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Author Rosager, A.M.; Sorensen, M.D.; Dahlrot, R.H.; Boldt, H.B.; Hansen, S.; Lathia, J.D.; Kristensen, B.W. url  doi
openurl 
  Title Expression and prognostic value of JAM-A in gliomas Type Journal Article
  Year 2017 Publication Journal of Neuro-Oncology Abbreviated Journal J Neurooncol  
  Volume Issue Pages  
  Keywords Astrocytic brain tumors; Glioma; Junctional adhesion molecule-A; Prognosis; Tumor stem cell  
  Abstract Gliomas are among the most lethal cancers, being highly resistant to both chemo- and radiotherapy. The expression of junctional adhesion molecule-A (JAM-A) was recently identified on the surface of stem cell-like brain tumor-initiating cells and suggested to function as a unique glioblastoma niche adhesion factor influencing the tumorigenic potential of brain tumor-initiating cells. We have recently identified high JAM-A expression to be associated with poor outcome in glioblastomas, and our aim was to further investigate the expression of JAM-A in gliomas focusing especially on the prognostic value in WHO grade II and III gliomas. JAM-A protein expression was evaluated by immunohistochemistry and advanced quantitative image analysis with continuous estimates of staining intensity. The JAM-A antibody stained tumor cell membranes and cytoplasm to various extent in different glioma subtypes, and the intensity was higher in glioblastomas than low-grade gliomas. We could not detect an association with overall survival in patients with grade II and III tumors. Double-immunofluorescence stainings in glioblastomas revealed co-expression of JAM-A with CD133, SOX2, nestin, and GFAP in tumor cells as well as some co-expression with the microglial/macrophage marker IBA-1. In conclusion, JAM-A expression was higher in glioblastomas compared to low-grade gliomas and co-localized with recognized stem cell markers suggesting an association of JAM-A with glioma aggressiveness. No significant association between JAM-A expression and overall survival was found in grade II and III gliomas. Further research is needed to determine the function and clinical impact of JAM-A in gliomas.  
  Address (up) Department of Clinical Research, University of Southern Denmark, Winslowparken 19, 3rd floor, 5000, Odense, Denmark  
  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 0167-594X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28677106 Approved no  
  Call Number ref @ user @ Serial 96579  
Permanent link to this record
 

 
Author Radbel, J.; Boutsikaris, D. url  doi
openurl 
  Title The New Usual Care Type Journal Article
  Year 2017 Publication Emergency Medicine Clinics of North America Abbreviated Journal Emerg Med Clin North Am  
  Volume 35 Issue 1 Pages 11-23  
  Keywords Anti-Bacterial Agents/therapeutic use; Catheterization, Central Venous; Clinical Protocols/standards; Evidence-Based Medicine; Fluid Therapy; Humans; Sepsis/diagnosis/*therapy; ARISE trial; Early goal-directed therapy (EGDT); ProCESS trial; ProMISe trial; Sepsis; Usual care  
  Abstract Recent literature continues to refine which components of the early goal-directed therapy (EGDT) algorithm are necessary. Given it utilizes central venous pressure, continuous central venous oxygen saturation, routine blood transfusions, and inotropic medications, this algorithm can be timely, invasive, costly, and potentially harmful. New trials highlight early recognition, early fluid resuscitation, appropriate antibiotic treatment, source control, and the application of a multidisciplinary evidence-based approach as essential components of current sepsis management. This article discusses the landmark sepsis trials that have been published over the past several decades and offers recommendations on what should currently be considered 'usual care'.  
  Address (up) Department of Emergency Medicine, Saint Peters University Hospital, 254 Easton Ave, New Brunswick, NJ 08901, USA; Division of Pulmonary and Critical Care, Department of Medicine, Rutgers Robert Wood Johnson Medical School, One Robert Johnson Place, New Brunswick, NJ 08903, USA. Electronic address: boutsida@rwjms.rutgers.edu  
  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 0733-8627 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27908328 Approved no  
  Call Number ref @ user @ Serial 99263  
Permanent link to this record
 

