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https://www.readbyqxmd.com/read/29226520/a-novel-homozygous-slc25a1-mutation-with-impaired-mitochondrial-complex-v-possible-phenotypic-expansion
#1
Idan Cohen, Orna Staretz-Chacham, Ohad Wormser, Yonatan Perez, Ann Saada, Rotem Kadir, Ohad S Birk
SLC25A1 mutations are associated with combined D,L-2-hydroxyglutaric aciduria (DL- 2HGA; OMIM #615182), characterized by muscular hypotonia, severe neurodevelopmental dysfunction and intractable seizures. SLC25A1 encodes the mitochondrial citrate carrier (CIC), which mediates efflux of the mitochondrial tricarboxylic acid (TCA) cycle intermediates citrate and isocitrate in exchange for cytosolic malate. Only a single family with an SLC25A1 mutation has been described in which mitochondrial respiratory chain dysfunction was documented, specifically in complex IV...
December 11, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29217296/smaller-hippocampal-volume-in-posttraumatic-stress-disorder-a-multisite-enigma-pgc-study-subcortical-volumetry-results-from-posttraumatic-stress-disorder-consortia
#2
Mark W Logue, Sanne J H van Rooij, Emily L Dennis, Sarah L Davis, Jasmeet P Hayes, Jennifer S Stevens, Maria Densmore, Courtney C Haswell, Jonathan Ipser, Saskia B J Koch, Mayuresh Korgaonkar, Lauren A M Lebois, Matthew Peverill, Justin T Baker, Premika S W Boedhoe, Jessie L Frijling, Staci A Gruber, Ilan Harpaz-Rotem, Neda Jahanshad, Sheri Koopowitz, Ifat Levy, Laura Nawijn, Lauren O'Connor, Miranda Olff, David H Salat, Margaret A Sheridan, Jeffrey M Spielberg, Mirjam van Zuiden, Sherry R Winternitz, Jonathan D Wolff, Erika J Wolf, Xin Wang, Kristen Wrocklage, Chadi G Abdallah, Richard A Bryant, Elbert Geuze, Tanja Jovanovic, Milissa L Kaufman, Anthony P King, John H Krystal, Jim Lagopoulos, Maxwell Bennett, Ruth Lanius, Israel Liberzon, Regina E McGlinchey, Katie A McLaughlin, William P Milberg, Mark W Miller, Kerry J Ressler, Dick J Veltman, Dan J Stein, Kathleen Thomaes, Paul M Thompson, Rajendra A Morey
BACKGROUND: Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)-Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group. METHODS: We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date...
September 20, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29211451/clip6-pna-peptide-conjugates-non-endosomal-delivery-of-splice-switching-oligonucleotides
#3
Terese Soudah, Maxim Mogilevsky, Rotem Karni, Eylon Yavin
Efficient delivery of oligonucleotides still remains a challenge in the field of oligonucleotide based therapy. Peptide nucleic acid (PNA), a DNA analogue that is typically synthesized by solid phase peptide chemistry, has been conjugated to a variety of cell penetrating peptides (CPP) as a means of improving its cellular uptake. These CPPs typically deliver their cargoes into cells by an endosomal-dependent mechanism resulting in lower bioavailability of the cargo. Herein, we designed and synthesized PNA-peptide conjugates as splice switching oligonucleotides (SSO) targeting the Mnk2 gene, a therapeutic target in cancer...
December 6, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29194320/no-iv-no-problem-intraosseous-administration-of-tranexamic-acid-is-as-effective-as-intravenous-in-a-porcine-hemorrhage-model
#4
Michael S Lallemand, Donald M Moe, John M McClellan, Michael Loughren, Shannon Marko, Matthew J Eckert, Matthew J Martin
BACKGROUND: The acute coagulopathy of trauma is often accompanied by hyperfibrinolysis. TXA can reverse this phenomenon, and, when given early, decreases mortality from bleeding. Establishing IV access can be difficult in trauma and IO access is often preferred for drug administration. Currently, there is no data on the efficacy of IO administered TXA. Our objectives were to compare serum concentrations of tranexamic acid (TXA) when given IV and intraosseous (IO) and to compare the efficacy of IO administered TXA to IV at reversing hyperfibrinolysis METHODS: Using a porcine hemorrhage and ischemia-reperfusion (IR) model, 18 swine underwent hemorrhagic shock followed by a tissue plasminogen activator (tPA) infusion to induce hyperfibrinolysis...
