bluuebunny/crossref_metadata_2025_split huggingface dataset:
Collapse of the native structure caused by a single amino acid exchange in human NAD(P)H:quinone oxidoreductase1
Authors: Lienhart Wolf‐Dieter , Gudipati Venugopal , Uhl Michael K. , Binter Alexandra , Pulido Sergio A. , Saf Robert , Zangger Klaus , Gruber Karl , Macheroux Peter 
Published: August 2014

Human NAD(P)H:quinone oxidoreductase 1 (NQO1) is essential for the antioxidant defense system, stabilization of tumor suppressors (e.g. p53, p33, and p73), and activation of quinone‐based chemotherapeutics. Overexpression of NQO1 in many solid tumors, coupled with its ability to convert quinone‐based chemotherapeutics into potent cytotoxic compounds, have made it a very attractive target for anticancer drugs. A naturally occurring single‐nucleotide polymorphism (C609T) leading to an amino acid exchange (P187S) has been implicated in the development of various cancers and poor survival rates following anthracyclin‐based adjuvant chemotherapy. Despite its importance for cancer prediction and therapy, the exact molecular basis for the loss of function in NQO1 P187S is currently unknown. Therefore, we solved the crystal structure of NQO1 P187S. Surprisingly, this structure is almost identical to NQO1. Employing a combination of NMR spectroscopy and limited proteolysis experiments, we demonstrated that the single amino acid exchange destabilized interactions between the core and C‐terminus, leading to depopulation of the native structure in solution. This collapse of the native structure diminished cofactor affinity and led to a less competent FAD‐binding pocket, thus severely compromising the catalytic capacity of the variant protein. Hence, our findings provide a rationale for the loss of function in NQO1 P187S with a frequently occurring single‐nucleotide polymorphism.DatabaseStructural data are available in the Protein Data Bank under the accession numbers 4cet (P187S variant with dicoumarol) and 4cf6 (P187S variant with Cibacron blue).Structured digital abstract

NQO1 P187S and NQO1 P187S bind by nuclear magnetic resonance (View interaction)

NQO1 P187S and NQO1 P187S bind by x-ray crystallography (1, 2)

NQO1 and NQO1 bind by molecular sieving (1, 2)
Regional media coverage influences the public's negative attitudes to policy implementation success in Sweden
Authors: Fredriksson Mio , Tiainen Anne , Hanning Marianne 
Published: August 2014

AbstractBackgroundOne central aspect of health literacy is knowledge of patients' rights. Being an important source of information about health and health care, the media may influence health literacy and act as a policy implementer.ObjectiveTo investigate whether regional news media coverage in Sweden is linked to (i) the public's awareness and knowledge of a patient's rights policy, the waiting‐time guarantee and (ii) the public's attitudes to how the guarantee's time limits are met, that is, implementation success.Design and dataThree types of data are used. First, a national telephone survey of the public's awareness, knowledge and attitudes; second, media coverage information from digital media monitoring; and third, official waiting‐time statistics. Bivariate and multivariate regression analyses are performed with the 21 Swedish county councils/regions as a base.ResultsIn the county councils/regions, non‐awareness ranged from 1 to 15% and knowledge from 47 to 67%. There are relatively large differences between population groups. The amount of regional media coverage shows no significant correlation to the level of awareness and knowledge. There is, however, a significant correlation to both positive and negative attitudes; the latter remains after controlling for actual waiting times.Discussion and conclusionsAt the national level, the media function as a policy implementer, being the primary source of information. At the regional level, the media are part of the political communication, reporting more extensively in county councils/regions where the population holds negative views towards the achievement in implementing the guarantee. We conclude that Swedish authorities should develop its communication strategies to bridge health literacy inequalities.
α1‐Blockers for the treatment of recurrent urinary tract infections in women with dysfunctional voiding: A prospective randomized study
Authors: Minardi Daniele , Pellegrinelli Francesco , Conti Alessandro , Fontana Donatella , Mattia Michela , Milanese Giulio , Muzzonigro Giovanni 
Published: August 2014

