bluuebunny/crossref_metadata_2025_split huggingface dataset:
Actions of the dual FAAH/MAGL inhibitor JZL195 in a murine neuropathic pain model
Authors: Adamson Barnes Nicholas S. , Mitchell Vanessa A. , Kazantzis Nicholas P. , Vaughan Christopher W. 
Published: September 2015

Background and PurposeWhile cannabinoids have been proposed as a potential treatment for neuropathic pain, they have limitations. Cannabinoid receptor agonists have good efficacy in animal models of neuropathic pain; they have a poor therapeutic window. Conversely, selective fatty acid amide hydrolase (FAAH) inhibitors that enhance the endocannabinoid system have a better therapeutic window, but lesser efficacy. We examined whether JZL195, a dual inhibitor of FAAH and monacylglycerol lipase (MAGL), could overcome these limitations.Experimental ApproachC57BL/6 mice underwent the chronic constriction injury (CCI) model of neuropathic pain. Mechanical and cold allodynia, plus cannabinoid side effects, were assessed in response to systemic drug application.Key ResultsJZL195 and the cannabinoid receptor agonist WIN55212 produced dose‐dependent reductions in CCI‐induced mechanical and cold allodynia, plus side effects including motor incoordination, catalepsy and sedation. JZL195 reduced allodynia with an ED50 at least four times less than that at which it produced side effects. By contrast, WIN55212 reduced allodynia and produce side effects with similar ED50s. The maximal anti‐allodynic effect of JZL195 was greater than that produced by selective FAAH, or MAGL inhibitors. The JZL195‐induced anti‐allodynia was maintained during repeated treatment.Conclusions and ImplicationsThese findings suggest that JZL195 has greater anti‐allodynic efficacy than selective FAAH, or MAGL inhibitors, plus a greater therapeutic window than a cannabinoid receptor agonist. Thus, dual FAAH/MAGL inhibition may have greater potential in alleviating neuropathic pain, compared with selective FAAH and MAGL inhibitors, or cannabinoid receptor agonists.
Effects of cost metric on cost‐effectiveness of protected‐area network design in urban landscapes
Authors: Burkhalter J.C. , Lockwood J.L. , Maslo B. , Fenn K.H. , Leu K. 
Published: September 2015

AbstractA common goal in conservation planning is to acquire areas that are critical to realizing biodiversity goals in the most cost‐effective manner. The way monetary acquisition costs are represented in such planning is an understudied but vital component to realizing cost efficiencies. We sought to design a protected‐area network within a forested urban region that would protect 17 birds of conservation concern. We compared the total costs and spatial structure of the optimal protected‐area networks produced using three acquisition‐cost surrogates (area, agricultural land value, and tax‐assessed land value). Using the tax‐assessed land values there was a 73% and 78% cost savings relative to networks derived using area or agricultural land value, respectively. This cost reduction was due to the considerable heterogeneity in acquisition costs revealed in tax‐assessed land values, especially for small land parcels, and the corresponding ability of the optimization algorithm to identify lower‐cost parcels for inclusion that had equal value to our target species. Tax‐assessed land values also reflected the strong spatial differences in acquisition costs (US$0.33/m2–$55/m2) and thus allowed the algorithm to avoid inclusion of high‐cost parcels when possible. Our results add to a nascent but growing literature that suggests conservation planners must consider the cost surrogate they use when designing protected‐area networks. We suggest that choosing cost surrogates that capture spatial‐ and size‐dependent heterogeneity in acquisition costs may be relevant to establishing protected areas in urbanizing ecosystems.
Challenging gender stereotypes: Theory of mind and peer group dynamics
Authors: Mulvey Kelly Lynn , Rizzo Michael T. , Killen Melanie 
Published: September 2015

AbstractTo investigate the social cognitive skills related to challenging gender stereotypes, children (N= 61, 3–6 years) evaluated a peer who challenged gender stereotypic norms held by the peer's group. Participants with false belief theory of mind (FBToM) competence were more likely than participants who did not haveFBToM to expect a peer to challenge the group's stereotypes and propose that the group engage in a non‐stereotypic activity. Further, participants withFBToM rated challenging the peer group more positively. Participants withoutFBToM did not differentiate between their own and the group's evaluation of challenges to the group's stereotypic norms, but those with ToM competence asserted that they would be more supportive of challenging the group norm than would the peer group. Results reveal the importance of social‐cognitive competencies for recognizing the legitimacy of challenging stereotypes, and for understanding one's own and other group perspectives.
Reduced risk of Efavirenz Discontinuation in Naïve Patients Starting First‐Line Antiretroviral Therapy with Single Tablet versus dual Tablet Regimen
Authors: Fabbiani M , Zaccarelli M , Latini A , Sterrantino G , D'Ettorre G , Grima P , Mondi A , Rossetti B , Borchi B , Giuliani M , Antinori A , De Luca A , Di Giambenedetto S 
Published: September 2015

