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https://www.readbyqxmd.com/read/28302483/production-of-an-active-form-of-vitamin-d2-by-genetically-engineered-cyp105a1
#1
Kaori Yasuda, Yuya Yogo, Hiroshi Sugimoto, Hiroki Mano, Teisuke Takita, Miho Ohta, Masaki Kamakura, Shinichi Ikushiro, Kiyoshi Yasukawa, Yoshitsugu Shiro, Toshiyuki Sakaki
Our previous studies revealed that CYP105A1 can convert vitamin D3 (VD3) to its active form, 1α,25-dihydroxyvitamin D3 (1,25D3). Site-directed mutagenesis of CYP105A1 based on its crystal structure dramatically enhanced its activity; the activity of double variants R73A/R84A and R73A/R84V was more than 100-fold higher than that of the wild type of CYP105A1. In contrast, these variants had a low ability to convert vitamin D2 (VD2) to 1α,25-dihydroxyvitamin D2 (1,25D2), whereas they catalyzed the sequential hydroxylation at positions C25 and C26 to produce 25,26D2...
March 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28300854/randomized-placebo-and-active-controlled-crossover-study-of-the-safety-and-efficacy-of-thvd-102-a-fixed-dose-combination-of-oxybutynin-and-pilocarpine-in-subjects-with-primary-focal-hyperhidrosis
#2
David M Pariser, Janakan Krishnaraja, Thomas M Tremblay, R Michael Rubison, Ted W Love, Benjamin F McGraw
BACKGROUND: While muscarinic antagonists (anticholinergics) have shown efficacy in treating primary focal hyperhidrosis (PFH), side effects - most commonly dry mouth - are intolerable for most patients. THVD-102, a fixed-dose combination product has been developed combining oxybutynin, a muscarinic antagonist, and pilocarpine, a muscarinic agonist. The pilocarpine is at a dose level and release profile optimized to correct salivary flow impaired by oxybutynin yet not interfere with the therapeutic muscarinic antagonist effect of oxybutynin upon the sweat glands...
February 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28299461/efficacy-of-higher-dose-levamisole-in-maintaining-remission-in-steroid-dependant-nephrotic-syndrome
#3
Asiri S Abeyagunawardena, Umeshi Karunadasa, Heshan Jayaweera, Shenal Thalgahagoda, Sampath Tennakoon, Shamali Abeyagunawardena
OBJECTIVE: Levamisole (LEV) has been used successfully on an alternate-day regime of 2.5 mg/kg in steroid-dependant nephrotic syndrome (SDNS) to maintain remission. This pilot study was carried out between 2010 and 2015 at a single center in Sri Lanka to evaluate the efficacy of LEV prescribed at 2.5 mg/kg daily, which is double the alternate-day dose. METHODS: Sequential children with SDNS, relapsing more than twice in the preceding 12 months and previously treated with LEV and low-dose alternate-day prednisolone (0...
March 15, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28290109/continuous-online-item-calibration-parameter-recovery-and-item-utilization
#4
Hao Ren, Wim J van der Linden, Qi Diao
Parameter recovery and item utilization were investigated for different designs for online test item calibration. The design was adaptive in a double sense: it assumed both adaptive testing of examinees from an operational pool of previously calibrated items and adaptive assignment of field-test items to the examinees. Four criteria of optimality for the assignment of the field-test items were used, each of them based on the information in the posterior distributions of the examinee's ability parameter during adaptive testing as well as the sequentially updated posterior distributions of the field-test item parameters...
March 13, 2017: Psychometrika
https://www.readbyqxmd.com/read/28281067/changes-in-structural-characteristics-and-metal-speciation-for-biochar-exposure-in-typic-udic-ferrisols
#5
Qi Lin, Xin Xu, Qian Chen, Jing Fang, Xiaodong Shen, Lijuan Zhang
Recent studies on biochars confirmed their potential benefits in improving soil fertility and sequestrating contaminants. However, little information on the changes in structural characteristics and metal speciation of biochars after exposure to soils is currently available. The aim of this study was to use double experimental bags to study the transformation of ozonized biochars derived from poultry manure and drying sludge (denoted PB and SB, respectively) in typic udic ferrisols. The carbon and sulfur functional groups and chemical characteristics of the biochars were determined using spectroscopic techniques, such as Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and near-edge X-ray absorption fine structure spectroscopy spectroscopy, combined with chemical extractions...
