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Author Allegretti, A.S.; Hundemer, G.; Chorghade, R.; Cosgrove, K.; Bajwa, E.; Bhan, I. openurl 
  Title Perspectives of continuous renal replacement therapy in the intensive care unit: a paired survey study of patient, physician, and nurse views Type Journal Article
  Year 2015 Publication Abbreviated Journal BMC Nephrol  
  Volume 16 Issue Pages 105  
  Keywords KRESCENT, jclub  
  Abstract BACKGROUND: Recent studies suggest discrepancies between patients and providers around perceptions of hemodialysis prognosis. Such data are lacking for continuous renal replacement therapy (CRRT). We aim to assess patient and provider understanding of outcomes around CRRT.
METHODS: From February 1 to August 31, 2013, a triad of (1) a patient on CRRT (or health care proxy [HCP]), (2) physician and (3) primary nurse from the intensive care unit (ICU) team were surveyed. Univariate chi-square and qualitative analysis techniques were used.
RESULTS: Ninety-six total participants (32 survey triads) were completed. Ninety one percent of patients/HCPs correctly identified that CRRT replaced the function of the kidneys. Six percent of patients/HCPs, 44 % of physicians, and 44 % of nurses identified rates of survival to hospital discharge that were consistent with published literature. Both physicians and nurses were more likely than patients/HCPs to assess survival consistently with published data (p = 0.001). Patients/HCPs were more likely to overestimate survival rates than physicians and nurses (p < 0.001). Thirty eight percent of patients/HCPs, 38 % of physicians, and 28 % of nurses identified rates of lifelong dialysis-dependence among surviving patients that were consistent with published literature.
CONCLUSIONS: There is mismatch between patients, HCPs, and providers around prognosis of CRRT. Patients/HCPs are more likely to overestimate chances of survival than physicians or nurses. Further intervention is needed to improve this knowledge gap.
 
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  Call Number UofT @ mathieu.lemaire @ Serial (down) 46000  
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Author Astanina, K.; Koch, M.; Jüngst, C.; Zumbusch, A.; Kiemer, A.K. url  openurl
  Title Lipid droplets as a novel cargo of tunnelling nanotubes in endothelial cells Type Journal Article
  Year 2015 Publication Abbreviated Journal Sci Rep  
  Volume 5 Issue Pages 11453  
  Keywords  
  Abstract Intercellular communication is a fundamental process in the development and functioning of multicellular organisms. Recently, an essentially new type of intercellular communication, based on thin membrane channels between cells, has been reported. These structures, termed intercellular or tunnelling nanotubes (TNTs), permit the direct exchange of various components or signals (e.g., ions, proteins, or organelles) between non-adjacent cells at distances over 100 μm. Our studies revealed the presence of tunnelling nanotubes in microvascular endothelial cells (HMEC-1). The TNTs were studied with live cell imaging, environmental scanning electron microscopy (ESEM), and coherent anti-Stokes Raman scattering spectroscopy (CARS). Tunneling nanotubes showed marked persistence: the TNTs could connect cells over long distances (up to 150 μm) for several hours. Several cellular organelles were present in TNTs, such as lysosomes and mitochondria. Moreover, we could identify lipid droplets as a novel type of cargo in the TNTs. Under angiogenic conditions (VEGF treatment) the number of lipid droplets increased significantly. Arachidonic acid application not only increased the number of lipid droplets but also tripled the extent of TNT formation. Taken together, our results provide the first demonstration of lipid droplets as a cargo of TNTs and thereby open a new field in intercellular communication research.  
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  Series Volume Series Issue Edition  
  ISSN 2045-2322 ISBN Medium  
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  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial (down) 45959  
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Author Andeen, N.K.; Nguyen, T.Q.; Steegh, F.; Hudkins, K.L.; Najafian, B.; Alpers, C.E. url  openurl
  Title The phenotypes of podocytes and parietal epithelial cells may overlap in diabetic nephropathy Type Journal Article
  Year 2015 Publication Abbreviated Journal Kidney Int  
  Volume 88 Issue 5 Pages 1099-1107  
  Keywords  
  Abstract Reversal of diabetic nephropathy (DN) has been achieved in humans and mice, but only rarely and under special circumstances. As progression of DN is related to podocyte loss, reversal of DN requires restoration of podocytes. Here, we identified and quantified potential glomerular progenitor cells that could be a source for restored podocytes. DN was identified in 31 human renal biopsy cases and separated into morphologically early or advanced lesions. Markers of podocytes (WT-1, p57), parietal epithelial cells (PECs) (claudin-1), and cell proliferation (Ki-67) were identified by immunohistochemistry. Podocyte density was progressively reduced with DN. Cells marking as podocytes (p57) were present infrequently on Bowman’s capsule in controls, but significantly increased in histologically early DN. Ki-67-expressing cells were identified on the glomerular tuft and Bowman’s capsule in DN, but rarely in controls. Cells marking as PECs were present on the glomerular tuft, particularly in morphologically advanced DN. These findings show evidence of phenotypic plasticity in podocyte and PEC populations and are consistent with studies in the BTBR ob/ob murine model in which reversibility of DN occurs with podocytes potentially regenerating from PEC precursors. Thus, our findings support, but do not prove, that podocytes may regenerate from PEC progenitors in human DN. If so, progression of DN may represent a modifiable net balance between podocyte loss and regeneration.  
