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https://www.readbyqxmd.com/read/28322270/huntington-s-disease-blood-and-brain-show-a-common-gene-expression-pattern-and-share-an-immune-signature-with-alzheimer-s-disease
#1
Davina J Hensman Moss, Michael D Flower, Kitty K Lo, James R C Miller, Gert-Jan B van Ommen, Peter A C 't Hoen, Timothy C Stone, Amelia Guinee, Douglas R Langbehn, Lesley Jones, Vincent Plagnol, Willeke M C van Roon-Mom, Peter Holmans, Sarah J Tabrizi
There is widespread transcriptional dysregulation in Huntington's disease (HD) brain, but analysis is inevitably limited by advanced disease and postmortem changes. However, mutant HTT is ubiquitously expressed and acts systemically, meaning blood, which is readily available and contains cells that are dysfunctional in HD, could act as a surrogate for brain tissue. We conducted an RNA-Seq transcriptomic analysis using whole blood from two HD cohorts, and performed gene set enrichment analysis using public databases and weighted correlation network analysis modules from HD and control brain datasets...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28315277/the-role-of-sigma1r-in-mammalian-retina
#2
Jing Wang, Xuezhi Cui, Penny Roon, Alan Saul, Sylvia B Smith
This review article focuses on studies of Sigma 1 Receptor (Sigma1R) and retina . It provides a brief overview of the earliest pharmacological studies performed in the late 1990s that provided evidence of the presence of Sigma1R in various ocular tissues. It then describes work from a number of labs concerning the location of Sigma1R in several retinal cell types including ganglion, Müller glia , and photoreceptors . The role of Sigma1R ligands in retinal neuroprotection is emphasized. Early studies performed in vitro clearly showed that targeting Sigma1R could attenuate stress-induced retinal cell loss...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28297047/patient-related-factors-influencing-patency-of-autogenous-brachiocephalic-haemodialysis-fistulas
#3
Alexander Lamprou, Cor de Bruin, Arie van Roon, Jan Loonstra, Maarten van der Laan, Ignace Tielliu, Clark Zeebregts
OBJECTIVE: The objective of this study was to analyse the outcome of autogenous brachiocephalic fistula for dialysis purposes and to determine modifiable and non-modifiable patient-related factors of influence on the patency of a newly created fistula. DESIGN OF STUDY: A single-centre retrospective cohort study with the aim of determining patient-related factors of influence on primary failure, primary, primary assisted and secondary patency of autogenous brachiocephalic fistulas...
March 6, 2017: Journal of Vascular Access
https://www.readbyqxmd.com/read/28289078/delivery-is-key-lessons-learnt-from-developing-splice-switching-antisense-therapies
#4
REVIEW
Caroline Godfrey, Lourdes R Desviat, Bård Smedsrød, France Piétri-Rouxel, Michela A Denti, Petra Disterer, Stéphanie Lorain, Gisela Nogales-Gadea, Valentina Sardone, Rayan Anwar, Samir El Andaloussi, Taavi Lehto, Bernard Khoo, Camilla Brolin, Willeke Mc van Roon-Mom, Aurélie Goyenvalle, Annemieke Aartsma-Rus, Virginia Arechavala-Gomeza
The use of splice-switching antisense therapy is highly promising, with a wealth of pre-clinical data and numerous clinical trials ongoing. Nevertheless, its potential to treat a variety of disorders has yet to be realized. The main obstacle impeding the clinical translation of this approach is the relatively poor delivery of antisense oligonucleotides to target tissues after systemic delivery. We are a group of researchers closely involved in the development of these therapies and would like to communicate our discussions concerning the validity of standard methodologies currently used in their pre-clinical development, the gaps in current knowledge and the pertinent challenges facing the field...
March 13, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28278719/restoration-of-renal-function-in-patients-with-newly-diagnosed-multiple-myeloma-is-not-associated-with-improved-survival-a-population-based-study
#5
Joost C de Vries, Berdien Oortgiesen, Marc H Hemmelder, Eric van Roon, Robby E Kibbelaar, Nic Veeger, Mels Hoogendoorn
Renal impairment (RI) in patients with multiple myeloma (MM) is associated with poor prognosis. In this population-based cohort study, we assessed the effects of renal response, evaluated according to the IMWG-criteria, on overall survival (OS) in patients with newly diagnosed MM with RI at presentation. All included patients were diagnosed between January 2005 and January 2014 with MM and RI in Friesland, a province of the Netherlands. Of the 131 included patients, 61% achieved renal response. Using a time-varying exposure Cox model, no difference in OS between renal response and non-response was observed (HR = 1...
