bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potent and selective pharmacodynamic synergy between the metabotropic glutamate receptor subtype 2–positive allosteric modulator JNJ‐46356479 and levetiracetam in the mouse 6‐Hz (44‐mA) model
Authors: Metcalf Cameron S. , Klein Brian D. , Smith Misty D. , Ceusters Marc , Lavreysen Hilde , Pype Stefan , Van Osselaer Nancy , Twyman Roy , White H. Steve 
Published: January 2018

SummaryObjectiveWe previously demonstrated that positive allosteric modulators (PAMs) of metabotropic glutamate subtype 2 (mGlu2) receptors have potential synergistic interactions with the antiseizure drug levetiracetam (LEV). The present study utilizes isobolographic analysis to evaluate the combined administration of JNJ‐46356479, a selective and potent mGlu2 PAM, with LEV as well as sodium valproate (VPA) and lamotrigine (LTG).MethodsThe anticonvulsant efficacy of JNJ‐46356479 was evaluated in the 6‐Hz model of psychomotor seizures in mice. JNJ‐46356479 was administered in combination with LEV using 3 fixed dose‐ratio treatment groups in the mouse 6‐Hz (44‐mA) seizure test. The combination of JNJ‐46356479 with LEV was also evaluated in the mouse corneal kindling model. The potential interactions of JNJ‐46356479 with the antiseizure drugs VPA and LTG were also evaluated using fixed dose‐ratio combinations. Plasma levels were obtained for analysis of potential pharmacokinetic interactions for each combination studied in the mouse 6‐Hz model.ResultsJNJ‐46356479 was active in the 6‐Hz model at both 32‐mA and 44‐mA stimulus intensities (median effective dose = 2.8 and 10.2 mg/kg, respectively). Using 1:1, 1:3, and 3:1 fixed dose‐ratio combinations (LEV:JNJ‐46356479), coadministration was significantly more potent than predicted for additive effects, and plasma levels suggest this synergism was not due to pharmacokinetic interactions. Studies in kindled mice further demonstrate the positive pharmacodynamic interaction of LEV with JNJ‐46356479. Using 1:1 dose‐ratio combinations of JNJ‐46356479 with either VPA or LTG, there were no significant differences observed for coadministration.SignificanceThese studies demonstrate a synergistic interaction of JNJ‐46356479 with LEV, whereas no such effect occurred for JNJ‐46356479 with either VPA or LTG. The synergy seems therefore to be specific to LEV, and the combination LEV/mGlu2 PAM has the potential to result in a rational polypharmacy approach to treat patients with refractory epilepsy, once it has been confirmed in clinical studies.
Real‐world experience with use of Antihemophilic Factor (Recombinant), PEGylated for prophylaxis in severe haemophilia A
Authors: Dunn A. L. , Ahuja S. P. , Mullins E. S. 
Published: January 2018

IntroductionProphylaxis with extended half‐life factor VIII (FVIII) is approved for haemophilia A, but data regarding routine clinical use are limited.AimTo assess real‐world experience of ADYNOVATE® (Antihemophilic Factor (Recombinant), PEGylated prophylaxis in children and adults with haemophilia A.MethodsA retrospective chart review was conducted in three US haemophilia treatment centres. Records of all patients who began Adynovate prophylaxis in routine clinical practice were identified. Demographic, clinical and patient‐reported information beginning 6 months before initiation of Adynovate until the record review was analysed.ResultsFifteen patients (aged 9 months to 28 years), with median 9 months’ use of Adynovate (range 1‐15 months), were identified. All had switched from another prophylactic regimen, 13 (87%) from standard half‐life recombinant FVIII. Nine (60%) patients had ≥1 bleed within 6 months preswitch. The most frequent reason for switching was to reduce infusion frequency (14 patients). After switching, infusion frequency reduced for 13 patients, and overall weekly factor consumption decreased by 19%. Eight (53%) patients had no bleeds postswitch, three (20%) had spontaneous joint bleeds (vs four pre‐switch), and three (20%) had only mild traumatic bleeds. Patient/parental satisfaction with Adynovate was documented as positive in 13 of 15 (87%) cases; 2 patients were not satisfied and discontinued Adynovate. No adverse events were considered related to Adynovate.ConclusionIn patients who switched from a standard half‐life FVIII to Adynovate prophylaxis in routine clinical practice, bleeding control was generally improved or maintained, with a lower infusion frequency and factor consumption in most patients.
Left ventricular assist device patient maintained on home hemodialysis: A novel class of patients to the home dialysis population
Authors: Hanna Ramy M. , Cruz Daniel , Selamet Umut , Hasnain Huma , Kwon Murray , Baas Arnold , Wilson James 
Published: January 2018

