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https://www.readbyqxmd.com/read/29778846/efficacy-and-tolerability-of-treatment-with-lacosamide-postmarketing-experience-from-the-middle-east-region
#1
Maher Arabi, Taoufik Alsaadi, Wassim Nasreddine, Jasem Al-Hashel, Maya Dirani, Ahmad Beydoun
PURPOSE: Lacosamide (LCM) was recently introduced in the Middle East. The aim of this study was to evaluate the safety, tolerability, and efficacy of LCM in patients with focal onset seizures and determine if our results are comparable with those derived from Western countries. METHODS: This is a retrospective analysis from two medical centers on consecutive patients diagnosed as having focal onset seizures and treated with add-on LCM. The primary efficacy variables were the 50% responder and seizure-free rates, and the secondary outcome variables included the percentages of patients who achieved seizure remission during the last 6-month follow-up period and the percentages of discontinuation due to lack of efficacy or tolerability...
May 17, 2018: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29777029/cd4-t-cell-affinity-diversity-is-equally-maintained-during-acute-and-chronic-infection
#2
Rakieb Andargachew, Ryan J Martinez, Elizabeth M Kolawole, Brian D Evavold
TCR affinity for peptide MHC dictates the functional efficiency of T cells and their propensity to differentiate into effectors and form memory. However, in the context of chronic infections, it is unclear what the overall profile of TCR affinity for Ag is and if it differs from acute infections. Using the comprehensive affinity analysis provided by the two-dimensional micropipette adhesion frequency assay and the common indirect affinity evaluation methods of MHC class II tetramer and functional avidity, we tracked IAb GP61-80 -specific cells in the mouse model of acute (Armstrong) and chronic (clone 13) lymphocytic choriomeningitis virus infection...
May 18, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29772090/lcm-seq-reveals-the-crucial-role-of-lssoc1-in-heat-promoted-bolting-of-lettuce-lactuca-sativa-l
#3
Zijing Chen, Wensheng Zhao, Danfeng Ge, Yingyan Han, Kang Ning, Chen Luo, Shenglin Wang, Renyi Liu, Xiaolan Zhang, Qian Wang
Lettuce (Lactuca sativa L.) is one of the most economically important vegetables. The floral transition in lettuce is accelerated under high temperatures, which can significantly decrease yields. However, the molecular mechanism underlying the floral tranition in lettuce is poorly known. Using laser capture microdissection coupled with RNA sequencing, we isolated shoot apical meristem cells from the bolting-sensitive lettuce line S39 at four critical stages of development. Subsequently, we screened specifically for the flowering-related gene LsSOC1 during the floral transition through comparative transcriptomic analysis...
May 17, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29768211/long-term-persistence-of-exhausted-cd8-t-cells-in-chronic-infection-is-regulated-by-microrna-155
#4
Erietta Stelekati, Zeyu Chen, Sasikanth Manne, Makoto Kurachi, Mohammed-Alkhatim Ali, Keith Lewy, Zhangying Cai, Kito Nzingha, Laura M McLane, Jennifer L Hope, Adam J Fike, Peter D Katsikis, E John Wherry
Persistent viral infections and tumors drive development of exhausted T (TEX ) cells. In these settings, TEX cells establish an important host-pathogen or host-tumor stalemate. However, TEX cells erode over time, leading to loss of pathogen or cancer containment. We identified microRNA (miR)-155 as a key regulator of sustained TEX cell responses during chronic lymphocytic choriomeningitis virus (LCMV) infection. Genetic deficiency of miR-155 ablated CD8 T cell responses during chronic infection. Conversely, enhanced miR-155 expression promoted expansion and long-term persistence of TEX cells...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29768177/expression-of-the-dna-binding-factor-tox-promotes-the-encephalitogenic-potential-of-microbe-induced-autoreactive-cd8-t-cells
#5
Nicolas Page, Bogna Klimek, Mathias De Roo, Karin Steinbach, Hadrien Soldati, Sylvain Lemeille, Ingrid Wagner, Mario Kreutzfeldt, Giovanni Di Liberto, Ilena Vincenti, Thomas Lingner, Gabriela Salinas, Wolfgang Brück, Mikael Simons, Rabih Murr, Jonathan Kaye, Dietmar Zehn, Daniel D Pinschewer, Doron Merkler
Infections are thought to trigger CD8+ cytotoxic T lymphocyte (CTL) responses during autoimmunity. However, the transcriptional programs governing the tissue-destructive potential of CTLs remain poorly defined. In a model of central nervous system (CNS) inflammation, we found that infection with lymphocytic choriomeningitis virus (LCMV), but not Listeria monocytogenes (Lm), drove autoimmunity. The DNA-binding factor TOX was induced in CTLs during LCMV infection and was essential for their encephalitogenic properties, and its expression was inhibited by interleukin-12 during Lm infection...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29765612/crystal-structures-of-lymphocytic-choriomeningitis-virus-endonuclease-domain-complexed-with-diketo-acid-ligands
#6
Magali Saez-Ayala, Elsie Laban Yekwa, Mauro Carcelli, Bruno Canard, Karine Alvarez, François Ferron
The Arenaviridae family, together with the Bunyaviridae and Orthomyxoviridae families, is one of the three negative-stranded RNA viral families that encode an endonuclease in their genome. The endonuclease domain is at the N-terminus of the L protein, a multifunctional protein that includes the RNA-dependent RNA polymerase. The synthesis of mRNA in arenaviruses is a process that is primed by capped nucleotides that are 'stolen' from the cellular mRNA by the endonuclease domain in cooperation with other domains of the L protein...
