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https://www.readbyqxmd.com/read/28641109/rare-copy-number-variants-in-nrxn1-and-cntn6-increase-risk-for-tourette-syndrome
#1
Alden Y Huang, Dongmei Yu, Lea K Davis, Jae Hoon Sul, Fotis Tsetsos, Vasily Ramensky, Ivette Zelaya, Eliana Marisa Ramos, Lisa Osiecki, Jason A Chen, Lauren M McGrath, Cornelia Illmann, Paul Sandor, Cathy L Barr, Marco Grados, Harvey S Singer, Markus M Nöthen, Johannes Hebebrand, Robert A King, Yves Dion, Guy Rouleau, Cathy L Budman, Christel Depienne, Yulia Worbe, Andreas Hartmann, Kirsten R Müller-Vahl, Manfred Stuhrmann, Harald Aschauer, Mara Stamenkovic, Monika Schloegelhofer, Anastasios Konstantinidis, Gholson J Lyon, William M McMahon, Csaba Barta, Zsanett Tarnok, Peter Nagy, James R Batterson, Renata Rizzo, Danielle C Cath, Tomasz Wolanczyk, Cheston Berlin, Irene A Malaty, Michael S Okun, Douglas W Woods, Elliott Rees, Carlos N Pato, Michele T Pato, James A Knowles, Danielle Posthuma, David L Pauls, Nancy J Cox, Benjamin M Neale, Nelson B Freimer, Peristera Paschou, Carol A Mathews, Jeremiah M Scharf, Giovanni Coppola
Tourette syndrome (TS) is a model neuropsychiatric disorder thought to arise from abnormal development and/or maintenance of cortico-striato-thalamo-cortical circuits. TS is highly heritable, but its underlying genetic causes are still elusive, and no genome-wide significant loci have been discovered to date. We analyzed a European ancestry sample of 2,434 TS cases and 4,093 ancestry-matched controls for rare (< 1% frequency) copy-number variants (CNVs) using SNP microarray data. We observed an enrichment of global CNV burden that was prominent for large (> 1 Mb), singleton events (OR = 2...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28640810/lassim-a-network-inference-toolbox-for-genome-wide-mechanistic-modeling
#2
Rasmus Magnusson, Guido Pio Mariotti, Mattias Köpsén, William Lövfors, Danuta R Gawel, Rebecka Jörnsten, Jörg Linde, Torbjörn Nordling, Elin Nyman, Sylvie Schulze, Colm E Nestor, Huan Zhang, Gunnar Cedersund, Mikael Benson, Andreas Tjärnberg, Mika Gustafsson
Recent technological advancements have made time-resolved, quantitative, multi-omics data available for many model systems, which could be integrated for systems pharmacokinetic use. Here, we present large-scale simulation modeling (LASSIM), which is a novel mathematical tool for performing large-scale inference using mechanistically defined ordinary differential equations (ODE) for gene regulatory networks (GRNs). LASSIM integrates structural knowledge about regulatory interactions and non-linear equations with multiple steady state and dynamic response expression datasets...
