keyword
MENU ▼
Read by QxMD icon Read
search

Unexpected

keyword
https://www.readbyqxmd.com/read/29458062/an-unexpected-degradation-pathway-of-a-1-2-4-triazolo-4-3-a-pyridine-derivative-the-formation-of-two-cationic-pseudodimers-of-an-11%C3%AE-hydroxysteroid-dehydrogenase-type-1-inhibitor-drug-candidate-in-a-stressed-capsule-formulation
#1
Yande Huang, Qinggang Wang, Yongmei Wu
Degradation of an active pharmaceutical ingredient (API), a 2-(3-(1-(4-chlorophenyl)cyclopropyl)-[1,2,4]triazolo[4,3-a]pyridin-8-yl)propan-2-ol hydrochloride salt, was observed in a capsule formulation stressed at 50°C or 40°C/75% relative humidity conditions for one month. Two unknown degradants were identified as cationic pseudodimers of the API via accurate mass liquid chromatography-mass spectrometry and one- and two-dimensional NMR analyses. A plausible degradation pathway of the API was postulated which led to the identification of two key N-oxide degradants in the stressed capsule formulation at trace levels...
February 16, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29457790/cd163-macrophages-promote-angiogenesis-and-vascular-permeability-accompanied-by-inflammation-in-atherosclerosis
#2
Liang Guo, Hirokuni Akahori, Emanuel Harari, Samantha L Smith, Rohini Polavarapu, Vinit Karmali, Fumiyuki Otsuka, Rachel L Gannon, Ryan E Braumann, Megan H Dickinson, Anuj Gupta, Audrey L Jenkins, Michael J Lipinski, Johoon Kim, Peter Chhour, Paul S de Vries, Hiroyuki Jinnouchi, Robert Kutys, Hiroyoshi Mori, Matthew D Kutyna, Sho Torii, Atsushi Sakamoto, Cheol Ung Choi, Qi Cheng, Megan L Grove, Mariem A Sawan, Yin Zhang, Yihai Cao, Frank D Kolodgie, David P Cormode, Dan E Arking, Eric Boerwinkle, Alanna C Morrison, Jeanette Erdmann, Nona Sotoodehnia, Renu Virmani, Aloke V Finn
Intake of hemoglobin by the hemoglobin-haptoglobin receptor CD163 leads to a distinct alternative non-foam cell antiinflammatory macrophage phenotype that was previously considered atheroprotective. Here, we reveal an unexpected but important pathogenic role for these macrophages in atherosclerosis. Using human atherosclerotic samples, cultured cells, and a mouse model of advanced atherosclerosis, we investigated the role of intraplaque hemorrhage on macrophage function with respect to angiogenesis, vascular permeability, inflammation, and plaque progression...
February 19, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29457349/impact-of-glutathione-modulation-on-stability-and-pharmacokinetic-profile-of-redox-sensitive-nanogels
#3
Natascha Drude, Oliver H Winz, Felix M Mottaghy, Marion Roller, Hiltrud Königs, Martin Möller, Smriti Singh, Agnieszka Morgenroth
Nanoparticles degradable upon external stimuli combine pharmacokinetic features of both small molecules as well as large nanoparticles. However, despite promising preclinical results, several redox responsive disulphide-linked nanoparticles failed in clinical translation, mainly due to their unexpected in vivo behavior. Glutathione (GSH) is one of the most evaluated antioxidants responsible for disulfide degradation. Herein, the impact of GSH on the in vivo behavior of redox-sensitive nanogels under physiological and modulated conditions is investigated...
February 19, 2018: Small
https://www.readbyqxmd.com/read/29457136/unexpected-evolutionary-benefit-to-phages-imparted-by-bacterial-crispr-cas9
#4
Pan Tao, Xiaorong Wu, Venigalla Rao
Bacteria and bacteriophages arm themselves with various defensive and counterdefensive mechanisms to protect their own genome and degrade the other's. CRISPR (clustered regularly interspaced short palindromic repeat)-Cas (CRISPR-associated) is an adaptive bacterial defense mechanism that recognizes short stretches of invading phage genome and destroys it by nuclease attack. Unexpectedly, we discovered that the CRISPR-Cas system might also accelerate phage evolution. When Escherichia coli bacteria containing CRISPR-Cas9 were infected with phage T4, its cytosine hydroxymethylated and glucosylated genome was cleaved poorly by Cas9 nuclease, but the continuing CRISPR-Cas9 pressure led to rapid evolution of mutants that accumulated even by the time a single plaque was formed...
