mm diameter trephine bur. Ratssized mandibular bone defects in rats was better promoted by PRF membranes seeded with BMSCs than with PRF membranes alone. ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. https://www.selleckchem.com/products/c-176-sting-inhibitor.html All rights reserved.BACKGROUND Keratoconus is a degenerative corneal disease characterised by aberrant cell behaviour and loss of matrix that can result in vision loss. Cells extracted from peripheral corneas can form stem cell-enriched spheres, which have shown the potential to repopulate the normal peripheral corneal stroma in vitro upon sphere implantation but have not been previously studied in keratoconic tissue. AIM To investigate the therapeutic potential of stem cell-enriched spheres formed from extracted peripheral human corneal cells when introduced to keratoconic tissue. METHODS Stem cell-enriched spheres were formed from extracts of normal cadaveric human peripheral corneal cells. These spheres were implanted into incisions created in full thickness and onto the surface of 10 µm thin sections of keratoconic and normal stromal tissues in vitro. Tissue sections were used to maximise use of limited keratoconic tissue available for research. Living cells were stained with Calcein-AM and visualised with stereo and fluores ABCB5, ∆Np63 and p63α were detectable by droplet digital PCR up to D14. Double immunolabelling revealed absence of ABCB5 staining in migrated cells but positive staining of alpha smooth muscle actin (myofibroblast marker) in some migrated cells. Droplet digital PCR showed similar expression patterns of differentiation markers but a reduction in stem cell markers between normal and keratoconic tissue with an increase in stromal cell markers and a reduction in epithelial cell markers, indicating an appropriate response to repopulating diseased tissue. CONCLUSION Cells from implanted stem cell-enriched spheres can repopulate a keratoconic corneal stromal surface in a directed manner and exhibit migratory stromal cell phenotypes. ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.Human induced pluripotent stem cells (hiPSCs) are invaluable resources for producing high-quality differentiated cells in unlimited quantities for both basic research and clinical use. They are particularly useful for studying human disease mechanisms in vitro by making it possible to circumvent the ethical issues of human embryonic stem cell research. However, significant limitations exist when using conventional flat culturing methods especially concerning cell expansion, differentiation efficiency, stability maintenance and multicellular 3D structure establishment, differentiation prediction. Embryoid bodies (EBs), the multicellular aggregates spontaneously generated from iPSCs in the suspension system, might help to address these issues. Due to the unique microenvironment and cell communication in EB structure that a 2D culture system cannot achieve, EBs have been widely applied in hiPSC-derived differentiation and show significant advantages especially in scaling up culturing, differentiation efficiency enhancement, ex vivo simulation, and organoid establishment. EBs can potentially also be used in early prediction of iPSC differentiation capability. To improve the stability and feasibility of EB-mediated differentiation and generate high quality EBs, critical factors including iPSC pluripotency maintenance, generation of uniform morphology using micro-pattern 3D culture systems, proper cellular density inoculation, and EB size control are discussed on the basis of both published data and our own laboratory experiences. Collectively, the production of a large quantity of homogeneous EBs with high quality is important for the stability and feasibility of many PSCs related studies. ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.Poor recovery of neuronal functions is one of the most common healthcare challenges for patients with different types of brain injuries and/or neurodegenerative diseases. Therapeutic interventions face two major challenges (1) How to generate neurons de novo to replenish the neuronal loss caused by injuries or neurodegeneration (restorative neurogenesis) and (2) How to prevent or limit the secondary tissue damage caused by long-term accumulation of glial cells, including microglia, at injury site (glial scar). In contrast to mammals, zebrafish have extensive regenerative capacity in numerous vital organs, including the brain, thus making them a valuable model to improve the existing therapeutic approaches for human brain repair. In response to injuries to the central nervous system (CNS), zebrafish have developed specific mechanisms to promote the recovery of the lost tissue architecture and functionality of the damaged CNS. These mechanisms include the activation of a restorative neurogenic program in a specific set of glial cells (ependymoglia) and the resolution of both the glial scar and inflammation, thus enabling proper neuronal specification and survival. In this review, we discuss the cellular and molecular mechanisms underlying the regenerative ability in the adult zebrafish brain and conclude with the potential applicability of these mechanisms in repair of the mammalian CNS. ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