June 22, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28636956/elicitation-of-robust-tier-2-neutralizing-antibody-responses-in-nonhuman-primates-by-hiv-envelope-trimer-immunization-using-optimized-approaches
#3
Matthias Pauthner, Colin Havenar-Daughton, Devin Sok, Joseph P Nkolola, Raiza Bastidas, Archana V Boopathy, Diane G Carnathan, Abishek Chandrashekar, Kimberly M Cirelli, Christopher A Cottrell, Alexey M Eroshkin, Javier Guenaga, Kirti Kaushik, Daniel W Kulp, Jinyan Liu, Laura E McCoy, Aaron L Oom, Gabriel Ozorowski, Kai W Post, Shailendra K Sharma, Jon M Steichen, Steven W de Taeye, Talar Tokatlian, Alba Torrents de la Peña, Salvatore T Butera, Celia C LaBranche, David C Montefiori, Guido Silvestri, Ian A Wilson, Darrell J Irvine, Rogier W Sanders, William R Schief, Andrew B Ward, Richard T Wyatt, Dan H Barouch, Shane Crotty, Dennis R Burton
The development of stabilized recombinant HIV envelope trimers that mimic the virion surface molecule has increased enthusiasm for a neutralizing antibody (nAb)-based HIV vaccine. However, there is limited experience with recombinant trimers as immunogens in nonhuman primates, which are typically used as a model for humans. Here, we tested multiple immunogens and immunization strategies head-to-head to determine their impact on the quantity, quality, and kinetics of autologous tier 2 nAb development. A bilateral, adjuvanted, subcutaneous immunization protocol induced reproducible tier 2 nAb responses after only two immunizations 8 weeks apart, and these were further enhanced by a third immunization with BG505 SOSIP trimer...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636851/first-line-nivolumab-in-stage-iv-or-recurrent-non-small-cell-lung-cancer
#4
COMMENT
David P Carbone, Martin Reck, Luis Paz-Ares, Benjamin Creelan, Leora Horn, Martin Steins, Enriqueta Felip, Michel M van den Heuvel, Tudor-Eliade Ciuleanu, Firas Badin, Neal Ready, T Jeroen N Hiltermann, Suresh Nair, Rosalyn Juergens, Solange Peters, Elisa Minenza, John M Wrangle, Delvys Rodriguez-Abreu, Hossein Borghaei, George R Blumenschein, Liza C Villaruz, Libor Havel, Jana Krejci, Jesus Corral Jaime, Han Chang, William J Geese, Prabhu Bhagavatheeswaran, Allen C Chen, Mark A Socinski
BACKGROUND: Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive NSCLC. METHODS: We randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles)...
June 22, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28636613/in-vivo-immune-signatures-of-healthy-human-pregnancy-inherently-inflammatory-or-anti-inflammatory
#5
Caroline Graham, Rishma Chooniedass, William P Stefura, Allan B Becker, Malcolm R Sears, Stuart E Turvey, Piush J Mandhane, Padmaja Subbarao, Kent T HayGlass
Changes in maternal innate immunity during healthy human pregnancy are not well understood. Whether basal immune status in vivo is largely unaffected by pregnancy, is constitutively biased towards an inflammatory phenotype (transiently enhancing host defense) or exhibits anti-inflammatory bias (reducing potential responsiveness to the fetus) is unclear. Here, in a longitudinal study of healthy women who gave birth to healthy infants following uncomplicated pregnancies within the Canadian Healthy Infant Longitudinal Development (CHILD) cohort, we test the hypothesis that a progressively altered bias in resting innate immune status develops...
2017: PloS One
https://www.readbyqxmd.com/read/28636593/t-cells-from-patients-with-parkinson-s-disease-recognize-%C3%AE-synuclein-peptides
#6
David Sulzer, Roy N Alcalay, Francesca Garretti, Lucien Cote, Ellen Kanter, Julian Agin-Liebes, Christopher Liong, Curtis McMurtrey, William H Hildebrand, Xiaobo Mao, Valina L Dawson, Ted M Dawson, Carla Oseroff, John Pham, John Sidney, Myles B Dillon, Chelsea Carpenter, Daniela Weiskopf, Elizabeth Phillips, Simon Mallal, Bjoern Peters, April Frazier, Cecilia S Lindestam Arlehamn, Alessandro Sette
Genetic studies have shown the association of Parkinson's disease with alleles of the major histocompatibility complex. Here we show that a defined set of peptides that are derived from α-synuclein, a protein aggregated in Parkinson's disease, act as antigenic epitopes displayed by these alleles and drive helper and cytotoxic T cell responses in patients with Parkinson's disease. These responses may explain the association of Parkinson's disease with specific major histocompatibility complex alleles.
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28636211/resolution-of-donor-non-alcoholic-fatty-liver-disease-following-liver-transplantation
#7
Andrew D Posner, Samuel T Sultan, Norann A Zaghloul, William S Twaddell, David A Bruno, Steven I Hanish, William R Hutson, Laci Hebert, Rolf N Barth, John C LaMattina
INTRODUCTION: Transplant surgeons conventionally select against livers displaying high degrees (>30%) of macrosteatosis (MaS), out of concern for primary non-function or severe graft dysfunction. As such, there is relatively limited experience with such livers, and the natural history remains incompletely characterized. We present our experience of transplanted livers with high degrees of MaS and microsteatosis (MiS), with a focus on the histopathologic and clinical outcomes. METHODS: 29 cases were identified with liver biopsies available from both the donor and the corresponding liver transplant recipient...
