المؤلفون: Gios, Lorenzo, Mirandola, Massimo, Cordioli, Maddalena, Zorzi, Antonella, Sherriff, Nigel, Vera, Jaime, Wlazly, Dominika, Hassan-Ibrahim, Mohammed Osman, Padovese, Valeska, Darmanin, Anabel, Peeling, Rosanna W., Unemo, Magnus, 1970, Blondeel, Karel, Toskin, Igor

المصدر: BMC Infectious Diseases. 24(Suppl 1)

مصطلحات موضوعية: Treponema pallidum particle agglutination, Chemo-luminescent assay, MSM, Syphilis

الوصف: INTRODUCTION: International guidelines recommend routine screening for syphilis (aetiological agent: Treponema pallidum subspecies pallidum) amongst key populations and vulnerable populations using tests detecting treponemal and non-treponemal antibodies. Whilst treponemal tests have high sensitivities and specificities, they differ regarding subjective or objective interpretation, throughput and workload. Chemiluminescence immunoassays (CLIAs) are cost- and time-effective automated methods for detecting treponemal antibodies. The Treponema pallidum particle agglutination assay (TPPA) has been considered the "gold standard" treponemal assay, however, this includes a highly manual procedure, low throughput and subjective interpretation. The present multi-country study evaluated the ADVIA Centaur® Syphilis CLIA (Siemens Healthcare) assay compared to the reference SERODIA-TP·PA® (Fujirebio Diagnostics) for the serodiagnosis of syphilis amongst men who have sex with men (MSM).METHOD: 1,485 MSM were enrolled in Brighton (UK), Malta, and Verona (Italy) as part of a larger WHO multi-country and multi-site ProSPeRo study. Ethical approval was obtained. Serum was tested with the ADVIA Centaur® Syphilis CLIA assay and SERODIA-TP·PA®, in accordance with the manufacturers' instructions, for a first round of validation. A second round of validation was carried out for discrepant results that were additionally tested with both Western Blot (Westernblot EUROIMMUN®) and an Immunoblot (INNO-LIA, Fujirebio Diagnostics). Sensitivity, specificity, positive and negative predictive value (PPV and NPV), likelihood ratios (positive/negative), and the Diagnostic Odds Ratio (DOR)/pre-post-test probability (Fagan's nomogram) were calculated.RESULTS: Out of 1,485 eligible samples analysed in the first phase, the SERODIA-TP·PA® identified 360 positive and 1,125 negative cases. The ADVIA Centaur® Syphilis CLIA assay (Siemens) identified 366 positives, missclassifying one TPPA-positive sample. In the second phase, the ADVIA Centaur® Syphilis CLIA resulted in 1 false negative and 4 false positive results. Considering the syphilis study prevalence of 24% (95% CI: 22-26.7), The sensitivity of the ADVIA Centaur® Syphilis CLIA assay was 99.7% (95% CI: 98.5-100), and the specificity was 99.4% (95% CI: 98.7-99.7). The ROC area values were 0.996 (95% CI: 0.992-0.999), and both the PPV and NPV values were above 98% (PPV 98.1%, 95% CI: 96.1-99.2; NPV 99.9%, 95% CI: 99.5-100).CONCLUSIONS: The ADVIA Centaur® Syphilis CLIA assay showed similar performance compared to the SERODIA-TP·PA®. Considering the study is based on QUADAS principles and with a homogeneous population, results are also likely to be generalisable to MSM population but potentially not applicable to lower prevalence populations routinely screened for syphilis. The automated CLIA treponemal assay confirmed to be accurate and appropriate for routine initial syphilis screening, i.e. when the reverse testing algorithm is applied.

وصف الملف: print

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-112420Test
https://doi.org/10.1186/s12879-024-09100-xTest

المؤلفون: Sherriff, Nigel, Mirandola, M., Silva, Ronaldo, Cordioli, Maddalena, Sawyer, Alexandra, Gios, Lorenzo, Zorzi, Antonella, Huber, Jörg, Vera, Jaime, Richardson, Daniel, Hassan-Ibrahim, Mohammed, Wlazly, Dominika, Padovese, Valeska, Barbara, Christopher, Darmanin, Anabel, Schembri, Aaron, Caceres, Carlos, Vargas, Silver, Blondeel, Karel, Kiarie, James, Kurbonov, Firdavs, Peeling, Rosanna, Thwin, Soe Soe, Toskin, Igor

المصدر: Sherriff , N , Mirandola , M , Silva , R , Cordioli , M , Sawyer , A , Gios , L , Zorzi , A , Huber , J , Vera , J , Richardson , D , Hassan-Ibrahim , M , Wlazly , D , Padovese , V , Barbara , C , Darmanin , A , Schembri , A , Caceres , C , Vargas , S , Blondeel , K , Kiarie , J , Kurbonov , F , Peeling , R , Thwin , S S & Toskin , I 2024 , ' ....

مصطلحات موضوعية: HIV, Syphilis, World Health Organization, Public Health, LGBT, MSM, Global health, Point of Care Tests, Clinic-based evaluation

الوصف: Introduction: Globally, the incidence of HIV and syphilis can be reduced by the use of validated point of care tests (POCTs). As part of the WHO PRoSPeRo Network, we aimed to evaluate the performance, acceptability, and operational characteristics of two dual HIV/syphilis POCTs (Bioline HIV/Syphilis Duo (Abbott) and DPP® HIV-Syphilis assay (Chembio) for the screening of HIV and syphilis amongst men who have sex with men (MSM). Method and analyses: A cross sectional study of 2,577 MSM in Italy, Malta, Peru, and the United Kingdom (UK) presenting to seven clinic sites, were enrolled. Finger prick blood was collected to perform POCTs and results compared with standard laboratory investigations on venepuncture blood. Acceptability and operational characteristics were assessed using questionnaires. Diagnostic meta-analysis was used to combine data from the evaluation sites. Results: Based on laboratory tests, 23.46% (n=598/2549) of participants were confirmed HIV positive, and 35.88% of participants (n=901/2511) were positive on treponemal reference testing. Of all participants showing evidence of antibodies to Treponema pallidum, 50.56% (n=455/900) were Rapid Plasma Reagin (RPR) test reactive. Of HIV positive individuals, 60.62% (n=354/584) had evidence of antibodies to T. pallidum, and of these 60.45 % (n=214/354) exhibited reactive RPR tests indicating probable (co)infection. For Bioline POCT, pooled sensitivities and specificities for HIV were 98.95% and 99.89% respectively, and for syphilis were 73.79% and 99.57%. For Chembio pooled sensitivities and specificities for HIV were 98.66% and 99.55%, and for syphilis were 78.60% and 99.48%. Both tests can detect greater than 90% of probable active syphilis cases, as defined by reactive RPR and treponemal test results. These dual POCTs were preferred by 74.77% (n=1,926) of participants, due to their convenience, and the operational characteristics made them acceptable to health care providers (HCPs). Conclusions: Both the Bioline and the Chembio dual POCT for syphilis ...

