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Silvia Carraro, Eugenio Baraldi, Giuseppe Giordano, Paola Pirillo, Matteo Stocchero, Michiel Houben, Louis Bont
OBJECTIVES: To apply metabolomic analysis of amniotic fluid in a discovery cohort to see whether a specific biochemical-metabolic profile at birth is associated with the subsequent onset of wheezing over the first year of life. STUDY DESIGN: This prospective exploratory study was conducted in a healthy term-born Dutch cohort recruited at 2 hospitals in Utrecht (UMCU, Utrecht, and Diakonessenhuis, Utrecht), The Netherlands. A metabolomic approach based on mass spectrometry was applied to analyze 142 amniotic fluid samples collected at birth...
March 13, 2018: Journal of Pediatrics
Geoffrey Masuyer, Sicai Zhang, Sulyman Barkho, Yi Shen, Linda Henriksson, Sara Košenina, Min Dong, Pål Stenmark
Botulinum neurotoxins (BoNTs) are among the most potent toxins known and are also used to treat an increasing number of medical disorders. There are seven well-established serotypes (BoNT/A-G), which all act as zinc-dependent endopeptidases targeting specific members of the SNARE proteins required for synaptic vesicle exocytosis in neurons. A new toxin serotype, BoNT/X, was recently identified. It cleaves not only the canonical targets, vesicle associated membrane proteins (VAMP) 1/2/3 at a unique site, but also has the unique ability to cleave VAMP4/5 and Ykt6...
March 14, 2018: Scientific Reports
Semra Aktürk, Raikan Büyükavcı, Yüksel Ersoy
OBJECTIVE: The aim of this study is to identify the effect on spasticity and walking of US-guided botulinum toxin type A (BoNT-A) injections administered to improve equinovarus walking pattern commonly observed in patients after stroke. MATERIAL AND METHOD: Twenty-three patients with post-stroke spastic equinovarus deformity were recruited. The US-guided BoNT-A injections were administered into the spastic muscles (including gastrocnemius; GK, soleus; S and tibialis posterior; TP) using a specific approach, and all of the patients were enrolled in rehabilitation programmes after the injections...
March 9, 2018: Toxicon: Official Journal of the International Society on Toxinology
Feixia Zheng, Xiuyun Ye, Xulai Shi, Neha Devi Poonit, Zhongdong Lin
The use of botulinum neurotoxin serotype A (BoNT-A) injections for the treatment of orofacial dyskinesia secondary to anti- N -methyl-d-aspartate receptor (NMDAR) encephalitis is rarely reported. Here, we report a case of an urgent, successful management of severe orofacial dyskinesia in an 8-year-old girl with anti-NMDAR encephalitis using BoNT-A injection. The patient presented with de novo unilateral paroxysmal movement disorder progressing to generalized dystonia and repetitive orofacial dyskinesia. Diagnosis was confirmed by the presence of NMDAR antibodies in serum and cerebrospinal fluid...
2018: Frontiers in Neurology
Teresa Mann, Jens Kurth, Alexander Hawlitschka, Jan Stenzel, Tobias Lindner, Stefan Polei, Alexander Hohn, Bernd J Krause, Andreas Wree
Intrastriatal injection of botulinum neurotoxin A (BoNT-A) results in improved motor behavior of hemiparkinsonian (hemi-PD) rats, an animal model for Parkinson's disease. The caudate-putamen (CPu), as the main input nucleus of the basal ganglia loop, is fundamentally involved in motor function and directly interacts with the dopaminergic system. To determine receptor-mediated explanations for the BoNT-A effect, we analyzed the dopamine D₂/D₃ receptor (D₂/D₃R) in the CPu of 6-hydroxydopamine (6-OHDA)-induced hemi-PD rats by [18 F]fallypride-PET/CT scans one, three, and six months post-BoNT-A or -sham-BoNT-A injection...
March 6, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Anneke D van Dijk, Chenyue W Hu, Eveline S J M de Bont, YiHua Qiu, Fieke W Hoff, Suk Young Yoo, Kevin R Coombes, Amina A Qutub, Steven M Kornblau
Post-translational histone tail modifications are known to play a role in leukemogenesis and are therapeutic targets. A global analysis of the level and patterns of expression of multiple histone modifying proteins (HMP) in acute myeloid leukemia (AML) and the effect of different patterns of expression on outcome and prognosis has not been investigated in AML patients. Here we analyzed 20 HMP by reverse phase protein array (RPPA) in a cohort of 205 newly diagnosed AML patients. Protein levels were correlated with patient and disease characteristics, including survival and mutational state...
