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https://www.readbyqxmd.com/read/30093567/unraveling-the-interaction-between-carboxylesterase-1c-and-the-antibody-drug-conjugate-syd985-improved-translational-pkpd-by-using-ces1c-knockout-mice
#1
Ruud Ubink, Eef Hc Dirksen, Myrthe Rouwette, Ebo Sijbren Bos, Ingrid Janssen, David F Egging, Eline M Loosveld, Tanja A van Achterberg, Kim Berentsen, Miranda M C van der Lee, Francis Bichat, Olivier Raguin, Monique A J van der Vleuten, Patrick G Groothuis, Wim H A Dokter
Carboxylesterase 1c (CES1c) is responsible for linker-drug instability and poor pharmacokinetics (PK) of several antibody-drug conjugates (ADCs) in mouse, but not in monkey or human. Preclinical development of these ADCs could be improved if the PK in mice would more closely resemble that of human and is not affected by an enzyme that is irrelevant for humans. SYD985, a HER2-targeting ADC based on trastuzumab and linker-drug vc-seco-DUBA is also sensitive to CES1c. In the present studies, we first focused on the interaction between CES1c and SYD985 by size- exclusion chromatography, Western blotting and LC-MS/MS analysis, using recombinant CES1c and plasma samples...
August 9, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/30074130/ten-pathways-to-elective-egg-freezing-a-binational-analysis
#2
Marcia C Inhorn, Daphna Birenbaum-Carmeli, Lynn M Westphal, Joseph Doyle, Norbert Gleicher, Dror Meirow, Martha Dirnfeld, Daniel Seidman, Arik Kahane, Pasquale Patrizio
PURPOSE: What are the specific pathways that lead women to freeze their eggs? In this binational study, women were asked directly about the life circumstances that led them on the path to elective egg freezing (EEF). METHODS: From June 2014 to August 2016, 150 women (114 in the USA, 36 in Israel) who had completed at least 1 cycle of EEF were interviewed by two medical anthropologists. Study participants were recruited through four American IVF clinics (two academic, two private) and three in Israel (one academic, two private)...
August 3, 2018: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/30055934/relationship-of-placido-corneal-topography-data-with-scleral-lens-fitting-parameters
#3
Rute J Macedo-de-Araújo, Ana Amorim-de-Sousa, António Queirós, Eef van der Worp, José M González-Méijome
PURPOSE: To analyze the relationship between corneal sagittal height and asymmetry parameters derived from Placido-videokeratoscopy with the parameters of fitted scleral lenses (ScCLs). METHODS: Corneal topographies were measured with MedmontE300 in a total of 126 eyes with irregular and regular corneas before ScCL fitting were analyzed. Measurements of sagittal height (OC-SAG) at steep and flat corneal meridians were obtained for 10 mm and 12 mm chords. Estimated Height (EHChord) parameters were taken for a chord equal to the diameter of the lens that each subject was wearing at different semi-meridians...
July 25, 2018: Contact Lens & Anterior Eye: the Journal of the British Contact Lens Association
https://www.readbyqxmd.com/read/30050434/safety-profile-and-neurocognitive-function-following-acute-4-fluoroamphetamine-4-fa-administration-in-humans
#4
Elizabeth B de Sousa Fernandes Perna, Eef L Theunissen, Patrick C Dolder, Natasha L Mason, Nadia R P W Hutten, Stefan W Toennes, Kim P C Kuypers, Johannes G Ramaekers
Availability of novel psychoactive substances (NPS) exponentially increased over the last years. Risk evaluations of NPS are hampered by the lack of pharmacological studies in humans on health parameters. The aim of the present study was to evaluate safety and neurocognitive function of healthy volunteers ( N = 12) who received single doses of 100 and 150 mg 4-fluoroamphetamine (4-FA), a phenethylamine that has been associated with severe cardiovascular and cerebrovascular complications. The study was set-up as a placebo controlled, within subject, phase 1 trial as it was the first to administer 4-FA to humans under controlled conditions...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/30037349/elective-egg-freezing-and-its-underlying-socio-demography-a-binational-analysis-with-global-implications
#5
M C Inhorn, D Birenbaum-Carmeli, J Birger, L M Westphal, J Doyle, N Gleicher, D Meirow, M Dirnfeld, D Seidman, A Kahane, P Patrizio
BACKGROUND: What are the underlying socio-demographic factors that lead healthy women to preserve their fertility through elective egg freezing (EEF)? Many recent reviews suggest that women are intentionally postponing fertility through EEF to pursue careers and achieve reproductive autonomy. However, emerging empirical evidence suggests that women may be resorting to EEF for other reasons, primarily the lack of a partner with whom to pursue childbearing. The aim of this study is thus to understand what socio-demographic factors may underlie women's use of EEF...
