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https://www.readbyqxmd.com/read/28441004/insights-into-the-mechanisms-by-which-clostridial-neurotoxins-discriminate-between-gangliosides
#1
Joshua R Burns, Gregory S Lambert, Michael R Baldwin
Botulinum neurotoxins (BoNTs) and Tetanus neurotoxin (TeNT) are the causative agents of the paralytic diseases botulism and tetanus, respectively. Entry of toxins into neurons is mediated through initial interactions with gangliosides, followed by binding to a protein co-receptor. Herein we aimed to understand the mechanism through which individual neurotoxins recognize the carbohydrate motif of gangliosides. Using cell-based and in vitro binding assays, in conjunction with structure-driven site directed mutagenesis, a conserved hydrophobic residue within the BoNTs that contributes to both affinity and specificity towards Sia5-containing gangliosides was identified...
April 25, 2017: Biochemistry
https://www.readbyqxmd.com/read/28425396/development-and-single-laboratory-validation-of-a-liquid-chromatography-tandem-mass-spectrometry-method-for-quantitation-of-tetrodotoxin-in-mussels-and-oysters
#2
Andrew D Turner, Michael J Boundy, Monika Dhanji Rapkova
In recent years, evidence has grown for the presence of tetrodotoxin (TTX) in bivalve mollusks, leading to the potential for consumers of contaminated products to be affected by Tetrodotoxin Shellfish Poisoning (TSP). A single-laboratory validation was conducted for the hydrophilic interaction LC (HILIC) tandem MS (MS/MS) analysis of TTX in common mussels and Pacific oysters-the bivalve species that have been found to contain TTXs in the United Kingdom in recent years. The method consists of a single-step dispersive extraction in 1% acetic acid, followed by a carbon SPE cleanup step before dilution and instrumental analysis...
April 20, 2017: Journal of AOAC International
https://www.readbyqxmd.com/read/28425027/10-year-results-of-on-x-bileaflet-mechanical-heart-valve-in-the-aortic-position-low-target-inr-regimen-in-japanese
#3
Hideki Teshima, Masahiko Ikebuchi, Yosuke Miyamoto, Ryuta Tai, Toshikazu Sano, Yusuke Kinugasa, Hiroyuki Irie
OBJECTIVES: This study was designed to establish clinical outcomes after aortic valve replacement (AVR) with On-X bileaflet mechanical heart valve. METHODS: Between 2006 and 2014, AVR was performed to 686 patients. Of them, 78 patients using On-X valve were enrolled. The mean age was 65 ± 11 years (ranged 33-85); 65% were men; and 81% were in sinus rhythm preoperatively. Calcific or degenerative tricuspid aortic valve was present in 73%. Concomitant procedures included coronary artery bypass grafting (22%), Bentall (8%), mitral valve procedure (3%) and other (9%)...
April 19, 2017: General Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28412073/pediatric-acute-flaccid-paralysis-enterovirus-d68-associated-anterior-myelitis
#4
James A Yoder, Michael Lloyd, Luke Zabrocki, Jonathan Auten
BACKGROUND: Enteroviral infections can cause acute flaccid paralysis secondary to anterior myelitis. Magnetic resonance imaging (MRI) is important in the diagnosis of this potentially devastating pediatric disease. Before the 2014 outbreak of Enterovirus D68 (EV-D68), the virus was considered a relatively benign disease. CASE REPORT: A fully immunized 8-year-old boy was brought to the emergency department complaining of a cough, headache, neck pain, and right arm pain and weakness...
April 12, 2017: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28404155/survival-outcomes-following-laparoscopic-versus-open-d3-dissection-for-stage-ii-or-iii-colon-cancer-jcog0404-a-phase-3-randomised-controlled-trial
#5
Seigo Kitano, Masafumi Inomata, Junki Mizusawa, Hiroshi Katayama, Masahiko Watanabe, Seiichiro Yamamoto, Masaaki Ito, Shuji Saito, Shoichi Fujii, Fumio Konishi, Yoshihisa Saida, Hirotoshi Hasegawa, Tomonori Akagi, Kenichi Sugihara, Takashi Yamaguchi, Tadahiko Masaki, Yosuke Fukunaga, Kohei Murata, Masazumi Okajima, Yoshihiro Moriya, Yasuhiro Shimada
BACKGROUND: Although benefits of laparoscopic surgery compared with open surgery have been suggested, the long-term survival of patients undergoing laparoscopic surgery for colon cancer requiring Japanese D3 dissection remains unclear. We did a randomised controlled trial to establish non-inferiority of laparoscopic surgery to open surgery. METHODS: We did an open-label, multi-institutional, randomised, two-arm phase 3 trial in 30 hospitals in Japan. Patients aged 20-75 years who had histologically proven colon cancer; tumours located in the caecum or ascending, sigmoid, or rectosigmoid colon; T3 or deeper lesions without involvement of other organs, node stages N0-2, and metastasis stage M0; and tumour size of 8 cm or smaller were included...