March 5, 2018: Proteomics
Nienke M Scheltema, Elisabeth E Nibbelke, Juliëtte Pouw, Maarten O Blanken, Maroeska M Rovers, Christiana A Naaktgeboren, Natalie I Mazur, Joanne G Wildenbeest, Cornelis K van der Ent, Louis J Bont
BACKGROUND: Respiratory syncytial virus (RSV) infection is associated with subsequent wheeze and asthma. We previously reported on the causal relationship between prevention of RSV infection during infancy and reduced frequency of subsequent wheeze using a double-blind, randomised, placebo-controlled trial (MAKI). We continued follow-up and analysed the effect of RSV prevention during infancy on asthma and lung function at age 6 years. METHODS: We studied 429 infants born at 32-35 weeks of gestation between 2008-10 who had randomly received either palivizumab for RSV immunoprophylaxis or placebo during the RSV season of their first year of life...
February 27, 2018: Lancet Respiratory Medicine
Désirée S Jansson, Caroline Bröjer, Aleksija Neimanis, Torsten Mörner, Charles L Murphy, Faruk Otman, Per Westermark
Since the late 1990s, high mortality and declining populations have been reported among sea birds including Herring gulls (Larus argentatus) from the Baltic Sea area in Northern Europe. Repeated BoNT type C/D botulism outbreaks have occurred, but it remains unclear whether this is the sole and primary cause of mortality. Thiamine deficiency has also been suggested as a causal or contributing factor. With this study, we aimed to investigate gross and microscopic pathology in Herring gulls from affected breeding sites in Sweden in search of contributing diseases...
2018: PloS One
Consuelo Garcia-Rodriguez, Ali Razai, Isin N Geren, Jianlong Lou, Fraser Conrad, Wei-Hua Wen, Shauna Farr-Jones, Theresa J Smith, Jennifer L Brown, Janet C Skerry, Leonard A Smith, James D Marks
Human botulism is most commonly caused by botulinum neurotoxin (BoNT) serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb)-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv) antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS). A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (KD )...
March 1, 2018: Toxins
Yasaman Safarpour, Bahman Jabbari
Botulinum neurotoxins (BoNTs) are now among the most widely used therapeutic agents in clinical medicine with indications applied to the fields of movement disorders, pain disorders, and autonomic dysfunction. In this literature review, the efficacy and utility of BoNTs in the field of movement disorders are assessed using the criteria of the Guideline Development Subcommittee of the American Academy of Neurology. The literature supports a level A efficacy (established) for BoNT therapy in cervical dystonia and a level B efficacy (probably effective) for blepharospasm, hemifacial spasm, laryngeal dystonia (spasmodic dysphonia), task-specific dystonias, essential tremor, and Parkinson rest tremor...
February 24, 2018: Current Treatment Options in Neurology
Jessica M Khouri, Ruth N Motter, Stephen S Arnon
OBJECTIVES: We undertook an open-label, uncontrolled study of investigational recombinant botulinum vaccine for botulinum neurotoxin (BoNT) serotypes A and B (rBV A/B) to assess its safety and immunogenicity in healthy volunteers who had been previously immunized with investigational pentavalent botulinum toxoid. Study participants who wished to do so could donate their hyperimmune plasma for production of Human Botulism Immune Globulin Intravenous (BIG-IV, BabyBIG®). STUDY DESIGN: A single 0...
February 20, 2018: Vaccine
Eric A F Simões, Louis Bont, Paolo Manzoni, Brigitte Fauroux, Bosco Paes, Josep Figueras-Aloy, Paul A Checchia, Xavier Carbonell-Estrany
INTRODUCTION: The REGAL (RSV Evidence - A Geographical Archive of the Literature) series has provided a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. This seventh and final publication covers the past, present and future approaches to the prevention and treatment of RSV infection among infants and children. METHODS: A systematic review was undertaken of publications between January 1, 1995 and December 31, 2017 across PubMed, Embase and The Cochrane Library...
February 22, 2018: Infectious Diseases and Therapy
Ankie C M Hazen, Esther de Groot, Antoinette A de Bont, Simone de Vocht, Johan J de Gier, Marcel L Bouvy, Niek J de Wit, Dorien L M Zwart
PURPOSE: To unravel boundary crossing as it relates to professional identity formation in pharmacists transitioning from a community pharmacy to working as nondispensing clinical pharmacists in general practice, with the aim of optimizing their education. METHOD: A multiple case study, including two-stage interviews, peer feedback, and individual reflection, that collected data in 2014 and 2015 from eight clinical pharmacists working in general practice in The Netherlands...