July 23, 2018: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/30029093/physical-frailty-and-cognitive-status-over-60-age-populations-a-systematic-review-with-meta-analysis
#6
REVIEW
Guilherme Eustáquio Furtado, Adriana Caldo, Taís Rieping, Edith Filaire, Eef Hogervorst, Ana Maria Botelho Teixeira, José Pedro Ferreira
The aim of this meta-analysis was to analyse the magnitude of the effect-size of the cognitive status of populations over 60 years of age, when comparing nonfrail versus pre-frail and nonfrail versus frail subgroups. A systematic review of prospective studies published from 2000 to 2017 was completed in Medline, B-on, Ebsco, Ebsco Health, Scielo, ERIC, LILACS and Sport discus databases and observational, cohort and cross-sectional studies were selected. The Mini-Mental State Examination to screening cognitive status and the Fried phenotype for assess physical frailty state was used as clinical outcomes...
September 2018: Archives of Gerontology and Geriatrics
https://www.readbyqxmd.com/read/29990883/a-high-crosslinking-grade-of-hyaluronic-acid-found-in-a-dermal-filler-causing-adverse-effects
#7
Peter H J Keizers, Celine Vanhee, Eef M W van den Elzen, Wim H de Jong, Bastiaan J Venhuis, Hennie M Hodemaekers, Paul Schwillens, Daan G W Lensen
Facial treatments with dermal fillers for medical or esthetic purposes occasionally give rise to adverse effects, ranging from temporary effects such as reddening of the skin, to long term effects such as hardening of tissue. There appears to be a relationship between the lifetime of the filler product and the risk for adverse effects. The lifetime of hyaluronic acid-based fillers is dependent on the presence and amount of crosslinking agents such as 1,4-butanediol diglycidyl ether (BDDE). It would therefore make sense to establish methodology to analyze the crosslinking grade of HA-based filler products on a routine basis...
July 2, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29979456/structure-and-reactivity-selectivity-control-by-oriented-external-electric-fields
#8
Sason Shaik, Rajeev Ramanan, David Danovich, Debasish Mandal
This is a tutorial on use of external-electric-fields (EEFs) as effectors of chemical change. The tutorial instructs readers how to conceptualize and design electric-field effects on bonds, structures, and reactions. Most effects can be comprehended as the field-induced stabilization of ionic structures. Thus, orienting the field along the "bond axis" will facilitate bond breaking. Similarly, orienting the field along the "reaction axis", the direction in which "electron pairs transform" from reactants- to products-like, will catalyse the reaction...
July 17, 2018: Chemical Society Reviews
https://www.readbyqxmd.com/read/29973686/correction-eef-2-kinase-is-a-critical-regulator-of-warbrug-effect-through-controlling-pp2a-a-synthesis
#9
Y Cheng, X Ren, Y Yuan, Y Shan, L Li, X Chen, L Zhang, Y Takahashi, J W Yang, B Han, J Liao, Y Li, H Harvey, A Ryazanov, G P Robertson, G Wan, D Liu, A F Chen, Y Tao, J-M Yang
In this article, the authors recently noticed that the tubulin blots in Figs. 2a and 6a were inadvertently misplaced during the preparation of these figures due to their similarity. The amended versions of the figures are now shown below. The conclusions of this paper are not affected. The authors sincerely apologize for these errors.
July 4, 2018: Oncogene
https://www.readbyqxmd.com/read/29971628/thymoquinone-inhibits-cell-proliferation-migration-and-invasion-by-regulating-the-elongation-factor-2-kinase-eef-2k-signaling-axis-in-triple-negative-breast-cancer
#10
Nashwa Kabil, Recep Bayraktar, Nermin Kahraman, Hamada A Mokhlis, George A Calin, Gabriel Lopez-Berestein, Bulent Ozpolat
BACKGROUND/PURPOSE: Triple-negative breast cancer (TNBC) is the most aggressive and chemoresistant subtype of breast cancer. Therefore, new molecular targets and treatments need to be developed to improve poor patient prognosis and survival. We have previously shown that eukaryotic elongation factor 2 kinase (eEF-2K) is highly expressed in TNBC cells, is associated with poor patient survival and prognosis, and promotes cell proliferation, migration, and invasion. In vivo targeting of eEF-2K significantly reduces the tumor growth of orthotopic TNBC xenograft mouse models, suggesting that eEF-2K may serve as a potential novel therapeutic target...