وصف الملف: application/pdf

العلاقة: https://research.brighton.ac.uk/en/publications/fa151c7d-5d6f-4bfd-a793-9837a2c520d5Test

الإتاحة: https://doi.org/10.1186/s12879-024-09019-3Test
https://research.brighton.ac.uk/en/publications/fa151c7d-5d6f-4bfd-a793-9837a2c520d5Test
https://cris.brighton.ac.uk/ws/files/43977111/Sherriff_et_al._2024_HIV_SYP.pdfTest
http://www.scopus.com/inward/record.url?scp=85186469010&partnerID=8YFLogxKTest

المؤلفون: Vicente-Rodríguez, Marta, Mancuso, Renzo, Peris-Yague, Alba, Simmons, Camilla, Wlazly, Dominika, Dickinson, Amber, Foster, Andy, Knight, Clare, Leckey, Claire, Morgan, Paul, Morgan, Angharad, O’Hagan, Caroline, Touchard, Samuel, Khan, Shahid, Murphy, Phil, Parker, Christine, Patel, Jai, Richardson, Jill, Acton, Paul, Austin, Nigel, Bhattacharya, Anindya, Carruthers, Nick, de Boer, Peter, Drevets, Wayne, Isaac, John, Jones, Declan, Kemp, John, Kolb, Hartmuth, Nye, Jeff, Wittenberg, Gayle, Barker, Gareth, Bogdanova, Anna, Byrom, Heidi, Cattaneo, Annamaria, Enache, Daniela, Gee, Tony, Hastings, Caitlin, Kose, Melisa, Lombardo, Giulia, Mariani, Nicole, McLaughlin, Anna, Mondelli, Valeria, Nettis, Maria, Nikkheslat, Naghmeh, Pariante, Carmine, Randall, Karen, Schubert, Julia, Sforzini, Luca, Sheridan, Hannah, Singh, Nisha

المساهمون: GlaxoSmithKline

المصدر: Journal of Neuroinflammation ; volume 20, issue 1 ; ISSN 1742-2094

مصطلحات موضوعية: Cellular and Molecular Neuroscience, Neurology, Immunology, General Neuroscience

الوصف: Neuroinflammation is an important component of many neurodegenerative diseases, whether as a primary cause or a secondary outcome. For that reason, either as diagnostic tools or to monitor progression and/or pharmacological interventions, there is a need for robust biomarkers of neuroinflammation in the brain. Mitochondrial TSPO (18 kDa Translocator protein) is one of few available biomarkers of neuroinflammation for which there are clinically available PET imaging agents. In this study, we further characterised neuroinflammation in a mouse model of prion-induced chronic neurodegeneration (ME7) including a pharmacological intervention via a CSF1R inhibitor. This was achieved by autoradiographic binding of the second-generation TSPO tracer, [3H]PBR28, along with a more comprehensive examination of the cellular contributors to the TSPO signal changes by immunohistochemistry. We observed regional increases of TSPO in the ME7 mouse brains, particularly in the hippocampus, cortex and thalamus. This increased TSPO signal was detected in the cells of microglia/macrophage lineage as well as in astrocytes, endothelial cells and neurons. Importantly, we show that the selective CSF1R inhibitor, JNJ-40346527 (JNJ527), attenuated the disease-dependent increase in TSPO signal, particularly in the dentate gyrus of the hippocampus, where JNJ527 attenuated the number of Iba1+ microglia and neurons, but not GFAP+ astrocytes or endothelial cells. These findings suggest that [3H]PBR28 quantitative autoradiography in combination with immunohistochemistry are important translational tools for detecting and quantifying neuroinflammation, and its treatments, in neurodegenerative disease. Furthermore, we demonstrate that although TSPO overexpression in the ME7 brains was driven by various cell types, the therapeutic effect of the CSF1R inhibitor was primarily to modulate TSPO expression in microglia and neurons, which identifies an important route of biological action of this particular CSF1R inhibitor and provides an example ...

الإتاحة: https://doi.org/10.1186/s12974-023-02769-yTest

المؤلفون: Schubert, Julia J., Veronese, Mattia, Fryer, Tim D., Manavaki, Roido, Kitzbichler, Manfred G., Nettis, Maria A., Mondelli, Valeria, Pariante, Carmine M., Bullmore, Edward T., Turkheimer, Federico E., Wlazly, Dominika, Dickinson, Amber, Foster, Andy, Knight, Clare, Leckey, Claire, Morgan, Paul, Morgan, Angharad, O'Hagan, Caroline, Touchard, Samuel, Khan, Shahid, Murphy, Phil, Parker, Christine, Patel, Jai, Richardson, Jill, Acton, Paul, Austin, Nigel, Bhattacharya, Anindya, Carruthers, Nick, de Boer, Peter, Drevets, Wayne, Isaac, John, Jones, Declan, Kemp, John, Kolb, Hartmuth, Nye, Jeff, Wittenberg, Gayle, Barker, Gareth, Bogdanova, Anna, Byrom, Heidi, Cash, Diana, Cattaneo, Annamaria, Enache, Daniela, Gee, Tony, Hastings, Caitlin, Kose, Melisa, Lombardo, Giulia, Mariani, Nicole, McLaughlin, Anna, Nettis, Maria

المساهمون: Wellcome Trust

المصدر: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging ; volume 6, issue 7, page 716-724 ; ISSN 2451-9022

مصطلحات موضوعية: Biological Psychiatry, Neurology (clinical), Cognitive Neuroscience, Radiology, Nuclear Medicine and imaging

الإتاحة: https://doi.org/10.1016/j.bpsc.2020.12.017Test
https://api.elsevier.com/content/article/PII:S2451902221000252?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2451902221000252?httpAccept=text/plainTest

