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https://read.qxmd.com/read/30877063/properties-of-fda-approved-small-molecule-protein-kinase-inhibitors
#1
REVIEW
Robert Roskoski
Because mutations, overexpression, and dysregulation of protein kinases play essential roles in the pathogenesis of many illnesses, this enzyme family has become one of the most important drug targets in the past 20 years. The US FDA has approved 48 small molecule protein kinase inhibitors, nearly all of which are orally effective with the exceptions of netarsudil (which is given as an eye drop) and temsirolimus (which is given intravenously). Of the 48 approved drugs, the majority (25) target receptor protein-tyrosine kinases, ten target non-receptor protein-tyrosine kinases, and 13 target protein-serine/threonine protein kinases...
March 12, 2019: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://read.qxmd.com/read/30872370/re-evaluation-of-hematocrit-as-a-determinant-of-thrombotic-risk-in-erythrocytosis
#2
Victor R Gordeuk, Nigel S Key, Josef T Prchal
Here we critically evaluate the role of elevated hematocrit as the principal determinant of thrombotic risk in polycythemia and erythrocytosis, defined by an expansion of red cell mass. Since red cell volume determination is no longer readily available, in clinical practice polycythemia and erythrocytosis are defined by elevated hemoglobin and hematocrit. Thrombosis is common in Chuvash erythrocytosis and polycythemia vera. Although the increased thrombotic risk is assumed to be due to the elevated hematocrit and an associated increase in blood viscosity, thrombosis does not accompany most types of erythrocytosis...
March 14, 2019: Haematologica
https://read.qxmd.com/read/30870306/pulmonary-insufficiency-advantage-of-pulmonary-regurgitation-volume-versus-pulmonary-regurgitation-fraction-in-a-congenital-heart-disease-mixed-population
#3
Francesco Secchi, Massimo Chessa, Marcello Petrini, Caterina B Monti, Marco Alì, Paola M Cannaò, Giovanni Di Leo, Francesco Sardanelli
OBJECTIVE: The objective of this study was to compare the use of pulmonary regurgitation volume (PRV) or indexed PRV (PRVi) with that of pulmonary regurgitation fraction (PRF) in the assessment of patients with pulmonary regurgitation (PR) undergoing cardiac magnetic resonance (CMR) imaging. MATERIALS AND METHODS: CMR of 176 patients with PR were retrospectively evaluated. Their right ventricular diastolic (end-diastolic volume index [EDVi]) and systolic (end-systolic volume index) volume indexes, stroke volume, and ejection fraction were obtained from cine CMR sequences, whereas phase-contrast flow sequences were analyzed to obtain PRV, PRVi, and PRF...
March 11, 2019: Journal of Thoracic Imaging
https://read.qxmd.com/read/30867461/piscine-orthoreovirus-demonstrates-high-infectivity-but-low-virulence-in-atlantic-salmon-of-pacific-canada
#4
Mark P Polinski, Gary D Marty, Heindrich N Snyman, Kyle A Garver
Piscine orthoreovirus (PRV) is ubiquitous in farmed Atlantic salmon and sometimes associated with disease - most notably, Heart and Skeletal Muscle Inflammation (HSMI). However, PRV is also widespread in non-diseased fish, particularly in Pacific Canada, where few cases of severe heart inflammation have been documented. To better understand the mechanisms behind PRV-associated disease, this study investigated the infection dynamics of PRV from Pacific Canada and the potential for experimental passage of putatively associated heart inflammation in Pacific-adapted Mowi-McConnell Atlantic salmon...
March 13, 2019: Scientific Reports
https://read.qxmd.com/read/30865581/viral-safety-of-aposec-%C3%A2-a-novel-peripheral-blood-mononuclear-cell-derived-biological-for-regenerative-medicine
#5
Alfred Gugerell, Dirk Sorgenfrey, Maria Laggner, Jürgen Raimann, Anja Peterbauer, Daniel Bormann, Susanne Suessner, Christian Gabriel, Bernhard Moser, Tobias Ostler, Michael Mildner, Hendrik J Ankersmit
BACKGROUND: Viral reduction and inactivation of cell-derived biologicals is paramount for patients' safety and so viral reduction needs to be demonstrated to regulatory bodies in order to obtain marketing authorisation. Allogeneic human blood-derived biological medicinal products require special attention. APOSEC™ , the secretome harvested from selected human blood cells, is a new biological with promising regenerative capabilities. We evaluated the effectiveness of inactivation of model viruses by methylene blue/light treatment, lyophilisation, and gamma irradiation during the manufacturing process of APOSEC™ ...
