Osteoimmunopathology in HIV/AIDS: A Translational Evidence-Based Perspective

Infection with the human immunodeficiency virus-1 (HIV) and the resulting acquired immune deficiency syndrome (AIDS) alter not only cellular immune regulation but also the bone metabolism. Since cellular immunity and bone metabolism are intimately intertwined in the osteoimmune network, it is to be expected that bone metabolism is also affected in patients with HIV/AIDS. The concerted evidence points convincingly toward impaired activity of osteoblasts and increased activity of osteoclasts in patients with HIV/AIDS, leading to a significant increase in the prevalence of osteoporosis. Research attributes these outcomes in part at least to the ART, PI, and HAART therapies endured by these patients. We review and discuss these lines of evidence from the perspective of translational clinically relevant complex systematic reviews for comparative effectiveness analysis and evidence-based intervention on a global scale

HER-2 overexpression differentially alters transforming growth factor-β responses in luminal versus mesenchymal human breast cancer cells

INTRODUCTION: Amplification of the HER-2 receptor tyrosine kinase has been implicated in the pathogenesis and aggressive behavior of approximately 25% of invasive human breast cancers. Clinical and experimental evidence suggest that aberrant HER-2 signaling contributes to tumor initiation and disease progression. Transforming growth factor beta (TGF-β) is the dominant factor opposing growth stimulatory factors and early oncogene activation in many tissues, including the mammary gland. Thus, to better understand the mechanisms by which HER-2 overexpression promotes the early stages of breast cancer, we directly assayed the cellular and molecular effects of TGF-β1 on breast cancer cells in the presence or absence of overexpressed HER-2. METHODS: Cell proliferation assays were used to determine the effect of TGF-β on the growth of breast cancer cells with normal or high level expression of HER-2. Affymetrix microarrays combined with Northern and western blot analysis were used to monitor the transcriptional responses to exogenous TGF-β1 in luminal and mesenchymal-like breast cancer cells. The activity of the core TGF-β signaling pathway was assessed using TGF-β1 binding assays, phospho-specific Smad antibodies, immunofluorescent staining of Smad and Smad DNA binding assays. RESULTS: We demonstrate that cells engineered to over-express HER-2 are resistant to the anti-proliferative effect of TGF-β1. HER-2 overexpression profoundly diminishes the transcriptional responses induced by TGF-β in the luminal MCF-7 breast cancer cell line and prevents target gene induction by a novel mechanism that does not involve the abrogation of Smad nuclear accumulation, DNA binding or changes in c-myc repression. Conversely, HER-2 overexpression in the context of the mesenchymal MDA-MB-231 breast cell line potentiated the TGF-β induced pro-invasive and pro-metastatic gene signature. CONCLUSION: HER-2 overexpression promotes the growth and malignancy of mammary epithelial cells, in part, by conferring resistance to the growth inhibitory effects of TGF-β. In contrast, HER-2 and TGF-β signaling pathways can cooperate to promote especially aggressive disease behavior in the context of a highly invasive breast tumor model

The phenomenon of killing in the eyes of Filipino police officers: A qualitative study

This phenomenological study will follows a transcendental approach that will focus on the experience of killing criminals by Filipino police officers. A transcendental approach is the use of the own meaning and interpretation of the police officers regarding their experience of killing. The police officers are from different city districts from Metro Manila. The participants are composed of 7 male police officers with a age range of 25-40 years old. The researchers conducted an interview that followed an open-ended set of questions that allowed the participants to further discuss their experience. There are three major themes formed of what the police officers experienced before, during, and after the act of killing. The themes are as follows: 1.) Internal Conflict, 2.) Preservation of image 3.) Psychological Health Concerns, and 4.) Police Culture and Identity. These three major themes encompass the experience of the police officers in killing criminals. Following a transcendental approach, this research produced the essence of the experience of killing criminals for the police officers

‘An exploration of the levels of clinical autonomy of advanced nurse practitioners’: A narrative literature review

Aims and Objectives The aims of the review are to synthesise current evidence about advanced nurse practitioner clinical autonomy and consider how this may inform clinical practice and research. Background Clinical autonomy is one of the cornerstones of advanced nursing practice globally, yet there is limited synthesis of clinical autonomy in the literature. Design This is a narrative literature review. Data sources The databases Cumulative Index to Nursing and Allied Health Literature, EBSCO host, Cochrane Library, CINAHL and MEDLINE were searched for publications between 2005 and 2020 inclusive. Review methods A systematic approach was used to analyse the literature reviewed. Two reviewers undertook quality appraisal. Results Nineteen articles were selected. Four major themes emerged: (1) ‘ANP Stepping Up’—moving into and accepting advanced nursing practice roles and clinical responsibilities; (2) ‘ANP Living It’—ANPs' ability to act independently including an understanding of task mastery and self-determination; (3) ‘ANP Bounce-back ability’—depicted in challenges that threaten their ability to practice clinically autonomously; (4) ‘ANP Setting in Motion’—indirect care activities and service-level improvements. Conclusion A clearer understanding of advanced nurse practitioner clinical autonomy could help develop more in-depth knowledge. Research of advanced nurse practitioners' clinical autonomy would improve full utilisation in clinical practice