ObjectivesTo evaluate the therapeutic effects of tamsulosin on recurrent urinary tract infections in women with dysfunctional voiding.MethodsA total of 155 women with recurrent urinary tract infections and dysfunctional voiding were included and randomly assigned to the following groups: uroflowmetry biofeedback (group 1), α1‐adrenoceptor antagonists (group 2), uroflowmetry biofeedback combined with α1‐adrenoceptor antagonists (group 3) and no treatment (group 4). Patients were evaluated by the American Urological Association Symptom Index at 3, 6 and 12 months. Urodynamics was carried out in patients of groups 1, 2, and 3 at 3, 6 and 12 months, whereas urodynamics was only carried out at 12 months in group 4. All patients were followed up for 1 year with monthly urine cultures.ResultsThe incidence of storage and emptying symptoms decreased significantly at 3, 6 and 12 months. Mean flow rate, flow time and voiding volume increased significantly (with a better outcome in patients of group 3), whereas post‐void residual urine decreased. Mean opening detrusor pressure and detrusor pressure at maximum flow decreased significantly (with a better outcome in patients of group 3). Mean urethral closure pressure and maximum urethral closure pressure decreased significantly with a more significant decrease for patients in group 3. The prevalence of urinary tract infection decreased significantly in all groups after treatment, and this decrease remained stable during the follow up.ConclusionsIn women with dysfunctional voiding and recurrent urinary tract infection, tamsulosin associated with uroflowmetry biofeedback might be an effective and safe treatment option for improving urinary symptoms and quality of life.
Pathophysiology of uveitis
Authors: DICK A 
Published: August 2014

AbstractThis talk will overview the pathophysiology of non‐infectious uveitis in relation to recent SUN (standardised uveitis nomenclature) disease classification. The experimental and translational human evidence of autoimmunity and activation of immunity will be discussed. In addition the talk will highlight the pathways and mechanisms of tissue damage that results in sight‐threatening disease.Traditionally, despite active immune regulatory mechanisms operative within the ocular environment, inflammation still occurs. Activated antigen and non‐antigen specific T cells are generated in uveitis. The interplay with innate immunity and in particular cells of myeloid lineage both systemically and within the local environment dictate the severity and extent of pathology we observe. The understanding of immune responses during the uveitis open many avenues to potential novel immunotherapies that not only suppress inflammation but attempt to redress immune balance, tolerance and local homeostasis within ocular tissues.
Does foveal anatomy influence macular pigment and its spatial profile? A bi‐racial study
Authors: CTORI I , HUNTJENS B 
Published: August 2014

AbstractPurpose To investigate the relationship of foveal architecture with macular pigment optical density (MPOD) and its spatial profile in south Asian and white females.Methods Foveal anatomy measurements, obtained using optical coherence tomography (Spectralis OCT; Heidelberg), were collected from 46 south Asian (age 21 ± 3 years) and 38 white healthy females (age 26 ± 5 years). Spatial distribution of MPOD, measured by heterochromatic flicker photometry, was classified as a typical exponential or an atypical profile.Results South Asian compared to white females had thinner central retinas (220 ± 14μm vs. 228 ± 19μm; P = 0.02), wider foveas (2526 ± 247μm vs. 2296 ± 228μm; P < 0.0005) and higher central MPOD (0.56 ± 0.18 vs. 0.44 ± 0.23; P = 0.001), after controlling for age. Central MPOD was greater in those with an atypical (0.61 ± 0.21) compared to a typical MPOD profile (0.47 ± 0.17, P < 0.005). Only white females presenting a typical MPOD profile showed a significant correlation between central MPOD and central retinal thickness (ρ = 0.403, P = 0.03) and between the foveal pit and MPOD profile slope gradients from 0 to 0.8° (r = ‐0.522, P = 0.004). We found no association between foveal width and central MPOD in either ethnicity regardless of MPOD profile type (P = 0.90).Conclusion Our findings show that there are significant differences in retinal morphology and central MPOD between south Asian and white females. However, foveal anatomy seems to correlate with central MPOD only in white females with typical MPOD profiles. We hypothesize that higher central MPOD associated with atypical MPOD profiles and south Asian ethnicity is not related to central foveal anatomy, but a feature of an individual’s congenital constitution.
Relation between the retinal reflectivity on SD‐OCT and the cone density measured using adaptive optics
Authors: FLORES M , DEBELLEMANIERE G , TUMAHAI P , KOEHL A , MEILLAT M , SCHWARTZ C , DELBOSC B , SALEH M 
Published: August 2014