المؤلفون: Morgan, Angharad R., Touchard, Samuel, Leckey, Claire, O'Hagan, Caroline, Nevado-Holgado, Alejo J., Barkhof, Frederik, Bertram, Lars, Blin, Olivier, Bos, Isabelle, Dobricic, Valerija, Engelborghs, Sebastiaan, Frisoni, Giovanni, Frölich, Lutz, Gabel, Silvey, Johannsen, Peter, Kettunen, Petronella, Koszewska, Iwona, Legido-Quigley, Cristina, Lleó, Alberto, Martinez-Lage, Pablo, Mecocci, Patrizia, Meersmans, Karen, Molinuevo, José Luis, Peyratout, Gwendoline, Popp, Julius, Richardson, Jill, Sala, Isabel, Scheltens, Philip, Streffer, Johannes, Soininen, Hikka, Tainta-Cuezva, Mikel, Teunissen, Charlotte, Tsolaki, Magda, Vandenberghe, Rik, Visser, Pieter Jelle, Vos, Stephanie, Wahlund, Lars-Olof, Wallin, Anders, Westwood, Sarah, Zetterberg, Henrik, Lovestone, Simon, Morgan, B. Paul, Bullmore, Edward T., Bhatti, Junaid, Chamberlain, Samuel J., Correia, Marta M., Crofts, Anna L., Dickinson, Amber, Foster, Andrew C., Kitzbichler, Manfred G., Knight, Clare, Lynall, Mary-Ellen, Maurice, Christina, O'Donnell, Ciara, Pointon, Linda J., St George Hyslop, Peter, Turner, Lorinda, Vertes, Petra, Widmer, Barry, Williams, Guy B., Cavanagh, Jonathan, Deith, Catherine, Farmer, Scott, McClean, John, McColl, Alison, McPherson, Andrew, Scouller, Paul, Sutherland, Murray, Boddeke, H.W.G.M., Richardson, Jill C., Khan, Shahid, Murphy, Phil, Parker, Christine A., Patel, Jai, Jones, Declan, de Boer, Peter, Kemp, John, Drevets, Wayne C., Nye, Jeffrey S., Wittenberg, Gayle, Isaac, John, Bhattacharya, Anindya, Carruthers, Nick, Kolb, Hartmuth, Pariante, Carmine M., Turkheimer, Federico, Barker, Gareth J., Byrom, Heidi, Cash, Diana, Cattaneo, Annamaria, Gee, Antony, Hastings, Caitlin, Mariani, Nicole, McLaughlin, Anna, Mondelli, Valeria, Nettis, Maria, Nikkheslat, Naghmeh, Randall, Karen, Sheridan, Hannah, Simmons, Camilla, Singh, Nisha, Van Loo, Victoria, Vicente-Rodriguez, Marta, Wood, Tobias C., Worrell, Courtney, Zajkowska, Zuzanna, Plath, Niels, Egebjerg, Jan, Eriksson, Hans, Gastambide, Francois, Adams, Karen Husted, Jeggo, Ross, Thomsen, Christian, Pederson, Jan Torleif, Campbell, Brian, Möller, Thomas, Nelson, Bob, Zorn, Stevin, O'Connor, Jason, Attenburrow, Mary Jane, Baird, Alison, Benjamin, Jithen, Clare, Stuart, Cowen, Philip, Huang, I-Shu (Dante), Hurley, Samuel, Jones, Helen, Mada, Francisca, Nevado-Holgado, Alejo, Oladejo, Akintayo, Ribe, Elena, Smith, Katy, Vyas, Anviti, Hughes, Zoe, Balice-Gordon, Rita, Duerr, James, Piro, Justin R., Sporn, Jonathan, Perry, V. Hugh, Cleal, Madeleine, Fryatt, Gemma, Gomez-Nicola, Diego, Mancuso, Renzo, Reynolds, Richard, Harrison, Neil A., Cercignani, Mara, Clarke, Charlotte L., Hoskins, Elizabeth, Kohn, Charmaine, Murray, Rosemary, Wilcock, Lauren, Wlazly, Dominika, Mount, Howard

الوصف: Introduction:Plasma biomarkers for Alzheimer’s disease (AD) diagnosis/stratification are a“Holy Grail” of AD research and intensively sought; however, there are no well-established plasmamarkers.Methods:A hypothesis-led plasma biomarker search was conducted in the context of internationalmulticenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL;259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed.Results:Ten analytes showed significant intergroup differences. Logistic regression identified five(FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD andCTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI(AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Twoanalytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71).Discussion:Plasma markers of inflammation and complement dysregulation support diagnosis andoutcome prediction in AD and MCI. Further replication is needed before clinical translation

وصف الملف: application/pdf

العلاقة: https://orca.cardiff.ac.uk/id/eprint/122268/1/Morgan_InfBiomarkers_AD_Plasma_2019.pdfTest; Morgan, Angharad R., Touchard, Samuel, Leckey, Claire, O'Hagan, Caroline, Nevado-Holgado, Alejo J., Barkhof, Frederik, Bertram, Lars, Blin, Olivier, Bos, Isabelle, Dobricic, Valerija, Engelborghs, Sebastiaan, Frisoni, Giovanni, Frölich, Lutz, Gabel, Silvey, Johannsen, Peter, Kettunen, Petronella, Koszewska, Iwona, Legido-Quigley, Cristina, Lleó, Alberto, Martinez-Lage, Pablo, Mecocci, Patrizia, Meersmans, Karen, Molinuevo, José Luis, Peyratout, Gwendoline, Popp, Julius, Richardson, Jill, Sala, Isabel, Scheltens, Philip, Streffer, Johannes, Soininen, Hikka, Tainta-Cuezva, Mikel, Teunissen, Charlotte, Tsolaki, Magda, Vandenberghe, Rik, Visser, Pieter Jelle, Vos, Stephanie, Wahlund, Lars-Olof, Wallin, Anders, Westwood, Sarah, Zetterberg, Henrik, Lovestone, Simon, Morgan, B. Paul https://orca.cardiff.ac.uk/view/cardiffauthors/A0083768.htmlTest orcid:0000-0003-4075-7676 orcid:0000-0003-4075-7676, Bullmore, Edward T., Bhatti, Junaid, Chamberlain, Samuel J., Correia, Marta M., Crofts, Anna L., Dickinson, Amber, Foster, Andrew C., Kitzbichler, Manfred G., Knight, Clare, Lynall, Mary-Ellen, Maurice, Christina, O'Donnell, Ciara, Pointon, Linda J., St George Hyslop, Peter, Turner, Lorinda, Vertes, Petra, Widmer, Barry, Williams, Guy B., Cavanagh, Jonathan, Deith, Catherine, Farmer, Scott, McClean, John, McColl, Alison, McPherson, Andrew, Scouller, Paul, Sutherland, Murray, Boddeke, H.W.G.M., Richardson, Jill C., Khan, Shahid, Murphy, Phil, Parker, Christine A., Patel, Jai, Jones, Declan, de Boer, Peter, Kemp, John, Drevets, Wayne C., Nye, Jeffrey S., Wittenberg, Gayle, Isaac, John, Bhattacharya, Anindya, Carruthers, Nick, Kolb, Hartmuth, Pariante, Carmine M., Turkheimer, Federico, Barker, Gareth J., Byrom, Heidi, Cash, Diana, Cattaneo, Annamaria, Gee, Antony, Hastings, Caitlin, Mariani, Nicole, McLaughlin, Anna, Mondelli, Valeria, Nettis, Maria, Nikkheslat, Naghmeh, Randall, Karen, Sheridan, Hannah, Simmons, Camilla, Singh, Nisha, Van Loo, Victoria, Vicente-Rodriguez, Marta, Wood, Tobias C., Worrell, Courtney, Zajkowska, Zuzanna, Plath, Niels, Egebjerg, Jan, Eriksson, Hans, Gastambide, Francois, Adams, Karen Husted, Jeggo, Ross, Thomsen, Christian, Pederson, Jan Torleif, Campbell, Brian, Möller, Thomas, Nelson, Bob, Zorn, Stevin, O'Connor, Jason, Attenburrow, Mary Jane, Baird, Alison, Benjamin, Jithen, Clare, Stuart, Cowen, Philip, Huang, I-Shu (Dante), Hurley, Samuel, Jones, Helen, Lovestone, Simon, Mada, Francisca, Nevado-Holgado, Alejo, Oladejo, Akintayo, Ribe, Elena, Smith, Katy, Vyas, Anviti, Hughes, Zoe, Balice-Gordon, Rita, Duerr, James, Piro, Justin R., Sporn, Jonathan, Perry, V. Hugh, Cleal, Madeleine, Fryatt, Gemma, Gomez-Nicola, Diego, Mancuso, Renzo, Reynolds, Richard, Harrison, Neil A. https://orca.cardiff.ac.uk/view/cardiffauthors/A2454750W.htmlTest orcid:0000-0002-9584-3769 orcid:0000-0002-9584-3769, Cercignani, Mara https://orca.cardiff.ac.uk/view/cardiffauthors/A2620326M.htmlTest orcid:0000-0002-4550-2456 orcid:0000-0002-4550-2456, Clarke, Charlotte L., Hoskins, Elizabeth, Kohn, Charmaine, Murray, Rosemary, Wilcock, Lauren, Wlazly, Dominika and Mount, Howard 2019. Inflammatory biomarkers in Alzheimer's disease plasma. Alzheimer's & Dementia 15 (6) , pp. 776-787. 10.1016/j.jalz.2019.03.007 https://doi.org/10.1016/j.jalz.2019.03.007Test file https://orca.cardiff.ac.uk/id/eprint/122268/1/Morgan_InfBiomarkers_AD_Plasma_2019.pdfTest

