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Find video protocols related to scientific articles indexed in Pubmed.
The Implications of the Affordable Care Act for Behavioral Health Services Utilization.
Adm Policy Ment Health
PUBLISHED: 11-20-2014
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This analysis estimates the number of currently uninsured adults who may gain coverage and access behavioral health (BH) services under the ACA. Data on BH status, socio-demographic characteristics, insurance coverage, and services utilization were drawn from the 2008-2012 National Survey on Drug Use and Health. Multivariate logistic regression modeling was used to estimate changes in services utilization under the ACA. Estimates indicate that 2.8 million adults may receive BH treatment through Medicaid expansions, and 3.1 million through participation in health insurance exchanges. This represents a 40 % increase in BH services utilization, primarily for mental health services.
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[(18)F]Fluoromethylcholine as a Chemotherapy Response Read-Out in Prostate Cancer Cells.
Mol Imaging Biol
PUBLISHED: 11-20-2014
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The objective of the present study is to determine whether uptake of [(18)F]fluoromethylcholine ([(18)F]FCH) in comparison with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) accurately reflects chemotherapy efficacy at the tumor cell level in prostate cancer (PC).
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Early-Stage Imaging of Nanocarrier Enhanced Chemotherapy Response in Living Subjects by Scalable Photoacoustic Microscopy.
ACS Nano
PUBLISHED: 11-20-2014
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Conventional evaluation methods of chemotherapeutic efficacy such as tissue biopsy and anatomical measurement are either invasive with potential complications or dilatory to capture the rapid pathological changes. Here, a sensitive and resolution-scalable photoacoustic microscopy (PAM) with theranostic nanoformulation was developed to noninvasively monitor the therapy response in a timely manner. Ultrasmall graphene oxide (GO) nanosheets were designed as both drug loading vehicle and photoacoustic signal amplifier to the tumor. With the signal enhancement by the injected contrast agents, the subtle microvascular changes of the chemotherapy response in tumor were advantagely revealed by our PAM system, which was much earlier than the morphological measurement by standard imaging techniques. High tumor uptake of the enhanced nanodrug with Cy5.5 labeling was validated by fluorescence imaging. At different observation scales, PAM offered unprecedented sensitivity of optical absorption and high spatial resolution over optical imaging. Our studies demonstrate the PAM system with synergistic theranostic strategy to be multiplexing platforms for tumor diagnosis, drug delivery, and chemotherapy response monitoring in a very early stage and effective way.
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Ambient Method for the Production of an Ionically Gated Carbon Nanotube Common Cathode in Tandem Organic Solar Cells.
J Vis Exp
PUBLISHED: 11-20-2014
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A method of fabricating organic photovoltaic (OPV) tandems that requires no vacuum processing is presented. These devices are comprised of two solution-processed polymeric cells connected in parallel by a transparent carbon nanotubes (CNT) interlayer. This structure includes improvements in fabrication techniques for tandem OPV devices. First the need for ambient-processed cathodes is considered. The CNT anode in the tandem device is tuned via ionic gating to become a common cathode. Ionic gating employs electric double layer charging to lower the work function of the CNT electrode. Secondly, the difficulty of sequentially stacking tandem layers by solution-processing is addressed. The devices are fabricated via solution and dry-lamination in ambient conditions with parallel processing steps. The method of fabricating the individual polymeric cells, the steps needed to laminate them together with a common CNT cathode, and then provide some representative results are described. These results demonstrate ionic gating of the CNT electrode to create a common cathode and addition of current and efficiency as a result of the lamination procedure.
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Dissection and Mounting of Drosophila Pupal Eye Discs.
J Vis Exp
PUBLISHED: 11-20-2014
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The Drosophila melanogaster eye disc is a powerful system that can be used to study many different biological processes. It contains approximately 800 separate eye units, termed ommatidia(1). Each ommatidium contains eight neuronal photoreceptors that develop from undifferentiated cells following the passage of the morphogenetic furrow in the third larval instar(2). Following the sequential differentiation of the photoreceptors, non-neuronal cells develop, including cone and pigment cells, along with mechanosensory bristle cells(3). Final differentiation processes, including the structured arrangement of all the ommatidial cell types, programmed cell death of undifferentiated cell types and rhodopsin expression, occurs through the pupal phase(4-7). This technique focuses on manipulating the pupal eye disc, providing insight and instruction on how to dissect the eye disc during the pupal phase, which is inherently more difficult to perform than the commonly dissected third instar eye disc. This technique also provides details on immunostaining to allow the visualization of various proteins and other cell components.
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Gold(I)-Catalyzed Intermolecular Cycloaddition of Allenamides with ?,?-Unsaturated Hydrazones: Efficient Access to Highly Substituted Cyclobutanes.
Org. Lett.
PUBLISHED: 11-20-2014
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?,?-Unsaturated N,N-dialkyl hydrazones undergo a mild [2 + 2] cycloaddition to allenamides when treated with a suitable gold catalyst. The method, which represents the first application of N,N-dialkyl hydrazones in gold catalysis, is compatible with a wide variety of substituents at the alkenyl moiety of the hydrazone component, proceeds with excellent levels of regio- and diastereoselectivity, and provides densely substituted cyclobutanes with good to excellent yields.
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EN-RAGE: A Novel Inflammatory Marker for Incident Coronary Heart Disease.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 10-23-2014
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Inflammation plays a key role in atherosclerosis. We hypothesized that novel inflammatory markers may predict the risk of coronary heart disease (CHD).
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Use of coumarin anticoagulants and cerebral microbleeds in the general population.
Stroke
PUBLISHED: 10-14-2014
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It remains undetermined whether the use of coumarin anticoagulants associates with cerebral microbleeds in the general population. We investigated whether (1) coumarin use relates to higher prevalence and incidence of microbleeds, (2) microbleeds are more frequent in people with higher maximum international normalized ratios (INRs), and (3) among coumarin users, variability in INR associates with microbleed presence.
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No association between CYP3A4*22 and statin effectiveness in reducing the risk for myocardial infarction.
Pharmacogenomics
PUBLISHED: 10-11-2014
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Genetic variation has been shown to influence statin response in terms of lowering LDL cholesterol. The recently discovered CYP3A4*22 allele (defined as rs35599367) has been shown to affect statin-induced LDL cholesterol lowering. Our objective was to investigate whether this polymorphism modifies the risk reduction for myocardial infarction (MI) by statins.
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Antidiabetic Effect of Schisandrae Chinensis Fructus Involves Inhibition of the Sodium Glucose Cotransporter.
Drug Dev. Res.
PUBLISHED: 10-10-2014
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Preclinical Research Schisandrae Chinensis Fructus (SCF), the fruit of Schisandra chinensis (Turcz.) Baill. (family Schisandraceae) is traditionally used as a tonic and antidiabetic agent in Asia. In this study, SCF was investigated for its effects on sodium glucose cotransporters 1 and 2 (SGLT 1 and 2) expressed in a COS-7 cell line for its specificity in inhibiting SGLT2, which is a novel mechanism to screen for potential antidiabetic agents. Using a bioassay-guided fractionation, we then tried to isolate and identify the active fraction(s)/component(s). The ethanol extract of SCF at a concentration of 1?mg/mL significantly inhibited 89% of SGLT1 and 73% of SGLT2 activities in a [(14) C]-?-methyl-d-glucopyranoside ([(14) C]-AMG) uptake assay. Fractionation of the ethanol extract yielded nine fractions, of which F8, at a concentration of 1?mg/mL, was specific in inhibiting SGLT 2 (42% inhibition, P?
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Migraine and cerebral blood flow in the general population.
Cephalalgia
PUBLISHED: 10-05-2014
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Observations that migraine increases risk of cardiovascular disease and ischemic brain changes may suggest sustained vascular differences between migraineurs and controls. In a population-based setting, we compared cerebral blood flow between migraineurs in the attack-free period and controls.
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A novel common variant in DCST2 is associated with length in early life and height in adulthood.