March 9, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28272748/sevoflurane-induced-isoelectric-eeg-and-burst-suppression-differential-and-antagonistic-effect-of-added-nitrous-oxide
#6
B Niu, J Y Xiao, Y Fang, B Y Zhou, J Li, F Cao, Y K Tian, W Mei
The objective of this study was to investigate whether nitrous oxide influenced the ED50 of sevoflurane for induction of isoelectric electroencephalogram (ED50isoelectric ) differently from its influence on the ED50 of sevoflurane for electroencephalogram burst suppression (ED50burst ). In a prospective, randomised, double-blind, parallel group, up-down sequential allocation study, 77 ASA physical status 1 and 2 patients received sevoflurane induction and, after tracheal intubation, were randomly allocated to receive sevoflurane with either 40% oxygen in air (control group) or 60% nitrous oxide in oxygen mixture (nitrous group)...
March 8, 2017: Anaesthesia
https://www.readbyqxmd.com/read/28267402/cd40-ligand-is-increased-in-mast-cells-in-psoriasis-and-actinic-keratosis-but-less-so-in-epithelial-skin-carcinomas
#7
Salla Haimakainen, Antti P Kaukinen, Mireille-Maria Suttle, Jukka Pelkonen, Ilkka T Harvima
The expression of CD40 ligand (CD40L) in mast cells was investigated in biopsies from lesional and non-lesional skin samples of patients with psoriasis, actinic keratosis (AK), basal cell carcinoma, and squamous cell carcinoma using a sequential double-staining technique. The percentage of CD40L(+) mast cells was higher in the lesional than in the non-lesional skin (p < .003). Interestingly, this percentage was lower in both carcinomas than in psoriasis and actinic keratosis (p < .025). Cells immunopositive for CD40 receptor were increased in all lesion types but especially so in carcinomas...
March 16, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28267344/synthesis-of-spiro-dihydroquinoline-and-octahydrophenanthrene-derivatives-via-palladium-catalyzed-intramolecular-oxidative-arylation
#8
Zhong-Lin Zang, Shuklachary Karnakanti, Sheng Zhao, Ping Hu, Zhen Wang, Pan-Lin Shao, Yun He
A method for intramolecular sp(2) C-H oxidative arylation of unactivated cyclic olefins has been developed to access spiro-dihydroquinoline and octahydrophenanthrene derivatives in a straightforward and efficient manner. Bearing picolinamide as a directing group, the alkenyl anilines cyclized to afford spiro-dihydroquinolines in moderate to excellent yields via direct oxidative arylation, while the alkenyl benzylamines furnished the octahydrophenanthrene derivatives in moderate yields via sequential oxidative arylation and double acetoxylation...
March 7, 2017: Organic Letters
https://www.readbyqxmd.com/read/28262529/effects-of-combined-prokinetic-administration-on-gastric-emptying-in-critically-ill-patients
#9
Afshin Gholipour Baradari, Mohammad Reza Khajavi, Abolfazl Firouzian, Abbas Alipour, Hojatallah Daneshpour, Yunes Panahi, Amirhossein Sahebkar
BACKGROUND AND STUDY AIMS: Combination of prokinetic drugs with different mechanisms of action is frequently used when feeding intolerance is not improved with a single agent. In this study, we evaluated the effect of combined infusion of neostigmine and metoclopramide on gastric passage in critically ill patients in the intensive care unit (ICU). PATIENTS AND METHODS: This study is a randomized double-blind controlled trial in 90 patients between 20 and 60years of age who were under mechanical ventilation and had gastric residual volumes (GRVs) >120mL 3h after the last lavage...
March 2, 2017: Arab Journal of Gastroenterology: the Official Publication of the Pan-Arab Association of Gastroenterology
https://www.readbyqxmd.com/read/28259785/protection-mechanisms-of-the-carapace-of-a-box-turtle
#10
Bingbing An, H Daniel Wagner
In this study we explore the materials design principles of the carapace of a Terrapene Carolina box turtle, which possesses a sandwich-like structure consisting of a foam-like interior layer (FIL) enclosed by two dense exterior layers (DEL). A constitutive scheme accounting for the large deformation, plastic yielding and post-yield strain hardening caused by densification of the cells in the foam is developed to model the mechanical properties of the FIL, and a large deformation elastic-plastic model for the DEL is proposed...
February 24, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/28252049/double-bond-containing-polyallene-based-triblock-copolymers-via-phenoxyallene-and-meth-acrylate
#11
Aishun Ding, Guolin Lu, Hao Guo, Xiaoyu Huang
A series of ABA triblock copolymers, consisting of double-bond-containing poly(phenoxyallene) (PPOA), poly(methyl methacrylate) (PMMA), or poly(butyl acrylate) (PBA) segments, were synthesized by sequential free radical polymerization and atom transfer radical polymerization (ATRP). A new bifunctional initiator bearing azo and halogen-containing ATRP initiating groups was first prepared followed by initiating conventional free radical homopolymerization of phenoxyallene with cumulated double bond to give a PPOA-based macroinitiator with ATRP initiating groups at both ends...
