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Sergei Fedorovich, Jeannette Hofmeijer, Michel J A M van Putten, Joost le Feber
Improvement of neuronal recovery in the ischemic penumbra, an area around the core of a brain infarct with some remaining perfusion, has a large potential for the development of therapy against acute ischemic stroke. However, mechanisms that lead to either recovery or secondary damage in the penumbra largely remain unclear. Recent studies in cultured networks of cortical neurons showed that failure of synaptic transmission (referred to as synaptic failure) is a critical factor in the penumbral area, but the mechanisms that lead to synaptic failure are still under investigation...
2017: Frontiers in Cellular Neuroscience
Andrew Feber, Pawan Dhami, Liqin Dong, Patricia de Winter, Wei Shen Tan, Mónica Martínez-Fernández, Dirk S Paul, Antony Hynes-Allen, Sheida Rezaee, Pratik Gurung, Simon Rodney, Ahmed Mehmood, Felipe Villacampa, Federico de la Rosa, Charles Jameson, Kar Keung Cheng, Maurice P Zeegers, Richard T Bryan, Nicholas D James, Jesus M Paramio, Alex Freeman, Stephan Beck, John D Kelly
BACKGROUND: Bladder cancer (BC) is one of the most common cancers in the western world and ranks as the most expensive to manage, due to the need for cystoscopic examination. BC shows frequent changes in DNA methylation, and several studies have shown the potential utility of urinary biomarkers by detecting epigenetic alterations in voided urine. The aim of this study is to develop a targeted bisulfite next-generation sequencing assay to diagnose BC from urine with high sensitivity and specificity...
2017: Clinical Epigenetics
Anna Karpathakis, Harpreet Dibra, Christodoulos Pipinikas, Andrew Feber, Tiffany Morris, Joshua M Francis, Dahmane Oukrif, Dalvinder Mandair, Marinos Pericleous, Mullan Mohmaduvesh, Stefano Serra, Olagunju Ogunbiyi, Marco Novelli, Tu Vinh Luong, Sylvia L Asa, Matthew H Kulke, Christos Toumpanakis, Tim Meyer, Martyn Caplin, Stephan Beck, Christina Thirlwell
Dear Editor The incidence of small intestinal neuroendocrine tumours (SINETs) is increasing and distant metastases are present at diagnosis in 70% of cases, the liver being the most common site of metastasis. Despite this, our understanding of the mechanisms underlying metastatic progression of SINETs is currently limited and prior studies of the molecular biology of SINET liver metastases (LM) have been performed predominantly in small cohorts utilising candidate based techniques.
January 3, 2017: Endocrine-related Cancer
Ankur Chakravarthy, Stephen Henderson, Stephen M Thirdborough, Christian H Ottensmeier, Xiaoping Su, Matt Lechner, Andrew Feber, Gareth J Thomas, Tim R Fenton
Purpose In squamous cell carcinomas of the head and neck (HNSCC), the increasing incidence of oropharyngeal squamous cell carcinomas (OPSCCs) is attributable to human papillomavirus (HPV) infection. Despite commonly presenting at late stage, HPV-driven OPSCCs are associated with improved prognosis compared with HPV-negative disease. HPV DNA is also detectable in nonoropharyngeal (non-OPSCC), but its pathogenic role and clinical significance are unclear. The objectives of this study were to determine whether HPV plays a causal role in non-OPSCC and to investigate whether HPV confers a survival benefit in these tumors...
December 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
E Kuijpers, C Bekker, D Brouwer, M Le Feber, W Fransman
Exposure assessment for nano-objects, and their aggregates and agglomerates (NOAA) has evolved from explorative research towards more comprehensive exposure assessment, providing data to further develop currently used conservative control banding (CB) tools for risk assessment. This study aims to provide an overview of current knowledge on emission potential of NOAA across the occupational life cycle stages by a systematic review and subsequently use the results in a data analysis. Relevant parameters that influence emission were collected from peer-reviewed literature with a focus on the four source domains (SD) in the source-receptor conceptual framework for NOAA...
