Carrilloritchie7636

BACKGROUND General practitioners' (GPs) play a central role in facilitating end-of-life discussions with older patients nearing the end-of-life. However, prognostic uncertainty of time to death is one important barrier to initiation of these discussions. OBJECTIVE To explore GPs' perceptions of the feasibility and acceptability of a risk prediction checklist to identify older patients in their last 12 months of life and describe perceived barriers and facilitators for implementing end-of-life planning. METHODS Qualitative, semi-structured interviews were conducted with 15 GPs practising in metropolitan locations in New South Wales and Queensland between May and June 2019. Data were analysed thematically. RESULTS Eight themes emerged accessibility and implementation of the checklist, uncertainty around checklist's accuracy and usefulness, time of the checklist, checklist as a potential prompt for end-of-life conversations, end-of-life conversations not an easy topic, end-of-life conversation requires time and effort, uncertainty in identifying end-of-life patients and limited community literacy on end-of-life. Most participants welcomed a risk prediction checklist in routine practice if assured of its accuracy in identifying which patients were nearing end-of-life. CONCLUSIONS Most participating GPs saw the value in risk assessment and end-of-life planning. Many emphasized the need for appropriate support, tools and funding for prognostic screening and end-of-life planning for this to become routine in general practice. learn more Well validated risk prediction tools are needed to increase clinician confidence in identifying risk of death to support end-of-life care planning. © The Author(s) 2020. Published by Oxford University Press. All rights reserved.For permissions, please e-mail journals.permissions@oup.com.Spinal cord injury (SCI) is a neurological disease commonly caused by traumatic events on spinal cords. MiRNA-92a-3p is reported to be down-regulated after SCI. Our study investigated the effects of up-regulated miR-92a-3p on SCI and the underlying mechanisms. SCI mice model was established to evaluate the functional recovery of hindlimbs of mice through open-field locomotion and scored by Basso, Beattie, and Bresnahan (BBB) locomotion scale. Apoptosis of spinal cord cells was determined by flow cytometry. The effects of miR-92a-3p on SCI were detected by intrathecally injecting miR-92a-3p agomiR (agomiR-92) into the mice prior to the establishment of SCI. Phosphatase and tensin homolog (PTEN) was predicted as a target of miR-29a-3p by TargetScan. We further assessed the effects of agomiR-92 or/and overexpressed PTEN on apoptosis rates and apoptotic protein expressions in SCI mice. Moreover, the activation of protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling was determined by Western blot. The results showed that compared with the sham-operated mice, SCI mice had much lower BBB scores, and their apoptosis rate of spinal cord cells was significantly increased. After SCI, the expression of miR-92a-3p was down-regulated, and increased expression of miR-92a-3p induced by agomiR-92 further significantly increased the BBB score and decreased apoptosis. PTEN was specifically targeted by miR-92a-3p. In addition, the phosphorylation levels of Akt and mTOR were up-regulated under the treatment of agomiR-92. Our data demonstrated that the neuro-protective effects of miR-92a-3p on spinal cords after SCI were highly associated with the activation of the PTEN/AKT/mTOR pathway. Copyright 2020 The Author(s).The Gremlin-2 (GREM2) plays crucial roles in modulating bone homeostasis through the bone morphogenetic protein-2 pathway. However, GREM2 gene variants in osteoporosis were less frequent in a Chinese population. Therefore, the present study recruited 310 patients with osteoporosis and 339 healthy postmenopausal women to assess the correlation of GREM2 gene polymorphisms with the risk of osteoporosis. Polymerase chain reaction (PCR) and Sanger sequencing were utilized to genotype samples. The results showed that GREM2 gene rs4454537, not rs11588607, polymorphism was significantly associated with an increased risk of osteoporosis in postmenopausal women. Moreover, stratified analyses indicated a significant association between rs4454537 polymorphisms and body mass index of less then 25 kg/m2. Additionally, the association between GREM2 rs4454537 polymorphism and clinical characteristics was assessed, which showed that this locus decreased the bone mineral density (BMD) in postmenopausal osteoporotic individuals. Furthermore, individuals with CC genotype appeared to have a higher GREM2 expression compared with those bearing the TT genotype of rs4454537 polymorphism. However, the genotype distribution of rs4454537 polymorphism showed no statistical difference between osteoporotic patients as a function of fracture status. In summary, GREM2 rs4454537 polymorphism decreases BMD and increases osteoporotic risk in postmenopausal women. © 2020 The Author(s).Osteosarcoma and chondrosarcoma are sarcomas of the bone and the cartilage that are primarily treated by surgical intervention combined with high toxicity chemotherapy. In search of alternative metabolic approaches to address the challenges in treating bone sarcomas, we assessed the growth dependence of these cancers on leucine, one of the branched chain amino acids (BCAAs), and BCAA metabolism. Tumor biopsies from bone sarcoma patients revealed differential expression of BCAA metabolic enzymes. The cytosolic branched chain aminotransferase (BCATc) that is commonly overexpressed in cancer cells, was downregulated in chondrosarcoma (SW1353) in contrast to osteosarcoma (143B) cells that expressed both BCATc and its mitochondrial isoform BCATm. Treating SW1353cells with gabapentin, a selective inhibitor of BCATc, further revealed that these cells failed to respond to gabapentin. Application of the structural analog of leucine, N-acetyl-leucine amide (NALA) to disrupt leucine uptake, indicated that all bone sarcoma cells used leucine to support their energy metabolism and biosynthetic demands. This was evident from the increased activity of the energy sensor AMP-activated protein kinase (AMPK), downregulation of complex 1 of the mammalian target of rapamycin (mTORC1), and reduced cell viability in response to NALA.  The observed changes were most profound in the 143B cells, which appeared highly dependent on cytosolic and mitochondrial BCAA metabolism. This study thus demonstrates that bone sarcomas rely on leucine and BCAA metabolism for energy and growth; however, the differential expression of BCAA enzymes and the presence of other carbon sources may dictate how efficiently these cancer cells take advantage of BCAA metabolism. Copyright 2020 The Author(s).