الإتاحة: https://doi.org/10.1016/j.jalz.2019.03.007Test
https://orca.cardiff.ac.uk/id/eprint/122268Test/
https://orca.cardiff.ac.uk/id/eprint/122268/1/Morgan_InfBiomarkers_AD_Plasma_2019.pdfTest

المؤلفون: Mancuso, Renzo, Fryatt, Gemma, Cleal, Madeleine, Obst, Juliane, Pipi, Elena, Monzón-Sandoval, Jimena, Ribe, Elena, Winchester, Laura, Webber, Caleb, Nevado, Alejo, Jacobs, Tom, Austin, Nigel, Theunis, Clara, Grauwen, Karolien, Ruiz, Eva Daniela, Mudher, Amrit, Vicente-Rodriguez, Marta, Parker, Christine A., Simmons, Camilla, Cash, Diana, Richardson, Jill, Bullmore, Edward T., Bhatti, Junaid, Chamberlain, Samuel J., Correia, Marta M., Crofts, Anna L., Dickinson, Amber, Foster, Andrew C., Kitzbichler, Manfred G., Knight, Clare, Lynall, Mary-Ellen, Maurice, Christina, O'Donnell, Ciara, Pointon, Linda J., Hyslop, Peter St. George, Turner, Lorinda, Vertes, Petra, Widmer, Barry, Williams, Guy B., Morgan, B. Paul, Leckey, Claire A., Morgan, Angharad R., O'Hagan, Caroline, Touchard, Samuel, Cavanagh, Jonathan, Deith, Catherine, Farmer, Scott, McClean, John, McColl, Alison, McPherson, Andrew, Scouller, Paul, Sutherland, Murray, Boddeke, H. W. G. M. (Erik), Richardson, Jill C., Khan, Shahid, Murphy, Phil, Patel, Jai, Jones, Declan, de Boer, Peter, Kemp, John, Drevets, Wayne C., Nye, Jeffrey S., Wittenberg, Gayle, Isaac, John, Bhattacharya, Anindya, Carruthers, Nick, Kolb, Hartmuth, Pariante, Carmine M., Turkheimer, Federico, Barker, Gareth J., Byrom, Heidi, Cattaneo, Annamaria, Gee, Antony, Hastings, Caitlin, Mariani, Nicole, McLaughlin, Anna, Mondelli, Valeria, Nettis, Maria, Nikkheslat, Naghmeh, Randall, Karen, Sheridan, Hannah, Singh, Nisha, VAn Loo, Victoria, Wood, Tobias C, Worrell, Courtney, Zajkowska, Zuzanna, Plath, Niels, Egebjerg, Jan, Eriksson, Hans, Gastambide, Francois, Adams, Karen Husted, Jeggo, Ross, Thomsen, Christian, Pederson, Jan Torleif, Campbell, Brian, Möller, Thomas, Nelson, Bob, Zorn, Stevin, O'Connor, Jason, Attenburrow, Mary Jane, Baird, Alison, Benjamin, Jithen, Clare, Stuart, Cowen, Philip, Huang, I-Shu (Dante), Hurley, Samuel, Jones, Helen, Lovestone, Simon, Mada, Francisca, Nevado-Holgado, Alejo, Oladejo, Akintayo, Smith, Katy, Vyas, Anviti, Hughes, Zoe, Balice-Gordon, Rita, Duerr, James, Piro, Justin R, Sporn, Jonathan, Perry (PI), V Hugh, Gomez-Nicola, Diego, Reynolds, Richard, Harrison, Neil A., Cercignani, Mara, Clarke, Charlotte L, Hoskins, Elizabeth, Kohn, Charmaine, Murray, Rosemary, Wilcock, Lauren, Wlazly, Dominika, Mount, Howard, Jones, Declan N. C., Perry, V. Hugh

الوصف: Neuroinflammation and microglial activation are significant processes in Alzheimer’s disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer’s disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer’s disease and other tau-mediated neurodegenerative diseases.

