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Latest Paper:
Kai Januschowski,
Ahmad Zhour,
Albert Lee,
Ramin Maddani,
Sebastien Mueller,
Martin S Spitzer,
Sven Schnichels,
Maximilian Schultheiss,
Deshka Doycheva,
Karl-Ulrich Bartz-Schmidt,
Peter Szurman
Centre for Ophthalmology, University Eye Hospital, Tuebingen, Germany.
The effects of a glutathione-containing intra-ocular irrigation solution, BSS Plus©, on retinal function and on the survival of ganglion cells in whole-mount retinal explants were studied. Evidence is provided that the perfused ex vivo bovine retina can serve as an alternative to in vivo animal testing. Isolated bovine retinas were prepared and perfused with an oxygen-saturated standard irrigation solution, and an electroretinogram was recorded to assess retinal function. After stable b-waves were detected, the isolated retinas were perfused with BSS Plus for 45 minutes. To investigate the effects of BSS Plus on photoreceptor function, 1mM aspartate was added to the irrigation solution in order to obtain a-waves, and the ERG trace was monitored for 75 minutes. For histological analysis, isolated whole retinal mounts were stored for 24 hours at 4°C, in the dark. The percentages of cell death in the retinal ganglion cell layer and in the outer and inner nuclear layers were estimated by using an ethidium homodimer-1 stain and the TUNEL assay. General swelling of the retina was examined with high-resolution optical coherence tomography. During perfusion with BSS Plus, no significant changes in a-wave and b-wave amplitudes were recorded. Retinas stored for 24 hours in BSS Plus showed a statistically significant smaller percentage (52.6%, standard deviation [SD]= 16.1%) of cell death in the retinal ganglion cell layer compared to the control group (69.6%, SD = 3.9, p = 0.0031). BSS Plus did not seem to affect short-term retinal function, and had a beneficial effect on the survival of retinal ganglion cells. This method for analysing the isolated perfused retina represents a valuable alternative for testing substances for their retinal biocompatibility and toxicity.
S Chatrchyan,
V Khachatryan,
A M Sirunyan,
A Tumasyan,
W Adam,
T Bergauer,
M Dragicevic,
J Erö,
C Fabjan,
M Friedl,
R Frühwirth,
V M Ghete,
J Hammer,
M Hoch,
N Hörmann,
J Hrubec,
M Jeitler,
W Kiesenhofer,
M Krammer,
D Liko,
I Mikulec,
M Pernicka,
B Rahbaran,
C Rohringer,
H Rohringer,
R Schöfbeck,
J Strauss,
A Taurok,
F Teischinger,
P Wagner,
W Waltenberger,
G Walzel,
E Widl,
C-E Wulz,
V Mossolov,
N Shumeiko,
J Suarez Gonzalez,
S Bansal,
L Benucci,
T Cornelis,
E A De Wolf,
X Janssen,
S Luyckx,
T Maes,
L Mucibello,
S Ochesanu,
B Roland,
R Rougny,
M Selvaggi,
H Van Haevermaet,
P Van Mechelen,
N Van Remortel,
A Van Spilbeeck,
F Blekman,
S Blyweert,
J D'Hondt,
R Gonzalez Suarez,
A Kalogeropoulos,
M Maes,
A Olbrechts,
W Van Doninck,
P Van Mulders,
G P Van Onsem,
I Villella,
O Charaf,
B Clerbaux,
G De Lentdecker,
V Dero,
A P R Gay,
G H Hammad,
T Hreus,
A Léonard,
P E Marage,
L Thomas,
C Vander Velde,
P Vanlaer,
J Wickens,
V Adler,
K Beernaert,
A Cimmino,
S Costantini,
G Garcia,
M Grunewald,
B Klein,
J Lellouch,
A Marinov,
J McCartin,
A A Ocampo Rios,
D Ryckbosch,
N Strobbe,
F Thyssen,
M Tytgat,
L Vanelderen,
P Verwilligen,
S Walsh,
E Yazgan,
N Zaganidis,
S Basegmez,
G Bruno,
L Ceard,
J De Favereau De Jeneret,
C Delaere,
T du Pree,
D Favart,
L Forthomme,
A Giammanco,
G Grégoire,
J Hollar,
V Lemaitre,
J Liao,
O Militaru,
C Nuttens,
D Pagano,
A Pin,
K Piotrzkowski,
N Schul,
N Beliy,
T Caebergs,
E Daubie,
G A Alves,
M Correa Martins Junior,
D De Jesus Damiao,
T Martins,
M E Pol,
M H G Souza,
W L Aldá Júnior,
W Carvalho,
A Custódio,
E M Da Costa,
C De Oliveira Martins,
S Fonseca De Souza,
D Matos Figueiredo,
L Mundim,
H Nogima,
V Oguri,
W L Prado Da Silva,
A Santoro,
S M Silva Do Amaral,
L Soares Jorge,
A Sznajder,
T S Anjos,
C A Bernardes,
F A Dias,
T R Fernandez Perez Tomei,
E M Gregores,
C Lagana,
F Marinho,
P G Mercadante,
S F Novaes,
Sandra S Padula,
V Genchev,
P Iaydjiev,
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M Rodozov,
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R Trayanov,
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A Dimitrov,
R Hadjiiska,
A Karadzhinova,
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X Meng,
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J Zang,
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C Asawatangtrakuldee,