February 14, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28258356/the-role-of-initial-clinical-presentation-comorbidity-and-treatment-in-multiple-myeloma-patients-on-survival-a-detailed-population-based-cohort-study
#6
B E Oortgiesen, E N van Roon, P Joosten, R E Kibbelaar, H Storm, S Hovenga, B van Rees, G Woolthuis, N Veeger, E G de Waal, M Hoogendoorn
PURPOSE: This prospective, observational population-based cohort study was performed to determine overall survival (OS) in multiple myeloma (MM) patients in Friesland, the Netherlands, in the era of novel agents and to analyse the influence of first-line treatment, MM-related end-organ damage and comorbidities at initial presentation on OS. METHODS: Detailed clinical information was obtained from the population-based registry 'HemoBase' during the period January 2005 to January 2013, with a follow-up to January 2014...
March 3, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28244635/effect-of-linagliptin-on-pulse-wave-velocity-in-early-type-2-diabetes-release-a-randomized-double-blind-controlled-26-week-trial
#7
Stefanie A de Boer, Hiddo J L Heerspink, Luis E Juárez Orozco, Arie M van Roon, Pieter W Kamphuisen, Andries J Smit, Riemer H J A Slart, Joop D Lefrandt, Douwe J Mulder
AIMS: To evaluate the effects of the DPP-4 inhibitor linagliptin on aortic pulse wave velocity (PWV) as a surrogate marker of arterial stiffness and early atherosclerosis in early type 2 diabetes subjects. MATERIALS AND METHODS: A total of 45 type 2 diabetes subjects (median age 63 (IQR: 54-66) years, 61% male, mean hemoglobinA1c (HbA1c ) 6.3 ± 0.4 % (45 ± 4.6 mmol/mol)) without cardiovascular disease and naïve to antidiabetic treatment were randomized (1:1) to treatment with linagliptin 5 mg once daily or placebo for 26 weeks in a double-blind fashion...
February 28, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28112627/high-prevalence-of-tula-hantavirus-in-common-voles-in-the-netherlands
#8
Miriam Maas, Ankje de Vries, Annika van Roon, Katsuhisa Takumi, Joke van der Giessen, Barry Rockx
Tula virus (TULV) is a zoonotic hantavirus. Knowledge about TULV in the Netherlands is very scarce. Therefore in 2014, 49 common voles (Microtus arvalis) from a region in the south of the Netherlands, and in 2015, 241 common voles from regions in the north of the Netherlands were tested with the TULV quantitative RT-PCR. In the southern region, prevalence of TULV was 41% (20/49). In the northern regions, prevalence ranged from 12% (4/34) to 45% (17/38). Phylogenetic analysis of the obtained sequences showed that the regions fall within different clusters...
March 2017: Vector Borne and Zoonotic Diseases
https://www.readbyqxmd.com/read/28076669/medication-discrepancies-at-outpatient-departments-for-mood-and-anxiety-disorders-in-the-netherlands-risks-and-clinical-relevance
#9
Mirjam Simoons, Hans Mulder, Arne J Risselada, Frederik W Wilmink, Robert Schoevers, Henricus G Ruhé, Eric N van Roon
OBJECTIVE: To identify discrepancies between actual drug use by outpatients with mood and anxiety disorders and medication overviews from health care providers as well as to investigate the clinical relevance of those discrepancies. METHODS: A cross-sectional study in adults visiting 1 of 4 participating outpatient departments for mood and anxiety disorders was conducted between March and November 2014. DSM-5 criteria were used to assign the psychiatric diagnosis...
November 2016: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28017939/huntingtin-is-a-scaffolding-protein-in-the-atm-oxidative-dna-damage-response-complex
#10
Tamara Maiuri, Andrew J Mocle, Claudia L Hung, Jianrun Xia, Willeke M C van Roon-Mom, Ray Truant
Huntington's disease (HD) is an age-dependent neurodegenerative disease. DNA repair pathways have recently been implicated as the most predominant modifiers of age of onset in HD patients. We report that endogenous huntingtin protein directly participates in oxidative DNA damage repair. Using novel chromobodies to detect endogenous human huntingtin in live cells, we show that localization of huntingtin to DNA damage sites is dependent on the kinase activity of ataxia telangiectasia mutated (ATM) protein. Super-resolution microscopy and biochemical assays revealed that huntingtin co-localizes with and scaffolds proteins of the DNA damage response pathway in response to oxidative stress...
