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https://www.readbyqxmd.com/read/29329111/severe-peri-ictal-respiratory-dysfunction-is-common-in-dravet-syndrome
#1
YuJaung Kim, Eduardo Bravo, Caitlin K Thirnbeck, Lori A Smith-Mellecker, Se Hee Kim, Brian K Gehlbach, Linda C Laux, Douglas R Nordli Jr, George B Richerson
Dravet syndrome (DS) is a severe childhood-onset epilepsy commonly due to mutations of the sodium channel gene SCN1A. DS patients have a high risk of sudden unexplained death in epilepsy (SUDEP), believed to be due to cardiac mechanisms. Here we show that DS patients have peri-ictal respiratory dysfunction. One patient who had severe and prolonged postictal hypoventilation later died of SUDEP. Mice with an Scn1aR1407X/+ loss of function mutation died after spontaneous and heat-induced seizures due to central apnea followed by progressive bradycardia...
January 11, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29324729/vital-signs-trends-and-disparities-in-infant-safe-sleep-practices-united-states-2009-2015
#2
Jennifer M Bombard, Katherine Kortsmit, Lee Warner, Carrie K Shapiro-Mendoza, Shanna Cox, Charlan D Kroelinger, Sharyn E Parks, Deborah L Dee, Denise V D'Angelo, Ruben A Smith, Kim Burley, Brian Morrow, Christine K Olson, Holly B Shulman, Leslie Harrison, Carri Cottengim, Wanda D Barfield
There have been dramatic improvements in reducing infant sleep-related deaths since the 1990s, when recommendations were introduced to place infants on their backs for sleep. However, there are still approximately 3,500 sleep-related deaths among infants each year in the United States, including those from sudden infant death syndrome, accidental suffocation and strangulation in bed, and unknown causes. Unsafe sleep practices, including placing infants in a nonsupine (on side or on stomach) sleep position, bed sharing, and using soft bedding in the sleep environment (e...
January 12, 2018: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/29319159/leveraging-big-data-in-pediatric-development-programs-proceedings-from-the-2016-american-college-of-clinical-pharmacology-annual-meeting-symposium
#3
REVIEW
Lily Yeruk Mulugeta, Lynne Yao, Diane Mould, Brian Jacobs, Jeffrey Florian, Brian Smith, Vikram Sinha, Jeffrey S Barrett
This article discusses the use of big data in pediatric drug development. The article covers key topics discussed at the ACCP annual meeting symposium in 2016 including the extent to which big data or real-world data can inform clinical trial design and substitute for efficacy and safety data typically obtained in clinical trials. The current states of use, opportunities, and challenges with the use of big data in future pediatric drug development are discussed.
January 10, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29314393/global-cerebral-atrophy-detected-by-routine-imaging-relationship-with-age-hippocampal-atrophy-and-white-matter-hyperintensities
#4
Omar M Al-Janabi, Pradeep Panuganti, Erin L Abner, Ahmed A Bahrani, Ronan Murphy, Shoshana H Bardach, Allison Caban-Holt, Peter T Nelson, Brian T Gold, Charles D Smith, Donna M Wilcock, Gregory A Jicha
BACKGROUND AND PURPOSE: Interpreting the clinical significance of moderate-to-severe global cerebral atrophy (GCA) is a conundrum for many clinicians, who visually interpret brain imaging studies in routine clinical practice. GCA may be attributed to normal aging, Alzheimer's disease (AD), or cerebrovascular disease (CVD). Understanding the relationships of GCA with aging, AD, and CVD is important for accurate diagnosis and treatment decisions for cognitive complaints. METHODS: To elucidate the relative associations of age, moderate-to-severe white matter hyperintensities (WMHs), and moderate-to-severe medial temporal lobe atrophy (MTA), with moderate-to-severe GCA, we visually rated clinical brain imaging studies of 325 participants from a community based sample...
January 5, 2018: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
https://www.readbyqxmd.com/read/29310899/efficacy-safety-and-tolerability-of-dolutegravir-rilpivirine-for-the-maintenance-of-virological-suppression-in-adults-with-hiv-1-phase-3-randomised-non-inferiority-sword-1-and-sword-2-studies
#5
Josep M Llibre, Chien-Ching Hung, Cynthia Brinson, Francesco Castelli, Pierre-Marie Girard, Lesley P Kahl, Elizabeth A Blair, Kostas Angelis, Brian Wynne, Kati Vandermeulen, Mark Underwood, Kim Smith, Martin Gartland, Michael Aboud
BACKGROUND: Lifelong HIV antiretroviral therapy (ART) has prompted an interest in two-drug regimens to minimise cumulative drug exposure and toxicities. The safety, tolerability, and efficacy of dolutegravir and rilpivirine suggest potential compatibility and effectiveness as a two-drug regimen. We aimed to investigate this two-drug regimen in a phase 3 study. METHODS: We identically designed SWORD-1 and SWORD-2, which were open-label, parallel-group, multicentre, phase 3, randomised, non-inferiority studies in 12 countries evaluating efficacy and safety of once-daily dolutegravir 50 mg plus rilpivirine 25 mg versus current ART regimen (CAR)...