February 21, 2019: Blood Transfusion
https://read.qxmd.com/read/30850994/mortality-outbreak-by-perch-rhabdovirus-in-european-perch-perca-fluviatilis-farmed-in-italy-clinical-presentation-and-phylogenetic-analysis
#6
Claudio Caruso, Andrea Gustinelli, Paolo Pastorino, Pier Luigi Acutis, Riccardo Prato, Loretta Masoero, Simone Peletto, Maria Letizia Fioravanti, Marino Prearo
This work reports a mortality outbreak, occurred in 2015 and affecting juveniles of European perch (Perca fluviatilis L.) farmed in Italy. Perch rhabdovirus (PRV) was detected by viral isolation and biomolecular investigations. Phylogenetic analysis clustered our isolate into genogroup B, which also includes PRV isolates from Perca fluviatilis identified in France (2004-2009); diagnostic investigations also revealed opportunistic bacteria (Aeromonas hydrophila) and parasites (Chilodonella piscicola). Since, occasionally, PRV has been reported in the natural environment, which is often a source of eggs and broodstock for farms, it could be possible that both similar France and Italian isolate were imported from a same place elsewhere and have a common origin...
March 8, 2019: Journal of Fish Diseases
https://read.qxmd.com/read/30848334/thromboembolic-events-in-polycythemia-vera
#7
Martin Griesshammer, Jean-Jacques Kiladjian, Carlos Besses
Thromboembolic events and cardiovascular disease are the most prevalent complications in patients with polycythemia vera (PV) compared with other myeloproliferative disorders and are the major cause of morbidity and mortality in this population. Moreover, a vascular complication such as arterial or venous thrombosis often leads to the diagnosis of PV. The highest rates of thrombosis typically occur shortly before or at diagnosis and decrease over time, probably due to the effects of treatment. Important risk factors include age (≥ 60 years old) and a history of thrombosis; elevated hematocrit and leukocytosis are also associated with an increased risk of thrombosis...
March 8, 2019: Annals of Hematology
https://read.qxmd.com/read/30845266/viral-labeling-of-neurons-synaptically-connected-to-nucleus-accumbens-somatostatin-interneurons
#8
Efrain A Ribeiro, Alexander R Nectow, Lisa E Pomeranz, Mats I Ekstrand, Ja Wook Koo, Eric J Nestler
The nucleus accumbens, a key brain reward region, receives synaptic inputs from a range of forebrain and brainstem regions. Many of these projections have been established using electrophysiology or fluorescent tract tracing. However, more recently developed viral tracing techniques have allowed for fluorescent labeling of synaptic afferents in a cell type-specific manner. Since the NAc is comprised of multiple cell types, these methods have enabled the delineation of the cell type-specific connectivity of principal medium spiny neurons in the region...
2019: PloS One
https://read.qxmd.com/read/30843892/diagnosing-or-ruling-out-polycythemia-vera-in-patients-with-erythrocytosis
#9
Josef T Prchal
No abstract text is available yet for this article.
January 2019: Clinical Advances in Hematology & Oncology: H&O
https://read.qxmd.com/read/30843330/milestones-in-the-discovery-of-budd-chiari-syndrome
#10
Alberto Zanetto, Monica Pellone, Marco Senzolo
In 1845, George Budd published a brief report regarding three patients who developed an obstruction of the hepatic veins. The condition has never been reported before, and was related to sepsis and alcoholism. Fifty-three years later, Hans Chiari postulated that syphilis was causing the obstruction of the hepatic veins, and enriched the debate with clinical and pathological correlations. Following the hypothesis on the "phlebitis obliterans", several authors proposed other pathophysiological explanations including congenital causes, chronic trauma, and exogenous toxins...