December 25, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27987023/comparative-study-of-episiotomy-angles-achieved-by-cutting-with-straight-mayo-scissors-and-the-episcissors-60-in-a-birth-simulation-model
#11
Yves van Roon, Latha Vinayakarao, Louise Melson, Rebecca Percival, Sangeeta Pathak, Ashish Pradhan
INTRODUCTION AND HYPOTHESIS: We compared the clinician's ability to cut episiotomies at the recommended 60° angle with traditional straight Mayo scissors compared with patented fixed-angle episiotomy scissors EPISCISSORS-60® in a simulated setting using mounted incision pads. The hypothesis was that fixed-angle episiotomies would achieve a more accurate cutting angle of 60°. METHODS: Angles were cut on episiotomy incision pads in a mounted birth model simulating crowning: 110 midwives and doctors cut an 60° episiotomy with Mayo scissors and then EPISCISSORS-60...
December 16, 2016: International Urogynecology Journal
https://www.readbyqxmd.com/read/27981025/long-term-effects-of-a-weight-loss-intervention-with-or-without-exercise-component-in-postmenopausal-women-a-randomized-trial
#12
Martijn de Roon, Willemijn A van Gemert, Petra H Peeters, Albertine J Schuit, Evelyn M Monninkhof
The aim of this study was to determine the long-term effects of a weight loss intervention with or without an exercise component on body weight and physical activity. Women were randomized to diet (n = 97) or exercise (N = 98) for 16 weeks. During the intervention, both groups had achieved the set goal of 5-6 kg weight loss. All women were re-contacted twelve months after study cessation for follow-up where body weight and physical activity were measured (PASE questionnaire and ActiGraph accelerometer)...
March 2017: Preventive Medicine Reports
https://www.readbyqxmd.com/read/27887781/high-psychosis-liability-is-associated-with-altered-autonomic-balance-during-exposure-to-virtual-reality-social-stressors
#13
Jacqueline Counotte, Roos Pot-Kolder, Arie M van Roon, Olivier Hoskam, Mark van der Gaag, Wim Veling
BACKGROUND: Social stressors are associated with an increased risk of psychosis. Stress sensitisation is thought to be an underlying mechanism and may be reflected in an altered autonomic stress response. Using an experimental Virtual Reality design, the autonomic stress response to social stressors was examined in participants with different liability to psychosis. METHOD: Fifty-five patients with recent onset psychotic disorder, 20 patients at ultra-high risk for psychosis, 42 siblings of patients with psychosis and 53 controls were exposed to social stressors (crowdedness, ethnic minority status and hostility) in a Virtual Reality environment...
November 22, 2016: Schizophrenia Research
https://www.readbyqxmd.com/read/27884437/evaluation-by-latent-class-analysis-of-a-magnetic-capture-based-dna-extraction-followed-by-real-time-qpcr-as-a-new-diagnostic-method-for-detection-of-echinococcus-multilocularis-in-definitive-hosts
#14
Miriam Maas, Annika van Roon, Cecile Dam-Deisz, Marieke Opsteegh, Alessandro Massolo, Gunita Deksne, Peter Teunis, Joke van der Giessen
A new method, based on a magnetic capture based DNA extraction followed by qPCR, was developed for the detection of the zoonotic parasite Echinococcus multilocularis in definitive hosts. Latent class analysis was used to compare this new method with the currently used phenol-chloroform DNA extraction followed by single tube nested PCR. In total, 60 red foxes and coyotes from three different locations were tested with both molecular methods and the sedimentation and counting technique (SCT) or intestinal scraping technique (IST)...
October 30, 2016: Veterinary Parasitology
https://www.readbyqxmd.com/read/27747155/first-findings-of-trichinella-spiralis-and-dna-of-echinococcus-multilocularis-in-wild-raccoon-dogs-in-the-netherlands
#15
Miriam Maas, Sanne van den End, Annika van Roon, Jaap Mulder, Frits Franssen, Cecile Dam-Deisz, Margriet Montizaan, Joke van der Giessen
The recent invasion of the raccoon dog in the Netherlands may be associated with the risk of introduction and spread of zoonotic pathogens. The aim of this study was to assess whether Echinococcus multilocularis and Trichinella spp. infections are present in Dutch raccoon dogs. Between 2013 and 2014, nine raccoon dogs, mainly road kills, were collected for necropsies. One raccoon dog tested repeatedly positive in the qPCR for E. multilocularis. The positive raccoon dog was collected in the province of Flevoland, which is not a known endemic region for E...