ObjectivesDespite not being approved in Europe as first‐line therapy, the efavirenz (EFV)‐containing single tablet regimen (STR) is frequently used in clinical practice in naïve patients but few data are available on this strategy. In our study, we aimed to assess the risk of EFV discontinuation in patients starting antiretroviral therapy with STR vs. nonSTR.MethodsThis was a multicentre study retrospectively enrolling naïve patients starting EFV+TDF+FTC. Patients were followed from the time of treatment initiation to the discontinuation of the EFV‐containing regimen, comparing STR vs. nonSTR. Two different analyses were performed: (A) nonSTR patients censored at the last observation (switch to STR not considered as the end of observation); (B) nonSTR patients censored at the time of switch to STR.ResultsThe study included 235 patients, of whom 74 (31.5%) directly started STR. Among patients starting nonSTR, 108 (67.1%) switched to STR after a median period of 6 months. Forty‐four EFV discontinuations were observed (13 among STR vs. 31 among nonSTR patients). The overall estimated probability of discontinuation was 30% at 5 years, about half (14.8%) of these occurring during the first year. Analysis A did not show significant differences between STR and nonSTR regarding the probability of efavirenz discontinuation (19.9% vs. 24.7% at 5 years, P = 0.630). In contrast, Analysis B showed that the probability of EFV discontinuation was similar (8.3%) between STR and nonSTR patients up to 8 months. Thereafter, a significantly higher rate of discontinuation was observed in nonSTR patients (47.5% vs. 19.9% at 5 years, P = 0.034).ConclusionsOur data suggest that an early switch to STR during the first months of treatment could reduce the risk of EFV discontinuation.
Pemphigus vulgaris: a clinical study of 44 cases over a 20‐year period
Authors: Svecova Danka 
Published: September 2015

AbstractBackgroundPemphigus vulgaris (PV) is a rare, life‐threatening, autoimmune bullous disease with unpredictable progression and prognosis.ObjectivesThis study aimed to analyze long‐term outcomes in patients with PV, focusing on factors that may influence the prognosis of the disease, including the phenotype of PV, age at onset, multiplicity of mucosal involvement, relapse and remission rates, and survival functions.MethodsA retrospective analysis was conducted in 44 patients who were diagnosed and monitored from 1993 to 2012. Statistical analyses were conducted using the Mann–Whitney test and Kruskal–Wallis test. Survival data were analyzed using Kaplan–Meier and log rank tests. Fisher's exact test was used to assess statistical significance at P < 0.05.ResultsA total of 79.5% of patients were identified as having mucocutaneous PV. The female : male gender ratio was 1.58; in severe PV, this increased to 2.8. The difference between the genders in age at onset was statistically significant (P = 0.05). Furthermore, multiple mucosal involvements in the oral cavity and at other sites were associated with severe mucocutaneous PV. Multiple relapses occurred more frequently in patients with severe PV than in those with mild PV (P = 0.001). The remission survival of females was longer than that of males (P = 0.003).ConclusionsPoor prognosis factors include the severe mucocutaneous type of PV, especially in female patients, and multiple mucosal involvements in the oral cavity and other mucosal sites. Female patients were younger than male patients and were more often observed to have severe mucocutaneous PV and to have a higher median period of remission survival than male patients.
The EGS Guidelines: a surgical approach to glaucoma
Authors: Hommer A. 
Published: September 2015

SummaryAlso the first step in treating glaucoma is medical therapy in most cases there are patients where lasertrabeculoplasty is the appropriate initial treatment. In addition there are patients, where the target pressure could not be reached and/or the disease is progressing despite maximum medical therapy. In consequence of the risk for the visual function incisional surgery is the next therapeutic step. In the presentation EGS recommendations and flow charts for the different glaucoma surgeries will be presented and discussed.
Fundus autofluorescence imaging in White Dot Syndromes
Authors: De Bats F. , Wolff B. , Mathis T. , Scemama Timsit C. , Cahuzac A. , Uzzan J. , Mauget‐Faÿsse M. 
Published: September 2015