AbstractSevere heart failure is increasingly being managed by cardiac transplantation, and in some cases mechanical support devices serve as destination therapies. Left ventricular assist devices (LVADs) were approved for destination therapy for end stage heart failure patients before the more advanced total artificial heart modality became available. One common complication of mechanical assist device placement is acute kidney injury. Historically, patients with mechanical support devices have had to have inpatient hemodialysis until combined heart kidney transplant. Though, some units have started accepting LVAD patients in outpatient dialysis clinics. The cost of in center hemodialysis remains high and home dialysis modalities are becoming increasingly popular. We report the first patient with an LVAD to undergo training and successful home hemodialysis while awaiting combined heart kidney transplantation.
Differentiating Contract Killers: A Narrative‐Based Approach
Authors: YANEVA MIROSLAVA , IOANNOU MARIA , HAMMOND LAURA , SYNNOTT JOHN 
Published: January 2018

AbstractPrevious attempts to determine contract killers’ behaviour have not benefited from any formal psychological framework of behavioural distinction. The Narrative Action System model (NAS model; Canter and Youngs 2009) offers an empirical basis for differentiating contract killings and examining the psychological underpinnings of different contract killer styles. The model identifies four major narrative offender types: Professional, Revenger, Hero, and Victim. The present study aims to examine whether these themes can be applied to contract killing. Content analysis of 75 contract killer cases identified 56 crime scene actions. Data were subjected to a non‐metric multidimensional scaling procedure, namely Smallest Space Analysis (SSA‐I). Findings revealed four distinct types of contract killers that could be related to the four modes of offending proposed by the NAS model. Differences in the thematic structure of contract killing offences are discussed, and implications are offered for clinical and investigative purposes.
Galectin‐3 is an amplifier of the interleukin‐1β‐mediated inflammatory response in corneal keratinocytes
Authors: Uchino Yuichi , Woodward Ashley M. , Mauris Jérôme , Peterson Kristoffer , Verma Priya , Nilsson Ulf J. , Rajaiya Jaya , Argüeso Pablo 
Published: January 2018

SummaryInterleukin‐1β (IL‐1β) is a potent mediator of innate immunity commonly up‐regulated in a broad spectrum of inflammatory diseases. When bound to its cell surface receptor, IL‐1β initiates a signalling cascade that cooperatively induces the expression of canonical IL‐1 target genes such as IL‐8 and IL‐6. Here, we present galectin‐3 as a novel regulator of IL‐1β responses in corneal keratinocytes. Using the SNAP‐tag system and digitonin semi‐permeabilization, we show that recombinant exogenous galectin‐3 binds to the plasma membrane of keratinocytes and is internalized into cytoplasmic compartments. We find that exogenous galectin‐3, but not a dominant negative inhibitor of galectin‐3 polymerization lacking the N‐terminal domain, exacerbates the response to IL‐1β by stimulating the secretion of inflammatory cytokines. The activity of galectin‐3 could be reduced by a novel d‐galactopyranoside derivative targeting the conserved galactoside‐binding site of galectins and did not involve interaction with IL‐1 receptor 1 or the induction of endogenous IL‐1β. Consistent with these observations, we demonstrate that small interfering RNA‐mediated suppression of endogenous galectin‐3 expression is sufficient to impair the IL‐1β‐induced secretion of IL‐8 and IL‐6 in a p38 mitogen‐activated protein kinase‐independent manner. Collectively, our findings provide a novel role for galectin‐3 as an amplifier of IL‐1β responses during epithelial inflammation through an as yet unidentified mechanism.
Recovery orientation in mental health inpatient settings: Inpatient experiences?
Authors: Waldemar Anna Kristine , Esbensen Bente Appel , Korsbek Lisa , Petersen Lone , Arnfred Sidse 
Published: January 2018

