Vastus lateralis motor unit firing rate is higher in females with patellofemoral pain

Publication date: Available online 10 February 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Alessio Gallina, Michael A. Hunt, Paul Hodges, S. Jayne Garland
ObjectiveTo compare neural drive, determined from motor unit firing rate, to the vastus medialis and lateralis in females with and without patellofemoral pain.DesignCross-sectional study.SettingUniversity research laboratory.ParticipantsFemales (N=56) 19-35 years old, 36 with patellofemoral pain and 20 controls. Interventions: Not applicable.Main Outcome Measure(s)Participants sustained an isometric knee extension contraction at 10% of their maximal voluntary effort for 70s. Motor units (N=414) were identified using high-density surface electromyography. Average firing rate was calculated between 5 and 35s after recruitment for each motor unit. Initial firing rate was the inverse of the first three motor unit inter-spike intervals.ResultsIn control participants, vastus medialis motor units discharged at higher rates than vastus lateralis (p=0.001). This was not observed in females with patellofemoral pain (p=0.78) due to a higher discharge rate of vastus lateralis compared to control participants (p=0.002). No between-group differences were observed for vastus medialis (p=0.93). Similar results were obtained for the initial motor unit firing rate.ConclusionsThese findings suggest that females with patellofemoral pain have a higher neural drive to vastus lateralis but not vastus medialis, which may be a contributor of the altered patellar kinematics observed in some studies. The different neural drive may be an adaptation to patellofemoral pain, possibly to compensate for decreased quadriceps force production, or a precursor of patellofemoral pain.



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The clinical assessment of spasticity in people with spinal cord damage: recommendations from the Ability Network, an international initiative

Publication date: Available online 10 February 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Anand V. Nene, Alexandre Rainha Campos, Klemen Grabljevec, Arminda Lopes, Bengt Skoog, Anthony S. Burns
A thorough assessment of the extent and severity of spasticity, and its impact on functioning, is central to the effective management of spasticity in persons with spinal cord damage (SCD). These individuals, however, do not always receive adequate assessment of their spasticity. Inadequate assessment compromises management when the impact of spasticity and/or need for intervention are not fully recognized. Assessment is also central to determining treatment efficacy. A barrier to spasticity assessment has been the lack of consensus on clinical and functional measures suitable for routine clinical practice. To extend upon existing work, a working group of the Ability Network identified and consolidated information on possible measures, then synthesized and formulated findings into practical recommendations for assessing spasticity and its impact on function in persons with SCD. Sixteen clinical and functional measures that have been used for this purpose were identified using a targeted literature review. These were mapped to the relevant domains of the International Classification of Functioning, Disability and Health (ICF) to assess the breadth of their coverage; coverage of many domains was found to be lacking, suggesting a focus for future work. The advantages, disadvantages and usefulness of the measures were assessed using a range of criteria, with a focus on usefulness and feasibility in routine clinical practice. Based on this evaluation, a selection of measures suitable for initial and follow-up assessments are recommended. The recommendations are intended to have broad applicability to a variety of healthcare settings where people with SCD are managed.



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Screening for Abdominal Aortic Aneurysm During Transthoracic Echocardiography: A Systematic Review and Meta-analysis

Publication date: Available online 9 February 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Christos Argyriou, George S. Georgiadis, Nikolaos Kontopodis, Arun D. Pherwani, Joost A. Van Herwaarden, Constantijn E.V.B. Hazenberg, George A. Antoniou
BackgroundScreening for abdominal aortic aneurysm (AAA) during transthoracic echocardiography (TTE) may be an effective targeted screening strategy.ObjectiveThe aim was to assess the feasibility of AAA screening during TTE and to estimate the prevalence of AAA in patients undergoing TTE.MethodsElectronic bibliographic sources were interrogated using a combination of free text and controlled vocabulary searches to identify studies reporting on AAA screening during TTE. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards. Fixed effect or random effects models were used to calculate pooled prevalence estimates.ResultsTwenty observational cohort studies were identified reporting a total of 43,341 participants (23,291 men and 20,050 women). Hypertension was reported in 41% (95% CI 38–43), hypercholesterolemia in 31% (95% CI 29–32), diabetes mellitus in 20% (95% CI 19–22), and tobacco use in 37% (95% CI 35–38). The aorta was visualised in 86% (95% CI 84–88) of the screened population. The pooled prevalence of AAA in the entire screened population was 0.033 (95% CI 0.024–0.044). The pooled prevalence of AAA in men was 0.046 (95% CI 0.032–0.065) and in women it was 0.014 (95% CI 0.008–0.022). The mean age of participants in whom an AAA was detected ranged across the studies from 66 to 85 years. The mean diameter of the aneurysm identified ranged across the studies from 35 mm to 45 mm. Clinical outcomes in participants with a detected AAA were poorly reported.ConclusionsScreening for AAA during TTE may identify a population group with a high risk of AAA in whom targeted screening may be beneficial. Further research is required to investigate the cost-effectiveness and clinical benefits of AAA screening in this setting.



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The Marburg-Münster Affective Disorders Cohort Study (MACS): A quality assurance protocol for MR neuroimaging data

Publication date: 15 May 2018
Source:NeuroImage, Volume 172
Author(s): Christoph Vogelbacher, Thomas W.D. Möbius, Jens Sommer, Verena Schuster, Udo Dannlowski, Tilo Kircher, Astrid Dempfle, Andreas Jansen, Miriam H.A. Bopp
Large, longitudinal, multi-center MR neuroimaging studies require comprehensive quality assurance (QA) protocols for assessing the general quality of the compiled data, indicating potential malfunctions in the scanning equipment, and evaluating inter-site differences that need to be accounted for in subsequent analyses.We describe the implementation of a QA protocol for functional magnet resonance imaging (fMRI) data based on the regular measurement of an MRI phantom and an extensive variety of currently published QA statistics. The protocol is implemented in the MACS (Marburg-Münster Affective Disorders Cohort Study, http://for2107.de/), a two-center research consortium studying the neurobiological foundations of affective disorders. Between February 2015 and October 2016, 1214 phantom measurements have been acquired using a standard fMRI protocol. Using 444 healthy control subjects which have been measured between 2014 and 2016 in the cohort, we investigate the extent of between-site differences in contrast to the dependence on subject-specific covariates (age and sex) for structural MRI, fMRI, and diffusion tensor imaging (DTI) data.We show that most of the presented QA statistics differ severely not only between the two scanners used for the cohort but also between experimental settings (e.g. hardware and software changes), demonstrate that some of these statistics depend on external variables (e.g. time of day, temperature), highlight their strong dependence on proper handling of the MRI phantom, and show how the use of a phantom holder may balance this dependence. Site effects, however, do not only exist for the phantom data, but also for human MRI data. Using T1-weighted structural images, we show that total intracranial (TIV), grey matter (GMV), and white matter (WMV) volumes significantly differ between the MR scanners, showing large effect sizes. Voxel-based morphometry (VBM) analyses show that these structural differences observed between scanners are most pronounced in the bilateral basal ganglia, thalamus, and posterior regions. Using DTI data, we also show that fractional anisotropy (FA) differs between sites in almost all regions assessed. When pooling data from multiple centers, our data show that it is a necessity to account not only for inter-site differences but also for hardware and software changes of the scanning equipment. Also, the strong dependence of the QA statistics on the reliable placement of the MRI phantom shows that the use of a phantom holder is recommended to reduce the variance of the QA statistics and thus to increase the probability of detecting potential scanner malfunctions.



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Triple representation of language, working memory, social and emotion processing in the cerebellum: convergent evidence from task and seed-based resting-state fMRI analyses in a single large cohort

Publication date: 15 May 2018
Source:NeuroImage, Volume 172
Author(s): Xavier Guell, John D.E. Gabrieli, Jeremy D. Schmahmann
Delineation of functional topography is critical to the evolving understanding of the cerebellum's role in a wide range of nervous system functions. We used data from the Human Connectome Project (n = 787) to analyze cerebellar fMRI task activation (motor, working memory, language, social and emotion processing) and resting-state functional connectivity calculated from cerebral cortical seeds corresponding to the peak Cohen's d of each task contrast. The combination of exceptional statistical power, activation from both motor and multiple non-motor tasks in the same participants, and convergent resting-state networks in the same participants revealed novel aspects of the functional topography of the human cerebellum. Consistent with prior studies there were two distinct representations of motor activation. Newly revealed were three distinct representations each for working memory, language, social, and emotional task processing that were largely separate for these four cognitive and affective domains. In most cases, the task-based activations and the corresponding resting-network correlations were congruent in identifying the two motor representations and the three non-motor representations that were unique to working memory, language, social cognition, and emotion. The definitive localization and characterization of distinct triple representations for cognition and emotion task processing in the cerebellum opens up new basic science questions as to why there are triple representations (what different functions are enabled by the different representations?) and new clinical questions (what are the differing consequences of lesions to the different representations?).