March 1, 2018: IUCrJ
https://www.readbyqxmd.com/read/29765295/incentives-for-blood-donation-a-discrete-choice-experiment-to-analyze-extrinsic-motivation
#7
Andrew Sadler, Ling Shi, Susanne Bethge, Axel Mühlbacher
Background: Demographic trends affect size and age structure of populations. One of the consequences will be an increasing need for blood products to treat age-related diseases. Donation services rely on voluntariness and charitable motivation. It might be questioned whether there will be sufficient blood supply with voluntary donation. The present study focused on elicitation of preferences for incentives and aimed to contribute to the discussion on how to increase donation rates. Methods: A self-administered discrete choice experiment (DCE) was applied...
April 2018: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/29762684/effective-treatment-of-experimental-lymphocytic-choriomeningitis-virus-infection-consideration-of-favipiravir-for-use-with-infected-organ-transplant-recipients
#8
Brady T Hickerson, Jonna B Westover, Kie-Hoon Jung, Takashi Komeno, Yousuke Furuta, Brian B Gowen
Lymphocytic choriomeningitis virus (LCMV) poses a substantial risk to immunocompromised individuals. The case fatality rate in recent clusters of LCMV infection in immunosuppressed organ transplantation recipients has exceeded 70%. In the present study, we demonstrate potent antiviral activity of favipiravir against acute, disseminated LCMV infection in NZB mice. Treatment resulted in complete protection against mortality and dramatic reductions in viral loads. In contrast, ribavirin, the current antiviral of choice, was mostly ineffective...
May 14, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29762619/isolation-and-genome-sequencing-of-individual-circulating-tumor-cells-using-hydrogel-encapsulation-and-laser-capture-microdissection
#9
Emily S Park, Justin P Yan, Richard A Ang, Jeong Hyun Lee, Xiaoyan Deng, Simon P Duffy, Kevin Beja, Matti Annala, Peter C Black, Kim N Chi, Alexander W Wyatt, Hongshen Ma
Circulating tumor cells (CTCs) are malignant cells released into the bloodstream with the potential to form metastases in secondary sites. These cells, acquired non-invasively, represent a sample of highly relevant tumor tissue that is an alternative to difficult and low-yield tumor biopsies. In recent years, there has been growing interest in genomic profiling of CTCs to enable longitudinal monitoring of the tumor's adaptive response to therapy. However, due to their extreme rarity, genotyping CTCs has proved challenging...
May 15, 2018: Lab on a Chip
https://www.readbyqxmd.com/read/29758584/inhibition-of-sympathetic-sprouting-in-ccd-rats-by-lacosamide
#10
Yuying Wang, Fuquan Huo
BACKGROUND: Early hyperexcitability activity of injured nerve/neuron is critical for developing sympathetic nerve sprouting within dorsal root ganglia (DRG). Since lacosamide (LCM), an anticonvulsant, inhibits Na+ channel. The present study tried to test the potential effect of LCM on inhibiting sympathetic sprouting in vivo. METHODS: LCM (50 mg/kg) was daily injected intraperitoneally into rats subjected to chronic compression DRG (CCD), an animal model of neuropathic pain that exhibits sympathetic nerve sprouting, for the 1st 7 days after injury...