Ralf J P van der Valk, Eskil Kreiner-Møller, Marjolein N Kooijman, Mònica Guxens, Evangelia Stergiakouli, Annika Sääf, Jonathan P Bradfield, Frank Geller, M Geoffrey Hayes, Diana L Cousminer, Antje Körner, Elisabeth Thiering, John A Curtin, Ronny Myhre, Ville Huikari, Raimo Joro, Marjan Kerkhof, Nicole M Warrington, Niina Pitkänen, Ioanna Ntalla, Momoko Horikoshi, Riitta Veijola, Rachel M Freathy, Yik-Ying Teo, Sheila J Barton, David M Evans, John P Kemp, Beate St Pourcain, Susan M Ring, George Davey Smith, Anna Bergström, Inger Kull, Hakon Hakonarson, Frank D Mentch, Hans Bisgaard, Bo Chawes, Jakob Stokholm, Johannes Waage, Patrick Eriksen, Astrid Sevelsted, Mads Melbye, , Cornelia M van Duijn, Carolina Medina-Gomez, Albert Hofman, Johan C de Jongste, H Rob Taal, André G Uitterlinden, Loren L Armstrong, Johan Eriksson, Aarno Palotie, Mariona Bustamante, Xavier Estivill, Juan R Gonzalez, Sabrina Llop, Wieland Kiess, Anubha Mahajan, Claudia Flexeder, Carla M T Tiesler, Clare S Murray, Angela Simpson, Per Magnus, Verena Sengpiel, Anna-Liisa Hartikainen, Sirkka Keinänen-Kiukaanniemi, Alexandra Lewin, Alexessander Da Silva Couto Alves, Alexandra I Blakemore, Jessica L Buxton, Marika Kaakinen, Alina Rodriguez, Sylvain Sebert, Marja Vaarasmaki, Timo Lakka, Virpi Lindi, Ulrike Gehring, Dirkje S Postma, Wei Ang, John P Newnham, Leo-Pekka Lyytikäinen, Katja Pahkala, Olli T Raitakari, Kalliope Panoutsopoulou, Eleftheria Zeggini, Dorret I Boomsma, Maria Groen-Blokhuis, Jorma Ilonen, Lude Franke, Joel N Hirschhorn, Tune H Pers, Liming Liang, Jinyan Huang, Berthold Hocher, Mikael Knip, Seang-Mei Saw, John W Holloway, Erik Melén, Struan F A Grant, Bjarke Feenstra, William L Lowe, Elisabeth Widén, Elena Sergeyev, Harald Grallert, Adnan Custovic, Bo Jacobsson, Marjo-Riitta Järvelin, Mustafa Atalay, Gerard H Koppelman, Craig E Pennell, Harri Niinikoski, George V Dedoussis, Mark I McCarthy, Timothy M Frayling, Jordi Sunyer, Nicholas J Timpson, Fernando Rivadeneira, Klaus Bønnelykke, Vincent W V Jaddoe.
Hum. Mol. Genet.
PUBLISHED: 10-03-2014
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Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; ? = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
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Ethnic disparities in general and abdominal adiposity at school age: a multiethnic population-based cohort study in the Netherlands.
Ann. Nutr. Metab.
PUBLISHED: 10-02-2014
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Ethnic differences in obesity prevalence have been reported. We examined ethnic differences in general and abdominal fat distribution in school-age children and the influence of parental prepregnancy, pregnancy, and childhood factors on these differences.
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In situ study of noncatalytic metal oxide nanowire growth.
Nano Lett.
PUBLISHED: 09-24-2014
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The majority of the nanowire synthesis methods utilize catalyst particles to guide the nanowire geometry. In contrast, catalyst-free methods are attractive for facile fabrication of pure nanowires without the need for catalyst preparation. Nonetheless, how nanowire growth is guided without a catalyst is still widely disputed and unclear. Here, we show that the nanowire growth during metal oxidation is limited by a nucleation of a new layer. On the basis of in situ transmission electron microscope investigations we found that the growth occurs layer by layer at the lowest specific surface energy planes. Atomic layers nucleate at the edge of twin boundary ridges and form a long-range ordering along the twin boundary. We anticipate our study to be a starting point to employ defects for nanowire growth control and consequently shaping the geometry of nanowires in a similar manner as in the catalyst-assisted growth method.
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Atherosclerotic plaque in the left carotid artery is more vulnerable than in the right.
Stroke
PUBLISHED: 09-16-2014
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Ischemic stroke is more often diagnosed in the left hemisphere than in the right. It is unknown whether this asymmetrical prevalence relates to differences in carotid atherosclerosis. We compared atherosclerotic plaque prevalence, severity, and composition between left and right carotid arteries.
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Evaluating the Endoscopic Reference Score for eosinophilic esophagitis: moderate to substantial intra- and interobserver reliability.
Endoscopy
PUBLISHED: 09-10-2014
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Background and study aims: Recently the Endoscopic Reference Score (EREFS) for endoscopic assessment of eosinophilic esophagitis was introduced, with good interobserver agreement for most signs. The EREFS has not yet been evaluated by other investigators and intraobserver agreement has not been assessed. The aim of this study was to further validate the EREFS by assessing interobserver and intraobserver agreement of endoscopic signs in patients with eosinophilic esophagitis. Patients and methods: High-quality endoscopic images were made of the esophagus of 30 patients with eosinophilic esophagitis (age 36 years, range 23?-?46 years; 5 female), 6 of whom were in remission. At least three depersonalized images per patient were incorporated into a slideshow. Images were scored by four expert and four trainee endoscopists who were blinded to the patients' conditions. Interobserver agreement was assessed. After 4 weeks, the images were rescored in a different order to assess intraobserver agreement. Results: Interobserver agreement was substantial for rings (? 0.70), white exudates (? 0.63), and crepe paper esophagus (? 0.62), moderate for furrows (? 0.49) and strictures (? 0.54), and slight for edema (? 0.12). Intraobserver agreement was substantial for rings (median ? 0.64, IQR 0.46?-?0.70), furrows (median ? 0.69, IQR 0.50?-?0.89), and crepe paper esophagus (median ? 0.69, IQR 0.62?-?0.83), moderate for white exudates (median ? 0.58, IQR 0.54?-?0.71) and strictures (median ? 0.54, IQR 0.33?-?0.70), and less than chance for edema (median ? 0.00, IQR 0.00?-?0.29). Inter- and intraobserver agreement was not substantially different between expert and trainee endoscopists. Conclusions: Using the EREFS, endoscopic signs of eosinophilic esophagitis were scored consistently by expert and trainee endoscopists.
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Feeding practices and child weight: is the association bidirectional in preschool children?
Am. J. Clin. Nutr.
PUBLISHED: 09-03-2014
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Parental feeding practices are associated with children's body mass index (BMI). It has been generally assumed that parental feeding determines children's eating behaviors and weight gain, but feeding practices could equally be a parent's response to child weight.
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Defining the role of common variation in the genomic and biological architecture of adult human height.