June 21, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28634467/brain-network-activation-technology-does-not-assist-with-concussion-diagnosis-and-return-to-play-in-football-athletes
#8
Steven P Broglio, Richelle Williams, Andrew Lapointe, Ashley Rettmann, Brandon Moore, Sean K Meehan, James T Eckner
BACKGROUND: Concussion diagnosis and management remains a largely subjective process. This investigation sought to evaluate the utility of a novel neuroelectric measure for concussion diagnosis and return to play decision-making. HYPOTHESIS: Brain Network Activation (BNA) scores obtained within 72-h of injury will be lower than the athlete's preseason evaluation and that of a matched control athlete; and the BNA will demonstrate ongoing declines at the return to play and post-season time points, while standard measures will have returned to pre-injury and control athlete levels...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28634284/co-administration-of-rankl-and-ctla4-antibodies-enhances-lymphocyte-mediated-anti-tumor-immunity-in-mice
#9
Elizabeth Ahern, Heidi Harjunpaa, Deborah Barkauskas, Stacey Allen, Kazuyoshi Takeda, Hideo Yagita, David Wyld, William C Dougall, Michele W L Teng, Mark J Smyth
Purpose: Novel partners for established immune checkpoint inhibitors in the treatment of cancer are needed to address the problems of primary and acquired resistance. The efficacy of combination RANKL and CTLA4 blockade in anti-tumor immunity has been suggested by recent case reports in melanoma. Here we provide a rationale for this combination in mouse models of cancer. <br />Experimental Design: The efficacy and mechanism of a combination of RANKL and CTLA4 blockade was examined by tumor infiltrating lymphocyte analysis, tumor growth and metastasis using a variety of neutralizing antibodies and gene-targeted mice...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28634096/reconstruction-of-disrupted-extensor-mechanism-after-total-knee-arthroplasty
#10
C T Lim, Derek F Amanatullah, James I Huddleston, Alex H S Harris, Katherine L Hwang, William J Maloney, Stuart B Goodman
BACKGROUND: Disruption of the extensor mechanism after total knee arthroplasty (TKA) is a debilitating complication that results in extension lag, limited range of motion, difficulty in walking, frequent falls, and chronic pain. This study presents the clinical and radiographic results of reconstruction after extensor mechanism disruption in TKA patients. METHODS: Consecutive patients with allograft reconstruction of extensor mechanism after TKA were identified retrospectively from an academic tertiary center for revision TKA...
May 11, 2017: Journal of Arthroplasty
https://www.readbyqxmd.com/read/28633951/beach-litter-sourcing-a-trawl-along-the-northern-ireland-coastline
#11
A T Williams, P Randerson, C Allen, J A G Cooper
Fourteen non-recreational coastal locations in Northern Ireland were investigated as to whether beach litter deposition was related to seasonal or site specific factors. Litter items were counted in 100m width transects and 1km strand-line surveys over a five-season period (autumn to autumn). Survey sites comprised fishing ports; estuarine areas, north (high energy) and east coast (low energy) beaches. Fishing ports accumulated the most litter. In the 100m beach surveys, plastics, string and cord, bottle caps, food items, rope, and drink containers dominated...
June 17, 2017: Marine Pollution Bulletin
https://www.readbyqxmd.com/read/28633782/factors-predicting-length-of-hospital-stay-and-extended-care-facility-admission-after-hindfoot-arthrodesis-procedures
#12
Jacob Deister, Brian G Cothern, Chad Williams, Andrew W Froehle, Richard T Laughlin
Delayed identification of patients requiring admission to extended care facilities (ECFs) can lead to greater healthcare costs through an increased length of hospital stay (LOHS). Previous studies of hip and knee arthroplasty identified factors associated with a likely discharge to an ECF. These issues have not been extensively studied for major hindfoot procedures. We conducted a retrospective review of 198 cases treated during a 3-year period to identify the risk factors for an extended LOHS and ECF admission after ankle arthrodesis, triple arthrodesis, pantalar arthrodesis, and subtalar arthrodesis...