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Alter spontaneous activity in amygdala and vmPFC during fear consolidation following 24 h sleep deprivation

Publication date: 15 May 2018
Source:NeuroImage, Volume 172
Author(s): Pan Feng, Benjamin Becker, Tingyong Feng, Yong Zheng
Sleep deprivation (SD) has been associated with cognitive and emotional disruptions, however its impact on the acquisition of fear and subsequent fear memory consolidation remain unknown. To address this question, we measured human brain activity before and after fear acquisition under conditions of 24 h sleep deprivation versus normal sleep using resting-state functional magnetic resonance imaging (rs-fMRI). Additionally, we explored whether the fear acquisition-induced change of brain activity during the fear memory consolidation window can be predicted by subjective fear ratings and autonomic fear response, assessed by skin conductance responses (SCR) during acquisition. Behaviorally, the SD group demonstrated increased subjective and autonomic fear responses compared to controls at the stage of fear acquisition. During the stage of fear consolidation, the SD group displayed decreased ventromedial prefrontal cortex (vmPFC) activity and concomitantly increased amygdala activity. Moreover, in the SD group fear acquisition-induced brain activity changes in amygdala were positively correlated with both, subjective and autonomic fear indices during acquisition, whereas in controls changes vmPFC activity were positively correlated with fear indices during acquisition. Together, the present findings suggested that SD may weaken the top-down ability of the vmPFC to regulate amygdala activity during fear memory consolidation. Moreover, subjective and objective fear at fear acquisition stage can predict the change of brain activity in amygdala in fear memory consolidation following SD.



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Probing biological activity through structural modelling of ligand-receptor interactions of 2,4-disubstituted thiazole retinoids

Publication date: Available online 10 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Hesham Haffez, David R. Chisholm, Natalie J. Tatum, Roy Valentine, Christopher Redfern, Ehmke Pohl, Andrew Whiting, Stefan Przyborski
Retinoids, such as all-trans-retinoic acid (ATRA), regulate cellular differentiation and signalling pathways in chordates by binding to nuclear retinoic acid receptors (RARα/β/γ). Polar interactions between receptor and ligand are important for binding and facilitating the non-polar interactions and conformational changes necessary for RAR-mediated transcriptional regulation. The constraints on activity and RAR-type specificity with respect to the structural link between the polar and non-polar functions of synthetic retinoids are poorly understood. To address this, predictions from in silico ligand-RAR docking calculations and molecular dynamics simulations for a small library of stable, synthetic retinoids (designated GZ series) containing a central thiazole linker structure and different hydrophobic region substituents, were tested using a ligand binding assay and a range of cellular biological assays. The docking analysis showed that these thiazole-containing retinoids were well suited to the binding pocket of RARα, particularly via a favorable hydrogen bonding interaction between the thiazole and Ser232 of RARα. A bulky hydrophobic region (i.e., present in compounds GZ23 and GZ25) was important for interaction with the RAR binding pockets. Ligand binding assays generally reflected the findings from in silico docking, and showed that GZ25 was a particularly strongly binding ligand for RARα/β. GZ25 also exhibited higher activity as an inducer of neuronal differentiation than ATRA and other GZ derivatives. These data demonstrate that GZ25 is a stable synthetic retinoid with improved activity which efficiently regulates neuronal differentiation and help to define the key structural requirements for retinoid activity enabling the design and development of the next generation of more active, selective synthetic retinoids as potential therapeutic regulators of neurogenesis.

Graphical abstract

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Design and synthesis of estrogen receptor ligands with a 4-heterocycle-4-phenylheptane skeleton

Publication date: Available online 9 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Ryo Eto, Takashi Misawa, Tomomi Noguchi-Yachide, Nobumichi Ohoka, Masaaki Kurihara, Mikihiko Naito, Masakazu Tanaka, Yosuke Demizu
The estrogen receptor (ER), a member of the nuclear receptor (NR) family, is involved in the regulation of physiological effects such as reproduction and bone homeostasis. Approximately 70% of human breast cancers are hormone-dependent and ERα-positive, and, thus, ER antagonists are broadly used in breast cancer therapy. We herein designed and synthesized a set of ER antagonists with a 4-heterocycle-4-phenylheptane skeleton.

Graphical abstract

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Design and Synthesis of 1-(1-Benzothiophen-7-yl)-1H-Pyrazole, a Novel Series of G Protein-coupled Receptor 52 (GPR52) Agonists

Publication date: Available online 10 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Takashi Nakahata, Kazuyuki Tokumaru, Yoshiteru Ito, Naoki Ishii, Masaki Setoh, Yuji Shimizu, Toshiya Harasawa, Kazunobu Aoyama, Teruki Hamada, Masakuni Kori, Kazuyoshi Aso
G-protein-coupled receptor 52 (GPR52) is classified as an orphan Gs-coupled G-protein-coupled receptor. GPR52 cancels dopamine D2 receptor signaling and activates dopamine D1/N-methyl-D-aspartate receptors via intracellular cAMP accumulation. Therefore, GPR52 agonists are expected to alleviate symptoms of psychotic disorders. A novel series of 1-(benzothiophen-7-yl)-1H-pyrazole as GPR52 agonists was designed and synthesized based on compound 1b. Compound 1b has been reported by our group as the first orally active GPR52 agonist, but high lipophilicity and poor aqueous solubility still remained as issues for candidate selection. To resolve these issues, replacement of the benzene ring at the 7-positon of compound 1b with heterocylic rings, such as pyrazole and pyridine, was greatly expected to reduce lipophilicity to levels for which calculated logD values were lower than that of compound 1b. While evaluating the pyrazole derivatives, introduction of a methyl substituent at the 3-position of the pyrazole ring led to increased GPR52 agonistic activity. Moreover, additional methyl substituent at the 5-position of the pyrazole and further introduction of hydroxy group to lower logD led to significant improvement of solubility while maintaining the activity. As a result, we identified 3-methyl-5-hydroxymethyl-1H-pyrazole derivative 17 (GPR52 EC50 = 21 nM, Emax = 103%, logD = 2.21, Solubility at pH 6.8 = 21 μg/mL) with potent GPR52 agonistic activity and good solubility compared to compound 1b. Furthermore, this compound 17 dose-dependently suppressed methamphetamine-induced hyperlocomotion in mice.

Graphical abstract

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Suspended particulate matter determines physical speciation of Fe, Mn , and trace metals in surface waters of Loire watershed

Abstract

This study investigates the spatiotemporal variability of major and trace elements, dissolved organic carbon (DOC), total dissolved solids (TDS), and suspended particulate matter (SPM) in surface waters of several hydrosystems of the Loire River watershed in France. In particular, this study aims to delineate the impact of the abovementioned water physicochemical parameters on natural iron and manganese physical speciation (homoaggregation/heteroaggregation) among fine colloidal and dissolved (< 10 nm), colloidal (10–450 nm) and particulate (> 450 nm) phases in Loire River watershed. Results show that the chemistry of the Loire River watershed is controlled by two end members: magmatic and metamorphic petrographic context on the upper part of the watershed; and sedimentary rocks for the middle and low part of the Loire. The percentage of particulate Fe and Mn increased downstream concurrent with the increase in SPM and major cations concentration, whereas the percentage of colloidal Fe and Mn decreased downstream. Transmission electron microscopy analyses of the colloidal and particulate fractions (from the non-filtered water sample) revealed that heteroaggregation of Fe and Mn rich natural nanoparticles and natural organic matter to the particulate phase is the dominant mechanism. The heteroaggregation controls the partitioning of Fe and Mn in the different fractions, potentially due to the increase in the ionic strength, and divalent cations concentration downstream, and SPM concentration. These findings imply that SPM concentration plays an important role in controlling the fate and behavior of Fe and Mn in various sized fractions.

Graphical abstract

Physical speciation by heteroaggregation of (Fe-Mn) compounds: high [SPM] → [Fe-Mn] particulate faction; low {SPM] → [Fe-Mn] colloid-dissolved fraction.

http://ift.tt/2EvacNb

Use of meta-analyses and joint analyses to select variants in whole genome sequences for genomic evaluation: An application in milk production of French dairy cattle breeds

Publication date: Available online 7 February 2018
Source:Journal of Dairy Science
Author(s): M. Teissier, M.P. Sanchez, M. Boussaha, A. Barbat, C. Hoze, C. Robert-Granie, P. Croiseau
As a result of the 1000 Bull Genome Project, it has become possible to impute millions of variants, with many of these potentially causative for traits of interest, for thousands of animals that have been genotyped with medium-density chips. This enormous source of data opens up very interesting possibilities for the inclusion of these variants in genomic evaluations. However, for computational reasons, it is not possible to include all variants in genomic evaluation procedures. One potential approach could be to select the most relevant variants based on the results of genome-wide association studies (GWAS); however, the identification of causative mutations is still difficult with this method, partly because of weak imputation accuracy for rare variants. To address this problem, this study assesses the ability of different approaches based on multi-breed GWAS (joint and meta-analyses) to identify single-nucleotide polymorphisms (SNP) for use in genomic evaluation in the 3 main French dairy cattle breeds. A total of 6,262 Holstein bulls, 2,434 Montbéliarde bulls, and 2,175 Normande bulls with daughter yield deviations for 5 milk production traits were imputed for 27 million variants. Within-breed and joint (including all 3 breeds) GWAS were performed and 3 models of meta-analysis were tested: fixed effect, random effect, and Z-score. Comparison of the results of within- and multi-breed GWAS showed that most of the quantitative trait loci identified using within-breed approaches were also found with multi-breed methods. However, the most significant variants identified in each region differed depending on the method used. To determine which approach highlighted the most predictive SNP for each trait, we used a marker-assisted best unbiased linear prediction model to evaluate lists of SNP generated by the different GWAS methods; each list contained between 25 and 2,000 candidate variants per trait, which were identified using a single within- or multi-breed GWAS approach. Among all the multi-breed methods tested in this study, variant selection based on meta-analysis (fixed effect) resulted in the most-accurate genomic evaluation (+1 to +3 points compared with other multi-breed approaches). However, the accuracies of genomic evaluation were always better when variants were selected using the results of within-breed GWAS. As has generally been found in studies of quantitative trait loci, these results suggest that part of the genetic variance of milk production traits is breed specific in Holstein, Montbéliarde, and Normande cattle.