April 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28403672/toxic-megacolon-as-a-rare-complication-following-atropine-therapy-due-to-organophosphate-poisoning-a-case-report
#6
Babak Mostafazadeh, Esmaeil Farzaneh, Maryam Paeezi, Farahnaz Nikkhah
The main therapeutic basis for a case of organophosphate poisoning is a combination therapy which includes atropine as an anticholinergic drug and pralidoxime. If the poisoning is severe, a high dose of this combination of medicines may be needed, but this may cause serious side effects: paralytic ileus or even megacolon; however, these gastrointestinal events are very rare. Here, we report a case of organophosphate poisoning where atropine therapy was given and led to drug-associated toxic megacolon.
January 1, 2017: Medico-legal Journal
https://www.readbyqxmd.com/read/28395782/colon-ischemia-right-sided-colon-involvement-has-a-different-presentation-etiology-and-worse-outcome-a-large-retrospective-cohort-study-in-histology-proven-patients
#7
REVIEW
Lotte B Ten Heggeler, Lisette J H van Dam, Alderina Bijlsma, Marijn C Visschedijk, Robert H Geelkerken, Maarten A C Meijssen, Jeroen J Kolkman
BACKGROUND: Colon ischemia (CI), is generally considered a non-occlusive mesenteric ischemia disorder that usually runs a benign course, but right-sided involvement (RCI) has been associated with worse outcome. The poor outcome of RCI has been associated with comorbidity, but more recently also with occlusions of the mesenteric arteries. We performed a retrospective analysis of a large cohort of CI-patients to assess differences in presentation, etiology, and comorbidity between right-sided colon ischemia (RCI) and non-right-sided colon ischemia (NRCI), and their relation to outcome...
February 2017: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/28385477/espen-guideline-clinical-nutrition-in-surgery
#8
Arved Weimann, Marco Braga, Franco Carli, Takashi Higashiguchi, Martin Hübner, Stanislaw Klek, Alessandro Laviano, Olle Ljungqvist, Dileep N Lobo, Robert Martindale, Dan L Waitzberg, Stephan C Bischoff, Pierre Singer
Early oral feeding is the preferred mode of nutrition for surgical patients. Avoidance of any nutritional therapy bears the risk of underfeeding during the postoperative course after major surgery. Considering that malnutrition and underfeeding are risk factors for postoperative complications, early enteral feeding is especially relevant for any surgical patient at nutritional risk, especially for those undergoing upper gastrointestinal surgery. The focus of this guideline is to cover nutritional aspects of the Enhanced Recovery After Surgery (ERAS) concept and the special nutritional needs of patients undergoing major surgery, e...
June 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28374313/differential-mobility-spectrometry-for-improved-selectivity-in-hydrophilic-interaction-liquid-chromatography-tandem-mass-spectrometry-analysis-of-paralytic-shellfish-toxins
#9
Daniel G Beach
Paralytic shellfish toxins (PSTs) are neurotoxins produced by dinoflagellates and cyanobacteria that cause paralytic shellfish poisoning in humans. PST quantitation by LC-MS is challenging because of their high polarity, lability as gas-phase ions, and large number of potentially interfering analogues. Differential mobility spectrometry (DMS) has the potential to improve the performance of LC-MS methods for PSTs in terms of selectivity and limits of detection. This work describes a comprehensive investigation of the separation of 16 regulated PSTs by DMS and the development of highly selective LC-DMS-MS methods for PST quantitation...
April 3, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28362135/immunogenicity-and-safety-evaluation-of-bivalent-types-1-and-3-oral-poliovirus-vaccine-by-comparing-different-poliomyelitis-vaccination-schedules-in-china-a-randomized-controlled-non-inferiority-clinical-trial
#10
Jingjun Qiu, Yunkai Yang, Lirong Huang, Ling Wang, Zhiwei Jiang, Jian Gong, Wei Wang, Hongyan Wang, Shaohong Guo, Chanjuan Li, Shuyuan Wei, Zhaojun Mo, Jielai Xia
BACKGROUND: The type 2 component of the oral poliovirus vaccine is targeted for global withdrawal through a switch from the trivalent oral poliovirus vaccine (tOPV) to a bivalent oral poliovirus vaccine (bOPV). The switch is intended to prevent paralytic polio caused by circulating vaccine-derived poliovirus type 2. We aimed to assess the immunogenicity and safety profile of 6 vaccination schedules with different sequential doses of inactivated poliovirus vaccine (IPV), tOPV, or bOPV...
