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https://www.readbyqxmd.com/read/28724765/translesion-polymerase-pol-%C3%AE-is-required-for-efficient-epstein-barr-virus-infectivity-and-is-regulated-by-the-viral-deubiquitinating-enzyme-bplf1
#1
Ossie F Dyson, Joseph S Pagano, Christopher B Whitehurst
Epstein-Barr Virus (EBV) infection and lytic replication are known to induce a cellular DNA damage response. Previously we showed that the virally encoded BPLF1 protein interacts with and regulates several members of the translesion synthesis pathway (TLS), a DNA damage tolerance pathway, and that these cellular factors enhance viral infectivity. BPLF1 is a late lytic cycle gene, but the protein is also packaged in the viral tegument indicating that BPLF1 may function both early and late during infection. BPLF1 expresses deubiquitinating activity that is strictly conserved across the Herpesviridae; mutation of the active-site cysteine results in loss of enzymatic activity...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28722015/trpv1-regulates-excitatory-innervation-of-olm-neurons-in-the-hippocampus
#2
Joaquin I Hurtado-Zavala, Binu Ramachandran, Saheeb Ahmed, Rashi Halder, Christiane Bolleyer, Ankit Awasthi, Markus A Stahlberg, Robin J Wagener, Kristin Anderson, Ryan M Drenan, Henry A Lester, Julie M Miwa, Jochen F Staiger, Andre Fischer, Camin Dean
TRPV1 is an ion channel activated by heat and pungent agents including capsaicin, and has been extensively studied in nociception of sensory neurons. However, the location and function of TRPV1 in the hippocampus is debated. We found that TRPV1 is expressed in oriens-lacunosum-moleculare (OLM) interneurons in the hippocampus, and promotes excitatory innervation. TRPV1 knockout mice have reduced glutamatergic innervation of OLM neurons. When activated by capsaicin, TRPV1 recruits more glutamatergic, but not GABAergic, terminals to OLM neurons in vitro...
July 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28717881/a-retrospective-comparison-of-inhaled-milrinone-and-iloprost-in-post-bypass-pulmonary-hypertension
#3
Kassiani Theodoraki, Apostolos Thanopoulos, Panagiota Rellia, Evangelos Leontiadis, Dimitrios Zarkalis, Konstantinos Perreas, Theophani Antoniou
During cardiac operations, weaning from cardiopulmonary bypass (CPB) may prove challenging as a result of superimposed acute right ventricular dysfunction in the setting of elevated pulmonary vascular resistance (PVR). The aim of this study was to retrospectively evaluate the effect of inhaled milrinone versus inhaled iloprost in patients with persistent pulmonary hypertension following discontinuation of CPB. Eighteen patients with elevated PVR post-bypass were administered inhaled milrinone at a cumulative dose of 50 μg kg(-1)...
July 17, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28705403/symptomatic-lower-limb-giant-cell-arteritis-characteristics-management-and-long-term-outcome
#4
C Le Hello, L Auboire, L Berger, D Gouicem, M T Barrellier, S Duthois
OBJECTIVE: To describe characteristics and long-term outcomes of the rare symptomatic lower-limb giant-cell arteritis (LL-GCA). METHODS: Retrospective analysis of 8 patients (6 women; mean±SD age, 63.6±10.9 years; follow-up, 137.3±57.3 months). RESULTS: Four patients satisfied≥3 American College of Rheumatology (ACR) GCA-classification criteria; 4 had<3 criteria and histological LL-GCA proof or associated typical upper-limb involvement...
May 2017: J Med Vasc
https://www.readbyqxmd.com/read/28704111/incomplete-dabigatran-reversal-with-idarucizumab
#5
Aaron P Steele, Jin A Lee, William E Dager
CONTEXT: With increasing use of direct oral anticoagulants (DOACs), urgent reversal of these agents becomes a growing concern. Idarucizumab is a humanized monoclonal antibody fragment that specifically binds to dabigatran with higher affinity than thrombin, rapidly neutralizing its anticoagulant effect without increased risk of thrombosis. CASE DETAILS: We describe two cases in which the recommended dose of idarucizumab was unsuccessful in completely reversing the anticoagulant effects of dabigatran...