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An Overview of the Emerging Interface Between Cardiac Metabolism, Redox Biology and the Circadian Clock

Publication date: Available online 10 February 2018
Source:Free Radical Biology and Medicine
Author(s): Rodrigo A. Peliciari-Garcia, Victor Darley-Usmar, Martin E. Young
At various biological levels, mammals must integrate with 24-hr rhythms in their environment. Daily fluctuations in stimuli/stressors of cardiac metabolism and oxidation-reduction (redox) status have been reported over the course of the day. It is therefore not surprising that the heart exhibits dramatic oscillations in various cellular processes over the course of the day, including transcription, translation, ion homeostasis, metabolism, and redox signaling. This temporal partitioning of cardiac processes is governed by a complex interplay between intracellular (e.g., circadian clocks) and extracellular (e.g., neurohumoral factors) influences, thus ensuring appropriate responses to daily stimuli/stresses. The purpose of the current article is to review knowledge regarding control of metabolism and redox biology in the heart over the course of the day, and to highlight whether disruption of these daily rhythms contribute towards cardiac dysfunction observed in various disease states.

Graphical abstract

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Mitochondrial protein S-nitrosation protects against ischemia reperfusion-induced denervation at neuromuscular junction in skeletal muscle

Publication date: Available online 9 February 2018
Source:Free Radical Biology and Medicine
Author(s): Rebecca J. Wilson, Joshua C. Drake, Di Cui, Bevan M. Lewellen, Carleigh C. Fisher, Mei Zhang, David F. Kashatus, Lisa A. Palmer, Michael P. Murphy, Zhen Yan
Deterioration of neuromuscular junction (NMJ) integrity and function is causal to muscle atrophy and frailty, ultimately hindering quality of life and increasing the risk of death. In particular, NMJ is vulnerable to ischemia reperfusion (IR) injury when blood flow is restricted followed by restoration. However, little is known about the underlying mechanism(s) and hence the lack of effective interventions. New evidence suggests that mitochondrial oxidative stress plays a causal role in IR injury, which can be precluded by enhancing mitochondrial protein S-nitrosation (SNO). To elucidate the role of IR and mitochondrial protein SNO in skeletal muscle, we utilized a clinically relevant model and showed that IR resulted in significant muscle and motor nerve injuries with evidence of elevated muscle creatine kinase in the serum, denervation at NMJ, myofiber degeneration and regeneration, as well as muscle atrophy. Interestingly, we observed that neuromuscular transmission improved prior to muscle recovery, suggesting the importance of the motor nerve in muscle functional recovery. Injection of a mitochondria-targeted S-nitrosation enhancing agent, MitoSNO, into ischemic muscle prior to reperfusion reduced mitochondrial oxidative stress in the motor nerve and NMJ, attenuated denervation at NMJ, and resulted in accelerated functional recovery of the muscle. These findings demonstrate that enhancing mitochondrial protein SNO protects against IR-induced denervation at NMJ in skeletal muscle and accelerates functional regeneration. This could be an efficacious intervention for protecting neuromuscular injury under the condition of IR and other related pathological conditions.

Graphical abstract

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Health risk assessment of drinking arsenic-containing groundwater in Hasilpur, Pakistan: effect of sampling area, depth, and source

Abstract

Currently, several news channels and research publications have highlighted the dilemma of arsenic (As)-contaminated groundwater in Pakistan. However, there is lack of data regarding groundwater As content of various areas in Pakistan. The present study evaluated As contamination and associated health risks in previously unexplored groundwater of Hasilpur-Pakistan. Total of 61 groundwater samples were collected from different areas (rural and urban), sources (electric pump, hand pump, and tubewell) and depths (35–430 ft or 11–131 m). The water samples were analyzed for As level and other parameters such as pH, electrical conductivity, total dissolved solids, cations, and anions. It was found that 41% (25 out of 61) water samples contained As (≥ 5 μg/L). Out of 25 As-contaminated water samples, 13 water samples exceeded the permissible level of WHO (10 μg/L). High As contents have been found in tubewell samples and at high sampling depths (> 300 ft). The major As-contaminated groundwater in Hasilpur is found in urban areas. Furthermore, health risk and cancer risk due to As contamination were also assessed with respect to average daily dose (ADD), hazard quotient (HQ), and carcinogenic risk (CR). The values of HQ and CR of As in Hasilpur were up to 58 and 0.00231, respectively. Multivariate analysis revealed a positive correlation between groundwater As contents, pH, and depth in Hasilpur. The current study proposed the proper monitoring and management of well water in Hasilpur to minimize the As-associated health hazards.

http://ift.tt/2BQxCM9

Glucosensing capacity of rainbow trout telencephalon

Abstract

To assess the hypothesis of glucosensing systems present in fish telencephalon, we first demonstrated in rainbow trout by in situ hybridization the presence of glucokinase (GK). Then, we assessed the response of glucosensing markers in rainbow trout telencephalon 6h after ICV treatment with glucose or 2-deoxyglucose (inducing glucoprivation). We evaluated the response of parameters related to the mechanisms dependent on GK, liver X receptor (LXR), mitochondrial activity, sweet taste receptor, and sodium-glucose linked transporter 1 (SGLT-1). We also assessed mRNA abundance of neuropeptides involved in the metabolic control of food intake (NPY, AgRP, POMC, and CART) as well as abundance and phosphorylation status of proteins possibly involved in linking glucosensing with neuropeptide expression such as Akt, AMPK, mTOR, and CREB. The responses obtained support the presence in telencephalon of a glucosensing mechanism based on GK and maybe one based on LXR, but do not support the presence of mechanisms dependent on mitochondrial activity and SGLT-1. The mechanism based on sweet taste receptor responded to glucose, but in a converse way to that characterized previously in hypothalamus. In general, systems responded only to glucose, but not to glucoprivation. Neuropeptides did not respond to glucose or glucoprivation. In contrast, the presence of glucose activates Akt and inhibits AMPK, CREB, and FoxO1. This is the first study in any vertebrate species in which the response to glucose of putative glucosensing mechanisms is demonstrated in telencephalon. Their role might relate to processes other than homeostatic control of food intake such as the hedonic and reward system.

This article is protected by copyright. All rights reserved.

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Hepatic heterogeneity and attenuation on contrast-enhanced CT in patients with the hypovolemic shock complex: Objective classification using a contemporary cohort

Publication date: Available online 10 February 2018
Source:Current Problems in Diagnostic Radiology
Author(s): Benjamin Wildman-Tobriner, Michael S. Enslow, Rendon C. Nelson
ObjectiveWhen objectively measured on computed tomography (CT), does either hepatic heterogeneity or overall liver attenuation predict the presence of shock?MethodsThis retrospective study included 73 patients (mean age 33 years) with the hypoperfusion shock complex (HSC) on CT (cases) and 100 patients (mean age 43 years) with negative trauma CT scans (controls). Liver heterogeneity was calculated by using consistently sized regions of interest (ROIs) to measure the 2 highest and 2 lowest areas of hepatic density (in Hounsfield units [HU]). The difference between the means of the 2 highest and 2 lowest ROIs was considered the heterogeneity. Attenuation was calculated using the mean of 3 randomly placed ROIs. Both heterogeneity and attenuation were then compared between cases and controls.ResultsMedian hepatic heterogeneity was 16.8 HU (IQR 10.7–23.4) for the HSC group and 9.0 HU (IQR 7.0–10.4) for the controls (p<0.001). The area under the curve was 0.79, and a threshold of 30 HU yielded a specificity of 100%. Median hepatic attenuation was not significantly different between the HSC and control groups, with an area under the curve of 0.56.ConclusionsIncreased hepatic heterogeneity may represent an objective marker of the HSC that performs similarly to other established signs. By comparison, overall hepatic hypoattenuation is a poor indicator of the HSC.



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A case of a primary hepatic so-called adenosarcoma with heterotopic ossification: possibly of biliary adenofibroma origin

Publication date: March 2018
Source:Human Pathology, Volume 73
Author(s): Shiori Meguro, Satoru Yamazaki, Sayomi Matsushima, Kazuhito Kawata, Hideya Kawasaki, Takashi Tsuchida, Isao Kosugi, Yoshimasa Kobayashi, Satoshi Baba, Toshihide Iwashita
We present an autopsy case of a "so-called adenosarcoma with ossification of the liver" in a 63-year-old man. Macroscopically, the well-circumscribed tumor with portal vein invasion was observed in the right lobe of the liver. The cut surface of the tumor had a solid and microcystic appearance. Microscopically, the tumor was characterized by a benign epithelial component and a malignant mesenchymal component. We believe the presence of biliary adenofibroma–like areas and the von Meyenburg complexes suggests that the tumor is possibly associated with a biliary adenofibroma. In addition, the present tumor was unique in that it showed scattered heterotopic ossification. Immunohistochemical study showed that the mesenchymal atypical spindle cells had characteristics of undifferentiated mesenchymal cells. This is the first report of a primary hepatic so-called adenosarcoma.