November 1, 2016: Journal of Occupational and Environmental Hygiene
Andrew E Teschendorff, Shijie C Zheng, Andy Feber, Zhen Yang, Stephan Beck, Martin Widschwendter
BACKGROUND: Hypermethylation of transcription factor promoters bivalently marked in stem cells is a cancer hallmark. However, the biological significance of this observation for carcinogenesis is unclear given that most of these transcription factors are not expressed in any given normal tissue. METHODS: We analysed the dynamics of gene expression between human embryonic stem cells, fetal and adult normal tissue, as well as six different matching cancer types. In addition, we performed an integrative multi-omic analysis of matched DNA methylation, copy number, mutational and transcriptomic data for these six cancer types...
August 25, 2016: Genome Medicine
Andrew Feber, Daniel C Worth, Ankur Chakravarthy, Patricia de Winter, Kunal Shah, Manit Arya, Muhammad Saqib, Raj Nigam, Peter R Malone, Wei Shen Tan, Simon Rodney, Alex Freeman, Charles Jameson, Gareth A Wilson, Tom Powles, Stephan Beck, Tim Fenton, Tyson V Sharp, Asif Muneer, John D Kelly
Other than an association with HPV infection, little is known about the genetic alterations determining the development of penile cancer. Although penile cancer is rare in the developed world, it presents a significant burden in developing countries. Here, we report the findings of whole-exome sequencing (WES) to determine the somatic mutational landscape of penile cancer. WES was performed on penile cancer and matched germline DNA from 27 patients undergoing surgical resection. Targeted resequencing of candidate genes was performed in an independent 70 patient cohort...
August 15, 2016: Cancer Research
Kevin C Harris, Geneviève Benoit, Janis Dionne, Janusz Feber, Lyne Cloutier, Kelly B Zarnke, Raj S Padwal, Doreen M Rabi, Anne Fournier
We present the inaugural evidence-based Canadian recommendations for the measurement of blood pressure in children and the diagnosis and evaluation of pediatric hypertension. Rates of pediatric hypertension are increasing concomitant with increased rates of childhood obesity. With this, there is growing awareness of the need to measure blood pressure in children. Consequently, the present recommendations have been developed to address an important gap and improve the clinical care of children. For 2016, a total of 15 recommendations are presented...
2016: Canadian Journal of Cardiology
Alexander A Leung, Kara Nerenberg, Stella S Daskalopoulou, Kerry McBrien, Kelly B Zarnke, Kaberi Dasgupta, Lyne Cloutier, Mark Gelfer, Maxime Lamarre-Cliche, Alain Milot, Peter Bolli, Guy Tremblay, Donna McLean, Sheldon W Tobe, Marcel Ruzicka, Kevin D Burns, Michel Vallée, G V Ramesh Prasad, Marcel Lebel, Ross D Feldman, Peter Selby, Andrew Pipe, Ernesto L Schiffrin, Philip A McFarlane, Paul Oh, Robert A Hegele, Milan Khara, Thomas W Wilson, S Brian Penner, Ellen Burgess, Robert J Herman, Simon L Bacon, Simon W Rabkin, Richard E Gilbert, Tavis S Campbell, Steven Grover, George Honos, Patrice Lindsay, Michael D Hill, Shelagh B Coutts, Gord Gubitz, Norman R C Campbell, Gordon W Moe, Jonathan G Howlett, Jean-Martin Boulanger, Ally Prebtani, Pierre Larochelle, Lawrence A Leiter, Charlotte Jones, Richard I Ogilvie, Vincent Woo, Janusz Kaczorowski, Luc Trudeau, Robert J Petrella, Swapnil Hiremath, Denis Drouin, Kim L Lavoie, Pavel Hamet, George Fodor, Jean C Grégoire, Richard Lewanczuk, George K Dresser, Mukul Sharma, Debra Reid, Scott A Lear, Gregory Moullec, Milan Gupta, Laura A Magee, Alexander G Logan, Kevin C Harris, Janis Dionne, Anne Fournier, Geneviève Benoit, Janusz Feber, Luc Poirier, Raj S Padwal, Doreen M Rabi
Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force provides annually updated, evidence-based recommendations to guide the diagnosis, assessment, prevention, and treatment of hypertension. This year, we present 4 new recommendations, as well as revisions to 2 previous recommendations. In the diagnosis and assessment of hypertension, automated office blood pressure, taken without patient-health provider interaction, is now recommended as the preferred method of measuring in-office blood pressure...