AbstractPurpose To assess the relation between the relative reflectivity of the inner segment ellipsoid (ISe) band on Spectral domain (SD)‐OCT and the cone density measured using adaptive optics.Methods Twenty eyes of 10 subjects were studied. Two subjects were healthy and the others were randomly chosen from a pool of patients presenting retinal diseases impairing bilaterally the ISe layer. Horizontal B‐scans were acquired using SD‐OCT (Spectralis, Heidelberg, Germany). The relative reflectivity, defined as the ratio between the reflectivity of the ISe layer and the reflectivity of the full retinal thickness was measured, together with ISe thickness, using ImageJ. Cone counts were performed at 2° eccentricity from the fovea (nasal, temporal, superior and inferior areas) using an Adaptive Optics retinal camera (RTX1, Imagine Eyes, Orsay, France) and its dedicated software (AOdetect v0.1™ ,Imagine Eyes, Orsay, France). Correlation coefficients (Pearson r) between the cone density and the others parameters were calculated for each area.Results Cone densities were significantly correlated with the ISe relative reflectivity (r = 0,70 [0,59 ; 0,79] p<0,01), and to a lesser extent with the ISe thickness (r = 0,32 [0,04 ; 0,56] p<0,01) and with BCVA (logMAR) (r = ‐0,38 [‐0,55;‐0,21] p<0,01).Conclusion The reflectivity on SD‐OCT of the outer retina brings valuable information on photoreceptor density in absence of adaptive optics camera. Further developments in OCT software enabling it uses in a clinical setting would be a useful advance.
The (new) place of laser treatment in RVO
Authors: PUCHE N 
Published: August 2014

AbstractThe appearance of injections in the treatment of macular edema has upsets the management of RVO. Now, What is the place of laser ? We will present the place of focal laser treatment of macular edema and remember the importance of panretinalphotocoagulation in the treatment of ischemic forms. The injection delay anti VEGF ischemic CRVO conversion.
Human induced pluripotent stem cells (hiPSC)‐derived endothelial cells: new opportunity for corneal bioengineering
Authors: THURET G , HE Z , SUFFEE N , FOREST F , BERNARD A , PISELLI S , PERRACHE C , DUMOLLARD JM , PEOC'H M , GAIN P 
Published: August 2014

AbstractPurpose hiPSCs can self‐renew indefinitely, while maintaining the capacity to differentiate into somatic cells. As such, they represent an essentially inexhaustible source of committed corneal endothelial cells (CECs) of potential use in cell‐based corneal therapies. We present a method of differentiation of hiPSCs into CE‐like cells.Methods hiPSCs reprogrammed from adipocytes by retrovirus (SBI) were expanded in mTSR1 medium. Differentiation was induced by sequential treatment mimicking the normal embryonic endothelial development, using co‐cultures during 3 weeks (not detailed because of ongoing patent application). Cells were sorted using magnetic beads with negative selection with anti‐K3/K12. Sorted cells were subsequently cultivated in maintenance medium for 3‐4 weeks. Differentiation was assessed by immunolabeling of ZO‐1, Glypican‐4, CD200R, Na/K/ATPase, CLCN3, MiTF, K3/K12. Stemcellness was assessed using anti‐OCT‐4.Results hiPSCs were successfully and stably differentiated into a monolayer of tightly packed cells expression typical ECs makers and neither keratocytes nor epithelial markers. We observed the consecutive formation of embryoïd bodies after 4 days (D), neural crest cells after 7D, mesenchymal cells after 10D and cells with CEC phenotype after 15D. They lost expression of OCT‐4.Conclusion hiPSCs are a promising source of CECs. In addition to the short‐circuit current measurement using a Ussing chamber, their ability to deswell corneas is being studied using our innovative bioreactor. Safe sources of cornea‐derived hiPSCs are also under study to facilitate clinical translation. Grants: ABM2013, IUF2012‐17, UJM2013
Influence of pressure on in vitro human corneal endothelial cells derived from human induced pluripotent stem cell (hIPSC)
Authors: JUMELLE C , SUFFEE N , FOREST F , HE Z , BERNARD A , NANGOUM‐FOSSO T , NAIGEON N , PERRACHE C , PEOC'H M , GAIN P , THURET G 
Published: August 2014