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Expression of MDM2 and p16 in Angiomyolipoma

Publication date: Available online 10 February 2018
Source:Human Pathology
Author(s): Xiaoqi Lin, William B. Laskin, Xinyan Lu, Yaxia Zhang
Angiomyolipoma (AML) arises primarily from the kidney, but may grow into the retroperitoneal space mimicking a primary retroperitoneal tumor. Fine needle aspiration (FNA) and core needle biopsy (CNB) of AML, particularly the fat-predominant variant, may be difficult to distinguish from retroperitoneal well-differentiated liposarcoma (WDLS) or lipoma. Commonly used immunomarkers, MDM2 and p16, have proven useful in diagnosing WDLS and dedifferentiated liposarcoma (DDLS), while HMB45 and Melan-A are melanocyte-related markers characteristically expressed in AML. In this study, we investigated the utility of MDM2 and p16 along with HMB45 and Melan-A immunohistochemical analysis in distinguishing AML from WDL/DDLS or lipoma. Immunohistochemically, AMLs demonstrated focal MDM2 expression (40% of cases) and focal/diffuse expression of p16 (60%). AMLs marked focally or diffusely with HMB45 (76% of cases) and Melan-A (96%). These latter two immunomarkers were not expressed in any of the WDLS/DDLSs or lipomas tested. WDLS/DDLSs showed focal/diffuse expression of MDM2 (91% of cases) and p16 (97%). While focal expression of MDM2 and p16 was observed in14% and 67% of lipomas, respectively, no lipoma exhibited diffuse MDM2 positivity. In our hands, MDM2 expression by itself cannot exclude the diagnosis of AML or lipoma, and p16 alone is not helpful in separating AML and conventional lipoma from WDLS/DDLS. However, along with morphology, an immunohistochemical battery including HMB45, Melan-A, MDM2 and p16 are useful in distinguishing AML from WDLS/DDLS or lipoma. For equivocal cases, fluorescence in situ hybridization for MDM2 should be performed.



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Scholar : These new articles for Amyloid are available online

The online platform for Taylor & Francis Online content New for Amyloid and online now on Taylor & Francis Online: Original Article Monoclonal gammopathy of undetermined significance in systemic transthyretin amyloidosis (ATTR) Pooja Phull, Vaishali Sanchorawala, Lawreen H. Connors, Gheorghe Doros, Frederick L. Ruberg, John L. Berk & Shayna Sarosiek Pages: 1-6 | DOI: 10.1080/13506129.2018.1436048 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for Creative Industries Journal are available online

The online platform for Taylor & Francis Online content New for Creative Industries Journal and online now on Taylor & Francis Online: Original Articles Assessing creativity: an index proposal Antonio Castro-Higueras & Miguel de Aguilera-Moyano Pages: 1-17 | DOI: 10.1080/17510694.2018.1434371 Browse this free access collection on: Communication, Media and Culture in Asia. To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Phosphorus sorption capacity of biochars varies with biochar type and salinity level

Abstract

Biochar is recognized as an effective material for recovering excess nutrients, including phosphorus (P), from aqueous solutions. Practically, that benefits the environment through reducing P losses from biochar-amended soils; however, how salinity influences P sorption by biochar is poorly understood and there has been no direct comparison on P sorption capacity between biochars derived from different feedstock types under non-saline and saline conditions. In this study, biochars derived from wheat straw, hardwood, and willow wood were used to compare P sorption at three levels of electrical conductivity (EC) (0, 4, and 8 dS m⁻¹) to represent a wide range of salinity conditions. Phosphorus sorption by wheat straw and hardwood biochars increased as aqueous solution P concentration increased, with willow wood biochar exhibiting an opposite trend for P sorption. However, the pattern for P sorption became the same as the other biochars after the willow wood biochar was de-ashed with 1 M HCl and 0.05 M HF. Willow wood biochar had the highest P sorption (1.93 mg g⁻¹) followed by hardwood (1.20 mg g⁻¹) and wheat straw biochars (1.06 mg g⁻¹) in a 25 mg L⁻¹ P solution. Although the pH in the equilibrium solution was higher with willow wood biochar (~ 9.5) than with the other two biochars (~ 6.5), solution pH had no or minor effects on P sorption by willow wood biochar. The high sorption rate of P by willow wood biochar could be attributed to the higher concentrations of salt and other elements (i.e., Ca and Mg) in the biochar in comparison to that in wheat straw and hardwood biochars; the EC values were 2.27, 0.53, and 0.27 dS m⁻¹ for willow wood, wheat straw, and hardwood biochars, respectively. A portion of P desorbed from the willow wood biochar; and that desorption increased with the decreasing P concentration in the aqueous solution. Salinity in the aqueous solution influenced P sorption by hardwood and willow wood but not by wheat straw biochar. We conclude that the P sorption capacity of the studied biochars is dependent on the concentration of the soluble element in the biochar, which is dependent on the biochar type, as well as the salinity level in the aqueous solution.

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Distribution of phosphorous pools in western river sediments of the Urmia Lake basin, Iran

Abstract

Impact of anthropogenic loading of phosphorous (P) to an aquatic ecosystem can be qualitatively assessed by measuring the buildup and distribution of P in sediments and by differentiating bioavailable and recalcitrant P pools. Distribution of P pools in sediments is affected by the physico-chemical properties including specific elements, particle size distribution, pH, electrical conductivity (EC), and carbonate content. We applied X-ray fluorescence and scanning electron microscopy (SEM) methods to characterize sediments from western rivers in the Urmia Lake basin in Iran with a particular focus on properties that are relevant to P speciation. Phosphorous pools were sequentially extracted into operationally defined exchangeable (EXCH-P), iron and aluminum oxide-bound (Fe/Al-P), calcium-bound (Ca-P), and residual (RES-P) P pools. In river sediments, the size of P pool was found to be in the order of Ca-P > RES-P > Fe/Al-P > EXCH-P indicating small fraction of bioavailable P pool and Ca-P minerals being the most dominant P sink. Carbonate-related properties had an inverse relationship with bioavailable P pools in the river sediments studied. The principal component analysis (PCA) of the sequential extraction data with sediment properties revealed that four principal components described 82.7% of total variation. Similarly, particle size-related properties were found to have the highest eigenvalues in the first PC. Electron diffraction spectra (EDS) and X-ray fluorescence (XRF) analyses showed a largely uniform distribution of P in the upstream sediment. However, limited evidence of local enrichment of P with Fe, Al, and Ca contents was observed in the downstream river sediments. Correlation of Fe/Al-P pool size with Al₂O₃ and SiO₂ contents indicated that P was associated with Al oxide and clay minerals in the sediment matrix. Overall, the results from this study provide insights into the variability of upstream and downstream river processes and their relationship with P pools with regard to their bioavailability. These results are expected to be useful in assessing the potential impact of P loading on the aquatic ecosystem in the Urmia Lake basin.

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Behaviour and risk assessment of fluopyram and its metabolite in cucumber ( Cucumis sativus ) fruit and in soil

Abstract

A field experiment was conducted to estimate residue persistence of fluopyram and its metabolite benzamide in cucumber fruits and soil and their risk assessment in humans and soil environment. Fluopyram (Kafka, 400 SC) was applied as soil drench twice at the interval of 15 days at the rate of 250 (standard dose) and 500 (double dose) g a.i. ha⁻¹ (active ingredient per hectare). Cucumber fruits were collected at 0 (1 h), 1, 3, 5, 7, 10, 15, 20, 30, 40 and 50 days after second application. Soil samples were collected on 15th day after second application. Drench application resulted in detection of residues on the third day in standard dose at the levels of 0.056 mg kg⁻¹ in cucumber fruit. The residue level increased until 20 days reaching 0.092 mg kg⁻¹ followed by decrease to 0.068 mg kg⁻¹ on 30th day after application. In double dose, the residues started accumulating from 0 day with initial levels of 0.093 mg kg⁻¹ and persisted until 30th day. The levels varied between 0.123 and 0.184 mg kg⁻¹ until 15th day of application followed by decrease to 0.127 mg kg⁻¹ by 30th day. The residues reached below determination level (< 0.05 mg kg⁻¹) on 40th day in both the doses after second application. The residue of metabolite benzamide was below determination level (< 0.05 mg kg⁻¹) at both the doses. Hazard quotient (HQ) for residues levels at 15th and 30th day was less than one (HQ < 1). Hence, a pre-harvest interval of 15 days is suggested. Present data can be used to establish maximum residue limit (MRL) in India. The residue of fluopyram in soil on 15th day and the data on soil adsorption coefficient of fluopyram from literature suggests moderate mobility of fluopyram in soil. However, residues of metabolite of benzamide were not detected in soil. Further studies on translocation of fluopyram in soil over the time can be conducted for better understanding of environmental risk. To our knowledge, this is the first report on residue levels of fluopyram in any crop when applied as soil drench.

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Efficacy of neurokinin-1 receptor antagonists in the prevention of chemotherapy-induced nausea and vomiting in patients receiving carboplatin-based chemotherapy: A systematic review and meta-analysis

Publication date: April 2018
Source:Critical Reviews in Oncology/Hematology, Volume 124
Author(s): Massimo Di Maio, Chiara Baratelli, Paolo Bironzo, Francesca Vignani, Emilio Bria, Elisa Sperti, Maddalena Marcato, Fausto Roila
According to current ESMO – MASCC guidelines, a combination of a neurokinin-1 receptor antagonist (NK1RA), dexamethasone and a 5-HT3 receptor antagonist (5-HT3RA) is recommended to prevent carboplatin-induced emesis, albeit with moderate level of confidence and not unanimous consensus. We performed a meta-analysis of randomized trials (RCTs) comparing NK1RA + dexamethasone + 5-HT3RA vs. dexamethasone + 5-HT3RA in patients receiving the first cycle of carboplatin-based chemotherapy. Primary outcome was complete response (CR), defined as no emesis and no use of rescue medication. 9 trials were eligible, and data of CR were available from 8 trials (1598 patients). Addition of NK1RA improves CR in all phases: acute phase, 94.5% vs. 90.1%; delayed phase, 76.4% vs. 61.7%; overall period, 75.3% vs. 60.4%. There was no significant heterogeneity among trials. In patients receiving carboplatin-based chemotherapy, the addition of NK1RA to dexamethasone and 5-HT3RA is associated with a statistically significant and clinically relevant improvement in CR.