2016: Canadian Journal of Cardiology
Mieczyslaw Litwin, Janusz Feber, Marcel Ruzicka
Hypertension (HTN) in children is associated with early vascular aging (EVA) and underlying immunologic-metabolic abnormalities and accelerated biological maturation. Morphologic and functional vascular changes underlying EVA and HTN in children resemble those seen in the elderly including but not limited to an increase in intima-media thickness (IMT) and arterial stiffness and endothelial dysfunction. Although progeria syndrome leading to EVA and the development of clinically manifested cardiovascular (CV) disease in the second decade of life is a rare hereditary disorder, primary HTN, which is also associated with EVA, is much more common (reported in up to 10% in adolescents)...
2016: Canadian Journal of Cardiology
Christian C Raiss, Theresa S Braun, Irene B M Konings, Heinrich Grabmayr, Gerco C Hassink, Arshdeep Sidhu, Joost le Feber, Andreas R Bausch, Casper Jansen, Vinod Subramaniam, Mireille M A E Claessens
The formation of α-synuclein (α-S) amyloid aggregates, called Lewy bodies (LBs), is a hallmark of Parkinson's disease (PD). The function of LBs in the disease process is however still unclear; they have been associated with both neuroprotection and toxicity. To obtain insight into this contradiction, we induced the formation of α-S inclusions, using three different induction methods in SH-SY5Y cells and rat-derived primary neuronal cells. Using confocal and STED microscopy we observed induction-dependent differences in α-S inclusion morphology, location and function...
March 17, 2016: Scientific Reports
I V Kabakova, A de Hoogh, R E C van der Wel, M Wulf, B le Feber, L Kuipers
Near-field imaging is a powerful tool to investigate the complex structure of light at the nanoscale. Recent advances in near-field imaging have indicated the possibility for the complete reconstruction of both electric and magnetic components of the evanescent field. Here we study the electro-magnetic field structure of surface plasmon polariton waves propagating along subwavelength gold nanowires by performing phase- and polarization-resolved near-field microscopy in collection mode. By applying the optical reciprocity theorem, we describe the signal collected by the probe as an overlap integral of the nanowire's evanescent field and the probe's response function...
2016: Scientific Reports
Joost le Feber, Stelina Tzafi Pavlidou, Niels Erkamp, Michel J A M van Putten, Jeannette Hofmeijer
Improvement of neuronal recovery in the ischemic penumbra around a brain infarct has a large potential to advance clinical recovery of patients with acute ischemic stroke. However, pathophysiological mechanisms leading to either recovery or secondary damage in the penumbra are not completely understood. We studied neuronal dynamics in a model system of the penumbra consisting of networks of cultured cortical neurons exposed to controlled levels and durations of hypoxia. Short periods of hypoxia (pO2≈20mmHg) reduced spontaneous activity, due to impeded synaptic function...
2016: PloS One
Mattheus T T Oosterwijk, Maaike Le Feber, Enrico Burello
We present a conceptual framework that can be used to assign risk bands to inhaled low aspect ratio nanoparticles starting from exposure bands assigned to a specific exposure situation. The framework mimics a basic physiological scheme that captures the essential mechanisms of fate and toxicity of inhaled nanoparticles and is composed of several models and rules that estimate the result of the following processes: the deposition of particles in the respiratory tract, their (de-)agglomeration, lung burden and clearance, their diffusion through the lung mucus layer, translocation and cellular uptake and local and systemic toxicity...
