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"text": "\n61722\nEffects of maximal and submaximal exercise on plasma electrolyte shifts\n\nWestmoreland, D\n\nAnderson, D\n\nPorta, S\n\nBeiträge in Fachzeitschriften\nISI:000241261700016\nNone\nNone\nNone\nBackground: Mineral fluctuations in the body have been extensively studied to determine effects on athletic performance, with magnesium in particular being the focus of many studies. As a general rule, high-intensity exercise induces an increase in plasma Mg, while submaximal exercise has the opposite effect. This generality is based on comparisons among studies that differed in subject pools and experimental design, however, and many exceptions to the general trend have been noted. In this study, we sought to control the effects of between-subject variability, exercise duration and time of day on the plasma Mg shift by having each subject take maximal and submaximal exercise trials at a standardized time of day within a 48-h period. Material and methods: 25 cadets of the United States Air Force Academy underwent both a submaximal cycle and a maximal-effort treadmill test in randomized order within a 48-h time period. Blood samples were drawn from each subject immediately before and after exercise and analyzed for whole blood Na, K, Mg, Ca, pH, PCO2, pO(2), HCO3-, base excess and hematocrit. Results: Submaximal exercise induced a significant change in K and Mg, while maximal exercise trials caused significant changes in all four measured electrolytes. The magnitude of electrolyte shifts was significantly different between trials for Na, Ca and Mg, and were in opposite directions for Ca and Mg. In both exercise regimens, there was a significant negative correlation between pre-exercise plasma Mg levels and the Mg shift during exercise. However, the thresholds that separated positive and negative Mg shifts were substantially different between the exercise regimens. Conclusion: Short exercise regimens differing in intensity have profound, and often opposite, effects on electrolyte shifts. This study supports the generality that high-intensity exercise leads to an increase in plasma Mg, while submaximal exercise leads to a decrease. Hypomagnesic individuals transfer Mg into the plasma compartment during exercise in proportion to workload. We hypothesize that the observed Mg rise in such individuals is a compensatory mechanism that involves rapid mobilization of Mg from apatite crystals in bone.\n\n\n"
},
{
"text": "\n63967\nEffects of parathyroid hormone and serum calcium on the phenotype and function of mononuclear cells in patients with primary hyperparathyroidism.\n\nKotzmann, H\n\nKöller, M\n\nAbela, C\n\nClodi, M\n\nRiedl, M\n\nGraninger, W\n\nNiederle, B\n\nLuger, A\n\nBeiträge in Fachzeitschriften\nISI:000074032500002\n9650007.0\nNone\nNone\nBACKGROUND: Several studies have demonstrated specific influence of parathyroid hormone (PTH) on immune parameters, especially on T- and B-cell function, migration of polymorphonuclear leucocytes (PMNLs) and antibody synthesis, in patients with secondary hyperparathyroidism and chronic renal failure and recently also in patients with primary hyperparathyroidism (pHPT). METHODS: We therefore examined 12 patients with pHPT before and 6 months after parathyroidectomy (PTX) and nine sex- and age-matched control subjects to determine the impact of PTH and serum calcium concentrations on several immune parameters, including (a) serum concentrations of immunoglobulins, (b) immunophenotype of peripheral blood lymphocytes, (c) phytohaemagglutinin (PHA)-induced lymphocyte proliferation and (d) monocytic surface marker expression. RESULTS: Serum concentrations of immunoglobulins (IgG, IgA, IgM) were unaffected by elevated serum PTH and calcium levels. T lymphocytes (CD3), B lymphocytes (CD19), NK cells (CD16/56) and monocytes (CD16) revealed a normal distribution and were not different before and after PTX in patients with pHPT when compared with the control group. CD4+ T-helper lymphocytes were significantly elevated pre- and post-operatively in patients with pHPT. The lymphocyte proliferation response to PHA in the highest concentration (12.5 micrograms L-1) tested was significantly suppressed in patients with pHPT preoperatively when compared with the patients post-operatively and the control group. In addition, both CD4+ and CD8+ lymphocytes showed a lower expression of activation markers, interleukin 2 (IL-2) receptor (CD25) and transferrin receptor (CD71), which could be partially restored 6 months after PTX, but did not reach normal values. CONCLUSION: In summary, in contrast to the findings in patients with secondary HPT, pHPT appears to be associated with less alterations of immune functions. Chronically elevated serum PTH and calcium concentrations in patients with pHPT induce a higher percentage of CD4+ helper T lymphocytes and a suppressed lymphocyte response to PHA as well as a reduced expression of activation markers on peripheral blood lymphocytes.\n\nGraninger, Winfried\n\n\n"
},
{
"text": "\n67864\nTheophylline blood levels in patients with asthma or COPD\n\nTrummer, M\n\nAberer, W\n\nKranke, B\n\nBeiträge in Fachzeitschriften\nISI:000246797700001\nNone\nNone\nNone\nBackground: Theophylline has been widely used for decades in the treatment of asthma and chronic obstructive pulmonary disease because of its bronchodilator activity as well as its immunomodulatory, antiinflammatory, and bronchoprotective effects. On the other hand, its use has declined with the advent of potent steroid inhalants. In Austria, the current frequency of prescription is 6 in 1, 00 insurants, according to Austrian health insurance data. Slow-release theophylline has become an established medication for asthma, and the development of adequate assays made drug monitoring readily available. Since the efficacy and toxicity of theophylline are closely related to the serum drug concentration, reflected by an adequate serum level of 10 - 20 mg/l, monitoring of its serum concentration is essential. Methods: This was an open-label, 1-year prospective, monocenter study, performed in male as well as female patients consecutively admitted to the Department of Environmental Dermatology, Medical University of Graz, Austria. The only inclusion criterion was taking a theophylline medication at the time of admission. Test parameters were gender, age, body mass index, nicotin abuse, medication, blood levels of the transaminases as well as serum levels of theophylline (measured by EIA). Results: 25 patients could be included (17 female, 8 male). At the time of admission, only 20% of the patients under theophylline medication had an adequate theophylline serum level, in 76% of the patients the drug was underdosed, in 4% the theophylline was found to be overdosed. After 3 days of controlled intake of theophylline preparations in 74% of the patients, an adequate theophylline level could be measured, but 36% of the patients continued to be underdosed. Conclusions: Because of the wide variation in theophylline metabolism between individuals and the narrow therapeutic index of its use, monitoring of theophylline serum levels is essential to reach an effective steady state. Despite this common knowledge, the data of our study suggest that the majority of outpatients may be below an effective level. Limitation of our study is the small number of patients included, and a larger study may be necessary to confirm the results.\n\nAberer, Werner\n\nKränke, Birger\n\n\n"
},
{
"text": "\n90650\nEffect of anterior capsule polishing on fibrotic capsule opacification: three-year results.\n\nSacu, S\n\nMenapace, R\n\nWirtitsch, M\n\nBuehl, W\n\nRainer, G\n\nFindl, O\n\nBeiträge in Fachzeitschriften\nISI:000225272000030\n15519082.0\n10.1016/j.jcrs.2004.02.092\nNone\nPURPOSE: To evaluate the long-term effect of anterior capsule polishing on anterior capsule opacification (ACO) and peripheral fibrotic posterior capsule opacification (PCO). SETTING: Department of Ophthalmology, Medical University of Vienna, Vienna, Austria. METHODS: This randomized double-blind study comprised 104 eyes of 52 patients with bilateral age-related cataract. All patients received round-edged intraocular lenses (IOLs); 26 received an SI-40 IOL (Advanced Medical Optics Inc.) in both eyes, and 26 received a Silens6 IOL (Domilens) in both eyes. Both IOLs consist of different silicone material and have different haptic angulation. The SI-40 IOL has 13.0 mm open-loop poly(methyl methacrylate) (PMMA) haptics angulated by 10 degrees. The Silens6 IOL has 12.5 mm open-loop PMMA haptics with no angulation. In 1 eye, the anterior capsule was extensively polished. The anterior capsule was left unpolished in the contralateral eye, which acted as a control. Digital slitlamp photographs of the ACO and fibrotic PCO were taken with a standardized technique for 3 years postoperatively. The intensity of ACO was measured objectively (score 0% to 100%) using Adobe Photoshop software. Fibrotic PCO was graded subjectively (score 0 to 4). RESULTS: The mean ACO was 17% in the polished eyes and 26% in the control eyes (P = .0001). The mean fibrotic PCO score was 0.5 and 1.0, respectively (P = .0007). The mean ACO was 15% in the polished SI-40 eyes and 26% in the control SI-40 eyes (P = .01). It was 19% in the polished Silens6 eyes and 26% in the control Silens6 eyes (P = .003). The mean fibrotic PCO score was 0.4 in the polished SI-40 eyes and 1.1 in the control SI-40 eyes (P = .0006). It was 0.6 in the polished Silens6 eyes and 0.9 in the control Silens6 eyes (P = .08). CONCLUSIONS: Three years after surgery, eyes in which the anterior capsule was extensively polished had less ACO and fibrotic PCO with both round-edged silicone IOLs. In eyes with Silens6 IOLs, however, the reduction in fibrotic PCO was not significant.\n\n\n"
},
{