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Dataset on predictive compressive strength model for self-compacting concrete

Publication date: Available online 9 February 2018
Source:Data in Brief
Author(s): O.M. Ofuyatan, S.O. Edeki
The determination of compressive strength is affected by many variables such as the water cement (WC) ratio, the superplasticizer (SP), the aggregate combination, and the binder combination. In this dataset article, 7, 28, and 90-day compressive strength models are derived using statistical analysis. The response surface methodology is used toinvestigate the effect of the parameters: Varying percentages of ash, cement, WC, and SP on hardened properties-compressive strengthat 7,28 and 90 days. Thelevels of independent parameters are determinedbased on preliminary experiments. The experimental values for compressive strengthat 7, 28 and 90 days and modulus of elasticity underdifferent treatment conditions arealso discussed and presented.These dataset can effectively be used for modelling and prediction in concrete production settings.



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Measured and Estimated data of Non-linear BRAN Channels Using HOS in 4G Wireless Communications

Publication date: Available online 10 February 2018
Source:Data in Brief
Author(s): Mohammed Zidane, Said Safi, Mohamed Sabri
The aim of this research is to develop a non-linear blind estimator able to represents a Broadband Radio Access Networks (BRAN) channels. In the one hand, we have used Higher Order Statistics (HOS) theory to build our algorithm. Indeed, we develop a non-linear method based only on fourth order cumulants for identifying the diagonal parameters of quadratic systems. In the other hand, the developed approach is applied to estimate the experimental channels, BRAN A, C and E data normalized for MC-CDMA, in non-linear case. However, the estimated data will be used in the blind equalization. The simulation results in noisy environment and for different signal to noise ratio (SNR) show the accuracy of develop estimator blindly (i.e., without any information about the input) with non-Gaussian signal input. Furthermore, in part of blind equalization problem the obtained results, using Zero forcing (ZF) and Minimum Mean Square Error (MMSE) equalizers, demonstrate that the proposed algorithm is very adequate to correct channel distortion in term the Bit Error Rate (BER). Finally, these estimated data present a necessary asset for conducting validation experiments, and can be also used as a baseline.



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Survey datasets on Women participation in Green jobs in the Construction Industry

Publication date: Available online 9 February 2018
Source:Data in Brief
Author(s): Adedeji O. Afolabi, Rapheal A. Ojelabi, Patience F. Tunji-Olayeni, Olabosipo I. Fagbenle, Timothy O. Mosaku
The unique qualities of women can make them bearers of solutions towards achieving sustainability and dealing with the dangers attributed to climate change. The attitudinal study utilized a questionnaire instrument to obtain perception of female construction professionals. By using a well-structured questionnaire, data was obtained on women participating in green jobs in the construction Industry. Descriptive statistics is performed on the collected data and presented in tables and mean scores (MS). In addition, inferential statistics of categorical regression was performed on the data to determine the level of influence (beta factor) the identified barriers had on the level of participation in green jobs. Barriers and the socio-economic benefits which can guide policies and actions on attracting, retaining and exploring the capabilities of women in green jobs can be obtained from the survey data when analyzed.



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Immunology of the Uterine and Vaginal Mucosae

Publication date: Available online 9 February 2018
Source:Trends in Immunology
Author(s): Jordan Z. Zhou, Sing Sing Way, Kang Chen
Along with the maintenance of symbiotic mutualism with commensal microbes and protection against invasive infections common to all mucosal barrier tissues, female reproductive tissues have additional, unique tasks that include dynamic cyclic cellular turnover in menstruation and immunological tolerance to genetically foreign fetal antigens in pregnancy. Here we review current knowledge on distinct features of the immune cells in female reproductive tissue with regard to antimicrobial host defense and adaptations to accommodate the fetus during pregnancy. Outstanding areas for future research to obtain new functional insights on this enigmatic mucosal barrier are also highlighted.



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Editorial Board

Publication date: February 2018
Source:Clinical Therapeutics, Volume 40, Issue 2





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Table of Contents

Publication date: February 2018
Source:Clinical Therapeutics, Volume 40, Issue 2





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A Phase III, Multicenter, Randomized, Double-blind, Active Comparator Clinical Trial to Compare the Efficacy and Safety of Combination Therapy With Ezetimibe and Rosuvastatin Versus Rosuvastatin Monotherapy in Patients With Hypercholesterolemia: I-ROSETTE (Ildong Rosuvastatin & Ezetimibe for Hypercholesterolemia) Randomized Controlled Trial

Publication date: February 2018
Source:Clinical Therapeutics, Volume 40, Issue 2
Author(s): Soon Jun Hong, Han Saem Jeong, Jeong Cheon Ahn, Dong-Hun Cha, Kyung Heon Won, Weon Kim, Sang Kyoon Cho, Seok-Yeon Kim, Byung-Su Yoo, Ki Chul Sung, Seung-Woon Rha, Joon-Han Shin, Kyoo Rok Han, Wook Sung Chung, Min Su Hyon, Han Cheol Lee, Jang-Ho Bae, Moo-Yong Rhee, Jun Kwan, Dong Woon Jeon, Ki Dong Yoo, Hyo-Soo Kim
PurposeCombination therapy with ezetimibe and statins is recommended in cases of statin intolerance or insufficiency. The objective of this study was to compare the efficacy and safety of combination therapy with ezetimibe and rosuvastatin versus those of rosuvastatin monotherapy in patients with hypercholesterolemia.MethodsI-ROSETTE (Ildong ROSuvastatin & ezETimibe for hypercholesTElolemia) was an 8-week, double-blind, multicenter, Phase III randomized controlled trial conducted at 20 hospitals in the Republic of Korea. Patients with hypercholesterolemia who required medical treatment according to National Cholesterol Education Program Adult Treatment Panel III guidelines were eligible for participation in the study. Patients were randomly assigned to receive ezetimibe 10 mg/rosuvastatin 20 mg, ezetimibe 10 mg/rosuvastatin 10 mg, ezetimibe 10 mg/rosuvastatin 5 mg, rosuvastatin 20 mg, rosuvastatin 10 mg, or rosuvastatin 5 mg in a 1:1:1:1:1:1 ratio. The primary end point was the difference in the mean percent change from baseline in LDL-C level after 8 weeks of treatment between the ezetimibe/rosuvastatin and rosuvastatin treatment groups. All patients were assessed for adverse events (AEs), clinical laboratory data, and vital signs.FindingsOf 396 patients, 389 with efficacy data were analyzed. Baseline characteristics among 6 groups were similar. After 8 weeks of double-blind treatment, the percent changes in adjusted mean LDL-C levels at week 8 compared with baseline values were –57.0% (2.1%) and –44.4% (2.1%) in the total ezetimibe/rosuvastatin and total rosuvastatin groups, respectively (P < 0.001). The LDL-C–lowering efficacy of each of the ezetimibe/rosuvastatin combinations was superior to that of each of the respective doses of rosuvastatin. The mean percent change in LDL-C level in all ezetimibe/rosuvastatin combination groups was >50%. The number of patients who achieved target LDL-C levels at week 8 was significantly greater in the ezetimibe/rosuvastatin group (180 [92.3%] of 195 patients) than in the rosuvastatin monotherapy group (155 [79.9%] of 194 patients) (P < 0.001). There were no significant differences in the incidence of overall AEs, adverse drug reactions, and serious AEs; laboratory findings, including liver function test results and creatinine kinase levels, were comparable between groups.ImplicationsFixed-dose combinations of ezetimibe/rosuvastatin significantly improved lipid profiles in patients with hypercholesterolemia compared with rosuvastatin monotherapy. All groups treated with rosuvastatin and ezetimibe reported a decrease in mean LDL-C level >50%. The safety and tolerability of ezetimibe/rosuvastatin therapy were comparable with those of rosuvastatin monotherapy. ClinicalTrials.gov identifier: NCT02749994.