July 3, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29962878/efficacy-efficiency-and-safety-of-magnetic-resonance-guided-high-intensity-focused-ultrasound-for-ablation-of-uterine-fibroids-comparison-with-ultrasound-guided-method
#11
Yi Wang, Zhi-Biao Wang, Yong-Hua Xu
Objective: The purpose of this study was to compare efficacy, sonication energy efficiency, treatment time and safety of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) and those of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for ablation of uterine fibroids. Materials and Methods: This study included 43 patients with 44 symptomatic uterine fibroids treated with MRgHIFU and 51 patients with 68 symptomatic uterine fibroids treated with USgHIFU...
July 2018: Korean Journal of Radiology: Official Journal of the Korean Radiological Society
https://www.readbyqxmd.com/read/29947572/a-single-dose-of-cocaine-enhances-prospective-memory-performance
#12
Nadia Rpw Hutten, Kim Pc Kuypers, Janelle Hp van Wel, Eef L Theunissen, Stefan W Toennes, Robbert-Jan Verkes, Johannes G Ramaekers
BACKGROUND: Prospective memory is the ability to recall intended actions or events at the right time or in the right context. While cannabis is known to impair prospective memory, the acute effect of cocaine is unknown. In addition, it is not clear whether changes in prospective memory represent specific alterations in memory processing or result from more general effects on cognition that spread across multiple domains such as arousal and attention. AIMS: The main objective of the study was, therefore, to determine whether drug-induced changes in prospective memory are memory specific or associated with more general drug-induced changes in attention and arousal...
August 2018: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29800565/structural-dynamics-of-the-activation-of-elongation-factor-2-kinase-by-ca-2-calmodulin
#13
Nathan Will, Kwangwoon Lee, Fatlum Hajredini, David H Giles, Rinat R Abzalimov, Michael Clarkson, Kevin N Dalby, Ranajeet Ghose
Eukaryotic elongation factor 2 kinase (eEF-2K), the only known calmodulin (CaM)-activated α-kinase, phosphorylates eukaryotic elongation factor 2 (eEF-2) on a specific threonine (Thr-56) diminishing its affinity for the ribosome and reducing the rate of nascent chain elongation during translation. Despite its critical cellular role, the precise mechanisms underlying the CaM-mediated activation of eEF-2K remain poorly defined. Here, employing a minimal eEF-2K construct (TR) that exhibits activity comparable to the wild-type enzyme and is fully activated by CaM in vitro and in cells, and using a variety of complimentary biophysical techniques in combination with computational modeling, we provide a structural mechanism by which CaM activates eEF-2K...
August 17, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29766906/n-type-rashba-spin-splitting-in-a-bilayer-inorganic-halide-perovskite-with-external-electric-field
#14
Xuejiao Chen, Lei Liu, Dezhen Shen
Here, we investigated the Rashba effect of the CsPbBr3 bilayers under the external electric field (EEF) with first-principles calculations. For the PbBr2 terminated bilayer, we found that only electrons experience the Rashba splitting under EEF, while holes do not. Such an n-type Rashba effect can be ascribed to the surface relaxation effect that reverses the positions of the top valence bands. The n-type Rashba parameter can be tuned monotonically to the maximum of 0.88 eV Å at EEF of 1.35 V nm-1 at which the sequence of top valence bands recover to the bulk style...
July 4, 2018: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/29761207/omics-based-responses-induced-by-bosentan-in-human-hepatoma-heparg-cell-cultures
#15
Robim M Rodrigues, Laxmikanth Kollipara, Umesh Chaudhari, Agapios Sachinidis, René P Zahedi, Albert Sickmann, Annette Kopp-Schneider, Xiaoqi Jiang, Hector Keun, Jan Hengstler, Marlies Oorts, Pieter Annaert, Eef Hoeben, Eva Gijbels, Joery De Kock, Tamara Vanhaecke, Vera Rogiers, Mathieu Vinken
Bosentan is well known to induce cholestatic liver toxicity in humans. The present study was set up to characterize the hepatotoxic effects of this drug at the transcriptomic, proteomic, and metabolomic levels. For this purpose, human hepatoma-derived HepaRG cells were exposed to a number of concentrations of bosentan during different periods of time. Bosentan was found to functionally and transcriptionally suppress the bile salt export pump as well as to alter bile acid levels. Pathway analysis of both transcriptomics and proteomics data identified cholestasis as a major toxicological event...