February 2018: Science Advances
https://www.readbyqxmd.com/read/29457052/an-unexpected-abdominal-radiographic-finding-chilaiditi-sign
#5
Rui Morais, Pedro Lopes, Guilherme Macedo
No abstract text is available yet for this article.
January 2018: GE Portuguese Journal of Gastroenterology
https://www.readbyqxmd.com/read/29456864/curative-gnrha-treatment-has-an-unexpected-repressive-effect-on-sertoli-cell-specific-genes
#6
Katharina Gegenschatz-Schmid, Gilvydas Verkauskas, Philippe Demougin, Vytautas Bilius, Darius Dasevicius, Michael B Stadler, Faruk Hadziselimovic
Background: Follicle stimulating hormone and testosterone stimulate Sertoli cells to support germ cell function and differentiation. During mini-puberty, when gonadotropin (GnRH) stimulates increases in plasma luteinizing hormone (LH) and testosterone levels, gonocytes are transformed into Ad spermatogonia. In cryptorchidism, impaired gonadotropin secretion during mini-puberty results in insufficient LH and testosterone secretion, impaired gonocyte transition to Ad spermatogonia, and perturbed Sertoli cell proliferation...
2018: Basic and Clinical Andrology
https://www.readbyqxmd.com/read/29456801/identification-of-potent-indoleamine-2-3-dioxygenase-1-ido1-inhibitors-based-on-a-phenylimidazole-scaffold
#7
Michael G Brant, Jake Goodwin-Tindall, Kurt R Stover, Paul M Stafford, Fan Wu, Autumn R Meek, Paolo Schiavini, Stephanie Wohnig, Donald F Weaver
Inhibition of indoleamine 2,3-dioxygenase (IDO1) is an attractive immunotherapeutic approach for the treatment of a variety of cancers. Dysregulation of this enzyme has also been implicated in other disorders including Alzheimer's disease and arthritis. Herein, we report the structure-based design of two related series of molecules: N 1-substituted 5-indoleimidazoles and N 1-substituted 5-phenylimidazoles. The latter (and more potent) series was accessed through an unexpected rearrangement of an imine intermediate during a Van Leusen imidazole synthesis reaction...
February 8, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29456496/how-do-acquired-political-identities-influence-our-neural-processing-toward-others-within-the-context-of-a-trust-game
#8
Chien-Te Wu, Yang-Teng Fan, Ye-Rong Du, Tien-Tun Yang, Ho-Ling Liu, Nai-Shing Yen, Shu-Heng Chen, Ray-May Hsung
Trust is essential for mutually beneficial human interactions in economic exchange and politics and people's social identities notably have dramatic effects on trust behaviors toward others. Previous literature concerning social identities generally suggests that people tend to show in-group favoritism toward members who share the same identity. However, how our brains process signals of identity while facing uncertain situations in interpersonal interactions remains largely unclear. To address this issue, we performed an fMRI experiment with 54 healthy adults who belonged to two identity groups of opposing political orientations...
2018: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/29456414/high-prevalence-of-hepatitis-b-antibody-loss-and-a-case-report-of-de-novo-hepatitis-b-virus-infection-in-a-child-after-living-donor-liver-transplantation
#9
Palittiya Sintusek, Nawarat Posuwan, Piyaporn Wanawongsawad, Suttiruk Jitraruch, Yong Poovorawan, Voranush Chongsrisawat
AIM: To assess the seroprevalence of hepatitis B virus (HBV) immunity among previously vaccinated pediatric liver transplant recipients and present a case report of de novo hepatitis B infection after liver transplantation. METHODS: This study focused on children with chronic liver diseases who received primary hepatitis B immunization and had a complete dataset of anti-HBs before and after liver transplantation between May 2001 and June 2017. Medical records were retrospectively reviewed for potential factors relating to HBV immunity loss...