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Relationship Between Atrasentan Concentrations and Urinary Albumin to Creatinine Ratio in Western and Japanese Patients With Diabetic Nephropathy

Publication date: February 2018
Source:Clinical Therapeutics, Volume 40, Issue 2
Author(s): Chih-Wei Lin, Nael M. Mostafa, Dennis L. Andress, John J. Brennan, Cheri E. Klein, Walid M. Awni
PurposeThe objective of the current analyses was to characterize the pharmacokinetic properties of atrasentan and the exposure-response relationships for the efficacy end point, urinary albumin to creatinine ratio (UACR), and the treatment-emergent adverse event, peripheral edema, during 8 or 12 weeks of treatment.MethodsResults from 3 Phase II, randomized, double-blind, placebo-controlled studies (N = 257) were used for the population pharmacokinetic and exposure-response models. Concentration-time and response data for efficacy and tolerability were analyzed using a nonlinear mixed-effects population analysis and logistic regression approaches.FindingsThe pharmacokinetic data were adequately described by a 2-compartment model with first-order absorption and elimination. After weight was accounted for, no clinically meaningful differences were found in CL/F or Vd/F of the central compartment between Western and Japanese patients. Exposure-response analyses confirmed the efficacy of atrasentan in reducing UACR, with an estimated decrease in UACR of ≥37% when the atrasentan dose was 0.75 mg or higher. No significant association between atrasentan exposure and the rate of edema was identified at atrasentan doses of 0.5, 0.75, and 1.25 mg. The rates of peripheral edema were comparable in patients receiving active treatment and placebo.ImplicationsThe exposure-response relationships for efficacy and tolerability were consistent between Western and Japanese patients. On the basis of these analyses, a dose of 0.75 mg/d was selected for the Phase III trial. ClinicalTrials.gov identifiers: NCT01356849, NCT01399580, and NCT01424319.



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Methotrexate Dose in Patients With Early Rheumatoid Arthritis Impacts Methotrexate Polyglutamate Pharmacokinetics, Adalimumab Pharmacokinetics, and Efficacy: Pharmacokinetic and Exposure-response Analysis of the CONCERTO Trial

Publication date: February 2018
Source:Clinical Therapeutics, Volume 40, Issue 2
Author(s): Sandra L. Goss, Cheri E. Klein, Ziyi Jin, Charles S. Locke, Ramona C. Rodila, Hartmut Kupper, Gerd-Rudiger Burmester, Walid M. Awni
PurposeMethotrexate (MTX) and adalimumab are well-recognized treatments of rheumatoid arthritis (RA), the efficacy of which may be driven by intracellular polyglutamates (PGs). The aim of this analysis was to characterize MTX PG concentrations and adalimumab pharmacokinetics in the CONCERTO trial. In addition, the relationships between MTX dose/pharmacokinetics, adalimumab pharmacokinetics, and efficacy were evaluated.MethodsCONCERTO was a double-blind, parallel-arm study in patients with early RA randomized to adalimumab 40 mg SC every other week plus blinded MTX 2.5, 5, 10, or 20 mg PO once weekly, for 26 weeks. Blood samples were obtained through week 26 for the determination of concentrations of MTX PG, adalimumab, and anti-adalimumab antibody (AAA). Clinical outcomes were also assessed.FindingsA total of 395 patients were included in the analysis (MTX, 329; adalimumab, 395). The mean time to steady-state MTX PG concentration was increased with MTX dose, from 8 to >26 weeks, depending on PG chain length. Dose proportionality changed with PG chain length. As MTX dose was increased, the percentage of short-chain PGs increased less than dose proportionally, while the percentage of long-chain PGs increased more than dose proportionally. For very-long-chain PGs, dose proportionality could not be assessed due to the nonmeasurable concentrations in the 2.5- and 5-mg MTX dose groups. As MTX dose increased, mean adalimumab concentrations also increased (P < 0.001). The percentage of patients with AAA decreased with increasing MTX dose, and at week 26, AAA⁺ status was significantly correlated with MTX dose level (P = 0.005). In general, rates of response, defined using the 28-joint count disease activity score based on C-reactive protein (DAS28[CRP]; response, <3.2), were greater in the subgroup without AAA. The likelihood of a patient achieving a DAS28(CRP) response was related to the baseline measurement (P < 0.001) and to the concentration of adalimumab (P = 0.001), but not to the MTX regimen (P = 0.689).ImplicationsThe dose–response characteristics of MTX PG pharmacokinetics and the resultant effects of MTX on adalimumab exposures should be considered when determining the benefit–risk profile of MTX and adalimumab combination therapy in patients with early RA. ClinicalTrials.gov identifier: NCT01185301.



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EACPT News

Publication date: February 2018
Source:Clinical Therapeutics, Volume 40, Issue 2





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Scholar : These new articles for Contemporary Music Review are available online

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The online platform for Taylor & Francis Online content New for Contemporary Music Review and online now on Taylor & Francis Online: Original Articles Performative Sounds: The Threatening Touch of Timbre Benjamin Vogels Pages: 1-18 | DOI: 10.1080/07494467.2018.1427185 The Sound's Remains: Some Thoughts on Harrison Birtwistle's Orpheus Elegies (2004) or: Timbre from Kant to Hegel Mauro Fosco Bertola Pages: 1-24 | DOI: 10.1080/07494467.2018.1427189 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Opioid and α2 adrenergic mechanisms are activated by GABA agonists in the lateral parabrachial nucleus to induce sodium intake

Publication date: Available online 9 February 2018
Source:Brain Research Bulletin
Author(s): Lisandra B. De Oliveira, Carina A.F. Andrade, Laurival A. De Luca, Débora S.A. Colombari, José V. Menani
The activation of GABA, opioid or α2 adrenergic mechanisms in the lateral parabrachial nucleus (LPBN) facilitates hypertonic NaCl intake in rats. In the present study, we combined opioid or α2 adrenergic antagonists with GABA agonists into the LPBN in order to investigate if NaCl intake caused by GABAergic activation in normohydrated rats depends on opioid or α2-adrenergic mechanisms in this area. Male Holtzman rats with stainless steel cannulas implanted bilaterally in the LPBN were used. Bilateral injections of muscimol or baclofen (GABAA and GABAB agonists, respectively, 0.5 nmol/0.2 μl) into the LPBN induced strong ingestion of 0.3 M NaCl (45.8 ± 7.3 and 21.8 ± 4.8 ml/240 min, respectively) and water intake (22.7 ± 3.4 and 6.6 ± 2.5 ml/240 min, respectively). Naloxone (opioid antagonist, 150 nmol/0.2 μl) into the LPBN abolished 0.3 M NaCl and water intake to muscimol (2.0 ± 0.6 and 0.9 ± 0.2 ml/240 min, respectively) or baclofen (2.3 ± 1.1 and 0.8 ± 0.4 ml/240 min, respectively). RX 821002 (α2 adrenoceptor antagonist, 10 nmol/0.2 μl) into the LPBN reduced 0.3 M NaCl intake induced by the injections of muscimol or baclofen (26.6 ± 8.0 and 10.1 ± 4.9 ml/240 min, respectively). RX 821002 reduced water intake induced by muscimol (7.7 ± 2.9 ml/240 min), not by baclofen. The results suggest that sodium intake caused by gabaergic activation in the LPBN in normohydrated rats is totally dependent on the activation of opioid mechanisms and partially dependent on the activation of α2 adrenergic mechanisms in the LPBN.



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Growth differentiation factor 11 improves neurobehavioral recovery and stimulates angiogenesis in rats subjected to cerebral ischemia/reperfusion

Publication date: Available online 9 February 2018
Source:Brain Research Bulletin
Author(s): Jingxi Ma, Lina Zhang, Tengfei Niu, Chibo Ai, Gongwei Jia, Xinhao Jin, Lan Wen, Keming Zhang, Qinbin Zhang, Changqing Li
The recent suggestion that growth differentiation factor 11 (GDF11) acts as a rejuvenation factor has remained controversial. However, in addition to its role in aging, the relationship between GDF11 and cerebral ischemia is still an important area that needs more investigation. Here we examined effects of GDF11 on angiogenesis and recovery of neurological function in a rat model of stroke.Exogenous recombinant GDF11 (rGDF11) at different doses were directly injected into the tail vein in rats subjected to cerebral ischemia/reperfusion (I/R). Neurobehavioral tests were performed, the proliferation of endothelial cells (ECs) and GDF11 downstream signal activin-like kinase 5 (ALK5) were assessed, and functional microvessels were measured.Results showed that rGDF11 at a dosage of 0.1 mg/kg/day could effectively activate cerebral angiogenesis in vivo. In addition, rGDF11 improved the modified neurological severity scores and the adhesive removal somatosensory test, promoted proliferation of ECs, induced ALK5 and increased vascular surface area and the number of vascular branch points in the peri-infarct cerebral cortex after cerebral I/R. These effects were suppressed by blocking ALK5.Our novel findings shed new light on the role of GDF11. Our results strongly suggest that GDF11 improves neurofunctional recovery from cerebral I/R injury and that this effect is mediated partly through its proangiogenic effect in the peri-infarct cerebral cortex, which is associated with ALK5. Thus, GDF11/ALK5 may represent new therapeutic targets for aiding recovery from stroke.



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Communication Practices of Mammography Facilities and Timely Follow-up of a Screening Mammogram with a BI-RADS 0 Assessment

Publication date: Available online 9 February 2018
Source:Academic Radiology
Author(s): Marilyn M. Schapira, William E. Barlow, Emily F. Conant, Brian L. Sprague, Anna N.A. Tosteson, Jennifer S. Haas, Tracy Onega, Elisabeth F. Beaber, Martha Goodrich, Anne Marie McCarthy, Sally D. Herschorn, Celette Sugg Skinner, Tory O. Harrington, Berta Geller
Rationale and ObjectivesThe objective of this study was to evaluate the association of communication practices with timely follow-up of screening mammograms read as Breast Imaging Reporting and Data Systems (BI-RADS) 0 in the Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium.Materials and MethodsA radiology facility survey was conducted in 2015 with responses linked to screening mammograms obtained in 2011–2014. We considered timely follow-up to be within 15 days of the screening mammogram. Generalized estimating equation models were used to evaluate the association between modes of communication with patients and providers and timely follow-up, adjusting for PROSPR site, patient age, and race and ethnicity.ResultsThe analysis included 34,680 mammography examinations with a BI-RADS 0 assessment among 28 facilities. Across facilities, 85.6% of examinations had a follow-up within 15 days. Patients in a facility where routine practice was to contact the patient by phone if follow-up imaging was recommended were more likely to have timely follow-up (odds ratio [OR] 4.63, 95% confidence interval [CI] 2.76–7.76), whereas standard use of mail was associated with reduced timely follow-up (OR 0.47, 95% CI 0.30–0.75). Facilities that had standard use of electronic medical records to report the need for follow-up imaging to a provider had less timely follow-up (OR 0.56, 95% CI 0.35–0.90). Facilities that routinely contacted patients by mail if they missed a follow-up imaging visit were more likely to have timely follow-up (OR 1.65, 95% CI 1.02–2.69).ConclusionsOur findings support the value of telephone communication to patients in relation to timely follow-up. Future research is needed to evaluate the role of communication in completing the breast cancer screening episode.



