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https://www.readbyqxmd.com/read/28535410/effect-of-enzyme-inhibition-on-perampanel-pharmacokinetics-why-study-design-matters
#1
Barry E Gidal, Rama Maganti, Antonio Laurenza, Haichen Yang, David A Verbel, Edgar Schuck, Jim Ferry
OBJECTIVES: Perampanel, a selective, noncompetitive AMPA receptor antagonist, is indicated as adjunctive therapy for the treatment of partial seizures with or without secondarily generalized seizures and primary generalized tonic-clonic seizures in patients with epilepsy aged 12years and older. In vitro studies and Phase I trials indicate that perampanel is metabolized almost exclusively by CYP3A, with an elimination half-life (t1/2) averaging approximately 105h. Understanding of pharmacokinetic (PK) interactions-enzyme inhibition or induction-and anticipating their occurrence are important for management of patients with epilepsy...
April 26, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28535173/invited-commentary-self-control-is-a-virtue
#2
C R Weinberg
The case-crossover design, introduced in 1991 by Malcolm Maclure (Am J Epidemiol. 1991;133(2):144-153), provided a precise and powerful tool for studying short-term effects of transient triggering exposures on abrupt outcomes like myocardial infarction. The design is an example of "self-control." One compares case-time intervals that include experiences that came just before the health event with control-time intervals that capture comparable experiences more remote from the event. Methodologists have since tweaked the general approach, recognizing issues that need to be considered to guard against time-driven confounders...
May 23, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28535142/srs2-promotes-synthesis-dependent-strand-annealing-by-disrupting-dna-polymerase-%C3%AE-extending-d-loops
#3
Jie Liu, Christopher Ede, William D Wright, Steven K Gore, Shirin S Jenkins, Bret D Freudenthal, M Todd Washington, Xavier Veaute, Wolf-Dietrich Heyer
Synthesis-dependent strand annealing (SDSA) is the preferred mode of homologous recombination in somatic cells leading to an obligatory non-crossover outcome, thus avoiding the potential for chromosomal rearrangements and loss of heterozygosity. Genetic analysis identified the Srs2 helicase as a prime candidate to promote SDSA. Here, we demonstrate that Srs2 disrupts D-loops in an ATP-dependent fashion and with a distinct polarity. Specifically, we partly reconstitute the SDSA pathway using Rad51, Rad54, RPA, RFC, DNA Polymerase δ with different forms of PCNA...
May 23, 2017: ELife
https://www.readbyqxmd.com/read/28535097/comparative-effectiveness-of-plantar-massage-techniques-on-postural-control-in-those-with-chronic-ankle-instability
#4
Erik A Wikstrom, Kyeongtak Song, Ashley Lea, Nastassia Brown
CONTEXT:   One of the major concerns after an acute lateral ankle sprain is the potential for development of chronic ankle instability (CAI). The existing research has determined that clinician-delivered plantar massage improves postural control in those with CAI. However, the effectiveness of self-administered treatments and the underlying cause of any improvements remain unclear. OBJECTIVES:   To determine (1) the effectiveness of a self-administered plantar-massage treatment in those with CAI as well and (2) whether the postural-control improvements were due to the stimulation of the plantar cutaneous receptors...
May 23, 2017: Journal of Athletic Training
https://www.readbyqxmd.com/read/28534875/dose-dependent-social-cognitive-effects-of-intranasal-oxytocin-delivered-with-novel-breath-powered-device-in-adults-with-autism-spectrum-disorder-a-randomized-placebo-controlled-double-blind-crossover-trial
#5
D S Quintana, L T Westlye, S Hope, T Nærland, T Elvsåshagen, E Dørum, Ø Rustan, M Valstad, L Rezvaya, H Lishaugen, E Stensønes, S Yaqub, K T Smerud, R A Mahmoud, P G Djupesland, O A Andreassen
The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin's dose-response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks...
May 23, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28534587/light-induced-relaxation-dynamics-of-the-ferricyanide-ion-revisited-by-ultrafast-xuv-photoelectron-spectroscopy
#6
Nicholas Engel, Sergey I Bokarev, Alexandre Moguilevski, Azhr A Raheem, Ruba Al-Obaidi, Tobias Möhle, Gilbert Grell, Katrin R Siefermann, Bernd Abel, Saadullah G Aziz, Oliver Kühn, Mario Borgwardt, Igor Yu Kiyan, Emad F Aziz
Photoinduced charge transfer in transition-metal coordination complexes plays a prominent role in photosynthesis and is fundamental for light-harvesting processes in catalytic materials. However, revealing the relaxation pathways of charge separation remains a very challenging task because of the complexity of relaxation channels and ultrashort time scales. Here, we employ ultrafast XUV photoemission spectroscopy to monitor fine mechanistic details of the electron dynamics following optical ligand-to-metal charge-transfer excitation of ferricyanide in aqueous solution...
