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"text": "\n71001\nActivation of the cAMP-protein kinase A pathway facilitates Na+ translocation by the Na+-K+ pump in guinea-pig ventricular myocytes.\n\nKockskamper, J\n\nErlenkamp, S\n\nGlitsch, HG\n\nBeiträge in Fachzeitschriften\nISI:000086243000003\n10718738.0\n10.1111/j.1469-7793.2000.t01-2-00561.x\nPMC2269834\n1. The effects of the adenylyl cyclase activator forskolin on steady-state and transient currents generated by the Na+-K+ pump were studied in guinea-pig ventricular myocytes by means of whole-cell voltage clamp at 30 C. 2. In external solution containing 144 mM Na+ (Na+o) and 10 mM K+ (K+o), steady-state Na+-K+ pump current (Ip) activated by 5 mM pipette Na+ (Na+pip) at -20 mV was reversibly augmented by forskolin (4 microM) to 133 +/- 4 % of the control current (n = 15). The forskolin analogue 1, 9-dideoxyforskolin (10 microM), which does not activate adenylyl cyclases, did not increase Ip (n = 2). Application of the protein kinase A (PKA) inhibitor H-89 (10 microM) in the continued presence of forskolin reversed the forskolin-induced elevation of Ip (n = 3). 3. The forskolin effect on Ip persisted in the presence of 50 mM Na+pip which ensured that the internal Na+-binding sites of the Na+-K+ pump were nearly saturated. Under these conditions, the drug increased Ip to 142 +/- 3 % of the control Ip when the pipette free Ca2+ concentration ([Ca2+]pip) was 0.013 nM (n = 5) and to 138 +/- 4 % of the control Ip when free [Ca2+]pip was 15 nM (n = 9). 4. In Na+-free external solution, Ip activated by 50 mM Na+pip and 1.5 mM K+o was likewise increased by forskolin but to a lesser extent than in Na+-containing medium (116 +/- 3 % of control, n = 10). 5. In order to investigate exclusively partial reactions in the Na+ limb of the pump cycle, transient pump currents under conditions of electroneutral Na+-Na+ exchange were studied. Transient pump currents elicited by voltage jumps displayed an initial peak and then decayed monoexponentially. Moved charge (Q) and the rate constant of current decay varied with membrane potential (V). The Q-V relationship followed a Boltzmann distribution characterized by the midpoint voltage (V0.5) and the maximum amount of movable charge (DeltaQmax). Forskolin (2-10 microM) shifted V0.5 to more negative values while DeltaQmax was not affected (n = 11). The effects of forskolin on transient pump currents were mimicked by 8-bromo-cAMP (500 microM; n = 2) and abolished by a peptide inhibitor of PKA (PKI, 10 microM; n = 5). 6. We conclude that activation of the cAMP-PKA pathway in guinea-pig ventricular myocytes increases Na+-K+ pump current at least in part by modulating partial reactions in the Na+ limb of the pump cycle. Under physiological conditions, the observed stimulation of the cardiac Na+-K+ pump may serve to shorten the action potential duration and to counteract the increased passive sarcolemmal Na+ and K+ fluxes during sympathetic stimulation of the heart.\n\n\n"
},
{
"text": "\n182907\nTumor-associated mortality and prognostic factors in myxofibrosarcoma - A retrospective review of 109 patients.\n\nGilg, MM\n\nSunitsch, S\n\nLeitner, L\n\nBergovec, M\n\nSzkandera, J\n\nLeithner, A\n\nLiegl-Atzwanger, B\n\nBeiträge in Fachzeitschriften\nISI:000577437900009\n32778437.0\n10.1016/j.otsr.2020.04.017\nNone\nMyxofibrosarcoma (MFS) is one of the most common sarcoma subtype in elderly patients. They are reported to recur locally independently of the tumour grade in 30-40% of cases and metastases are reported to develop in high-grade tumours in 20-35% cases. As MFS is a rare diagnosis, data investigating specific survival and independent risk factors are lacking and have mostly been limited to single orthopaedic oncology centre studies so far. Thus we set up a pathology-based retrospective study and analyzed all MFS diagnosed in our institution with the following aims: (1) analysis of independent risk factors for overall survival, disease specific survival, local recurrence-free survival and distant metastasis free survival following resection of MFS; (2) analysis of resection margin status.\n High-grade MFS have a low survival distant metastasis free survival and local recurrence free survival is dependent on surgical margin status.\n We retrospectively analysed 109 patients (median 66 years [range, 21-96]) diagnosed with MFS and a median follow-up of 42 months at one centre between 1990 and 2014. Tumor-associated survival, including competing risk analysis, and prognostic factors for local recurrence, metastatic disease and death from disease were investigated and included in a multivariate analysis.\n Overall survival was 79% [95%CI: 71.9-87.5] at 3 years and 76% [95%CI: 67.4-84.6] at 5 years. Disease specific survival was 85% [95%CI: 78.4-92.2] at 3 years and 80% [95%CI: 72.2-88.2] at 5 years. There were local recurrences in 11/109 patients (10%). Local recurrence free survival (LRFS) was 95% [95%CI: 92.0-99.8] at 3 and 88% [95%CI: 84.3-96.4] at 5 years. Metastatic disease (n=25; 23%) occurred after a median follow-up of 10 months. Distant metastasis free survival was 78% [95%CI: 69.9-85.9] at 3 and 77% [95%CI: 68.4-84.8] at 5 years. R1 status at primary resection was an independent risk factor for decreased Local Recurrence-free survival (OR: 8.5, 95%CI: 1.59-49.79 [p=0.01]). Grading was an independent risk factor for decreased Disease specific survival (OR 13.4, 95%CI: 1.65-1734.84 [p=0.01]) and Distant metastasis free survival (OR 16.2, 95%CI: 2.0-2110.5 [p=0.004]). Primary resection achieved R0 margins in 63 (58%) of 109 patients. Margins were adequate significantly more often (p<0.001) in patients treated primarily at a sarcoma centre (R0=58/68, 85%) than in those treated primarily at non-sarcoma centres (R0= 5/41, 12%), whereby the latter significantly more often treated superficial tumours (p=0.001) with a size of less than 5cm (p<0.001).\n Patients with high-grade MFS had a poorer prognosis with respect to Disease specific survival/Distant metastasis free survival than low-grade MFS. Local recurrence did not significantly affect disease specific survival.\n IV.\n Copyright © 2020 Elsevier Masson SAS. All rights reserved.\n\nBergovec, Marko\n\nGilg, Magdalena Maria\n\nLeithner, Andreas\n\nLeitner, Lukas\n\nLiegl-Atzwanger, Bernadette\n\nSunitsch, Sandra\n\nSzkandera, Joanna\n\n\n"
},
{
"text": "\n156148\nVideo-game-assisted physiotherapeutic scoliosis-specific exercises for idiopathic scoliosis: case series and introduction of a new tool to increase motivation and precision of exercise performance.\n\nWibmer, C\n\nGroebl, P\n\nNischelwitzer, A\n\nSalchinger, B\n\nSperl, M\n\nWegmann, H\n\nHolzer, HP\n\nSaraph, V\n\nBeiträge in Fachzeitschriften\nISI:000395314200001\n27896317.0\n10.1186/s13013-016-0104-9\nPMC5121954\nIt is important to monitor how patients with juvenile and adolescent idiopathic scoliosis comply with their physiotherapeutic scoliosis-specific exercises (PSSE). Physiogame, a newly developed video game using the Game-Trak 3D interactive game controller, combines correct PSSE performance with gaming. It tracks the position of the working limb in 3D space during the exercises as participants aim to hit certain targets and avoid others, and gives direct feedback by stopping the game if the working limb leaves the target 3D space, which is chosen to secure the corrective position according to the Schroth method. Physiogame records the quality and frequency of the exercises performed. We aimed to investigate the influence of this tool on motivation to perform regularly and, correctly, and with self-assessment of performance quality.