وصف الملف: application/pdf

العلاقة: https://orca.cardiff.ac.uk/id/eprint/125159/7/awz241.pdfTest; Mancuso, Renzo, Fryatt, Gemma, Cleal, Madeleine, Obst, Juliane, Pipi, Elena, Monzón-Sandoval, Jimena, Ribe, Elena, Winchester, Laura, Webber, Caleb https://orca.cardiff.ac.uk/view/cardiffauthors/A2393081Q.htmlTest orcid:0000-0001-8063-7674 orcid:0000-0001-8063-7674, Nevado, Alejo, Jacobs, Tom, Austin, Nigel, Theunis, Clara, Grauwen, Karolien, Ruiz, Eva Daniela, Mudher, Amrit, Vicente-Rodriguez, Marta, Parker, Christine A., Simmons, Camilla, Cash, Diana, Richardson, Jill, Bullmore, Edward T., Bhatti, Junaid, Chamberlain, Samuel J., Correia, Marta M., Crofts, Anna L., Dickinson, Amber, Foster, Andrew C., Kitzbichler, Manfred G., Knight, Clare, Lynall, Mary-Ellen, Maurice, Christina, O'Donnell, Ciara, Pointon, Linda J., Hyslop, Peter St. George, Turner, Lorinda, Vertes, Petra, Widmer, Barry, Williams, Guy B., Morgan, B. Paul https://orca.cardiff.ac.uk/view/cardiffauthors/A0083768.htmlTest orcid:0000-0003-4075-7676 orcid:0000-0003-4075-7676, Leckey, Claire A., Morgan, Angharad R. https://orca.cardiff.ac.uk/view/cardiffauthors/A0083768.htmlTest orcid:0000-0003-4075-7676 orcid:0000-0003-4075-7676, O'Hagan, Caroline, Touchard, Samuel, Cavanagh, Jonathan, Deith, Catherine, Farmer, Scott, McClean, John, McColl, Alison, McPherson, Andrew, Scouller, Paul, Sutherland, Murray, Boddeke, H. W. G. M. (Erik), Richardson, Jill C., Khan, Shahid, Murphy, Phil, Parker, Christine A., Patel, Jai, Jones, Declan, de Boer, Peter, Kemp, John, Drevets, Wayne C., Nye, Jeffrey S., Wittenberg, Gayle, Isaac, John, Bhattacharya, Anindya, Carruthers, Nick, Kolb, Hartmuth, Pariante, Carmine M., Turkheimer, Federico, Barker, Gareth J., Byrom, Heidi, Cash, Diana, Cattaneo, Annamaria, Gee, Antony, Hastings, Caitlin, Mariani, Nicole, McLaughlin, Anna, Mondelli, Valeria, Nettis, Maria, Nikkheslat, Naghmeh, Randall, Karen, Sheridan, Hannah, Simmons, Camilla, Singh, Nisha, VAn Loo, Victoria, Vicente-Rodriguez, Marta, Wood, Tobias C, Worrell, Courtney, Zajkowska, Zuzanna, Plath, Niels, Egebjerg, Jan, Eriksson, Hans, Gastambide, Francois, Adams, Karen Husted, Jeggo, Ross, Thomsen, Christian, Pederson, Jan Torleif, Campbell, Brian, Möller, Thomas, Nelson, Bob, Zorn, Stevin, O'Connor, Jason, Attenburrow, Mary Jane, Baird, Alison, Benjamin, Jithen, Clare, Stuart, Cowen, Philip, Huang, I-Shu (Dante), Hurley, Samuel, Jones, Helen, Lovestone, Simon, Mada, Francisca, Nevado-Holgado, Alejo, Oladejo, Akintayo, Ribe, Elena, Smith, Katy, Vyas, Anviti, Hughes, Zoe, Balice-Gordon, Rita, Duerr, James, Piro, Justin R, Sporn, Jonathan, Perry (PI), V Hugh, Cleal, Madeleine, Fryatt, Gemma, Gomez-Nicola, Diego, Mancuso, Renzo, Reynolds, Richard, Harrison, Neil A. https://orca.cardiff.ac.uk/view/cardiffauthors/A2454750W.htmlTest orcid:0000-0002-9584-3769 orcid:0000-0002-9584-3769, Cercignani, Mara https://orca.cardiff.ac.uk/view/cardiffauthors/A2620326M.htmlTest orcid:0000-0002-4550-2456 orcid:0000-0002-4550-2456, Clarke, Charlotte L, Hoskins, Elizabeth, Kohn, Charmaine, Murray, Rosemary, Wilcock, Lauren, Wlazly, Dominika, Mount, Howard, Jones, Declan N. C., Lovestone, Simon, Gomez-Nicola, Diego and Perry, V. Hugh 2019. CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice. Brain 142 (10) , pp. 3243-3264. 10.1093/brain/awz241 https://doi.org/10.1093/brain%2Fawz241Test file https://orca.cardiff.ac.uk/id/eprint/125159/7/awz241.pdfTest

الإتاحة: https://doi.org/10.1093/brain/awz241Test
https://orca.cardiff.ac.uk/id/eprint/125159Test/
https://orca.cardiff.ac.uk/id/eprint/125159/7/awz241.pdfTest

