bluuebunny/crossref_metadata_2025 huggingface dataset:
Macromolecular Pt(IV) Prodrugs from Poly(organo)phosphazenes
Authors: Henke Helena , Kryeziu Kushtrim , Banfić Jelena , Theiner Sarah , Körner Wilfried , Brüggemann Oliver , Berger Walter , Keppler Bernhard K. , Heffeter Petra , Teasdale Ian
Published: May 2016

The preparation of novel macromolecular prodrugs via the conjugation of two platinum(IV) complexes to suitably functionalized poly(organo)phosphazenes is presented. The inorganic/organic polymers provide carriers with controlled dimensions due to the use of living cationic polymerization and allow the preparation of conjugates with excellent aqueous solubility but long‐term hydrolytic degradability. The macromolecular Pt(IV) prodrugs are designed to undergo intracellular reduction and simultaneous release from the macromolecular carrier to present the active Pt(II) drug derivatives. In vitro investigations show a significantly enhanced intracellular uptake of Pt for the macromolecular prodrugs when compared to small molecule Pt complexes, which is also reflected in an increase in cytotoxicity. Interestingly, drug‐resistant sublines also show a significantly smaller resistance against the conjugates compared to clinically established platinum drugs, indicating that an alternative uptake route of the Pt(IV) conjugates might also be able to overcome acquired resistance against Pt(II) drugs. In vivo studies of a selected conjugate show improved tumor shrinkage compared to the respective Pt(IV) complex.

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On a non‐stationary fluid flow problem in an infinite periodic pipe
Authors: Chipot M. , Klovienė N. , Pileckas K. , Zube S.
Published: May 2016

We study linearized, non‐stationary Navier–Stokes type equations with the given flux in an infinite pipe periodic of period length L with respect to . The existence and uniqueness of the solution is proved. Moreover, the convergence of the solution in a finite pipe of length to the L‐periodic solution as is investigated.
On the dynamics of a third order Newton's approximation method
Authors: Gheondea Aurelian , Şamcı Mehmet Emre
Published: May 2016

We provide an answer to a question raised by S. Amat, S. Busquier, S. Plaza on the qualitative analysis of the dynamics of a certain third order Newton type approximation function , by proving that for functions f twice continuously differentiable and such that both f and its derivative do not have multiple roots, with at least four roots and infinite limits of opposite signs at , has periodic points of any prime period and that the set of points a at which the approximation sequence does not converge is uncountable. In addition, we observe that in their Scaling Theorem analyticity can be replaced with differentiability.
Structure and properties of ultra fine grained aluminium alloys after laser surface treatment
Authors: Tański T. , Snopiński P. , Pakieła W.
Published: May 2016

The presented investigation results concern the influence of laser heat treatment on the structure and properties of aluminium alloys that underwent severe plastic deformation using the equal channel angular pressing method. The initial stage of this study aimed at determining the possibility of improving the mechanical properties of core material using the severe plastic deformation process method and the subsequent partial recrystallization process that allows obtaining equivalent ductility and grain refinement. The next stage involving investigating the surface modification of the fine grained alloy by remelting and feeding silicon carbide powder into the molten material and to end solidification. To modify the surface layer of aluminium alloy, the Ytterbium Laser System YLS‐4000 has been used, with the applied power of the laser beam in the range of 1.2 kW and 2.0 kW. The linear laser scan rate was 0.4 m/min. Results of the conducted treatments a core material with better mechanical properties, in comparison to initial state, was obtained whereas laser surface treatment allows to obtain composite surface with increased hardness and enhanced wear resistance when compared to substrate material.
GLIMPSED: An Improved Docking Protocol for Cognate Docking
Authors: Rizzi Andrea , Ciacci Andrea , Capelli Anna Maria
Published: May 2016

The cognate docking performance of Glide was evaluated using the Astex diverse set. The standard Glide SP protocol obtained a 85.7 % success rate when the shape similarity cutoff was set to 0.625. The analysis of docking failures pointed out that, when the SiteMap binding site exposure is less than 0.491, 51 out of 52 ligands are correctly positioned. In light of this important finding, an improved docking protocol called GLIMPSED was set up. GLIMPSED relies on the standard Glide SP protocol for binding sites with low exposure, while a more accurate sampling of docking poses followed by a final MM‐GBSA rescoring is performed for those highly exposed to the solvent. GLIMPSED and Glide SP were compared applying an accurate and rigorous metrics described in the literature by Hawkins et al. As a result, GLIMPSED was able to dock 89.3 % of the ligands in a correct way. Even though this number is not remarkably different from that obtained with the standard method, it is indeed statistically significant. Applying the Cohen's effect size test, a small, but not trivial, superiority of GLIMPSED was found with respect to standard Glide SP protocol. In our view the SiteMap binding site exposure parameter should be used as guideline to decide whether either a standard or a more extended docking protocol has to be adopted to predict good binding poses.
O2‐sensitive MRI distinguishes brain tumor versus radiation necrosis in murine models
Authors: Beeman Scott C. , Shui Ying‐Bo , Perez‐Torres Carlos J. , Engelbach John A. , Ackerman Joseph J. H. , Garbow Joel R.
Published: May 2016

Purpose

The goal of this study was to quantify the relationship between the 1H longitudinal relaxation rate constant, R1, and oxygen (O2) concentration (relaxivity, r1) in tissue and to quantify O2‐driven changes in R1 (ΔR1) during a breathing gas challenge in normal brain, radiation‐induced lesions, and tumor lesions.