December 1, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/29192294/primary-burning-mouth-syndrome-literature-review-and-preliminary-findings-suggesting-possible-association-with-pain-modulation
#5
Cibele Nasri-Heir, Diana Shigdar, Deyaaeddin Alnaas, Olga Anna Korczeniewska, Rotem Eliav, Gary M Heir
Primary burning mouth syndrome (BMS) is a chronic pain of a burning quality affecting the tongue and intraoral mucosa. Currently, there are no definite diagnostic criteria; therefore, the diagnosis is made by exclusion of potential local and systemic causes that could justify the burning sensation. The etiology behind primary BMS remains unclear; however, the most acceptable theories link primary BMS with neuropathic pain. This article provides a review of primary BMS diagnosis, mechanisms, and treatment with focus on the association of BMS with pain modulation...
November 30, 2017: Quintessence International
https://www.readbyqxmd.com/read/29188749/bleeding-during-veno-venous-ecmo-cannot-reliably-be-predicted-by-rotational-thrombelastometry-rotem%C3%A2
#6
Christina Hellmann, Axel Schmutz, Johannes Kalbhenn
INTRODUCTION: Veno-venous extracorporeal membrane oxygenation (vvECMO) used for respiratory support is associated with clinical bleeding in at least one third of patients. Mechanisms promoting bleeding, like acquired von Willebrand syndrome, cannot be identified by routine coagulation tests. This study was performed to evaluate rotational Thrombelastography (ROTEM™) for specific results predicting bleeding events during vvECMO. METHODS: Five hundred and thirty-four ROTEM™ analyses of 57 patients over 574 days have been evaluated...
November 1, 2017: Perfusion
https://www.readbyqxmd.com/read/29172227/apolipoprotein-e-gene-polymorphism-trauma-burden-and-posttraumatic-stress-symptoms-in-u-s-military-veterans-results-from-the-national-health-and-resilience-in-veterans-study
#7
Natalie P Mota, Shizhong Han, Ilan Harpaz-Rotem, Paul Maruff, John H Krystal, Steven M Southwick, Joel Gelernter, Robert H Pietrzak
BACKGROUND: Previous research examining the association between apolipoprotein E (APOE) gene polymorphism and risk for posttraumatic stress disorder (PTSD) has been inconsistent due to the use of small and select samples. This study examined the relation between APOE genotype and PTSD symptoms in two nationally representative samples of U.S. military veterans. The potential effect of cumulative trauma burden and social support in moderating this association was also evaluated. METHODS: The main sample consisted of 1,386 trauma-exposed European American (EA) veterans (mean age: 62-63 years) who participated in the National Health and Resilience in Veterans Study (NHRVS) in 2011...
November 24, 2017: Depression and Anxiety
https://www.readbyqxmd.com/read/29165666/differences-in-outcomes-over-time-with-exclusive-enteral-nutrition-compared-to-steroids-in-children-with-mild-to-moderate-crohn-s-disease-results-from-the-growth-cd-study
#8
Noa Cohen-Dolev, Malgorata Sladek, Seamus Hussey, Dan Turner, Gabor Veres, Sibylle Koletzko, Javier Martin de Carpi, Annamaria Staiano, Ron Shaoul, Paolo Lionetti, Jorge Amil Dias, Anders Paerregaard, Federica Nuti, Tamar Pfeffer Gik, Tomer Ziv-Baran, Sivan Ben Avraham Shulman, Chen Sarbagili Shabat, Rotem Sigall Boneh, Richard K Russell, Arie Levine
Background: Exclusive enteral nutrition (EEN) and corticosteroids (CS) both induce similar rates of remission in mild to moderate pediatric Crohn's disease (CD), but differ with regard to mucosal healing. Our goal was to evaluate if EEN at diagnosis was superior to CS for improving long term outcomes. Methods: We prospectively followed newly diagnosed children <17 years with mild to moderate disease at baseline for two years in the GROWTH CD study. Patients were evaluated at baseline and at 8, 12, 78, and 104 weeks...
