Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

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Effects of music therapy on occupational stress and burn-out risk of operating room staff

The operating theatre staff is exposed to various constraints such as excessive working hours, severe medical conditions and dreadful consequences in case of malpractice. These working conditions may lead to high and chronic levels of stress, which can interfere with medical staff well-being and patients quality of care. The aim of this study is to assess the impact of music therapy on stress levels and burn-out risk on the operating room staff. This is a pre-experimental study including the operating rooms staff of urology and maxillofacial surgery in the academic hospital of Sahloul Sousse (Tunisia) over a period of six weeks. The study consisted of three phases. The first was an initial assessment of stress level with a predefined survey. The second included three music therapy sessions per day over one month. The third was an immediate stress level reassessment following the intervention. Stress levels were evaluated using the Perceived Stress Scale version PSS-10 and the Maslach Burnout Inventory. The overall response rate was 73.9%.The average age of the study population was 37.8 ± 7.7 years with a female predominance (64.7%). After the music therapy program, Perceived Stress Scale average score decreased from 22 ± 8.9 to 16 ± 7.9 (p = 0.006). Concerning the burnout, only the average score of emotional exhaustion decreased signifi- cantly from 27 ± 10.8 to 19.2 ± 9.5 (p = 0.004). Music therapy is an innovative approach that seems to reduce operating theatre staff stress. It must be considered as a non pharmacological, simple, economic and non invasive preventive tool

Pilocytic astrocytoma of the optic pathway: a tumour deriving from radial glia cells with a specific gene signature

International audienc

Correction: The natural compound Jatrophone interferes with Wnt/β-catenin signaling and inhibits proliferation and EMT in human triple-negative breast cancer.

[This corrects the article DOI: 10.1371/journal.pone.0189864.]

Simultaneous multi-organ metastases from chemo-resistant triple-negative breast cancer are prevented by interfering with WNT-signaling

Triple-negative breast cancers (TNBCs), which lack specific targeted therapy options, evolve into highly chemo-resistant tumors that metastasize to multiple organs simultaneously. We have previously shown that TNBCs maintain an activated WNT10B-driven network that drives metastasis. Pharmacologic inhibition by ICG-001 decreases β-catenin-mediated proliferation of multiple TNBC cell lines and TNBC patient-derived xenograft (PDX)-derived cell lines. In vitro, ICG-001 was effective in combination with the conventional cytotoxic chemotherapeutics, cisplatin and doxorubicin, to decrease the proliferation of MDA-MB-231 cells. In contrast, in TNBC PDX-derived cells doxorubicin plus ICG-001 was synergistic, while pairing with cisplatin was not as effective. Mechanistically, cytotoxicity induced by doxorubicin, but not cisplatin, with ICG-001 was associated with increased cleavage of PARP-1 in the PDX cells only. In vivo, MDA-MB-231 and TNBC PDX orthotopic primary tumors initiated de novo simultaneous multi-organ metastases, including bone metastases. WNT monotherapy blocked multi-organ metastases as measured by luciferase imaging and histology. The loss of expression of the WNT10B/β-catenin direct targets HMGA2, EZH2, AXIN2, MYC, PCNA, CCND1, transcriptionally active β-catenin, SNAIL and vimentin both in vitro and in vivo in the primary tumors mechanistically explains loss of multi-organ metastases. WNT monotherapy induced VEGFA expression in both tumor model systems, whereas increased CD31 was observed only in the MDA-MB-231 tumors. Moreover, WNT-inhibition sensitized the anticancer response of the TNBC PDX model to doxorubicin, preventing simultaneous metastases to the liver and ovaries, as well as to bone. Our data demonstrate that WNT-inhibition sensitizes TNBC to anthracyclines and treats multi-organ metastases of TNBC

The WNT10B network is associated with survival and metastases in chemoresistant triple-negative breast cancer

Triple-negative breast cancer (TNBC) commonly develops resistance to chemotherapy, yet markers predictive of chemoresistance in this disease are lacking. Here, we define WNT10B-dependent biomarkers for β-CATENIN/HMGA2/EZH2 signaling predictive of reduced relapse-free survival. Concordant expression of HMGA2 and EZH2 proteins is observed in MMTV-Wnt10bLacZ transgenic mice during metastasis, and Hmga2 haploinsufficiency decreased EZH2 protein expression, repressing lung metastasis. A novel autoregulatory loop interdependent on HMGA2 and EZH2 expression is essential for β-CATENIN/TCF-4/LEF-1 transcription. Mechanistically, both HMGA2 and EZH2 displaced Groucho/TLE1 from TCF-4 and served as gatekeepers for K49 acetylation on β-CATENIN, which is essential for transcription. In addition, we discovered that HMGA2-EZH2 interacts with the PRC2 complex. Absence of HMGA2 or EZH2 expression or chemical inhibition of Wnt signaling in a chemoresistant patient-derived xenograft (PDX) model of TNBC abolished visceral metastasis, repressing AXIN2, MYC, EZH2, and HMGA2 expression in vivo. Combinatorial therapy of a WNT inhibitor with doxorubicin synergistically activated apoptosis in vitro, resensitized PDX-derived cells to doxorubicin, and repressed lung metastasis in vivo. We propose that targeting the WNT10B biomarker network will provide improved outcomes for TNBC. SIGNIFICANCE: These findings reveal targeting the WNT signaling pathway as a potential therapeutic strategy in triple-negative breast cancer.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/5/982/F1.large.jpg