Methods

R1 data were collected in control‐state mice (n = 4) during three different breathing gas (and thus tissue O2) conditions. In parallel experiments, pO2 was measured in the thalamus of control‐state mice (n = 4) under the same breathing gas conditions using an O2‐sensitive microprobe. The relaxivity of tissue O2 was calculated using the R1 and pO2 data. R1 data were collected in control‐state (n = 4) mice, a glioma model (n = 7), and a radiation necrosis model (n = 6) during two breathing gas (thus tissue O2) conditions. R1 and ΔR1 were calculated for each cohort.

Results

O2 r1 in the brain was 9 × 10−4 ± 3 × 10−4 mm Hg−1· s−1 at 4.7T. R1 and ΔR1 measurements distinguished radiation necrosis from tumor (P< 0.03 and P< 0.01, respectively).

Conclusion

The relaxivity of O2 in the brain is determined. R1 and ΔR1 measurements differentiate tumor lesions from radiation necrosis lesions in the mouse models. These pathologies are difficult to distinguish by traditional imaging techniques; O2‐driven changes in R1 holds promise in this regard. Magn Reson Med 75:1–2, 2016. © 2015 Wiley Periodicals, Inc.
An adaptive level‐set method with enhanced volume conservation for simulations in multiphase domains
Authors: Shakoor M. , Bouchard P.‐O. , Bernacki M.
Published: May 2016

Mechanical computations in multiphase domains raise numerous difficulties from the generation of the initial mesh to its adaptation throughout the simulation. All alternatives to mesh adaptation, such as level‐set methods, have the well‐known drawback of inducing volume conservation issues. In this paper, a moving mesh method is coupled to a topological mesh adaptation technique in order to track moving and deforming interfaces in multiphase simulations, with a robust control of mesh quality. Level‐set functions are used as intermediaries to enhance the mesh adaptation technique with a volume conservation constraint, which is compatible both with implicit and with body‐fitted interfaces. Results show that this method has the same advantage of permitting important displacements, deformations, and topological changes (coalescence of interfaces, for example) as a standard level‐set method, while volume diffusion is drastically reduced. Copyright © 2016 John Wiley & Sons, Ltd.
Rely on transparency and process to limit liability related to academic dismissals
Authors: Porter Michael
Published: May 2016

Students invest increasingly more money and time to earn a college degree. Meanwhile, colleges vigorously market the long‐term value of a two‐year, four‐year or graduate degree by pointing out postdegree income differentials.
A Phos‐tag SDS‐PAGE method that effectively uses phosphoproteomic data for profiling the phosphorylation dynamics of MEK1
Authors: Kinoshita Eiji , Kinoshita‐Kikuta Emiko , Kubota Yuji , Takekawa Mutsuhiro , Koike Tohru
Published: May 2016

MEK1, an essential component of the mitogen‐activated protein kinase (MAPK) pathway, is phosphorylated during activation of the pathway; 12 phosphorylation sites have been identified in human MEK1 by MS‐based phosphoproteomic methods. By using Phos‐tag SDS‐PAGE, we found that multiple variants of MEK1 with different phosphorylation states are constitutively present in typical human cells. The Phos‐tag‐based strategy, which makes effective use of existing information on the location of phosphorylation sites, permits quantitative time‐course profiling of MEK1 phosphospecies in their respective phosphorylation states. By subsequent immunoblotting with an anti‐HaloTag antibody, we analyzed a HaloTag‐fused MEK1 protein and 12 potential phosphorylation‐site‐directed mutants of the protein transiently expressed in HEK 293 cells. This strategy revealed that MEK1 is constitutively and mainly phosphorylated at the Thr‐292, Ser‐298, Thr‐386, and Thr‐388 residues in vivo, and that combinations of phosphorylations at these four residues produce at least six phosphorylated variants of MEK1. Like the levels of phosphorylation of the Ser‐218 and Ser‐222 residues by RAF1, which have been well studied, the phosphorylation statuses of Thr‐292, Ser‐298, Thr‐386, and Thr‐388 residues vary widely during activation and deactivation of the MAPK pathway. Furthermore, we demonstrated inhibitor‐specific profiling of MEK1 phosphospecies by using three MEK inhibitors: TAK‐733, PD98059, and U0126.
A review of Neuropharmacology Effects ofNigella sativaand Its Main Component, Thymoquinone
Authors: Javidi Soheila , Razavi Bibi Marjan , Hosseinzadeh Hossein
Published: May 2016

Neuropharmacology is the scientific study of drug effect on nervous system. In the last few years, different natural plants and their active constituents have been used in neurological therapy. The availability, lower price, and less toxic effects of herbal medicines compared with synthetic agents make them as simple and excellent choice in the treatment of nervous diseases.Nigella sativa, which belongs to the botanical family of Ranunculaceae, is a widely used medicinal plant all over the world. In traditional and modern medicines several beneficial properties have been attributed toN. sativaand its main component, thymoquinone (TQ). In this review, various studies in scientific databases regarding the neuropharmacological aspects ofN. sativaand TQ have been introduced. Results of these studies showed thatN. sativaand TQ have several properties including anticonvulsant, antidepressant, anxiolytic, anti‐ischemic, analgesic, antipsychotic, and memory enhancer. Furthermore, its protective effects against neurodegenerative diseases such as Alzheimer, Parkinson and multiple sclerosis have been discussed. Although there are many studies indicating the beneficial actions of this plant in nervous system, the number of research projects relating to the human reports is rare. Copyright © 2016 John Wiley & Sons, Ltd.
The Effects of Pycnogenol® as Add‐on Drug to Metformin Therapy in Diabetic Rats
Authors: Jankyova Stanislava , Rubintova Dominika , Janosikova Lenka , Panek Peter , Foltanova Tatiana , Kralova Eva
Published: May 2016