\n This case series included 8 consecutive patients with idiopathic scoliosis (thoracolumbar 7, lumbar 1), ages 7-13 years, all female and treated according to SOSORT guidelines; the COBB angle of primary curve at the start of brace therapy was 22-34°. In addition to Full Time Rigid Bracing (FTRB, Cheneau) and PSSE (Schroth), the participants were to perform two standardized Schroth exercises (muscle cylinder in standing position, mainly addressing the thoracic curve, and in side-lying position, mainly addressing the lumbar curve) with video game assistance every day for 6 months. The development (first to last month) of the following parameters was analyzed with descriptive methods: the actual training time to assess motivation, the ratio of the actual playing time versus total playing time to assess exercise improvement, and self-assessment of quality of performance.\n The average number of sessions with Physiogame was 217 per study participant (range 24 to 572, the study protocol targeted at least 180); actual training time decreased from 79 to 52 min (first to last month). Actual playing time increased from 73% of the total playing time to 83% (first to last month), and positive hits per second from 0.33 to 0.56. Self-assessment increased from "good" to "very good". The curve angles (°Cobb) were maintained over the study period (upper thoracic mean -1.3°, median -1°; lower thoracic mean 3°, median 2°; lumbar mean 0.5, median 0).\n The improvement we saw in exercise performance, is thought to result primarily from the direct given feedback during the game, as the exercises themselves were already familiar to the patients. The synchronous recording of actual training time allows evaluation of Schroth therapy for idiopathic scoliosis, since both prescribed training time and actual training time are captured. No comparable tool was found in literature.\n\nSperl, Matthias\n\n\n"
},
{
"text": "\n151993\nEFQM (European foundation for quality management): is a repeated C2E (Committed to Excellence) assessment a necessary condition on the way to the Recognised for Excellence (R4E) award?\n\nLangmann, G\n\nGranitz, E\n\nMaier, R\n\nLechner, H\n\nBauer, H\n\nTheisl, A\n\nKohlhofer, L\n\nWohlfart, C\n\nFoussek, C\n\nLangmann, A\n\nWedrich, A\n\nBeiträge in Fachzeitschriften\nISI:000371315400011\nNone\n10.1007/s00717-015-0281-6\nNone\nThe EFQM (European Foundation for Quality Management) has on the way to its highest excellence level (the European quality award), the Committed to Excellence milestone (C2E (optional), the Recognised for Excellence Quality Award (R4E, 3, 4 and 5 stars) positioned. Our study examines whether the repetition of the C2E award is a necessary prerequisite for achieving the R4E award. The Department of Ophthalmology has structured its quality management according to EFQM since 2006 along with four model clinics of the LKH Univ.Klinikum Graz. The central philosophy of the EFQM work is the RADAR cycle according which the results are determined at the beginning of the circle (R). A set of sound approaches (A) are developed to deliver the required results (D). The approaches are deployed in a systematic way to ensure implementation. The deployed approaches based on monitoring and analysis of the results are assessed and refined (AR). In 2008 for the first time the Department of Ophthalmology achieved the Committed to Excellence (C2E) award. Project work comprised three projects which had to be finalisied within 6 months.The projects were: (1) The admittance of a cataract patient to the Department of Ophthalmology. (2) The information management between different groups of the department. (3) The common goal of agreement between the Medical University of Graz (MUG), the KAGES (Krankenanstalten Gesellschaft) and the Department of Ophthalmology. In 2009 as an alternative to the R4E approach the Department of Ophthalmology again achieved the C2E Quality Award with 3 new projects. The new projects were: (1) the development of a vision, mission statement, values and principles for the Department of Ophthalmology. (2) The reduction of outpatient patients without an appointment or allocation. (3) A concept of a curriculum of Strabism and Paediatric Neuroophthalmology at the Department of Opthalmology Graz. In the second Committed to Excellence level (C2E) all three projects were sucessfully accomplished. The repetition of the Committed to Excellence (C2) award in 2010 after initial achievement of its first quality award in 2008 is less of a time delay on the way to the Recognised for Excellence (R4E) level. Thereby the philosophy of the EFQM with its RADAR logic could be implemented in all professions (e.g. physicians, nursing, auxiliary nurses (SHD). This broad-based integration of the EFQM philosophy in turn is a prerequisite for the next higher level, the R4E (Recognised for Excellence). In daily life, the radar circle has proven to be an optimum working tool.\n\nBauer, Heimo\n\nLangmann, Andrea\n\nLangmann, Gerald\n\nWedrich, Andreas\n\n\n"
},
{
"text": "\n143520\nChitinase 3-like 1: prognostic biomarker in clinically isolated syndromes.\n\nCantó, E\n\nTintoré, M\n\nVillar, LM\n\nCosta, C\n\nNurtdinov, R\n\nÁlvarez-Cermeño, JC\n\nArrambide, G\n\nReverter, F\n\nDeisenhammer, F\n\nHegen, H\n\nKhademi, M\n\nOlsson, T\n\nTumani, H\n\nRodríguez-Martín, E\n\nPiehl, F\n\nBartos, A\n\nZimova, D\n\nKotoucova, J\n\nKuhle, J\n\nKappos, L\n\nGarcía-Merino, JA\n\nSánchez, AJ\n\nSaiz, A\n\nBlanco, Y\n\nHintzen, R\n\nJafari, N\n\nBrassat, D\n\nLauda, F\n\nRoesler, R\n\nRejdak, K\n\nPapuc, E\n\nde Andrés, C\n\nRauch, S\n\nKhalil, M\n\nEnzinger, C\n\nGalimberti, D\n\nScarpini, E\n\nTeunissen, C\n\nSánchez, A\n\nRovira, A\n\nMontalban, X\n\nComabella, M\n\nBeiträge in Fachzeitschriften\nISI:000353522100019\n25688078.0\n10.1093/brain/awv017\nNone\nChitinase 3-like 1 (CHI3L1) has been proposed as a biomarker associated with the conversion to clinically definite multiple sclerosis in patients with clinically isolated syndromes, based on the finding of increased cerebrospinal fluid CHI3L1 levels in clinically isolated syndrome patients who later converted to multiple sclerosis compared to those who remained as clinically isolated syndrome. Here, we aimed to validate CHI3L1 as a prognostic biomarker in a large cohort of patients with clinically isolated syndrome. This is a longitudinal cohort study of clinically isolated syndrome patients with clinical, magnetic resonance imaging, and cerebrospinal fluid data prospectively acquired. A total of 813 cerebrospinal fluid samples from patients with clinically isolated syndrome were recruited from 15 European multiple sclerosis centres. Cerebrospinal fluid CHI3L1 levels were measured by enzyme-linked immunosorbent assay. Multivariable Cox regression models were used to investigate the association between cerebrospinal fluid CHI3L1 levels and time to conversion to multiple sclerosis and time to reach Expanded Disability Status Scale 3.0. CHI3L1 levels were higher in patients who converted to clinically definite multiple sclerosis compared to patients who continued as clinically isolated syndrome (P = 8.1 × 10(-11)). In the Cox regression analysis, CHI3L1 levels were a risk factor for conversion to multiple sclerosis (hazard ratio = 1.7; P = 1.1 × 10(-5) using Poser criteria; hazard ratio = 1.6; P = 3.7 × 10(-6) for McDonald criteria) independent of other covariates such as brain magnetic resonance imaging abnormalities and presence of cerebrospinal fluid oligoclonal bands, and were the only significant independent risk factor associated with the development of disability (hazard ratio = 3.8; P = 2.5 × 10(-8)). High CHI3L1 levels were associated with shorter time to multiple sclerosis (P = 3.2 × 10(-9) using Poser criteria; P = 5.6 × 10(-11) for McDonald criteria) and more rapid development of disability (P = 1.8 × 10(-10)). These findings validate cerebrospinal fluid CHI3L1 as a biomarker associated with the conversion to multiple sclerosis and development of disability and reinforce the prognostic role of CHI3L1 in patients with clinically isolated syndrome. We propose that determining cerebrospinal fluid chitinase 3-like 1 levels at the time of a clinically isolated syndrome event will help identify those patients with worse disease prognosis. \n © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.\n\nEnzinger, Christian\n\nKhalil, Michael\n\n\n"