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  Series Volume Series Issue Edition  
  ISSN 0085-2538 ISBN Medium  
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  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial (down) 45953  
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Author Aiff, H.; Attman, P.O.; Aurell, M.; Bendz, H.; Ramsauer, B.; Schön, S.; Svedlund, J. url  openurl
  Title Effects of 10 to 30 years of lithium treatment on kidney function Type Journal Article
  Year 2015 Publication Abbreviated Journal J Psychopharmacol  
  Volume 29 Issue 5 Pages 608-614  
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  Abstract Long-term lithium treatment is associated with end-stage renal disease, but there is little evidence of a clinically significant reduction in renal function in most patients. We previously found that 1.5% of people who took lithium from the 1960s and 1970s developed end-stage renal disease; however, none of the patients who started after 1980 had end-stage renal disease. Here we aimed to study the prevalence and extent of kidney damage during the course of long-term lithium treatment since 1980. We retrieved serum lithium and creatinine levels from 4879 patients examined between 1 January 1981 and 31 December 2010. Only patients who started their lithium treatment during the study period and had at least 10 years of cumulative treatment were included. The study group comprised 630 adult patients (402 women and 228 men) with normal creatinine levels at the start of lithium treatment. There was a yearly increase in median serum creatinine levels already from the first year of treatment. About one-third of the patients who had taken lithium for 10-29 years had evidence of chronic renal failure but only 5% were in the severe or very severe category. The results indicate that a substantial proportion of adult patients who are treated with lithium for more than a decade develop signs of renal functional impairment, also when treated according to modern therapeutic principles. Our results emphasise that lithium treatment requires continuous monitoring of kidney function.  
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  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0269-8811 ISBN Medium  
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  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial (down) 45943  
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Author isbn  openurl
  Title Mechanobiology of the Endothelium Type Book Whole
  Year 2015 Publication Abbreviated Journal  
  Volume Issue Pages  
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  Abstract The endothelium is an excellent example of where biology meets physics and engineering. It must convert mechanical forces into chemical signals to maintain homeostasis. It also controls the immune response, drug delivery through the vasculature, and cancer metastasis. Basic understanding of these processes is starting to emerge and the knowledge gained from research is now being used in applications from drug delivery to imaging modalities. This book reviews current knowledge in mechanobiology of the endothelium and its implications for the development of theranostic devices.  
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  Publisher CRC Press Place of Publication Editor  
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  Series Volume Series Issue Edition  
  ISSN ISBN 9781482207255 Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial (down) 45932  
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Author Aichler, M.; Walch, A. url  openurl
  Title MALDI Imaging mass spectrometry: current frontiers and perspectives in pathology research and practice Type Journal Article
  Year 2015 Publication Abbreviated Journal Lab Invest  
  Volume 95 Issue 4 Pages 422-431  
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  Abstract MALDI Imaging mass spectrometry has entered the field of tissue-based research by providing unique advantages for analyzing tissue specimen in an unprecedented detail. A broad spectrum of analytes ranging from proteins, peptides, protein modification over small molecules, drugs and their metabolites as well as pharmaceutical components, endogenous cell metabolites, lipids, and other analytes are made accessible by this in situ technique in tissue. Some of them were even not accessible in tissues within the histological context before. Thereby, the great advantage of MALDI Imaging is the correlation of molecular information with traditional histology by keeping the spatial localization information of the analytes after mass spectrometric measurement. This method is label-free and allows multiplex analysis of hundreds to thousands of molecules in the very same tissue section simultaneously. Imaging mass spectrometry brings a new quality of molecular data and links the expert discipline of pathology and deep molecular mass spectrometric analysis to tissue-based research. This review will focus on state-of-the-art of MALDI Imaging mass spectrometry, its recent applications by analyzing tissue specimen and the contributions in understanding the biology of disease as well as its perspectives for pathology research and practice.  