The progression of diabetes mellitus leads in time to the development of serious cardiovascular complications. Pycnogenol® (PYC) belongs to strong antioxidants that may interfere with different pathways playing an important role in diseases associated with oxidative stress. Metformin (MET), commonly used antidiabetic drug, has cardio‐protective effects via activation of AMP kinase (AMPK). In our study, we examined the effects of PYC as add‐on drug to metformin therapy in streptozotocin (STZ)‐induced diabetic rats. Our results revealed that both used agents, PYC and MET, showed improvement of blood glucose levels, vascular reactivity, left ventricular hypertrophy, expression of AMPK, glucose transporter 4 (GLUT4) and calcium/calmodulin‐dependent protein kinase II (CaMKII) in left ventricle of the hearts. However, the combination of these interventions has failed to possess higher efficacy. Copyright © 2016 John Wiley & Sons, Ltd.
How Can SMEs Benefit from Big Data? Challenges and a Path Forward
Authors: Coleman Shirley , Göb Rainer , Manco Giuseppe , Pievatolo Antonio , Tort‐Martorell Xavier , Reis Marco Seabra
Published: May 2016

Big data is big news, and large companies in all sectors are making significant advances in their customer relations, product selection and development and consequent profitability through using this valuable commodity. Small and medium enterprises (SMEs) have proved themselves to be slow adopters of the new technology of big data analytics and are in danger of being left behind. In Europe, SMEs are a vital part of the economy, and the challenges they encounter need to be addressed as a matter of urgency. This paper identifies barriers to SME uptake of big data analytics and recognises their complex challenge to all stakeholders, including national and international policy makers, IT, business management and data science communities.

The paper proposes a big data maturity model for SMEs as a first step towards an SME roadmap to data analytics. It considers the ‘state‐of‐the‐art’ of IT with respect to usability and usefulness for SMEs and discusses how SMEs can overcome the barriers preventing them from adopting existing solutions. The paper then considers management perspectives and the role of maturity models in enhancing and structuring the adoption of data analytics in an organisation. The history of total quality management is reviewed to inform the core aspects of implanting a new paradigm. The paper concludes with recommendations to help SMEs develop their big data capability and enable them to continue as the engines of European industrial and business success. Copyright © 2016 John Wiley & Sons, Ltd.
Board representation in international joint ventures
Authors: Cuypers Ilya R. P. , Ertug Gokhan , Reuer Jeffrey J. , Bensaou Ben
Published: May 2016

Research summary: Relatively little attention has been paid to boards in international joint ventures (IJVs), and the composition of these boards in particular. We examine the determinants of foreign partners' representation on IJV boards in order to advance our knowledge of this facet of IJV governance. We argue that a foreign partner's representation on the IJV board is related to its equity contribution. However, we hypothesize that this relationship is moderated by IJV and host country characteristics that affect the importance of the internal and external roles IJV boards serve. These results provide insights into the conditions under which a partner might wish to secure greater board representation for its level of equity, or utilize less board representation than might be suggested by its equity level alone.

Managerial summary: The functioning and composition of corporate boards have long been seen as critical to managers and shareholders alike. In contrast, the boards of IJVs have been relatively neglected. We advance our knowledge of this important facet of IJV governance. Specifically, we highlight the importance of two roles (i.e., an internal and external role) that IJV boards and directors fulfill. We find that the importance of these internal and external roles of boards determines whether a foreign partner might wish to secure greater board representation for its level of equity, or utilize less board representation than might be suggested by its equity level alone. Our results provide novel insights that can help managers structure their IJV boards. Copyright © 2016 John Wiley & Sons, Ltd.
Cross‐border acquisitions and the asymmetric effect of power distance value difference on long‐term post‐acquisition performance
Authors: Huang Zhi , Zhu Hong (Susan) , Brass Daniel J.
Published: May 2016

Research summary: Inconclusive findings about the effect of national cultural differences on post‐acquisition performance may be created by the failure to distinguish among the different cultural dimensions and the asymmetry of cultural differences. To demonstrate a different approach, this study focuses on one dimension of national cultural values—power distance value (PDV) and develops a framework for the asymmetric effect ofPDVdifferences in creating two types of conflicts. The analysis of 2,115 cross‐border acquisitions in the global information technology industry shows thatPDVdifferences undermine the long‐term post‐acquisition performance of acquirers. This effect is stronger when acquirers are higher than targets inPDVthan when the opposite is the case. This asymmetric effect ofPDVdifference depends on national status difference, business relatedness, and acquisition experience.