February 14, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29456166/head-stabilisation-in-fast-running-lizards
#10
Jana Goyens, Peter Aerts
The cyclic patterns of terrestrial animal locomotion are frequently perturbed in natural environments. The terrain can be complex or inclined, the substrate can move unexpectedly and animals can misjudge situations. Loosing stability due to perturbations increases the probability of capture by predators and decreases the chance of successful prey capture and winning intraspecific battles. When controlled corrective actions are necessary to negotiate perturbations, animals rely on their exteroceptive and proprioceptive senses to monitor the environment and their own body movements...
November 29, 2017: Zoology: Analysis of Complex Systems, ZACS
https://www.readbyqxmd.com/read/29456081/lysozyme-counteracts-%C3%AE-lactam-antibiotics-by-promoting-the-emergence-of-l-form-bacteria
#11
Yoshikazu Kawai, Katarzyna Mickiewicz, Jeff Errington
β-lactam antibiotics inhibit bacterial cell wall assembly and, under classical microbiological culture conditions that are generally hypotonic, induce explosive cell death. Here, we show that under more physiological, osmoprotective conditions, for various Gram-positive bacteria, lysis is delayed or abolished, apparently because inhibition of class A penicillin-binding protein leads to a block in autolytic activity. Although these cells still then die by other mechanisms, exogenous lytic enzymes, such as lysozyme, can rescue viability by enabling the escape of cell wall-deficient "L-form" bacteria...
January 31, 2018: Cell
https://www.readbyqxmd.com/read/29456023/alternative-mode-of-e-site-trna-binding-in-the-presence-of-a-downstream-mrna-stem-loop-at-the-entrance-channel
#12
Yan Zhang, Samuel Hong, Ajchareeya Ruangprasert, Georgios Skiniotis, Christine M Dunham
Structured mRNAs positioned downstream of the ribosomal decoding center alter gene expression by slowing protein synthesis. Here, we solved the cryo-EM structure of the bacterial ribosome bound to an mRNA containing a 3' stem loop that regulates translation. Unexpectedly, the E-site tRNA adopts two distinct orientations. In the first structure, normal interactions with the 50S and 30S E site are observed. However, in the second structure, although the E-site tRNA makes normal interactions with the 50S E site, its anticodon stem loop moves ∼54 Å away from the 30S E site to interact with the 30S head domain and 50S uL5...
February 8, 2018: Structure
https://www.readbyqxmd.com/read/29455741/young-immigrants-host-country-identification-and-their-friendships-with-natives-does-relative-group-size-matter
#13
Lars Leszczensky
Recent network research indicates that native youth prefer to befriend immigrants with stronger rather than weaker host country identification. Surprisingly, however, no respective preference of high-identifying immigrants for native friends has been found, and there is little evidence that friends influence immigrants' identification. Seeking to make sense of these unexpected findings, my aims are twofold: First, I reproduce an earlier study using three waves of newly collected network panel data. Second, going beyond a robustness test with better data, I suggest that relative group size within school accounts for earlier findings...
February 2018: Social Science Research
https://www.readbyqxmd.com/read/29455526/structure-based-optimization-strategies-for-g-protein-coupled-receptor-gpcr-allosteric-modulators-a-case-study-from-analyses-of-new-metabotropic-glutamate-receptor-5-mglu-5-x-ray-structures
#14
John Christopher, Zoltán Orgován, Miles Congreve, Andrew S Dore, James C Errey, Fiona H Marshall, Jonathan S Mason, Krzysztof Okrasa, Prakash Rucktooa, Maria J Serrano-Vega, György G Ferenczy, Gyorgy M Keseru
Two interesting new X-ray structures of negative allosteric modulator (NAM) ligands for the mGlu5 receptor, M-MPEP (3) and fenobam (4), are reported. The new structures show how the binding of the ligands induces different receptor water channel conformations to previously published structures. The structure of fenobam, where a urea replaces the acetylenic linker in M-MPEP and mavoglurant, reveals a binding mode where the ligand is rotated by 180º compared to a previously proposed docking model. The need for multiple ligand structures for accurate GPCR structure-based drug design is demonstrated by the different growing vectors identified for the head groups of M-MPEP and mavoglurant and by the unexpected water mediated receptor interactions of a new chemotype represented by fenobam...