January 5, 2018: Lancet
https://www.readbyqxmd.com/read/29302006/transferrin-receptor-1-is-a-reticulocyte-specific-receptor-for-plasmodium-vivax
#6
Jakub Gruszczyk, Usheer Kanjee, Li-Jin Chan, Sébastien Menant, Benoit Malleret, Nicholas T Y Lim, Christoph Q Schmidt, Yee-Foong Mok, Kai-Min Lin, Richard D Pearson, Gabriel Rangel, Brian J Smith, Melissa J Call, Michael P Weekes, Michael D W Griffin, James M Murphy, Jonathan Abraham, Kanlaya Sriprawat, Maria J Menezes, Marcelo U Ferreira, Bruce Russell, Laurent Renia, Manoj T Duraisingh, Wai-Hong Tham
Plasmodium vivax shows a strict host tropism for reticulocytes. We identified transferrin receptor 1 (TfR1) as the receptor for P. vivax reticulocyte-binding protein 2b (PvRBP2b). We determined the structure of the N-terminal domain of PvRBP2b involved in red blood cell binding, elucidating the molecular basis for TfR1 recognition. We validated TfR1 as the biological target of PvRBP2b engagement by means of TfR1 expression knockdown analysis. TfR1 mutant cells deficient in PvRBP2b binding were refractory to invasion of P...
January 5, 2018: Science
https://www.readbyqxmd.com/read/29298242/contemporary-management-of-high-grade-renal-trauma-results-from-the-american-association-for-the-surgery-of-trauma-aast-genitourinary-trauma-study
#7
Sorena Keihani, Yizhe Xu, Angela P Presson, James M Hotaling, Raminder Nirula, Joshua Piotrowski, Christopher M Dodgion, Cullen M Black, Kaushik Mukherjee, Bradley J Morris, Sarah Majercik, Brian P Smith, Ian Schwartz, Sean P Elliott, Erik S DeSoucy, Scott Zakaluzny, Peter B Thomsen, Bradley A Erickson, Nima Baradaran, Benjamin N Breyer, Brandi Miller, Richard A Santucci, Matthew M Carrick, Timothy Hewitt, Frank N Burks, Jurek F Kocik, Reza Askari, Jeremy B Myers
BACKGROUND: The rarity of renal trauma limits its study and the strength of evidence-based guidelines. Although management of renal injuries has shifted towards a non-operative approach, nephrectomy remains the most common intervention for high-grade renal trauma (HGRT). We aimed to describe the contemporary management of HGRT in the United States and also evaluate clinical factors associated with nephrectomy after HGRT. METHODS: From 2014 to 2017, data on HGRT (American Association for the Surgery of Trauma [AAST] grades III-V) were collected from 14 participating Level-1 trauma centers...
January 2, 2018: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/29287910/ventral-tegmental-area-d2-receptor-knockdown-enhances-choice-impulsivity-in-a-delay-discounting-task-in-rats
#8
Kimberly A Bernosky-Smith, Yan-Yan Qiu, Malte Feja, Yun Beom Lee, Brian Loughlin, Jun-Xu Li, Caroline E Bass
Impulsivity associated with abnormal dopamine (DA) function has been observed in several disorders, including addiction. Choice impulsivity is the preference for small, immediate rewards over larger rewards after a delay, caused by excessive discounting of future rewards. Addicts have abnormally high discount rates and prefer the smaller rewards sooner. While impulsivity has been inversely correlated with DA D2 receptor (D2R) availability in the midbrain and striatum, it is difficult to mechanistically link the two, due to the diverse neuroanatomical localization of D2Rs, which are found throughout the brain, in many types of neurons and neuronal subcompartments...