Andrew R Wood, Tonu Esko, Jian Yang, Sailaja Vedantam, Tune H Pers, Stefan Gustafsson, Audrey Y Chu, Karol Estrada, Jian'an Luan, Zoltan Kutalik, Najaf Amin, Martin L Buchkovich, Damien C Croteau-Chonka, Felix R Day, Yanan Duan, Tove Fall, Rudolf Fehrmann, Teresa Ferreira, Anne U Jackson, Juha Karjalainen, Ken Sin Lo, Adam E Locke, Reedik Mägi, Evelin Mihailov, Eleonora Porcu, Joshua C Randall, André Scherag, Anna A E Vinkhuyzen, Harm-Jan Westra, Thomas W Winkler, Tsegaselassie Workalemahu, Jing Hua Zhao, Devin Absher, Eva Albrecht, Denise Anderson, Jeffrey Baron, Marian Beekman, Ayse Demirkan, Georg B Ehret, Bjarke Feenstra, Mary F Feitosa, Krista Fischer, Ross M Fraser, Anuj Goel, Jian Gong, Anne E Justice, Stavroula Kanoni, Marcus E Kleber, Kati Kristiansson, Unhee Lim, Vaneet Lotay, Julian C Lui, Massimo Mangino, Irene Mateo Leach, Carolina Medina-Gomez, Michael A Nalls, Dale R Nyholt, Cameron D Palmer, Dorota Pasko, Sonali Pechlivanis, Inga Prokopenko, Janina S Ried, Stephan Ripke, Dmitry Shungin, Alena Stančáková, Rona J Strawbridge, Yun Ju Sung, Toshiko Tanaka, Alexander Teumer, Stella Trompet, Sander W van der Laan, Jessica van Setten, Jana V van Vliet-Ostaptchouk, Zhaoming Wang, Loïc Yengo, Weihua Zhang, Uzma Afzal, Johan Arnlöv, Gillian M Arscott, Stefania Bandinelli, Amy Barrett, Claire Bellis, Amanda J Bennett, Christian Berne, Matthias Blüher, Jennifer L Bolton, Yvonne Böttcher, Heather A Boyd, Marcel Bruinenberg, Brendan M Buckley, Steven Buyske, Ida H Caspersen, Peter S Chines, Robert Clarke, Simone Claudi-Boehm, Matthew Cooper, E Warwick Daw, Pim A de Jong, Joris Deelen, Graciela Delgado, Josh C Denny, Rosalie Dhonukshe-Rutten, Maria Dimitriou, Alex S F Doney, Marcus Dörr, Niina Eklund, Elodie Eury, Lasse Folkersen, Melissa E Garcia, Frank Geller, Vilmantas Giedraitis, Alan S Go, Harald Grallert, Tanja B Grammer, Jürgen Gräßler, Henrik Grönberg, Lisette C P G M de Groot, Christopher J Groves, Jeffrey Haessler, Per Hall, Toomas Haller, Göran Hallmans, Anke Hannemann, Catharina A Hartman, Maija Hassinen, Caroline Hayward, Nancy L Heard-Costa, Quinta Helmer, Gibran Hemani, Anjali K Henders, Hans L Hillege, Mark A Hlatky, Wolfgang Hoffmann, Per Hoffmann, Oddgeir Holmen, Jeanine J Houwing-Duistermaat, Thomas Illig, Aaron Isaacs, Alan L James, Janina Jeff, Berit Johansen, Asa Johansson, Jennifer Jolley, Thorhildur Juliusdottir, Juhani Junttila, Abel N Kho, Leena Kinnunen, Norman Klopp, Thomas Kocher, Wolfgang Kratzer, Peter Lichtner, Lars Lind, Jaana Lindström, Stéphane Lobbens, Mattias Lorentzon, Yingchang Lu, Valeriya Lyssenko, Patrik K E Magnusson, Anubha Mahajan, Marc Maillard, Wendy L McArdle, Colin A McKenzie, Stela McLachlan, Paul J McLaren, Cristina Menni, Sigrun Merger, Lili Milani, Alireza Moayyeri, Keri L Monda, Mario A Morken, Gabriele Müller, Martina Müller-Nurasyid, Arthur W Musk, Narisu Narisu, Matthias Nauck, Ilja M Nolte, Markus M Nöthen, Laticia Oozageer, Stefan Pilz, Nigel W Rayner, Frida Renstrom, Neil R Robertson, Lynda M Rose, Ronan Roussel, Serena Sanna, Hubert Scharnagl, Salome Scholtens, Fredrick R Schumacher, Heribert Schunkert, Robert A Scott, Joban Sehmi, Thomas Seufferlein, Jianxin Shi, Karri Silventoinen, Johannes H Smit, Albert Vernon Smith, Joanna Smolonska, Alice V Stanton, Kathleen Stirrups, David J Stott, Heather M Stringham, Johan Sundström, Morris A Swertz, Ann-Christine Syvänen, Bamidele O Tayo, Gudmar Thorleifsson, Jonathan P Tyrer, Suzanne van Dijk, Natasja M van Schoor, Nathalie van der Velde, Diana van Heemst, Floor V A van Oort, Sita H Vermeulen, Niek Verweij, Judith M Vonk, Lindsay L Waite, Melanie Waldenberger, Roman Wennauer, Lynne R Wilkens, Christina Willenborg, Tom Wilsgaard, Mary K Wojczynski, Andrew Wong, Alan F Wright, Qunyuan Zhang, Dominique Arveiler, Stephan J L Bakker, John Beilby, Richard N Bergman, Sven Bergmann, Reiner Biffar, John Blangero, Dorret I Boomsma, Stefan R Bornstein, Pascal Bovet, Paolo Brambilla, Morris J Brown, Harry Campbell, Mark J Caulfield, Aravinda Chakravarti, Rory Collins, Francis S Collins, Dana C Crawford, L Adrienne Cupples, John Danesh, Ulf de Faire, Hester M den Ruijter, Raimund Erbel, Jeanette Erdmann, Johan G Eriksson, Martin Farrall, Ele Ferrannini, Jean Ferrières, Ian Ford, Nita G Forouhi, Terrence Forrester, Ron T Gansevoort, Pablo V Gejman, Christian Gieger, Alain Golay, Omri Gottesman, Vilmundur Gudnason, Ulf Gyllensten, David W Haas, Alistair S Hall, Tamara B Harris, Andrew T Hattersley, Andrew C Heath, Christian Hengstenberg, Andrew A Hicks, Lucia A Hindorff, Aroon D Hingorani, Albert Hofman, G Kees Hovingh, Steve E Humphries, Steven C Hunt, Elina Hyppönen, Kevin B Jacobs, Marjo-Riitta Järvelin, Pekka Jousilahti, Antti M Jula, Jaakko Kaprio, John J P Kastelein, Manfred Kayser, Frank Kee, Sirkka M Keinanen-Kiukaanniemi, Lambertus A Kiemeney, Jaspal S Kooner, Charles Kooperberg, Seppo Koskinen, Peter Kovacs, Aldi T Kraja, Meena Kumari, Johanna Kuusisto, Timo A Lakka, Claudia Langenberg, Loic Le Marchand, Terho Lehtimäki, Sara Lupoli, Pamela A F Madden, Satu Mannisto, Paolo Manunta, André Marette, Tara C Matise, Barbara McKnight, Thomas Meitinger, Frans L Moll, Grant W Montgomery, Andrew D Morris, Andrew P Morris, Jeffrey C Murray, Mari Nelis, Claes Ohlsson, Albertine J Oldehinkel, Ken K Ong, Willem H Ouwehand, Gerard Pasterkamp, Annette Peters, Peter P Pramstaller, Jackie F Price, Lu Qi, Olli T Raitakari, Tuomo Rankinen, D C Rao, Treva K Rice, Marylyn Ritchie, Igor Rudan, Veikko Salomaa, Nilesh J Samani, Jouko Saramies, Mark A Sarzynski, Peter E H Schwarz, Sylvain Sebert, Peter Sever, Alan R Shuldiner, Juha Sinisalo, Valgerdur Steinthorsdottir, Ronald P Stolk, Jean-Claude Tardif, Anke Tönjes, Angelo Tremblay, Elena Tremoli, Jarmo Virtamo, Marie-Claude Vohl, , Philippe Amouyel, Folkert W Asselbergs, Themistocles L Assimes, Murielle Bochud, Bernhard O Boehm, Eric Boerwinkle, Erwin P Bottinger, Claude Bouchard, Stéphane Cauchi, John C Chambers, Stephen J Chanock, Richard S Cooper, Paul I W de Bakker, George Dedoussis, Luigi Ferrucci, Paul W Franks, Philippe Froguel, Leif C Groop, Christopher A Haiman, Anders Hamsten, M Geoffrey Hayes, Jennie Hui, David J Hunter, Kristian Hveem, J Wouter Jukema, Robert C Kaplan, Mika Kivimäki, Diana Kuh, Markku Laakso, Yongmei Liu, Nicholas G Martin, Winfried März, Mads Melbye, Susanne Moebus, Patricia B Munroe, Inger Njølstad, Ben A Oostra, Colin N A Palmer, Nancy L Pedersen, Markus Perola, Louis Pérusse, Ulrike Peters, Joseph E Powell, Chris Power, Thomas Quertermous, Rainer Rauramaa, Eva Reinmaa, Paul M Ridker, Fernando Rivadeneira, Jerome I Rotter, Timo E Saaristo, Danish Saleheen, David Schlessinger, P Eline Slagboom, Harold Snieder, Tim D Spector, Konstantin Strauch, Michael Stumvoll, Jaakko Tuomilehto, Matti Uusitupa, Pim van der Harst, Henry Völzke, Mark Walker, Nicholas J Wareham, Hugh Watkins, H-Erich Wichmann, James F Wilson, Pieter Zanen, Panos Deloukas, Iris M Heid, Cecilia M Lindgren, Karen L Mohlke, Elizabeth K Speliotes, Unnur Thorsteinsdottir, Inês Barroso, Caroline S Fox, Kari E North, David P Strachan, Jacques S Beckmann, Sonja I Berndt, Michael Boehnke, Ingrid B Borecki, Mark I McCarthy, Andres Metspalu, Kari Stefansson, André G Uitterlinden, Cornelia M van Duijn, Lude Franke, Cristen J Willer, Alkes L Price, Guillaume Lettre, Ruth J F Loos, Michael N Weedon, Erik Ingelsson, Jeffrey R O'Connell, Gonçalo R Abecasis, Daniel I Chasman, Michael E Goddard, Peter M Visscher, Joel N Hirschhorn, Timothy M Frayling.
Nat. Genet.
PUBLISHED: 08-29-2014
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Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ?2,000, ?3,700 and ?9,500 SNPs explained ?21%, ?24% and ?29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/?-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
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Dye-loaded ferritin nanocages for multimodal imaging and photothermal therapy.
Adv. Mater. Weinheim
PUBLISHED: 08-14-2014
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Multimodal imaging-guided photothermal therapy (PTT), for the therapy of cancer, based on a ferritin (FRT) nanocage loaded with the near-infrared dye IR820 (designated DFRT) is demonstrated. The dual roles of DFRT (in imaging and PTT) are successfully balanced by using two different excitation wavelengths: 550 nm for high quantum-yield fluorescence imaging on the one hand and 808 nm for photoacoustic imaging and PTT with high photothermal conversion efficiency on the other.
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Infant feeding and anti-tissue transglutaminase antibody concentrations in the Generation R Study.
Am. J. Clin. Nutr.