Managerial summary:National cultural differences can create “cultural clashes” to undermine the value creation by cross‐border acquisitions. During integration, individuals react to the acquirer–target hierarchy according to their respective power distance value (PDV): the extent to which they value equality (lowPDV) or hierarchy (highPDV).PDVdivergence results in two types of conflicts, depending on whether acquirers are higher or lower than targets inPDV. The two types of conflicts vary in the magnitude of their harmful effect on post‐acquisition performance. Both types of conflicts are more detrimental when acquirers are higher than targets in country status and when individuals need to interact more intensely. Acquisition experience can both help and harm post‐acquisition performance. These findings offer important implications for managing cross‐border acquisitions. Copyright © 2016 John Wiley & Sons, Ltd.
Tunable Design of Structural Colors Produced by Pseudo‐1D Photonic Crystals of Graphene Oxide
Authors: Tong Liping , Qi Wei , Wang Mengfan , Huang Renliang , Su Rongxin , He Zhimin
Published: May 2016

It is broadly observed that graphene oxide (GO) films appear transparent with a thickness of about several nanometers, whereas they appear dark brown or almost black with thickness of more than 1 μm. The basic color mechanism of GO film on a sub‐micrometer scale, however, is not well understood. This study reports on GO pseudo‐1D photonic crystals (p1D‐PhCs) exhibiting tunable structural colors in the visible wavelength range owing to its 1D Bragg nanostructures. Striking structural colors of GO p1D‐PhCs could be tuned by simply changing either the volume or concentration of the aqueous GO dispersion during vacuum filtration. Moreover, the quantitative relationship between thickness and reflection wavelength of GO p1D‐PhCs has been revealed, thereby providing a theoretical basis to rationally design structural colors of GO p1D‐PhCs. The spectral response of GO p1D‐PhCs to humidity is also obtained clearly showing the wavelength shift of GO p1D‐PhCs at differently relative humidity values and thus encouraging the integration of structural color printing and the humidity‐responsive property of GO p1D‐PhCs to develop a visible and fast‐responsive anti‐counterfeiting label. The results pave the way for a variety of potential applications of GO in optics, structural color printing, sensing, and anti‐counterfeiting.
Separating efficacy and sedative effects of guanfacine extended release in children and adolescents with ADHD from four randomized, controlled, phase 3 clinical trials
Authors: Huss M. , McBurnett K. , Cutler A.J. , Hervás A. , Gu J. , Dirks B. , Newcorn J.H.
Published: May 2016

Introduction

Guanfacine extended release (GXR) is a non-stimulant treatment for attention-deficit/hyperactivity disorder (ADHD).

Objective

To separate efficacy and sedative treatment-emergent adverse events (TEAEs) associated with GXR in four randomized, controlled trials in children (6–12 years) and adolescents (13–17 years) with ADHD.

Methods

SPD503-301 (n = 345) and SPD503-304 (n = 324) were 8 and 9 week studies of fixed-dose GXR (≤ 4 mg/day). SPD503-312 (n = 314; adolescents only) and SPD503-316 (n = 338) were 10–13 week studies of dose-optimized GXR (1–7 mg/day).

Results

In fixed-dose studies, pooled incidences of sedative TEAEs with GXR were highest at week 1 (GXR, 13.9–18.7%; placebo, 8.7%) and decreased to placebo levels at week 8 (0–1.4%; placebo, 0%). In contrast, proportions of responders (≥ 30% reduction from baseline in ADHD Rating Scale IV [ADHD-RS-IV] total score) increased from week 1 (GXR, 29.6–34.8%; placebo, 25.0%) through endpoint (GXR, 66.7–72.2%; placebo, 42.6%). Incidences of sedative TEAEs, but not proportions of responders, increased with GXR dosing. GXR was associated with a statistically significant reduction in ADHD-RS-IV total score from baseline to endpoint in patients without sedative TEAEs in both fixed-dose and dose-optimized studies (GXR versus placebo, effect size = 0.49 and 0.67, respectively; P < 0.001). GXR was associated with statistically significant improvements compared with placebo in both ADHD-RS-IV Hyperactivity/Impulsivity and Inattentiveness subscale scores (P < 0.001).

Conclusion

These data from pooled GXR clinical trials indicate that incident sedative TEAEs do not contribute to increased treatment response over time, and that sedation and symptomatic improvement are distinct effects of GXR.

Disclosure of interest

The authors have not supplied their declaration of competing interest.
The EVACO Project: A new battery for assessing social cognition disorders and related psychiatric disability in schizophrenia
Authors: Roux P. , Urbach M. , Fonteneau S. , Aouizerate B. , Berna F. , Brunel L. , Capdevielle D. , Chereau I. , Danion J. , Dorey J. , Dubertret C. , Dubreucq J. , Faget C. , Gabayet F. , Llorca P.M. , Mallet J. , Misdrahi D. , Rey R. , Richieri R. , Schürhoff F. , Yazbek H. , Passerieux C. , Brunet-Gouet E. ,   FACE-SCZ-Group
Published: May 2016

The relation of social cognitive disorders and schizophrenic symptoms are well-established. Yet, assessment methods have not reached a consensus. In addition, causal paths between neurocognition, social cognition, symptoms and functional expression are not clearly understood. During the past few years, some authoritative accounts proposed specialized batteries of tests and emphasized theory of mind, emotion recognition, and interpretation bias constructs:

– NIMH's “Social cognition psychometric evaluation” battery (Pinkham AE, Penn DL, Green MF, Harvey PD. Schizophrenia Bulletin, 2015);

– “Social cognition and functioning in schizophrenia” (Green MF, Lee J, Ochsner KN. Schizophrenia Bulletin, 2013).