May 14, 2018: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/29758445/intravenous-lacosamide-lcm-in-status-epilepticus-se-weight-adjusted-dose-and-efficacy
#11
Estevo Santamarina, Montserrat González-Cuevas, Manuel Toledo, Marta Jiménez, Juan Luis Becerra, Alex Quílez, Ana Suller, J A Mauri, Ángel Fernández, Ainhoa Marinas, Manuel Quintana, Xavier Salas Puig
BACKGROUND: Some studies suggest higher efficacy of lacosamide (LCM) in status epilepticus (SE) with higher loading doses; however, this weight-adjusted dose has not been evaluated. OBJECTIVE: The objective was to evaluate the relationship between loading weight-adjusted dose and efficacy of LCM in SE. METHODS: A group of patients with SE treated with LCM from Spanish hospitals was examined retrospectively. Demographic data, type of SE, etiology, response rate, last antiepileptic drug (AED) used, treatment line in which LCM was used, total loading dose, and weight-adjusted dose were collected...
May 11, 2018: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29753575/quantitative-apparent-diffusion-coefficient-mapping-may-predict-seizure-onset-in-children-with-sturge-weber-syndrome
#12
Anna L R Pinto, Yangming Ou, Mustafa Sahin, P Ellen Grant
BACKGROUND: Sturge-Weber syndrome (SWS) is often accompanied by seizures, stroke-like episodes, hemiparesis, and visual field deficits. This study aimed to identify early pathophysiologic changes that exist before the development of clinical symptoms and to evaluate if the apparent diffusion coefficient (ADC) map is a candidate early biomarker of seizure risk in patients with SWS. METHODS: This is a prospective cross-sectional study using quantitative ADC analysis to predict onset of epilepsy...
April 12, 2018: Pediatric Neurology
https://www.readbyqxmd.com/read/29751624/influence-of-aln-0001-surface-reconstructions-on-the-wettability-of-an-al-aln-system-a-first-principle-study
#13
Junhua Cao, Yang Liu, Xiao-Shan Ning
A successful application of a hot dip coating process that coats aluminum (Al) on aluminum nitride (AlN) ceramics, revealed that Al had a perfect wettability to the ceramics under specific circumstances, which was different from previous reports. In order to elucidate the mechanism that controlled the supernormal wetting phenomenon during the dip coating, a first-principle calculation of an Al(111)/AlN(0001) interface, based on the density functional theory (DFT), was employed. The wettability of the Al melt on the AlN(0001) surface, as well as the effect that the surface reconstruction of AlN and the oxygen adsorption had on Al for the adhesion and the wettability of the Al/AlN system, were studied...
May 11, 2018: Materials
https://www.readbyqxmd.com/read/29739688/resources-to-handle-childhood-asthma-in-spain-the-role-of-plans-and-guides-and-the-participation-of-nurses
#14
M I Úbeda-Sansano, A Cano-Garcinuño, S Rueda-Esteban, M Praena-Crespo
BACKGROUND: Describe the assistance provided to asthmatic patients by Primary Care Paediatricians (PCP) in Spain and the material and human resources available for diagnosis and follow-up. METHODS: A cross-sectional descriptive study using an on-line survey, sent to PCP regarding the availability of diagnostic resources, carrying out programmed and educational activities, collaboration of nursing staff and their relationship with existing institutional plans to care for children with asthma...
May 5, 2018: Allergologia et Immunopathologia
https://www.readbyqxmd.com/read/29734372/the-adaptor-molecule-cd2ap-in-cd4-t-cells-modulates-differentiation-of-follicular-helper-t-cells-during-chronic-lcmv-infection
#15
Saravanan Raju, Kohei Kometani, Tomohiro Kurosaki, Andrey S Shaw, Takeshi Egawa
CD4 T cell-mediated help to CD8 T cells and B cells is a critical arm of the adaptive immune system required for control of pathogen infection. CD4 T cells express cytokines and co-stimulatory molecules that support a sustained CD8 T cell response and also enhance generation of protective antibody by germinal center B cells. However, the molecular components that modulate CD4 T cell functions in response to viral infection or vaccine is incompletely understood. Here we demonstrate that inactivation of the signaling adaptor CD2-associated protein (CD2AP) promotes CD4 T cell differentiation towards the follicular helper lineage, leading to enhanced control of viral infection by augmented germinal center response in chronic lymphocytic choriomeningitis virus (LCMV) infection...
