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Double Sequential

Weihua Chen, Hooman Salari, Matthew C Taylor, Ricarda Jost, Oliver Berkowitz, Russell Barrow, Deyun Qiu, Remi Branco, Josette Masle
Phosphatidylcholine (PC) is a major membrane phospholipid and a precursor for most signalling molecules. Understanding its synthesis is important for improving plant growth, nutritional value and resistance to stress. PC synthesis is complex, involving several interconnected pathways, one of which proceeds from serine-derived phosphoethanolamine (PEA) to form phosphocholine (PCho) through three sequential phospho-base methylations catalysed by phosphoethanolamine N-methyltransferases (PEAMTs). The contribution of this pathway to the production of PC and plant growth has been a matter of some debate...
May 18, 2018: Plant Physiology
Victor Shi, Michele Senni, Hendrik Streefkerk, Vikas Modgill, Wenchun Zhou, Allen Kaplan
BACKGROUND: PARADIGM-HF demonstrated significant clinical benefits for sacubitril/valsartan (LCZ696, an angiotensin receptor neprilysin inhibitor) versus the angiotensin-converting enzyme inhibitor (ACEI) enalapril in patients with heart failure with reduced ejection fraction. As inhibition of ACE, and co-inhibition of ACE and neprilysin, may increase the risk of angioedema, this was an adverse event of special interest. METHODS: Following sequential enalapril and sacubitril/valsartan run-ins, patients were randomized to twice-daily sacubitril/valsartan 200 mg or enalapril 10 mg...
August 1, 2018: International Journal of Cardiology
Ee Teng Goh, Caroline S Stokes, Sandeep S Sidhu, Hendrik Vilstrup, Lise Lotte Gluud, Marsha Y Morgan
BACKGROUND: Hepatic encephalopathy is a common complication of cirrhosis and has high associated morbidity and mortality. The condition is classified as overt if it is clinically apparent or minimal if only evident though psychometric testing. The exact pathogenesis of this syndrome is unknown although ammonia is thought to play a key role. L-ornithine L-aspartate has ammonia-lowering properties and may, therefore, benefit people with cirrhosis and hepatic encephalopathy. OBJECTIVES: To evaluate the beneficial and harmful effects of L-ornithine L-aspartate versus placebo, no intervention, or other active interventions in people with cirrhosis and hepatic encephalopathy...
May 15, 2018: Cochrane Database of Systematic Reviews
Masumeh Ghazanfarpour, Mona Najaf Najafi, Nosrat Baharian Sharghi, Mahsa Sadat Mousavi, Masoudeh Babakhanian, Hassan Rakhshanded
OBJECTIVE: The present study aimed to evaluate the oral fennel effects on the menopausal symptoms. MATERIAL AND METHODS: This double-blind, randomized, placebo-controlled trial was conducted on fifty postmenopausal women in Mashhad (Iran). Patients randomly divided into two groups of fennel ( n = 25) and placebo ( n= 25). The measurements were carried out at the baseline and after three months through Menopause-Specific Quality of Life (MENQOL) questionnaire. RESULTS: Both placebo and treatment groups revealed significant improvement in the hot flush score ( p< 0...
May 14, 2018: Journal of the Turkish German Gynecological Association
Toshimi Kaido, Masahiro Shinoda, Yukihiro Inomata, Takahito Yagi, Nobuhisa Akamatsu, Yasutsugu Takada, Hideki Ohdan, Tsuyoshi Shimamura, Yasuhiro Ogura, Susumu Eguchi, Hidetoshi Eguchi, Satoshi Ogata, Tomoharu Yoshizumi, Toshihiko Ikegami, Michio Yamamoto, Satoshi Morita, Shinji Uemoto
OBJECTIVE: Postoperative early oral or enteral intake is a crucial element of the Enhanced Recovery After Surgery (ERAS) protocol. However, normal food intake or enteral feeding cannot be started early in the presence of coexisting bowel dysfunction in patients undergoing liver transplantation (LT). The aim of this multicenter, randomized, double-blinded, placebo-controlled trial was to determine the enhancement effects of the Japanese herbal medicine Daikenchuto (DKT) on oral/enteral caloric intake in patients undergoing LT...