December 26, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29284022/a-transcriptomics-approach-uncovers-novel-roles-for-poly-adp-ribosyl-ation-in-the-basal-defense-response-in-arabidopsis-thaliana
#9
Amy G Briggs, Lori C Adams-Phillips, Brian D Keppler, Sophia G Zebell, Kyle C Arend, April A Apfelbaum, Joshua A Smith, Andrew F Bent
Pharmacological inhibition of poly(ADP-ribose) polymerase (PARP) or loss of Arabidopsis thaliana PARG1 (poly(ADP-ribose) glycohydrolase) disrupt a subset of plant defenses. In the present study we examined the impact of altered poly(ADP-ribosyl)ation on early gene expression induced by the microbe-associate molecular patterns (MAMPs) flagellin (flg22) and EF-Tu (elf18). Stringent statistical analyses and filtering identified 178 genes having MAMP-induced mRNA abundance patterns that were altered by either PARP inhibitor 3-aminobenzamide (3AB) or PARG1 knockout...
2017: PloS One
https://www.readbyqxmd.com/read/29281107/outcomes-of-operative-treatment-for-adult-cervical-deformity-a-prospective-multicenter-assessment-with-1-year-follow-up
#10
Tamir Ailon, Justin S Smith, Christopher I Shaffrey, Han Jo Kim, Gregory Mundis, Munish Gupta, Eric Klineberg, Frank Schwab, Virginie Lafage, Renaud Lafage, Peter Passias, Themistocles Protopsaltis, Brian Neuman, Alan Daniels, Justin K Scheer, Alex Soroceanu, Robert Hart, Rick Hostin, Douglas Burton, Vedat Deviren, Todd J Albert, K Daniel Riew, Shay Bess, Christopher P Ames
BACKGROUND: Despite the potential for profound impact of adult cervical deformity (ACD) on function and health-related quality of life (HRQOL), there are few high-quality studies that assess outcomes of surgical treatment for these patients. OBJECTIVE: To determine the impact of surgical treatment for ACD on HRQOL. METHODS: We conducted a prospective cohort study of surgically treated ACD patients eligible for 1-yr follow-up. Baseline deformity characteristics, surgical parameters, and 1-yr HRQOL outcomes were assessed...
December 21, 2017: Neurosurgery
https://www.readbyqxmd.com/read/29276339/frog-foams-and-natural-protein-surfactants
#11
Alan Cooper, Steven J Vance, Brian O Smith, Malcolm W Kennedy
Foams and surfactants are relatively rare in biology because of their potential to harm cell membranes and other delicate tissues. However, in recent work we have identified and characterized a number of natural surfactant proteins found in the foam nests of tropical frogs and other unusual sources. These proteins, and their associated foams, are relatively stable and bio-compatible, but with intriguing molecular structures that reveal a new class of surfactant activity. Here we review the structures and functional mechanisms of some of these proteins as revealed by experiments involving a range of biophysical and biochemical techniques, with additional mechanistic support coming from more recent site-directed mutagenesis studies...
December 5, 2017: Colloids and Surfaces. A, Physicochemical and Engineering Aspects
https://www.readbyqxmd.com/read/29260811/the-aggregation-of-an-alkyl-c60-derivative-as-a-function-of-concentration-temperature-and-solvent-type
#12
Martin J Hollamby, Catherine F Smith, Melanie M Britton, Ashleigh E Danks, Zoe Schnepp, Isabelle Grillo, Brian R Pauw, Akihiro Kishimura, Takashi Nakanishi
Contrast-variation small-angle neutron scattering (CV-SANS), small-angle X-ray scattering (SAXS), nuclear magnetic resonance (NMR) measurements of diffusion and isothermal titration calorimetry (ITC) are used to gain insight into the aggregation of an alkyl-C60 derivative, molecule 1, in n-hexane, n-decane and toluene as a function of concentration and temperature. Results point to an associative mechanism of aggregation similar to other commonly associating molecules, including non-ionic surfactants or asphaltenes in non-aqueous solvents...
December 20, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29259248/aav-vector-meditated-expression-of-hla-g-reduces-injury-induced-corneal-vascularization-immune-cell-infiltration-and-fibrosis
#13
Matthew L Hirsch, Laura M Conatser, Sara M Smith, Jacklyn H Salmon, Jerry Wu, Nicholas E Buglak, Rich Davis, Brian C Gilger
Over 1.5 million individuals suffer from cornea vascularization due to genetic and/or environmental factors, compromising visual acuity and often resulting in blindness. Current treatments of corneal vascularization are limited in efficacy and elicit undesirable effects including, ironically, vision loss. To develop a safe and effective therapy for corneal vascularization, adeno-associated virus (AAV) gene therapy, exploiting a natural immune tolerance mechanism induced by human leukocyte antigen G (HLA-G), was investigated...