July 13, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28691557/emicizumab-prophylaxis-in-hemophilia-a-with-inhibitors
#6
Johannes Oldenburg, Johnny N Mahlangu, Benjamin Kim, Christophe Schmitt, Michael U Callaghan, Guy Young, Elena Santagostino, Rebecca Kruse-Jarres, Claude Negrier, Craig Kessler, Nancy Valente, Elina Asikanius, Gallia G Levy, Jerzy Windyga, Midori Shima
Background Emicizumab (ACE910) bridges activated factor IX and factor X to restore the function of activated factor VIII, which is deficient in persons with hemophilia A. This phase 3, multicenter trial assessed once-weekly subcutaneous emicizumab prophylaxis in persons with hemophilia A with factor VIII inhibitors. Methods We enrolled participants who were 12 years of age or older. Those who had previously received episodic treatment with bypassing agents were randomly assigned in a 2:1 ratio to emicizumab prophylaxis (group A) or no prophylaxis (group B)...
July 10, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28691229/desmopressin-use-for-minimising-perioperative-blood-transfusion
#7
REVIEW
Michael J Desborough, Kathryn Oakland, Charlotte Brierley, Sean Bennett, Carolyn Doree, Marialena Trivella, Sally Hopewell, Simon J Stanworth, Lise J Estcourt
BACKGROUND: Blood transfusion is administered during many types of surgery, but its efficacy and safety are increasingly questioned. Evaluation of the efficacy of agents, such as desmopressin (DDAVP; 1-deamino-8-D-arginine-vasopressin), that may reduce perioperative blood loss is needed. OBJECTIVES: To examine the evidence for the efficacy of DDAVP in reducing perioperative blood loss and the need for red cell transfusion in people who do not have inherited bleeding disorders...
July 10, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28689155/combination-of-hemostatic-therapies-for-treatment-of-patients-with-hemophilia-a-and-inhibitors
#8
Tami Livnat, Ivan Budnik, Sarina Levy-Mendelovich, Einat Avishai, Mudi Misgav, Assaf Arie Barg, Aharon Lubetsky, Tami Brutman-Barazani, Gili Kenet
BACKGROUND: Therapy application and monitoring of patients with hemophilia A (HA) and inhibitors are challenging. In the current study, combined FVIII - bypass therapy was implemented for a cohort of severe HA patients with inhibitors. METHODS: Plasma of 15 HA patients with inhibitors was spiked ex vivo with FVIII, rFVIIa, FEIBA and their combinations and thrombin generation (TG) was studied. Some patients who experienced hemarthroses or required minor surgeries were treated by a combined concomitant administration of FVIII+FEIBA as IV bolus doses...
June 27, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28686157/the-role-of-recombinant-activated-factor-vii-in-the-haematological-management-of-elective-orthopaedic-surgery-in-haemophilia-a-patients-with-inhibitors
#9
REVIEW
Giancarlo Castaman
The clinical profile and expectations of haemophilic patients with inhibitors have changed over the last three decades, mainly because of the prolongation of life-expectancy, often resulting in an increase of the orthopaedic burden. Recombinant activated factor VII (rFVIIa) is the most frequently used bypassing agent in haemophilia patients with inhibitors during elective orthopaedic surgery. For nearly 30 years, rFVIIa has been successfully used to control haemostasis in several major and minor surgical procedures...
May 16, 2017: Blood Transfusion, Trasfusione del Sangue
https://www.readbyqxmd.com/read/28681633/major-and-minor-classifications-for-surgery-in-people-with-hemophilia-a-literature-review
#10
Luigi Piero Solimeno, Miguel A Escobar, Snejana Krassova, Stephanie Seremetis
Agents that control bleeding and the usage of bypassing agents have made surgery an option to consider in people with hemophilia. However, the lack of consistent definitions for major or minor surgery may lead to inconsistencies in patient management. This literature review has evaluated how surgical procedures in people with hemophilia were categorized as major or minor surgery and assessed the consistency across publications. After screening 926 potentially relevant articles, 547 were excluded and 379 full-text articles were reviewed...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28679305/iatrogenic-aortic-dissection-during-percutaneous-coronary-intervention-a-case-report-and-review-of-the-literature
#11
Jia-Chen Li, Xin-Liang Guan, Ming Gong, Hong-Jia Zhang
A 64-year-old female complaining of unrelieved chest pain for 2 days was admitted to the Emergency Room of the Beijing Anzhen Hospital, Beijing, China. After definitive diagnosis, a percutaneous coronary intervention was implemented, but immediately after embedding the stent in the distal area of the right coronary artery, an acute coronary and aortic dissection was found. Cardiologists immediately gave the patient conservative management. At the same time, another smaller stent was immediately embedded in the proximal area of the right coronary artery and plunged into the ascending aorta by 2 mm, with the intention of covering the tear of the dissection...