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An ontology-driven clinical decision support system (IDDAP) for infectious disease diagnosis and antibiotic prescription

Publication date: Available online 9 February 2018
Source:Artificial Intelligence in Medicine
Author(s): Ying Shen, Kaiqi Yuan, Daoyuan Chen, Joël Colloc, Min Yang, Yaliang Li, Kai Lei
BackgroundThe available antibiotic decision-making systems were developed from a physician's perspective. However, because infectious diseases are common, many patients desire access to knowledge via a search engine. Although the use of antibiotics should, in principle, be subject to a doctor's advice, many patients take them without authorization, and some people cannot easily or rapidly consult a doctor. In such cases, a reliable antibiotic prescription support system is needed.Methods and resultsThis study describes the construction and optimization of the sensitivity and specificity of a decision support system named IDDAP, which is based on ontologies for infectious disease diagnosis and antibiotic therapy. The ontology for this system was constructed by collecting existing ontologies associated with infectious diseases, syndromes, bacteria and drugs into the ontology's hierarchical conceptual schema. First, IDDAP identifies a potential infectious disease based on a patient's self-described disease state. Then, the system searches for and proposes an appropriate antibiotic therapy specifically adapted to the patient based on factors such as the patient's body temperature, infection sites, symptoms/signs, complications, antibacterial spectrum, contraindications, drug–drug interactions between the proposed therapy and previously prescribed medication, and the route of therapy administration.The constructed domain ontology contains 1,267,004 classes, 7,608,725 axioms, and 1,266,993 members of "SubClassOf" that pertain to infectious diseases, bacteria, syndromes, anti-bacterial drugs and other relevant components. The system includes 507 infectious diseases and their therapy methods in combination with 332 different infection sites, 936 relevant symptoms of the digestive, reproductive, neurological and other systems, 371 types of complications, 838,407 types of bacteria, 341 types of antibiotics, 1504 pairs of reaction rates (antibacterial spectrum) between antibiotics and bacteria, 431 pairs of drug interaction relationships and 86 pairs of antibiotic-specific population contraindicated relationships.Compared with the existing infectious disease-relevant ontologies in the field of knowledge comprehension, this ontology is more complete. Analysis of IDDAP's performance in terms of classifiers based on receiver operating characteristic (ROC) curve results (89.91%) revealed IDDAP's advantages when combined with our ontology.Conclusions and significanceThis study attempted to bridge the patient/caregiver gap by building a sophisticated application that uses artificial intelligence and machine learning computational techniques to perform data-driven decision-making at the point of primary care. The first level of decision-making is conducted by the IDDAP and provides the patient with a first-line therapy. Patients can then make a subjective judgment, and if any questions arise, should consult a physician for subsequent decisions, particularly in complicated cases or in cases in which the necessary information is not yet available in the knowledge base.



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High strength, biodegradable and cytocompatible alpha tricalcium phosphate-iron composites for temporal reduction of bone fractures

Publication date: Available online 9 February 2018
Source:Acta Biomaterialia
Author(s): E.B. Montufar, M. Casas-Luna, M. Horynová, S. Tkachenko, Z. Fohlerová, S. Diaz-de-la-Torre, K. Dvorak, L. Celko, J. Kaiser
In this work alpha tricalcium phosphate (α-TCP)/ iron (Fe) composites were developed as a new family of biodegradable, load-bearing and cytocompatible materials. The composites with composition from pure ceramic to pure metallic samples were consolidated by pulsed electric current assisted sintering to minimise processing time and temperature while improving their mechanical performance. The mechanical strength of the composites was increased and controlled with the Fe content, passing from brittle to ductile failure. In particular, the addition of 25 vol.% of Fe produced a ceramic matrix composite with elastic modulus much closer to cortical bone than that of titanium or biodegradable magnesium alloys and specific compressive strength above that of stainless steel, chromium-cobalt alloys and pure titanium, currently used in clinic for internal fracture fixation. All the composites studied exhibited higher degradation rate than their individual components, presenting values around 200 μm/year, but also their compressive strength did not show a significant reduction in the period required for bone fracture consolidation. Composites showed preferential degradation of α-TCP areas rather than β-TCP areas, suggesting that α-TCP can produce composites with higher degradation rate. The composites were cytocompatible both in indirect and direct contact with bone cells. Osteoblast-like cells attached and spread on the surface of the composites, presenting proliferation rate similar to cells on tissue culture-grade polystyrene and they showed alkaline phosphatase activity. Therefore, this new family of composites is a potential alternative to produce implants for temporal reduction of bone fractures.Statement of SignificanceBiodegradable alpha-tricalcium phosphate/iron (α-TCP/Fe) composites are promising candidates for the fabrication of temporal osteosynthesis devices. Similar to biodegradable metals, these composites can avoid implant removal after bone fracture healing, particularly in young patients. In this work, α-TCP/Fe composites are studied for the first time in a wide range of compositions, showing not only higher degradation rate in vitro than pure components, but also good cytocompatibility and mechanical properties controllable with the Fe content. Ceramic matrix composites show high specific strength and low elastic modulus, thus better fulfilling the requirements for bone fractures fixation. A significant advance over previous works on the topic is the use of pulsed electric current assisted sintering together with α-TCP, convenient to improve the mechanical performance and degradation rate, respectively.

Graphical abstract

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A Continuum of Mineralization from Human Renal Pyramid to Stones on Stems

Publication date: Available online 9 February 2018
Source:Acta Biomaterialia
Author(s): Benjamin A Sherer, Ling Chen, Misun Kang, Alex R. Shimotake, Scott V Wiener, Tom Chi, Marshall L Stoller, Sunita P. Ho
The development of new modalities for kidney stone prevention rests upon understanding the progression of mineralization within the renal pyramid. The progression from small foci of mineralization within the renal pyramid to larger interstitial plaques that ultimately lead to the formation of clinically detectable calcium-based stones on calcium phosphate stems will be presented through correlative microscopy approach. High resolution X-ray computed tomography (micro-XCT), electron microscopy, and energy dispersive X-ray (EDX) compositional analyses of interstitial plaques, stems, and attached stones were performed.Increase in mineral density progressed with mineralization severity, with the highest mineral densities detected within mature Randall's plaque and stems to which kidney stones were attached. EDX analyses revealed variable elemental composition within interstitial plaque, stems, and stones. Micro-XCT reconstructions of stones with stems enabled visualization of unoccluded tubules within stems, with average tubule diameters corresponding to thin limbs of Henle, blood vessels, and collecting ducts. Correlative microscopy confirmed that the progression of mineralization leading to calcium-based nephrolithiasis occurs through a continuum involving four anatomically and structurally distinct biomineralization regions: 1) proximal intratubular mineralization within the renal pyramid; 2) interstitial Randall's plaque near the tip of the papilla; 3) emerging plaque (stems); and, 4) the body of heterogeneous stones.Statement of SignificanceNephrolithiasis is a common condition affecting nearly 1 in 11 Americans. The most common type of stone, calcium oxalate is known to form on a calcium phosphate deposit on the renal papilla known as Randall's plaque. Novel imaging techniques have identified distinct regions of biomineralization not just at the tip, but throughout the renal papilla. The classic understanding of Randall's plaque formation is reformulated using correlative imaging techniques. This study establishes a stepwise progression of anatomically-specific biomineralization events including, 1) proximal intratubular mineralization within the renal pyramid; 2) interstitial Randall's plaque near the tip of the papilla; 3) emerging plaque (stems); and, 4) the body of heterogeneous stones, and provides insights into the need for plausible site-specific therapeutic intervention.