المؤلفون: Thwaites, Guy E, Scarborough, Matthew, Szubert, Alexander, Nsutebu, Emmanuel, Tilley, Robert, Greig, Julia, Wyllie, Sarah A, Wilson, Peter, Auckland, Cressida, Cairns, Janet, Ward, Denise, Lal, Pankaj, Guleri, Achyut, Jenkins, Neil, Sutton, Julian, Wiselka, Martin, Armando, Gonzalez-Ruiz, Graham, Clive, Chadwick, Paul R, Barlow, Gavin, Gordon, N Claire, Young, Bernadette, Meisner, Sarah, McWhinney, Paul, Price, David A, Harvey, David, Nayar, Deepa, Jeyaratnam, Dakshika, Planche, Tim, Minton, Jane, Hudson, Fleur, Hopkins, Susan, Williams, John, Török, M Estee, Llewelyn, Martin J, Edgeworth, Jonathan D, Walker, A Sarah, Kamfose, Musa, de Veciana, Ana, Gordon, Nicola Claire, Peto, Leon, Pill, Gemma, Clarke, Tiphanie, Watson, Laura, Griffiths, Dai, Vaughn, Ali, Anson, Luke, Liu, Elian, Perera, Sanuki, Rylance-Knight, Lydia, Cantell, Carmen, Moroney, Ruth, Thwaites, Guy, Bisnauthsing, Karen, Querol-Rubiera, Antonio, Gibbs, Charlotte, Patel, Amita, Hemsley, Carolyn, Goodman, Anna L, Wyncoll, Duncan, Biswas, Jason, Fitzpatrick, Jennifer, Roberts, Lizzie, Millard, James, Stone, Neil, Cape, Angela, Hurley, Lisa, Tam, Chi Kai, Hoyle, Marie-Claire, Maitland, Kate, Trainor, Leona, Reynolds, Helen, Harrison, Jennifer, Anson, Jim, Lewis, Joseph, Folb, Jonathan, Goodwin, Lynsey, Beeching, Nicholas, Dyas, Sarah, Winslow, Helen, Foote, Elizabeth, Roberts, Paul, Natarajan, Pavithra, Chrdle, Alex, Fenech, Manuel, Allsop, Hannah, Austin-Hutchison, Rachel, Barrett, Louise, Brookes, Karen, Carwithen, Leanne, Conbeer, Andrew, Cunningham, Richard, Eglinton, Charlotte, Fok, Rosie, Gott, Hannah, Hughes, Shona, Jones, Lewis, Kalita, Maggie, King, Angela, March, Linda, Marner, Mike, Mynes, Tracey, Plant, Aiden, Price, Suzanne, Sercombe, Judy, Stolton, Alison, Wallis, Mark, West, Marie-Claire, Westcott, Jackie, Williams, Claire, Wosley, Rob, Yabsley, Leona, Butland, Laura, Sorrell, Julie, Mitchell, Tamara, Alli, Abiola, Meiring, James, Masake, Boingotlo, Rowson, Carlene, Smart, Lynne, Makey, Laura, Moll, Sarah, Cunningham, Jane, Ryalls, Kim, Birchall, Kathryn, Middle, Janet, Jackson, Yvonne, Swift, Diane, Cole, Joby, Subramanian, Bala, Okhuoya, Faith, Edwards, Maria, Bailey, Cheryl, Warren, Rebecca, Islam, Gayti, Ankcorn, Michael, Birchall, Sarah, Jones, Paul, Humphries, John, Booth, Stephen, Evan, Cariad, Wyllie, Sarah, Flatt, Andrew, Strakova, Lenka, Hayes, Maria, Valentine, Stacey, James, Clare, Wands, Mary, Cortes, Nicolas, Khan, Nisa, Porter, Robert, Martin, Zoe, Yip, Keith, Preedy, Helen, Chesterfield, Helen, Dobson, Tracey, Walker, Colin, Llewelyn, Martin, Dunne, Angela, Latter, Laura, Porges, Alison, Price, James, Paul, John, Behar, Laura, Robinson, Louise, Murray, Amy, Sargent, Tenessa, Ridley, Carrie, de Gordoa, Laura Ortiz-Ruiz, Gilliam, Deborah, McPherson, Carole, Matthews, Simon, Foreman, Emma, Jarghese, Rajesh, Beddoe, Alisha, Martin, Sebastien, Shaw, Sephora, Wlazly, Dominika, Cole, Maggie, Gihawi, Abraham, Cole, Kevin, Török, M Estée, Gouliouris, Theodore, Bedford, Luke, Saunderson, Rebecca B, Mariolis, Ilias, Bousfield, Rachel, Ramsay, Isobel, Greaves, Daniel, Aliyu, Sani, Cox, Kim, Mlemba, Lois, Whitehead, Lynne, Vyse, Naval, Bolton, Mark, Lambert, Pauline, Chadwick, David, Baillie, Kirsty, Cain, Martyn, Bellamy, Richard, Wong, Jason, Thompson, Jane, Vassallo, Helen, Skotnicka, Agnieszka, Boyce, Andrea, Donnelly, Anthony, FitzGerald, Graham, Dean, Victoria, Warnes, Kristian, Reyes, Anna, Rahman, Saadia, Tsang, Lillian, Williams, Joanne, Morris-Jones, Stephen, Witness, Elen, Brady, Orla, Woodford, Elizabeth, Pettifer, Teresa, McCadden, Angela, Marks, Ben, Collier, Sophie, Mack, Damien, Warren, Simon, Brown, Colin, Lyons, Adrian, Taiyari, Sara, Mepham, Stephen, Sweeney, Anna, Brown, Li-An, Potter, Alison, Mandiza, Jess, Hough, Maxine, Williams, Sue, Renton, Caroline, Walters, Fiona, Nadolski, Maria, Evans, Andree, Tarrant, Polly, Curley, Katherine, Whiteley, Sophie, Halpin, Julia, Hutchings, Melanie, Todd, Shirley, Lohan, Christop, Chapter, Tamika, Folland, Emma, Colville, Alaric, Marden, Katy, Morgan, Marina, Porter, Rob, Baxter, Mel, Rippon, Sarah, Cevik, Muge, Chapman, Judith, Kemp, Tim, Vincent, Rachel, Osborne, Dave, Platt, Tracey, Calderwood, James, Cook, Bernadette, Bedford, Caroline, Galloway-Browne, Leanne, Abberley, Nadine, Attack, Kelly, Allen, Joanna, Harrison, Melanie, Stevenson, Sarah, Brooks, Carol, Harlow, Paula, Ewing, Jordan, Cooper, Shirley, Balancio-Tolentino, Roderick, O'Neil, Laura, Tagney, Rebecca, Shackcloth, Daniela, Fellows, James, Millett, Ruth, Studham, Jo, de Souza, Cherrelle, Howell, Geoffrey, Greaves, Hezron, Foncel, Ella, Kurup, Rahul, Briggs, Jack, Smith, Melody, Suarez, Cristina, Sorrentino, Giordana, Scobie, Antonia, Houston, Angela, Ahmad, Fozia, Breathnach, Aodhan, Chahuan, Rakhee, Wilkins, Katie, Waddington, Natalia, Sharma, Rashmi, Flegg, Peter, Kollipara, Veenu, Alam, Mazhar, Potter, Andrew, Donaldson, Stacey, Armer, Charlote, Frudd, Julie, Joy, Manju, Mathews, Asha, Glass, Stephen K, Ajayi, Ayodele, Fife, Amanda, Qaiser, Saba, Sheehan, Sharon, Muñoz-Villaverde, Sergio, Yogo, Noah, De Abreu, Ines, Notcheva, Gaynor, Flanagan, Joanna, Watson, Cordelia, Sais, Efisia, Adedayo, Adetunji, Chu, Vicky, Shaw, Georgina, Graver, Michelle A, Palmer, Rebecca, Palmer, Donna, Haile, Senait, Gordon, Joanne, Mandar, Kirandip, Szypura, Weronika, Marange, Josephine, Shabangu, Vusumuzi, Moore, Katy, Lyons, Jill, Munang, Melinda, Sangombe, Mirriam, Moran, Ed, Hussain, Abid, Lewszuk, Adam, Batham, Sally, Ellis, Kate, Bahadur, Leila, White, Helena, Pareek, Manish, Sahota, Amandip, Coleman, Stephen, Pateman, Hilary, Kotecha, Atul, Sim, Christopher, Rosser, Andrew, Deane, Jill, Nendick, Richard, Aldridge, Catherine, Clarke, Anne, Wood, Michelle, Marshall, Adele, Stephenson, Lynsey, Matheson-Smith, Tracy, Sloss, John, Potts, Kathryn, Malkin, Joanne, Ftika, Lemonia, Raviprakash, Veena, Malachira, Ahalya, Kean, Miranda, Criste, Kristine, Gladas, Kirsty, Andrews, Caroline, Hutchison, Clare, Adams, Ellen, Andrews, Janet, Romans, Belinda, Ridley, Nicola, Ekani, Melanie, Mitchell, Julie, Smith, Nicola, Clark, Tristan, Glover, Sarah, Reed, Robert, Yam, Tat, Burton, Holly, Said, Rasha, Janvier, Amy, Jacob, Reni, Smalley, Chris, Fair, Alison, Lord, Susan, Ripalda, Kate, Wooldridge, Helen, Cotter, Luis, Cardoso, Gus, Strachan, Elaine, Kaler, Gagan, Mohamoodally, Adam, Lawrence, Emma, Prime, Zoe, Abrahams, Rachel, Price, David Ashley, Rigden, Lesley, Shewan, Laura, Cullen, Katherine, Emmerson, Ingrid, Martin, Karen, Wilson, Hesther, Higham, Charley, Taylor, Kathryn Louise, Ong, Edmund, Patel, Bijal, Bond, Helena, Gradwell, Janine, Widdrington, John, Thornthwaite, Sarah, Prentice, Scott, Poultney, Una, Crowther, Hannah, Fairlamb, Helen, Hetherington, Emily, Brewer, Chris, Banerjee, Suryabrata, Hamson, Clare, McSkeane, Anna, Sharratt, Paula, Thorpe, Joanne, Kimachia, Sue, Wilson, Helen, Jeffs, Benjamin, Masters, Leslie, Wilson, Jonathan, Platt, Judith, Burgess, Lisa, Chadwick, Paul, Jeans, Adam, Keatley, Claire, Moran, Amanda, Swann, Zoe, Pagett, Katherine, Peel, Alex, Howard, Jason, Maloney, Kate, Masdin, Avril, Wright, Louise, Crossman, Samantha, Lowthorpe, Vicki, Moore, Emma, Moss, Peter, Parkin, Angela, Wolstencroft, Adam, Warner, Bev, Tarbotton, Clare, Eyre, Alison, Anderson, Anne, Burdett, Tina, Driffill, Amy, Walker, Ann Sarah, Szubert, Alex, Webb, Helen, Russell, Charlotte, Jackson, Brooke, Otiko, Damilola, Borg, Chiara, Masters, Lindsey, Islam, Zaheer, Díaz-Montaña, Carlos, Johnson, Debbie

المصدر: Thwaites , G E , Scarborough , M , Szubert , A , Nsutebu , E , Tilley , R , Greig , J , Wyllie , S A , Wilson , P , Auckland , C , Cairns , J , Ward , D , Lal , P , Guleri , A , Jenkins , N , Sutton , J , Wiselka , M , Armando , G-R , Graham , C , Chadwick , P R , Barlow , G , Gordon , N C , Young , B , Meisner , S , McWhinney , P ....

الوصف: Background Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. Methods In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. Findings Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18–45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference −1·4%, 95% ...