May 23, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28533438/high-resolution-mapping-of-crossover-events-in-the-hexaploid-wheat-genome-suggests-a-universal-recombination-mechanism
#7
Benoit Darrier, Hélène Rimbert, François Balfourier, Lise Pingault, Ambre-Aurore Josselin, Bertrand Servin, Julien Navarro, Frédéric Choulet, Etienne Paux, Pierre Sourdille
During meiosis, crossovers (COs) create new allele associations by reciprocal exchange of DNA. In bread wheat (Triticum aestivum L.), COs are almost limited to subtelomeric regions of chromosomes resulting in a substantial loss of breeding efficiency in the proximal regions though these latter carry ~60-70% of the genes. Identifying sequence and/or chromosome features impacting recombination occurrence is thus relevant to improve and drive recombination. Using the recent release of a reference sequence of chromosome 3B and of the draft assemblies of the 20 other wheat chromosomes, we performed a fine-scale mapping of COs and we revealed that 82% of COs located in the distal ends of chromosome 3B representing 19% of the chromosome length...
May 22, 2017: Genetics
https://www.readbyqxmd.com/read/28533402/behavioral-and-neural-correlates-to-multisensory-detection-of-sick-humans
#8
Christina Regenbogen, John Axelsson, Julie Lasselin, Danja K Porada, Tina Sundelin, Moa G Peter, Mats Lekander, Johan N Lundström, Mats J Olsson
Throughout human evolution, infectious diseases have been a primary cause of death. Detection of subtle cues indicating sickness and avoidance of sick conspecifics would therefore be an adaptive way of coping with an environment fraught with pathogens. This study determines how humans perceive and integrate early cues of sickness in conspecifics sampled just hours after the induction of immune system activation, and the underlying neural mechanisms for this detection. In a double-blind placebo-controlled crossover design, the immune system in 22 sample donors was transiently activated with an endotoxin injection [lipopolysaccharide (LPS)]...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533136/effect-of-artificial-pancreas-systems-on-glycaemic-control-in-patients-with-type-1-diabetes-a-systematic-review-and-meta-analysis-of-outpatient-randomised-controlled-trials
#9
Alanna Weisman, Johnny-Wei Bai, Marina Cardinez, Caroline K Kramer, Bruce A Perkins
BACKGROUND: Closed-loop artificial pancreas systems have been in development for several years, including assessment in numerous varied outpatient clinical trials. We aimed to summarise the efficacy and safety of artificial pancreas systems in outpatient settings and explore the clinical and technical factors that can affect their performance. METHODS: We did a systematic review and meta-analysis of randomised controlled trials comparing artificial pancreas systems (insulin only or insulin plus glucagon) with conventional pump therapy (continuous subcutaneous insulin infusion [CSII] with blinded continuous glucose monitoring [CGM] or unblinded sensor-augmented pump [SAP] therapy) in adults and children with type 1 diabetes...
May 19, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28533108/hyaluronidase-administered-with-xylazine-tiletamine-zolazepam-into-adipose-tissue-shortens-recovery-from-anesthesia-in-pigs
#10
Shayne P Bisetto, Adriano B Carregaro, André E S Nicolai, Thais F Bressan, William P Leal, Nathalia V Xavier, Diego F Leal, André F C Andrade
OBJECTIVE: To evaluate the effect of hyaluronidase on uptake, duration and speed of elimination of xylazine-tiletamine-zolazepam administered in the subcutaneous fat over the dorsal lumbar region of swine. STUDY DESIGN: Blinded, randomized, crossover study. ANIMALS: Six healthy Landrace/Large White pigs weighing 132±24 kg (mean±standard deviation). METHODS: Animals were administered xylazine (1 mg kg(-1)) and tiletamine-zolazepam (8 mg kg(-1)) (control treatment, CON), or xylazine-tiletamine-zolazepam at the same doses with hyaluronidase (400 IU) (treatment HYA)...