March 1, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28361789/vaccine-associated-paralytic-poliomyelitis-unmasking-common-variable-immunodeficiency
#11
Sunil Gomber, Vanny Arora, Pooja Dewan
BACKGROUND: Oral polio vaccine can rarely lead to Vaccine-associated paralytic poliomyelitis (VAPP). CASE CHARACTERISTICS: A 2-year-old child with asymmetric paralysis of lower limbs following first booster of oral polio vaccine; type 2 Vaccine-derived poliovirus (VDPV) isolated. Subsequently, the child was diagnosed to have common variable immunodeficiency. OUTCOME: Paralysis gradually improved on follow-up; monthly intravenous immunoglobulin therapy started for primary immunodeficiency...
March 15, 2017: Indian Pediatrics
https://www.readbyqxmd.com/read/28359137/an-ultrasensitive-gold-nanoparticle-based-lateral-flow-test-for-the-detection-of-active-botulinum-neurotoxin-type-a
#12
Jing Liu, Shan Gao, Lin Kang, Bin Ji, Wenwen Xin, Jingjing Kang, Ping Li, Jie Gao, Hanbin Wang, Jinglin Wang, Hao Yang
Botulism is a severe and potentially lethal paralytic disease caused by several botulinum neurotoxin-producing Clostridia spp. In China, the majority of the cases caused by botulism were from less-developed rural areas. Here, we designed specific substrate peptides and reconfigured gold nanoparticle-based lateral flow test strip (LFTS) to develop an endopeptidase-based lateral flow assay for the diagnosis of botulism. We performed this lateral flow assay on botulinum neurotoxin-spiked human serum samples. The as-prepared LFTS had excellent performance in the detection of botulinum neurotoxin using only 1 μL of simulated serum, and its sensitivity and specificity were comparable to that of mouse lethality assay...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28359039/spatiotemporal-patterns-of-paralytic-shellfish-toxins-and-their-relationships-with-environmental-variables-in-british-columbia-canada-from-2002-to-2012
#13
Stephen Finnis, Nikolas Krstic, Lorraine McIntyre, Trisalyn A Nelson, Sarah B Henderson
BACKGROUND: Harmful algal blooms produce paralytic shellfish toxins that accumulate in the tissues of filter feeding shellfish. Ingestion of these toxic shellfish can cause a serious and potentially fatal condition known as paralytic shellfish poisoning (PSP). The coast of British Columbia is routinely monitored for shellfish toxicity, and this study uses data from the monitoring program to identify spatiotemporal patterns in shellfish toxicity events and their relationships with environmental variables...
March 27, 2017: Environmental Research
https://www.readbyqxmd.com/read/28357566/mutant-tdp-43-within-motor-neurons-drives-disease-onset-but-not-progression-in-amyotrophic-lateral-sclerosis
#14
Dara Ditsworth, Marcus Maldonado, Melissa McAlonis-Downes, Shuying Sun, Amanda Seelman, Kevin Drenner, Eveline Arnold, Shuo-Chien Ling, Donald Pizzo, John Ravits, Don W Cleveland, Sandrine Da Cruz
Mutations in TDP-43 cause amyotrophic lateral sclerosis (ALS), a fatal paralytic disease characterized by degeneration and premature death of motor neurons. The contribution of mutant TDP-43-mediated damage within motor neurons was evaluated using mice expressing a conditional allele of an ALS-causing TDP-43 mutant (Q331K) whose broad expression throughout the central nervous system mimics endogenous TDP-43. TDP-43(Q331K) mice develop age- and mutant-dependent motor deficits from degeneration and death of motor neurons...
March 29, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28356537/pathogenic-events-in-a-nonhuman-primate-model-of-oral-poliovirus-infection-leading-to-paralytic-poliomyelitis
#15
Ling Shen, Crystal Y Chen, Dan Huang, Richard Wang, Meihong Zhang, Lixia Qian, Yanfen Zhu, Alvin Zhuoran Zhang, Enzhuo Yang, Arwa Qaqish, Konstantin Chumakov, Diana Kouiavskaia, Marco Vignuzzi, Neal Nathanson, Andrew J Macadam, Raul Andino, Olen Kew, Junfa Xu, Zheng W Chen
Despite a great deal of prior research, the early pathogenic events in natural oral poliovirus infection remain poorly defined. To establish a model for study, we infected 39 macaques by feeding single high doses of the virulent Mahoney strain of wild type 1 poliovirus. Doses ranging from10(7)-10(9) TCID50 consistently infected all animals, and most monkeys receiving 10(8) or 10(9) TCID50 developed paralysis. There was no apparent difference in the susceptibility of the three macaque species (rhesus, cynomolgus, and bonnet) used...
