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Author Basso, C.; Garcia da Rosa, E.; Lairihoy, R.; Caffera, R.M.; Roche, I.; Gonzalez, C.; da Rosa, R.; Gularte, A.; Alfonso-Sierra, E.; Petzold, M.; Kroeger, A.; Sommerfeld, J. url  doi
openurl 
  Title Scaling Up of an Innovative Intervention to Reduce Risk of Dengue, Chikungunya, and Zika Transmission in Uruguay in the Framework of an Intersectoral Approach with and without Community Participation Type Journal Article
  Year 2017 Publication The American Journal of Tropical Medicine and Hygiene Abbreviated Journal Am J Trop Med Hyg  
  Volume Issue Pages  
  Keywords  
  Abstract To contribute to the prevention of dengue, chikungunya, and Zika, a process of scaling up an innovative intervention to reduce Aedes aegypti habitats, was carried out in the city of Salto (Uruguay) based on a transdisciplinary analysis of the eco-bio-social determinants. The intervention in one-third of the city included the distributions of plastic bags for all households to collect all discarded water containers that were recollected by the Ministry of Health and the Municipality vector control services. The results were evaluated in 20 randomly assigned clusters of 100 households each, in the intervention and control arm. The intervention resulted in a significantly larger decrease in the number of pupae per person index (as a proxy for adult vector abundance) than the corresponding decrease in the control areas (both areas decreased by winter effects). The reduction of intervention costs (“incremental costs”) in relation to routine vector control activities was 46%. Community participation increased the collaboration with the intervention program considerably (from 48% of bags handed back out of the total of bags delivered to 59% of bags handed back). Although the costs increased by 26% compared with intervention without community participation, the acceptability of actions by residents increased from 66% to 78%.  
  Address Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization (WHO), Geneva, Switzerland  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN (up) 0002-9637 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28820690 Approved no  
  Call Number ref @ user @ Serial 97631  
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Author Cole, D.C.; Giordano, C.R.; Vasilopoulos, T.; Fahy, B.G. url  doi
openurl 
  Title Resident Physicians Improve Nontechnical Skills When on Operating Room Management and Leadership Rotation Type Journal Article
  Year 2017 Publication Anesthesia and Analgesia Abbreviated Journal Anesth Analg  
  Volume 124 Issue 1 Pages 300-307  
  Keywords  
  Abstract BACKGROUND: Anesthesiology residency primarily emphasizes the development of medical knowledge and technical skills. Yet, nontechnical skills (NTS) are also vital to successful clinical practice. Elements of NTS are communication, teamwork, situational awareness, and decision making. METHODS: The first 10 consecutive senior residents who chose to participate in this 2-week elective rotation of operating room (OR) management and leadership training were enrolled in this study, which spanned from March 2013 to March 2015. Each resident served as the anesthesiology officer of the day (AOD) and was tasked with coordinating OR assignments, managing care for 2 to 4 ORs, and being on call for the trauma OR; all residents were supervised by an attending AOD. Leadership and NTS techniques were taught via a standardized curriculum consisting of leadership and team training articles, crisis management text, and daily debriefings. Resident self-ratings and attending AOD and charge nurse raters used the Anaesthetists' Non-Technical Skills (ANTS) scoring system, which involved task management, situational awareness, teamwork, and decision making. For each of the 10 residents in their third year of clinical anesthesiology training (CA-3) who participated in this elective rotation, there were 14 items that required feedback from resident self-assessment and OR raters, including the daily attending AOD and charge nurse. Results for each of the items on the questionnaire were compared between the beginning and the end of the rotation with the Wilcoxon signed-rank test for matched samples. Comparisons were run separately for attending AOD and charge nurse assessments and resident self-assessments. Scaled rankings were analyzed for the Kendall coefficient of concordance (omega) for rater agreement with associated chi and P value. RESULTS: Common themes identified by the residents during debriefings were recurrence of challenging situations and the skills residents needed to instruct and manage clinical teams. For attending AOD and charge nurse assessments, resident performance of NTS improved from the beginning to the end of the rotation on 12 of the 14 NTS items (P < .05), whereas resident self-assessment improved on 3 NTS items (P < .05). Interrater reliability (across the charge nurse, resident, and AOD raters) ranged from omega = .36 to .61 at the beginning of the rotation and omega = .27 to .70 at the end of the rotation. CONCLUSIONS: This rotation allowed for teaching and resident assessment to occur in a way that facilitated resident education in several of the skills required to meet specific milestones. Resident physicians are able to foster NTS and build a framework for clinical leadership when completing a 2-week senior elective as an OR manager.  