Interestingly, these accounts stemming either from expert consensus and psychometric considerations or from neuroscience knowledge recognized some difficulties in providing a fully usable set of instruments. The project described here (EVACO protocol, funded by the Programme Hospitalier de Recherche Clinique national) follows an alternative approach and aims at providing a psychometrically validated battery. Based on a cognitive neuropsychology view on schizophrenic functional disability, several tests were gathered and are assessed in a 12-months multi-center follow-up of 160 individuals with schizophrenia. The FondaMental foundation network of Expert Centers is involved in recruiting patients from eight centers (Clermont-Ferrand, Colombes, Créteil, Grenoble, Marseille, Montpellier, Strasbourg, Versailles). To-date, the first evaluation of the population has been achieved. Experience reports and inclusions follow-up demonstrate the good acceptability of this battery both on the patients and the evaluator's side. We emphasize the usefulness of this project to meet the clinicians’ needs of validated social cognition tools, by describing different scenarios of use.

Disclosure of interest

The authors have not supplied their declaration of competing interest.
Association between physical frailty and inflammation in late-life depression
Authors: Arts M. , Collard R. , Comijs H. , Naudé P. , Risselada R. , Naarding P. , Oude Voshaar R.
Published: May 2016

Introduction

Although the criteria for physical frailty and depression partly overlap, both represent unique, but reciprocally related constructs. The association between inflammation and frailty has been reported consistently, in contrast to the association between inflammation and late-life depression (LLD).

Aim and objectives

To determine whether physical frailty is associated with low-grade inflammation in LLD.

Methods

The physical frailty phenotype, defined as three out of five criteria (weight loss, weakness, exhaustion, slowness, low physical activity level), and three inflammatory markers [C-reactive protein (CRP), interleukin-6 (IL-6), and neutrophil gelatinase–associated lipocalin (NGAL)] were assessed in a sample of individuals aged 60 and older with depression according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria (n = 366).

Results

The physical frailty phenotype was not associated with inflammatory markers in linear regression models adjusted for sociodemographic characteristics, lifestyle characteristics, and somatic morbidity. Of the individual criteria, handgrip strength was associated with CRP and IL-6, and gait speed was associated with NGAL. Principal component analysis identified two dimensions within the physical frailty phenotype: performance-based physical frailty (encompassing gait speed, handgrip strength, and low physical activity) and vitality-based physical frailty (encompassing weight loss and exhaustion). Only performance-based physical frailty was associated with higher levels of inflammatory markers.

Conclusion

The physical frailty phenotype is not a unidimensional construct in individuals with depression. Only performance-based physical frailty is associated with low-grade inflammation in LLD, which might point to a specific depressive subtype.

Disclosure of interest

The authors have not supplied their declaration of competing interest.
Specific personality changes in subjects with MCI and mild dementia are associated with cerebral Alzheimer's pathology as measured by CSF biomarkers
Authors: Tautvydaitė D. , Antonietti J.P. , Von Gunten A. , Henry H. , Popp J.
Published: May 2016

Introduction

Specific changes in personality profiles may represent early symptoms of Alzheimer's disease (AD). Knowledge about relationship between personality changes and biomarkers of cerebral pathology can contribute to early diagnosis of AD.

Objectives

To investigate to what extent the personality changes predict the cerebral AD pathology.

Aims

To describe the relationship between the personality changes and pathological cerebro-spinal fluid (CSF) biomarkers.

Method

One hundred and ten subjects, of whom 57 patients with mild cognitive impairment (MCI), 9 subjects with mild dementia, and 44 healthy controls had an extensive medical and neuropsychological examination as well as lumbar puncture to evaluate concentrations of CSF biomarkers of AD pathology [amyloid-β1-42 (Aβ1-42), phosphorylated tau (ptau-181), and total-tau (tau)]. The proxies of the participants completed the Revised NEO Personality Inventory (NEO-PI-R) to assess subjects’ personality at the time being and 5 years retrospectively.

Results

In a hierarchical multivariate regression analysis, including age, gender, education, Mini Mental State Examination (MMSE), and APOEe4 status, lower Aβ1-42 concentrations in CSF were associated with increasing neuroticism, and decreasing extraversion and conscientiousness. Decreasing extraversion, openness to experience and conscientiousness were associated with higher tau/Aβ1-42 ratio, and higher ptau-181/Aβ1-42 ratio was related to decreasing extraversion. Personality changes in the domain of agreeableness did not yield any significant effect as a predictor on any of CSF biomarkers.

Conclusions

Our findings suggest that early and specific changes in personality traits are associated with cerebral AD pathology, in particular with amyloid pathology, and may serve as clinical signs to consider when evaluating MCI and mild dementia.

Disclosure of interest

The authors have not supplied their declaration of competing interest.
The role of neurometabolites in emotional processing
Authors: Denzel D. , Demenescu L.R. , Colic L. , von Düring F. , Nießen H. , Walter M.
Published: May 2016

Objective

To investigate how brain metabolites, especially glutamate and glutamate to glutamine ratio of pgACC modulate the neural response within these areas and how this affects their function during emotion facial expression matching task.