PUBLISHED: 08-13-2014
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Celiac disease (CD) has emerged as a common, but largely undiagnosed health problem. Numerous studies examined the influence of infant nutrition on the development of diagnosed CD. However, results are still inconsistent. In addition, the effect of infant feeding practices on the development of potential forms of CD might be different.
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Low-educated women have an increased risk of gestational diabetes mellitus: the Generation R Study.
Acta Diabetol
PUBLISHED: 08-11-2014
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To investigate whether maternal educational level is associated with gestational diabetes mellitus (GDM), and to what extent risk factors for GDM mediate the effect of educational level.
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Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process.
Nat Commun
PUBLISHED: 08-04-2014
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Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition.
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Prenatal exposure to selective serotonin reuptake inhibitors and social responsiveness symptoms of autism: population-based study of young children.
Br J Psychiatry
PUBLISHED: 08-01-2014
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Selective serotonin reuptake inhibitors (SSRIs) are considered safe and are frequently used during pregnancy. However, two case-control studies suggested an association between prenatal SSRI exposure with childhood autism.
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Utilization of esophageal function testing for the diagnosis of the rumination syndrome and belching disorders.
Gastrointest. Endosc. Clin. N. Am.
PUBLISHED: 08-01-2014
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Rumination is a phenomenon characterized by retrograde flow of gastric contents into the mouth, otherwise known as regurgitation. Repetitive excessive occurrence of rumination is considered pathologic and is known as the rumination syndrome. Belching occurs occasionally in everyone and is often not related to a disease or a pathologic condition. Gastric belches are physiologic events caused by retrograde flow of air into the esophagus and mouth; however, supragastric belching is associated with belching disorders and is considered pathologic behavior.
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GWAS identifies four novel eosinophilic esophagitis loci.
Nat Commun
PUBLISHED: 07-18-2014
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Eosinophilic esophagitis (EoE) is an allergic disorder characterized by infiltration of the oesophagus with eosinophils. We had previously reported association of the TSLP/WDR36 locus with EoE. Here we report genome-wide significant associations at four additional loci; c11orf30 and STAT6, which have been previously associated with both atopic and autoimmune diseases, and two EoE-specific loci, ANKRD27 that regulates the trafficking of melanogenic enzymes to epidermal melanocytes and CAPN14, that encodes a calpain whose expression is highly enriched in the oesophagus. The identification of five EoE loci, not only expands our aetiological understanding of the disease but may also represent new therapeutic targets to treat the most debilitating aspect of EoE, oesophageal inflammation and remodelling.
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DRD4 VNTRs, observed stranger fear in preschoolers and later ADHD symptoms.
Psychiatry Res
PUBLISHED: 07-14-2014
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Fear of strangers is a developmental milestone in childhood that encompasses behavioral inhibition and decreased novelty seeking. Children with attention deficit/hyperactivity disorder (ADHD) often exhibit fearless and impulsive behaviors, similar to those observed in children with atypically low levels of stranger fear. It is currently unknown whether these behaviors share common underlying biological mechanisms. Polymorphisms in the dopamine receptor 4 gene (DRD4) have been implicated in the risk for developing ADHD symptoms in childhood. Here we investigate whether (1) DRD4 variable number tandem repeats (VNTRs) are associated with both stranger fear and ADHD symptoms, and (2) stranger fear in preschoolers mediates the link between DRD4 VNTRs and ADHD in later childhood. Stranger fear was observed in a large sample (N=589) of 3-year-old Caucasian children and ADHD symptoms were assessed by a validated, mother-rated questionnaire at 6 years. We found evidence that longer DRD4 variants were associated with increased ADHD symptoms at 6 years, and that this relationship was partially mediated by lower levels of observed stranger fear at 3 years. Our results suggest a common underlying neurobiological mechanism in the association between low stranger fear and ADHD symptoms; variation in DRD4 may be an important contributor to this mechanism.
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Atrial fibrillation in patients with cryptogenic stroke.
N. Engl. J. Med.
PUBLISHED: 06-26-2014
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Atrial fibrillation is a leading preventable cause of recurrent stroke for which early detection and treatment are critical. However, paroxysmal atrial fibrillation is often asymptomatic and likely to go undetected and untreated in the routine care of patients with ischemic stroke or transient ischemic attack (TIA).
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Tyrosinase inhibitory activity of a glucosylated hydroxystilbene in mouse melan-a melanocytes.
J. Nat. Prod.
PUBLISHED: 06-16-2014
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2,3,5,4'-Tetrahydroxystilbene-2-O-?-D-glucopyranoside (1), isolated from Polygonum multiflorum, is a noncompetitive inhibitor of tyrosinase in cell-free kinetics; it reduced the Vmax values in a dose-dependent manner. Compound 1 inhibited PKA-induced melanogenesis, reduced the protein expression of tyrosinase and its transcription factor, the microphthalmia-associated transcription factor, and lowered the complex formation between tyrosinase and tyrosinase-related protein 1 (TRP-1). Immunofluorescence microscopy revealed no association of tyrosinase with the endoplasmic reticulum or lysosomes, implying the absence of a direct effect of 1 on the maturation process of the enzyme. The antimelanogenic activity of 1 is likely mediated through a noncompetitive inhibition on tyrosinase, down-regulation of the expression of melanogenic proteins, and reduction of tyrosinase/TRP-1 complex formation.
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Inefficacy of therapeutic cancer vaccines and proposed improvements. Casus of prostate cancer.
Anticancer Res.
PUBLISHED: 06-13-2014
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Prophylactic vaccination is arguably the most effective medical preventative method. After local inoculation, vaccines induce antigen-specific systemic immunity, protecting the whole body. Systemic antitumour immunity can cure advanced cancer, but will therapeutic vaccination suffice? A vaccine for castration-refractory prostate cancer (CRPC) was approved by regulatory authority, but its evidence is disputed. We critically reviewed the clinical efficacy of therapeutic cancer vaccines for prostate cancer, including the results of 31 clinical studies employing vaccines-only, and another 10 studies combining vaccines with immune co-stimulation. Vaccinations yielded immunological responses, but no study showed evidence for clinically relevant therapeutic improvement. Clinical failure of therapeutic vaccination is discussed in the light of immunological dogmas and mechanisms of antitumour therapies. We propose that cancer immunotherapy might be improved by immunological danger, i.e. disturbing tumour homeostasis by destroying the tumour tissue or inducing local inflammation. Such danger might override immunological tolerance, and thereby allow clinically relevant anticancer results.
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Current diagnosis and management of the rumination syndrome.
J. Clin. Gastroenterol.
PUBLISHED: 06-13-2014
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The rumination syndrome is a behavioral condition characterized by postprandial regurgitation. In contrast to what many think, the disorder does not exclusively occur in mentally disabled patients or children but also in otherwise healthy adults. As symptoms of postprandial regurgitation are often mistaken for gastroesophageal reflux disease or vomiting, the rumination syndrome is an underappreciated condition. Rumination episodes are caused by an intragastric pressure increases which forces the gastric content into the esophagus and mouth and occurs during 3 distinct mechanisms: primary rumination, secondary rumination, and supragastric belch-associated rumination. Combined manometry-impedance can distinguish rumination from gastroesophageal reflux disease. Treatment of the rumination syndrome consists of a thorough explanation of the mechanisms underlying the rumination episodes and behavioral therapy. As behavioral therapy is a time-consuming and often expensive treatment, we propose that a clinical suspicion of the disorder is always confirmed by a manometry-impedance measurement.
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Hypersensitivity to acid is associated with impaired esophageal mucosal integrity in patients with gastroesophageal reflux disease with and without esophagitis.
Am. J. Physiol. Gastrointest. Liver Physiol.
PUBLISHED: 06-12-2014
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Increased esophageal sensitivity and impaired mucosal integrity have both been described in patients with gastroesophageal reflux disease, but the relationship between hypersensitivity and mucosal integrity is unclear. The aim of the present study was to investigate acid sensitivity in patients with erosive and nonerosive reflux disease and control subjects to determine the relation with functional esophageal mucosal integrity changes as well as to investigate cellular mechanisms of impaired mucosal integrity in these patients. In this prospective experimental study, 12 patients with nonerosive reflux disease, 12 patients with esophagitis grade A or B, and 11 healthy control subjects underwent an acid perfusion test and upper endoscopy. Mucosal integrity was measured during endoscopy by electrical tissue impedance spectroscopy and biopsy specimens were analyzed in Ussing chambers for transepithelial electrical resistance, transepithelial permeability and gene expression of tight junction proteins and filaggrin. Patients with nonerosive reflux disease and esophagitis were more sensitive to acid perfusion compared with control subjects, having a shorter time to perception of heartburn and higher perceived intensity of heartburn. In reflux patients, enhanced acid sensitivity was associated with impairment of in vivo and vitro esophageal mucosal integrity. Mucosal integrity was significantly impaired in patients with esophagitis, displaying higher transepithelial permeability and lower extracellular impedance. Although no significant differences in the expression of tight junction proteins were found in biopsies among patient groups, mucosal integrity parameters in reflux patients correlated negatively with the expression of filaggrin. In conclusion, sensitivity to acid is enhanced in patients with gastroesophageal reflux disease, irrespective of the presence of erosions, and is associated with impaired esophageal mucosal integrity. Mucosal integrity of the esophagus is associated with the expression of filaggrin.