},
{
"text": "\n129786\nEAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2013.\n\nBabjuk, M\n\nBurger, M\n\nZigeuner, R\n\nShariat, SF\n\nvan Rhijn, BW\n\nCompérat, E\n\nSylvester, RJ\n\nKaasinen, E\n\nBöhle, A\n\nPalou Redorta, J\n\nRouprêt, M\n\nEuropean Association of Urology\n\nBeiträge in Fachzeitschriften\nISI:000323939900028\n23827737.0\n10.1016/j.eururo.2013.06.003\nNone\nContext: The first European Association of Urology (EAU) guidelines on bladder cancer were published in 2002 [1]. Since then, the guidelines have been continuously updated. Objective: To present the 2013 EAU guidelines on non-muscle-invasive bladder cancer (NMIBC). Evidence acquisition: Literature published between 2010 and 2012 on the diagnosis and treatment of NMIBC was systematically reviewed. Previous guidelines were updated, and the levels of evidence and grades of recommendation were assigned. Evidence synthesis: Tumours staged as Ta, T1, or carcinoma in situ (CIS) are grouped as NMIBC. Diagnosis depends on cystoscopy and histologic evaluation of the tissue obtained by transurethral resection (TUR) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TUR is essential for the patient's prognosis. Where the initial resection is incomplete, where there is no muscle in the specimen, or where a high-grade or T1 tumour is detected, a second TUR should be performed within 2-6 wk. The risks of both recurrence and progression may be estimated for individual patients using the EORTC scoring system and risk tables. The stratification of patients into low-, intermediate-, and high-risk groups is pivotal to recommending adjuvant treatment. For patients with a low-risk tumour, one immediate instillation of chemotherapy is recommended. Patients with an intermediate-risk tumour should receive one immediate instillation of chemotherapy followed by 1 yr of full-dose bacillus Calmette-Guerin (BCG) intravesical immunotherapy or by further instillations of chemotherapy for a maximum of 1 yr. In patients with high-risk tumours, full-dose intravesical BCG for 1-3 yr is indicated. In patients at highest risk of tumour progression, immediate radical cystectomy should be considered. Cystectomy is recommended in BCG-refractory tumours. The long version of the guidelines is available from the EAU Web site: http://www.uroweb.org/guidelines/. Conclusions: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice. Patient summary: The EAU Panel on Non-muscle Invasive Bladder Cancer released an updated version of their guidelines. Current clinical studies support patient selection into different risk groups; low, intermediate and high risk. These risk groups indicate the likelihood of the development of a new (recurrent) cancer after initial treatment (endoscopic resection) or progression to more aggressive (muscle-invasive) bladder cancer and are most important for the decision to provide chemo-or immunotherapy (bladder installations). Surgical removal of the bladder (radical cystectomy) should only be considered in patients who have failed chemo-or immunotherapy, or who are in the highest risk group for progression. (C) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n155757\nEndothelin-1 down-regulates matrix metalloproteinase 14 and 15 expression in human first trimester trophoblasts via endothelin receptor type B.\n\nMajali-Martinez, A\n\nVelicky, P\n\nPollheimer, J\n\nKnöfler, M\n\nYung, HW\n\nBurton, GJ\n\nTabrizi-Wizsy, NG\n\nLang, U\n\nHiden, U\n\nDesoye, G\n\nDieber-Rotheneder, M\n\nBeiträge in Fachzeitschriften\nISI:000394815100007\n27864359.0\n10.1093/humrep/dew295\nPMC5165079\nDoes endothelin-1 (ET-1) regulate matrix metalloproteinase (MMP) 14 and 15 production and invasion of human first trimester trophoblasts?\n ET-1 in pathophysiological concentrations down-regulates MMP14 and MMP15 expression via endothelin receptor (ETR) type B and decreases trophoblast migration and invasion.\n MMP14 and MMP15 are involved in trophoblast invasion. Impairment of invasion has been linked to pregnancy complications such as pre-eclampsia (PE). ET-1 is up-regulated in PE.\n In vitro study using primary human trophoblasts from 50 first trimester placentas (gestational week 7-12).\n Trophoblasts were cultured in the absence or presence of 10-100 nM ET-1. MMP14 and MMP15 mRNA and protein were quantified by RT-qPCR and Western blotting, respectively. Selective antagonists for ETRA (BQ-123) or ETRB (BQ-788) were used to identify ETR subtypes involved. Functional ET-1 effects were tested in first trimester chorionic villous explants and transwell invasion assays. The roles of tumor necrosis factor (TNF)-α (25 ng/ml) and oxygen (1%) in ET-1 regulation of MMP14 and 15 expression were assessed by Western blotting.\n ET-1 down-regulated MMP14 and MMP15 mRNA (-21% and -26%, respectively, P < 0.05) and protein levels (-18% and -22%, respectively, P < 0.05). This effect was mediated via ETRB. ET-1 decreased trophoblast outgrowth in placental explants (-24%, P < 0.05) and trophoblast invasion (-26%, P ≤ 0.01). TNF-α enhanced ET-1 mediated MMP15 down-regulation (by 10%, P < 0.05), whereas hypoxia abolished the effect of ET-1 on both MMPs.\n N/A.\n Only primary trophoblasts were used in this study. Since trophoblast yield from first trimester placental material is limited, further aspects of MMP14 and 15 regulation could not be characterized. Other anti-invasive factors may be altered by ET-1 in trophoblasts and, thus, contribute to the reduced invasion, but have not been investigated. Oxygen levels similar to those found in the decidua (5-8% O2) were not analyzed in this study.\n ET-1 modifies placental function already during the first trimester of pregnancy, the time-window when the placental changes implicated in PE occur. Thus, our results improve the understanding of the placental mechanisms underlying trophoblast invasion and PE.\n The study was funded by the Oesterreichische Nationalbank (Anniversary Fund, project number: 14796) and the Herzfelder'sche Familienstiftung (to J.P.; number: 00685). AMM received funding from the Austrian Science Fund FWF (W1241) and the Medical University Graz through the PhD Program Molecular Fundamentals of Inflammation (DK-MOLIN). The authors have no conflict of interest.\n © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.\n\nDesoye, Gernot\n\nGhaffari Tabrizi-Wizsy, Nassim\n\nHiden, Ursula\n\nMajali Martinez, Alejandro\n\n\n"
},
{