Methods

Seventy healthy volunteers underwent magnetic resonance spectroscopy (MRS) and task functional magnetic resonance imaging (fMRI) in 7 Tesla scanner. PgACC MRS data were obtained using STEAM sequence and analyzed using LCModel.

Angry, fearful, and happy facial expressions were presented in an affect-matching block where one of the two facial expressions presented matched the target facial expression. The control condition was form matching. Data were preprocessed and analyzed in SPM 8.

Results

Glutamate to Creatine ratio measured in pgACC positively correlated with BOLD response in the right DLPFC during negative emotional perception (FWE = 0.05) Glutamate to glutamine ratio indicating on-off mechanisms in pgACC positively correlated with BOLD responses in FFA extending to cerebellum cluster (FWE < 0.05).

Conclusion

This study indicate that pgACC, baseline metabolism predicts neural response to emotional processing. We conclude that individuals with higher glutamate ratios, an excitatory neurotransmitter, in pgACC during rest might have a better coping mechanism to potential danger indicated by perception of angry or afraid faces.

The higher glutamate to glutamine ratio in pgACC indicates a higher turnover of excitatory metabolite glutamate. This mechanism is associated with higher emotional response in fusiform area and cerebellum suggesting higher visual attention towards negative emotions.

Disclosure of interest

The authors have not supplied their declaration of competing interest.
Correlation between attachment and personality dimensions and their association to the catechol-O-methyltransferase Val158Met polimorphism
Authors: Erkoreka L. , Macías M.I. , Arrue A. , Basterreche N. , Arnaiz A. , Gordo E. , Olivas O. , Santos B. , Zamalloa M.I. , Zumárraga M. , González-Torres M.A.
Published: May 2016

Introduction

Both attachment style and personality traits are closely related to individual's interpersonal patterns. Association between these constructs has been widely studied, but variability in results makes it difficult to reach definite conclusions. Similarly, dopaminergic pathways are considered to underlie some personality traits and to be related to attachment styles, but evidence, hitherto, remain inconclusive.

Aims

To assess the correlation between personality and attachment dimensions and to study whether a common association to the catechol-O-methyltransferase (COMT) Val158Met polymorphism exists.

Methods

One hundred and three Caucasian controls (mean age 39.6 ± 6.4; 65% women) were recruited in the province of Biscay, Spain. DAPP-BQ and ECR-Spanish scales were administered to assess personality and attachment dimensions respectively. DNA was obtained from saliva and the COMT Val158Met polymorphism was determined. Pearson's correlation coefficient and ANOVA were calculated using R statistical software.

Results

High positive correlation is observed between inhibition personality dimension and attachment avoidance (r = 0.75). Besides, both inhibition and avoidance dimensions’ scores are significantly higher in the COMT ValMet genotype than in the other genotypes. MetMet: 63.1 ± 13.6; ValMet: 71.0 ± 13.9; ValVal: 63.0 ± 16.7 (ANOVA F = 3.75, P = 0.027) for inhibition and MetMet: 3.44 ± 0.17; ValMet: 3.82 ± 0.2; ValVal: 3.33 ± 0.23 (ANOVA F = 3.83, P = 0.025) for avoidance.

Conclusions

Attachment patterns are rooted in early interactions with parental figures, and according to our results they could be linked to self-perceived personality traits in adulthood. Our study also suggests that genetics may predispose individuals to certain interaction styles. Our findings, linking ValMet individuals to avoidant attachment, are similar to Luijk's (2011) results, and would support a genetic-environmental model of both attachment and personality.

Disclosure of interest

The authors have not supplied their declaration of competing interest.
Co-occurrence of PTSD and cardiovascular disease among ethnic/racial groups in the United States
Authors: Vidal Mariño C. , Polo del Rio R. , Alegría M. , Wang Y. , Carmona R.
Published: May 2016

Introduction

Some inconsistent evidence indicates experiences of trauma and the presence of symptoms of PTSD are associated with increased risk of cardiovascular diseases. This relation has rarely been explored with community samples including participants with PTSD symptoms or who fulfill criteria for PTSD disorders.

Objectives

We identify those with a high number of PTSD symptoms and those fulfilling criteria for PTSD are more likely to have CVD than those without a PTSD syndrome or diagnosis. We examine rates of mental health access for those with PTSD and CVD.

Methods

We use Collaborative Psychiatric Epidemiology Surveys (CPES) to examine differences in trauma/PTSD prevalence and the association of prior trauma exposure and PTSD diagnoses with CVD (n = 13,286). CIDI was used to make psychiatric diagnoses and medical data was acquired regarding onset and severity of CVD.

Results

Individuals with prior exposure to trauma and PTSD diagnoses had twice the likelihood of developing a cardiovascular disease as those without trauma exposure [OR = 1.77, 95% CI (1.0, 2.94)]. Having a PTSD diagnosis is a significant predictor of having a CVD for individuals who experienced a traumatic event.

The probability of developing a CVD was higher when patients had prior diagnosis of substance abuse [OR = 1.36, 95% CI (1.11, 1.65)] or mental health disorders [OR = 1.43, 95% CI (1.10, 1.87) for depression; OR = 1.33, 95% CI (1.04, 1.69) for anxiety]. Men were almost twice as likely as women to be diagnosed with a CVD [OR = 1.67, 95% CI (1.37, 2.00)].

Conclusions

Exposure to trauma and the presence of PTSD symptoms are significantly associated with CVD.