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S Guo,
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W Li,
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Y Mao,
S J Qian,
H Teng,
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B Zhu,
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A Cabrera,
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A F Osorio Oliveros,
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F Ptochos,
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A Ellithi Kamel,
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A Radi,
A Hektor,
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A Tiko,
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A Heikkinen,
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M J Kortelainen,
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T Lindén,
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I Shreyber,
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C Mironov,
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Y Sirois,
C Thiebaux,
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A Zabi,
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J Andrea,
D Bloch,
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M Cardaci,
E C Chabert,
C Collard,
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F Drouhin,
C Ferro,
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U Goerlach,
P Juillot,
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A-C Le Bihan,
P Van Hove,
F Fassi,
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G Boudoul,
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A Falkiewicz,
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B Ille,
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C Kleinwort,
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A Petrukhin,
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T Schoerner-Sadenius,
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A Spiridonov,
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C Wissing,
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U Gebbert,
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G B Mohanty,
B Parida,
A Saha,
K Sudhakar,
N Wickramage,
S Dugad,
N K Mondal,
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H Bakhshiansohi,
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C Lazaridis,
J Leonard,
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A Mohapatra,
I Ojalvo,
G A Pierro,
I Ross,
A Savin,
W H Smith,
J Swanson
Yerevan Physics Institute, Yerevan, Armenia.
A search for a Higgs boson in the four-lepton decay channel H→ZZ, with each Z boson decaying to an electron or muon pair, is reported. The search covers Higgs boson mass hypotheses in the range of 110<m_{H}<600 GeV. The analysis uses data corresponding to an integrated luminosity of 4.7 fb^{-1} recorded by the CMS detector in pp collisions at sqrt[s]=7 TeV from the LHC. Seventy-two events are observed with four-lepton invariant mass m_{4ℓ}>100 GeV (with 13 below 160 GeV), while 67.1±6.0 (9.5±1.3) events are expected from background. The four-lepton mass distribution is consistent with the expectation of standard model background production of ZZ pairs. Upper limits at 95% confidence level exclude the standard model Higgs boson in the ranges of 134-158 GeV, 180-305 GeV, and 340-465 GeV. Small excesses of events are observed around masses of 119, 126, and 320 GeV, making the observed limits weaker than expected in the absence of a signal.
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W H Smith,
J Swanson,
M Weinberg
Yerevan Physics Institute, Yerevan, Armenia.
A search for signatures of extra spatial dimensions in the diphoton invariant-mass spectrum has been performed with the CMS detector at the LHC. No excess of events above the standard model expectation is observed using a data sample collected in proton-proton collisions at sqrt[s]=7 TeV corresponding to an integrated luminosity of 2.2 fb^{-1}. In the context of the large-extra-dimensions model, lower limits are set on the effective Planck scale in the range of 2.3-3.8 TeV at the 95% confidence level. These limits are the most restrictive bounds on virtual-graviton exchange to date. The most restrictive lower limits to date are also set on the mass of the first graviton excitation in the Randall-Sundrum model in the range of 0.86-1.84 TeV, for values of the associated coupling parameter between 0.01 and 0.10.