March 29, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28356250/pseudotumor-cerebri-syndrome-in-childhood-incidence-clinical-profile-and-risk-factors-in-a-national-prospective-population-based-cohort-study
#16
Yim-Yee Matthews, Fiona Dean, Ming J Lim, Karen Mclachlan, Alan S Rigby, Guirish A Solanki, Catharine P White, William P Whitehouse, Colin R Kennedy
AIM: To investigate the epidemiology, clinical profile and risk factors of pseudotumor cerebri syndrome (PTCS) in children aged 1-16 years. METHODS: A national prospective population-based cohort study over 25 months. Newly diagnosed PTCS cases notified via British Paediatric Surveillance Unit were ascertained using classical diagnostic criteria and categorised according to 2013 revised diagnostic criteria. We derived national age, sex and weight-specific annual incidence rates and assessed effects of sex and weight categories...
March 29, 2017: Archives of Disease in Childhood
https://www.readbyqxmd.com/read/28349703/comparative-effectiveness-of-botulinum-toxin-versus-non-surgical-treatments-for-treating-lateral-epicondylitis-a-systematic-review-and-meta-analysis
#17
Yu-Ching Lin, Wei-Ting Wu, Yu-Chun Hsu, Der-Sheng Han, Ke-Vin Chang
OBJECTIVES: To explore the effectiveness of botulinum toxin compared with non-surgical treatments in patients with lateral epicondylitis. METHODS: Data sources including PubMed, Scopus, Embase and Airity Library from the earliest record to February 2017 were searched. Study design, patients' characteristics, dosage/brand of botulinum toxin, injection techniques, and measurements of pain and hand grip strength were retrieved. The standardized mean differences (SMDs) in pain relief and grip strength reduction were calculated at the following time points: 2-4, 8-12, and 16 weeks or more after injection...
March 1, 2017: Clinical Rehabilitation
https://www.readbyqxmd.com/read/28347837/a-novel-therapeutic-with-two-snap-25-inactivating-proteases-shows-long-lasting-anti-hyperalgesic-activity-in-a-rat-model-of-neuropathic-pain
#18
Jiafu Wang, Laura Casals-Diaz, Tomas Zurawski, Jianghui Meng, Orla Moriarty, John Nealon, Om Prakash Edupuganti, Oliver Dolly
A pressing need exists for long-acting, non-addictive medicines to treat chronic pain, a major societal burden. Botulinum neurotoxin type A (BoNT/A) complex - a potent, specific and prolonged inhibitor of neuro-exocytosis - gives some relief in several pain disorders, but not for all patients. Our study objective was to modify BoNT/A to overcome its inability to block transmitter release elicited by high [Ca(2+)]i and increase its limited analgesic effects. This was achieved by fusing a BoNT/A gene to that for the light chain (LC) of type/E...
March 24, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28346224/mutant-%C3%AE-2-chimaerin-signals-via-bidirectional-ephrin-pathways-in-duane-retraction-syndrome
#19
Alicia A Nugent, Jong G Park, Yan Wei, Alan P Tenney, Nicole M Gilette, Michelle M DeLisle, Wai-Man Chan, Long Cheng, Elizabeth C Engle
Duane retraction syndrome (DRS) is the most common form of congenital paralytic strabismus in humans and can result from α2-chimaerin (CHN1) missense mutations. We report a knockin α2-chimaerin mouse (Chn1KI/KI) that models DRS. Whole embryo imaging of Chn1KI/KI mice revealed stalled abducens nerve growth and selective trochlear and first cervical spinal nerve guidance abnormalities. Stalled abducens nerve bundles did not reach the orbit, resulting in secondary aberrant misinnervation of the lateral rectus muscle by the oculomotor nerve...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28340348/the-evolutionary-pathway-to-virulence-of-an-rna-virus
#20
Adi Stern, Ming Te Yeh, Tal Zinger, Matt Smith, Caroline Wright, Guy Ling, Rasmus Nielsen, Andrew Macadam, Raul Andino
Paralytic polio once afflicted almost half a million children each year. The attenuated oral polio vaccine (OPV) has enabled world-wide vaccination efforts, which resulted in nearly complete control of the disease. However, poliovirus eradication is hampered globally by epidemics of vaccine-derived polio. Here, we describe a combined theoretical and experimental strategy that describes the molecular events leading from OPV to virulent strains. We discover that similar evolutionary events occur in most epidemics...
March 23, 2017: Cell
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