March 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28251056/sequential-double-clicks-toward-structurally-well-defined-heterogeneous-n-glycoclusters-the-importance-of-cluster-heterogeneity-on-pattern-recognition-in-vivo
#12
Liliya Latypova, Regina Sibgatullina, Akihiro Ogura, Katsumasa Fujiki, Alsu Khabibrakhmanova, Tsuyoshi Tahara, Satoshi Nozaki, Sayaka Urano, Kazuki Tsubokura, Hirotaka Onoe, Yasuyoshi Watanabe, Almira Kurbangalieva, Katsunori Tanaka
Structurally well-defined heterogeneous N-glycoclusters are prepared on albumin via a double click procedure. The number of glycan molecules present, in addition to the spatial arrangement of glycans in the heterogeneous glycoclusters, plays an important role in the in vivo kinetics and organ-selective accumulation through glycan pattern recognition mechanisms.
February 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/28250601/early-administration-of-selenium-in-patients-with-acute-traumatic-brain-injury-a-randomized-double-blinded-controlled-trial
#13
Omid Moradi Moghaddam, Mohammad Niakan Lahiji, Valiollah Hassani, Shakiba Mozari
AIM: The present study was carried out to examine this hypothesis that administration of selenium can prevent the development of injuries by brain trauma and thus can modulate patients' functional recovery and also improve posttraumatic outcome. MATERIALS AND METHODS: This double-blinded controlled trial was carried out on 113 patients who were hospitalized following traumatic brain injury (TBI) with Glasgow Coma Scale score of 4-12 that were randomly assigned to receive selenium within 8 h after injury plus standard treatment group or routine standard treatment alone as the control...
February 2017: Indian Journal of Critical Care Medicine
https://www.readbyqxmd.com/read/28248702/norepinephrine-intermittent-intravenous-boluses-to-prevent-hypotension-during-spinal-anesthesia-for-cesarean-delivery-a-sequential-allocation-dose-finding-study
#14
Desire N Onwochei, Warwick D Ngan Kee, Lillia Fung, Kristi Downey, Xiang Y Ye, Jose C A Carvalho
BACKGROUND: The use of phenylephrine as the first-line agent for prevention and treatment of maternal hypotension during cesarean delivery (CD) may reduce cardiac output, posing a theoretical risk to mother and fetus. Norepinephrine has been suggested as a potential alternative, because its β-adrenergic effects might result in greater heart rate and cardiac output than phenylephrine. The use of norepinephrine to prevent and treat hypotension during CD is new, and its use as a bolus has not been fully determined in this context...
February 28, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28242626/atr-inhibition-disrupts-rewired-homologous-recombination-and-fork-protection-pathways-in-parp-inhibitor-resistant-brca-deficient-cancer-cells
#15
Stephanie A Yazinski, Valentine Comaills, Rémi Buisson, Marie-Michelle Genois, Hai Dang Nguyen, Chu Kwen Ho, Tanya Todorova Kwan, Robert Morris, Sam Lauffer, André Nussenzweig, Sridhar Ramaswamy, Cyril H Benes, Daniel A Haber, Shyamala Maheswaran, Michael J Birrer, Lee Zou
Poly-(ADP-ribose) polymerase (PARP) inhibitors (PARPis) selectively kill BRCA1/2-deficient cells, but their efficacy in BRCA-deficient patients is limited by drug resistance. Here, we used derived cell lines and cells from patients to investigate how to overcome PARPi resistance. We found that the functions of BRCA1 in homologous recombination (HR) and replication fork protection are sequentially bypassed during the acquisition of PARPi resistance. Despite the lack of BRCA1, PARPi-resistant cells regain RAD51 loading to DNA double-stranded breaks (DSBs) and stalled replication forks, enabling two distinct mechanisms of PARPi resistance...
February 27, 2017: Genes & Development
https://www.readbyqxmd.com/read/28237912/vestibular-stimulation-improves-insight-into-illness-in-schizophrenia-spectrum-disorders
#16
Philip Gerretsen, David D Pothier, Carolyn Falls, Maxine Armstrong, Thushanthi Balakumar, Hiroyuki Uchida, David C Mamo, Bruce G Pollock, Ariel Graff-Guerrero
Impaired insight into illness (IMP-INS) is common among individuals with schizophrenia spectrum disorders (SSD), contributing to medication nonadherence and poor clinical outcomes. Caloric vestibular simulation (CVS) is typically used to assess peripheral vestibular system function. Left cold CVS is also a transiently effective treatment for IMP-INS and hemineglect secondary to right brain hemisphere stroke, and possibly for IMP-INS and mood stabilization in patients with SSD. Participants with SSD and moderate-to-severe IMP-INS participated in an exploratory double blind, crossover, randomized controlled study of the effects of CVS on IMP-INS...