November 18, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29157015/influence-of-selected-antithrombotic-treatment-on-thromboelastometric-results
#9
Mia Hammer Holck, Thomas Decker Christensen, Anne-Mette Hvas
Rotatory thromboelastometry (ROTEM(®)) is used for diagnosing and monitoring bleeding patients. Some of these patients receive antithrombotic treatment, thus having an increased risk of bleeding. Only sparse knowledge exists about whether the ROTEM(®) analysis is influenced by antithrombotic treatment. The objective of the present study was to examine if the ROTEM(®) results are affected in patients receiving antithrombotic treatment. This prospective observational study included patients receiving either vitamin K-antagonists (VKA), aspirin (ASA) or ASA combined with an adenosine diphosphate (ADP) receptor antagonist (ASA + ADP)...
November 20, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/29151081/association-between-standard-laboratory-and-functional-tests-of-coagulation-in-dilutional-coagulopathy-an-in-vitro-study
#10
L J Krzych, P F Czempik
Standard laboratory tests (SLTs) of coagulation are in common use in clinical practice. We aimed to determine the association between SLTs and functional tests of coagulation in blood samples diluted with balanced crystalloid and colloid solutions in an ex vivo setting. The study group comprised 32 healthy young male volunteers. Whole blood samples were diluted at a 4:1 ratio with balanced crystalloid (Plasmalyte®) and two balanced colloids, 6% hydroxyethyl starch 130/0.4 (Volulyte®) and succinylated gelatin (Geloplasma®)...
August 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29150842/the-effect-of-6-hydroxyethyl-starch-130-0-4-on-acute-kidney-injury-in-paediatric-cardiac-surgery-a-prospective-randomised-trial
#11
H-W Oh, J-H Lee, H-C Kim, E-H Kim, I-K Song, H-S Kim, J-T Kim
We have evaluated the effect of a colloid solution on acute kidney injury in paediatric cardiac surgery. A total of 195 patients were ramdomly divided into an hydroxyethyl starch group and a control group. In the starch group, 6% hydroxyethyl starch 130/0.4 (Volulyte® ) was used as the primary fluid for volume resuscitation but was limited to 30 ml.kg-1 . In the control group, only crystalloid fluid was used during the peri-operative period. The incidence of acute kidney injury, peri-operative transfusion, clinical outcomes and laboratory data were compared...
November 17, 2017: Anaesthesia
https://www.readbyqxmd.com/read/29149971/fibrinolysis-in-living-donor-liver-transplantation-recipients-evaluated-using-thromboelastometry-impact-on-mortality
#12
T Shimauchi, K Yamaura, M Higashi, K Abe, T Yoshizumi, S Hoka
BACKGROUND: Inadequate hemostasis during living donor liver transplantation (LDLT) is mainly due to coagulopathy but may also include fibrinolysis. The purpose of this study was to determine the incidence of fibrinolysis and assess its relevance to mortality in LDLT. METHODS: The incidence and prognosis of fibrinolysis were retrospectively studied in 76 patients who underwent LDLT between April 2010 and February 2013. Fibrinolysis was evaluated and defined by maximum lysis (ML) >15% within a 60-minute run time using thromboelastometry (ROTEM)...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29140832/platelet-function-changes-in-a-time-dependent-manner-following-traumatic-brain-injury-in-a-murine-model
#13
Grace E Martin, Brent Xia, Young Kim, Mark D Johnson, Rosalie Veile, Lou Ann Friend, Amy T Makley, Charles C Caldwell, Michael D Goodman
Traumatic brain injury (TBI) results in systemic changes in coagulation and inflammation that contribute to post-traumatic morbidity and mortality. The potential interaction of platelets and pro-inflammatory cytokines in the modulation of coagulation, microthrombosis, and venous thromboembolic events after moderate TBI (TBI) has not been determined. Using a murine model, we hypothesized 1) that the degree of platelet-induced coagulation varies depending on the platelet aggregation agonist 2) platelet-induced coagulation changes in a time-dependent manner following TBI, and 3) changes in platelet-induced coagulation are mirrored by changes in the levels of circulating pro-inflammatory cytokines...