February 18, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29455370/incomplete-copolymer-degradation-of-in-situ-chemotherapy
#15
Pierre Bourdillon, Tanguy Boissenot, Lauriane Goldwirt, Julien Nicolas, Caroline Apra, Alexandre Carpentier
In situ carmustine wafers containing 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) are commonly used for the treatment of recurrent glioblastoma to overcome the brain-blood barrier. In theory, this chemotherapy diffuses into the adjacent parenchyma and the excipient degrades in maximum 8 weeks but no clinical data confirms this evolution, because patients are rarely operated again. A 75-year-old patient was operated twice for recurrent glioblastoma, and a carmustine wafer was implanted during the second surgery...
February 17, 2018: Journal of Materials Science. Materials in Medicine
https://www.readbyqxmd.com/read/29455316/investigation-of-major-genetic-alterations-in-neuroblastoma
#16
Régis Afonso Costa, Héctor N Seuánez
Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. This malignancy shows a wide spectrum of clinical outcome and its prognosis is conditioned by manifold biological and genetic factors. We investigated the tumor genetic profile and clinical data of 29 patients with NB by multiplex ligation-dependent probe amplification (MLPA) to assess therapeutic risk. In 18 of these tumors, MYCN status was assessed by fluorescence in situ hybridization (FISH). Copy number variation was also determined for confirming MLPA findings in two 6p loci...
February 17, 2018: Molecular Biology Reports
https://www.readbyqxmd.com/read/29455034/preoperative-risk-factors-for-unexpected-postoperative-intensive-care-unit-admission-a-retrospective-case-analysis
#17
Joshua B Knight, Evan E Lebovitz, Theresa A Gelzinis, Ibtesam A Hilmi
INTRODUCTION: The purpose of this retrospective case-control study was to investigate preoperative risk factors for unexpected postoperative intensive care unit (ICU) admissions in patients undergoing non-emergent surgical procedures in a tertiary medical centre. METHODS: A medical record review of adult patients undergoing elective non-cardiac and non-transplant major surgical procedures during the period of January 2011 through December 2015 in the operating rooms of a large university hospital was carried out...
February 15, 2018: Anaesthesia, Critical Care & Pain Medicine
https://www.readbyqxmd.com/read/29455019/ocular-myasthenia-induced-by-rivaroxaban-in-patient-with-deep-vein-thrombosis
#18
Enrique M San Norberto, Irene García-Saiz, Diana Gutiérrez, Liliana Domingos, Carlos Vaquero
The non-VKA oral anticoagulant rivaroxaban is indicated in prevention and treatment of venous thromboembolism. A 60-year-old male patient complained of bilateral ptosis after administration of rivaroxaban for deep vein thrombosis. Myasthenia gravis was confirmed by positive serum antiacetylcholine receptor antibody test. No mediastinal thymoma was found. The ocular myasthenia reversed after discontinuing rivaroxaban treatment. Nevertheless, ptosis recurred and chronic oral pyridostigmine bromide treatment was necessary...
February 15, 2018: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/29454605/knowledge-of-sudden-unexpected-death-in-epilepsy-sudep-among-372-patients-attending-a-german-tertiary-epilepsy-center
#19
Rainer Surges, Randi von Wrede, Thomas Porschen, Christian E Elger
BACKGROUND: There is evidence that the sudden unexpected death in epilepsy (SUDEP) risk can be reduced by good seizure control, nocturnal supervision, and by early cardiopulmonary resuscitation if cardiorespiratory arrest occurs in the aftermaths of generalized tonic-clonic seizures (GTCS). These measures, however, may critically depend on the knowledge of patients and relatives on SUDEP. Here, we assessed the basic knowledge on SUDEP of people with epilepsy at a tertiary epilepsy center in Germany...
February 14, 2018: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29454561/flexible-neural-hardware-supports-dynamic-computations-in-retina
#20
REVIEW
Michal Rivlin-Etzion, William N Grimes, Fred Rieke
The ability of the retina to adapt to changes in mean light intensity and contrast is well known. Classically, however, adaptation is thought to affect gain but not to change the visual modality encoded by a given type of retinal neuron. Recent findings reveal unexpected dynamic properties in mouse retinal neurons that challenge this view. Specifically, certain cell types change the visual modality they encode with variations in ambient illumination or following repetitive visual stimulation. These discoveries demonstrate that computations performed by retinal circuits with defined architecture can change with visual input...
February 14, 2018: Trends in Neurosciences
keyword
keyword
63005
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"