AbstractOffering mental health treatment in line with a recovery‐oriented practice has become an objective in the mental health services in many countries. However, applying recovery‐oriented practice in inpatient settings seems challenged by unclear and diverging definitions of the concept in and the organization of these settings. In Denmark, educational and organizational efforts have been made to organize inpatient services with a recovery‐oriented approach. Hence, we aimed to explore whether and how these efforts are reflected in the inpatients’ experiences of their care and treatment. Semi‐structured interviews were conducted with 14 inpatients from two mental health inpatient wards using an interview guide based on factors from the Recovery Self‐Assessment. Qualitative content analysis was applied in the analysis. Six themes covering the participants’ experiences were identified. The participants felt accepted and protected in the ward and found comfort in being around other people but missed talking and engaging with health professionals. They described limited choice and influence on the course of their treatment, and low information levels regarding their treatment, which they considered to consist predominantly of medication. Furthermore, they described feeling continuously observed and assessed from a distance by health professionals. Like the sparse previous research among inpatients, the results highlight ambivalent experiences of health professionals’ support and ward structure as well as the medical treatment hegemony. As such, the educational and organizational efforts of introducing recovery‐oriented practices in the wards seemed not very well reflected in the participants’ experiences of their stay.
The Alleged Opposition Deficit in European Union Politics: Myth or Reality?
Authors: Karlsson Christer , Persson Thomas 
Published: January 2018

AbstractAccording to the ‘opposition deficit thesis’ European Union politics is characterized by a conspicuous absence of opposition to the policies promoted by the EU. However, once we start looking for systematic evidence supporting the claim of an opposition deficit in EU politics, we come up surprisingly empty handed. This article seeks to rectify the lacuna in previous research by examining how much and what type of opposition actually exist in EU politics. The study formulates four hypotheses on the state of political opposition in EU politics, and breaks new ground by testing their validity by use of unique data collected from the Swedish European Affairs Committee for the period 1995–2016. The results show there is in fact considerably more opposition present in EU politics than has previously been assumed. The opposition deficit thesis thus seems to be more myth than reality.
Adapting the vertical position of implants with a conical connection in relation to soft tissue thickness prevents early implant surface exposure: A 2‐year prospective intra‐subject comparison
Authors: Vervaeke Stijn , Matthys Carine , Nassar Rima , Christiaens Veronique , Cosyn Jan , De Bruyn Hugo 
Published: January 2018

AbstractAimTo evaluate the effect of soft tissue thickness on bone remodelling and to investigate whether implant surface exposure can be avoided by adapting the vertical implant position in relation to the soft tissue thickness.Materials and MethodsTwenty‐five patients received two non‐splinted implants supporting an overdenture in the mandible. Soft tissue thickness was measured using bone sounding and ultrasonically. One implant was installed equicrestally (control), and the vertical position of the second implant was adapted to the site‐specific soft tissue thickness (test). Crestal bone levels were determined on digital peri‐apical radiographs and compared with baseline (implant placement).ResultsTwenty‐five patients were consecutively treated. No implants failed during the follow‐up. A significant correlation was observed between soft tissue thickness and bone level alterations after 6 months (ultrasound ICC = 0.610; bone sounding ICC = 0.641) with inferior bone levels for equicrestal implants when thin tissues are present. Subcrestal implants showed significantly better bone levels after 6‐month (n = 24, 0.04 mm versus 0.72 mm; p < .001), 1‐year (n = 24, 0.03 mm versus 0.77 mm; p < .001) and 2‐year follow‐up (n = 24, 0.04 mm versus 0.73 mm; p < .001).ConclusionInitial bone remodelling was affected by soft tissue thickness. Anticipating biologic width re‐establishment by adapting the vertical position of the implant seemed highly successful to avoid implant surface exposure.
Effects of nanostructured essential oils against subterranean termites (Coptotermes gestroi)
Authors: Clerici D. J. , de Souza M. E. , Quatrin P. M. , Vianna Santos R. C. , Costa‐Leonardo A. M. , Ourique A. F. , Raffin R. P. , Marques C. T. , de Camargo Dietrich C. R. R. , de Silva Gündel S. , Klein B. , Wagner R. 
Published: January 2018