December 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29258568/establishing-core-outcome-sets-for-phenylketonuria-pku-and-medium-chain-acyl-coa-dehydrogenase-mcad-deficiency-in-children-study-protocol-for-systematic-reviews-and-delphi-surveys
#14
Beth K Potter, Brian Hutton, Tammy J Clifford, Nicole Pallone, Maureen Smith, Sylvia Stockler, Pranesh Chakraborty, Pauline Barbeau, Chantelle M Garritty, Michael Pugliese, Alvi Rahman, Becky Skidmore, Laure Tessier, Kylie Tingley, Doug Coyle, Cheryl R Greenberg, Lawrence Korngut, Alex MacKenzie, John J Mitchell, Stuart Nicholls, Martin Offringa, Andreas Schulze, Monica Taljaard
BACKGROUND: Inherited metabolic diseases (IMD) are a large group of rare single-gene disorders that are typically diagnosed early in life. There are important evidence gaps related to the comparative effectiveness of therapies for IMD, which are in part due to challenges in conducting randomized controlled trials (RCTs) for rare diseases. Registry-based RCTs present a unique opportunity to address these challenges provided the registries implement standardized collection of outcomes that are important to patients and their caregivers and to clinical providers and healthcare systems...
December 19, 2017: Trials
https://www.readbyqxmd.com/read/29251394/optic-neuritis-in-dogs-96-cases-1983-2016
#15
Sara M Smith, Hans D Westermeyer, Christopher L Mariani, Brian C Gilger, Michael G Davidson
OBJECTIVE: To characterize ocular and neurologic findings, causes, and treatment outcomes of dogs with optic neuritis. PROCEDURE: Medical records from dogs with a diagnosis of optic neuritis at North Carolina State University, College of Veterinary Medicine, Veterinary Hospital between 1983 and 2016 were reviewed. RESULTS: Ninety-six cases (20 unilateral, 76 bilateral), comprised of 38 males and 58 females with a mean age of 6.1 ± 3.0 years (range 0...
December 18, 2017: Veterinary Ophthalmology
https://www.readbyqxmd.com/read/29248781/drivers-of-cervical-deformity-have-a-strong-influence-on-achieving-optimal-radiographic-and-clinical-outcomes-at-1-year-following-cervical-deformity-surgery
#16
Peter G Passias, Cole Bortz, Samantha Horn, Frank Segreto, Gregory Poorman, Cyrus Jalai, Alan Daniels, D Kojo Hamilton, Han Jo Kim, Daniel Sciubba, Justin S Smith, Brian Neuman, Christopher Shaffrey, Virginie Lafage, Themistocles Protopsaltis, Christopher Ames, Robert Hart, Gregory Mundis, Robert Eastlack
OBJECTIVE: The primary driver (PD) of cervical malalignment is important in characterizing cervical deformity(CD) and should be included in fusion to achieve alignment and quality-of-life goals. This study aims to define how PDs improve understanding of the mechanisms of cervical deformity, and assesses the impact of driver region on re-alignment/outcomes. METHODS: Inclusion: radiographic cervical deformity, >18 years, 1-year follow-up. PD apex was classified by spinal region: cervical, cervicothoracic junction(CTJ), thoracic, or spino-pelvic by panel of spine deformity surgeons...
December 14, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/29246701/stool-donor-body-mass-index-does-not-affect-recipient-weight-after-a-single-fecal-microbiota-transplantation-for-c-difficile-infection
#17
Monika Fischer, Dina Kao, Zain Kassam, Justin Smith, Thomas Louie, Brian Sipe, Michelle Torbeck, Huiping Xu, Fangqian Ouyang, Dariush Mozaffarian, Jessica R Allegretti
No abstract text is available yet for this article.