January 1, 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28651167/error-prone-bypass-of-o-6-methylguanine-by-dna-polymerase-of-pseudomonas-aeruginosa-phage-pap1
#12
Shiling Gu, Jingyuan Xiong, Ying Shi, Jia You, Zhenyu Zou, Xiaoying Liu, Huidong Zhang
O(6)-Methylguanine (O(6)-MeG) is highly mutagenic and is commonly found in DNA exposed to methylating agents, generally leads to G:C to A:T mutagenesis. To study DNA replication encountering O(6)-MeG by the DNA polymerase (gp90) of P. aeruginosa phage PaP1, we analyzed steady-state and pre-steady-state kinetics of nucleotide incorporation opposite O(6)-MeG by gp90 exo(-). O(6)-MeG partially inhibited full-length extension by gp90 exo(-). O(6)-MeG greatly reduces dNTP incorporation efficiency, resulting in 67-fold preferential error-prone incorporation of dTTP than dCTP...
June 10, 2017: DNA Repair
https://www.readbyqxmd.com/read/28648139/mutagenic-analysis-of-an-adeno-associated-virus-variant-capable-of-simultaneously-promoting-immune-resistance-and-robust-gene-delivery
#13
Yoojin Kim, Eunmi Kim, Seokmin Oh, Ye-Eun Yoon, Jae-Hyung Jang
In addition to the ability to boost gene delivery efficiency in many therapeutically relevant cells, the capability of circumventing neutralizing antibody (NAb) inactivation is a key prerequisite that gene carriers must fulfill for their extensive applications as therapeutic agents in many gene therapy trials, especially for cancer treatments. This study revealed that a genetically engineered adeno-associated viral (AAV) variant, AAVr3.45, inherently possesses dual beneficial properties as a gene carrier: i) efficiently delivering therapeutic genes to many clinically valuable cells (e...
June 24, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28645858/vascular-adaptation-pattern-formation-and-cross-validation-between-an-agent-based-model-and-a-dynamical-system
#14
Marc Garbey, Stefano Casarin, Scott A Berceli
Myocardial infarction is the global leading cause of mortality (Go et al., 2014). Coronary artery occlusion is its main etiology and it is commonly treated by Coronary Artery Bypass Graft (CABG) surgery (Wilson et al, 2007). The long-term outcome remains unsatisfactory (Benedetto, 2016) as the graft faces the phenomenon of restenosis during the post-surgery, which consists of re-occlusion of the lumen and usually requires secondary intervention even within one year after the initial surgery (Harskamp, 2013)...
June 21, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28641362/estimating-the-potential-cost-of-a-high-dose-immune-tolerance-induction-iti-therapy-relative-to-the-cost-of-a-combined-therapy-of-a-low-dose-iti-therapy-with-bypassing-agent-prophylaxis
#15
G Kenet, A Oladapo, J D Epstein, C Thompson, A Novack, D J Nugent
INTRODUCTION: The International Immune Tolerance Study (I-ITI) demonstrated comparable success rates between low (FVIII 50 IU/kg/TIW) and high dose (FVIII 200 IU/kg/day) regimens. While costlier, the high dose ITI regimen achieved shorter time-to-treatment success with fewer bleeding episodes compared to the low dose ITI regimen. Adding bypassing agent prophylaxis (BAP) to a low dose ITI regimen may reduce bleeding while still being less costly than high dose ITI. AIM AND METHODS: An economic model was developed to compare high dose ITI to low dose ITI with BAP...