November 14, 2017: Shock
https://www.readbyqxmd.com/read/29126686/transfusion-threshold-of-hemoglobin-80-g-l-is-comparable-to-100-g-l-in-terms-of-bleeding-in-cardiac-surgery-a-prospective-randomized-study
#14
Antti Laine, Tomi Niemi, Alexey Schramko
OBJECTIVE: Anemia is common after cardiac surgery and, according to some suggestive evidence, may be associated with increased bleeding, other morbidity, and mortality. However, transfusion of red blood cells (RBC) may cause adverse effects and increase cost. The authors hypothesized that the restrictive hemoglobin threshold (Hb of 80 g/L) may aggravate bleeding more than the higher Hb threshold (Hb 100 g/L). DESIGN: Prospective randomized trial. TYPE OF HOSPITAL: University Hospital of Helsinki, Finland...
August 30, 2017: Journal of Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/29112094/thrombelastography-early-amplitudes-in-bleeding-and-coagulopathic-trauma-patients-results-from-a-multicenter-study
#15
Thomas H Laursen, Martin A S Meyer, Anna Sina P Meyer, Tina Gaarder, Paal A Naess, Jakob Stensballe, Sisse R Ostrowski, Pär I Johansson
BACKGROUND: Early amplitudes in the viscoelastic hemostatic assays Thrombelastography (TEG) and Rotation Thromboelastometry (ROTEM) provide fast results, which is critical in resuscitation of bleeding patients. This study investigated associations between TEG early amplitudes and standard TEG variables in a large multicenter cohort of moderately to severely injured trauma patients admitted at three North European level 1 Trauma Centers. METHODS: Prospective observational study of 404 trauma patients with clinical suspicion of severe injury from London, UK, Copenhagen, Denmark and Oslo, Norway...
November 3, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/29110832/thromboelastometric-profile-and-acute-coagulopathy-of-the-polytraumatized-patient-clinical-and-prognostic-implications
#16
Antònia Bonet, Zoilo Madrazo, Maylin Koo, Israel Otero, Montserrat Mallol, Irene Macia, Luciano Ramirez, Antoni Sabaté
INTRODUCTION: About 25-35% of polytraumatized patients have a profound alteration of hemostasis on arrival at the hospital (acute traumatic coagulopathy [CAT]). Viscoelastic tests (ROTEM(®)) measure the hemostatic capacity and provide an early detection of CAT. The objectives of this study are to describe the initial thromboelastogram of these patients and to determine the prevalence of CAT according to predefined thromboelastographic profiles. METHODS: Single-center, observational, prospective study in polytraumatic patients...
October 27, 2017: Cirugía Española
https://www.readbyqxmd.com/read/29109393/scalable-whole-exome-sequencing-of-cell-free-dna-reveals-high-concordance-with-metastatic-tumors
#17
Viktor A Adalsteinsson, Gavin Ha, Samuel S Freeman, Atish D Choudhury, Daniel G Stover, Heather A Parsons, Gregory Gydush, Sarah C Reed, Denisse Rotem, Justin Rhoades, Denis Loginov, Dimitri Livitz, Daniel Rosebrock, Ignaty Leshchiner, Jaegil Kim, Chip Stewart, Mara Rosenberg, Joshua M Francis, Cheng-Zhong Zhang, Ofir Cohen, Coyin Oh, Huiming Ding, Paz Polak, Max Lloyd, Sairah Mahmud, Karla Helvie, Margaret S Merrill, Rebecca A Santiago, Edward P O'Connor, Seong H Jeong, Rachel Leeson, Rachel M Barry, Joseph F Kramkowski, Zhenwei Zhang, Laura Polacek, Jens G Lohr, Molly Schleicher, Emily Lipscomb, Andrea Saltzman, Nelly M Oliver, Lori Marini, Adrienne G Waks, Lauren C Harshman, Sara M Tolaney, Eliezer M Van Allen, Eric P Winer, Nancy U Lin, Mari Nakabayashi, Mary-Ellen Taplin, Cory M Johannessen, Levi A Garraway, Todd R Golub, Jesse S Boehm, Nikhil Wagle, Gad Getz, J Christopher Love, Matthew Meyerson
Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling of tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies tumor content in cfDNA from 0.1× coverage whole-genome sequencing data without prior knowledge of tumor mutations. We apply ichorCNA to 1439 blood samples from 520 patients with metastatic prostate or breast cancers. In the earliest tested sample for each patient, 34% of patients have ≥10% tumor-derived cfDNA, sufficient for standard coverage whole-exome sequencing...