August 2016: Nanotoxicology
Katarina Prochotska, Laszlo Kovacs, Eva Vitariusova, Janusz Feber
The aim of the article was to evaluate arterial stiffness, an early marker of increased cardiovascular risk, in relation to obesity. The continuous metabolic syndrome (cMetS) score was calculated as sum of Z score of mean arterial pressure, body mass index, serum glucose, triglyceride, and high-density lipoprotein cholesterol in 144 obese patients and 66 nonobese controls. Ambulatory arterial stiffness index (AASI) was calculated as 1 minus regression slope of diastolic on systolic blood pressure from ambulatory blood pressure measurements...
January 2016: Journal of the American Society of Hypertension: JASH
Dirk S Paul, Allison Jones, Rob S Sellar, Neema P Mayor, Andrew Feber, Amy P Webster, Neuza Afonso, Ruhena Sergeant, Richard M Szydlo, Jane F Apperley, Martin Widschwendter, Stephen Mackinnon, Steven G E Marsh, J Alejandro Madrigal, Vardhman K Rakyan, Karl S Peggs, Stephan Beck
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hematological conditions. Acute graft-versus-host disease (aGVHD) is a prevalent immune-mediated complication following HSCT. Current diagnostic biomarkers that correlate with aGVHD severity, progression, and therapy response in graft recipients are insufficient. Here, we investigated whether epigenetic marks measured in peripheral blood of healthy graft donors stratify aGVHD severity in human leukocyte antigen (HLA)-matched sibling recipients prior to T cell-depleted HSCT...
December 15, 2015: Genome Medicine
Helena Carén, Stefan H Stricker, Harry Bulstrode, Sladjana Gagrica, Ewan Johnstone, Thomas E Bartlett, Andrew Feber, Gareth Wilson, Andrew E Teschendorff, Paul Bertone, Stephan Beck, Steven M Pollard
Glioblastoma (GBM) is an aggressive brain tumor whose growth is driven by stemcell-like cells. BMP signaling triggers cell-cycle exit and differentiation of GBM stemcells (GSCs) and, therefore, might have therapeutic value. However, the epigenetic mechanisms that accompany differentiation remain poorly defined. It is also unclear whether cell-cycle arrest is terminal. Herewe find only a subset ofGSCcultures exhibit astrocyte differentiation in response to BMP. Although overtly differentiated non-cycling astrocytes are generated, they remain vulnerable to cell-cycle re-entry and fail to appropriately reconfigure DNA methylation patterns...
November 10, 2015: Stem Cell Reports
Joost le Feber, Wybren Postma, Eddy de Weerd, Marcel Weusthof, Wim L C Rutten
Cultured neurons on multi electrode arrays (MEAs) have been widely used to study various aspects of neuronal (network) functioning. A possible drawback of this approach is the lack of structure in these networks. At the single cell level, several solutions have been proposed to enable directed connectivity, and promising results were obtained. At the level of connected sub-populations, a few attempts have been made with promising results. First assessment of the designs' functionality, however, suggested room for further improvement...
2015: Frontiers in Neuroscience
Joost le Feber, Tim Witteveen, Tamar M van Veenendaal, Jelle Dijkstra
During systems consolidation, memories are spontaneously replayed favoring information transfer from hippocampus to neocortex. However, at present no empirically supported mechanism to accomplish a transfer of memory from hippocampal to extra-hippocampal sites has been offered. We used cultured neuronal networks on multielectrode arrays and small-scale computational models to study the effect of memory replay on the formation of memory traces. We show that input-deprived networks develop an activity⇔connectivity balance where dominant activity patterns support current connectivity...
December 2015: Learning & Memory
Irina I Stoyanova, Jeannette Hofmeijer, Michel J A M van Putten, Joost le Feber
Comatose patients after cardiac arrest have a poor prognosis. Approximately half never awakes as a result of severe diffuse postanoxic encephalopathy. Several neuroprotective agents have been tested, however without significant effect. In the present study, we used cultured neuronal networks as a model system to study the general synaptic damage caused by temporary severe hypoxia and the possibility to restrict it by ghrelin treatment. Briefly, we applied hypoxia (pO2 lowered from 150 to 20 mmHg) during 6 h in 55 cultures...
November 2016: Molecular Neurobiology
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