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Retained host Descemet membrane (Auto-DMET) during conversion of deep anterior lamellar keratoplasty to penetrating keratoplasty: a case report.
Cornea
PUBLISHED: 06-11-2014
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The aim of this study was to relate a case of deep anterior lamellar keratoplasty (DALK) converted to penetrating keratoplasty in which the host central Descemet membrane (DM) with a large perforation was left attached to the host cornea.
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Transcript Profile of Cellular Senescence-related Genes in Fuchs Endothelial Corneal Dystrophy.
Exp. Eye Res.
PUBLISHED: 06-04-2014
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Fuchs endothelial corneal dystrophy (FECD) is a genetically heterogeneous disease. Hypothesizing that cellular senescence may be relevant in FECD pathogenesis, genetically undifferentiated late-onset FECD endothelial samples were analyzed to identify common changes of specific senescence-related transcripts. Total RNA was extracted from 21 FECD endothelial samples retrieved from patients undergoing lamellar keratoplasty due to clinically diagnosed end-stage FECD and from 12 endothelial samples retrieved from normal autopsy eyes. Taqman low density array (TLDA) cards were used to analyze differential expression of 89 cellular senescence-related transcripts. Result validation was performed using individual real-time PCR assays. TLDA-analysis demonstrated differential expression of 31 transcripts (fold-change >1.5; p<0.05). Thereof, 27 showed significant up-regulation and 4 significant down-regulation. Markedly elevated mRNA-levels of the constitutively active and reactive oxygen species-generating enzyme NOX4 were found in all evaluable FECD samples. In addition, increased expression of CDKN2A and its transcriptional activators ETS1 and ARHGAP18 (SENEX) along with decreased expression of CDKN2A inhibitor ID1 were detected in FECD samples. Consistent over-expression of NOX4 in FECD endothelial samples suggests a role as pathogenic factor and as a potential new treatment target in FECD. Transcriptional up-regulation of the CDKN2A-pathway provides further evidence for increased cellular senescence in FECD endothelium.
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Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.
John R B Perry, Felix Day, Cathy E Elks, Patrick Sulem, Deborah J Thompson, Teresa Ferreira, Chunyan He, Daniel I Chasman, Tonu Esko, Gudmar Thorleifsson, Eva Albrecht, Wei Q Ang, Tanguy Corre, Diana L Cousminer, Bjarke Feenstra, Nora Franceschini, Andrea Ganna, Andrew D Johnson, Sanela Kjellqvist, Kathryn L Lunetta, George McMahon, Ilja M Nolte, Lavinia Paternoster, Eleonora Porcu, Albert V Smith, Lisette Stolk, Alexander Teumer, Natalia Tšernikova, Emmi Tikkanen, Sheila Ulivi, Erin K Wagner, Najaf Amin, Laura J Bierut, Enda M Byrne, Jouke-Jan Hottenga, Daniel L Koller, Massimo Mangino, Tune H Pers, Laura M Yerges-Armstrong, Jing Hua Zhao, Irene L Andrulis, Hoda Anton-Culver, Femke Atsma, Stefania Bandinelli, Matthias W Beckmann, Javier Benitez, Carl Blomqvist, Stig E Bojesen, Manjeet K Bolla, Bernardo Bonanni, Hiltrud Brauch, Hermann Brenner, Julie E Buring, Jenny Chang-Claude, Stephen Chanock, Jinhui Chen, Georgia Chenevix-Trench, J Margriet Collée, Fergus J Couch, David Couper, Andrea D Coviello, Angela Cox, Kamila Czene, Adamo Pio D'adamo, George Davey Smith, Immaculata De Vivo, Ellen W Demerath, Joe Dennis, Peter Devilee, Aida K Dieffenbach, Alison M Dunning, Gudny Eiriksdottir, Johan G Eriksson, Peter A Fasching, Luigi Ferrucci, Dieter Flesch-Janys, Henrik Flyger, Tatiana Foroud, Lude Franke, Melissa E Garcia, Montserrat Garcia-Closas, Frank Geller, Eco E J de Geus, Graham G Giles, Daniel F Gudbjartsson, Vilmundur Gudnason, Pascal Guénel, Suiqun Guo, Per Hall, Ute Hamann, Robin Haring, Catharina A Hartman, Andrew C Heath, Albert Hofman, Maartje J Hooning, John L Hopper, Frank B Hu, David J Hunter, David Karasik, Douglas P Kiel, Julia A Knight, Veli-Matti Kosma, Zoltan Kutalik, Sandra Lai, Diether Lambrechts, Annika Lindblom, Reedik Mägi, Patrik K Magnusson, Arto Mannermaa, Nicholas G Martin, Gisli Masson, Patrick F McArdle, Wendy L McArdle, Mads Melbye, Kyriaki Michailidou, Evelin Mihailov, Lili Milani, Roger L Milne, Heli Nevanlinna, Patrick Neven, Ellen A Nohr, Albertine J Oldehinkel, Ben A Oostra, Aarno Palotie, Munro Peacock, Nancy L Pedersen, Paolo Peterlongo, Julian Peto, Paul D P Pharoah, Dirkje S Postma, Anneli Pouta, Katri Pylkäs, Paolo Radice, Susan Ring, Fernando Rivadeneira, Antonietta Robino, Lynda M Rose, Anja Rudolph, Veikko Salomaa, Serena Sanna, David Schlessinger, Marjanka K Schmidt, Mellissa C Southey, Ulla Sovio, Meir J Stampfer, Doris Stöckl, Anna M Storniolo, Nicholas J Timpson, Jonathan Tyrer, Jenny A Visser, Peter Vollenweider, Henry Völzke, Gérard Waeber, Melanie Waldenberger, Henri Wallaschofski, Qin Wang, Gonneke Willemsen, Robert Winqvist, Bruce H R Wolffenbuttel, Margaret J Wright, , Dorret I Boomsma, Michael J Econs, Kay-Tee Khaw, Ruth J F Loos, Mark I McCarthy, Grant W Montgomery, John P Rice, Elizabeth A Streeten, Unnur Thorsteinsdottir, Cornelia M van Duijn, Behrooz Z Alizadeh, Sven Bergmann, Eric Boerwinkle, Heather A Boyd, Laura Crisponi, Paolo Gasparini, Christian Gieger, Tamara B Harris, Erik Ingelsson, Marjo-Riitta Järvelin, Peter Kraft, Debbie Lawlor, Andres Metspalu, Craig E Pennell, Paul M Ridker, Harold Snieder, Thorkild I A Sørensen, Tim D Spector, David P Strachan, André G Uitterlinden, Nicholas J Wareham, Elisabeth Widén, Marek Zygmunt, Anna Murray, Douglas F Easton, Kari Stefansson, Joanne M Murabito, Ken K Ong.
Nature
PUBLISHED: 05-30-2014
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Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P?
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Fuchs endothelial corneal dystrophy in patients with myotonic dystrophy: a case series.
Cornea
PUBLISHED: 05-29-2014
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The aim was to report 4 cases of Fuchs endothelial corneal dystrophy (FECD) in patients with an established diagnosis of myotonic dystrophy (DM) and suggest a mechanism for their association based on the known molecular genetics and potential pathophysiological parallels of DM and FECD.
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Design and analysis of keratoconus tissue microarrays.
Cornea
PUBLISHED: 05-29-2014
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The aim was to produce 2 tissue microarrays (TMAs) for keratoconus (KC) corneas and to evaluate the expression of stress-related markers, epidermal growth factor receptor (EGFR), and 8-oxo-2'-deoxyguanosine (8-OHdG), in KC corneas.
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Gait shows a sex-specific pattern of associations with daily functioning in a community-dwelling population of older people.
Gait Posture
PUBLISHED: 05-22-2014
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Gait is increasingly considered an important indicator of health. Yet, little is known on the relation of gait with established health indicators, e.g. daily functioning. Although gait differs by sex, it is unknown whether different gait domains provide different health indicators in men or women. We investigated how gait associates with basic and instrumental activities of daily living (BADL and IADL) in community-dwelling persons.
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Associations of Heart Failure with Sleep Quality: The Rotterdam Study.
J Clin Sleep Med
PUBLISHED: 05-13-2014
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The prevalence of sleep disturbances and heart failure increases with age. We aimed to evaluate the associations of incident heart failure and cardiac dysfunction with changes in sleep quality.