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  • INTRODUCTION Orthopaedic injuries affect almost 90% of trauma patients. A previous scoping review and expert consultation survey identified 15 potential low-value intra-hospital practices in the adult orthopaedic trauma population. Limiting the frequency of such practices could reduce adverse events, improve clinical outcomes and free up resources. The aim of this study is to synthesise the evidence on intra-hospital practices for orthopaedic injuries, previously identified as potentially of low value. METHODS AND ANALYSIS We will search Medline, Excerpta Medica Database (EMBASE), the Cochrane Central Register of Controlled Trials and Epistemonikos to identify systematic reviews, randomised controlled trials (RCTs), quasi-RCTs, cohort studies and case-control studies that evaluate selected practices according to a priori PICOS statements (Population-Intervention-Comparator-Outcome-Study design) . We will evaluate the methodological quality for systematic reviews using the Measurement Tool to Assess Systematicll be disseminated in a peer-reviewed journal, at national and international scientific meetings and to healthcare associations. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES There has been increased interest in screening for atrial fibrillation (AF) with commissioned pilot schemes, ongoing large clinical trials and the emergence of inexpensive consumer single-lead ECG devices that can be used to detect AF. This qualitative study aimed to explore patients' views and understanding of AF and AF screening to determine acceptability and inform future recommendations. SETTING A single primary care practice in Hampshire, UK. PARTICIPANTS 15 participants (11 female) were interviewed from primary care who had taken part in an AF screening trial. A semistructured interview guide was used flexibly to enable the interviewer to explore any relevant topics raised by the participants. Interviews were recorded, transcribed verbatim and analysed using inductive thematic analysis. RESULTS Participants generally had an incomplete understanding of AF and conflated it with other heart problems or with raised blood pressure. With regards to potential drawbacks from screening, some participants considered anxiety and the cost of implementation, but none acknowledged potential harms associated with screening such as side effects of anticoagulation treatment or the risk of further investigations. The screening was generally well accepted, and participants were generally in favour of engaging with prolonged screening. CONCLUSIONS Our study highlights that there may be poor understanding (of both the nature of AF and potential negatives of screening) among patients who have been screened for AF. Further work is required to determine if resources including decision aids can address this important knowledge gap and improve clinical informed consent for AF screening. TRIAL REGISTRATION NUMBER ISRCTN 17495003. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.OBJECTIVES To study physician culture in relation to shared decision making (SDM) practice. DESIGN Execution of a hospital ethnography, combined with interviews and a study of clinical guidelines. Ten-week observations by an insider (physician) and an outsider (student medical anthropology) observer. The use of French sociologist Bourdieu's 'Theory of Practice' and its description of habitus, field and capital, as a lens for analysing physician culture. SETTING The gynaecological oncology department of a university hospital in the Netherlands. Observations were executed at meetings, as well as individual patient contacts. PARTICIPANTS Six gynaecological oncologists, three registrars and two specialised nurses. Nine of these professionals were also interviewed. https://www.selleckchem.com/products/cdk2-inhibitor-73.html MAIN OUTCOME MEASURES Common elements in physician habitus that influence the way SDM is being implemented. RESULTS Three main elements of physician habitus were identified. First of all, the 'emphasis on medical evidence' in group meetings as well as i-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES The study was designed to examine the sufficiency of general practitioners' (GPs) follow-up of patients on sick leave, assessed by independent medical evaluators. DESIGN Cross-sectional study SETTING Primary health care in the Western part of Norway. The study reuses data from a randomised controlled trial-the Norwegian independent medical evaluation trial (NIME trial). PARTICIPANTS The intervention group in the NIME trial Sick-listed workers having undergone an independent medical evaluation by an experienced GP at 6 months of unremitting sick leave (n=937; 57% women). In the current study, the participants were distributed into six exposure groups defined by gender and main sick leave diagnoses (women/musculoskeletal, men/musculoskeletal, women/mental, men/mental, women/all other diagnoses and men/all other diagnoses). OUTCOME MEASURE The independent medical evaluators assessment (yes/no) of the sufficiency of the regular GPs follow-up of their sick-listed patients. RESULTS Estimates from generalmployer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.INTRODUCTION Hepatitis B virus (HBV) is a bloodborne virus which can be transmitted via percutaneous and mucocutaneous exposure to infected body fluid. Healthcare workers (HCWs) who are continuously exposed to different body fluids are at an increased risk of contracting and transmitting this virus. It is thus important to evaluate the knowledge and attitude of HCWs towards HBV and the prevalence of HBV infection among them. METHODS This cross-sectional study was carried out between April and September 2017. Overall, 398 HCWs were recruited for this study. Knowledge on the route of HBV transmission and attitude towards HBV were evaluated using a well-structured questionnaire. Hepatitis B surface antigen (HBsAg) positivity was obtained using the Monolisa HBsAg ULTRA kit (Bio-Rad). Data were analysed using SPSS V.20. RESULTS Among the HCWs who participated in this study, 338 (84.9%) had heard of HBV, and 269 (67.6%) of them had adequate knowledge on the route of HBV transmission. Medical doctors were the most knowledgeable among biomedical workers and students (76.