الإتاحة: https://doi.org/10.1016/S0140-6736Test(17)32456-X
https://kclpure.kcl.ac.uk/portal/en/publications/fb44bb7b-45e0-4c02-a162-4a3fe2f073f2Test

المؤلفون: Morgan, Angharad R, Touchard, Samuel, Leckey, Claire, O'Hagan, Caroline, Nevado-Holgado, Alejo J, Barkhof, Frederik, Bertram, Lars, Blin, Olivier, Bos, Isabelle, Dobricic, Valerija, Engelborghs, Sebastiaan, Frisoni, Giovanni, Froelich, Lutz, Gabel, Silvey, Johannsen, Peter, Kettunen, Petronella, Koszewska, Iwona, Legido-Quigley, Cristina, Lleo, Alberto, Martinez-Lage, Pablo, Mecocci, Patrizia, Meersmans, Karen, Luis Molinuevo, Jose, Peyratout, Gwendoline, Popp, Julius, Richardson, Jill, Sala, Isabel, Scheltens, Philip, Streffer, Johannes, Soininen, Hikka, Tainta-Cuezva, Mikel, Teunissen, Charlotte, Tsolaki, Magda, Vandenberghe, Rik, Visser, Pieter Jelle, Vos, Stephanie, Wahlund, Lars-Olof, Wallin, Anders, Westwood, Sarah, Zetterberg, Henrik, Lovestone, Simon, Morgan, B Paul, Bullmore, Edward T, Bhatti, Junaid, Chamberlain, Samuel J, Correia, Marta M, Crofts, Anna L, Dickinson, Amber, Foster, Andrew C, Kitzbichler, Manfred G, Knight, Clare, Lynall, Mary-Ellen, Maurice, Christina, O'Donnell, Ciara, Pointon, Linda J, Hyslop, Peter St George, Turner, Lorinda, Vertes, Petra, Widmer, Barry, Williams, Guy B, Leckey, ClaireA, Cavanagh, Jonathan, Deith, Catherine, Farmer, Scott, McClean, John, McColl, Alison, McPherson, Andrew, Scouller, Paul, Sutherland, Murray, Boddeke, HWGM Erik, Richardson, Jill C, Khan, Shahid, Murphy, Phil, Parker, Christine A, Patel, Jai, Jones, Declan, de Boer, Peter, Kemp, John, Drevets, Wayne C, Nye, Jeffrey S, Wittenberg, Gayle, Isaac, John, Bhattacharya, Anindya, Carruthers, Nick, Kolb, Hartmuth, Pariante, Carmine M, Turkheimer, Federico, Barker, Gareth J, Byrom, Heidi, Cash, Diana, Cattaneo, Annamaria, Gee, Antony, Hastings, Caitlin, Mariani, Nicole, McLaughlin, Anna, Mondelli, Valeria, Nettis, Maria, Nikkheslat, Naghmeh, Randall, Karen, Sheridan, Hannah, Simmons, Camilla, Singh, Nisha, Van Loo, Victoria, Vicente-Rodriguez, Marta, Wood, Tobias C, Worrell, Courtney, Zajkowska, Zuzanna, Plath, Niels, Egebjerg, Jan, Eriksson, Hans, Gastambide, Francois, Adams, Karen Husted, Jeggo, Ross, Thomsen, Christian, Pederson, Jan Torleif, Campbell, Brian, Moller, Thomas, Nelson, Bob, Zorn, Stevin, O'Connor, Jason, Attenburrow, Mary Jane, Baird, Alison, Benjamin, Jithen, Clare, Stuart, Cowen, Philip, Huang, I-Shu Dante, Hurley, Samuel, Jones, Helen, Mada, Francisca, Nevado-Holgado, Alejo, Oladejo, Akintayo, Ribe, Elena, Smith, Katy, Vyas, Anviti, Hughes, Zoe, Balice-Gordon, Rita, Duerr, James, Piro, Justin R, Sporn, Jonathan, Perry, V Hugh, Cleal, Madeleine, Fryatt, Gemma, Gomez-Nicola, Diego, Mancuso, Renzo, Reynolds, Richard, Harrison, Neil A, Cercignani, Mara, Clarke, Charlotte L, Hoskins, Elizabeth, Kohn, Charmaine, Murray, Rosemary, Wilcock, Lauren, Wlazly, Dominika

مصطلحات موضوعية: Inflammation, RISK, MILD COGNITIVE IMPAIRMENT, FACTOR-H, Science & Technology, Clinical Neurology, Complement, Biomarker, NONSTEROIDAL ANTIINFLAMMATORY DRUGS, Alzheimer's disease, IDENTIFIES VARIANTS, SERUM, Plasma, CEREBROSPINAL-FLUID, IMMUNE-SYSTEM, Neurosciences & Neurology, GENOME-WIDE ASSOCIATION, Life Sciences & Biomedicine

الوصف: INTRODUCTION: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a "Holy Grail" of AD research and intensively sought; however, there are no well-established plasma markers. METHODS: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed. RESULTS: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71). DISCUSSION: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation. ispartof: ALZHEIMERS & DEMENTIA vol:15 issue:6 pages:776-787 ispartof: location:United States status: published

وصف الملف: Print-Electronic

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=od______1131::d377ef3e0ff06c427898a72e20a4478cTest
https://lirias.kuleuven.be/handle/123456789/665989Test