  Address From the Department of Anesthesiology, University of Florida, College of Medicine, Gainesville, Fla  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN (up) 0003-2999 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27918336 Approved no  
  Call Number ref @ user @ Serial 95061  
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Author Hira, V.V.V.; Verbovsek, U.; Breznik, B.; Srdic, M.; Novinec, M.; Kakar, H.; Wormer, J.; der Swaan, B.V.; Lenarcic, B.; Juliano, L.; Mehta, S.; Van Noorden, C.J.F.; Lah, T.T. url  doi
openurl 
  Title Cathepsin K cleavage of SDF-1alpha inhibits its chemotactic activity towards glioblastoma stem-like cells Type Journal Article
  Year 2017 Publication Biochimica et Biophysica Acta Abbreviated Journal Biochim Biophys Acta  
  Volume 1864 Issue 3 Pages 594-603  
  Keywords Amino Acid Sequence; Cathepsin K/genetics/*metabolism; Cell Line, Tumor; Chemokine CXCL12/chemistry/genetics/*metabolism; Chemotaxis; Gene Expression; Heterocyclic Compounds/pharmacology; Humans; Neoplastic Stem Cells/*metabolism/pathology; Neuroglia/*metabolism/pathology; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Proteolysis; Receptors, CXCR/genetics/metabolism; Receptors, CXCR4/antagonists & inhibitors/genetics/*metabolism; Stem Cell Niche/genetics; *Cathepsin K; *Glioma stem-like cells; *Niche; *Stromal-derived factor-1alpha  
  Abstract Glioblastoma (GBM) is the most aggressive primary brain tumor with poor patient survival that is at least partly caused by malignant and therapy-resistant glioma stem-like cells (GSLCs) that are protected in GSLC niches. Previously, we have shown that the chemo-attractant stromal-derived factor-1alpha (SDF-1alpha), its C-X-C receptor type 4 (CXCR4) and the cysteine protease cathepsin K (CatK) are localized in GSLC niches in glioblastoma. Here, we investigated whether SDF-1alpha is a niche factor that through its interactions with CXCR4 and/or its second receptor CXCR7 on GSLCs facilitates their homing to niches. Furthermore, we aimed to prove that SDF-1alpha cleavage by CatK inactivates SDF-1alpha and inhibits the invasion of GSLCs. We performed mass spectrometric analysis of cleavage products of SDF-1alpha after proteolysis by CatK. We demonstrated that CatK cleaves SDF-1alpha at 3 sites in the N-terminus, which is the region of SDF-1alpha that binds to its receptors. Confocal imaging of human GBM tissue sections confirmed co-localization of SDF-1alpha and CatK in GSLC niches. In accordance, 2D and 3D invasion experiments using CXCR4/CXCR7-expressing GSLCs and GBM cells showed that SDF-1alpha had chemotactic activity whereas CatK cleavage products of SDF-1alpha did not. Besides, CXCR4 inhibitor plerixafor inhibited invasion of CXCR4/CXCR7-expressing GSLCs. In conclusion, CatK can cleave and inactivate SDF-1alpha. This implies that CatK activity facilitates migration of GSLCs out of niches. We propose that activation of CatK may be a promising strategy to prevent homing of GSLCs in niches and thus render these cells sensitive to chemotherapy and radiation.  