January 11, 2017: Veterinary Anaesthesia and Analgesia
https://www.readbyqxmd.com/read/28532881/preliminary-evidence-of-regional-interdependent-inhibition-using-a-diaphragm-release-to-specifically-induce-an-immediate-hypoalgesic-effect-in-the-cervical-spine
#11
Calum A McCoss, Ross Johnston, Darren J Edwards, Charles Millward
In clinical practice, Osteopaths and Manual Therapists commonly direct treatment towards the diaphragm by the use of a 'Diaphragm Release'. Currently, there is paucity within the literature to support the use of this technique, specifically in pain outcomes. This research aims to support a neurophysiological mechanism based upon the osteopathic principle "The body is a unit". Demonstrating that directing treatment to distal tissue which is neurologically related can reduce pain in the originating spinal segments...
April 2017: Journal of Bodywork and Movement Therapies
https://www.readbyqxmd.com/read/28532471/perfusion-by-arterial-spin-labelling-following-single-dose-tadalafil-in-small-vessel-disease-pastis-study-protocol-for-a-randomised-controlled-trial
#12
Mathilde M H Pauls, Natasha Clarke, Sarah Trippier, Shai Betteridge, Franklyn A Howe, Usman Khan, Christina Kruuse, Jeremy B Madigan, Barry Moynihan, Anthony C Pereira, Debbie Rolfe, Egill Rostrup, Caroline E Haig, Thomas R Barrick, Jeremy D Isaacs, Atticus H Hainsworth
BACKGROUND: Cerebral small vessel disease is a common cause of vascular cognitive impairment in older people, with no licensed treatment. Cerebral blood flow is reduced in small vessel disease. Tadalafil is a widely prescribed phosphodiesterase-5 inhibitor that increases blood flow in other vascular territories. The aim of this trial is to test the hypothesis that tadalafil increases cerebral blood flow in older people with small vessel disease. METHODS/DESIGN: Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS) is a phase II randomised double-blind crossover trial...
May 22, 2017: Trials
https://www.readbyqxmd.com/read/28530505/ingestion-of-sodium-bicarbonate-nahco3-following-a-fatiguing-bout-of-exercise-accelerates-post-exercise-acid-base-balance-recovery-and-improves-subsequent-high-intensity-cycling-time-to-exhaustion
#13
Lewis A Gough, Steven Rimmer, Callum J Osler, Matthew F Higgins
This study evaluated the ingestion of sodium bicarbonate (NaHCO3) on post-exercise acid-base balance recovery kinetics and subsequent high-intensity cycling time to exhaustion. In a counterbalanced, crossover design, nine healthy and active males (age: 23±2 years, height: 179±5 cm, body mass: 74±9 kg, peak mean minute power (WPEAK) 256±45 W, peak oxygen uptake (V̇O2PEAK) 46±8 ml.kg(-1).min(-1)) performed a graded incremental exercise test, two familiarisation and two experimental trials. Experimental trials consisted of cycling to volitional exhaustion (TLIM1) at 100% WPEAK on two occasions (TLIM1 and TLIM2) interspersed by a 90 min passive recovery period...
May 22, 2017: International Journal of Sport Nutrition and Exercise Metabolism
https://www.readbyqxmd.com/read/28530402/spin-crossover-in-double-salts-containing-six-and-four-coordinate-cobalt-ii-ions
#14
Joanna Palion-Gazda, Barbara Machura, Rafal Kruszynski, Thais Grancha, Nicolás Moliner, Francesc Lloret, Miguel Julve
The preparation and spectroscopic and structural characterization of three cobalt(II) complexes of formulas [Co(tppz)2](dca)2 (1), [Co(tppz)2][Co(NCS)4]·MeOH (2), and [Co(tppz)2][Co(NCO)4]·2H2O (3) [tppz = 2,3,5,6-tetrakis(2-pyridyl)pyrazine and dca = dicyanamide] are reported here. Compounds 1-3 have in common the presence of the cationic [Co(tppz)2](2+) entity where each mer-tridentate tppz ligand coordinates to the cobalt(II) ion equatorially through two pyridyl donors and axially via the pyrazine, completing the six-coordination...
May 22, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28528760/experimental-evaluation-of-four-airway-devices-in-anaesthetized-new-zealand-white-rabbits
#15
Sandra Wenger, Désirée Müllhaupt, Stefanie Ohlerth, Sarah Prasse, Karina Klein, Bianca da Silva Valente, Martina Mosing
OBJECTIVE: To compare airway management during induction of anaesthesia, spontaneous ventilation (SV) and controlled mechanical ventilation (CMV), using an endotracheal tube (ETT), laryngeal mask (LM), rabbit-specific supraglottic airway device (v-gel) or facemask (FM). STUDY DESIGN: Prospective randomized crossover experiment. ANIMALS: Ten New Zealand White rabbits. METHODS: After premedication, rabbits were randomly allocated to four groups: 1) ETT; 2) LM; 3) v-gel or 4) FM...