Environ Sci Technol. 2012 Apr 25;:
22533454
Timothy John Wallington,
James E Anderson,
Sherry Mueller,
Emily Kolinski Morris,
Sandy Winkler,
John Ginder,
Ole John Nielsen
The approximately 100 million tonne per year increase in the use of corn to produce ethanol in the U.S. over the past 10 years, and projections of greater future use, have raised concerns that reduced exports of corn (and other agricultural products) and higher commodity prices would lead to land-use changes and consequently, negative environmental impacts in other countries. The concerns have been driven by agricultural and trade models which project that large-scale corn ethanol production leads to substantial decreases in food exports, increases in food prices, and greater deforestation globally. Over the past decade the increased use of corn for ethanol has been largely matched by the increased corn harvest attributable mainly to increased yields. U.S. exports of corn, wheat, soybeans, pork, chicken, and beef either increased or remained unchanged. Exports of distillers' dry grains (DDG, a co-product of ethanol production and a valuable animal feed) increased by more than an order of magnitude to 9 million tonnes in 2010. Increased biofuel production may lead to intensification (higher yields) and extensification (more land) of agricultural activities. Intensification and extensification have opposite impacts on land use change. We highlight the lack of information concerning the magnitude of intensification effects and the associated large uncertainties in assessments of the indirect land use change associated with corn ethanol.
J Mol Med (Berl). 2012 Apr 15;:
22527885
Zhuoming Liu,
Robert Lanford,
Sebastian Mueller,
Glenn S Gerhard,
Sara Luscieti,
Mayka Sanchez,
L Devireddy
Case Comprehensive Cancer Center and Department of Pathology, Case Western Reserve University, Cleveland, OH, 44106, USA.
Siderophores are best known as small iron binding molecules that facilitate microbial iron transport. In our previous study we identified a siderophore-like molecule in mammalian cells and found that its biogenesis is evolutionarily conserved. A member of the short chain dehydrogenase family of reductases, 3-hydroxy butyrate dehydrogenase (BDH2) catalyzes a rate-limiting step in the biogenesis of the mammalian siderophore. We have shown that depletion of the mammalian siderophore by inhibiting expression of bdh2 results in abnormal accumulation of cellular iron and mitochondrial iron deficiency. These observations suggest that the mammalian siderophore is a critical regulator of cellular iron homeostasis and facilitates mitochondrial iron import. By utilizing bioinformatics, we identified an iron-responsive element (IRE; a stem-loop structure that regulates genes expression post-transcriptionally upon binding to iron regulatory proteins or IRPs) in the 3'-untranslated region of the human BDH2 (hBDH2) gene. In cultured cells as well as in patient samples we now demonstrate that the IRE confers iron-dependent regulation on hBDH2 and binds IRPs in RNA electrophoretic mobility shift assays. In addition, we show that the hBDH2 IRE associates with IRPs in cells and that abrogation of IRPs by RNAi eliminates the iron-dependent regulation of hBDH2 mRNA. The key physiologic implication is that iron-mediated post-transcriptional regulation of hBDH2 controls mitochondrial iron homeostasis in human cells. These observations provide a new and an unanticipated mechanism by which iron regulates its intracellular trafficking.
Senior Physician, Black Forrest Hospital, Villingen, Germany.
Originally, sleeve gastrectomy (SG) was part of biliopancreatic diversion (BPD), which is the most effective bariatric procedure for super obese patients. As BPD is a complex procedure with substantial morbidity and mortality, attempts were undertaken to split the procedure into two steps. SG became the first step in a staged BPD procedure assuming that this less-invasive operation would reduce the surgical risk in super obese patients. The second step - the duodenal switch - was thus postponed until after a major weight loss. Several studies have since been published showing data that, besides the successful weight loss, the procedure itself had a positive effect on obesity-associated comorbidities. Sleeve gastrectomy has gained widespread acceptance as a primary and definite bariatric procedure. SG has become an innovative tool in the battle against obesity. Although several variations of SG have been described, standardization is paramount for optimal results. Of particular interest are: the minimally invasive access, the dissection, preservation of the antrum, position of staple-line and buttress material, as well as the size of the bougie and the extent of fundal resection. This article describes the different procedural and technical aspects of the operation. In addition, it will line out how we transferred our skills and experience in single incision laparoscopic surgery (SILS) from cholecystectomy and sigmoid resection to sleeve gastrectomy.
