704 research outputs found

    Temporal Gene Expression Profiling during Rat Femoral Marrow Ablation-Induced Intramembranous Bone Regeneration

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    Enhanced understanding of differential gene expression and biological pathways associated with distinct phases of intramembranous bone regeneration following femoral marrow ablation surgery will improve future advancements regarding osseointegration of joint replacement implants, biomaterials design, and bone tissue engineering. A rat femoral marrow ablation model was performed and genome-wide microarray data were obtained from samples at 1, 3, 5, 7, 10, 14, 28, and 56 days post-ablation, with intact bones serving as controls at Day 0. Bayesian model-based clustering produced eight distinct groups amongst 9,062 significant gene probe sets based on similar temporal expression profiles, which were further categorized into three major temporal classes of increased, variable, and decreased expression. Osteoblastic- and osteoclastic-associated genes were found to be significantly expressed within the increased expression groups. Chondrogenesis was not detected histologically. Adipogenic marker genes were found within variable/decreased expression groups, emphasizing that adipogenesis was inhibited during osteogenesis. Differential biological processes and pathways associated with each major temporal group were identified, and significantly expressed genes involved were visually represented by heat maps. It was determined that the increased expression group exclusively contains genes involved in pathways for matrix metalloproteinases (MMPs), Wnt signaling, TGF-β signaling, and inflammatory pathways. Only the variable expression group contains genes associated with glycolysis and gluconeogenesis, the notch signaling pathway, natural killer cell mediated cytotoxicity, and the B cell receptor signaling pathway. The decreased group exclusively consists of genes involved in heme biosynthesis, the p53 signaling pathway, and the hematopoietic cell lineage. Significant biological pathways and transcription factors expressed at each time point post-ablation were also identified. These data present the first temporal gene expression profiling analysis of the rat genome during intramembranous bone regeneration induced by femoral marrow ablation

    The failure of suicide prevention in primary care: family and GP perspectives - a qualitative study

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    Background Although Primary care is crucial for suicide prevention, clinicians tend to report completed suicides in their care as non-preventable. We aimed to examine systemic inadequacies in suicide prevention from the perspectives of bereaved family members and GPs.Methods Qualitative study of 72 relatives or close friends bereaved by suicide and 19 General Practitioners who have experienced the suicide of patients.Results Relatives highlight failures in detecting symptoms and behavioral changes and the inability of GPs to understand the needs of patients and their social contexts. A perceived overreliance on anti-depressant treatment is a major source of criticism by family members. GPs tend to lack confidence in the recognition and management of suicidal patients, and report structural inadequacies in service provision.Conclusions Mental health and primary care services must find innovative and ethical ways to involve families in the decision-making process for patients at risk of suicide

    Finding Apparent Horizons in Dynamic 3D Numerical Spacetimes

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    We have developed a general method for finding apparent horizons in 3D numerical relativity. Instead of solving for the partial differential equation describing the location of the apparent horizons, we expand the closed 2D surfaces in terms of symmetric trace--free tensors and solve for the expansion coefficients using a minimization procedure. Our method is applied to a number of different spacetimes, including numerically constructed spacetimes containing highly distorted axisymmetric black holes in spherical coordinates, and 3D rotating, and colliding black holes in Cartesian coordinates.Comment: 19 pages, 13 figures, LaTex, to appear in Phys. Rev. D. Minor changes mad

    Sexual behaviour among casual workers in an international nightlife resort: a case control study

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    BACKGROUND: Young holidaymakers report increased sexual risk-taking abroad, yet little is currently known about the sexual behaviour of those who extend time abroad through casual work. METHODS: Information on sexual behaviour was collected via an anonymous questionnaire administered to British bar and nightclub workers in Ibiza (cases, n = 92) and British people visiting Ibiza for holiday purposes only (controls, n = 868). RESULTS: Four in five (80.5%) cases who arrived in Ibiza without a partner had sex during their stay and of these two thirds (65.5%) had unprotected sex. Cases were more likely to report sexual risk-taking in Ibiza than controls and reported greater numbers of sexual partners prior to their visit. However, they had fewer sexual partners per week of stay. CONCLUSION: Casual workers in bars and nightclubs abroad are a key risk group for sexual health and a potential conduit for the international spread of sexually transmitted infections. While they are an important target group for sexual health promotion, appropriately trained they are also ideally placed to deliver sexual health interventions to other young travellers