AbstractCurrently, the control of termites is mainly carried out with the use of chemical pesticides, which although effective, pose risks to the environment and to human beings. An alternative to using such chemical pesticides is natural products such as essential oils in insecticidal action. Despite the fact of being effective, essential oils are unstable, poorly soluble in water, and degrade from the action of light, oxygen even at moderate temperatures. Thus, the nanostructuring of essential oils could circumvent such problems and ensure its effectiveness. The following study aimed to assess for the first time the effects of nanostructured systems of essential oils of Cymbopogon flexuosus, Eucalyptus globulus and Melaleuca alternifolia in subterranean termites (Coptotermes gestroi). The results showed that the solid lipid nanoparticles of M. alternifolia have both repellent and insecticide action. The following study showed that nanostructuring of essential oils with insecticidal action is a promising tool in the fight against termites.
Silencing GRAS2 reduces fruit weight in tomato
Authors: Li Miao , Wang Xin , Li Changxing , Li Hanxia , Zhang Junhong , Ye Zhibiao 
Published: January 2018

AbstractGRAS family transcription factors are involved in multiple biological processes in plants. Here, we report that GRAS2 plays a vital role in regulating fruit weight in tomato (Solanum lycopersicum). We establish that the expression of GRAS2 was elevated in ovaries and maintained at a constant level in fertilized ovules. Reduction of GRAS2 expression in transgenic plants reduced fruit weight through modulating ovary growth and cell size. At the metabolic level, downregulation of GRAS2 decreased activities of the gibberellic acid biosynthesis and signal transduction pathways, leading to insufficient levels of active gibberellic acid during the initial ovary development of tomato. Moreover, genotypic diversity of GRAS2 was consistent with the molecular basis of fruit weight evolution, suggesting that GRAS2 contributes to the molecular basis of the evolution of fruit weight in tomato. Collectively, these findings enhance our understanding of GRAS2 functions, in fruit development of tomato, and demonstrate a strong association between the GRAS gene family and fruit development.
Considerations for Implementing Group‐Level Prenatal Health Interventions in Low‐Resource Communities: Lessons Learned From Haiti
Authors: Abrams Jasmine A. , Forte Janett , Bettler Clarie , Maxwell Morgan 
Published: January 2018

AbstractHaiti's high maternal and infant mortality rates evidence an urgent need for implementation of evidence‐based strategies. A potential cost‐effective strategy to mitigate high maternal and infant mortality rates is group prenatal care, an innovative model that combines antenatal clinical assessment with pregnancy education. Despite research demonstrating the effectiveness of this model in high‐resource settings, less is known about the challenges of implementing it in low‐resource settings. The purpose of this article is to provide recommendations for overcoming challenges of implementing group prenatal care in low‐resources communities globally. Challenges addressed include language, literacy, space, cultural appropriateness of intervention content, and sociopolitical climate. Using examples from work conducted in Haiti, this information can be used to assist practitioners and researchers with overcoming challenges of implementing models of group care in international low‐resource communities.
Neuromuscular disease‐specific questionnaire to assess quality of life in patients with chronic inflammatory demyelinating polyradiculoneuropathy
Authors: Kacar Aleksandra , Bjelica Bogdan , Bozovic Ivo , Peric Stojan , Nikolic Ana , Cobeljic Mina , Petrovic Milutin , Stojanov Aleksandar , Djordjevic Gordana , Vukojevic Zoran , Dominovic‐Kovacevic Aleksandra , Stojanovic Miroslav , Stevic Zorica , Rakocevic‐Stojanovic Vidosava , Lavrnic Dragana , Basta Ivana 
Published: January 2018