Kai Januschowski,
Ramin Maddani,
Sebastian Mueller,
Matthias Lueke,
Martin S Spitzer,
Maximilian Schultheiss,
Karl-Ulrich Bartz-Schmidt,
Peter Szurman
Department of Ophthalmology I, Eberhard Karls University of Tübingen, Tübingen, Germany.
Purpose: To compare the effect of a taurine-containing intraocular irrigation solution (PuriProtect™) to a standard irrigation solution (BSS™) we evaluated the retinal function using an electroretinogram (ERG) and analyzed the survival of retinal ganglion cells on isolated whole mount retinas. Materials and Methods: During ERG recordings, each irrigation solution was superfused for 45 min with the relevant irrigation solution. To investigate the effects on photoreceptor function, 1 mM asparate was added to obtain a-waves. The recovery of the a- and b-wave was monitored after superfusing the retinas with standard medium again. To evaluate the percentage of dead ganglion cells, retinas were stored for 24 h at 4°C in darkness and after staining the retinas with ethidium homodimer-1 the retinas were analyzed using fluorescence microscopy. Results: The application of standard medium supplemented with 2 mM taurine resulted in a significant increase of the b-wave amplitude compared to standard medium alone. The a-wave amplitudes showed no significant changes under taurine supplementation. Compared to standard medium BSS showed no significant decrease in b-wave amplitudes, but a significant decrease in a-wave amplitudes. In contrast to BSS there were no significant changes in the a- or b-wave amplitudes detectable after the application of PuriProtect. At the end of the washout period no significant changes in a- or b-wave amplitudes were recorded for any tested irrigation solution. Retinas stored for 24 h in PuriProtect or in standard medium with taurine had a statistically significant smaller amount of dead cells than retinas stored in standard medium without taurine supplementation. Conclusions: BSS does not seem to be an ideal irrigation solution, because it compromises the a-wave in the ERG. In contrast to BSS, PuriProtect showed no significant impact on the ERG and showed a better long-term effect on ganglion cell survival. Taurine supplementation, therefore, seems to be neuroprotective and its supplementation to an intraocular irrigation solution favorable for the retina.
Kai Januschowski,
Sebastian Mueller,
Martin S Spitzer,
Charlotte Schramm,
Deshka Doycheva,
Karl-Ulrich Bartz-Schmidt,
Peter Szurman
Department of Ophthalmology I, Eberhard-Karls University of Tuebingen, Schleichstr 12, 72076, Tuebingen, Germany, Kai.januschowski@med.uni-tuebingen.de.
BACKGROUND: Dyes such as brilliant blue (BBG) are used during vitreoretinal surgery to visualize anatomical structures. By adding deuterium oxide (D2O), surgeons have tried to create a dye mixture heavier than water to facilitate staining of the inner limiting membrane (ILM) without prior fluid-air exchange. This study investigated the effect of 0.4 ml BBG (Fluoron, Ulm, Germany) mixed with 0.13 ml/ml D2O and D2O on retinal function of a pseudo in vivo model using bovine and human whole mount cultures. METHODS: Bovine and human retinas were superfused, and the electroretinogram (ERG) was recorded. BBG with 0.13 ml/ml D2O and D2O were applied epiretinally, different staining periods (10, 30, 60 and 120 s) were tested, and ERG recovery was monitored. 1 mM aspartate was added to the nutrient solution to examine the photoreceptor reaction. RESULTS: Reductions of the a- and b-wave amplitudes were found directly after exposure with BBG with 0.13 ml/ml D2O and with D2O in all test series. These effects on the electroretinogram were rapidly and completely reversible within the recovery time for all exposure times. ERG amplitudes measured after dye application at the end of the washout did not differ significantly from those recorded before staining. CONCLUSIONS: The clinically used mixture of BBG/D2O seems to be safe for clinical use. Staining periods of more than 120 seconds were not tested.