AbstractPurpose Human induced pluripotent stem cells (hIPSC) have infinite self‐renewal capacity and can differentiate into somatic cells. We obtained hIPSC‐derived corneal endothelial‐like cells (CE‐likeC) using a sequential supply of growth factors. As, in vivo, the functionality of CEC may depend on various environmental factors, including intraocular pressure, we investigated whether pressure could influence the hIPSC differentiation into ECMethods We developed a specific device for pressurizing cell cultures placed in a CO2 incubator. The device consists of a pump injecting the gas mixture from the incubator into a sealed container equipped with a pressure sensor and an electronic control system. hIPSC‐derived CEC were cultured in the differentiation medium for 1 week either in a standard incubator at atmospheric pressure or under a pressure of 20 mmHg. The medium was changed every 2 days. Differentiation was determined by cell morphology analysis and ionic pumps immunostaining (CLCN3, VDAC3, SLC4A and Na+/K+/ATPase) and tight junctions (ZO‐1).Results At D8, the 2 cultures showed similar endothelial morphology, ZO‐1 and SLC4A, but expression of ionic pumps CLCN3, VDAC3, and Na+/K+/ATPase were increased under pressure.Conclusion The device developed is fully functional. Our results show that, in vivo, a pressure of 20 mmHg did not modify the cell morphology. However, it tends to modulate the expression of some ionic pumps. Pressure level seems to be an important parameter in the differentiation into EC. Considering this, it could improve the EC functionality, i.e. deswelling capacity Grants: ABM2013, IUF2012‐2017 and postdoc UJM 2013
Positive cultures in corneas stored with cold storage technique to be used for corneal grafting
Authors: JULIAN HO , LINDEGAARD J , HØJGAARD‐OLSEN K , HEEGAARD S 
Published: August 2014

AbstractPurpose Tissue for cornea grafting processed in the US is stored using cold storage method whereas corneas processed in the EU is stored in organ culture. The two preservation techniques differ in technical aspects, evaluation techniques, storage time and microbiological safety. Both techniques are considered to result in similar graft survival. Due to low availability of Danish donor tissue, we have used US donor tissue for more than seven years in Denmark.Methods Routine microbiological culturing of the cornea‐scleral ring was performed at the time of DSAEK surgery.Results From April 2013 to March 2014 a total of 11 donor rims tested after grafting were positive for bacteria or fungi with the cold storage technique. Microbiological testing of donor rims stored with organ culture were all negative. Total number of grafts, n = 210. Six candida, one MRSA, two E. Faecium and two E.coli were cultured. Two eyes had severe and vision threatening infection (fungi). Four eyes showed primary graft failure. Five eyes showed no signs of infection.Conclusion Corneas prepared with the cold storage technique were more prone to microbiological contamination, some with vision‐threatning fungal infection. Anti‐mycotics are now added to the current hypothermic storage solution.
Rho Kinase Inhibitor AMA0526 improves surgical outcome in a rabbit model of glaucoma filtration surgery
Authors: VAN DE VELDE S , VAN BERGEN T , VANDEWALLE E , STALMANS I 
Published: August 2014