May 14, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29752212/scleral-lenses-history-future
#16
EDITORIAL
Eef van der Worp, Melissa Barnett, Lynette Johns
No abstract text is available yet for this article.
June 2018: Contact Lens & Anterior Eye: the Journal of the British Contact Lens Association
https://www.readbyqxmd.com/read/29668881/hyperactive-ryanodine-receptors-in-human-heart-failure-and-ischemic-cardiomyopathy-reside-outside-of-couplons
#17
Eef Dries, Demetrio J Santiago, Guillaume Gilbert, Ilse Lenaerts, Bert Vandenberk, Chandan K Nagaraju, Daniel M Johnson, Patricia Holemans, H Llewelyn Roderick, Niall Macquaide, Piet Claus, Karin R Sipido
Aims: In ventricular myocytes from humans and large mammals, the transverse and axial tubular system (TATS) network is less extensive than in rodents with consequently a greater proportion of ryanodine receptors (RyRs) not coupled to this membrane system. TATS remodeling in heart failure (HF) and after myocardial infarction (MI) increases the fraction of non-coupled RyR. Here we investigate whether this remodeling alters the activity of coupled and non-coupled RyR sub-populations through changes in local signaling...
April 14, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29666477/single-cell-analysis-of-pyroptosis-dynamics-reveals-conserved-gsdmd-mediated-subcellular-events-that-precede-plasma-membrane-rupture
#18
Nathalia M de Vasconcelos, Nina Van Opdenbosch, Hanne Van Gorp, Eef Parthoens, Mohamed Lamkanfi
Pyroptosis is rapidly emerging as a mechanism of anti-microbial host defense, and of extracellular release of the inflammasome-dependent cytokines interleukin (IL)-1β and IL-18, which contributes to autoinflammatory pathology. Caspases 1, 4, 5 and 11 trigger this regulated form of necrosis by cleaving the pyroptosis effector gasdermin D (GSDMD), causing its pore-forming amino-terminal domain to oligomerize and perforate the plasma membrane. However, the subcellular events that precede pyroptotic cell lysis are ill defined...
April 17, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29548814/renin-and-aldosterone-are-not-associated-with-vulnerable-plaque-characteristics-in-patients-with-carotid-artery-disease
#19
MULTICENTER STUDY
Marieke A Hillaert, Hester M den Ruijter, Imo E Hoefer, Eef G Lentjes, Gert J de Borst, Jean-Paul P M de Vries, Pieter A Doevendans, Gerard Pasterkamp, Leo Timmers
BACKGROUND: The renin-angiotensin-aldosterone system is increasingly being recognized to play an important role in the development and clinical course of cardiovascular diseases. Renin-angiotensin-aldosterone system activation is associated with clinical outcome in various populations of cardiovascular patients, such as patients with coronary artery, peripheral artery, and cerebrovascular disease. In this study, we investigated the associations between plasma renin and aldosterone concentrations and atherosclerotic plaque characteristics and secondary vascular events in patients undergoing carotid endarterectomy...
July 2018: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/29542317/developing-plasmodium-vivax-resources-for-liver-stage-study-in-the-peruvian-amazon-region
#20
Pamela Orjuela-Sanchez, Zaira Hellen Villa, Marta Moreno, Carlos Tong-Rios, Stephan Meister, Gregory M LaMonte, Brice Campo, Joseph M Vinetz, Elizabeth A Winzeler
To develop new drugs and vaccines for malaria elimination, it will be necessary to discover biological interventions, including small molecules that act against Plasmodium vivax exoerythrocytic forms. However, a robust in vitro culture system for P. vivax is still lacking. Thus, to study exoerythrocytic forms, researchers must have simultaneous access to fresh, temperature-controlled patient blood samples, as well as an anopheline mosquito colony. In addition, researchers must rely on native mosquito species to avoid introducing a potentially dangerous invasive species into a malaria-endemic region...
April 13, 2018: ACS Infectious Diseases
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