SummaryThe term ‘white dot syndromes’ (WDS) refers to several inflammatory diseases of the retina and choroid caused by immune dysregulation. Retinal and choroidal changes observed with multimodal imaging are transient and may disappear quickly in some cases. Multimodal imaging with color fundus photography, fluorescein, indocyanine green angiographies, spectral Domain Optical Coherence Tomography help in identifying the diagnosis. They also help assess the level of inflammatory activity and detect complications. Fundus autofluorescence (AF) imaging is an in vivo imaging method that allows a metabolic mapping of natural or pathological fundus fluorophores. Blue fundus AF imaging is obtained with a confocal laser scanning ophthalmoscope using an excitation short wavelength (SW) at 488 nanometers. In this work, SW‐AF imaging was obtained using a HRA Heidelberg instrument. SW‐AF imaging is an important, non invasive and complementary technique that helps early diagnosis and follow‐up of WDS. The characteristics of the SW‐AF abnormalities are often pathognomonic of each inflammatory disease. Further prospective studies including more patients will be necessary to confirm these results.
General structure of the retina
Authors: Grzybowski A. 
Published: September 2015

SummaryThe invention of the ophthalmoscope in the 19th century led to the development of ophthalmology as a discipline. The retina is an accessible part of the central nervous system and has consequently been studied extensively. There is now a growing use of OCT to obtain information related to brain neurodegenerative disorders like multiple sclerosis, Alzheimer's and Parkinson diseases as well as migraine.Two aspects of human retinal structure based on physiology and morphology can be distinguished. They are the various retinal layers that consist of either neuron perikarya or neuronal processes. The other, is the distinction between central (macula, fovea) and periphery parts of the retina. Major cell‐types in the retina are pigment epithelial, photoreceptor, horizontal, bipolar, amacrine, ganglion and glial cells and an understanding of their roles in healthy and unhealthy retina remains a challenge. Ocular photoreception for example, was thought to be mediated exclusively by rods and cones until the beginning of the 21st century and only recently have photosensitive retinal ganglion cells (pRGCs) been discovered. The aim is to discuss certain aspects of retinal structure related to function.
Role of SD‐OCT in the follow‐up of a patient with macular edema associated with mucopoysaccharidosis type II (Hunter syndrome) undergoing idursulfase enzyme replacement therapy
Authors: Sanchez J.I. , Ascaso F.J. , Perez I. , Almenara C. , Esteban O. , Martinez M. , Idoate A. , Torralba M.A. 
Published: September 2015

PurposePurpose: Mucopolysaccharidosis (MPS) type II (Hunter syndrome) is a variable, progressive, multisystem disorder including severe airway obstruction, cardiomyopathy, skeletal deformities and neurological problems. It is an X‐linked recessive disease caused by deficiency of the lysosomal enzyme iduronate‐2‐sulphatase, leading to accumulation of glycosaminoglycans. Several ophthalmological disorders, including corneal opacities, glaucoma and retinal degeneration, have been previously reported. This is the first case of bilateral macular edema associated with MPS II. The patient underwent idursulfase enzyme replacement therapy with good response. We point out the utility of spectral domain optical coherence tomography (SD‐OCT) in the diagnosis and follow‐up of this condition.MethodsSD‐OCT, fundus autofluorescence and retinography were used in the diagnosis and follow‐up of the visual disorder.ResultsMacular edema was successfully managed with idursulfase enzyme replacement therapy stabilizing visual loss. Central macular thickness measured by SD‐OCT decreased significantly.ConclusionIdursulfase enzyme replacement therapy seems to be a good treatment option for macular edema associated with MPS II. Furthermore, SD‐OCT played a key role in the diagnosis and follow‐up of this condition.
TrkB signaling in Müller glia stimulates neuroprotection after optic nerve injury
Authors: Harada T. , Namekata K. , Guo X. , Kimura A. , Harada C. 
Published: September 2015