Thromb Haemost. 2012 Mar 8;107 (6):
22398417
T Wilke,
A Groth,
S Mueller,
M Pfannkuche,
F Verheyen,
R Linder,
U Maywald,
T Kohlmann,
Y-S Feng,
G Breithardt,
R Bauersachs
Thomas Wilke, IPAM, University of Wismar, PF 1210, 23952 Wismar, Germany, Tel.:+49 3841 753 504, E-mail: Thomas.wilke@hs-wismar.de.
Atrial fibrillation (AF) is the most common significant cardiac rhythm disorder. Oral anticoagulation (OAC) is recommended by guidelines in the presence of a moderate to high risk of stroke. Based on an analysis of claims-based data, the aim of this contribution is to quantify the stroke-risk dependent OAC utilisation profile of German AF patients as well as the possible causes and the associated clinical outcomes of OAC under-use. Our data set was derived from two large mandatory German medical insurance funds. Risk stratification of patients was based on the CHADS2-score and the CHA2DS2-VASc-score. Two different scenarios were constructed to deal with factors potentially disfavouring OAC use. Causes of OAC under-use and its clinical consequences were analysed using multivariate analysis. Observation year was 2008. A total of 183,448 AF patients met the inclusion criteria. This represents an AF prevalence of 2.21%. The average CHADS2-score was 2.8 (CHA2DS2-VASc-score: 4.3). On between 40.5 and 48.7% of the observed patient-days, there was no antithrombotic protection by OAC, other anticoagulants or aspirin. Older female patients with a high number of comorbidities had a higher risk of OAC under-use. Patients who had already experienced a thromboembolic event had a lower risk of OAC under-use. In the observation year, 3,367 patients experienced a stroke (incidence rate 1.8%). In our multi-level Poisson random effects estimate, OAC use decreases the stroke rate by almost 80%(IRR 0.236). In conclusion, OAC under-use is widespread in the German market. It is associated with severe clinical consequences.
Adam Schoenfeld,
Melike Pekmezci,
Michael J Barnes,
Tarik Tihan,
Nalin Gupta,
Kathleen R Lamborn,
Anu Banerjee,
Sabine Mueller,
Susan Chang,
Mitchel S Berger,
Daphne Haas-Kogan
Department of Radiation Oncology, University of California, San Francisco (UCSF), 1600 Divisadero St. Suite H1031, San Francisco, CA, 94143-1708, USA.
The purpose of this study is to evaluate the roles of resection extent and adjuvant radiation in the treatment of craniopharyngiomas. We reviewed the records of 122 patients ages 11-52 years who received primary treatment for craniopharyngioma between 1980 and 2009 at the University of California, San Francisco (UCSF). Primary endpoints were progression free survival (PFS) and overall survival (OS). Secondary endpoints were development of panhypopituitarism, diabetes insipidus (DI), and visual field defects. Of 122 patients, 30 (24%) were treated with gross total resection (GTR) without radiation therapy (RT), 3 (3%) with GTR + RT, 41 (33.6%) with subtotal resection (STR) without RT, and 48 (39.3%) with STR + RT. Median age at diagnosis was 30 years, with 46 patients 18 years or younger. Median follow-up for all patients was 56.4 months (interquartile range 18.9-144.2 months) and 47 months (interquartile range 12.3-121.8 months) for the 60 patients without progression. Fifty six patients progressed, 10 have died, 6 without progression. Median PFS was 61.1 months for all patients. PFS rate at 2 years was 61.5%(95% CI: 52.1-70.9). OS rate at 10 years was 91.1%(95% CI 84.3-97.9). There was no significant difference in PFS and OS between patients treated with GTR vs. STR + XRT (PFS; p = 0.544, OS; p = 0.735), but STR alone resulted in significantly shortened PFS compared to STR + RT or GTR (p < 0.001 for both). STR was associated with significantly shortened OS compared to STR + RT (p = 0.050) and trended to shorter OS compared to GTR (p = 0.066). GTR was associated with significantly greater risk of developing DI (56.3 vs. 13.3% with STR + XRT, p < 0.001) and panhypopituitarism (54.8 vs. 26.7% with STR + XRT, p = 0.014). In conclusion, for patients with craniopharyngioma, STR + RT may provide superior clinical outcome, achieving better disease control than STR and limiting side effects associated with aggressive surgical resection.
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