March 6, 2019: Liver International: Official Journal of the International Association for the Study of the Liver
https://read.qxmd.com/read/30843002/the-role-of-18-f-fdg-pet-in-the-assessment-of-a-benign-hematological-disorder-polycythemia
#11
EDITORIAL
Cyrus Ayubcha, Hitomi Hosoya, Siavash M Seraj, Mahdi Z Zadeh, Thomas Werner, Abass Alavi
Fluorine-18 fluorodeoxyglucose positron emission tomography (18 F-FDG PET) imaging was conceived in the early 1970 by investigators at the University of Pennsylvania as a research technique to measure brain metabolism and function by employing a non-invasive imaging approach. Soon after the introduction of whole-body PET instruments, 18 F-FDG was utilized in the assessment of a variety of solid tumors and certain hematological malignancies. Yet, the role of 18 F-FDG in assessing benign and uncommon malignant disorders of the bone marrow has not been investigated to a great extent...
March 5, 2019: Hellenic Journal of Nuclear Medicine
https://read.qxmd.com/read/30842401/irreversible-chorea-as-the-initial-presentation-of-polycythemia-rubra-vera-in-an-elderly-woman
#12
Shakya Bhattacharjee
No abstract text is available yet for this article.
January 2019: Neurosciences: the Official Journal of the Pan Arab Union of Neurological Sciences
https://read.qxmd.com/read/30837221/-bif1-a-new-bmp-signaling-inhibitor-regulates-embryonic-hematopoiesis-in-the-zebrafish
#13
Joey J Ghersi, Christopher B Mahony, Julien Y Bertrand
Hematopoiesis maintains the entire blood system and dysregulation of this process can lead to malignancies (leukemia), immunodeficiencies or red blood cell diseases (anemia, polycythemia vera). We took advantage of the zebrafish model that shares most of the genetic program involved in hematopoiesis with mammals to characterize a new gene of unknown function, si:ch73-299h12.2, expressed in the erythroid lineage during primitive, definitive and adult hematopoiesis. This gene, required during primitive and definitive erythropoiesis, encodes a C2H2 zinc finger protein that inhibits BMP signaling...
March 5, 2019: Development
https://read.qxmd.com/read/30824279/3023-mayo-clinic-patients-with-myeloproliferative-neoplasms-risk-stratified-comparison-of-survival-and-outcomes-data-among-disease-subgroups
#14
Natasha Szuber, Mythri Mudireddy, Maura Nicolosi, Domenico Penna, Rangit R Vallapureddy, Terra L Lasho, Christy Finke, Kebede H Begna, Michelle A Elliott, C Christopher Hook, Alexandra P Wolanskyj, Mrinal M Patnaik, Curtis A Hanson, Rhett P Ketterling, Shireen Sirhan, Animesh Pardanani, Naseema Gangat, Lambert Busque, Ayalew Tefferi
OBJECTIVE: To document the Mayo Clinic decades-long experience with myeloproliferative neoplasms (MPNs) and provide mature risk-stratified survival data and disease complication estimates. PATIENTS AND METHODS: All Mayo Clinic patients with World Health Organization-defined MPNs constituted the core study group and included those with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). RESULTS: A total of 3023 consecutive patients (median age, 62 years; range, 18-96 years) were considered: 665 PV, 1076 ET, and 1282 PMF...
February 26, 2019: Mayo Clinic Proceedings
https://read.qxmd.com/read/30805220/polycythemia-vera-presenting-as-cardiac-arrest-novel-management-strategies
#15
Mark I Davis, Brian K Courtney, Gideon Cohen, Stephanie Poon, Mina Madan
Acute coronary syndromes (ACS) usually occur in patients with multiple cardiac risk factors. In young adults, drug use and hypercoagulable states are common causes for ACS presentations. We report a case of a man in his early 30s who was diagnosed with polycythemia vera (PV) and had a cardiac arrest due to an anterolateral ST elevation myocardial infarction. We discuss his unique management and review the evidence on the management of arterial thromboembolism in PV patients.