July 2017: Journal of Foot and Ankle Surgery: Official Publication of the American College of Foot and Ankle Surgeons
https://www.readbyqxmd.com/read/28633446/genetic-indicators-of-drug-resistance-in-the-highly-repetitive-genome-of-trichomonas-vaginalis
#13
Martina Bradic, Sally D Warring, Grace E Tooley, Paul Scheid, William E Secor, Kirkwood M Land, Po-Jung Huang, Ting-Wen Chen, Chi-Ching Lee, Petrus Tang, Steven A Sullivan, Jane M Carlton
Trichomonas vaginalis, the most common non-viral sexually transmitted parasite, causes ∼283 million trichomoniasis infections annually and is associated with pregnancy complications and increased risk of HIV-1 acquisition. The antimicrobial drug metronidazole is used for treatment, but in a fraction of clinical cases, the parasites can become resistant to this drug. We undertook sequencing of multiple clinical isolates and lab derived lines to identify genetic markers and mechanisms of metronidazole resistance...
June 19, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28633394/diagnostic-accuracy-of-somatosensory-evoked-potential-monitoring-in-evaluating-neurological-complications-during-endovascular-aneurysm-treatment
#14
William J Ares, Ramesh M Grandhi, David M Panczykowski, Gregory M Weiner, Parthasarathy Thirumala, Miguel E Habeych, Donald J Crammond, Michael B Horowitz, Brian T Jankowitz, Ashutosh Jadhav, Tudor G Jovin, Andrew F Ducruet, Jeffrey Balzer
BACKGROUND: Somatosensory evoked potential (SSEP) monitoring is used extensively for early detection and prevention of neurological complications in patients undergoing many different neurosurgical procedures. However, the predictive ability of SSEP monitoring during endovascular treatment of cerebral aneurysms is not well detailed. OBJECTIVE: To evaluate the performance of intraoperative SSEP in the prediction postprocedural neurological deficits (PPNDs) after coil embolization of intracranial aneurysms...
June 14, 2017: Operative Neurosurgery (Hagerstown, Md.)
https://www.readbyqxmd.com/read/28633147/tranexamic-acid-safely-reduced-blood-loss-in-hemi-and-total-hip-arthroplasty-for-acute-femoral-neck-fracture-a-randomized-clinical-trial
#15
Chad D Watts, Matthew T Houdek, S Andrew Sems, William W Cross, Mark W Pagnano
OBJECTIVES: We aimed to determine whether (1) tranexamic acid (TXA) reduces the incidence of transfusion (2) TXA reduces the calculated blood loss, and (3) there are any observable differences in 30- and 90-day complications with TXA administration during arthroplasty for femoral neck fracture (FNF). DESIGN: Prospective, double-blinded, randomized controlled trial. SETTING: Level 1 Academic Trauma Center. PATIENTS/PARTICIPANTS: One hundred thirty-eight patients who presented with a low-energy, isolated, FNF (AO 31B) treated with either hemi- or total hip arthroplasty within 72 hours of injury were randomized to either the TXA group (69 patients) or placebo group (69 patients)...
July 2017: Journal of Orthopaedic Trauma
https://www.readbyqxmd.com/read/28632582/the-effect-of-resuscitative-endovascular-balloon-occlusion-of-the-aorta-partial-aortic-occlusion-and-aggressive-blood-transfusion-on-traumatic-brain-injury-in-a-swine-multiple-injuries-model
#16
M Austin Johnson, Timothy K Williams, Sarah-Ashley E Ferencz, Anders J Davidson, Rachel M Russo, William T O'Brien, Joseph M Galante, J Kevin Grayson, Lucas P Neff
BACKGROUND: Despite clinical reports of poor outcomes, the degree to which resuscitative endovascular balloon occlusion of the aorta (REBOA) exacerbates traumatic brain injury (TBI) is not known. We hypothesized that combined effects of increased proximal mean arterial pressure (pMAP), carotid blood flow (Qcarotid), and intracranial pressure (ICP) from REBOA would lead to TBI progression compared with partial aortic occlusion (PAO) or no intervention. METHODS: Twenty-one swine underwent a standardized TBI via computer Controlled cortical impact followed by 25% total blood volume rapid hemorrhage...