November 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/29102170/protection-of-vaccinated-mice-against-pneumonic-tularemia-is-associated-with-an-early-memory-sentinel-response-in-the-lung
#18
Liat Bar-On, Hila Cohen, Uri Elia, Shahar Rotem, Adi Bercovich-Kinori, Erez Bar-Haim, Theodor Chitlaru, Ofer Cohen
Francisella tularensis is the intracellular bacterial pathogen causing the respiratory life-threatening disease tularemia. Development of tularemia vaccines has been hampered by an incomplete understanding of the correlates of immunity. Moreover, the importance of lung cellular immunity in vaccine-mediated protection against tularemia is a controversial matter. Live attenuated vaccine strains of F. tularensis such as LVS (Live Vaccine Strain), elicit an immune response protecting mice against subsequent challenge with the virulent SchuS4 strain, yet the protective immunity against pulmonary challenge is limited in its efficacy and longevity...
October 25, 2017: Vaccine
https://www.readbyqxmd.com/read/29101162/ex-vivo-profiling-of-pd-1-blockade-using-organotypic-tumor-spheroids
#19
Russell W Jenkins, Amir R Aref, Patrick H Lizotte, Elena Ivanova, Susanna Stinson, Chensheng W Zhou, Michaela Bowden, Jiehui Deng, Hongye Liu, Diana Miao, Meng Xiao He, William Walker, Gao Zhang, Tian Tian, Chaoran Cheng, Zhi Wei, Sangeetha Palakurthi, Mark Bittinger, Hans Vitzthum, Jong Wook Kim, Ashley Merlino, Max Quinn, Chandrasekar Venkataramani, Joshua A Kaplan, Andrew Portell, Prafulla C Gokhale, Bart Phillips, Alicia Smart, Asaf Rotem, Robert E Jones, Lauren Keogh, Maria Anguiano, Lance Stapleton, Zhiheng Jia, Michal Barzily-Rokni, Israel Cañadas, Tran C Thai, Marc R Hammond, Raven Vlahos, Eric S Wang, Hua Zhang, Shuai Li, Glenn J Hanna, Wei Huang, Mai P Hoang, Adriano Piris, Jean-Pierre Eliane, Anat O Stemmer-Rachamimov, Lisa Cameron, Mei-Ju Su, Parin Shah, Benjamin Izar, Manisha Thakuria, Nicole R LeBoeuf, Guilherme Rabinowits, Viswanath Gunda, Sareh Parangi, James M Cleary, Brian C Miller, Shunsuke Kitajima, Rohit Thummalapalli, Benchun Miao, Thanh U Barbie, Vivek Sivathanu, Joshua Wong, William G Richards, Raphael Bueno, Charles H Yoon, Juan Miret, Meenhard Herlyn, Levi A Garraway, Eliezer M Van Allen, Gordon J Freeman, Paul T Kirschmeier, Jochen H Lorch, Patrick A Ott, F Stephen Hodi, Keith T Flaherty, Roger D Kamm, Genevieve M Boland, Kwok-Kin Wong, David Dornan, Cloud Peter Paweletz, David A Barbie
Ex vivo systems that incorporate features of the tumor microenvironment (TME) and model the dynamic response to immune checkpoint blockade (ICB) may facilitate efforts in precision immuno-oncology and the development of effective combination therapies. Here, we demonstrate the ability to interrogate ex vivo response to ICB using murine- and patient-derived organotypic tumor spheroids (MDOTS/PDOTS). MDOTS/PDOTS isolated from mouse and human tumors retain autologous lymphoid and myeloid cell populations, and respond to ICB in short-term 3-dimensional microfluidic culture...
November 3, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29098290/fluid-structure-interaction-models-of-bicuspid-aortic-valves-the-effects-of-non-fused-cusp-angles
#20
Karin Lavon, Rotem Halevi, Gil Marom, Sagit Ben Zekry, Ashraf Hamdan, Hans Joachim Schäfers, Ehud Raanani, Rami Haj-Ali
Bicuspid aortic valve (BAV) is the most common type of congenital heart disease, occurring in 0.5-2% of the population, where the valve has only two rather than the three normal cusps. Valvular pathologies, such as aortic regurgitation and aortic stenosis, are associated with BAVs, thereby increasing the need for a better understanding of BAV kinematics and geometrical characteristics. The aim of this study is to investigate the influence of the non-fused cusp (NFC) angle in BAV type-1 configuration on the valve's structural and hemodynamic performance...
November 2, 2017: Journal of Biomechanical Engineering
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