June 22, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28636992/acetylsalicylic-acid-inhibits-the-growth-of-melanoma-tumors-via-sox2-dependent-paf-r-independent-signaling-pathway
#16
Anita Thyagarajan, Jeremiah Saylae, Ravi P Sahu
Acquired resistance to standard therapies remains a serious challenge, requiring novel therapeutic approaches that incorporate potential factors involved in tumor resistance. As cancers including melanoma express inflammatory cyclooxygenases generating prostaglandins implicated in tumor growth, we investigated mechanism of anti-inflammatory drug, acetylsalicylic acid (ASA) which has been shown to inhibit various tumor types, however, its effects against highly aggressive melanoma model are unclear. Given our reports that an activation of platelet-activating factor-receptor (PAF-R) augments the growth and impede efficacies of therapeutic agents in experimental melanoma, we also sought to determine if PAF-R mediates anti-melanoma activity of ASA...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28625750/postoperative-delirium-in-patients-undergoing-off-pump-coronary-artery-bypass-grafting-according-to-the-anesthetic-agent-a-retrospective-study
#17
Chung-Sik Oh, Sewon Park, Seung Wan Hong, Woon-Seok Kang, Tae-Gyoon Yoon, Seong-Hyop Kim
OBJECTIVE: To evaluate the effect of two anesthetic agents (sevoflurane or propofol) on postoperative delirium (POD) in patients undergoing off-pump coronary artery bypass grafting (CABG). DESIGN: Retrospective observational design. SETTING: University hospital. PARTICIPANTS: Two hundred ninety-two patients undergoing off-pump CABG who were anesthetized with sevoflurane or propofol. METHODS: Incidence of POD, laboratory data, and pre-, intra-, and 24-hour postoperative clinical variables were reviewed retrospectively...
February 12, 2017: Journal of Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/28602895/risk-factors-for-sub-optimal-utilization-of-statins-and-antiplatelet-therapy-in-patients-undergoing-revascularization-for-symptomatic-peripheral-arterial-disease
#18
Andrew J Meltzer, Art Sedrakyan, Peter H Connolly, Sharif Ellozy, Darren B Schneider
OBJECTIVE: The objective of this study is to identify risk factors for sub-optimal medical therapy (defined as reported antiplatelet and statin use) among patients undergoing lower extremity bypass (LEB) and percutaneous interventions (PVI) for symptomatic peripheral arterial disease (PAD). METHODS: The Vascular Study Group of Greater New York (VSGGNY) database was used to identify all patients undergoing PVI or LEB for PAD (2011-2013). Bivariate analyses were performed to identifycharacteristics of patients who were not prescribed statins and/or antiplatelet agents prior to revascularization...
June 7, 2017: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/28601937/nerve-perivascular-fat-communication-as-a-potential-influence-on-the-performance-of-blood-vessels-used-as-coronary-artery-bypass-grafts
#19
Andrzej Loesch, Michael R Dashwood
Perivascular fat, the cushion of adipose tissue surrounding blood vessels, possesses dilator, anti-contractile and constrictor actions. The majority of these effects have been demonstrated in vitro and may depend on the vessel and/or the experimental method or species used. In general, the relaxant effect of perivascular adipose tissue is local and may be either endothelium-dependent or endothelium-independent. However, nerve stimulation studies show that, in general, perivascular adipose tissue (PVAT) has an anti-contractile vascular effect likely to involve an action of the autonomic vascular nerves...
June 10, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28600023/contrast-enhanced-ultrasound-in-vascular-surgery-review-and-update
#20
REVIEW
K Bredahl, X M Mestre, R V Coll, Q M Ghulam, H Sillesen, J Eiberg
Accurate imaging methods associated with minimum patient risk are important tools for clinical decision-making in vascular surgery. Today, traditional imaging methods, such as computed tomography angiography, magnetic resonance angiography and digital subtraction angiography are the preferred modalities. Ultrasound has only challenged these methods in assessment of carotid disease, aortic aneurysms, venous insufficiency and thromboembolism and in surveillance of in-situ bypasses. These practice patterns may change with the introduction of second generation ultrasound contrast agents which are easy to use, manageable and safe...
June 6, 2017: Annals of Vascular Surgery
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