"text": "\n173472\nDetection of circulating tumor cells using manually performed immunocytochemistry (MICC) does not correlate with outcome in patients with early breast cancer - Results of the German SUCCESS-A- trial.\n\nJueckstock, J\n\nRack, B\n\nFriedl, TW\n\nScholz, C\n\nSteidl, J\n\nTrapp, E\n\nTesch, H\n\nForstbauer, H\n\nLorenz, R\n\nRezai, M\n\nHäberle, L\n\nAlunni-Fabbroni, M\n\nSchneeweiss, A\n\nBeckmann, MW\n\nLichtenegger, W\n\nFasching, PA\n\nPantel, K\n\nJanni, W\n\nSUCCESS Study Group\n\nBeiträge in Fachzeitschriften\nISI:000379122500001\n27387743.0\n10.1186/s12885-016-2454-3\nPMC4936301\nRecently, the prognostic significance of circulating tumor cells (CTCs) in primary breast cancer as assessed using the Food-and-Drug-Administration-approved CellSearch® system has been demonstrated. Here, we evaluated the prognostic relevance of CTCs, as determined using manually performed immunocytochemistry (MICC) in peripheral blood at primary diagnosis, in patients from the prospectively randomized multicenter SUCCESS-A trial (EudraCT2005000490-21).\n We analyzed 23 ml of blood from 1221 patients with node-positive or high risk node-negative breast cancer before adjuvant taxane-based chemotherapy. Cells were separated using a density gradient followed by epithelial cell labeling with the anti-cytokeratin-antibody A45-B/B3, immunohistochemical staining with new fuchsin, and cytospin preparation. All cytospins were screened for CTCs, and the cutoff for positivity was at least one CTC. The prognostic value of CTCs with regard to disease-free survival (DFS), distant disease-free survival (DDFS), breast-cancer-specific survival (BCSS), and overall survival (OS) was assessed using both univariate analyses applying the Kaplan-Meier method and log-rank tests, and using multivariate Cox regressions adjusted for other predictive factors.\n In 20.6 % of all patients (n = 251) a median of 1 (range, 1-256) CTC was detected, while 79.4 % of the patients (n = 970) were negative for CTCs before adjuvant chemotherapy. A pT1 tumor was present in 40.0 % of patients, 4.8 % had G1 grading and 34.6 % were node-negative. There was no association between CTC positivity and tumor stage, nodal status, grading, histological type, hormone receptor status, Her2 status, menopausal status or treatment. Univariate survival analyses based on a median follow-up of 64 months revealed no significant differences between CTC-positive and CTC-negative patients with regard to DFS, DDFS, BCSS, or OS. This was confirmed by fully adjusted multivariate Cox regressions, showing that the presence of CTCs (yes/no) as assessed by MICC did not predict DFS, DDFS, BCSS or OS.\n We could not demonstrate prognostic relevance regarding CTCs that were quantified using the MICC method at the time of primary diagnosis in our cohort of early breast cancer patients. Further studies are necessary to evaluate if the presence of CTCs assessed using MICC has prognostic relevance, or can be used for risk stratification and treatment monitoring in adjuvant breast cancer.\n The ClinicalTrial.gov registration ID of this prospectively randomized trial is NCT02181101 ; the (retrospective) registration date was June 2014 (study start date September 2005).\n\nTrapp, Elisabeth Katharina\n\n\n"
},
{
"text": "\n20593\nOxidative stress caused by acute and chronic exposition to altitude.\n\nFöldes-Papp, Z\n\nDomej, W\n\nDemel, U\n\nTilz, GP\n\nBeiträge in Fachzeitschriften\nNone\n15966258.0\nNone\nNone\nIn this article, current views on cellular and molecular biology (biochemical) mechanisms are discussed under the aspect of altitude exposition. The Andean, Tibetan, and Ethiopian patterns of adaptation to high-altitude hypoxia are known [Beal et al. (2002) Proc Natl Acad Sci USA 99: 17215-17218]. The phylogenetic tree of the human species suggests that there are genetic differences in adaptation patterns to chronic hypoxic hypoxia. Five defense mechanisms are well established for lowlanders who are exposed to acute hypoxic hypoxia. Consequences of the cellular decrease in ATP are the formation of hypoxanthine and xanthine, which are the substrates for the massive formation of superoxide anion radicals and hydrogen peroxide via the oxidase activity of the xanthine oxidoreductase reaction. Under severe hypoxia, about 51 % of the total inhaled oxygen is used to form superoxide anion radicals in rat liver [Gerber et al. (1989) Adv Exp Med Biol 253B, Plenum Press, New York, 497-504]. The reactivity and selectivity of the superoxide anion radical are modified by specific interactions and electron exchange. It is commonly accepted that the superoxide anion radical in aqueous solutions has a lifetime in the millisecond range. However, electron spin resonance spectroscopy studies in a KO2/H2O/iron ion system revealed for the first time a stabilization of a part of the initially added superoxide anion radicals lasting up to hours at room temperature [Földes-Papp (1992) Gen Physiol Biophys 11: 3-38]. Superoxide anion radicals adsorbed on an oxidic iron hydrate phase in aqueous systems might function as a strong oxidant similar to that species which has been suggested to be a complex between oxygen and different valence states of iron in the initiation of lipid peroxidation by ferrous iron. There were serious doubts about the identity of alkoxy radicals. For the first time, alkoxy radicals were directly demonstrated in solution by electron spin resonance spectroscopy [Földes-Papp et al. (1991) Adv Synth Catal 333: 293-301]. The redox status in mammalian cells is mainly determined by the antioxidant glutathione, which is a key player in maintaining the intracellular redox equilibrium and in the metabolic regulation of the cellular defense against oxidative stress. As reactive oxygen species occupy an essential role in membrane damage, the idea of membrane-bound enzymatic defense mechanisms gets a new dimension [Földes-Papp et al. (1981) Acta Biol Med Ger 40: 1129-1132; Földes-Papp and Maretzki (1982) Acta Biol Med Ger 41: 1003-1008]. The steady-state between antioxidants and pro-oxidants affects the gene expression via hypoxia-induced transcription activities. The transcription factor hypoxia-inducible factor 1 (HIF-1) is a global regulator of oxygen homeostasis. As discussed in this article, hypoxia or 'oxidative stress' is accompanied by appropriate molecular adaptation mechanisms at the enzymatic or epigenetic level (enzymatic and non-enzymatic radical inhibitors, posttranslational modifications) and at the genetic level (transcription, translation).\n\nDemel, Ulrike\n\nDomej, Wolfgang\n\nTilz, Gernot\n\n\n"
},
{
"text": "\n160225\n1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function.\n\nGorski, M\n\nvan der Most, PJ\n\nTeumer, A\n\nChu, AY\n\nLi, M\n\nMijatovic, V\n\nNolte, IM\n\nCocca, M\n\nTaliun, D\n\nGomez, F\n\nLi, Y\n\nTayo, B\n\nTin, A\n\nFeitosa, MF\n\nAspelund, T\n\nAttia, J\n\nBiffar, R\n\nBochud, M\n\nBoerwinkle, E\n\nBorecki, I\n\nBottinger, EP\n\nChen, MH\n\nChouraki, V\n\nCiullo, M\n\nCoresh, J\n\nCornelis, MC\n\nCurhan, GC\n\nd'Adamo, AP\n\nDehghan, A\n\nDengler, L\n\nDing, J\n\nEiriksdottir, G\n\nEndlich, K\n\nEnroth, S\n\nEsko, T\n\nFranco, OH\n\nGasparini, P\n\nGieger, C\n\nGirotto, G\n\nGottesman, O\n\nGudnason, V\n\nGyllensten, U\n\nHancock, SJ\n\nHarris, TB\n\nHelmer, C\n\nHöllerer, S\n\nHofer, E\n\nHofman, A\n\nHolliday, EG\n\nHomuth, G\n\nHu, FB\n\nHuth, C\n\nHutri-Kähönen, N\n\nHwang, SJ\n\nImboden, M\n\nJohansson, Å\n\nKähönen, M\n\nKönig, W\n\nKramer, H\n\nKrämer, BK\n\nKumar, A\n\nKutalik, Z\n\nLambert, JC\n\nLauner, LJ\n\nLehtimäki, T\n\nde Borst, M\n\nNavis, G\n\nSwertz, M\n\nLiu, Y\n\nLohman, K\n\nLoos, RJF\n\nLu, Y\n\nLyytikäinen, LP\n\nMcEvoy, MA\n\nMeisinger, C\n\nMeitinger, T\n\nMetspalu, A\n\nMetzger, M\n\nMihailov, E\n\nMitchell, P\n\nNauck, M\n\nOldehinkel, AJ\n\nOlden, M\n\nWjh Penninx, B\n\nPistis, G\n\nPramstaller, PP\n\nProbst-Hensch, N\n\nRaitakari, OT\n\nRettig, R\n\nRidker, PM\n\nRivadeneira, F\n\nRobino, A\n\nRosas, SE\n\nRuderfer, D\n\nRuggiero, D\n\nSaba, Y\n\nSala, C\n\nSchmidt, H\n\nSchmidt, R\n\nScott, RJ\n\nSedaghat, S\n\nSmith, AV\n\nSorice, R\n\nStengel, B\n\nStracke, S\n\nStrauch, K\n\nToniolo, D\n\nUitterlinden, AG\n\nUlivi, S\n\nViikari, JS\n\nVölker, U\n\nVollenweider, P\n\nVölzke, H\n\nVuckovic, D\n\nWaldenberger, M\n\nJin Wang, J\n\nYang, Q\n\nChasman, DI\n\nTromp, G\n\nSnieder, H\n\nHeid, IM\n\nFox, CS\n\nKöttgen, A\n\nPattaro, C\n\nBöger, CA\n\nFuchsberger, C\n\nBeiträge in Fachzeitschriften\nISI:000400432700001\n28452372.0\n10.1038/srep45040\nPMC5408227\nHapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110, 17 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10-8 previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples.\n\nHofer, Edith\n\nSABA, Yasaman\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n2993\nA comparison of growth impairment and orthodontic results in adult patients with clefts of palate and unilateral clefts of lip, palate and alveolus.\n\nSchultes, G\n\nGaggl, A\n\nKärcher, H\n\nBeiträge in Fachzeitschriften\nISI:000086091000009\n10783444.0\n10.1054/bjom.1999.0132\nNone\nObjective: To evaluate and compare the long-term aesthetic and functional results of surgical and orthodontic treatment in patients with cleft palate and unilateral cleft lip, palate, and alveolus.Design: 30 patients with unilateral cleft lip, palate, and alveolus and 30 patients with isolated deft palate, mean age of 18.9 years, were evaluated by cephalometric and model analysis a mean of 1.5 years after orthodontic treatment. In each group the surgical treatment has been similar.Results: Model analysis: The sum of every mesiodistal tooth diameter in the maxilla and in the mandible was recorded according to the Bolton analysis, Twenty patients with unilateral cleft lip, palate and alveolus had relatively! large upper dental arches and nine had relatively large loner dental arches. Twenty-two patients with cleft palates had targe upper dental arches and seven had large mandibular arches. Eleven patients with unilateral cleft lip, palate, and alveolus and 18 patients with cleft palate had a negative space supply (the sum of the mesiodistal tooth diameters compared with the sagittal length of the alveolar ridge) in the region of the lateral teeth, All patients had persistent transverse space deficits that were increased on the side of the cleft in patients with cleft lip, palate, and alveolus, These unilateral transversal space deficits were recorded in 22 patients with unilateral cleft tip, palate, and alveolus and in 8 patients with isolated cleft palate. Sagittal measurements were reduced in 26 patients with unilateral cleft lip, palate, and alveolus and in 23 patients with cleft palate alone. The alveolar midline of the maxilla and the mandible were displaced in 25 patients with unilateral cleft lip, palate, and alveolus and in 19 patients with isolated cleft palate. Lateral cephalometric analysis: The lateral cephalograms taken at the same time as the models showed a mean SNA of 76.8 degrees and a NL-NSL angle of 8.7 degrees, indications of a tendency towards maxillary retrognathia in patients with unilateral cleft Lip, palate, and alveolus. Patients with cleft palate had a mean SNA of 79.6 degrees and NL-NSL angle of 8.1 degrees. The anterior facial vertical index was within normal limits in patients with cleft Lip, palate, and alveolus (44% vs 56%). An anterior facial height index of 42% compared with 58% in patients with isolated cleft palate indicated a slight reduction in midface height with an increase in the loner face as a consequence.Conclusion: Orthodontic and surgical treatment can result in satisfactory results on model analysis, However, there is specific growth impairment of the maxilla 1.5 years after termination of orthodontic treatment and this influences the final cephalometric analysis, particularly. in patients with cleft lip, palate, and alveolus.\n\nKärcher, Hans\n\n\n"
},
{
"text": "\n170072\nOverview of the current status of familial hypercholesterolaemia care in over 60 countries - The EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC).\n\nEAS Familial Hypercholesterolaemia Studies Collaboration\n\nVallejo-Vaz, AJ\n\nDe Marco, M\n\nStevens, CAT\n\nAkram, A\n\nFreiberger, T\n\nHovingh, GK\n\nKastelein, JJP\n\nMata, P\n\nRaal, FJ\n\nSantos, RD\n\nSoran, H\n\nWatts, GF\n\nAbifadel, M\n\nAguilar-Salinas, CA\n\nAl-Khnifsawi, M\n\nAlKindi, FA\n\nAlnouri, F\n\nAlonso, R\n\nAl-Rasadi, K\n\nAl-Sarraf, A\n\nAshavaid, TF\n\nBinder, CJ\n\nBogsrud, MP\n\nBourbon, M\n\nBruckert, E\n\nChlebus, K\n\nCorral, P\n\nDescamps, O\n\nDurst, R\n\nEzhov, M\n\nFras, Z\n\nGenest, J\n\nGroselj, U\n\nHarada-Shiba, M\n\nKayikcioglu, M\n\nLalic, K\n\nLam, CSP\n\nLatkovskis, G\n\nLaufs, U\n\nLiberopoulos, E\n\nLin, J\n\nMaher, V\n\nMajano, N\n\nMarais, AD\n\nMärz, W\n\nMirrakhimov, E\n\nMiserez, AR\n\nMitchenko, O\n\nNawawi, HM\n\nNordestgaard, BG\n\nParagh, G\n\nPetrulioniene, Z\n\nPojskic, B\n\nPostadzhiyan, A\n\nReda, A\n\nReiner, Ž\n\nSadoh, WE\n\nSahebkar, A\n\nShehab, A\n\nShek, AB\n\nStoll, M\n\nSu, TC\n\nSubramaniam, T\n\nSusekov, AV\n\nSymeonides, P\n\nTilney, M\n\nTomlinson, B\n\nTruong, TH\n\nTselepis, AD\n\nTybjærg-Hansen, A\n\nVázquez-Cárdenas, A\n\nViigimaa, M\n\nVohnout, B\n\nWidén, E\n\nYamashita, S\n\nBanach, M\n\nGaita, D\n\nJiang, L\n\nNilsson, L\n\nSantos, LE\n\nSchunkert, H\n\nTokgözoğlu, L\n\nCar, J\n\nCatapano, AL\n\nRay, KK\n\nEAS Familial Hypercholesterolaemia Studies Collaboration (FHSC) Investigators\n\nBeiträge in Fachzeitschriften\nISI:000445908000037\n30270054.0\n10.1016/j.atherosclerosis.2018.08.051\nNone\nManagement of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries.\n Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management.\n 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in ∼2/3 countries. Lipoprotein-apheresis is offered in ∼60% countries, although access is limited.\n FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed.\n Copyright © 2018 Elsevier B.V. All rights reserved.\n\nMärz, Winfried\n\n\n"
},
{
"text": "\n183622\nSurgical Outcome and Oncological Survival of Osteofibrous Dysplasia-Like and Classic Adamantinomas: An International Multicenter Study of 318 Cases.\n\nSchutgens, EM\n\nPicci, P\n\nBaumhoer, D\n\nPollock, R\n\nBovée, JVMG\n\nHogendoorn, PCW\n\nDijkstra, PDS\n\nRueten-Budde, AJ\n\nJutte, PC\n\nTraub, F\n\nLeithner, A\n\nTunn, PU\n\nFunovics, P\n\nSys, G\n\nSan-Julian, M\n\nSchaap, GR\n\nDürr, HR\n\nHardes, J\n\nHealey, J\n\nCapanna, R\n\nBiau, D\n\nGomez-Brouchet, A\n\nWunder, J\n\nCosker, TDA\n\nLaitinen, MK\n\nNiu, X\n\nKostiuk, V\n\nvan de Sande, MAJ\n\nAdamantinoma Research Group\n\nBeiträge in Fachzeitschriften\nISI:000587857900011\n33027124.0\n10.2106/JBJS.19.01056\nNone\nOsteofibrous dysplasia-like adamantinoma (OFD-AD) and classic adamantinoma (AD) are rare, neoplastic diseases with only limited data supporting current treatment protocols. We believe that our retrospective multicenter cohort study is the largest analysis of patients with adamantinoma to date. The primary purpose of this study was to describe the disease characteristics and evaluate the oncological outcomes. The secondary purpose was to identify risk factors for local recurrence after surgical treatment and propose treatment guidelines.\n Three hundred and eighteen confirmed cases of OFD-AD and AD for which primary treatment was carried out between 1985 and 2015 were submitted by 22 tertiary bone tumor centers. Proposed clinical risk factors for local recurrence such as size, type, and margins were analyzed using univariable and multivariate Cox regression analysis.\n Of the 318 cases, 128 were OFD-AD and 190 were AD. The mean age at diagnosis was 17 years (median, 14.5 years) for OFD-AD and 32 years (median, 28 years) for AD; 53% of the patients were female. The mean tumor size in the OFD-AD and AD groups combined was 7.8 cm, measured histologically. Sixteen percent of the patients sustained a pathological fracture prior to treatment. Local recurrence was recorded in 22% of the OFD-AD cases and 24% of the AD cases. None of the recurrences in the OFD-AD group progressed to AD. Metastatic disease was found in 18% of the AD cases and fatal disease, in 11% of the AD cases. No metastatic or fatal disease was reported in the OFD-AD group. Multivariate Cox regression analysis demonstrated that uncontaminated resection margins (hazard ratio [HR] = 0.164, 95% confidence interval [CI] = 0.092 to 0.290, p < 0.001), pathological fracture (HR = 1.968, 95% CI = 1.076 to 3.600, p = 0.028), and sex (female versus male: HR = 0.535, 95% CI = 0.300 to 0.952, p = 0.033) impacted the risk of local recurrence.\n OFD-AD and AD are parts of a disease spectrum but should be regarded as different entities. Our results support reclassification of OFD-AD into the intermediate locally aggressive category, based on the local recurrence rate of 22% and absence of metastases. In our study, metastatic disease was restricted to the AD group (an 18% rate). We advocate wide resection with uncontaminated margins including bone and involved periosteum for both OFD-AD and AD.\n Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.\n\nLeithner, Andreas\n\n\n"