Disclosure of interest

The authors have not supplied their declaration of competing interest.
Inflammatory cytokines and glutaminergic excitotoxicity in patients with obsessive-compulsive disorder (OCD)
Authors: Gnanavel S. , Parmar A. , Sharan P. , Subbiah V. , Sharma U. , Jagannathan N.R.
Published: May 2016

Introduction

In vitro studies have demonstrated possible neuroprotective effects of the following pro-inflammatory cytokines: IL-6, IL-1β and TNF-α against glutaminergic excitotoxicity in brain through different pathways.

Objectives

In the current study, we aim to correlate level of the above pro-inflammatory cytokines in serum with glutamate levels in head of caudate nucleus measured using Proton Magnetic Resonance Spectroscopy (1H-MRS) in patients with obsessive-compulsive disorder (OCD), a neuropsychiatric illness with possible multifactorial aetiology including immunological and excitotoxic factors.

Method

Thirty psychotropic-naïve patients with OCD and an equal number of gender and age-matched normal controls were recruited in the study. A detailed psychiatric assessment was carried out including sociodemographic and clinical variables. A 3T MR imaging and spectroscopy session was carried out in head of caudate nucleus. Further, absolute quantification of glutamate level was obtained using LC model. Simultaneously, 5 mL of blood sample was collected and assayed for the above pro-inflammatory cytokines (Siemens, Immulite™). The level of glutamate was correlated with the cytokine levels in patients with OCD.

Results

The level of Glx was significantly higher in patients with OCD as compared to controls (P < 0.05). The Glx level negatively correlated with two of the three pro-inflammatory cytokines: IL-6 and TNF-α (r = −0.807; r = −0.838; P < 0.05) while no significant correlation was demonstrated with IL-1β.

Conclusions

The findings provide preliminary evidence regarding possible neuroprotective effects of pro-inflammatory cytokines against glutaminergic excitotoxicity in patients with OCD. Further studies including patients with other psychiatric illnesses as controls are required for confirmation of the above findings.

Disclosure of interest

The authors have not supplied their declaration of competing interest.
Impact of DRD2 polymorphisms on prolactin level in risperidone-treated Thai children and adolescent with autism spectrum disorders
Authors: Sukasem C. , Hongkaew Y.
Published: May 2016

Introduction

A large number of studies have reported that the prolactin concentration was significantly increased in the Taq1A A1 allele carriers because several reports revealed that individuals with the DRD2 Taq1A A1 allele have a reduced density of brain D2 receptors.

Objective

The main aim of this study was to identify the impact of pharmacogenetic markers associated with prolactin concentration in risperidone-treated children and adolescents with autism spectrum disorders.

Methods

One hundred and forty-seven children and adolescents with autism, aged 3 to 19, received risperidone. The clinical data of patients were recorded from medical records. Prolactin levels were measured by chemiluminescence immunoassay. Three CYP2D6 single nucleotide polymorphisms (SNPs), CYP2D6*4 (1846G>A), *10 (100C>T), and *41 (2988G>A), one gene deletion (*5), and DRD2 Taq1A (rs1800497) polymorphism were genotyped by TaqMan real-time PCR.

Results

The three common allelic frequencies were CYP2D6*10 (55.10%), *1 (32.65%) and *5 (6.12%), respectively. Patients were grouped according to their CYP2D6 genotypes. The DRD2 genotype frequencies were Taq1A A2A2 (38.77%), A1A2 (41.50%), and A1A1 (19.73%), respectively. There were statistically significant differences in prolactin level of patients among the three groups (P = 0.033). The median prolactin level in patients with DRD2 Taq1A A2A2 (17.80 ng/mL) was significantly higher than A1A2 (17.10 ng/mL) and A1A1 (12.70 ng/mL).

Conclusion

DRD2 Taq1A A2A2 polymorphisms may be a critical role in an influence prolactin elevation during risperidone treatment in ASD.

Disclosure of interest

The authors have not supplied their declaration of competing interest.
Akathisia: Prevalence and risk factors in a community-dwelling sample of patients with schizophrenia. Results from the multi-center FACE-SZ Dataset
Authors: Berna F. , Misdrahi D. , Boyer L. , Llorca P.M. , Fond G. , Face-sz W.G.
Published: May 2016

The main objective of this study was to determine the prevalence of akathisia in a community-dwelling sample of patients with schizophrenia, and to determine the effects of treatments and the clinical variables associated with akathisia. Three hundred and seventy-two patients with schizophrenia or schizoaffective disorder were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with validated scales. Akathisia was measured with the Barnes Akathisia Scale (BAS). Ongoing psychotropic treatment was recorded. The global prevalence of akathisia (as defined by a score of 2 or more on the global akathisia subscale of the BAS) in our sample was 18.5%. Patients who received antipsychotic polytherapy were at higher risk of akathisia and this result remained significant (adjusted odd ratio = 2.04, P = .025) after controlling the influence of age, gender, level of education, level of psychotic symptoms, substance use comorbidities, current administration of antidepressant, anticholinergic drugs, benzodiazepines, and daily-administered antipsychotic dose. Our results indicate that antipsychotic polytherapy should be at best avoided and suggest that monotherapy should be recommended in cases of akathisia. Long-term administration of benzodiazepines or anticholinergic drugs does not seem to be advisable in cases of akathisia, given the potential side effects of these medications.