February 20, 2018: Academic Medicine: Journal of the Association of American Medical Colleges
Jianlong Lou, Weihua Wen, Fraser Conrad, Qi Meng, Jianbo Dong, Zhengda Sun, Consuelo Garcia-Rodriguez, Shauna Farr-Jones, Luisa W Cheng, Thomas D Henderson, Jennifer L Brown, Theresa J Smith, Leonard A Smith, Anthony Cormier, James D Marks
The standard of treatment for botulism, equine antitoxin, is a foreign protein with associated safety issues and a short serum half-life which excludes its use as a prophylactic antitoxin and makes it a less-than-optimal therapeutic. Due to these limitations, a recombinant monoclonal antibody (mAb) product is preferable. It has been shown that combining three mAbs that bind non-overlapping epitopes leads to highly potent botulinum neurotoxin (BoNT) neutralization. Recently, a triple human antibody combination for BoNT/A has demonstrated potent toxin neutralization in mouse models with no serious adverse events when tested in a Phase I clinical trial...
February 15, 2018: Toxins
Cynthia L Comella
Oromandibular dystonia (OMD) is an isolated focal dystonia that affects the muscles of the jaw, lower face and tongue. It is a rare disorder but is associated with significant impairment in quality of life. Treatment with oral medications has not been successful. Surgical interventions, such as deep brain stimulation, may be of benefit but have not been adequately evaluated. Currently, botulinum toxin (BoNT) injections are regarded as the treatment of choice for OMD. However, the evidence supporting this is not available...
February 14, 2018: Toxicon: Official Journal of the International Society on Toxinology
Kristina Tedroff, Gustaf Befrits, Carl Johan Tedroff, Stefan Gantelius
BACKGROUND AND OBJECTIVES: Children with cerebral palsy (CP) are routinely treated with botulinum toxin A (BoNT-A). Two non dose-equivalent and differently priced products, Botox and Dysport are used. Depending on the conversion one of the products is considerably cheaper. However, the dose conversion factors studied to date have varied widely and relevant studies have not included children. Our objective here was to compare the efficacy and health economics of the switch from Botox to Dysport in children with CP when conversion was set to 1:2...
February 3, 2018: European Journal of Paediatric Neurology: EJPN
Caitlyn M Swinney, Karen Bau, Karen L Oakley Burton, Stephen J O'Flaherty, Natasha L Bear, Simon P Paget
AIM: To determine the incidence of common adverse events after botulinum toxin A (BoNT-A) injections in children with cerebral palsy (CP) and to identify whether the severity of CP influences the incidence of adverse events. METHOD: This was an observational study of patients attending a BoNT-A clinic at a tertiary paediatric hospital (2010-2014). Data examined included procedural adverse events at the time of injection and at follow-up. Systemic adverse events were defined as lower respiratory tract illnesses, generalized weakness, dysphagia, and death...
February 16, 2018: Developmental Medicine and Child Neurology
Erin M Nawrocki, Marite Bradshaw, Eric A Johnson
Most Group I Clostridium botulinum strains harbor botulinum neurotoxin (bont) genes on their chromosome, while some carry these genes (including bont/a, bont/b, and bont/f) on large plasmids. Prior work in our laboratory demonstrated that Group I BoNT plasmids were mobilized to C. botulinum recipient strains containing the Tn916 transposon. Here, we show that Tn916 is nonessential for plasmid transfer. Relying on an auxotrophic donor phenotype and a plasmid-borne selectable marker, we observed the transfer of pCLJ, a 270 kb plasmid harboring two bont genes, from its host strain to various clostridia...
February 15, 2018: Scientific Reports
Michel R Popoff
Botulinum neurotoxins (BoNTs) are potent bacterial toxins mostly produced by genetically diverse clostridial strains. Recently, BoNT variants have been reported in non-clostridial strains. In this issue of Cell Host & Microbe, Zhang et al. (2018) describe a novel BoNT in Entecoccus faecium.
February 14, 2018: Cell Host & Microbe
David van den Berg, Paul A J M de Bont, Berber M van der Vleugel, Carlijn de Roos, Ad de Jongh, Agnes van Minnen, Mark van der Gaag
We present 12-month follow-up results for a randomised controlled trial of prolonged exposure and eye movement desensitisation and reprocessing (EMDR) therapy in 85 (78.8%) participants with psychotic disorder and comorbid post-traumatic stress disorder (PTSD). Positive effects on clinician-rated PTSD, self-rated PTSD, depression, paranoid-referential thinking and remission from schizophrenia were maintained up to 12-month follow-up. Negative post-traumatic cognitions declined in prolonged exposure and were stable in EMDR...
March 2018: British Journal of Psychiatry: the Journal of Mental Science
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