},
{
"text": "\n7938\nStudies on the role of specific cell surface receptors in the removal of lipoprotein (a) in man.\n\nKrempler, F\n\nKostner, GM\n\nRoscher, A\n\nHaslauer, F\n\nBolzano, K\n\nSandhofer, F\n\nBeiträge in Fachzeitschriften\nISI:A1983QR78900042\n6304146.0\n10.1172/JCI110896\nPMC437007\nThe binding of 125I-lipoprotein (a) [Lp(a)] to cell surface receptors was studied on cultured human fibroblasts. The results were compared with corresponding data obtained with 125I-low density lipoproteins (LDL). Equilibrium binding studies showed that Lp(a) is bound with high affinity by the cell surface receptors. The maximum binding capacity for Lp(a) was 37% lower than for LDL. For Lp(a) and LDL, the Scatchard plots displayed linearity, indicating a single category of binding sites. Half-maximal saturation occurred at a concentration of 9.52 +/- 1.04 nM for Lp(a) and 7.76 +/- 1.29 nM for LDL. Competition binding experiments revealed that Lp(a) and LDL are nearly equally potent in competing each other for the binding sites. Binding of Lp(a) and LDL were followed by suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Cyclohexanedione treatment of Lp(a) and LDL completely abolished receptor binding. Neither Lp(a) nor LDL were specifically bound by fibroblasts obtained from a patient with homozygous familial hypercholesterolemia (FH). The removal mechanisms for Lp(a) and LDL were further compared by in vivo studies. Radioiodinated Lp(a) and LDL were injected intravenously into 12 normolipemic individuals to measure kinetic parameters of these two lipoproteins simultaneously in each subject. Mean fractional catabolic rate (FCR) of Lp(a) was 0.260 +/- 0.060 and mean FCR of LDL was 0.377 +/- 0.077 (mean +/- SD). In each subject, FCR of Lp(a) was lower than the FCR of LDL; the mean difference was 31%. The absolute synthetic rate of Lp(a) was significantly lower than the corresponding value of LDL. In each individual, the percentage of total Lp(a) that was contained in the intravascular space was higher than the corresponding value of LDL; the mean difference was 19%. A highly significant positive correlation was found between FCR of LDL and FCR of Lp(a) (r = 0.853, P less than 0.01). No relationship was found between the serum concentration of LDL-apolipoprotein B and Lp(a). The serum level of Lp(a) was positively related to the absolute rate of Lp(a) synthesis (r = 0.979, P less than 0.01). The serum level of LDL-apolipoprotein B was inversely related to FCR of LDL (r = 0.613, P less than 0.05). In a patient with homozygous FH, FCR of LDL was 0.205 and FCR of Lp(a) was 0.210. The results of these studies show that Lp(a) is specifically bound with high affinity to the same receptors of human fibroblasts as LDL. The affinity and maximum binding capacity are slightly lower for Lp(a) than for LDL. The results of the turnover studies are consistent with the assumption that Lp(a) is removed from the plasma by similar mechanisms as LDL.\n\nKostner, Gerhard\n\n\n"
},
{
"text": "\n118324\nUtility of whole slide imaging and virtual microscopy in prostate pathology.\n\nCamparo, P\n\nEgevad, L\n\nAlgaba, F\n\nBerney, DM\n\nBoccon-Gibod, L\n\nComperat, E\n\nEvans, AJ\n\nGrobholz, R\n\nKristiansen, G\n\nLangner, C\n\nLopez-Beltran, A\n\nMontironi, R\n\nOliveira, P\n\nVainer, B\n\nVarma, M\n\nBeiträge in Fachzeitschriften\nISI:000301656000005\n22429212.0\n10.1111/j.1600-0463.2011.02872.x\nNone\nWhole slide imaging (WSI) has been used in conjunction with virtual microscopy (VM) for training or proficiency testing purposes, multicentre research, remote frozen section diagnosis and to seek specialist second opinion in a number of organ systems. The feasibility of using WSI/VM for routine surgical pathology reporting has also been explored. In this review, we discuss the utility and limitations of WSI/VM technology in the histological assessment of specimens from the prostate. Features of WSI/VM that are particularly well suited to assessment of prostate pathology include the ability to examine images at different magnifications as well as to view histology and immunohistochemistry side-by-side on the screen. Use of WSI/VM would also solve the difficulty in obtaining multiple identical copies of small lesions in prostate biopsies for teaching and proficiency testing. It would also permit annotation of the virtual slides, and has been used in a study of inter-observer variation of Gleason grading to facilitate precise identification of the foci on which grading decisions had been based. However, the large number of sections examined from each set of prostate biopsies would greatly increase time required for scanning as well as the size of the digital file, and would also be an issue if digital archiving of prostate biopsies is contemplated. Z-scanning of glass slides, a process that increases scanning time and file size would be required to permit focusing a virtual slide up and down to assess subtle nuclear features such as nucleolar prominence. The common use of large blocks to process prostatectomy specimens would also be an issue, as few currently available scanners can scan such blocks. A major component of proficiency testing of prostate biopsy assessment involves screening of the cores to detect small atypical foci. However, screening virtual slides of wavy fragmented prostate cores using a computer mouse aided by an overview image is very different from screening glass slides using a microscope stage. Hence, it may be more appropriate in this setting to mark the lesional area and focus only on the interpretation component of competency testing. Other issues limiting the use of digital pathology in prostate pathology include the cost of high quality slide scanners for WSI and high resolution monitors for VM as well as the requirement for fast Internet connection as even a subtle delay in presentation of images on the screen may be very disturbing for a pathologist used to the rapid viewing of glass slides under a microscope. However, these problems are likely to be overcome by technological advances in the future. © 2012 The Authors APMIS © 2012 APMIS.\n\nLangner, Cord\n\n\n"
},
{