March 20, 2018: Nutrition
Kunpeng Chang, Qiong Wang, Xiaofei Shi, Shuixing Wang, Hongjing Wu, Lijuan Nie, Haixing Li
A stepwise partially overlapping primer-based PCR (SWPOP-PCR) method for isolating flanking unknown DNA regions was developed, which comprises three rounds of nested PCRs sequentially driven by SWPOP primer-nested specific primer pairs. SWPOP primer set is characterized by a partial overlap of 10 bp with 3'-part of the latter primer is identical to 5'-part of the former one, which makes the SWPOP primer in use anneal to SWPOP site of the prior PCR product only at relatively low temperature. For each PCR, target single-stranded DNA primed by the SWPOP primer in the exclusive one low-stringency cycle is converted into double-stranded form in the following high-stringency cycle due to the presence of a perfect annealing site for the specific primer...
May 9, 2018: AMB Express
Keiji Mori, Ryo Isogai, Yuto Kamei, Masahiro Yamanaka, Takahiko Akiyama
Described herein is a chiral magnesium bisphosphate catalyzed asymmetric double C(sp3 )-H bond functionalization triggered by a sequential hydride shift/cyclization process. This reaction consists of stereoselective domino C(sp3 )-H bond functionalization: (1) a highly enantio- and diastereoselective C(sp3 )-H bond functionalization by chiral magnesium bisphosphate (first [1,5]-hydride shift), and (2) a highly diastereoselective C(sp3 )-H bond functionalization by an achiral catalyst (Yb(OTf)3 , second [1,5]-hydride shift)...
May 9, 2018: Journal of the American Chemical Society
Charlie L Dorer, Anne E Manktelow, Judith Allanson, Barbara J Sahakian, John D Pickard, Andrew Bateman, David K Menon, Emmanuel A Stamatakis
PRIMARY OBJECTIVE: To investigate functional improvement late (>6 months) after traumatic brain injury (TBI). To this end, we conducted a double-blind, placebo-controlled experimental medicine study to test the hypothesis that a widely used cognitive enhancer would benefit patients with TBI. RESEARCH DESIGN: We focused on motor control function using a sequential finger opposition fMRI paradigm in both patients and age-matched controls. METHODS AND PROCEDURES: Patients' fMRI and DTI scans were obtained after randomised administration of methylphenidate or placebo...
May 8, 2018: Brain Injury: [BI]
Marion Eisenhuta, Natalie Hoecker, Sidsel Birkelund Schmidt, Rubek Merina Basgaran, Samantha Flachbart, Peter Jahns, Tabea Eser, Stefan Geimer, Søren Husted, Andreas P M Weber, Dario Leister, Anja Schneider
The transition metal manganese (Mn) is indispensable for photoautotrophic growth, since photosystem II (PSII) employs an inorganic Mn4 CaO5 cluster for water splitting. Here, we show that the Arabidopsis membrane protein CHLOROPLAST MANGANESE TRANSPORTER 1 (CMT1) is involved in chloroplast Mn homeostasis. CMT1 is the closest homolog of -the previously characterized thylakoid Mn transporter- PHOTOSYNTHESIS AFFECTED MUTANT71 (PAM71). In contrast to PAM71, CMT1 resides at the chloroplast envelope and is ubiquitously expressed...
May 4, 2018: Molecular Plant
Karim Hajjar, Iskandar Berbari, Chady El Tawil, Ralphe Bou Chebl, Gilbert Abou Dagher
In the setting of cardiac arrest, refractory ventricular fibrillation (VF) is difficult to manage, and mortality rates are high. Double sequential defibrillation (DSD) has been described in the literature as a successful means to terminate this malignant rhythm, after failure of traditional Advanced Cardiac Life Support (ACLS) measures. The authors herein present a case of refractory VF in a patient with cardiac arrest, on whom DSD was successful in reversion to sinus rhythm, and provide a thorough review of similar cases in the literature...