July 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28632576/understanding-the-constipation-conundrum-predictors-of-obtaining-an-abdominal-radiograph-during-the-emergency-department-evaluation-of-pediatric-constipation
#17
Claire A MacGeorge, Daniel C Williams, Natalie Vajta, Kristen Morella, Paul G Thacker, Scott Russell, William T Basco, David G Bundy
OBJECTIVES: Many children with constipation who are evaluated in emergency departments (EDs) receive an abdominal radiograph (AR) despite evidence-based guidelines discouraging imaging. The objectives of this study were to identify predictors associated with obtaining an AR and to determine if ARs were associated with a longer length of stay (LOS) among children with constipation evaluated in the ED. METHODS: A review of billing and electronic health records was conducted in an academic pediatric ED for children ages 0 to 17 years who had a primary discharge diagnosis of constipation from July 2013 to June 2014...
June 20, 2017: Pediatric Emergency Care
https://www.readbyqxmd.com/read/28632323/clinical-outcomes-of-hla-dpb1-mismatches-in-10-10-hla-matched-unrelated-donor-recipient-pairs-undergoing-allogeneic-stem-cell-transplant
#18
Ann M Moyer, Shahrukh K Hashmi, Cynthia M Kroning, Walter K Kremers, Steven R De Goey, Mrinal Patnaik, Mark Litzow, Dennis A Gastineau, William J Hogan, Eapen K Jacob, Justin D Kreuter, Laurie L Wakefield, Manish J Gandhi
OBJECTIVE: HLA-DPB1 matching may impact allogeneic hematopoietic stem cell transplantation (ASCT) outcomes; however, this locus is not in linkage disequilibrium with the remainder of the HLA genes. After classifying HLA-DPB1 mismatches based on T-cell epitope, avoiding non-permissive mismatches may impact survival. We tested this hypothesis at a single academic institution. METHODS: Retrospective HLA-DPB1 genotyping was performed on 153 adult patients who underwent ASCT and unrelated donors matched for HLA-A, B, C, DRB1 and DQB1 loci (10/10)...
June 20, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28631970/computerized-neuropsychological-test-performance-of-youth-football-players-at-different-positions-a-comparison-of-high-and-low-contact-players
#19
William T Tsushima, Hyeong Jun Ahn, Andrea M Siu, Tama Fukuyama, Nathan M Murata
The aim of this study was to examine the effects of head impact frequency on the neuropsychological test results of football players who participate in different positions on the team. Based on the biomechanical measures of head impact frequency reported in high school football, a High Contact group (n = 480) consisting of offensive and defensive linemen was compared with a Low Contact group (n = 640) comprised of receivers and defensive backs. The results revealed that the High Contact group obtained poorer performances on the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) on three Composite scores (Verbal Memory, Visual Motor Speed, Impulse Control) and the Total Symptom score compared to the Low Contact group...
February 28, 2017: Applied Neuropsychology. Child
https://www.readbyqxmd.com/read/28631862/thalamic-deep-brain-stimulation-for-orthostatic-tremor-a-multicenter-international-registry
#20
Aristide Merola, Alfonso Fasano, Anhar Hassan, Jill L Ostrem, Maria Fiorella Contarino, Mark Lyons, Joachim K Krauss, Marc E Wolf, Bryan T Klassen, Anne-Fleur van Rootselaar, Ignacio Regidor, Andrew P Duker, William Ondo, Jorge Guridi, Jens Volkmann, Aparna Wagle Shukla, George T Mandybur, Michael S Okun, Karsten Witt, Philip A Starr, Günther Deuschl, Alberto J Espay
BACKGROUND: We report the accumulated experience with ventral intermediate nucleus deep brain stimulation for medically refractory orthostatic tremor. METHODS: Data from 17 patients were reviewed, comparing presurgical, short-term (0-48 months), and long-term (≥48 months) follow-up. The primary end point was the composite activities of daily living/instrumental activities of daily living score. Secondary end points included latency of symptoms on standing and treatment-related complications...
June 20, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
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