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Total dietary antioxidant capacity, individual antioxidant intake and breast cancer risk: The Rotterdam study.
Int. J. Cancer
PUBLISHED: 05-06-2014
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Some studies suggest a favorable role of antioxidants on breast cancer risk but this is still inconclusive. The aim of this study was to assess whether overall dietary antioxidant capacity, as assessed by dietary ferric reducing antioxidant potential (FRAP), and individual dietary antioxidant intake were associated with breast cancer risk. Data was used from women participating in the Rotterdam Study, a prospective cohort study among subjects aged 55 years and older (N?=?3,209). FRAP scores and antioxidant intake (i.e., vitamin A, C, E, selenium, flavonoids and carotenoids) was assessed at baseline by a food frequency questionnaire. Incident cases of breast cancer were confirmed through medical reports. During a median follow-up of 17 years, 199 cases with breast cancer were identified. High dietary FRAP score was associated with a lower risk of breast cancer [hazard ratio (HR): 0.68; 95% confidence intervals (CI): 0.49, 0.96]. No overall association between individual antioxidant intake and breast cancer risk was found. However, low intake of alpha carotene and beta carotene was associated with a higher risk of breast cancer among smokers (HR: 2.48; 95% CI: 1.21, 5.12 and HR: 2.31; 95% CI: 1.12, 4.76 for alpha and beta carotene, respectively) and low intake of flavonoids was associated with breast cancer risk in women over the age of 70 (HR: 1.80; 95% CI: 1.09, 2.99). These results suggest that high overall dietary antioxidant capacity is associated with a lower risk of breast cancer. Individual effects of dietary carotenoids and dietary flavonoids may be restricted to subgroups such as smokers and elderly.
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Dairy products and the risk of stroke and coronary heart disease: the Rotterdam Study.
Eur J Nutr
PUBLISHED: 04-30-2014
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We examined whether consumption of total dairy and dairy subgroups was related to incident stroke and coronary heart disease (CHD) in a general older Dutch population.
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Descemet stripping automated endothelial keratoplasty after failed penetrating keratoplasty: survival, rejection risk, and visual outcome.
JAMA Ophthalmol
PUBLISHED: 04-26-2014
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Descemet stripping automated endothelial keratoplasty (DSAEK) for isolated endothelial dysfunction has become the preferred surgical option for many corneal surgeons. However, there are limited large-scale reports on DSAEK survival and clinical variables affecting the risk of rejection and failure after failed penetrating keratoplasty (PK).
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Simple, inexpensive, and effective injector for descemet membrane endothelial keratoplasty.
Cornea
PUBLISHED: 04-26-2014
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We describe an inexpensive, simple, and effective endothelium-Descemet membrane (EDM) graft injector assembled from regular operating room supplies in Descemet membrane endothelial keratoplasty (DMEK).
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The pathophysiology, diagnosis and treatment of excessive belching symptoms.
Am. J. Gastroenterol.
PUBLISHED: 04-18-2014
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Excessive belching is a commonly observed complaint in clinical practice that can occur not only as an isolated symptom but also as a concomitant symptom in patients with gastroesophageal reflux disease (GERD) or functional dyspepsia. Impedance monitoring has revealed that there are two mechanisms through which belching can occur: the gastric belch and the supragastric belch. The gastric belch is the result of a vagally mediated reflex leading to relaxation of the lower esophageal sphincter and venting of gastric air. The supragastric belch is a behavioral peculiarity. During this type of belch, pharyngeal air is sucked or injected into the esophagus, after which it is immediately expulsed before it has reached the stomach. Patients who belch excessively invariably exhibit an increased incidence of supragastric, not of gastric belches. Moreover, supragastric belches can elicit regurgitation episodes in patients with the rumination syndrome and sometimes appear to induce reflux episodes as well. Behavioral therapy has been proven to decrease belching complaints in patients with isolated excessive belching, but its effect is unknown in frequently belching patients with GERD, functional dyspepsia or rumination.
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A Genetic Variant in the Seed Region of Mir-4513 Shows Pleiotropic Effects on Lipid and Glucose Homeostasis, Blood Pressure and Coronary Artery Disease.
Hum. Mutat.
PUBLISHED: 04-15-2014
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MicroRNAs (miRNA) play a crucial role in the regulation of diverse biological processes by post-transcriptional modulation of gene expression. Genetic polymorphisms in miRNA-related genes can potentially contribute to a wide range of phenotypes. The effect of such variants on cardiometabolic diseases has not yet been defined. We systematically investigated the association of genetic variants in the seed regions of miRNAs with cardiometabolic phenotypes, using the thus far largest genome wide association studies on 17 cardiometabolic traits/diseases. We found that rs2168518:G>A, a seed region variant of miR-4513, associates with fasting glucose, LDL-cholesterol and total cholesterol, systolic and diastolic blood pressure and risk of coronary artery disease. We experimentally showed that miR-4513 expression is significantly reduced in presence of the rs2168518 mutant allele. We sought to identify miR-4513 target genes that may mediate these associations and revealed five genes (PCSK1, BNC2, MTMR3, ANK3 and GOSR2) through which these effects might be taking place. Using luciferase reporter assays we validated GOSR2 as a target of miR-4513 and further demonstrated that the miRNA mediated regulation of this gene is changed by rs2168518. Our findings indicate a pleiotropic effect of miR-4513 on cardiometabolic phenotypes and may improve our understanding of the pathophysiology of cardiometabolic diseases. This article is protected by copyright. All rights reserved.
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Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium.
Hum. Genet.
PUBLISHED: 04-14-2014
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To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E-8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E-07), TOX (rs7823467, P = 3.47E-07) and LINC00340 (rs12212674, P = 1.49E-06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = -0.59, P = 2.10E-04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors.
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Coronene encapsulation in single-walled carbon nanotubes: stacked columns, peapods, and nanoribbons.
Chemphyschem
PUBLISHED: 04-11-2014
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Encapsulation of coronene inside single-walled carbon nanotubes (SWNTs) was studied under various conditions. Under high vacuum, two main types of molecular encapsulation were observed by using transmission electron microscopy: coronene dimers and molecular stacking columns perpendicular or tilted (45-60°) with regard to the axis of the SWNTs. A relatively small number of short nanoribbons or polymerized coronene molecular chains were observed. However, experiments performed under an argon atmosphere (0.17 MPa) revealed reactions between the coronene molecules and the formation of hydrogen-terminated graphene nanoribbons. It was also observed that the morphology of the encapsulated products depend on the diameter of the SWNTs. The experimental results are explained by using density functional theory calculations through the energies of the coronene molecules inside the SWNTs, which depend on the orientation of the molecules and the diameter of the tubes.
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Growth Trajectories and Bone Mineral Density in Anti-tissue Transglutaminase Antibody- positive Children: The Generation R study.
Clin. Gastroenterol. Hepatol.
PUBLISHED: 04-09-2014
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Increased levels of anti-tissue transglutaminase (tTG) have been associated with reduced weight and bone mineral density (BMD) in symptomatic patients with celiac disease. Little is known about the effects of these antibodies in patients with subclinical or other forms of celiac disease. We examined associations between anti-tTG positivity and growth and BMD.
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Prevalence of esophageal motility abnormalities increases with longer disease duration in adult patients with eosinophilic esophagitis.
Neurogastroenterol. Motil.
PUBLISHED: 04-07-2014
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During the natural course of eosinophilic esophagitis (EoE), the risk for esophageal stricture formation increases. It remains unknown whether motility abnormalities in EoE also develop over time. We aimed to determine the relationship between disease duration, clinical characteristics, and manometric pattern of EoE patients.
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Visual Consequences of Refractive Errors in the General Population.
Ophthalmology
PUBLISHED: 04-04-2014
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To study the frequency and causes of visual impairment in relation to refractive error.
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A lab-on-chip for malaria diagnosis and surveillance.
Malar. J.
PUBLISHED: 03-13-2014
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Access to timely and accurate diagnostic tests has a significant impact in the management of diseases of global concern such as malaria. While molecular diagnostics satisfy this need effectively in developed countries, barriers in technology, reagent storage, cost and expertise have hampered the introduction of these methods in developing countries. In this study a simple, lab-on-chip PCR diagnostic was created for malaria that overcomes these challenges.
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Development of an in vitro model to measure bioactivity of botulinum neurotoxin A in rat bladder muscle strips.
BMC Urol
PUBLISHED: 03-04-2014
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Botulinum toxin A (BoNT-A) is a new treatment modality in various causes of bladder dysfunction; like neurogenic detrusor overactivity and overactive bladder. The best technique of administrating BoNT-A in patients is unknown. A validated in vitro model could be used to investigate newer intravesical administration techniques of BoNT-A. In this study, we describe the development and validation of in vitro model to measure inhibitory effects of BoNT-A on bladder strip contractions.