February 13, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28235994/mass-spectrometry-profiling-of-oxylipins-endocannabinoids-and-n-acylethanolamines-in-human-lung-lavage-fluids-reveals-responsiveness-of-prostaglandin-e2-and-associated-lipid-metabolites-to-biodiesel-exhaust-exposure
#17
Sandra Gouveia-Figueira, Masoumeh Karimpour, Jenny A Bosson, Anders Blomberg, Jon Unosson, Jamshid Pourazar, Thomas Sandström, Annelie F Behndig, Malin L Nording
The adverse effects of petrodiesel exhaust exposure on the cardiovascular and respiratory systems are well recognized. While biofuels such as rapeseed methyl ester (RME) biodiesel may have ecological advantages, the exhaust generated may cause adverse health effects. In the current study, we investigated the responses of bioactive lipid mediators in human airways after biodiesel exhaust exposure using lipidomic profiling methods. Lipid mediator levels in lung lavage were assessed following 1-h biodiesel exhaust (average particulate matter concentration, 159 μg/m(3)) or filtered air exposure in 15 healthy individuals in a double-blinded, randomized, controlled, crossover study design...
February 24, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28229599/palladium-catalyzed-arylcarboxylation-of-propargylic-alcohols-with-co2-and-aryl-halides-access-to-functionalized-%C3%AE-alkylidene-cyclic-carbonates
#18
Song Sun, Bingbing Wang, Ning Gu, Jin-Tao Yu, Jiang Cheng
A palladium-catalyzed, three-component reaction between propargylic alcohols, CO2, and aryl halides was developed whereby a sequential carboxylation, trans-oxopalladation of the C≡C bond by an ArPdX species, and a reductive elimination procedure afforded a series of functionalized α-alkylidene cyclic carbonates in moderate to excellent yields. Notably, the configuration of these tetrasubstituted olefins was dominated by the trans-oxopalladation step where the aryl group derived from ArX is located trans to the oxygen attached in the double bond...
February 23, 2017: Organic Letters
https://www.readbyqxmd.com/read/28225674/inhibiting-plasma-kallikrein-for-hereditary-angioedema-prophylaxis
#19
RANDOMIZED CONTROLLED TRIAL
Aleena Banerji, Paula Busse, Mustafa Shennak, William Lumry, Mark Davis-Lorton, Henry J Wedner, Joshua Jacobs, James Baker, Jonathan A Bernstein, Richard Lockey, H Henry Li, Timothy Craig, Marco Cicardi, Marc Riedl, Ahmad Al-Ghazawi, Carolyn Soo, Ryan Iarrobino, Daniel J Sexton, Christopher TenHoor, Jon A Kenniston, Ryan Faucette, J Gordon Still, Harvey Kushner, Robert Mensah, Chris Stevens, Joseph C Biedenkapp, Yung Chyung, Burt Adelman
Background Hereditary angioedema with C1 inhibitor deficiency is characterized by recurrent, unpredictable swelling episodes caused by uncontrolled plasma kallikrein generation and excessive bradykinin release resulting from cleavage of high-molecular-weight kininogen. Lanadelumab (DX-2930) is a new kallikrein inhibitor with the potential for prophylactic treatment of hereditary angioedema with C1 inhibitor deficiency. Methods We conducted a phase 1b, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial...
February 23, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28225182/double-sequential-encrypted-targeting-sequence-a-new-concept-for-bone-cancer-treatment
#20
Gonzalo Villaverde, Valentina Nairi, Alejandro Baeza, Maria Vallet-Regi
The selective transportation of therapeutic agents to tumoral cells is usually achieved by their conjugation with targeting moieties able to recognize these cells. Unfortunately, simple and static targeting systems usually show selectivity lacks. Herein, double sequential encrypted targeting system is proposed as stimuli-responsive targeting analogue for selectivity enhancement. The system is able to recognize diseased bone tissue in first place, and once there, a hidden secondary targeting group is activated by the presence of an enzyme overproduced in the malignant tissue (cathepsin K), triggering the recognition of diseased cells...
February 22, 2017: Chemistry: a European Journal
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