PurposeBrain‐derived neurotrophic factor (BDNF) is a neurotrophic factor that regulates neural cell survival mainly by activating TrkB receptors. Several lines of evidence support a key role for BDNF‐TrkB signaling in survival of adult retinal ganglion cells (RGCs) in acute and chronic models of optic nerve damage. On the other hand, glial cells have recently attracted considerable attention as mediators of neural cell survival. To further elucidate the role of glial cells in BDNF‐mediated neuroprotection, we examined the effect of optic nerve injury (ONI) on TrkBGFAP KO mice, in which TrkB is deleted in retinal glial cells.MethodsWe examined the effect of ONI in WT and TrkBGFAP KO mice at day (d) 7 and 14 after ONI by spectral‐domain optical coherence tomography (SD‐OCT), retrograde labeling of RGCs, immunohistochemistry and quantitative real‐time PCR analyses.ResultsONI‐induced RGC loss and retinal degeneration occurred quickly in TrkBGFAP KO mice at d7 after ONI, but the severity was comparable with WT mice at d14. We next examined the effects of ONI on the production of trophic factors in the retina. ONI markedly increased mRNA expression levels of basic fibroblast growth factor (bFGF) in WT mice at d3, but not in TrkBGFAP KO mice. Immunohistochemical analysis at d7 revealed that ONI induced bFGF upregulation mainly in Müller glia. On the other hand, glial cell line‐derived neurotrophic factor (GDNF) expression level was slightly decreased in TrkBGFAP KO mice compared with WT mice at d3, but not at d10.ConclusionsThese results demonstrate that BDNF signaling in retinal glia plays important roles in the early stage of neural protection after traumatic injury. Additionally, our genetic models provide a system in which glia‐specific gene functions can be examined in central nervous system tissues in vivo.
A novel mutation in CNNM4 (G492C) associated with Jalili Syndrome
Authors: Lopez Torres L.T. , Schorderet D. , Valmaggia C. , Todorova M. 
Published: September 2015

PurposeTo describe a new G492C homozygous mutation in a consanguineous family from Saudi Arabia with autosomal recessive cone‐rod dystrophy (arCRD) associated with amelogenesis imperfecta and mental deficiency (Jalili syndrome).MethodsBoth parents and their five children were included in the study. They underwent a complete ophthalmic examination including fundus imaging and optical coherence tomography. Both affected children underwent electrophysiological evaluation including full‐field ERG and EOG (ISCEV standard). Direct Sanger sequencing of all exons and intron‐exon junctions of CNNM4 was conducted.ResultsArCRD was diagnosed in two children with childhood‐onset visual impairment and nystagmus. Ophthalmoscopy showed macular atrophy with pigment mottling, attenuated retinal vasculatur and optic disc pallor. Electrophysiology revealed non‐recordable scotopic and photopic ERGs, completely attenuated off‐response of the on‐off ERG and reduced Arden‐ratio of the EOG. Both affected children showed mental deficiency and had clinical signs of amelogenesis imperfecta presenting with dysplastic, hypomineralized teeth.Sanger sequencing identified a new c.[1474G>T] mutation in CNNM4, located in exon 2 leading to a substitution of the glycine amino acid to cystein at cDNA position 492. This mutation was homozygous in the two affected children and was heterozygous in the unaffected father, mother and both sisters. One unaffected son was homozygous normal.ConclusionsGenetic testing enabled to confirm the diagnosis of Jalili syndrome by identifying a yet unreported G492C mutation in CNNM4.
Predicting island beetle faunas by their climate ranges: thetabula rasa/refugia theory in the North Atlantic
Authors: Vickers Kim , Buckland Philip I. 
Published: September 2015

AbstractAimThis paper addresses two opposing theories put forward for the origins of the beetle fauna of the North Atlantic islands. The first is that the biota of the isolated oceanic islands of the Faroes, Iceland and Greenland immigrated across a Palaeogene–Neogene land bridge from Europe, and survived Pleistocene glaciations in ameliorated refugia. The second argues for atabula rasain which the biota of the islands was exterminated during glaciations and is Holocene in origin. The crux of these theories lies in the ability of the flora and fauna to survive in a range of environmental extremes. This paper sets out to assess the viability of the refugia hypothesis using the climatic tolerances of one aspect of the biota: the beetle fauna.LocationThe paper focuses on Iceland, the Faroe Islands and Greenland.MethodsThe known temperature requirements of the recorded beetle faunas of the North Atlantic islands were compared with published proxy climate reconstructions for successive climate periods since the severing of a North Atlantic land bridge. We used theMCR(mutual climatic range) method available in the open access BugsCEPdatabase software.ResultsWe show that most of theMCRfaunas of the North Atlantic islands could not have survivedin situsince the Palaeogene–Neogene, and are likely to have been exterminated by the Pleistocene glaciations.Main conclusionsThe discrepancy between the climatic tolerances of the North Atlantic beetle fauna and the estimated climatic regimes since the severing of a land bridge strongly support thetabula rasatheory and suggests that the North Atlantic coleopteran fauna is Holocene in origin.
DKK3 blocked translocation of β‐catenin/EMT induced by hypoxia and improved gemcitabine therapeutic effect in pancreatic cancer Bxpc‐3 cell
Authors: Guo Qingqu , Qin Wenjie 
Published: September 2015