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  Series Volume Series Issue Edition  
  ISSN 0023-6837 ISBN Medium  
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  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial (down) 45924  
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Author Ariceta, G.; Lara, E.; Camacho, J.A.; Oppenheimer, F.; Vara, J.; Santos, F.; Muñoz, M.A.; Cantarell, C.; Gil Calvo, M.; Romero, R.; Valenciano, B.; García-Nieto, V.; Sanahuja, M.J.; Crespo, J.; Justa, M.L.; Urisarri, A.; Bedoya, R.; Bueno, A.; Daza, A.; Bravo, J.; Llamas, F.; Jiménez Del Cerro, L.A. url  openurl
  Title Cysteamine (Cystagon®) adherence in patients with cystinosis in Spain: successful in children and a challenge in adolescents and adults Type Journal Article
  Year 2015 Publication Abbreviated Journal Nephrol Dial Transplant  
  Volume 30 Issue 3 Pages 475-480  
  Keywords  
  Abstract BACKGROUND: Cysteamine has improved survival and prognosis in cystinosis. Increasing numbers of patients reach adulthood and face new challenges such as compliance that wanes over time. The aim of this study was to evaluate adherence to cysteamine treatment in a group of cystinotic patients in Spain in an attempt to identify potential therapy pitfalls and improve the overall care of affected individuals. Despite the impact of cysteamine on prognosis, there is a paucity of data regarding adherence. METHOD: Thirty-four cystinotic patients (21 male) 38% ≥18 years were enrolled in a voluntary, anonymous survey. Replies were obtained from patients (15/34), mothers (11/34), fathers (4/34) and both parents (4/34). RESULTS: Patient age (median and interquartile range) at diagnosis was 1 year (0.57-1), and patient age at Cystagon® initiation was also 1 year (0.8-1.8). Sixteen (47%) were kidney transplant (KTx) recipients; six were retransplanted. Age at first KTx 10 years (8.7-13.7). Patient understanding of multiorgan involvement in cystinosis: 4.1 organs reported; eye 97% and kidney 91%. Cysteamine was given by mother (100%) and father (83%) in <11 year olds, or self-administered (94%) in ≥11 year olds. Four daily doses in 89% versus 56% in <11 year olds or ≥11 year olds, with fixed schedule in 94% versus 50% in <11 or ≥11 year olds and progressive loss of reminders over time. Furthermore, 44% complained of unpleasant smell. Motivation for treatment compliance was 100% versus 40% in <11 versus ≥11 year olds, respectively. Disease impact in patients <18 years is as follows: school (29%), social (14%), ‘feeling different’ (10%); in patients ≥18 years: ‘feeling different’ (62%), professional (39%) and job absenteeism (31%). Referring physician: paediatric nephrologist (94%) and nephrologist (63%) in <11 versus ≥11 year olds. Ophthalmological follow-up: 83% versus 38% in <11 versus ≥11 year olds. Patient opinion of physician expertise: paediatric nephrologist (94%) and nephrologist (44%). New treatment options (65%) and better information (42%) were demanded to improve adherence. CONCLUSION: Treatment with Cystagon is effective in young patients. However, adherence diminishes over time in adolescents and adults despite disease impact. Strategies such as better information on the disease, patient self-care promotion and facilitated transition to adult healthcare services are required to improve compliance and the clinical management of cystinosis.  
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  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0931-0509 ISBN Medium  
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  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial (down) 45856  
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Author Alkuraya, F.S. url  openurl
  Title Natural human knockouts and the era of genotype to phenotype Type Journal Article
  Year 2015 Publication Abbreviated Journal Genome Med  
  Volume 7 Issue 1 Pages 48  
  Keywords  
  Abstract Complete loss of gene function in humans by naturally occurring biallelic loss-of-function mutations (human knockout) is not a new concept. However, the recent identification of human knockouts along the entire spectrum of health and disease by next-generation sequencing promises to unlock their full potential to accelerate the medical and functional annotation of the human genome.  