December 2016: International Journal for Parasitology. Parasites and Wildlife
https://www.readbyqxmd.com/read/27731380/antisense-oligonucleotide-mediated-exon-skipping-as-a-strategy-to-reduce-proteolytic-cleavage-of-ataxin-3
#16
Lodewijk J A Toonen, Iris Schmidt, Martijn S Luijsterburg, Haico van Attikum, Willeke M C van Roon-Mom
Spinocerebellar ataxia type-3 (SCA3) is a neurodegenerative disorder caused by a polyglutamine repeat expansion in the ataxin-3 protein. Cleavage of mutant ataxin-3 by proteolytic enzymes yields ataxin-3 fragments containing the polyglutamine stretch. These shorter ataxin-3 fragments are thought to be involved in SCA3 pathogenesis due to their increased cellular toxicity and their involvement in formation of the characteristic neuronal aggregates. As a strategy to prevent formation of toxic cleavage fragments, we investigated an antisense oligonucleotide-mediated modification of the ataxin-3 pre-mRNA through exon skipping of exon 8 and 9, resulting in the removal of a central 88 amino acid region of the ataxin-3 protein...
October 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27639545/in-vivo-proof-of-concept-of-removal-of-the-huntingtin-caspase-cleavage-motif-encoding-exon-12-approach-in-the-yac128-mouse-model-of-huntington-s-disease
#17
João Casaca-Carreira, Lodewijk J A Toonen, Melvin M Evers, Ali Jahanshahi, Willeke M C van-Roon-Mom, Yasin Temel
Huntington's disease (HD) is a progressive autosomal dominant disease, caused by a CAG repeat expansion in the HTT gene, resulting in an expanded polyglutamine stretch at the N-terminal of the huntingtin protein. An important event in HD pathogenesis appears to be the proteolysis of the mutant protein, which forms N-terminal huntingtin fragments. These fragments form insoluble aggregates and are found in nuclei and cytoplasm of affected neurons where they interfere with normal cell functioning. Important cleavage sites are encoded by exon 12 of HTT...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27615381/frequency-of-nuclear-mutant-huntingtin-inclusion-formation-in-neurons-and-glia-is-cell-type-specific
#18
Anne H P Jansen, Maurik van Hal, Ilse C Op den Kelder, Romy T Meier, Anna-Aster de Ruiter, Menno H Schut, Donna L Smith, Corien Grit, Nieske Brouwer, Willem Kamphuis, H W G M Boddeke, Wilfred F A den Dunnen, Willeke M C van Roon, Gillian P Bates, Elly M Hol, Eric A Reits
Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder that is caused by a CAG expansion in the Huntingtin (HTT) gene, leading to HTT inclusion formation in the brain. The mutant huntingtin protein (mHTT) is ubiquitously expressed and therefore nuclear inclusions could be present in all brain cells. The effects of nuclear inclusion formation have been mainly studied in neurons, while the effect on glia has been comparatively disregarded. Astrocytes, microglia, and oligodendrocytes are glial cells that are essential for normal brain function and are implicated in several neurological diseases...
January 2017: Glia
https://www.readbyqxmd.com/read/27571731/4-aminopyridine-as-a-life-saving-treatment-in-calcium-channel-antagonist-intoxication
#19
P H J van der Voort, B Wilffert, E N van Roon, D R A Uges
No abstract text is available yet for this article.
July 2016: Netherlands Journal of Medicine
https://www.readbyqxmd.com/read/27524956/integration-of-targeted-metabolomics-and-transcriptomics-identifies-deregulation-of-phosphatidylcholine-metabolism-in-huntington-s-disease-peripheral-blood-samples
#20
Anastasios Mastrokolias, Rene Pool, Eleni Mina, Kristina M Hettne, Erik van Duijn, Roos C van der Mast, GertJan van Ommen, Peter A C 't Hoen, Cornelia Prehn, Jerzy Adamski, Willeke van Roon-Mom
INTRODUCTION: Metabolic changes have been frequently associated with Huntington's disease (HD). At the same time peripheral blood represents a minimally invasive sampling avenue with little distress to Huntington's disease patients especially when brain or other tissue samples are difficult to collect. OBJECTIVES: We investigated the levels of 163 metabolites in HD patient and control serum samples in order to identify disease related changes. Additionally, we integrated the metabolomics data with our previously published next generation sequencing-based gene expression data from the same patients in order to interconnect the metabolomics changes with transcriptional alterations...
2016: Metabolomics: Official Journal of the Metabolomic Society
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