December 12, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29244532/risk-factors-and-predictors-of-significant-chondral-surface-change-from-primary-to-revision-anterior-cruciate-ligament-reconstruction-a-moon-and-mars-cohort-study
#18
Robert A Magnussen, James R Borchers, Angela D Pedroza, Laura J Huston, Amanda K Haas, Kurt P Spindler, Rick W Wright, Christopher C Kaeding, Christina R Allen, Allen F Anderson, Daniel E Cooper, Thomas M DeBerardino, Warren R Dunn, Brett A Lantz, Barton Mann, Michael J Stuart, John P Albright, Annunziato Amendola, Jack T Andrish, Christopher C Annunziata, Robert A Arciero, Bernard R Bach, Champ L Baker, Arthur R Bartolozzi, Keith M Baumgarten, Jeffery R Bechler, Jeffrey H Berg, Geoffrey A Bernas, Stephen F Brockmeier, Robert H Brophy, Charles A Bush-Joseph, J Brad Butler, John D Campbell, James L Carey, James E Carpenter, Brian J Cole, Jonathan M Cooper, Charles L Cox, R Alexander Creighton, Diane L Dahm, Tal S David, David C Flanigan, Robert W Frederick, Theodore J Ganley, Elizabeth A Garofoli, Charles J Gatt, Steven R Gecha, James Robert Giffin, Sharon L Hame, Jo A Hannafin, Christopher D Harner, Norman Lindsay Harris, Keith S Hechtman, Elliott B Hershman, Rudolf G Hoellrich, Timothy M Hosea, David C Johnson, Timothy S Johnson, Morgan H Jones, Ganesh V Kamath, Thomas E Klootwyk, Bruce A Levy, C Benjamin Ma, G Peter Maiers, Robert G Marx, Matthew J Matava, Gregory M Mathien, David R McAllister, Eric C McCarty, Robert G McCormack, Bruce S Miller, Carl W Nissen, Daniel F O'Neill, Brett D Owens, Richard D Parker, Mark L Purnell, Arun J Ramappa, Michael A Rauh, Arthur C Rettig, Jon K Sekiya, Kevin G Shea, Orrin H Sherman, James R Slauterbeck, Matthew V Smith, Jeffrey T Spang, Steven J Svoboda, Timothy N Taft, Joachim J Tenuta, Edwin M Tingstad, Armando F Vidal, Darius G Viskontas, Richard A White, James S Williams, Michelle L Wolcott, Brian R Wolf, James J York
BACKGROUND: Articular cartilage health is an important issue following anterior cruciate ligament (ACL) injury and primary ACL reconstruction. Factors present at the time of primary ACL reconstruction may influence the subsequent progression of articular cartilage damage. HYPOTHESIS: Larger meniscus resection at primary ACL reconstruction, increased patient age, and increased body mass index (BMI) are associated with increased odds of worsened articular cartilage damage at the time of revision ACL reconstruction...
December 1, 2017: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/29242111/autologous-transplantation-in-follicular-lymphoma-with-early-therapy-failure-a-nlcs-and-cibmtr-analysis
#19
Carla Casulo, Jonathan W Friedberg, Kwang Woo Ahn, Christopher Flowers, Alyssa DiGilio, Sonali M Smith, Sairah Ahmed, David Inwards, Mahmoud Aljurf, Andy I Chen, Hannah Choe, Jonathon Cohen, Edward Copelan, Umar Farooq, Timothy S Fenske, Cesar Freytes, Sameh Gaballa, Siddhartha Ganguly, Yogesh Jethava, Rammurti T Kamble, Vaishalee P Kenkre, Hillard Lazarus, Aleksandr Lazaryan, Richard F Olsson, Andrew R Rezvani, David Rizzieri, Sachiko Seo, Gunjan L Shah, Nina Shah, Melham Solh, Anna Sureda, Basem William, Aaron Cumpston, Andrew D Zelenetz, Brian K Link, Mehdi Hamadani
Patients with follicular lymphoma (FL) experiencing early therapy failure (ETF) within two years of frontline chemoimmunotherapy have poor overall survival (OS). We analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR) and the National LymphoCare Study (NLCS) to determine whether autologous hematopoietic cell transplant (autoHCT) can improve outcomes in this high-risk FL subgroup.ETF was defined as failure to achieve at least partial response after frontline chemoimmunotherapy or lymphoma progression within two years of frontline chemoimmunotherapy...
December 11, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29239081/development-and-validation-of-2d-difference-intensity-analysis-for-chemical-library-screening-by-protein-detected-nmr
#20
John M Egner, Davin R Jensen, Mike D Olp, Nolan W Kennedy, Brian F Volkman, Francis C Peterson, Brian C Smith, R Blake Hill
An academic chemical screening approach was developed and a 352-chemical fragment library screened against 3 different protein targets using 2D protein-detected NMR. The approach was optimized against 2 protein targets with known ligands, CXCL12 and BRD4. Principal component analysis reliably identified compounds that induced NMR crosspeak broadening, but did not unambiguously identify ligands with specific affinity (hits). For improved hit detection, a novel scoring metric - difference intensity analysis (DIA) - was devised that sums all positive and negative intensities from 2D difference spectra...
December 13, 2017: Chembiochem: a European Journal of Chemical Biology
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