AbstractThe Wnt/β‐catenin signalling pathway is activated in pancreatic cancer initiation and progression. Dickkopf‐related protein 3 (DKK3) is a member of the human Dickkopf family and an antagonist of Wnt ligand activity. However, the function of DKK3 in this pathway in pancreatic cancer is rarely known. We examined the expression of DKK3 in six human pancreatic cancer cell lines, 75 pancreatic cancer and 75 adjacent non‐cancerous tissues. Dickkopf‐related protein 3 was frequently silenced and methylation in pancreatic cancer cell lines (3/6). The expression of DKK3 was significantly lower in pancreatic cancer tissues than in adjacent normal pancreas tissues. Further, ectopic expression of DKK3 inhibits nuclear translocation of β‐catenin induced by hypoxia in pancreatic cancer Bxpc‐3 cell. The forced expression of DKK3 markedly suppressed migration and the stem cell‐like phenotype of pancreatic cancer Bxpc‐3 cell in hypoxic conditions through reversing epithelial–mesenchymal transition (EMT). The stable expression of DKK3 sensitizes pancreatic cancer Bxpc‐3 cell to gemcitabine, delays tumour growth and augments gemcitabine therapeutic effect in pancreatic cancer xenotransplantation model. Thus, we conclude from our finding that DKK3 is a tumour suppressor and improved gemcitabine therapeutic effect through inducing apoptosis and regulating β‐catenin/EMT signalling in pancreatic cancer Bxpc‐3 cell.
Identifying mechanisms that underlie links between COMT genotype and aggression in male adolescents with ADHD
Authors: van Goozen Stephanie H.M. , Langley Kate , Northover Clare , Hubble Kelly , Rubia Katya , Schepman Karen , O'Donovan Michael C. , Thapar Anita 
Published: September 2015

BackgroundThere is a known strong genetic contribution to aggression in those with ADHD. In a previous investigation of a large population cohort, impaired ‘emotional/social cognitive’ processing, assessed by questionnaire, was observed to mediate the link between COMT Val158Met and aggression in individuals with ADHD. We set out to replicate and extend this finding in a clinical sample, using task‐based and physiological assessments of emotional and cognitive processing. Our aim was to test the hypothesis that directly assessed emotional processing mediates the link between COMT Val158Met and aggression in young people with ADHD.MethodsMales aged 10–17 years with ADHD were recruited from UK community clinics (n = 194). Research diagnostic interviews (parent and child) were used to assess psychopathology and generate DSM‐IV Conduct Disorder symptom scores. Participants completed tasks assessing executive function (response inhibition and set shifting), empathy for fear, sadness and happiness, and fear conditioning [measured using skin conductance responses (SCR) to aversive stimuli].ResultsCOMT Val allele carriers showed poorer response inhibition (F = 5.27, p = .02) and set shifting abilities (F = 6.45, p = .01), reduced fear empathy (F = 4.33, p = .04) and reduced autonomic responsiveness (lower SCRs) to the conditioned aversive stimulus (F = 11.74, p = .001). COMT Val158Met did not predict impairments in recognising others' emotions or affective empathy for happiness or sadness. Mediation analysis revealed that impaired fear‐related mechanisms indirectly mediated the link between COMT Val158Met and aggression.ConclusionOur findings suggest fear mechanisms as possible targets for psychological interventions to disrupt links between genetic risk and aggressive outcomes in ADHD. Our findings also reveal the potential of hypothesis‐driven approaches for identifying neuropsychological mechanisms that mediate genetic risk effects on behaviour and psychopathology.
Calculation of Bohmian quantum trajectories for STEM
Authors: ZHANG M. , MING Y. , ZENG R.G. , DING Z.J. 
Published: September 2015

SummaryWe present in this work the calculation of Bohmian quantum trajectories representing the wave function propagation in a crystal for a focused electron probe in a scanning transmission electron microscope (STEM). The wave function and quantum trajectories are obtained from the calculation of time‐dependent Schrödinger equation by fast Fourier transformation multislice algorithm. In our work, the Bohmian quantum trajectories of a scanning probe penetrating a Cu crystal are studied as an example of this calculation scheme. The results help us to better understand the electron diffraction process in a microscopic imaging from a trajectory‐based point of view. This Bohmian quantum trajectory method can be used to extend the application of classical Monte Carlo method from the study of electron interaction with amorphous solid to crystalline structure.