2019: Case Reports in Cardiology
https://read.qxmd.com/read/30802147/evaluation-of-an-in-ear-sensor-for-quantifying-head-impacts-in-youth-soccer
#16
Stian Bahr Sandmo, Andrew S McIntosh, Thor Einar Andersen, Inga Katharina Koerte, Roald Bahr
BACKGROUND: Wearable sensor systems have the potential to quantify head kinematic responses of head impacts in soccer. However, on-field use of sensors (eg, accelerometers) remains challenging, owing to poor coupling to the head and difficulties discriminating low-severity direct head impacts from inertial loading of the head from human movements, such as jumping and landing. PURPOSE: To test the validity of an in-ear sensor for quantifying head impacts in youth soccer...
February 25, 2019: American Journal of Sports Medicine
https://read.qxmd.com/read/30795904/therapeutic-erythroapheresis-experience-in-patients-with-polycythemia-vera-and-secondary-erythrocytosis
#17
Ingrid Parra Salinas, Valle Recasens Flores, María Ángeles Montañés, José Antonio García-Erce
Therapeutic erythrocytapheresis (TE) is a more efficient strategy compared to phlebotomy to deplete levels of haematocrit in primary and secondary erythrocytosis. OBJECTIVE: To analyse response rate and safety profile of TE in polycythemia vera (PV) and secondary erythrocytosis (SE). PATIENTS AND METHOD: Retrospective review of all patients with PV or SE treated with TE, due to phlebotomy failure, or comorbidities that prevented changes of blood volumen. RESULTS: 217 TE sessions (48 PV and 79 SE) corresponding to 20 patients (12 ES and 8 PV)...
February 19, 2019: Medicina Clínica
https://read.qxmd.com/read/30795541/intensive-distribution-of-g%C3%A2-quaduplexes-in-the-pseudorabies-virus-genome-and-their-sensitivity-to-cations-and-g-quadruplex-ligands
#18
Hui Deng, Bowen Gong, Zhiquan Yang, Zhen Li, Huan Zhou, Yashu Zhang, Xiaohui Niu, Sisi Liu, Dengguo Wei
Guanine-rich sequences in the genomes of herpesviruses can fold into G-quadruplexes. Compared with the widely-studied G₃-quadruplexes, the dynamic G₂-quadruplexes are more sensitive to the cell microenvironment, but they attract less attention. Pseudorabies virus (PRV) is the model species for the study of the latency and reactivation of herpesvirus in the nervous system. A total of 1722 G₂-PQSs and 205 G₃-PQSs without overlap were identified in the PRV genome. Twelve G₂-PQSs from the CDS region exhibited high conservation in the genomes of the Varicellovirus genus...
February 21, 2019: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/30793774/a-common-neural-substrate-for-elevated-ptsd-symptoms-and-reduced-pulse-rate-variability-in-combat-exposed-veterans
#19
Daniel W Grupe, Ted Imhoff-Smith, Joseph Wielgosz, Jack B Nitschke, Richard J Davidson
Previous studies have identified reduced heart rate variability (HRV) in post-traumatic stress disorder (PTSD), which may temporally precede the onset of the disorder. A separate line of functional neuroimaging research in PTSD has consistently demonstrated hypoactivation of the ventromedial prefrontal cortex (vmPFC), a key aspect of a descending neuromodulatory system that exerts inhibitory control over heart rate. No research to date, however, has simultaneously investigated whether altered vmPFC activation is associated with reduced HRV and elevated PTSD symptoms in the same individuals...
February 22, 2019: Psychophysiology
https://read.qxmd.com/read/30793328/viral-inactivation-of-human-platelet-lysate-by-gamma-irradiation-preserves-its-optimal-efficiency-in-the-expansion-of-human-bone-marrow-mesenchymal-stromal-cells
#20
Sabrina Viau, Sandy Eap, Lucie Chabrand, Anaïs Lagrange, Bruno Delorme
BACKGROUND: Human platelet lysate (hPL) represents a powerful medium supplement for human mesenchymal stromal cell (hMSC) expansion. The recently published general chapters of the Pharmacopeia require the addition of a step of viral inactivation during the production process of such raw biological material used for cell-based medicinal products. STUDY DESIGN AND METHODS: The ability of gamma irradiation to inactivate viruses from a panel representative of the virus diversity was evaluated...
February 21, 2019: Transfusion
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