April 30, 2018: American Journal of Emergency Medicine
Aharon Azagury, Vera C Fonseca, Daniel Y Cho, James Perez-Rogers, Christopher M Baker, Elaine Steranka, Victoria Goldenshtein, Dominick Calvao, Eric M Darling, Edith Mathiowitz
A quick fabrication method for making double-walled (DW) polymeric nanospheres is presented. The process uses sequential precipitation of two polymers. By choosing an appropriate solvent and non-solvent polymer pair, and engineering two sequential phase inversions which induces first precipitation of the core polymer followed by precipitation of the shell polymer, DW nanospheres can be created instantaneously. A series of DW formulations were prepared with various core and shell polymers, then characterized using laser diffraction particle sizing, scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry (DSC)...
May 2, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Satyananda Kashyap, Honghai Zhang, Karan Rao, Milan Sonka
A fully automated knee magnetic resonance imaging (MRI) segmentation method to study osteoarthritis (OA) was developed using a novel hierarchical set of random forests (RF) classifiers to learn the appearance of cartilage regions and their boundaries. A neighborhood approximation forest is used first to provide contextual feature to the second-level RF classifier that also considers local features and produces location-specific costs for the layered optimal graph image segmentation of multiple objects and surfaces (LOGISMOS) framework...
May 2018: IEEE Transactions on Medical Imaging
Michael F Egan, James Kost, Pierre N Tariot, Paul S Aisen, Jeffrey L Cummings, Bruno Vellas, Cyrille Sur, Yuki Mukai, Tiffini Voss, Christine Furtek, Erin Mahoney, Lyn Harper Mozley, Rik Vandenberghe, Yi Mo, David Michelson
BACKGROUND: Alzheimer's disease is characterized by the deposition of amyloid-beta (Aβ) plaques in the brain. Aβ is produced from the sequential cleavage of amyloid precursor protein by β-site amyloid precursor protein-cleaving enzyme 1 (BACE-1) followed by γ-secretase. Verubecestat is an oral BACE-1 inhibitor that reduces the Aβ level in the cerebrospinal fluid of patients with Alzheimer's disease. METHODS: We conducted a randomized, double-blind, placebo-controlled, 78-week trial to evaluate verubecestat at doses of 12 mg and 40 mg per day, as compared with placebo, in patients who had a clinical diagnosis of mild-to-moderate Alzheimer's disease...
May 3, 2018: New England Journal of Medicine
Ka Lai Yee, Jacqueline McCrea, Deborah Panebianco, Wen Liu, Nicole Lewis, Tamara Cabalu, Steven Ramael, Rebecca E Wrishko
BACKGROUND AND OBJECTIVES: Suvorexant (MK-4305) is an orexin receptor antagonist approved for the treatment of insomnia in the USA and other regions. This randomized, double-blind, placebo-controlled, sequential-panel, Phase 1 trial assessed the safety, tolerability, and pharmacokinetic data following single and multiple dosing of suvorexant in healthy men (aged 18-45 years). METHODS: Within allocated panels, subjects (n = 8) were randomized to receive nightly doses of suvorexant (10, 20, 40, 80, and 100 mg) administered orally for 14 days, or placebo...