AbstractTo date, generic questionnaires have been used to investigate quality of life (QoL) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients. Although these measures are very useful, they are not usually precise enough to measure all specific characteristics of the disease. Our aim was to investigate QoL using the neuromuscular disease‐specific questionnaire (individualized neuromuscular quality of life, INQoL) in a large cohort of patients with CIDP. Our study comprised 106 patients diagnosed with CIDP. INQoL questionnaire, Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) disability score, Visual Analogue Pain Scale, Beck Depression Inventory, and Krupp's Fatigue Severity Scale were used in our study. Physical domains of INQoL were more affected than mental, and the overall score was 57 ± 25. Significant predictors of higher INQoL score in our patients with CIDP were severe fatigue (β = 0.35, p < 0.01), higher INCAT disability score at time of testing (β = 0.29, p < 0.01), and being unemployed/retired (β = 0.22, p < 0.05). QoL was reduced in our cohort of CIDP patients, which was more pronounced in physical segments. Patients with fatigue, more severe disability, and unemployed/retired need special attention of neurologists because they could be at greater risk to have worse QoL.
Clinical study to evaluate the performance of a noninvasive focused ultrasound device for thigh fat and circumference reduction compared to control
Authors: Wilkerson Eric C. , Bloom Bradley S. , Goldberg David J. 
Published: January 2018

SummaryBackground and objectivesAn FDA‐cleared focused ultrasound device (UltraShape, Syneron Candela®, Yokneam, Israel) for noninvasive abdominal fat reduction produces localized mechanical cellular membrane disruption in adipocytes. This study seeks to determine the safety and efficacy of this device for use on the thighs.Study designs/Materials and methodsFourteen women aged 33‐60 were selected to receive 3 biweekly treatments to one thigh with the other thigh serving as an internal control. The subjects had a BMI range of 18‐30 kg/m2 and a weight range of 54‐83 kg. After the third treatment, patients were followed at 4, 8, and 16 weeks. Fat thickness was measured by both caliper and ultrasound. In addition, thigh circumference and the patient's weight were measured. Pain, edema, erythema, and adverse events as well as investigator and patient overall satisfaction were recorded at all visits.ResultsIn comparison with the control, there was a statistically significant average reduction in fat thickness measured by calipers at all time points with a 22.20% (P = .0165) improvement in 16 weeks. By ultrasound, there was a 19.23% (4.03 mm P = .0051) reduction in fat thickness at 16 weeks with statistically significant improvement at the other follow‐up visits. At 16 weeks, thigh circumference improved, on average, 2.8 cm (P = .0059) at the midline. 90.0% of the subjects were satisfied with the results at 16 weeks, and the investigator was 100% satisfied. No adverse events were reported; no edema was observed in any subject. All subjects experienced mild erythema. All reported zero pain on a 0‐10 scale.ConclusionFocused ultrasound is safe, effective, and well tolerated to improve the circumference and fat thickness of the thighs without significant side effects. There were no significant adverse events. Investigators and subjects were highly satisfied with the results.
SKILLS MISMATCH: CONCEPTS, MEASUREMENT AND POLICY APPROACHES
Authors: McGuinness Seamus , Pouliakas Konstantinos , Redmond Paul 
Published: January 2018

AbstractThe term skills mismatch is very broad and can relate to many forms of labour market friction, including vertical mismatch, skill gaps, skill shortages, field of study (horizontal) mismatch and skill obsolescence. In this paper, we provide a clear overview of each concept and discuss the measurement and inter‐relatedness of different forms of mismatch. We present a comprehensive analysis of the current position of the literature on skills mismatch and highlight areas which are relatively underdeveloped and may warrant further research. Using data from the European Skills and Jobs Survey, we assess the incidence of various combinations of skills mismatch across the EU. Finally, we review the European Commission's country‐specific recommendations and find that skills mismatch, when referring to underutilized human capital in the form of overeducation and skills underutilization, receives little policy attention. In cases where skills mismatch forms part of policy recommendations, the policy advice is either vague or addresses the areas of mismatch for which there is the least available evidence.