    A map for successful CCNE accreditation

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    The purpose of this article is to provide nurse educators with recommendations on how to develop the needed structures and processes that lead to accreditation success. We provide a comprehensive list of 28 recommendations, a timeline for completion of tasks, and specific information on how to document the achievement of the four CCNE Standards. The first two recommendations deal with two vital structures that comprise a well-functioning program: an effective committee structure and a robust evaluation plan. Recommendations 3 to 12 concern the process steps for preparing for an accreditation visit and are aligned with a timeline for completion. The remaining recommendations address how to document compliance with each CCNE standard

    Prevalence of frailty and pain in hospitalised cancer patients: Implications for older adult care

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    A hospital-wide point prevalence study investigated frailty and pain in patients with a cancer-related admission. Modifiable factors associated with frailty in people with cancer were determined through logistic regression. Forty-eight patients (19%) with cancer-related admissions were 2.65 times more likely to be frail and 2.12 more likely to have moderate pain. Frailty and pain were highly prevalent among cancer-related admissions, reinforcing the need for frailty screening and importance of pain assessment for patients with cancer

    Update to the study protocol for an implementation-effectiveness trial comparing two education strategies for improving the uptake of noninvasive ventilation in patients with severe COPD exacerbation

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    BACKGROUND: There is strong evidence that noninvasive ventilation (NIV) improves the outcomes of patients hospitalized with severe COPD exacerbation, and NIV is recommended as the first-line therapy for these patients. Yet, several studies have demonstrated substantial variation in NIV use across hospitals, leading to preventable morbidity and mortality. In addition, prior studies suggested that efforts to increase NIV use in COPD need to account for the complex and interdisciplinary nature of NIV delivery and the need for team coordination. Therefore, our initial project aimed to compare two educational strategies: online education (OLE) and interprofessional education (IPE), which targets complex team-based care in NIV delivery. Due to the impact of the COVID-19 pandemic on recruitment and planned intervention, we had made several changes in the study design, statistical analysis, and implementation strategies delivery as outlined in the methods. METHODS: We originally proposed a two-arm, pragmatic, cluster, randomized hybrid implementation-effectiveness trial comparing two education strategies to improve NIV uptake in patients with severe COPD exacerbation in 20 hospitals with a low baseline rate of NIV use. Due to logistical constrains and slow recruitment, we changed the study design to an opened cohort stepped-wedge design with three steps which will allow the institutions to enroll when they are ready to participate. Only the IPE strategy will be implemented, and the education will be provided in an online virtual format. Our primary outcome will be the hospital-level risk-standardized NIV proportion for the period post-IPE training, along with the change in rate from the period prior to training. Aim 1 will compare the change over time of NIV use among patients with COPD in the step-wedged design. Aim 2 will explore the mediators\u27 role (respiratory therapist autonomy and team functionality) on the relationship between the implementation strategies and effectiveness. Finally, in Aim 3, through interviews with providers, we will assess the acceptability and feasibility of the educational training. CONCLUSION: The changes in study design will result in several limitation. Most importantly, the hospitals in the three cohorts are not randomized as they enroll based on their readiness. Second, the delivery of the IPE is virtual, and it is not known if remote education is conducive to team building. However, this study will be among the first to test the impact of IPE in the inpatient setting carefully and may generalize to other interventions directed to seriously ill patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04206735 . Registered on December 20, 2019

    CXC chemokines exhibit bactericidal activity against multidrug-resistant gram-negative pathogens

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    The continued rise and spread of antimicrobial resistance among bacterial pathogens pose a serious challenge to global health. Countering antimicrobial-resistant pathogens requires a multifaceted effort that includes the discovery of novel therapeutic approaches. Here, we establish the capacity of the human CXC chemokines CXCL9 and CXCL10 to kill multidrug-resistant Gram-negative bacteria, including New Delhi metallo-beta-lactamase-1-producing Klebsiella pneumoniae and colistin-resistant members of the family Enterobacteriaceae that harbor the mobile colistin resistance protein MCR-1 and thus possess phosphoethanolamine-modified lipid A. Colistin-resistant K. pneumoniae isolates affected by genetic mutation of the PmrA/PmrB two-component system, a chromosomally encoded regulator of lipopolysaccharide modification, and containing 4-amino-4-deoxy-l-arabinose-modified lipid A were also found to be susceptible to chemokine-mediated antimicrobial activity. However, loss of PhoP/PhoQ autoregulatory control, caused by disruption of the gene encoding the negative regulator MgrB, limited the bactericidal effects of CXCL9 and CXCL10 in a variable, strain-specific manner. Cumulatively, these findings provide mechanistic insight into chemokine-mediated antimicrobial activity, highlight disparities amongst determinants of colistin resistance, and suggest that chemokine-mediated bactericidal effects merit additional investigation as a therapeutic avenue for treating infections caused by multidrug-resistant pathogens
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