April 28, 2018: Clinical Drug Investigation
Wendy W Yeh, Iain P Fraser, Patricia Jumes, Amelia Petry, Inge De Lepeleire, Martine Robberechts, Christina Reitmann, Kristien Van Dyck, Xiaobi Huang, Zifang Guo, Deborah Panebianco, Robert B Nachbar, Edward O'Mara, John A Wagner, Joan R Butterton, Frank J Dutko, Valentin Moiseev, Zhanna Kobalava, Andreas Hüser, Sorin Visan, Christian Schwabe, Edward Gane, Serghei Popa, Nelea Ghicavii, Markus Uhle, Frank Wagner
PURPOSE: Elbasvir (MK-8742) and grazoprevir (MK-5172; Merck & Co, Inc, Kenilworth, New Jersey) are hepatitis C virus (HCV)-specific inhibitors of the nonstructural protein 5A phosphoprotein and the nonstructural protein 3/4A protease, respectively. The aims of these studies were to evaluate the antiviral activity and safety of different doses of elbasvir or grazoprevir each administered as monotherapy to participants infected with either HCV genotype (GT) 1 or GT3. METHODS: These 2 double-blind, randomized, placebo-controlled, sequential-panel, multiple ascending dose studies were conducted to assess the safety and pharmacodynamics of 5 days of once-daily elbasvir or 7 days of once-daily grazoprevir in adult male participants chronically infected with either HCV GT1 or GT3...
April 24, 2018: Clinical Therapeutics
Tomas Tomka, Dagmar Iber, Marcelo Boareto
The sculpturing of the vertebrate body plan into segments begins with the sequential formation of somites in the presomitic mesoderm (PSM). The rhythmicity of this process is controlled by travelling waves of gene expression. These kinetic waves emerge from coupled cellular oscillators and sweep across the PSM. In zebrafish, the oscillations are driven by autorepression of her genes and are synchronized via Notch signalling. Mathematical modelling has played an important role in explaining how collective properties emerge from the molecular interactions...
April 24, 2018: Progress in Biophysics and Molecular Biology
Robijanto Soetedjo
Saccades adapt to persistent natural or artificially imposed dysmetrias. The characteristics and circuitry of saccade adaptation have been revealed using a visually guided task (VGT) where the vectors of the target step and the intended saccade command are the same. However, in real life, another saccade occasionally intervenes before the saccade to the target occurs. This necessitates an updating of the intended saccade to account for the intervening saccadic displacement, which dissociates the visual target signal and the intended saccade command...
April 25, 2018: Journal of Neurophysiology
Manabu Kato, Hidetoshi Furuie, Takako Shimizu, Atsuhiro Miyazaki, Fumiaki Kobayashi, Hitoshi Ishizuka
AIMS: To characterise the pharmacokinetics, pharmacodynamics, and safety of esaxerenone, a mineralocorticoid receptor antagonist, in healthy adult Japanese men. METHODS: Double-blind, placebo-controlled, sequential, dose-escalation studies were conducted in subjects randomised to receive oral once-daily esaxerenone (ranges: 5-200 mg [single-dose]; 10-100 mg over 10 days [multiple-dose]) or placebo under fasting conditions. Plasma concentrations were analysed by liquid chromatograph-tandem mass spectrometry...
April 24, 2018: British Journal of Clinical Pharmacology
Revannath L Sutar, Saumik Sen, Or Eivgi, Gal Segalovich, Igor Schapiro, Ofer Reany, N Gabriel Lemcoff
Allylic and acrylic substrates may be efficiently transformed by a sequential bichromatic photochemical process into derivatives of levulinates or butenolides with high selectivity when phenanthrene is used as a regulator. Thus, UV-A photoinduced cross-metathesis (CM) couples the acrylic and allylic counterparts and subsequent UV-C irradiation initiates E - Z isomerization of the carbon-carbon double bond, followed by one of two competing processes; namely, cyclization by transesterification or a 1,5-H shift and tautomerization...
February 7, 2018: Chemical Science
Alexander D Dilman, Vitalij V Levin
Compounds containing a difluoromethylene unit have gained increasing attention due to their utility in drug design. Classic methods for the synthesis of these compounds rely on either harsh deoxofluorination reactions or laborious functional group manipulation sequences. In 2013, we proposed a method for assembling gem-difluorinated molecules from a difluorocarbene, a nucleophile, and an electrophile. In this process, a difluorocarbene can be considered an equivalent of a bipolar CF2 unit. Performing consecutive bond-forming reactions by sequential attachment of a nucleophile and an electrophile to a difluorocarbene provides the opportunity for the synthesis of a wide variety of organofluorine compounds...
April 17, 2018: Accounts of Chemical Research
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