Graphical abstract

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In vitro methods for the evaluation of antimicrobial surface designs

Publication date: Available online 10 February 2018
Source:Acta Biomaterialia
Author(s): Jelmer Sjollema, Sebastian A.J. Zaat, Veronique Fontaine, Madeleine Ramstedt, Reto Luginbuehl, Karin Thevissen, Jiuyi Li, Henny C. van der Mei, Henk J. Busscher
Bacterial adhesion and subsequent biofilm formation on biomedical implants and devices are a major cause of their failure. As systemic antibiotic treatment is often ineffective, there is an urgent need for antimicrobial biomaterials and coatings. The term "antimicrobial" can encompass different mechanisms of action (here termed "antimicrobial surface designs"), such as antimicrobial-releasing, contact-killing or non-adhesivity. Biomaterials equipped with antimicrobial surface designs based on different mechanisms of action require different in vitro evaluation methods. Available industrial standard evaluation tests do not address the specific mechanisms of different antimicrobial surface designs and have therefore been modified over the past years, adding to the myriad of methods available in the literature to evaluate antimicrobial surface designs. The aim of this review is to categorize fourteen presently available methods including industrial standard tests for the in vitro evaluation of antimicrobial surface designs according to their suitability with respect to their antimicrobial mechanism of action. There is no single method or industrial test that allows to distinguish antimicrobial designs according to all three mechanisms identified here. However, critical consideration of each method clearly relates the different methods to a specific mechanism of antimicrobial action. It is anticipated that use of the provided table with the fourteen methods will avoid the use of wrong methods for evaluating new antimicrobial designs and therewith facilitate translation of novel antimicrobial biomaterials and coatings to clinical use. The need for more and better updated industrial standard tests is emphasized.Statement of SignificanceEuropean COST-action TD1305, IPROMEDAI aims to provide better understanding of mechanisms of antimicrobial surface designs of biomaterial implants and devices. Current industrial evaluation standard tests do not sufficiently account for different, advanced antimicrobial surface designs, yet are urgently needed to obtain convincing in vitro data for approval of animal experiments and clinical trials. This review aims to provide an innovative and clear guide to choose appropriate evaluation methods for three distinctly different mechanisms of antimicrobial design: (1) antimicrobial-releasing, (2) contact-killing and (3) non-adhesivity. Use of antimicrobial evaluation methods and definition of industrial standard tests, tailored toward the antimicrobial mechanism of the design, as identified here, fulfill a missing link in the translation of novel antimicrobial surface designs to clinical use.

Graphical abstract

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Cyclic RGD functionalized liposomes encapsulating urokinase for thrombolysis

Publication date: Available online 9 February 2018
Source:Acta Biomaterialia
Author(s): Nengpan Zhang, Chunlin Li, Dayong Zhou, Chen Ding, Yaqing Jin, Qingmei Tian, Xiangzhou Meng, Kefeng Pu, Yimin Zhu
Thrombosis, a critical event in blood vessels, not only is associated with myocardial infarction and stroke, but also accounts for considerable morbidity and mortality. Thrombolytic drugs are usually applied to the treatment of acute myocardial infarction, acute cerebral infarction and pulmonary embolism. However, thrombolytic drugs show limited efficacy in clinical practice because of the short half-life in plasma and systemic side effects. In this study, the cyclic RGD (cRGD) functionalized liposomes were prepared to encapsulate urokinase, a cheap and widely used thrombolytic drug in clinic and better thrombolysis efficacy was achieved. The flow cytometry analysis showed that the cRGD liposomes could bind to the activated platelets while not to the resting platelets. In vitro release study revealed that the release percentage reached plateau in about 5 h with 60% urokinase being released from liposomes. Results from the in vitro thrombolysis experiments demonstrated a good thrombolysis potential of the cRGD urokinase liposomes. The in vivo thrombolysis study demonstrated that the cRGD liposomes could significantly reduce the dose of urokinase by 75% while achieving the equivalent thrombolysis effect as the free urokinase in mouse mesenteric thrombosis model. In conclusion, the cRGD liposomes encapsulating urokinase hold great promise in clinic for better thrombolytic efficacy.Statement of SignificanceIn this paper, the cRGD liposomes were prepared to encapsulate urokinase for targeted thrombolysis therapy. The cRGD liposomes could specifically bind to the activated platelets and could stably and continuously release its loaded urokinase. The mouse mesenteric thrombosis model was established to evaluate the thrombolysis effect of the cRGD urokinase liposomes. The results demonstrated that the cRGD liposomes could improve the thrombolytic efficacy by almost 4-fold over free urokinase. In conclusion, the cRGD liposomes encapsulating urokinase had great potential for the clinical treatment of thrombosis.

Graphical abstract

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Improvement studies on emission and combustion characteristics of DICI engine fuelled with colloidal emulsion of diesel distillate of plastic oil, TiO 2 nanoparticles and water

Abstract

Experimentation was conducted on a single cylinder CI engine using processed colloidal emulsions of TiO₂ nanoparticle-water-diesel distillate of crude plastic diesel oil as test fuel. The test fuel was prepared with plastic diesel oil as the principal constituent by a novel blending technique with an aim to improve the working characteristics. The results obtained by the test fuel from the experiments were compared with that of commercial petro-diesel (CPD) fuel for same engine operating parameters. Plastic oil produced from high density polyethylene plastic waste by pyrolysis was subjected to fractional distillation for separating plastic diesel oil (PDO) that contains diesel range hydrocarbons. The blending process showed a little improvement in the field of fuel oil-water-nanometal oxide colloidal emulsion preparation due to the influence of surfactant in electrostatic stabilization, dielectric potential, and pH of the colloidal medium on the absolute value of zeta potential, a measure of colloidal stability. The engine tests with nano-emulsions of PDO showed an increase in ignition delay (23.43%), and decrease in EGT (6.05%), BSNO_x (7.13%), and BSCO (28.96%) relative to PDO at rated load. Combustion curve profiles, percentage distribution of compounds, and physical and chemical properties of test fuels ascertains these results. The combustion acceleration at diffused combustion phase was evidenced in TiO₂ emulsion fuels under study.

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In vitro assessment of the interactions of dopamine β-hydroxylase inhibitors with human P-glycoprotein and Breast Cancer Resistance Protein

Publication date: 30 May 2018
Source:European Journal of Pharmaceutical Sciences, Volume 117
Author(s): Joana Bicker, Gilberto Alves, Ana Fortuna, Patrício Soares-da-Silva, Amílcar Falcão
Inhibition of the biosynthesis of noradrenaline is a currently explored strategy for the treatment of hypertension, congestive heart failure and pulmonary arterial hypertension. While some dopamine β-hydroxylase (DBH) inhibitors cross the blood-brain barrier (BBB) and cause central as well as peripheral effects (nepicastat), others have limited access to the brain (etamicastat, zamicastat). In this context, peripheral selectivity is clinically advantageous, in order to prevent alterations of noradrenaline levels in the CNS and the occurrence of adverse central effects. A limited brain exposure results from the combination of several factors, such as a reduced passive permeability or affinity for efflux transporters, but efflux liabilities may also lead to unwanted drug-drug interactions (DDIs) in the presence of co-administered substrates or inhibitors.Thus, the purpose of the study herein presented was to explore the interaction of P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP), the two major efflux transporters of the BBB that hamper the entry of several drugs to the brain, with the DBH inhibitors, etamicastat, nepicastat and zamicastat. Madin-Darby canine kidney cells (MDCK II) and transfected lines with human MDR1 (MDCK-MDR1) and ABCG2 (MDCK-BCRP) genes were used as a BBB surrogate model. P-gp and BCRP substrates and/or inhibitors were identified through intracellular accumulation and bidirectional permeability assays. The obtained data revealed that zamicastat is a concentration-dependent dual P-gp and BCRP inhibitor with IC50 values of 73.8 ± 7.2 μM and 17.0 ± 2.7 μM, while etamicastat and nepicastat inhibited BCRP to greater extent than P-gp, with IC50 values of 47.7 ± 1.8 μM and 59.2 ± 9.4 μM, respectively. Additionally, etamicastat was identified as P-gp and BCRP dual substrate, as demonstrated by net flux ratios of 5.84 and 3.87 and decreased >50% by verapamil and Ko143. Conversely, nepicastat revealed to be a P-gp-only substrate, with a net flux ratio of 2.01, reduced to 0.92 in the presence of verapamil. Furthermore, nepicastat displayed a consistently higher apparent permeability (>8.49 × 10⁻⁶ cm s⁻¹) than etamicastat (<0.58 × 10⁻⁶ cm s⁻¹).The identification of etamicastat as a dual efflux substrate suggests that P-gp and BCRP may be partially responsible for the limited central exposure of this compound, in association with its low passive permeability. Moreover, the weak efflux inhibitory potencies of etamicastat and nepicastat revealed a low DDI risk, while the dual P-gp/BCRP inhibition of zamicastat could be studied in the future with synergically effluxed compounds, for which BBB penetration is severely impaired.

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Catalytic oxidation of trichloroethylene from gas streams by perovskite-type catalysts

Abstract

Three perovskite-type catalysts including LaMnO₃, La_0.8Ce_0.2MnO₃, and La_0.8Ce_0.2 Mn_0.8Ni_0.2O₃ are prepared using citric acid sol-gel method and evaluated as catalyst for the oxidation of trichloroethylene (TCE) in air with temperature ranging from 100 to 600 °C. The physicochemical properties of three perovskite-type catalysts were characterized by SEM, EDS, XRD, BET, and XPS to investigate the relationship with catalytic activities. The results show that the removal efficiency of TCE achieved with La_0.8Ce_0.2Mn_0.8Ni_0.2O₃ (the best one) reaches 100% at 400 °C and the mineralization efficiency reaches 100% at 600 °C. The enhanced activity can be attributed to the addition of Ce and Ni which increases the surface areas, active oxygen species, and the redox ability of the Mn⁴⁺/Mn³⁺ ratio on the catalyst surface. As La_0.8Ce_0.2Mn_0.8Ni_0.2O₃ is applied for TCE oxidation, the main intermediate chlorinated byproduct detected is tetrachloroethylene (C₂Cl₄) which is generated by the reaction of TCE and chlorine (Cl₂). The activation energy for the TCE oxidation with La_0.8Ce_0.2Mn_0.8Ni_0.2O₃ catalyst is 51 kJ/mol using kinetic models of power–law type.

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