 
Author Radbel, J.; Boutsikaris, D. url  doi
openurl 
  Title The New Usual Care Type Journal Article
  Year 2017 Publication Emergency Medicine Clinics of North America Abbreviated Journal Emerg Med Clin North Am  
  Volume 35 Issue 1 Pages 11-23  
  Keywords Anti-Bacterial Agents/therapeutic use; Catheterization, Central Venous; Clinical Protocols/standards; Evidence-Based Medicine; Fluid Therapy; Humans; Sepsis/diagnosis/*therapy; ARISE trial; Early goal-directed therapy (EGDT); ProCESS trial; ProMISe trial; Sepsis; Usual care  
  Abstract Recent literature continues to refine which components of the early goal-directed therapy (EGDT) algorithm are necessary. Given it utilizes central venous pressure, continuous central venous oxygen saturation, routine blood transfusions, and inotropic medications, this algorithm can be timely, invasive, costly, and potentially harmful. New trials highlight early recognition, early fluid resuscitation, appropriate antibiotic treatment, source control, and the application of a multidisciplinary evidence-based approach as essential components of current sepsis management. This article discusses the landmark sepsis trials that have been published over the past several decades and offers recommendations on what should currently be considered 'usual care'.  
  Address (up) Department of Emergency Medicine, Saint Peters University Hospital, 254 Easton Ave, New Brunswick, NJ 08901, USA; Division of Pulmonary and Critical Care, Department of Medicine, Rutgers Robert Wood Johnson Medical School, One Robert Johnson Place, New Brunswick, NJ 08903, USA. Electronic address: boutsida@rwjms.rutgers.edu  
  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 0733-8627 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27908328 Approved no  
  Call Number ref @ user @ Serial 100293  
Permanent link to this record
 

 
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 (up) 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  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0006-3002 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28040478 Approved no  
  Call Number ref @ user @ Serial 96615  
Permanent link to this record
 

 
Author Harling, G.; Lima Neto, A.S.; Sousa, G.S.; Machado, M.M.T.; Castro, M.C. url  doi
openurl 
  Title Determinants of tuberculosis transmission and treatment abandonment in Fortaleza, Brazil Type Journal Article
  Year 2017 Publication BMC Public Health Abbreviated Journal BMC Public Health  
  Volume 17 Issue 1 Pages 508  
  Keywords Brazil; Epidemiology; Fortaleza; Social determinants; Spatial analysis; Treatment; Treatment failure; Tuberculosis  
  Abstract BACKGROUND: Tuberculosis (TB) remains a public health problem, despite recent achievements in reducing incidence and mortality rates. In Brazil, these achievements were above the worldwide average, but marked by large regional heterogeneities. In Fortaleza (5th largest city in Brazil), the tuberculosis cure rate has been declining and treatment abandonment has been increasing in the past decade, despite a reduction in incidence and an increase in directly observed therapy (DOT). These trends put efforts to eliminate tuberculosis at risk. We therefore sought to determine social and programmatic determinants of tuberculosis incidence and treatment abandonment in Fortaleza. METHODS: We analyzed sociodemographic and clinical data for all new tuberculosis cases notified in the Notifiable Diseases Information System (SINAN) from Fortaleza between 2007 and 2014. We calculated incidence rates for 117 neighborhoods in Fortaleza, assessed their spatial clustering, and used spatial regression models to quantify associations between neighborhood-level covariates and incidence rates. We used hierarchical logistic regression models to evaluate how individual- and neighborhood-level covariates predicted tuberculosis treatment abandonment. RESULTS: There were 12,338 new cases reported during the study period. Case rates across neighborhoods were significantly positively clustered in two low-income areas close to the city center. In an adjusted model, tuberculosis rates were significantly higher in neighborhoods with lower literacy, higher sewerage access and homicide rates, and a greater proportion of self-reported black residents. Treatment was abandoned in 1901 cases (15.4%), a rate that rose by 71% between 2007 and 2014. Abandonment was significantly associated with many individual sociodemographic and clinical factors. Notably, being recommended for DOT was protective for those who completed DOT, but associated with abandonment for those who did not. CONCLUSION: Low socioeconomic status areas have higher tuberculosis rates, and low socioeconomic individuals have higher risk of treatment abandonment, in Fortaleza. Treatment abandonment rates are growing despite the advent of universal DOT recommendations in Brazil. Proactive social policies, and active contact tracing to find missed cases, may help reduce the tuberculosis burden in this setting.  
  Address (up) Department of Global Health and Population, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Building I, Room 1113, Boston, MA, 02115, USA. mcastro@hsph.harvard.edu  
  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 1471-2458 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28545423 Approved no  
  Call Number ref @ user @ Serial 97635  
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