January 11, 2017: Veterinary Anaesthesia and Analgesia
https://www.readbyqxmd.com/read/28528275/it-is-not-all-bad-for-the-grey-city-a-crossover-study-on-physiological-and-psychological-restoration-in-a-forest-and-an-urban-environment
#16
Ulrika K Stigsdotter, Sus Sola Corazon, Ulrik Sidenius, Jesper Kristiansen, Patrik Grahn
Today, urbanization presents a challenge to urban planning with regard to creating healthy living environments. The aim of this research is to gain further knowledge of the restorativeness of a best case urban and natural environment: that is a historic down town urban environment and forest environment located in an arboretum. The study has a cross-over design where 51 (N) female university students are exposed to the two environments through both seated viewing and walking. A mixed method approach is used with both physiological measurements of blood pressure (BP) and heart rate variability (HRV) and psychological measurements of mood change and perceived restorativeness...
May 18, 2017: Health & Place
https://www.readbyqxmd.com/read/28527873/comparison-of-xenon-with-led-illuminant-in-difficult-and-inhalation-injury-airway-scenario-a-randomized-crossover-manikin-study
#17
Andreas Moritz, Johannes Prottengeier, Joachim Schmidt
PURPOSE: The purpose of this study was to compare the effectiveness of a Xenon halogen with a light-emitting diode (LED) laryngoscope light handle in a difficult airway scenario, as well as in an inhalation injury airway scenario that combines a difficult airway and a limited view. METHODS: We recruited forty-two anesthetists into a randomized crossover trial. Each performed tracheal intubation (TI) with a Xenon halogen and a LED light handle in the two manikin scenarios...
May 8, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28527798/short-communication-effect-of-a-citrus-extract-in-lactating-dairy-cows
#18
Y Ying, M Niu, A R Clarke, K J Harvatine
Dry matter intake is a main driver of energy balance in lactating dairy cows, and some plant extracts have been commercially fed to dairy cows to stimulate feed intake. Citrus extracts contain several bioactive components and have been shown to modify metabolism in other animal models. Our hypothesis was that a citrus extract would increase dry matter intake. Two experiments were conducted to determine the effect of a citrus extract on intake and milk production in lactating dairy cows. In experiment one, 11 early-lactation dairy cows (experiment 1; 77 ± 15 d in milk, mean ± standard deviation) were used in a switchback design, and in experiment two, 15 mid-lactation Holstein cows (experiment 2; 157 ± 44 d in milk, mean ± standard deviation) were used in a crossover design...
May 17, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28527746/sugar-restriction-leads-to-increased-ad-libitum-sugar-intake-by-overweight-adolescents-in-an-experimental-test-meal-setting
#19
Gillian A O'Reilly, David S Black, Jimi Huh, Jaimie N Davis, Jennifer Unger, Donna Spruijt-Metz
BACKGROUND: The impact of sugar restriction on subsequent sugar intake by overweight adolescents is unknown. OBJECTIVE: Our aim was to examine the effect of sugar restriction on subsequent ad libitum sugar intake by overweight adolescents and whether habitual sugar intake and impulsivity influence the effect of sugar restriction on subsequent sugar intake. DESIGN: This was an in-laboratory crossover feeding trial with sugar-exposure and sugar-restriction conditions...
May 18, 2017: Journal of the Academy of Nutrition and Dietetics
https://www.readbyqxmd.com/read/28527615/a-multicenter-randomized-trial-comparing-the-use-of-touch-versus-no-touch-guidewire-technique-for-deep-biliary-cannulation-the-tnt-study
#20
Marco Bassi, Carmelo Luigiano, Stefania Ghersi, Carlo Fabbri, Giulia Gibiino, Lucio Balzani, Giuseppe Iabichino, Alberto Tringali, Raffaele Manta, Massimiliano Mutignani, Vincenzo Cennamo
BACKGROUND AND AIMS: There are 2 techniques described for selective bile duct guidewire cannulation, the touch (T) technique (engaging the papilla with a sphincterotome and then advancing the guidewire) and the no-touch (NT) technique (engaging the papilla only with the guidewire). The aim of this prospective, multicenter randomized study was to compare the outcomes of the 2 guidewire cannulation techniques. METHODS: 300 consecutive patients with naive papillae were enrolled in 2 groups (150 to T group and 150 to NT group)...
May 17, 2017: Gastrointestinal Endoscopy
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