    INTRODUCTION Orthopaedic injuries affect almost 90% of trauma patients. A previous scoping review and expert consultation survey identified 15 potential low-value intra-hospital practices in the adult orthopaedic trauma population. Limiting the frequency of such practices could reduce adverse events, improve clinical outcomes and free up resources. The aim of this study is to synthesise the evidence on intra-hospital practices for orthopaedic injuries, previously identified as potentially of low value. METHODS AND ANALYSIS We will search Medline, Excerpta Medica Database (EMBASE), the Cochrane Central Register of Controlled Trials and Epistemonikos to identify systematic reviews, randomised controlled trials (RCTs), quasi-RCTs, cohort studies and case-control studies that evaluate selected practices according to a priori PICOS statements (Population-Intervention-Comparator-Outcome-Study design) . We will evaluate the methodological quality for systematic reviews using the Measurement Tool to Assess Systematicll be disseminated in a peer-reviewed journal, at national and international scientific meetings and to healthcare associations. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES There has been increased interest in screening for atrial fibrillation (AF) with commissioned pilot schemes, ongoing large clinical trials and the emergence of inexpensive consumer single-lead ECG devices that can be used to detect AF. This qualitative study aimed to explore patients' views and understanding of AF and AF screening to determine acceptability and inform future recommendations. SETTING A single primary care practice in Hampshire, UK. PARTICIPANTS 15 participants (11 female) were interviewed from primary care who had taken part in an AF screening trial. A semistructured interview guide was used flexibly to enable the interviewer to explore any relevant topics raised by the participants. Interviews were recorded, transcribed verbatim and analysed using inductive thematic analysis. RESULTS Participants generally had an incomplete understanding of AF and conflated it with other heart problems or with raised blood pressure. With regards to potential drawbacks from screening, some participants considered anxiety and the cost of implementation, but none acknowledged potential harms associated with screening such as side effects of anticoagulation treatment or the risk of further investigations. The screening was generally well accepted, and participants were generally in favour of engaging with prolonged screening. CONCLUSIONS Our study highlights that there may be poor understanding (of both the nature of AF and potential negatives of screening) among patients who have been screened for AF. Further work is required to determine if resources including decision aids can address this important knowledge gap and improve clinical informed consent for AF screening. TRIAL REGISTRATION NUMBER ISRCTN 17495003. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.OBJECTIVES To study physician culture in relation to shared decision making (SDM) practice. DESIGN Execution of a hospital ethnography, combined with interviews and a study of clinical guidelines. Ten-week observations by an insider (physician) and an outsider (student medical anthropology) observer. The use of French sociologist Bourdieu's 'Theory of Practice' and its description of habitus, field and capital, as a lens for analysing physician culture. SETTING The gynaecological oncology department of a university hospital in the Netherlands. Observations were executed at meetings, as well as individual patient contacts. PARTICIPANTS Six gynaecological oncologists, three registrars and two specialised nurses. Nine of these professionals were also interviewed. https://www.selleckchem.com/products/cdk2-inhibitor-73.html MAIN OUTCOME MEASURES Common elements in physician habitus that influence the way SDM is being implemented. RESULTS Three main elements of physician habitus were identified. First of all, the 'emphasis on medical evidence' in group meetings as well as i-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES The study was designed to examine the sufficiency of general practitioners' (GPs) follow-up of patients on sick leave, assessed by independent medical evaluators. DESIGN Cross-sectional study SETTING Primary health care in the Western part of Norway. The study reuses data from a randomised controlled trial-the Norwegian independent medical evaluation trial (NIME trial). PARTICIPANTS The intervention group in the NIME trial Sick-listed workers having undergone an independent medical evaluation by an experienced GP at 6 months of unremitting sick leave (n=937; 57% women). In the current study, the participants were distributed into six exposure groups defined by gender and main sick leave diagnoses (women/musculoskeletal, men/musculoskeletal, women/mental, men/mental, women/all other diagnoses and men/all other diagnoses). OUTCOME MEASURE The independent medical evaluators assessment (yes/no) of the sufficiency of the regular GPs follow-up of their sick-listed patients. RESULTS Estimates from generalmployer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.INTRODUCTION Hepatitis B virus (HBV) is a bloodborne virus which can be transmitted via percutaneous and mucocutaneous exposure to infected body fluid. Healthcare workers (HCWs) who are continuously exposed to different body fluids are at an increased risk of contracting and transmitting this virus. It is thus important to evaluate the knowledge and attitude of HCWs towards HBV and the prevalence of HBV infection among them. METHODS This cross-sectional study was carried out between April and September 2017. Overall, 398 HCWs were recruited for this study. Knowledge on the route of HBV transmission and attitude towards HBV were evaluated using a well-structured questionnaire. Hepatitis B surface antigen (HBsAg) positivity was obtained using the Monolisa HBsAg ULTRA kit (Bio-Rad). Data were analysed using SPSS V.20. RESULTS Among the HCWs who participated in this study, 338 (84.9%) had heard of HBV, and 269 (67.6%) of them had adequate knowledge on the route of HBV transmission. Medical doctors were the most knowledgeable among biomedical workers and students (76.
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