المؤلفون: Thwaites, Guy E, Scarborough, Matthew, Szubert, Alexander, Nsutebu, Emmanuel, Tilley, Robert, Greig, Julia, Wyllie, Sarah A, Wilson, Peter, Auckland, Cressida, Cairns, Janet, Ward, Denise, Lal, Pankaj, Guleri, Achyut, Jenkins, Neil, Sutton, Julian, Wiselka, Martin, Armando, Gonzalez-Ruiz, Graham, Clive, Chadwick, Paul R, Barlow, Gavin, Gordon, N Claire, Young, Bernadette, Meisner, Sarah, McWhinney, Paul, Price, David A, Harvey, David, Nayar, Deepa, Jeyaratnam, Dakshika, Planche, Tim, Minton, Jane, Hudson, Fleur, Hopkins, Susan, Williams, John, Török, M Estee, Llewelyn, Martin J, Edgeworth, Jonathan D, Walker, A Sarah, Scarborough, Matthew, Kamfose, Musa, de Veciana, Ana, Gordon, Nicola Claire, Peto, Leon, Pill, Gemma, Clarke, Tiphanie, Watson, Laura, Young, Bernadette, Griffiths, Dai, Vaughn, Ali, Anson, Luke, Liu, Elian, Perera, Sanuki, Rylance-Knight, Lydia, Cantell, Carmen, Moroney, Ruth, Edgeworth, Jonathan D, Thwaites, Guy, Bisnauthsing, Karen, Querol-Rubiera, Antonio, Gibbs, Charlotte, Patel, Amita, Hemsley, Carolyn, Goodman, Anna L, Wyncoll, Duncan, Biswas, Jason, Fitzpatrick, Jennifer, Roberts, Lizzie, Millard, James, Stone, Neil, Cape, Angela, Hurley, Lisa, Tam, Chi Kai, Nsutebu, Emmanuel, Hoyle, Marie-Claire, Maitland, Kate, Trainor, Leona, Reynolds, Helen, Harrison, Jennifer, Anson, Jim, Lewis, Joseph, Folb, Jonathan, Goodwin, Lynsey, Beeching, Nicholas, Dyas, Sarah, Winslow, Helen, Foote, Elizabeth, Roberts, Paul, Natarajan, Pavithra, Chrdle, Alex, Fenech, Manuel, Allsop, Hannah, Tilley, Robert, Austin-Hutchison, Rachel, Barrett, Louise, Brookes, Karen, Carwithen, Leanne, Conbeer, Andrew, Cunningham, Richard, Eglinton, Charlotte, Fok, Rosie, Gott, Hannah, Hughes, Shona, Jones, Lewis, Kalita, Maggie, King, Angela, March, Linda, Marner, Mike, Mynes, Tracey, Plant, Aiden, Price, Suzanne, Sercombe, Judy, Stolton, Alison, Wallis, Mark, West, Marie-Claire, Westcott, Jackie, Williams, Claire, Wosley, Rob, Yabsley, Leona, Greig, Julia, Butland, Laura, Sorrell, Julie, Mitchell, Tamara, Alli, Abiola, Meiring, James, Masake, Boingotlo, Rowson, Carlene, Smart, Lynne, Makey, Laura, Moll, Sarah, Cunningham, Jane, Ryalls, Kim, Birchall, Kathryn, Middle, Janet, Jackson, Yvonne, Swift, Diane, Cole, Joby, Subramanian, Bala, Okhuoya, Faith, Edwards, Maria, Bailey, Cheryl, Warren, Rebecca, Islam, Gayti, Ankcorn, Michael, Birchall, Sarah, Jones, Paul, Humphries, John, Booth, Stephen, Evan, Cariad, Wyllie, Sarah, Flatt, Andrew, Strakova, Lenka, Hayes, Maria, Valentine, Stacey, James, Clare, Wands, Mary, Cortes, Nicolas, Khan, Nisa, Porter, Robert, Martin, Zoe, Yip, Keith, Preedy, Helen, Chesterfield, Helen, Dobson, Tracey, Walker, Colin, Llewelyn, Martin, Dunne, Angela, Latter, Laura, Porges, Alison, Price, James, Paul, John, Behar, Laura, Robinson, Louise, Murray, Amy, Fitzpatrick, Jennifer, Sargent, Tenessa, Ridley, Carrie, de Gordoa, Laura Ortiz-Ruiz, Gilliam, Deborah, McPherson, Carole, Matthews, Simon, Foreman, Emma, Jarghese, Rajesh, Beddoe, Alisha, Martin, Sebastien, Shaw, Sephora, Wlazly, Dominika, Cole, Maggie, Gihawi, Abraham, Cole, Kevin, Török, M Estée, Gouliouris, Theodore, Bedford, Luke, Saunderson, Rebecca B, Mariolis, Ilias, Bousfield, Rachel, Ramsay, Isobel, Greaves, Daniel, Aliyu, Sani, Cox, Kim, Mlemba, Lois, Whitehead, Lynne, Vyse, Naval, Bolton, Mark, Williams, John, Lambert, Pauline, Chadwick, David, Baillie, Kirsty, Cain, Martyn, Bellamy, Richard, Wong, Jason, Thompson, Jane, Vassallo, Helen, Skotnicka, Agnieszka, Boyce, Andrea, Donnelly, Anthony, Wilson, Peter, FitzGerald, Graham, Dean, Victoria, Warnes, Kristian, Reyes, Anna, Rahman, Saadia, Tsang, Lillian, Williams, Joanne, Morris-Jones, Stephen, Hopkins, Susan, Witness, Elen, Brady, Orla, Woodford, Elizabeth, Pettifer, Teresa, McCadden, Angela, Marks, Ben, Collier, Sophie, Mack, Damien, Warren, Simon, Brown, Colin, Lyons, Adrian, Taiyari, Sara, Mepham, Stephen, Sweeney, Anna, Brown, Li-An, Auckland, Cressida, Potter, Alison, Mandiza, Jess, Hough, Maxine, Williams, Sue, Renton, Caroline, Walters, Fiona, Nadolski, Maria, Evans, Andree, Tarrant, Polly, Curley, Katherine, Whiteley, Sophie, Halpin, Julia, Hutchings, Melanie, Todd, Shirley, Lohan, Christop, Chapter, Tamika, Folland, Emma, Colville, Alaric, Marden, Katy, Morgan, Marina, Fok, Rosie, Porter, Rob, Baxter, Mel, Minton, Jane, Rippon, Sarah, Cevik, Muge, Chapman, Judith, Kemp, Tim, Vincent, Rachel, Osborne, Dave, Platt, Tracey, Calderwood, James, Cook, Bernadette, Bedford, Caroline, Galloway-Browne, Leanne, Abberley, Nadine, Attack, Kelly, Allen, Joanna, Lal, Pankaj, Harrison, Melanie, Stevenson, Sarah, Brooks, Carol, Harlow, Paula, Ewing, Jordan, Cooper, Shirley, Balancio-Tolentino, Roderick, O'Neil, Laura, Tagney, Rebecca, Shackcloth, Daniela, Planche, Tim, Fellows, James, Millett, Ruth, Studham, Jo, de Souza, Cherrelle, Howell, Geoffrey, Greaves, Hezron, Foncel, Ella, Kurup, Rahul, Briggs, Jack, Smith, Melody, Suarez, Cristina, Sorrentino, Giordana, Scobie, 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Atul, Sim, Christopher, Rosser, Andrew, Deane, Jill, Nendick, Richard, Aldridge, Catherine, Clarke, Anne, Wood, Michelle, Marshall, Adele, Stephenson, Lynsey, Matheson-Smith, Tracy, Sloss, John, Potts, Kathryn, Malkin, Joanne, Ftika, Lemonia, Raviprakash, Veena, Sutton, Julian, Malachira, Ahalya, Kean, Miranda, Criste, Kristine, Gladas, Kirsty, Andrews, Caroline, Hutchison, Clare, Adams, Ellen, Andrews, Janet, Romans, Belinda, Ridley, Nicola, Ekani, Melanie, Mitchell, Julie, Smith, Nicola, Clark, Tristan, Glover, Sarah, Reed, Robert, Yam, Tat, Burton, Holly, Said, Rasha, Harvey, David, Janvier, Amy, Jacob, Reni, Smalley, Chris, Fair, Alison, Lord, Susan, Ripalda, Kate, Wooldridge, Helen, Cotter, Luis, Cardoso, Gus, Strachan, Elaine, Kaler, Gagan, Mohamoodally, Adam, Lawrence, Emma, Prime, Zoe, Abrahams, Rachel, Price, David Ashley, Rigden, Lesley, Shewan, Laura, Cullen, Katherine, Emmerson, Ingrid, Martin, Karen, Wilson, Hesther, Higham, Charley, Taylor, Kathryn Louise, Ong, Edmund, 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Díaz-Montaña, Carlos, Johnson, Debbie

المصدر: The Lancet; February 2018, Vol. 391 Issue: 10121 p668-678, 11p

مستخلص: Staphylococcus aureusbacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureuskilling, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection.