bluuebunny/crossref_metadata_2025 huggingface dataset:
Nicotine oxidation by genetic variants of CYP2B6 and in human brain microsomes
Authors: Bloom Adam Joseph , Wang Pan‐Fen , Kharasch Evan D.
Published: March 2019

Common variation in the CYP2B6 gene, encoding the cytochrome P450 2B6 enzyme, is associated with substrate‐specific altered clearance of multiple drugs. CYP2B6 is a minor contributor to hepatic nicotine metabolism, but the enzyme has been proposed as relevant to nicotine‐related behaviors because of reported CYP2B6 mRNA expression in human brain tissue. Therefore, we hypothesized that CYP2B6 variants would be associated with altered nicotine oxidation, and that nicotine metabolism by CYP2B6 would be detected in human brain microsomes. We generated recombinant enzymes in insect cells corresponding to nine common CYP2B6 haplotypes and demonstrate genetically determined differences in nicotine oxidation to nicotine iminium ion and nornicotine for both (S) and (R)‐nicotine. Notably, the CYP2B6.6 and CYP2B6.9 variants demonstrated lower intrinsic clearance relative to the reference enzyme, CYP2B6.1. In the presence of human brain microsomes, along with nicotine‐N‐oxidation, we also detect nicotine oxidation to nicotine iminium ion. However, unlike N‐oxidation, this activity is NADPH independent, does not follow Michaelis‐Menten kinetics, and is not inhibited by NADP or carbon monoxide. Furthermore, metabolism of common CYP2B6 probe substrates, methadone and ketamine, is not detected in the presence of brain microsomes. We conclude that CYP2B6 metabolizes nicotine stereoselectively and common CYP2B6 variants differ in nicotine metabolism activity, but did not find evidence of CYP2B6 activity in human brain.
Insight into antioxidant properties of milk‐derived bioactive peptides in vitro and in a cellular model
Authors: Tonolo Federica , Moretto Laura , Ferro Stefania , Folda Alessandra , Scalcon Valeria , Sandre Michele , Fiorese Federico , Marin Oriano , Bindoli Alberto , Rigobello Maria Pia
Published: March 2019

Milk is a nutritionally important source of bioactive peptides with anti‐inflammatory, immunomodulatory, anticancer, and antioxidant properties. These compounds can be useful as ingredients of functional food. For this reason, in the last decades, bioactive peptides attracted the interest of researchers and food companies. In this work, the results obtained with six milk‐derived bioactive peptides (Y‐4‐R, V‐6‐R, V‐7‐K, A‐10‐F, R‐10‐M, and H‐9‐M) synthesized and studied for their antioxidant properties in vitro and in a cellular model, are reported. These molecules correspond to peptide fragments derived from parent compounds able to cross the apical membrane of Caco‐2 cell layer and released in the basolateral compartment. In vitro, antioxidant tests such as 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulphonic acid) (ABTS) and crocin bleaching showed antioxidant activity mainly for peptides Y‐4‐R and V‐6‐R, respectively. In Caco‐2 cells, peptides V‐6‐R, H‐9‐R, Y‐4‐R, and particularly R‐10‐M and V‐7‐K are able to prevent the decrease of viability due to oxidative stress. The latter peptide is also the most effective in protecting cells from lipid peroxidation. In conclusion, the reported hydrolyzed peptides are shown to exert the antioxidant properties both in vitro and in a cellular model.
Effect of turmeric on glycemic status, lipid profile, hs‐CRP, and total antioxidant capacity in hyperlipidemic type 2 diabetes mellitus patients
Authors: Adab Zohreh , Eghtesadi Shahryar , Vafa Mohammad‐Reza , Heydari Iraj , Shojaii Asieh , Haqqani Hamid , Arablou Tahereh , Eghtesadi Maryam
Published: March 2019

Diabetes mellitus is the most common metabolic disorder worldwide. This study examined the effect of turmeric supplementation on glycemic status, lipid profile, hs‐CRP and total antioxidant capacity in hyperlipidemic type 2 diabetic patients. In this double‐blind, randomized clinical trial, 80 hyperlipidemic type 2 diabetic patients were divided into turmeric (2,100 mg powdered rhizome of turmeric daily) and placebo groups for 8 weeks. Body weight, fasting plasma glucose, hemoglobin A1c (HbA1c), serum insulin, triglyceride (TG), total cholesterol, low density lypoprotein cholesterol (LDL‐c), high density lypoprotein cholesterol, apolipoprotein A1, apolipoprotein B, high sensitivity C‐reactive protein (hs‐CRP), and total antioxidant capacity were measured before and after intervention. Statistical analysis was carried out using paired and independent t and chi‐square tests. Seventy five patients completed the study. The turmeric group showed significant decreases in body weight, TG, and LDL‐c compared with baseline (p value < 0.05). Body mass index, TG, and total cholesterol decreased significantly in the turmeric group compared with the placebo group (p value < 0.05). No significant changes were observed in other parameters between the two groups after intervention (p value < 0.05). Turmeric improved some fractions of lipid profile and decreased body weight in hyperlipidemic patients with type 2 diabetes. It had no significant effect on glycemic status, hs‐CRP, and total antioxidant capacity in these patients.
First‐principles study of vibrational properties of TiSiO4 clusters
Authors: Majid Abdul , Batool Amber , Khan Salah Ud‐Din , Haider Sajjad
Published: March 2019

First‐principles calculations were performed to investigate the vibrational properties of monomers and dimers of titania, silica, and titania‐silica hybrid clusters. Density functional theory‐based formulism was employed to optimize the geometry at the B3LYP level and calculate the infrared and Raman spectra of the clusters by using the GGA‐PBE exchange‐correlation functional. It was found that the vibrational spectra of Ti2O4, Si2O4, and TiSiO4 hybrid clusters provide fingerprint information about structures and structural transitions during the formation of cluster structures. In the case of Si2O4 the mode at 410 cm−1 exhibited the largest vibration of Si atoms, whereas in the case of Ti2O4 the mode at 442 cm−1 exhibited the largest vibration of Ti atoms. The hybrid cluster TiSiO4 was structured using two different methods to explore the effects of starting geometry on the structures and vibrational modes of the clusters. The structural properties of the clusters remained unchanged but vibrational modes were found to be different. It is found that Si shows notable vibrations, but the metal atom Ti merely shows any vibration in the case of TiSiO4 hybrid clusters. The low and intermediate frequency modes were stiffened, whereas the three highest frequency modes were softened when the starting geometry of the hybrid clusters was changed from Si2O4 to Ti2O4.
Reducing ion reflections at the quadrupole pre‐filter/mass filter boundary: Simulation and experiment
Authors: Collings Bruce A.
Published: March 2019

Rationale

Ion reflections at the quadrupole pre‐filter/mass filter boundary lead to the trapping of ions within the pre‐filter. The trapped ions lead to space charge effects on the transmission of ions through this region which become more of an issue with the development of high sensitivity mass spectrometers which have bright ions beams.

Methods

Simulations were carried out matching the effective potentials at the pre‐filter/mass filter boundary to reduce the field gradients across the boundary by reducing the field radius of the pre‐filter. A further rotation of the pre‐filter relative to the mass filter was incorporated into the model. Experiments were carried out to reproduce the conditions of the simulations.

Results

Simulations show that matching the effective potentials at the pre‐filter/mass filter boundary and rotating the pre‐filter by 45° reduced the number of reflected ion trajectories when the mass filter was operated in either the radiofrequency (RF)‐only mode or in mass resolving mode. Experiments confirmed the reduced effects of space charge on the transmission of ions through the pre‐filter through the measurement of pre‐filter transmission profiles with and without the use of an empty step to remove any trapped ions. These results showed significant improvement over the typical pre‐filter/mass filter set‐up.

Conclusions

Matching the effective potentials at the quadrupole pre‐filter/mass filter boundary and rotating the pre‐filter result in a pre‐filter/mass filter set‐up that does not lead to ions that are reflected at the boundary. The modified set‐up does not result in the presence of unwanted trapped ions in the quadrupole pre‐filter.
Small cell lung cancer and interstitial pneumonia associated with anti‐transcriptional intermediary factor‐1γ‐positive dermatomyositis
Authors: Kato Toshio , Ito Satoru , Tsuzuki Toyonori , Watanabe Daisuke , Kubo Akihito , Yamaguchi Etsuro
Published: March 2019

Antibodies to transcriptional intermediary factor‐1γ (TIF‐1γ) are strongly associated with malignancy in patients with dermatomyositis but a relatively low risk for interstitial lung disease. We report the case of a 68‐year‐old female with small cell lung cancer (SCLC) and interstitial pneumonia who was diagnosed first with dermatomyositis positive for serum anti‐TIF‐1γ antibodies. Because interstitial pneumonia co‐existed, she was treated with carboplatin and etoposide without radiotherapy. A significant improvement in skin disease and SCLC was seen in response to chemotherapy. The levels of anti‐TIF‐1γ antibodies were also decreased by chemotherapy. Her interstitial pneumonia was mild with normal pulmonary function and did not change during the observation period. This is the first report of dermatomyositis associated with anti‐TIF‐1γ antibodies co‐existing with interstitial pneumonia and SCLC. Because cases with interstitial pneumonia in cancer‐associated dermatomyositis positive for anti‐TIF‐1γ antibodies are few in number, further studies are necessary to elucidate the clinical features.
A rare case of lymphadenitis and pulmonary disease caused by Mycobacterium paraffinicum
Authors: Tan Pei Sze Carmen , Perera Ruad
Published: March 2019

With over 150 species, non‐tuberculous mycobacteria are increasingly recognized to be important human pathogens that pose diagnostic and management challenges. We report a rare case of cervical lymphadenitis and pulmonary disease caused by Mycobacterium paraffinicum in a 64‐year‐old man who presented with three‐month history of increasing right‐sided painless neck lump. His medical history included rheumatoid arthritis, which was managed with leflunomide and methotrexate. Computed tomography scans of his neck and thorax revealed a right lower neck and supraclavicular fossa cystic mass with peripheral enhancement and bilateral multiple small pulmonary nodules. M. paraffinicum was cultured from a fine‐needle aspiration of the mass. Two out of three sputa were acid‐fast bacilli smear positive but cultures did not yield any viable organism. He developed spontaneous discharge of purulent material via a sinus, which drained over two months and recovered with a completely healed sinus without any further treatment.
The power‐integrated discriminant improvement: An accurate measure of the incremental predictive value of additional biomarkers
Authors: Hayashi Kenichi , Eguchi Shinto
Published: March 2019

The predictive performance of biomarkers is a central concern in biomedical research. This is often evaluated by comparing two statistical models: a “new” model incorporating additional biomarkers and an “old” model without them. In 2008, the integrated discrimination improvement (IDI) was proposed for cases when the response variable is binary, and it is now widely applied as a promising alternative to conventional measures, such as the difference of the area under the receiver operating characteristic curve. However, the IDI can erroneously identify a significant improvement in the new model even if no additional information has been provided by new biomarkers. In order to overcome problems with existing measures, in this study, we propose the power‐IDI as a measure of incremental predictive value. Our study explains why the IDI cannot avoid false detection of apparent improvements in a new model and we show that our proposed measure is better able to capture improvements in prediction. Numerical simulations and examples using real empirical data reveal that the power‐IDI is not only more powerful but also incurs fewer false detections of improvement.
TMSOTf‐Catalysed Synthesis of 2,4,5‐Trisubstituted Imidazoles from Vinyl Azides and Nitriles
Authors: Harisha Mysore Bhyrappa , Dhanalakshmi Pandi , Suresh Rajendran , Kumar Raju Ranjith , Muthusubramanian Shanmugam , Bhuvanesh Nattamai
Published: March 2019

TMSOTf‐catalysed generation of 2,4,5‐trisubstituted imidazoles by a simple [3+2] addition reaction of azido chalcones and organic nitriles is described. This transformation generates two new C‐N bonds under mild reaction conditions. The substrate scope of the reaction is excellent with good number of vinyl azides and aromatic and aliphatic nitriles tolerating the reaction. It has been shown that the reaction can also be conducted under microwave condition successfully. These newly synthesized imidazoles are shown to exist as tautomeric mixture and the subsequent methylated as well as benzylated compounds have been obtained as a single regioisomer. The synthesised N‐methyl Imidazole derivative is a potential structural unit towards biologically active compounds.
Total Synthesis of (+)‐Sacrolide A
Authors: Thirupathi Barla , Jena Bighnanshu K.
Published: March 2019

A simple and an efficient synthesis of (+)‐sacrolide A has been achieved from a known compound 10 in 12 steps with 9% overall yield. Key steps involved are Jacobsen's hydrolytic kinetic resolution, Sharpless asymmetric epoxidation, trans‐selective hydrometallation of the propargylic alcohol, and acid‐catalyzed Kita macrolactonization.
A Fluorescent Chemosensor with a Hybridized Local and Charge Transfer Nature and Aggregation‐Induced Emission Effect for the Detection of Picric Acid
Authors: Zhou Chuanting , Han Xiangting , Liao Guifen , Zhou Chaotong , Jin Peng , Guo Yuhua , Gao Huiwen , Zhang Yujian , Yang Shengchen , Sun Jingwei
Published: March 2019

A novel fluorescent molecule TPA‐CO, which exhibited a hybridized local and charge transfer (HLCT) nature and aggregation‐induced emission (AIE) effect, was developed and utilized as a chemosensor for the detection of picric acid (PA) in both organic solution and water. It was found that TPA‐CO exhibited apparent fluorescent quenching along with the color change to yellow upon the addition of PA. Notably, more sensitive detection was achieved in the H2O: THF (9:1) medium, with the LOD almost two third lower than that in pure THF. Such more sensitive response in aqueous solution was accomplished by the synergy of HLCT and AIE effects in TPA‐CO nanoparticles, which facilitated both highly efficient fluorescence in the absence of PA and rapid quenching rate in the presence of PA, respectively. Therefore, it is proposed an effective design strategy by integrating HLCT and AIE effects for developing PA chemosensors.
Mesh‐Like Carbon Nanosheets with High‐Level Nitrogen Doping for High‐Energy Dual‐Carbon Lithium‐Ion Capacitors
Authors: Li Zhao , Cao Liujun , Chen Wei , Huang Zechuan , Liu Hao
Published: March 2019

Li‐ion capacitors (LICs) have demonstrated great potential for bridging the gap between lithium‐ion batteries and supercapacitors in electrochemical energy storage area. The main challenge for current LICs (contain a battery‐type anode as well as a capacitor‐type cathode) lies in circumventing the mismatched electrode kinetics and cycle degradation. Herein, a mesh‐like nitrogen (N)‐doped carbon nanosheets with multiscale pore structure is adopted as both cathode and anode for a dual‐carbon type of symmetric LICs to alleviate the above mentioned problems via a facile and green synthesis approach. With rational design, this dual‐carbon LICs exhibits a broad high working voltage window (0–4.5 V), an ultrahigh energy density of (), the highest power density of () even under an ultrahigh energy density of (), as well as reasonably good cycling stability with capacity retention of 84.5% (only 0.0016% capacity loss per cycle) within 10 000 cycles under a high current density of 5 A g−1. This study provides an efficient method and option for the development of high performance LIC devices.
A robust power control strategy to enhance LVRT capability of grid‐connected DFIG‐based wind energy systems
Authors: Ardjoun Sid Ahmed El Mehdi , Denai Mouloud , Abid Mohamed
Published: March 2019

This paper presents a new robust and effective control strategy to mitigate symmetrical voltage dips in a grid‐connected doubly fed induction generator (DFIG) wind energy conversion system without any additional hardware in the system. The aim is to control the power transmitted to the grid so as to keep the electrical and mechanical quantities above their threshold protection values during a voltage dip transient. To achieve this, the references of the powers are readjusted to adapt the wind energy conversion system to the fault conditions. Robust control strategies, combining the merits of sliding mode theory and fuzzy logic, are then proposed in this paper. These controllers are derived from the dynamic model of the DFIG considering the variations in the stator flux generated by the voltage drop. This approach is found to yield better performance than other control design methods which assume the flux in the stator to remain constant in amplitude. This control scheme is compliant with the fault‐ride‐through grid codes which require the wind turbine generator to remain connected during voltage dips. A series of simulation scenarios are carried out on a 3‐MW wind turbine system to demonstrate the effectiveness of the proposed control schemes under voltage dips and parameter uncertainty conditions.
Gold, gildings, and tumbaga from the Moche tomb of the Lady of Cao: An EDXRF test for the internal ratio method
Authors: Cesareo Roberto
Published: March 2019

Gold, gilded copper, gilded silver, and tumbaga artifacts from the Moche tomb of the Lady of Cao, dated around 300 A.D., were analyzed by energy‐dispersive X‐ray fluorescence analysis. These artifacts are multilayered structures, which can be “reconstructed” using the K or L rays ratio of the chemical elements present in the layers. For example, in the case of gilded copper, the ratios Au (Lα/Lß), Cu (Kα/Kß), and Au‐Lα/Cu‐Kα, altered with respect to bulk gold or copper, can be used to determine the gilding thickness.

An ideal test of this method was recently offered by the study of 15 big spears on gilded copper, a necklace composed of 12 small heads on tumbaga (a poor gold‐alloy subject to depletion gilding), and a nose decoration on gilded silver. All these artifacts were found in (or close to) the tomb of the Lady of Cao, discovered 10 years ago in the north of Peru, close to Trujillo. The “internal ratio” method is described and discussed.
Magnesium enhances dehydration tolerance in Schizosaccharomyces pombe by promoting intracellular 5′‐methylthioadenosine accumulation
Authors: Roca‐Domènech Gemma , Poblet Montse , Rozès Nicolas , Cordero‐Otero Ricardo
Published: March 2019

In the present study, we analysed metabolite features during the dehydration–rehydration process for two Schizosaccharomyces pombe strains with different viability rate, in order to determine whether metabolite contents were affected by the presence of magnesium during cell rehydration. The qualitative changes of the intracellular metabolites of both strains were determined by comparing the metabolic profiles of cells before dehydration, after rehydration in water or magnesium solution, and after 2‐hr inoculation of cells in complete medium. Our results suggest that changes of metabolites from the methionine salvage pathway, in particular 5′‐methylthioadenosine, triggered by the increasing intracellular magnesium content may participate in the dehydration tolerance of Sp97 cells.
Austrian economics without extreme apriorism: construing the fundamental axiom of praxeology as analytic
Authors: Linsbichler Alexander
Published: March 2019

Current debates between behavioural and orthodox economists indicate that the role and epistemological status of first principles is a particularly pressing problem in economics. As an alleged paragon of extreme apriorism, the methodology of Austrian economics in Mises’ tradition is often dismissed as untenable in the light of modern philosophy. In particular, the defence of the so-called fundamental axiom of praxeology—“Man acts.”—by means of pure intuition is almost unanimously rejected. However, in recently resurfacing debates, the extremeness of Mises’ epistemological position has been called into question. Rather than directly engaging in these exegetical discussions, this paper aims to substantiate the possibility and plausibility of conventionalist defences of praxeology per se. The proposed shift includes settling for an analytic fundamental axiom and acknowledging the prima facie tenability of other research programs than praxeology. Since conventionalist praxeology is only moderately aprioristic, mainstream economists and philosophers might be more likely to engage in fruitful discussions with those Austrian scholars who elaborate pragmatic arguments for praxeology instead of invoking pure intuition.
The pre-service practicum experience and inquiry-oriented pedagogy: Evidence from student teachers’ lesson planning
Authors: Marino Michael P. , Crocco Margaret S.
Published: March 2019

This paper addresses whether, how, and to what extent social studies student teachers who have been introduced to inquiry-oriented teaching (as manifest in the National Council for the Social Studies C3 Framework) in their secondary social studies methods course incorporate this approach into the planning for their practicum experience. Based on analysis of lesson plans used in the practicum and follow-up interviews with a small subset of student teachers, this paper analyzes the factors that promote or inhibit use of this approach to teaching in their practicum experience. Results indicate the C3-oriented teaching approach, as taught in the methods course, did appear in the student teachers’ lesson plans. A small subset of student teachers used the framework competently while two smaller subsets were less adept in their application. The degree of application was affected by student teachers’ perceptions of their school placements and students’ needs.
Securing the Emergency Department During Terrorism Incidents: Lessons Learned From the Boston Marathon Bombings
Authors: Hojman Horacio , Rattan Rishi , Osgood Rob , Yao Mengdi , Bugaev Nikolay
Published: March 2019

Terrorist incidents that target hospitals magnify morbidity and mortality. Before a real or perceived terrorist mass casualty incident threatens a hospital and its providers, it is essential to have protocols in place to minimize damage to the infrastructure, morbidity, and mortality. In the years following the Boston Marathon bombings, much has been written about the heroic efforts of survivors and responders. Far less has been published about near misses due to lack of experience responding to a mass casualty incident resulting from terrorism. After an extensive review of the medical literature and published media in English, Spanish, and Hebrew, we were unable to identify a similar event. To the best of our knowledge, this is the first reported experience of a bomb threat caused evacuation of an emergency department in the United States while actively responding to multiple casualty terrorist incidents. We summarized the chronology of the events that led to a bomb threat being identified and the subsequent evacuation of the emergency department. We then reviewed the problematic nature of our response and described evidence-based policy changes based on data from health care, law enforcement, and counterterrorism. (Disaster Med Public Health Preparedness. 2019;13:791–798)
Gender Stereotyping and Chivalry in International Negotiations: A Survey Experiment in the Council of the European Union
Authors: Naurin Daniel , Naurin Elin , Alexander Amy
Published: March 2019

Gender stereotypes—stylized expectations of individuals’ traits and capabilities based on their gender—may affect the behavior of diplomats and the processes of international negotiations. In a survey experiment in the Council of the European Union, we find that female representatives behaving stereotypically weak and vulnerable may trigger a chivalry reaction among male representatives, increasing the likelihood that the men will agree to support a bargaining proposal from the women. The effect is conditional on the negotiators’ cultural background—the chivalry reaction is displayed mainly by diplomats from countries with relatively low levels of gender equality. Our study contributes to the research on nonstandard behavior in international relations, and in particular the expression and reception of emotions in diplomacy. We argue that gender stereotypes may have a moderating impact on decision making based on such intuitive cognitive processes. We also add to the broader negotiation literature, both by showing the pervasiveness of gender stereotyping, and by testing at the elite level the generalizability of claims regarding gender effects derived from laboratory experiments. Overall, our findings demonstrate the importance of bringing gender into the study of international negotiations, where it has been largely and surprisingly ignored.
Negative effects of parasitic lung nematodes on the fitness of a Neotropical toad (Rhinella horribilis)
Authors: Kelehear Crystal , Saltonstall Kristin , Torchin Mark E.
Published: March 2019

Pathogens are increasingly implicated in amphibian declines but less is known about parasites and the role they play. We focused on a genus of nematodes (Rhabdias) that is widespread in amphibians and examined their genetic diversity, abundance (prevalence and intensity), and impact in a common toad (Rhinella horribilis) in Panama. Our molecular data show that toads were infected by at least four lineages ofRhabdias, most likelyRhabdias pseudosphaerocephala,and multiple lineages were present in the same geographic locality, the same host and even the same lung. Mean prevalence of infection per site was 63% and mean intensity of infection was 31 worms. There was a significant effect of host size on infection status in the wild: larger toads were more likely to be infected than were smaller conspecifics. Our experimental infections showed that toadlets that were penetrated by many infectiveRhabdiaslarvae grew less than those who were penetrated by few larvae. Exposure toRhabdiasreduced toadlet locomotor performance (both sustained speed and endurance) but did not influence toadlet survival. The effects ofRhabdiasinfection on their host appear to be primarily sublethal, however, dose-dependent reduction in growth and an overall impaired locomotor performance still represents a significant reduction in host fitness.
Development of EST-derived microsatellite markers to investigate the population structure of sparganum — the causative agent of zoonotic sparganosis
Authors: Zhang Xi , Hong Xiu , Duan Jiang Yang , Han Lu Lu , Hong Zi Yang , Jiang Peng , Wang Zhong Quan , Cui Jing
Published: March 2019

The plerocercoid (sparganum) ofSpirometra erinaceieuropaeiis the main aetiological agent of human sparganosis. To improve the current knowledge onS. erinaceieuropaeievolution, we performed multi-locus microsatellite typing of sparganum isolates from China for the first time. All available expressed sequence tag (EST) sequences for theSpirometrawere downloaded from the GenBank. The identification and localization of microsatellites in ESTs was accomplished byMISA. Based on the selected microsatellites, the genetic structure of 64 sparganum isolates collected from 11 geographical locations in southwest China were investigated through principal component analysis, STRUCTURE analysis and neighbour-joining clustering. A total of 522 non-redundant ESTs containing 915 simple sequence repeats were identified from 12 481 ESTs screened. Five primer pairs were finally selected. Using these loci, a total of 12 alleles were detected in 64 sparganum isolates. Little variability was observed within each of geographical population, especially among isolates derived from Kunming of Yunnan (YN-KM) province. Both STRUCTURE analysis and the clustering analysis supported that two genotypes existed among the sparganum isolates from southwest China. In conclusion, five microsatellite markers were successfully developed, and sparganum population was observed to harbour low genetic variation, further investigation with deeper sampling was needed to elucidate the population structure.
Repurposing strategies for Chagas disease therapy: the effect of imatinib and derivatives againstTrypanosoma cruzi
Authors: Simões-Silva M. R. , De Araújo J. S. , Peres R. B. , Da Silva P. B. , Batista M. M. , De Azevedo L. D. , Bastos M. M. , Bahia M. T. , Boechat N. , Soeiro M. N. C.
Published: March 2019

Chagas disease (CD) is a neglected parasitic condition endemic in the Americas caused byTrypanosoma cruzi. Patients present an acute phase that may or not be symptomatic, followed by lifelong chronic stage, mostly indeterminate, or with cardiac and/or digestive progressive lesions. Benznidazole (BZ) and nifurtimox are the only drugs approved for treatment but not effective in the late chronic phase and many strains of the parasite are naturally resistant. New alternative therapy is required to address this serious public health issue. Repositioning and combination represent faster, and cheaper trial strategies encouraged for neglected diseases. The effect of imatinib (IMB), a tyrosine kinase inhibitor designed for use in neoplasias, was assessedin vitroonT. cruziand mammalian host cells. In comparison with BZ, IMB was moderately active against different strains and forms of the parasite. The combination IMB + BZ in fixed-ratio proportions was additive. Novel 14 derivatives of IMB were screened and a 3,2-difluoro-2-phenylacetamide (3e) was as potent as BZ onT. cruzibut had low selectivity index. The results demonstrate the importance of phenotypic assays, encourage the improvement of IMB derivatives to reach selectivity and testify to the use of repurposing and combination in drug screening for CD.
Hybrid Strategy-based Coordinate Controller for an Underwater Vehicle Manipulator System Using Nonlinear Disturbance Observer
Authors: Li Jiyong , Huang Hai , Wan Lei , Zhou Zexing , Xu Yang
Published: March 2019

This paper presents a hybrid strategy-based coordinate controller with a novel nonlinear disturbance observer for autonomous underwater vehicle manipulator systems (UVMSs). This method can reduce the influence from external unknown disturbances, inner coupling effects and model uncertainties by using a modified disturbance observer. Considering the natural redundancy property of the UVMS, the redundancy resolution algorithm is often utilized to give desired trajectories in the vehicle–joint space. However, because of the calibration errors, assembling errors and numerical errors, these desired trajectories may not lead the end-effector to the goal point accurately. To realize accurate motion control even when small errors exist in the planning phase, a hybrid strategy is introduced to transform the controller in the joint–vehicle space to the controller in the task space. Numerical simulations based on a UVMS have been carried out to testify the effectiveness of the proposed coordinate controller and the hybrid strategy. During the simulations, unknown disturbances are exerted upon the system. The trajectory tracking and error fixing performances are discussed in comparative analyses. The controller also maintains robust characteristics in comparison with the passivity-based controller and the proposed controller but without the disturbance observer. Experiments are also carried out to test its performance.
TOWARD A DYNAMIC VIEW OF SECOND LANGUAGE COMPREHENSIBILITY
Authors: Nagle Charles , Trofimovich Pavel , Bergeron Annie
Published: March 2019

This study took a dynamic approach to second language (L2) comprehensibility, examining how listeners construct comprehensibility profiles for L2 Spanish speakers during the listening task and what features enhance or diminish comprehensibility. Listeners were 24 native Spanish speakers who evaluated 2–5 minute audio clips recorded by three university-level L2 Spanish speakers responding to two prompts. Listeners rated comprehensibility dynamically, using Idiodynamic Software to upgrade or downgrade comprehensibility over the course of the listening task. Dynamic ratings for one audio clip were video-captured for stimulated recall, and listeners were interviewed to understand which aspects of L2 speech were associated with enhanced versus diminished comprehensibility. Results indicated that clips that were downgraded more often received lower global ratings but upgrading was not associated with higher ratings. Certain problematic features and individual episodes caused listeners’ impressions to converge, though substantial individual variation among listeners was evident.
Antidepressant Advertising in China and the UK: The Strengths and Limits of Policy Learning
Authors: Geyer Robert , Wang Fang
Published: March 2019

China is expected to become one of the largest markets for prescription drugs in the world and pharmaceutical advertising is becoming increasingly important, particularly in the socially and culturally contested area of mental health. This article briefly explores the background of drug advertising policies in China and the UK and focuses on the distinctive challenges of antidepressant drug regulation. Then, using tools of critical discourse analysis, it examines Chinese antidepressant adverts, and compares them with relevant British adverts. The findings indicate that, relative to the UK, Chinese antidepressant adverts are generally oversimplified, and the critical information concerning the concepts of caution, danger and adverse effects are underrepresented. However, there are many interdependent factors that contribute to the distinctive Chinese antidepressant drug regulatory regime. Hence, Chinese policymakers must maintain a delicate balance between learning from Western regulatory regimes, but also avoiding borrowing too heavily from them.
A Profile of Regulated Nurses Employed in Canadian Long-Term Care Facilities
Authors: Squires Janet E. , Baumbusch Jennifer , Demery Varin Melissa , MacDonald Ibo , Chamberlain Stephanie , Boström Anne-Marie , Thompson Genevieve , Cummings Greta , Estabrooks Carole A.
Published: March 2019

Le personnel infirmier autorisé (PIA) et les infirmiers auxiliaires (Iaux) fournissent le volet spécialisé des soins infirmiers dans les centres de soins de longue durée au Canada. Cependant, peu d’études se sont penchées sur cette main-d’œuvre importante. Une enquête a été réalisée chez 309 PIS et 448 Iaux provenant de 91 centres pour personnes âgées situés dans l’Ouest canadien afin de décrire leur profil démographique et certaines variables associées à leur travail et à leur santé. Les Iaux étaient significativement plus jeunes que les PIA, travaillaient un plus grand nombre d’heures et avaient moins d’expérience en soins infirmiers. Ils étaient aussi davantage confrontés à des comportements réactifs d’aînés atteints de démence, comparativement aux PIA. Les PIA et les Iaux plus jeunes rapportaient un épuisement professionnel (burnout, épuisement émotionnel) plus sévère et davantage de problèmes de santé mentale que les groupes plus âgés. Des différences significatives ont également été observées entre les provinces, les régions et les propriétaires exploitants en ce qui concerne les variables démographiques, ainsi que les variables liées au travail et à la santé des PIA et des Iaux. Ces résultats permettront d’informer les décisions politiques importantes à venir et la planification de la main d’œuvre afin d’améliorer la qualité de vie au travail pour le personnel infirmier œuvrant en centres de soins de longue durée.
Epidemiology of two decades of invasive meningococcal disease in the Republic of Ireland: an analysis of national surveillance data on laboratory-confirmed cases from 1996 to 2016
Authors: Bennett D. , O'Lorcain P. , Morgan S. , Cotter S. , Cafferkey M. , Cunney R.
Published: March 2019

We examined the epidemiology of invasive meningococcal disease (IMD) in the Republic of Ireland (ROI) between epidemiological year (EY) 1996/1997 and EY2015/2016. Over the 20 EYs, 3707 cases were reported with annual incidence rates per 100 000 peaking at 11.6 in EY1999/2000, decreasing significantly to 1.5 in EY2015/2016. The highest disease burden was in infants and children <5, whereas adults aged ⩾65 years experienced the highest case fatality ratio (CFR) of 15.7% but over the study period the median annual CFR remained low (4.4%). Meningococcal serogroup B (menB) dominated (78%), followed by menC (17%), menW (1%) and menY (1%). The incidence of menC IMD declined significantly in all age groups after menC vaccine introduction in 2000. MenB incidence also declined over the 20 EYs with decreasing trends in all age groups under 65, including an almost 50% decrease in infants over the final four EYs. IMD incidence in the ROI has declined, partly attributable to menC vaccination success, coupled with a spontaneous decline in menB. However, recent gradual increases in non-menB IMD and the introduction of vaccines targeting menB demand continued detailed surveillance to accurately monitor trends and to assess vaccine impact.
Credit, confidence and the circulation of Exchequer bills in the early financial revolution
Authors: Graham Aaron
Published: March 2019

The Exchequer bills were a key component in Britain's financial revolution of the 1690s. Using a range of archival sources not examined in previous work, this article argues that closer study of how these bills were given credit and circulation between 1696 and 1698 can offer a more nuanced reading of the mechanisms which helped to create credible commitment in this period. Though proper institutional design did help to give the bills credit, it was only one part of a wider series of informal measures used by the Treasury to secure subscribers for the fund for circulating the bills and to manage the emission of bills to prevent high discounts. This reflects the fact that credit and confidence in this period were influenced by a wide range of factors, including commercial advantage, patriotism and the example offered by other investors, all of which could be manipulated by the Treasury to promote the credibility of the Exchequer bills. Proper institutional and financial incentives were therefore not the only factors which could create credible commitment in Britain's financial revolution.
23 “To die, to sleep – to sleep, perchance to dream..." Inhibition of Nightmares with Pramipexole: A Possible Treatment for PTSD
Authors: Escobar-Montealegre Freddy , Brar Preet , Hirsch Alan Richard
Published: March 2019

Introduction

The association of sleep disorders and post-traumatic stress disorder (PTSD) is almost universal. Nightmares are not only one of the most commonly associated but also featured as a diagnostic criterion for PTSD. PTSD-related nightmares are particularly distressing, may impair functioning and increase risk of suicide. No specific pharmacologic agent has been demonstrated to impair dreaming. Inhibition of PTSD-related nightmares with pramipexole has not heretofore been described. Such a case is presented.

Methods

Case study - This 60 year-old male with PTSD and trauma-related nightmares upon introduction of pramipexole 0.5mg PO qHS for Restless Leg Syndrome (RLS) had total elimination of dreams, which recurred upon discontinuation of this agent as a result of insomnia and increased anxiety. A lower dose of 0.375mg qHS provided optimal RLS-symptom control and overall improved tolerance despite nightmare recurrence.

Results

Abnormalities on Neurological examination: Recent recall: 2 of 4 objects without improvement with reinforcement. Able to spell the word “world” forwards but not backwards. Abstract thought impaired. Chemosensory testing: Anosmia and normogeusia. Motor: Drift: mild right pronator drift with right cerebellar spooning and right abductor digiti minimi sign. Reflexes: 3+ brachioradialis and biceps bilaterally, absent ankle jerks. Other: CT scan with and without contrast: normal.

Discussion

Nightmares related to PTSD may occur during Rapid Eye Movement (REM) sleep and non-REM sleep. Underlying sympathetic activation may lead to disruptive motor behavior similar to that seen in REM sleep behavior disorder. The exact mechanism of action by which inhibition of dreams occurred with use of pramipexole is unclear. Such a response is consistent with prior documented evidence of REM sleep suppression with low-dose pramipexole such as it‘s efficacy in reducing the intensity and frequency of nightmares and dream enactment related to REM sleep behavior disorder. Further research on therapeutic interventions that target nightmares directly may be beneficial for the management of patients with PTSD.
33 An Intervention to Decrease Benzodiazepine Prescribing by Providers in an Urban Clinic
Authors: Platt Lois , Savage Teresa A. , Rajagopal Nimmi
Published: March 2019

STUDY OBJECTIVES

Outpatient benzodiazepine use can cause side effects including dependence (20–30%) and death from respiratory depression when used with alcohol or opioids. Benzodiazepine use is on the rise in the U.S., increasing 67% from 1996–2013. In this quality improvement project, two educational interventions were combined with the intent of decreasing benzodiazepine prescribing by providers (MDs, APRNs) in an urban university clinic.

STUDY QUESTION

When prescribers working in a low-income clinic receive an intervention to increase awareness of benzodiazepine dangers and promote harm reduction strategies compared to treatment as usual, do they write fewer benzodiazepine prescriptions in the month following the intervention?

METHOD

A hybrid intervention combining academic detailing (educational outreach visits) and pharmaceutical industry detailing (merchandising, relationship building) was provided in two sessions to family practice providers (salaried and residents) working in a university outpatient clinic in Chicago. The subject matter included benzodiazepine risks, alternative treatments for anxiety & insomnia, and methods to deal with patient demand. All clinic providers (n=40) were invited to participate. Participants were self-selected to attend each session (although resident physicians were obligated to attend). A total of 20–24 providers attended each session.

Benzodiazepine prescription information was extracted by clinic information systems for two periods: 12months pre-intervention, and 30days post-intervention. For ease of comparison, each prescription was converted to a common denominator: the diazepam-equivalent dose. The pre-intervention monthly average (for one year) was compared to 30-day post-intervention data. The outcome measure was the numeric difference in the prescribed diazepam-equivalents pre- and post-intervention. This number was used as a measure of the effectiveness of the intervention. A decrease in prescribing post- compared to pre-intervention would indicate a successful intervention.

RESULTS

There was an 80% decrease in benzodiazepine prescribing in the 30-day post-intervention period compared to the 12-month pre-intervention monthly average. This result cannot be explained by personnel changes at the clinic. Although these did occur in 2017, the pattern of prescribing was stable throughout the year prior to this intervention.

CONCLUSIONS

The combination of academic and pharmaceutical industry detailing influenced family practice providers in an urban clinic setting to decrease benzodiazepine prescribing by 80%. Decreased benzodiazepine prescribing should decrease patient morbidity and mortality.
40 Pseudo Cranial Nerve I Dysfunction: Subjective Hyposmia and Subjective Hypogeusia but Normosmia and Normogeusia - 3 cases
Authors: Benskin Kristal , Hirsch Alan R.
Published: March 2019

INTRODUCTION

Hyposmia refers to reduced ability to smell and hypogeusia is a partial loss of the ability to taste (Hummel, Basile, & Huttenbrink, 2016). Complaints of hyposmia and hypogeusia in the presence of normosmia and normogeusia has not heretofore been described. Three such cases are presented.

OBJECTIVE

To explore the complaints of reduced smell and taste with normal objective olfaction and gustation.

METHOD

All patients were given screening tests for smell and taste and obtained scores consistent with normosmia and normogeusia. The 12-item version of the Brief Smell Identification Test (B-SIT), using the odorants banana, chocolate, cinnamon, gasoline, lemon, onion, paint thinner, pineapple, rose, soap, smoke and turpentine was used. The Retronasal Olfactory Test was used to determine their perception of flavour and the Proplythiouracil Disc Taste Test used for gustation. Each patient also underwent a complete physical and neurological examination with any abnormalities mentioned.

RESULTS

Case 1: This 53 year old female, 8months prior to presentation, developed the flu followed by the inability to taste any foods and differentiate between smells, with everything smelling bitter.

Results: Chemosensory testing: Olfaction: Brief Smell Identification Test (B-SIT): 10 (normosmia). Retronasal Olfactory Test: Retronasal Smell Index: 9 (normal). Gustation: Propylthiouracil Disc Taste Test: 7 (normal).

Case 2: This 86 year old female, 6months prior to presentation, developed reduced taste, of gradual onset, to the point upon presentation was only 10% normal. She was able to taste lemons but very little else.

Results: B-SIT: 9 (normosmia). Retronasal Smell Index: 10 (normal). Propylthiouracil Disc Taste Test: 10 (normogeusia).

Case 3: This 63 year old female was nasute until 3months prior to presentation, when she developed an upper respiratory infection, followed by loss of smell and taste to 20% of normal.

Results: B-SIT: 10 (normosmia). Retronasal Smell Index: 7 (normal). Propylthiouracil Disc Taste Test: 10 (normogeusia).

CONCLUSION

Discordance between subjective and objective findings may be due to the wide distribution of normal in the general population in olfactory ability. The associated reduction in retronasal smell may then be interpreted by the patient as reduced ability to taste. Alternatively, complaints of hyposmia and hypogeusiamay be due to a non-organic need such as malingering or psychosomatic illness, or could represent a primary defect in the cortical integration of smell and taste, interpreted as reduction in perceived flavor, yet the primary sensory neurons and threshold as tested would appear to be normal. This disparity possibly indicates that the testing modalities are too insensitive to demonstrate more subtle sensory perception findings, and suggests the need for more refined testing methods for smell and taste.