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  ISSN 1756-994x ISBN Medium  
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  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial (down) 45850  
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Author Afshinnekoo, E.; Meydan, C.; Chowdhury, S.; Jaroudi, D.; Boyer, C.; Bernstein, N.; Maritz, J.M.; Reeves, D.; Gandara, J.; Chhangawala, S.; Ahsanuddin, S.; Simmons, A.; Nessel, T.; Sundaresh, B.; Pereira, E.; Jorgensen, E.; Kolokotronis, S.O.; Kirchberger, N.; Garcia, I.; Gandara, D.; Dhanraj, S.; Nawrin, T.; Saletore, Y.; Alexander, N.; Vijay, P.; Hénaff, E.M.; Zumbo, P.; Walsh, M.; O’Mullan, G.D.; Tighe, S.; Dudley, J.T.; Dunaif, A.; Ennis, S.; O’Halloran, E.; Magalhaes, T.R.; Boone, B.; Jones, A.L.; Muth, T.R.; Paolantonio, K.S.; Alter, E.; Schadt, E.E.; Garbarino, J.; Prill, R.J.; Carlton, J.M.; Levy, S.; Mason, C.E. url  openurl
  Title Geospatial Resolution of Human and Bacterial Diversity with City-Scale Metagenomics Type Journal Article
  Year 2015 Publication Abbreviated Journal Cell Syst  
  Volume 1 Issue Pages 72-87  
  Keywords Aop  
  Abstract The panoply of microorganisms and other species present in our environment influence human health and disease, especially in cities, but have not been profiled with metagenomics at a city-wide scale. We sequenced DNA from surfaces across the entire New York City (NYC) subway system, the Gowanus Canal, and public parks. Nearly half of the DNA (48%) does not match any known organism; identified organisms spanned 1,688 bacterial, viral, archaeal, and eukaryotic taxa, which were enriched for harmless genera associated with skin (e.g., Acinetobacter). Predicted ancestry of human DNA left on subway surfaces can recapitulate U.S. Census demographic data, and bacterial signatures can reveal a station’s history, such as marine-associated bacteria in a hurricane-flooded station. Some evidence of pathogens was found (Bacillus anthracis), but a lack of reported cases in NYC suggests that the pathogens represent a normal, urban microbiome. This baseline metagenomic map of NYC could help long-term disease surveillance, bioterrorism threat mitigation, and health management in the built environment of cities.  
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  Series Volume Series Issue Edition  
  ISSN 2405-4712 ISBN Medium  
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  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial (down) 45849  
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Author Albers, J.; Danzer, C.; Rechsteiner, M.; Lehmann, H.; Brandt, L.P.; Hejhal, T.; Catalano, A.; Busenhart, P.; Gonçalves, A.F.; Brandt, S.; Bode, P.K.; Bode-Lesniewska, B.; Wild, P.J.; Frew, I.J. url  openurl
  Title A versatile modular vector system for rapid combinatorial mammalian genetics Type Journal Article
  Year 2015 Publication Abbreviated Journal J Clin Invest  
  Volume 125 Issue 4 Pages 1603-1619  
  Keywords Animals; Apoptosis; Caspase 9; Cells, Cultured; Cloning, Molecular; Clustered Regularly Interspaced Short Palindromic Repeats; Doxycycline; Drug Resistance; Gene Deletion; Gene Knockdown Techniques; Genetic Vectors; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Lentivirus; Mice; Mice, SCID; PTEN Phosphohydrolase; Recombination, Genetic; research support, non-u.s. gov’t; Retinoblastoma Protein; RNA, Small Interfering; Sarcoma, Experimental; Transduction, Genetic; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays; Cas9/CRIPSR; Journal club  
  Abstract Here, we describe the multiple lentiviral expression (MuLE) system that allows multiple genetic alterations to be introduced simultaneously into mammalian cells. We created a toolbox of MuLE vectors that constitute a flexible, modular system for the rapid engineering of complex polycistronic lentiviruses, allowing combinatorial gene overexpression, gene knockdown, Cre-mediated gene deletion, or CRISPR/Cas9-mediated (where CRISPR indicates clustered regularly interspaced short palindromic repeats) gene mutation, together with expression of fluorescent or enzymatic reporters for cellular assays and animal imaging. Examples of tumor engineering were used to illustrate the speed and versatility of performing combinatorial genetics using the MuLE system. By transducing cultured primary mouse cells with single MuLE lentiviruses, we engineered tumors containing up to 5 different genetic alterations, identified genetic dependencies of molecularly defined tumors, conducted genetic interaction screens, and induced the simultaneous CRISPR/Cas9-mediated knockout of 3 tumor-suppressor genes. Intramuscular injection of MuLE viruses expressing oncogenic H-RasG12V together with combinations of knockdowns of the tumor suppressors cyclin-dependent kinase inhibitor 2A (Cdkn2a), transformation-related protein 53 (Trp53), and phosphatase and tensin homolog (Pten) allowed the generation of 3 murine sarcoma models, demonstrating that genetically defined autochthonous tumors can be rapidly generated and quantitatively monitored via direct injection of polycistronic MuLE lentiviruses into mouse tissues. Together, our results demonstrate that the MuLE system provides genetic power for the systematic investigation of the molecular mechanisms that underlie human diseases.  
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  Series Volume Series Issue Edition  
  ISSN 0021-9738 ISBN Medium  
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  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial (down) 45848  
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