AbstractPurpose To elucidate the effect of the ROCK inhibitor AMA0526 on the wound healing process and surgical outcome of glaucoma filtration surgery.Methods The in vitro effect of ROCK inhibitor AMA0526 on human brain microvascular endothelial cells (HBMEC) and human Tenon fibroblasts (HTF) was determined using a proliferation assay. Secondly the in vivo effect of topical AMA0526 0.3% TID was investigated in a rabbit model of glaucoma filtration surgery (n=5/time point). Treatment outcome was studied by clinical investigation of the bleb area as well as immunohistological analyses for inflammation (CD45), angiogenesis (CD31) and collagen deposition at day 8, 14 and 30 after surgery. Contralateral eyes were used as control and were treated with vehicle.Results A dose‐dependent reduction of HBMEC and HTF proliferation was measured after incubation with AMA0526. Incubation with the highest concentration of AMA0526 reduced proliferation of HBMEC and HTF to 22 and 35%. In the surgery model, AMA0526 significantly improved bleb area and survival compared to vehicle treated eyes. Immunohistological analyses showed significant reduction of inflammation, angiogenesis and collagen deposition after treatment with the ROCK inhibitor. Compared to vehicle, inflammation was decreased by 33% at 8 days and angiogenesis by 52% on day 8 and by 29% at 14 days. Collagen deposition was significantly reduced by 11 and 42% on day 14 and 30.Conclusion This study shows that AMA0526 is able to inhibit proliferation of microvascular endothelial cells and Tenon fibroblasts in vitro, and to improve glaucoma surgery outcome in rabbits. In addition to improved bleb area, AMA0526 led to decreased inflammation, angiogenesis and fibrosis.
Selective laser trabeculoplasty in pseudophakic eyes with glaucoma
Authors: MAGOURITSAS G , PORTALIOU DM , MOSCHONAS K , GEORGOPOULOS V 
Published: August 2014

AbstractPurpose To evaluate the efficacy and safety of selective laser trabeculoplasty(SLT) in patients with open angle glaucoma, which had previously undergone uneventful phacoemulsification with intraocular lens implantation. We also studied the intraocular pressure(IOP) lowering effect in association with the stage of glaucoma and the customized for each patient target‐IOP.Methods In this prospective study we enrolled 30 consecutive pseudophakic patients (30 eyes) with uncontrolled glaucoma under maximum tolerated medical treatment and without any previous filtering surgery. We performed a 360° treatment using the Ellex Solo laser system. Mean IOP measurements were carried out month 1, month 6 and month 12 post‐laser treatment. Glaucoma stage was classified according to visual field loss as early, moderate or advanced. A range of target IOP was determined for each glaucomatous eye and used as an absolute success criterion. An IOP <21 mmHg was defined as a relative success.Results During the mean follow up of 15±2 months 12(40%) eyes required either acetazolamide per os or surgical intervention. Clinically significant complications did not occur. At the last visit, the mean post‐laser IOP reduction of the remaining 18 eyes was 4.4±0,7(20%)mmHg. An IOP‐ reduction of <21 mmHg was found in 73% (month6) and in 57% (month12) of the eyes, whereas the overall absolute success was 50% and 37% respectively. SLT was significantly successful in eyes with early glaucoma.Conclusion SLT is useful and safe for pseudophakic eyes with early to moderate glaucoma, which cannot be controlled under maximum tolerated medical treatment.
Pediatric uveitis
Authors: BODAGHI B 
Published: August 2014

AbstractThe etiology and treatment of uveitis in children remains different from adults. Infectious and auto‐immune conditions must be identified. Juvenile idiopathic arthritis‐associated uveitis is the main etiology of chronic anterior uveitis. Pars planitis is another frequent etiology of bilateral auto‐immune uveitis. On the other hand, toxoplasmic retinochoroiditis, ocular toxocariasis and cat scratch disease should be excluded in children with unilateral posterior uveitis. Case reports will be presented in order to illustrate the management of different pediatric uveitis entities.
The aging phenotype of microglia in the retina and its relationship to AMD
Authors: WONG W 
Published: August 2014

AbstractThe association between age‐related retinal diseases and chronic inflammatory change in the retina raises the hypothesis that microglia, the resident immune cell in the retina, may undergo aging related changes that drive pathological change. In live imaging experiments, we discovered that “resting” microglia in the inner retina undergo aging changes in the forms of decreased ramification and slowed dynamic behavior. Also, dynamic responses to injury in aged microglia were slowed in the acute phase, but more prolonged in the chronic phase. These changes indicated that aged microglia may be less able to carry constitutive functions and have abnormal and more chronic responses to injury. Also, the age‐associated translocation of microglia into the subretinal space has been associated with intracellular lipofuscin accumulation. We found that microglial uptake of A2E, a key bisretinoid component of lipofuscin, increases activation, decreases chemotaxis, and dysregulates complement activation. Taken together, aging‐related changes in retinal microglia may result in increased neuronal vulnerability, dysregulated injury responses, and altered complement regulation in the outer retina that together contribute to AMD pathogenesis.