May 7, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29733984/long-chain-metabolites-of-vitamin-e-interference-with-lipotoxicity-via-lipid-droplet-associated-protein-plin2
#16
Lisa Schmölz, Martin Schubert, Jasmin Kirschner, Stefan Kluge, Francesco Galli, Marc Birringer, Maria Wallert, Stefan Lorkowski
The long-chain metabolites of vitamin E (LCM) emerge as a new class of regulatory metabolites and have been considered as the active compounds formed during vitamin E metabolism. The bioactivity of the LCM is comparable to the already established role of other fat-soluble vitamins. The biological modes of action of the LCM are far from being unraveled, but first insights pointed to distinct effects and suggested a specific receptor, which in turn lead to the aforementioned hypothesis. Here, a new facet on the interaction of LCM with foam cell formation of THP-1 macrophages is presented...
May 4, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29733464/randomized-trial-of-lacosamide-vs-fosphenytoin-for-nonconvulsive-seizures
#17
Aatif M Husain, Jong W Lee, Bradley J Kolls, Lawrence J Hirsch, Jonathan J Halford, Puneet K Gupta, Yafa Minazad, Jennifer M Jones, Suzette M LaRoche, Susan T Herman, Christa B Swisher, Saurabh R Sinha, Adriana Palade, Keith E Dombrowski, William B Gallentine, Cecil D Hahn, Elizabeth E Gerard, Manjushri Bhapkar, Yuliya Lokhnygina, M Brandon Westover
OBJECTIVE: The optimal treatment of nonconvulsive seizures in critically ill patients is uncertain. We evaluated the comparative effectiveness of antiseizure drugs (ASD) lacosamide (LCM) and fosphenytoin (fPHT) in this population. METHODS: The Treatment of Recurrent Electrographic Nonconvulsive Seizures (TRENdS) study was a non-inferiority, prospective, multicenter, randomized treatment trial of patients diagnosed with NCS by continuous electroencephalography (cEEG)...
May 7, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29733325/spatial-quantification-of-drugs-in-pulmonary-tuberculosis-lesions-by-laser-capture-microdissection-liquid-chromatography-mass-spectrometry-lcm-lc-ms
#18
Matthew Zimmerman, Landry Blanc, Pei-Yu Chen, Véronique Dartois, Brendan Prideaux
Tuberculosis is still a leading cause of morbidity and mortality worldwide. Improvements to existing drug regimens and the development of novel therapeutics are urgently required. The ability of dosed TB drugs to reach and sterilize bacteria within poorly-vascularized necrotic regions (caseum) of pulmonary granulomas is crucial for successful therapeutic intervention. Effective therapeutic regimens must therefore contain drugs with favorable caseum penetration properties. Current LC/MS methods for quantifying drug levels in biological tissues have limited spatial resolution capabilities, making it difficult to accurately determine absolute drug concentrations within small tissue compartments such as those found within necrotic granulomas...
April 18, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29719595/proteomic-alterations-in-early-stage-cervical-cancer
#19
Coşkun Güzel, Natalia I Govorukhina, G Bea A Wisman, Christoph Stingl, Lennard J M Dekker, Harry G Klip, Harry Hollema, Victor Guryev, Peter L Horvatovich, Ate G J van der Zee, Rainer Bischoff, Theo M Luider
Laser capture microdissection (LCM) allows the capture of cell types or well-defined structures in tissue. We compared in a semi-quantitative way the proteomes from an equivalent of 8,000 tumor cells from patients with squamous cell cervical cancer (SCC, n = 22) with healthy epithelial and stromal cells obtained from normal cervical tissue ( n = 13). Proteins were enzymatically digested into peptides which were measured by high-resolution mass spectrometry and analyzed by "all-or-nothing" analysis, Bonferroni, and Benjamini-Hochberg correction for multiple testing...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29715623/weak-vaccinia-virus-induced-nk-cell-regulation-of-cd4-t-cells-is-associated-with-reduced-nk-cell-differentiation-and-cytolytic-activity
#20
Steven D Hatfield, Keith A Daniels, Carey L O'Donnell, Stephen N Waggoner, Raymond M Welsh
Natural killer (NK) cells control antiviral adaptive immune responses in mice during some virus infections, but the universality of this phenomenon remains unknown. Lymphocytic choriomeningitis virus (LCMV) infection of mice triggered potent cytotoxic activity of NK cells (NKLCMV ) against activated CD4 T cells, tumor cells, and allogeneic lymphocytes. In contrast, NK cells activated by vaccinia virus (VACV) infection (NKVACV ) exhibited weaker cytolytic activity against each of these target cells. Relative to NKLCMV cells, NKVACV cells exhibited a more immature (CD11b- CD27+ ) phenotype, and lower expression levels of the activation marker CD69, cytotoxic effector molecules (perforin, granzyme B), and the transcription factor IRF4...
April 28, 2018: Virology
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