  Address Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Vecna pot 111, 1000 Ljubljana, Slovenia; Jozef Stefan International Postgraduate School, Jamova 39, 1000 Ljubljana, Slovenia; Department of Biochemistry, Faculty of Chemistry and Chemical Engineering, University of Ljubljana, Vecna pot 113, 1000 Ljubljana, Slovenia  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN (up) 0006-3002 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28040478 Approved no  
  Call Number ref @ user @ Serial 96615  
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Author Yin, J.; Oh, Y.T.; Kim, J.-Y.; Kim, S.S.; Choi, E.; Kim, T.H.; Hong, J.H.; Chang, N.; Cho, H.J.; Sa, J.K.; Kim, J.C.; Kwon, H.J.; Park, S.; Lin, W.; Nakano, I.; Gwak, H.-S.; Yoo, H.; Lee, S.-H.; Lee, J.; Kim, J.H.; Kim, S.-Y.; Nam, D.-H.; Park, M.-J.; Park, J.B. url  doi
openurl 
  Title Transglutaminase 2 Inhibition Reverses Mesenchymal Transdifferentiation of Glioma Stem Cells by Regulating C/EBPbeta Signaling Type Journal Article
  Year 2017 Publication Cancer Research Abbreviated Journal Cancer Res  
  Volume 77 Issue 18 Pages 4973-4984  
  Keywords  
  Abstract Necrosis is a hallmark of glioblastoma (GBM) and is responsible for poor prognosis and resistance to conventional therapies. However, the molecular mechanisms underlying necrotic microenvironment-induced malignancy of GBM have not been elucidated. Here, we report that transglutaminase 2 (TGM2) is upregulated in the perinecrotic region of GBM and triggered mesenchymal (MES) transdifferentiation of glioma stem cells (GSC) by regulating master transcription factors (TF), such as C/EBPbeta, TAZ, and STAT3. TGM2 expression was induced by macrophages/microglia-derived cytokines via NF-kappaB activation and further degraded DNA damage-inducible transcript 3 (GADD153) to induce C/EBPbeta expression, resulting in expression of the MES transcriptome. Downregulation of TGM2 decreased sphere-forming ability, tumor size, and radioresistance and survival in a xenograft mouse model through a loss of the MES signature. A TGM2-specific inhibitor GK921 blocked MES transdifferentiation and showed significant therapeutic efficacy in mouse models of GSC. Moreover, TGM2 expression was significantly increased in recurrent MES patients and inversely correlated with patient prognosis. Collectively, our results indicate that TGM2 is a key molecular switch of necrosis-induced MES transdifferentiation and an important therapeutic target for MES GBM. Cancer Res; 77(18); 4973-84. (c)2017 AACR.  
  Address Specific Organs Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang, Korea  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN (up) 0008-5472 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28754668 Approved no  
  Call Number ref @ user @ Serial 96575  
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Author Yan, H.; Romero-Lopez, M.; Benitez, L.I.; Di, K.; Frieboes, H.B.; Hughes, C.C.W.; Bota, D.A.; Lowengrub, J.S. url  doi
openurl 
  Title 3D Mathematical Modeling of Glioblastoma Suggests That Transdifferentiated Vascular Endothelial Cells Mediate Resistance to Current Standard-of-Care Therapy Type Journal Article
  Year 2017 Publication Cancer Research Abbreviated Journal Cancer Res  
  Volume 77 Issue 15 Pages 4171-4184  
  Keywords Brain Neoplasms/*pathology; Cell Transdifferentiation/physiology; Endothelial Cells/*pathology; Glioblastoma/*pathology; Humans; *Models, Theoretical; Neoplastic Stem Cells/*pathology  
  Abstract Glioblastoma (GBM), the most aggressive brain tumor in human patients, is decidedly heterogeneous and highly vascularized. Glioma stem/initiating cells (GSC) are found to play a crucial role by increasing cancer aggressiveness and promoting resistance to therapy. Recently, cross-talk between GSC and vascular endothelial cells has been shown to significantly promote GSC self-renewal and tumor progression. Furthermore, GSC also transdifferentiate into bona fide vascular endothelial cells (GEC), which inherit mutations present in GSC and are resistant to traditional antiangiogenic therapies. Here we use three-dimensional mathematical modeling to investigate GBM progression and response to therapy. The model predicted that GSCs drive invasive fingering and that GEC spontaneously form a network within the hypoxic core, consistent with published experimental findings. Standard-of-care treatments using DNA-targeted therapy (radiation/chemo) together with antiangiogenic therapies reduced GBM tumor size but increased invasiveness. Anti-GEC treatments blocked the GEC support of GSCs and reduced tumor size but led to increased invasiveness. Anti-GSC therapies that promote differentiation or disturb the stem cell niche effectively reduced tumor invasiveness and size, but were ultimately limited in reducing tumor size because GECs maintain GSCs. Our study suggests that a combinatorial regimen targeting the vasculature, GSCs, and GECs, using drugs already approved by the FDA, can reduce both tumor size and invasiveness and could lead to tumor eradication. Cancer Res; 77(15); 4171-84. (c)2017 AACR.  
  Address Center for Complex Biological Systems, University of California, Irvine, California  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN (up) 0008-5472 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28536277 Approved no  
  Call Number ref @ user @ Serial 96585  
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