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Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
Iris Postmus, Stella Trompet, Harshal A Deshmukh, Michael R Barnes, Xiaohui Li, Helen R Warren, Daniel I Chasman, Kaixin Zhou, Benoit J Arsenault, Louise A Donnelly, Kerri L Wiggins, Christy L Avery, Paula Griffin, QiPing Feng, Kent D Taylor, Guo Li, Daniel S Evans, Albert V Smith, Catherine E de Keyser, Andrew D Johnson, Anton J M de Craen, David J Stott, Brendan M Buckley, Ian Ford, Rudi G J Westendorp, P Eline Slagboom, Naveed Sattar, Patricia B Munroe, Peter Sever, Neil Poulter, Alice Stanton, Denis C Shields, Eoin O'Brien, Sue Shaw-Hawkins, Y-D Ida Chen, Deborah A Nickerson, Joshua D Smith, Marie Pierre Dubé, S Matthijs Boekholdt, G Kees Hovingh, John J P Kastelein, Paul M McKeigue, John Betteridge, Andrew Neil, Paul N Durrington, Alex Doney, Fiona Carr, Andrew Morris, Mark I McCarthy, Leif Groop, Emma Ahlqvist, , Joshua C Bis, Kenneth Rice, Nicholas L Smith, Thomas Lumley, Eric A Whitsel, Til Stürmer, Eric Boerwinkle, Julius S Ngwa, Christopher J O'Donnell, Ramachandran S Vasan, Wei-Qi Wei, Russell A Wilke, Ching-Ti Liu, Fangui Sun, Xiuqing Guo, Susan R Heckbert, Wendy Post, Nona Sotoodehnia, Alice M Arnold, Jeanette M Stafford, Jingzhong Ding, David M Herrington, Stephen B Kritchevsky, Gudny Eiriksdottir, Leonore J Launer, Tamara B Harris, Audrey Y Chu, Franco Giulianini, Jean G MacFadyen, Bryan J Barratt, Fredrik Nyberg, Bruno H Stricker, André G Uitterlinden, Albert Hofman, Fernando Rivadeneira, Valur Emilsson, Oscar H Franco, Paul M Ridker, Vilmundur Gudnason, Yongmei Liu, Joshua C Denny, Christie M Ballantyne, Jerome I Rotter, L Adrienne Cupples, Bruce M Psaty, Colin N A Palmer, Jean-Claude Tardif, Helen M Colhoun, Graham Hitman, Ronald M Krauss, J Wouter Jukema, Mark J Caulfield.
Nat Commun
PUBLISHED: 02-27-2014
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Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
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Vitamin D deficiency in Crohn's disease and healthy controls: a prospective case-control study in the Netherlands.
J Crohns Colitis
PUBLISHED: 02-26-2014
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Vitamin D deficiency has been observed in a wide range of medical conditions including Crohn's disease (CD). We aimed to assess whether CD patients have lower vitamin D levels than healthy controls, and to determine risk factors for vitamin D deficiency.
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Comparing a marginal structural model with a Cox proportional hazard model to estimate the effect of time-dependent drug use in observational studies: statin use for primary prevention of cardiovascular disease as an example from the Rotterdam Study.
Eur. J. Epidemiol.
PUBLISHED: 02-25-2014
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When studying the causal effect of drug use in observational data, marginal structural modeling (MSM) can be used to adjust for time-dependent confounders that are affected by previous treatment. The objective of this study was to compare traditional Cox proportional hazard models (with and without time-dependent covariates) with MSM to study causal effects of time-dependent drug use. The example of primary prevention of cardiovascular disease (CVD) with statins was examined using up to 17.7 years of follow-up from 4,654 participants of the observational prospective population-based Rotterdam Study. In the MSM model, the weight was based on measurements of established cardiovascular risk factors and co-morbidity. In general, we could not demonstrate important differences in results from the Cox models and MSM. Results from analysis on duration of statin use suggested that substantial residual confounding by indication was not accounted for during the period shortly after statin initiation. In conclusion, although on theoretical grounds MSM is an elegant technique, lack of data on the precise time-dependent confounders, such as indication of treatment or other considerations of the prescribing physician jeopardizes the calculation of valid weights. Confounding remains a hurdle in observational effectiveness research on preventive drugs with a multitude of prescription determinants.
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Proton Pump Inhibitors Partially Restore Mucosal Integrity in Patients With Proton Pump Inhibitor-Responsive Esophageal Eosinophilia but Not Eosinophilic Esophagitis.
Clin. Gastroenterol. Hepatol.
PUBLISHED: 02-23-2014
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Histologic analysis is used to distinguish patients with proton pump inhibitor-responsive eosinophilia (PPI-REE) from those with eosinophilic esophagitis (EoE). It is not clear whether these entities have different etiologies. Exposure to acid reflux can impair the integrity of the esophageal mucosal. We proposed that patients with EoE and PPI-REE might have reflux-induced esophageal mucosal damage that promotes transepithelial flux of allergens. We therefore assessed the integrity of the esophageal mucosal in these patients at baseline and after PPI.
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Tract-specific white matter degeneration in aging. The Rotterdam Study.
Alzheimers Dement
PUBLISHED: 02-08-2014
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Loss of brain white matter microstructure is presumed to be an early sign of neurodegenerative disease. Yet, little is known on microstructural changes of various white matter tracts with normal aging.
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Utilizing hardware culture in a case of atypical keratitis.
Semin Ophthalmol
PUBLISHED: 02-07-2014
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This case report describes the diagnosis and management of a 22-year-old male soft contact lens wearer, who presented with an atypical corneal ulcer in the right eye. The patient presented with a one-day history of significant eye pain, photophobia, and multiple pseudodendritic lesions on the cornea with stromal infiltrate; the differential remained broad. The management was guided by the culture of hardware of the patient's contact lenses, which grew aspergillus only in the affected contact. In cases where corneal culture is negative, multiple organisms have been isolated from the corneal culture, or in cases where there is no response to medical treatment, culture of hardware may be a useful methodology for isolating the offending microbe in infectious corneal ulcers.
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Post-fusion structural changes and their roles in exocytosis and endocytosis of dense-core vesicles.
Nat Commun
PUBLISHED: 01-30-2014
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Vesicle fusion with the plasma membrane generates an ?-shaped membrane profile. Its pore is thought to dilate until flattening (full-collapse), followed by classical endocytosis to retrieve vesicles. Alternatively, the pore may close (kiss-and-run), but the triggering mechanisms and its endocytic roles remain poorly understood. Here, using confocal and stimulated emission depletion microscopy imaging of dense-core vesicles, we find that fusion-generated ?-profiles may enlarge or shrink while maintaining vesicular membrane proteins. Closure of fusion-generated ?-profiles, which produces various sizes of vesicles, is the dominant mechanism mediating rapid and slow endocytosis within ~1-30 s. Strong calcium influx triggers dynamin-mediated closure. Weak calcium influx does not promote closure, but facilitates the merging of ?-profiles with the plasma membrane via shrinking rather than full-collapse. These results establish a model, termed ?-exo-endocytosis, in which the fusion-generated ?-profile may shrink to merge with the plasma membrane, change in size or change in size then close in response to calcium, which is the main mechanism to retrieve dense-core vesicles.
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Water-perfused esophageal high-resolution manometry: normal values and validation.
Am. J. Physiol. Gastrointest. Liver Physiol.
PUBLISHED: 01-30-2014
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Water-perfused high-resolution manometry (HRM) catheters with 36 unidirectional pressure channels have recently been developed, but normal values are not yet available. Furthermore, the technique has not been validated and compared with solid-state HRM. We therefore aimed to develop normal values for water-perfused HRM and to assess the level of agreement between water-perfused HRM and solid-state HRM. We included 50 healthy volunteers (mean age 35 yr, range 21-64 yr; 15 women, 35 men). Water-perfused HRM and solid-state HRM were performed in a randomized order. Normal values were calculated as 5th and 95th percentile ranges, and agreement between the two systems was assessed with intraclass correlation coefficient (ICC) statistics. The 5th-95th percentile range was 3.0-6.6 cm/s for contractile front velocity (CFV), 141.6-3,674 mmHg·s·cm for distal contractile integral (DCI), 6.2-8.7 s for distal contraction latency (DL), and 1.0-18.8 mmHg for integrated relaxation pressure (IRP 4s). Mean (SD) and ICC for water-perfused HRM and solid-state HRM were 4.4 (1.1) vs. 3.9 (0.9) cm/s, ICC: 0.49 for CFV; 1,189 (1,023) vs. 1,092 (1,019) mmHg·s·cm, ICC: 0.90 for DCI; 7.4 (0.8) vs. 6.9 (0.9) s, ICC: 0.50 for DL; and 8.1 (4.8) vs. 7.9 (5.1), ICC: 0.39 for IRP 4s. The normal values for this water-perfused HRM system are only slightly different from previously published values with solid-state HRM, and moderate to good agreement was observed between the two systems, with only small differences in outcome measures.