Disclosure of interest

The authors have not supplied their declaration of competing interest.
Antipsychotic-induced tardive dyskinesia: The role of glutamatergic system
Authors: Boiko A. , Ivanova S. , Semke A.
Published: May 2016

Tardive dyskinesia (TD) occurs in 20–25% of patients with long-term antipsychotic therapy. Abnormalities in glutamatergic transmission are considered one of the key components of the pathogenesis of drug-induced side effects. Glutamate acts as excitotoxin under certain conditions and in excessive concentrations.

Aim is to study the concentration of glutamate and analysis of single nucleotide polymorphisms (SNP) in genes coding the glutamate transporter and NMDA-receptors in schizophrenic patients with TD and without it.

The study group included 156 patients with schizophrenia receiving long-term antipsychotic treatment. Patients were divided into two groups: 63 patients with TD and 93 patients without it. Glutamate was determined in serum by spectrophotometric method. Determination of allelic variants of gene SLC1A2 (rs4354668) and GRIN2A (rs2650427, rs1969060) was performed by polymerase chain reaction in real-time.

We found a significant (P < 0.05) increase of the concentration of glutamate in patients with TD. Significant (P < 0.05) reduction in frequency of genotype GG of GRIN2A (rs1969060) and TT of SLC1A2 (rs4354668) were found in patients with TD in comparison to group without TD. In the study of glutamate concentration depending on the genotype GRIN2A (rs1969060) and genotype SLC1A2 (rs4354668) we observed a statistically significant change: elevated levels of glutamic acid identified with the heterozygous genotype in patients.

It is possible to suggest that reduction in frequency of these genotypes increases the risk of movement disorders due to the protective effect of these genotypes.

Disclosure of interest

The authors have not supplied their declaration of competing interest.
Cognitive function in female patients with schizophrenia and metabolic syndrome
Authors: Botis A.C. , Miclutia I. , Vlasin N.
Published: May 2016

Introduction

The metabolic syndrome (MetS) and cognitive impairments, both related with poor outcomes in schizophrenia, are common in patients with this disorder. MetS has been associated with cognitive impairments in schizophrenia, but there is no general consensus regarding the description of various domains of neurocognition in patients with schizophrenia related to MetS.

Objectives

The goal of this study was to assess cognitive functions in female patients with schizophrenia complicated by metabolic syndrome compared to those with schizophrenia without metabolic syndrome.

Methods

Fifty-four female patients diagnosed with schizophrenia were divided into two groups: MetS group (MetS+) and non-MetS group (MetS−). Cognitive functioning were investigated using the Brief Assessment of Cognition in Schizophrenia (BACS).

Results

Twenty-seven (52%) patients with schizophrenia met criteria for the MetS diagnosis. Mean age of patients was 40.80. Patients from MetS+ group performed significantly worse on verbal memory (P = 0.005), executive functions (P = 0.028) and motor speed (P = 0.035) as compared to MetS− group. Patients with schizophrenia who were hypertensive showed cognitive impairments in 2 domains of cognition: attention and speed of information processing (P = 0.004) and verbal fluency (P = 0.001). Patients with hypertriglyceridemia performed significantly worse on verbal memory (P = 0.005). Motor speed was associated with waist circumference (P = 0.02).

Conclusions

At a mean age of 40 years old, female patients with schizophrenia and metabolic syndrome show difficulties in more domains of cognitive function compared to female patients with schizophrenia without metabolic syndrome. Our findings suggest a link between cognition and metabolic syndrome in female patients with schizophrenia.

Disclosure of interest

The authors have not supplied their declaration of competing interest.
Comparing cognitive functions in medication adherent and non-adherent patients with schizophrenia
Authors: El-Missiry A.
Published: May 2016

Background

Medication non-adherence presents a considerable problem in patients with schizophrenia. Cognitive and executive functions can affect adherence. The association between medication non-adherence and cognitive impairment in schizophrenia is under investigated with limited and conflicting research data.

Purpose of the study

To prospectively assess the rate of drug adherence among a sample of patients with schizophrenia and to compare the cognitive and executive functions between adherent and non-adherent patients.

Subjects and methods

One hundred and nine patients with schizophrenia diagnosed according to the DSM-IV classification were initially assessed by the Wechsler Adult Intelligence Scale (WAIS), Wechsler Memory Scale-Revised (WMS-R) and Wisconsin Card Sorting Test (WCST) and six months later by the Brief Adherence Rating Scale (BARS).

Results

Among the patients, 68.8% were non-adherent to their antipsychotic medication. Adherent patients (31.2%) had significantly higher mean scores for the total, verbal and performance IQ. Moreover, they had significantly higher mean scores in most of WMS subtests (orientation, information, verbal paired association, digit span, visual memory span), and higher mean scores for; total correct, conceptual level response, percentage and categories completed on the WSCT subscales (P < 0.0001). Whereas the non-adherent group had higher mean scores in; trials administered, total errors, perseverative responses, and perseverative errors (P < 0.0001). In a step regression analysis, digit span, conceptualization, total and percentage of errors were putative predictors of non-adherence to antipsychotic medications.

Conclusion

Cognitive deficits, especially verbal memory and executive functions were the strongest patients’ related factors associated with non-adherence to medication. Psychiatrists should consider possible cognitive factors influencing adherence to enable offering proper interventions.

Disclosure of interest

The author has not supplied his declaration of competing interest.