"text": "\n147540\nBiomechanical properties and microstructure of human ventricular myocardium.\n\nSommer, G\n\nSchriefl, AJ\n\nAndrä, M\n\nSacherer, M\n\nViertler, C\n\nWolinski, H\n\nHolzapfel, GA\n\nBeiträge in Fachzeitschriften\nISI:000360867700017\n26141152.0\n10.1016/j.actbio.2015.06.031\nNone\nIn the multidisciplinary field of heart research it is of utmost importance to identify accurate myocardium material properties for the description of phenomena such as mechano-electric feedback or heart wall thickening. A rationally-based material model is required to understand the highly nonlinear mechanics of complex structures such as the passive myocardium under different loading conditions. Unfortunately, to date there are no experimental data of human heart tissues available to estimate material parameters and to develop adequate material models. This study aimed to determine biaxial extension and triaxial shear properties and the underlying microstructure of the passive human ventricular myocardium. Using new state-of-the-art equipment, planar biaxial extension tests were performed to determine the biaxial extension properties of the passive ventricular human myocardium. Shear properties of the myocardium were examined by triaxial simple shear tests performed on small cubic specimens excised from an adjacent region of the biaxial extension specimens. The three-dimensional microstructure was investigated through second-harmonic generation (SHG) microscopy on optically cleared tissues, which emphasized the 3D orientation and dispersion of the myofibers and adjacent collagen fabrics. The results suggest that the passive human LV myocardium under quasi-static and dynamic multiaxial loadings is a nonlinear, anisotropic (orthotropic), viscoelastic and history-dependent soft biological material undergoing large deformations. Material properties of the tissue components along local microstructural axes drive the nonlinear and orthotropic features of the myocardium. SHG microscopy investigation revealed detailed information about the myocardial microstructure due to its high resolution. It enabled the identification of structural parameters such as the fiber and the sheet orientations and corresponding dispersions. With this complete set of material data, a sophisticated material model and associated material parameters can be defined for a better description of the biomechanical response of the ventricular myocardium in humans. Such a model will lead to more accurate computational simulations to better understand the fundamental underlying ventricular mechanics, a step needed in the improvement of medical treatment of heart diseases.\n Unfortunately, to date there are no experimental data of human heart tissues available for material parameter estimation and the development of adequate material models. In this manuscript novel biaxial tensile and shear test data at different specimen orientations are presented, which allowed to adequately capture the direction-dependent material response. With these complete sets of mechanical data, combined with their underlying microstructural data (also presented herein), sophisticated material models and associated material parameters can be defined for the description of the mechanical behavior of the ventricular myocardium in humans. Such models will lead to accurate computational simulations to better understand the fundamental underlying ventricular mechanics, a step needed in the improvement of medical treatment of heart diseases.\n Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.\n\nSacherer, Michael\n\nViertler, Christian\n\n\n"
},
{
"text": "\n187266\nProfiling Tissue and Biofluid miR-155-5p, miR-155<sup>*</sup>, and miR-146a-5p Expression in Graft vs. Host Disease.\n\nCrossland, RE\n\nNorden, J\n\nGhimire, S\n\nJuric, MK\n\nPearce, KF\n\nLendrem, C\n\nCollin, M\n\nMischak-Weissinger, E\n\nHoller, E\n\nGreinix, HT\n\nDickinson, AM\n\nBeiträge in Fachzeitschriften\nISI:000634274600001\n33790910.0\n10.3389/fimmu.2021.639171\nPMC8005601\nIntroduction: Acute graft vs. host disease (aGvHD) is a frequent complication following allogeneic haematopoeitic transplantation (HSCT). Despite recent advances, there are no universally accepted biomarkers to determine development of aGvHD. MicroRNAs miR-146a and miR-155 have been previously associated with aGvHD and show promise as clinically translatable biomarkers. In this study, we performed comprehensive expression profiling of miR-146a, miR-155, and miR-155* expression in aGvHD target tissue and biofluids and relate expression to post-HSCT outcomes. Materials and Methods: MicroRNA expression was assessed by qRT-PCR in gastrointestinal (n = 31) and skin (n = 31) biopsies as well as serum (exploratory cohort n = 34, verification cohort n = 81, diagnostic cohort n = 65) and urine (exploratory cohort n = 30, verification cohort n = 56, diagnostic cohort n = 20) biofluids, including extracellular vesicle (EV) cohorts (serum EV n = 15, urine EV n = 30). Expression was related to aGvHD incidence, severity and overall survival. Results: In GI samples, expression of miR-155 (p = 0.03) and miR-146a (p = 0.03) was higher at aGvHD onset compared to patients with no GvHD. In skin biopsies, expression of miR-155 (p = 0.004) was upregulated in aGvHD patients compared to normal control skin. Expression of miR-146a was higher in aGvHD compared to no aGvHD biopsies (p = 0.002). In serum, miR-155 (p = 0.03) and miR-146a (p = 0.02) expression was higher at day 14 (D14), while in urine expression was elevated at D7 post-HSCT in patients who developed aGvHD compared to those disease-free. This was verified in an independent serum (miR-155 p = 0.005, miR-146a p = 0.003) and urine (miR-155 p = 0.02, miR-146a p = 0.04) cohort, where both microRNAs were also associated with aGvHD by ROC analysis. In serum and urine samples taken at the time of aGvHD symptoms, expression of miR-155 and miR-146a was also elevated (serum miR-155 p = 0.03, miR-146a p < 0.001; urine miR-155 p = 0.02, miR-146a p = 0.02). In contrast, miR-146a and miR-155 were downregulated at D14 in serum EVs and at D7 in urine EVs in patients who developed aGvHD compared to those that remained disease-free, in both an exploratory (serum miR-155 p = 0.02, miR-146a p = 0.06; urine miR-155 p = 0.02, miR-146a p = 0.07) and an independent cohort (serum miR-155 p = 0.01, miR-146a p = 0.02). Conclusions: These results further support a role for miR-155 and miR-146a as non-invasive, clinically relevant biomarkers for aGvHD. However, the link between their involvement in generalized inflammation and in specific pathophysiology requires further investigation at a systemic level.\n Copyright © 2021 Crossland, Norden, Ghimire, Juric, Pearce, Lendrem, Collin, Mischak-Weissinger, Holler, Greinix and Dickinson.\n\nGreinix, Hildegard\n\n\n"
},
{
"text": "\n155954\nControlled-surgical education in clinical liver transplantation is not associated with increased patient risks.\n\nJurgaitis, J\n\nPaskonis, M\n\nMehrabi, A\n\nKashfi, A\n\nGragert, S\n\nHinz, U\n\nSchemmer, P\n\nStrupas, K\n\nBüchler, MW\n\nSchmidt, J\n\nKraus, TW\n\nBeiträge in Fachzeitschriften\nISI:000242602600011\n17100704.0\n10.1111/j.1399-0012.2006.00603.x\nNone\nA qualified surgical team is required to perform liver transplantation (LTX). Growing numbers of transplants at transplant centers and large variations of transplant frequencies make a continuous education to train young surgeons on this complex field of hepato-biliary surgery mandatory, both from the organizational and motivational point of view (job enrichment and professional growth). On the contrary, perioperative patient risk management is of major importance in surgical practice and given growing organizational concern in hospitals. A retrospective clinical study was performed to describe and evaluate the process of surgical training for orthotopic LTX. Patient risks associated with or caused by the education process in clinical LTX were analyzed.\n Perioperative patient data and details of surgical strategies were collected for 155 consecutive LTX carried out at a single center. Operative and follow-up data were correlated with the degree of surgical experience of the first operating surgeon. Two groups were defined. In group A, transplant surgeons with >30 personally performed LTXs (n = 3) and in group B, transplant fellows with >30 assistance in LTx (n = 3) performed the operations. All LTX operations were standardized based on modified piggyback technique described by Belghiti. Group B operations were performed under close supervision/assistance of the ''transplant surgeon.'' Selection of patients for exposure to surgical training was based on the pre-operative estimation of surgical difficulty. Operative time, blood loss, liver function, post-operative morbidity, and survival rate data were compared in both groups.\n A total of 155 LTX were performed in 131 patients and were analyzed, and 106 operations (68.3%) were performed by group A and 49 operations (31.6%) were performed by transplant fellows under supervision (group B). No significant differences concerning mean patient age, distribution of type of disease, operating time, the Model for Endstage Liver Disease (MELD) score and frequency of category Child A, B and C were detected between groups. Overall post-operative complication rate was 21.9% (n = 34). Transplant surgeons and transplant fellows had 19.8% (n = 21) and 26.5% (n = 13) of complication rate, respectively (p > 0.05). Overall patients survival rate was 94% and 89% at 45 days for the patients operated in groups A and B, respectively (p > 0.05). Survival rate, blood loss, intraoperative transfusion requirements and operating time did not differ significantly between groups.\n Liver transplantation requires team performance to minimize patient risks. Incidence of complications was associated with the severity of disease but not with the education process. It could be demonstrated that with careful patient selection and supervision of the transplant fellow with a more experienced surgeon, the results are equal to those obtained when the experienced transplant surgeon is the prime operator.\n\nSchemmer, Peter\n\n\n"
},
{
"text": "\n170469\nInterdisciplinary Screening, Diagnosis, Therapy and Follow-up of Breast Cancer. Guideline of the DGGG and the DKG (S3-Level, AWMF Registry Number 032/045OL, December 2017) - Part 1 with Recommendations for the Screening, Diagnosis and Therapy of Breast Cancer.\n\nWöckel, A\n\nFestl, J\n\nStüber, T\n\nBrust, K\n\nStangl, S\n\nHeuschmann, PU\n\nAlbert, US\n\nBudach, W\n\nFollmann, M\n\nJanni, W\n\nKopp, I\n\nKreienberg, R\n\nKühn, T\n\nLanger, T\n\nNothacker, M\n\nScharl, A\n\nSchreer, I\n\nLink, H\n\nEngel, J\n\nFehm, T\n\nWeis, J\n\nWelt, A\n\nSteckelberg, A\n\nFeyer, P\n\nKönig, K\n\nHahne, A\n\nKreipe, HH\n\nKnoefel, WT\n\nDenkinger, M\n\nBrucker, S\n\nLüftner, D\n\nKubisch, C\n\nGerlach, C\n\nLebeau, A\n\nSiedentopf, F\n\nPetersen, C\n\nBartsch, HH\n\nSchulz-Wendtland, R\n\nHahn, M\n\nHanf, V\n\nMüller-Schimpfle, M\n\nHenscher, U\n\nRoncarati, R\n\nKatalinic, A\n\nHeitmann, C\n\nHonegger, C\n\nParadies, K\n\nBjelic-Radisic, V\n\nDegenhardt, F\n\nWenz, F\n\nRick, O\n\nHölzel, D\n\nZaiss, M\n\nKemper, G\n\nBudach, V\n\nDenkert, C\n\nGerber, B\n\nTesch, H\n\nHirsmüller, S\n\nSinn, HP\n\nDunst, J\n\nMünstedt, K\n\nBick, U\n\nFallenberg, E\n\nTholen, R\n\nHung, R\n\nBaumann, F\n\nBeckmann, MW\n\nBlohmer, J\n\nFasching, PA\n\nLux, MP\n\nHarbeck, N\n\nHadji, P\n\nHauner, H\n\nHeywang-Köbrunner, S\n\nHuober, J\n\nHübner, J\n\nJackisch, C\n\nLoibl, S\n\nLück, HJ\n\nvon Minckwitz, G\n\nMöbus, V\n\nMüller, V\n\nNöthlings, U\n\nSchmidt, M\n\nSchmutzler, R\n\nSchneeweiss, A\n\nSchütz, F\n\nStickeler, E\n\nThomssen, C\n\nUntch, M\n\nWesselmann, S\n\nBücker, A\n\nKrockenberger, M\n\nBeiträge in Fachzeitschriften\nISI:000447951900007\n30369626.0\n10.1055/a-0646-4522\nPMC6202580\nPurpose The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer. Methods The process of updating the S3 guideline dating from 2012 was based on the adaptation of identified source guidelines which were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and the results of a systematic search of literature databases and the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point to develop recommendations and statements which were modified and graded in a structured consensus procedure. Recommendations Part 1 of this short version of the guideline presents recommendations for the screening, diagnosis and follow-up care of breast cancer. The importance of mammography for screening is confirmed in this updated version of the guideline and forms the basis for all screening. In addition to the conventional methods used to diagnose breast cancer, computed tomography (CT) is recommended for staging in women with a higher risk of recurrence. The follow-up concept includes suggested intervals between physical, ultrasound and mammography examinations, additional high-tech diagnostic procedures, and the determination of tumor markers for the evaluation of metastatic disease.\n\nBjelic-Radisic, Vesna\n\n\n"
},
{
"text": "\n187760\nEarly Intervention for Children Aged 0 to 2 Years With or at High Risk of Cerebral Palsy: International Clinical Practice Guideline Based on Systematic Reviews.\n\nMorgan, C\n\nFetters, L\n\nAdde, L\n\nBadawi, N\n\nBancale, A\n\nBoyd, RN\n\nChorna, O\n\nCioni, G\n\nDamiano, DL\n\nDarrah, J\n\nde Vries, LS\n\nDusing, S\n\nEinspieler, C\n\nEliasson, AC\n\nFerriero, D\n\nFehlings, D\n\nForssberg, H\n\nGordon, AM\n\nGreaves, S\n\nGuzzetta, A\n\nHadders-Algra, M\n\nHarbourne, R\n\nKarlsson, P\n\nKrumlinde-Sundholm, L\n\nLatal, B\n\nLoughran-Fowlds, A\n\nMak, C\n\nMaitre, N\n\nMcIntyre, S\n\nMei, C\n\nMorgan, A\n\nKakooza-Mwesige, A\n\nRomeo, DM\n\nSanchez, K\n\nSpittle, A\n\nShepherd, R\n\nThornton, M\n\nValentine, J\n\nWard, R\n\nWhittingham, K\n\nZamany, A\n\nNovak, I\n\nBeiträge in Fachzeitschriften\nISI:000653083200005\n33999106.0\n10.1001/jamapediatrics.2021.0878\nNone\nCerebral palsy (CP) is the most common childhood physical disability. Early intervention for children younger than 2 years with or at risk of CP is critical. Now that an evidence-based guideline for early accurate diagnosis of CP exists, there is a need to summarize effective, CP-specific early intervention and conduct new trials that harness plasticity to improve function and increase participation. Our recommendations apply primarily to children at high risk of CP or with a diagnosis of CP, aged 0 to 2 years.\n To systematically review the best available evidence about CP-specific early interventions across 9 domains promoting motor function, cognitive skills, communication, eating and drinking, vision, sleep, managing muscle tone, musculoskeletal health, and parental support.\n The literature was systematically searched for the best available evidence for intervention for children aged 0 to 2 years at high risk of or with CP. Databases included CINAHL, Cochrane, Embase, MEDLINE, PsycInfo, and Scopus. Systematic reviews and randomized clinical trials (RCTs) were appraised by A Measurement Tool to Assess Systematic Reviews (AMSTAR) or Cochrane Risk of Bias tools. Recommendations were formed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and reported according to the Appraisal of Guidelines, Research, and Evaluation (AGREE) II instrument.\n Sixteen systematic reviews and 27 RCTs met inclusion criteria. Quality varied. Three best-practice principles were supported for the 9 domains: (1) immediate referral for intervention after a diagnosis of high risk of CP, (2) building parental capacity for attachment, and (3) parental goal-setting at the commencement of intervention. Twenty-eight recommendations (24 for and 4 against) specific to the 9 domains are supported with key evidence: motor function (4 recommendations), cognitive skills (2), communication (7), eating and drinking (2), vision (4), sleep (7), tone (1), musculoskeletal health (2), and parent support (5).\n When a child meets the criteria of high risk of CP, intervention should start as soon as possible. Parents want an early diagnosis and treatment and support implementation as soon as possible. Early intervention builds on a critical developmental time for plasticity of developing systems. Referrals for intervention across the 9 domains should be specific as per recommendations in this guideline.\n\nEinspieler, Christa\n\n\n"
}
]
}