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Differential susceptibility in a developmental perspective: DRD4 and maternal sensitivity predicting externalizing behavior.
Dev Psychobiol
PUBLISHED: 01-27-2014
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This study is the first to investigate the longitudinal effects of gene-environment interplay between DRD4 genotype and maternal sensitivity on child externalizing behavior. Multiple measures of maternal sensitivity (14, 36, and 48 months) and externalizing behavior (18 months, 36 months, and 5 years) were assessed in a large cohort study (N?=?548). Early maternal insensitivity (14 months) was associated with early externalizing behavior (18 months) in a for better and for worse manner, but only in children with at least one DRD4 7-repeat, consistent with a differential susceptibility model. Later insensitivity (48 months) predicted externalizing behavior at age 5 independent of DRD4 genotype. A structural equation model including all measures across time supported the differential susceptibility model: The overall effect of early maternal sensitivity on later externalizing behavior was significant only for children with a DRD4 7-repeat allele. The results highlight the importance of studying gene-environment interactions across development. © 2014 Wiley Periodicals, Inc. Dev Psychobiol.
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Effects of Antidepressants in Patients With Functional Esophageal Disorders or Gastroesophageal Reflux Disease: A Systematic Review.
Clin. Gastroenterol. Hepatol.
PUBLISHED: 01-17-2014
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Patients with functional esophageal disorders present with symptoms of chest pain, heartburn, dysphagia, or globus in the absence of any structural abnormality. Visceral hypersensitivity is a feature of these functional disorders, and might be modulated by antidepressant therapy. We evaluated evidence for the efficacy of antidepressant therapy for symptoms associated with esophageal visceral hypersensitivity in patients with functional esophageal disorders or gastroesophageal reflux disease (GERD).
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Common variation near ROBO2 is associated with expressive vocabulary in infancy.
Nat Commun
PUBLISHED: 01-15-2014
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Twin studies suggest that expressive vocabulary at ~24 months is modestly heritable. However, the genes influencing this early linguistic phenotype are unknown. Here we conduct a genome-wide screen and follow-up study of expressive vocabulary in toddlers of European descent from up to four studies of the EArly Genetics and Lifecourse Epidemiology consortium, analysing an early (15-18 months, 'one-word stage', N(Total) = 8,889) and a later (24-30 months, 'two-word stage', N(Total)=10,819) phase of language acquisition. For the early phase, one single-nucleotide polymorphism (rs7642482) at 3p12.3 near ROBO2, encoding a conserved axon-binding receptor, reaches the genome-wide significance level (P=1.3 × 10(-8)) in the combined sample. This association links language-related common genetic variation in the general population to a potential autism susceptibility locus and a linkage region for dyslexia, speech-sound disorder and reading. The contribution of common genetic influences is, although modest, supported by genome-wide complex trait analysis (meta-GCTA h(2)(15-18-months) = 0.13, meta-GCTA h(2)(24-30-months) = 0.14) and in concordance with additional twin analysis (5,733 pairs of European descent, h(2)(24-months) = 0.20).
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N-Acetylcysteine increases corneal endothelial cell survival in a mouse model of Fuchs endothelial corneal dystrophy.
Exp. Eye Res.
PUBLISHED: 01-14-2014
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The present study evaluated survival effects of N-acetylcysteine (NAC) on cultured corneal endothelial cells exposed to oxidative and endoplasmic reticulum (ER) stress and in a mouse model of early-onset Fuchs endothelial corneal dystrophy (FECD). Cultured bovine corneal endothelial cell viability against oxidative and ER stress was determined by CellTiter-Glo(®) luminescent reagent. Two-month-old homozygous knock-in Col8a2(L450W/L450W) mutant (L450W) and C57/Bl6 wild-type (WT) animals were divided into two groups of 15 mice. Group I received 7 mg/mL NAC in drinking water and Group II received control water for 7 months. Endothelial cell density and morphology were evaluated with confocal microscopy. Antioxidant gene (iNos) and ER stress/unfolded protein response gene (Grp78 and Chop) mRNA levels and protein expression were measured in corneal endothelium by real time PCR and Western blotting. Cell viability of H2O2 and thapsigargin exposed cells pre-treated with NAC was significantly increased compared to untreated controls (p < 0.01). Corneal endothelial cell density (CD) was higher (p = 0.001) and percent polymegathism was lower (p = 0.04) in NAC treated L450W mice than in untreated L450W mice. NAC treated L450W endothelium showed significant upregulation of iNos, whereas Grp78 and Chop were downregulated compared to untreated L450W endothelium by real time PCR and Western blotting. NAC increases survival in cultured corneal endothelial cells exposed against ER and oxidative stress. Systemic NAC ingestion increases corneal endothelial cell survival which is associated with increased antioxidant and decreased ER stress markers in a mouse model of early-onset FECD. Our study presents in vivo evidence of a novel potential medical treatment for FECD.
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Hydrogen-Driven Cage Unzipping of C60 into Nano-Graphenes.
J Phys Chem C Nanomater Interfaces
PUBLISHED: 01-13-2014
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Annealing of C60 in hydrogen at temperatures above the stability limit of C-H bonds in C60H x (500-550 °C) is found to result in direct collapse of the cage structure, evaporation of light hydrocarbons, and formation of solid mixture composed of larger hydrocarbons and few-layered graphene sheets. Only a minor part of this mixture is soluble; this was analyzed using matrix-assisted laser desorption/ionization MS, Fourier transform infrared (FTIR), and nuclear magnetic resonance spectroscopy and found to be a rather complex mixture of hydrocarbon molecules composed of at least tens of different compounds. The sequence of most abundant peaks observed in MS, which corresponds to C2H2 mass difference, suggests a stepwise breakup of the fullerene cage into progressively smaller molecular fragments edge-terminated by hydrogen. A simple model of hydrogen-driven C60 unzipping is proposed to explain the observed sequence of fragmentation products. The insoluble part of the product mixture consists of large planar polycyclic aromatic hydrocarbons, as evidenced by FTIR and Raman spectroscopy, and some larger sheets composed of few-layered graphene, as observed by transmission electron microscopy. Hydrogen annealing of C60 thin films showed a thickness-dependent results with reaction products significantly different for the thinnest films compared to bulk powders. Hydrogen annealing of C60 films with the thickness below 10 nm was found to result in formation of nanosized islands with Raman spectra very similar to the spectra of coronene oligomers and conductivity typical for graphene.
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Characterization of and protection from neurotoxicity induced by oxaliplatin, bortezomib and epothilone-B.
Anticancer Res.
PUBLISHED: 01-10-2014
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To characterize neurotoxicity induced by oxaliplatin, bortezomib, and epothilone-B as well as protection against their neurotoxicity using an in vitro model.
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The dystrophin gene and cognitive function in the general population.
Eur. J. Hum. Genet.
PUBLISHED: 01-07-2014
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The aim of our study is to investigate whether single-nucleotide dystrophin gene (DMD) variants associate with variability in cognitive functions in healthy populations. The study included 1240 participants from the Erasmus Rucphen family (ERF) study and 1464 individuals from the Rotterdam Study (RS). The participants whose exomes were sequenced and who were assessed for various cognitive traits were included in the analysis. To determine the association between DMD variants and cognitive ability, linear (mixed) modeling with adjustment for age, sex and education was used. Moreover, Sequence Kernel Association Test (SKAT) was used to test the overall association of the rare genetic variants present in the DMD with cognitive traits. Although no DMD variant surpassed the prespecified significance threshold (P<1 × 10(-4)), rs147546024:A>G showed strong association (?=1.786, P-value=2.56 × 10(-4)) with block-design test in the ERF study, while another variant rs1800273:G>A showed suggestive association (?=-0.465, P-value=0.002) with Mini-Mental State Examination test in the RS. Both variants are highly conserved, although rs147546024:A>G is an intronic variant, whereas rs1800273:G>A is a missense variant in the DMD which has a predicted damaging effect on the protein. Further gene-based analysis of DMD revealed suggestive association (P-values=0.087 and 0.074) with general cognitive ability in both cohorts. In conclusion, both single variant and gene-based analyses suggest the existence of variants in the DMD which may affect cognitive functioning in the general populations.European Journal of Human Genetics advance online publication, 17 September 2014; doi:10.1038/ejhg.2014.183.
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Rhodotorula Keratitis: A Rarely Encountered Ocular Pathogen.
Case Rep Ophthalmol
PUBLISHED: 01-01-2014
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To describe a case of fungal keratitis involving an atypical organism with confirmatory in vivo confocal microscopy and to review the literature on Rhodotorula keratitis.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.