"text": "\n119126\nEuropean Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) host factors and invasive fungal infections in patients with haematological malignancies.\n\nHoenigl, M\n\nStrenger, V\n\nBuzina, W\n\nValentin, T\n\nKoidl, C\n\nWölfler, A\n\nSeeber, K\n\nValentin, A\n\nStrohmeier, AT\n\nZollner-Schwetz, I\n\nRaggam, RB\n\nUrban, C\n\nLass-Flörl, C\n\nLinkesch, W\n\nKrause, R\n\nBeiträge in Fachzeitschriften\nISI:000306366000031\n22566591.0\n10.1093/jac/dks155\nNone\nFulfilment of host factors defined by the revised European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria is required for establishing the diagnosis of possible or probable invasive fungal infection (IFI). This casecontrol study evaluates EORTC/MSG host factors among patients with haematological malignancies. Fifty-eight patients with haematological malignancies who developed probable (n38) or proven (n20) IFI over a 5 year period were retrospectively evaluated regarding EORTC/MSG host factors. Results were compared with those obtained from patients with haematological malignancies who did not develop IFI (116 patients who received systemic antifungal prophylaxis or empirical therapy and 116 patients who did not; all data collected in 2010). Fourteen patients had invasive yeast infection and 44 patients had invasive mould infection (IMI). Prolonged neutropenia (35/58, 60 versus 29/116, 25), prolonged systemic corticosteroid (cut-off 21 days: 13/58, 22 versus 6/116, 5; cut-off 14 days: 18/58, 31 versus 9/116, 8) and T cell suppressive therapy (35/44, 80 versus 69/116, 59) were significantly associated with development of IFI/IMI in our cohort. Previous allogeneic stem cell transplantation (SCT; 6 months prior to episode) was not significantly associated with development of IMI (8/44, 18 versus 22/116, 19), while recent SCT (6 months prior to episode) was (11/44, 25 versus 12/116, 10). We conclude that host factors according to revised EORTC/MSG criteria were significantly associated with the development of IFI/IMI in our patients. Previous allogeneic SCT was not a predisposing host factor for the development of IMI. Concerning prolonged corticosteroid treatment, a cut-off of 14 days seems preferable to the proposed cut-off.\n\nBuzina, Walter\n\nHönigl, Martin\n\nKoidl, Christoph\n\nKrause, Robert\n\nRaggam, Reinhard Bernd\n\nStrenger, Volker\n\nUrban, Ernst-Christian\n\nValentin, Thomas\n\nWoelfler, Albert\n\nZollner-Schwetz, Ines\n\n\n"
},
{
"text": "\n124637\nA Preclinical Evaluation of Alternative Synthetic Biomaterials for Fascial Defect Repair Using a Rat Abdominal Hernia Model.\n\nUlrich, D\n\nEdwards, SL\n\nWhite, JF\n\nSupit, T\n\nRamshaw, JAM\n\nLo, C\n\nRosamilia, A\n\nWerkmeister, JA\n\nGargett, CE\n\n\n\nBeiträge in Fachzeitschriften\nISI:000311535700065\n23185528.0\n10.1371/journal.pone.0050044\nPMC3502256\nIntroduction: Fascial defects are a common problem in the abdominal wall and in the vagina leading to hernia or pelvic organ prolapse that requires mesh enhancement to reduce operation failure. However, the long-term outcome of synthetic mesh surgery may be unsatisfactory due to post-surgical complications. We hypothesized that mesh fabricated from alternative synthetic polymers may evoke a different tissue response, and provide more appropriate mechanical properties for hernia repair. Our aim was to compare the in vivo biocompatibility of new synthetic meshes with a commercial mesh.\nMethods: We have fabricated 3 new warp-knitted synthetic meshes from different polymers with different tensile properties polyetheretherketone (PEEK), polyamide (PA) and a composite, gelatin coated PA (PA+G). The rat abdominal hernia model was used to implant the meshes (25x35 mm, n = 24/group). After 7, 30, 60, 90 days tissues were explanted for immunohistochemical assessment of foreign body reaction and tissue integration, using CD31, CD45, CD68, alpha-SMA antibodies. The images were analysed using an image analysis software program. Biomechanical properties were uniaxially evaluated using an Instron Tensile (R) Tester.\nResults: This study showed that the new meshes induced complex differences in the type of foreign body reaction over the time course of implantation. The PA, and particularly the composite PA+G meshes, evoked a milder early inflammatory response, and macrophages were apparent throughout the time course. Our meshes led to better tissue integration and new collagen deposition, particularly with the PA+G meshes, as well as greater and sustained neovascularisation compared with the PP meshes.\nConclusion: PA, PA+G and PEEK appear to be well tolerated and are biocompatible, evoking an overlapping and different host tissue response with time that might convey mechanical variations in the healing tissue. These new meshes comprising different polymers may provide an alternative option for future treatment of fascial defects.\n\nGold ehem Ulrich, Daniela\n\n\n"
},
{
"text": "\n140789\nElevation in high-sensitivity troponin T in heart failure and preserved ejection fraction and influence of treatment with the angiotensin receptor neprilysin inhibitor LCZ696.\n\nJhund, PS\n\nClaggett, BL\n\nVoors, AA\n\nZile, MR\n\nPacker, M\n\nPieske, BM\n\nKraigher-Krainer, E\n\nShah, AM\n\nPrescott, MF\n\nShi, V\n\nLefkowitz, M\n\nMcMurray, JJ\n\nSolomon, SD\n\nPARAMOUNT Investigators\n\nBeiträge in Fachzeitschriften\nISI:000345288800013\n25277997.0\n10.1161/CIRCHEARTFAILURE.114.001427\nNone\nElevated high-sensitivity troponin is associated with increasing disease severity in patients with stable heart failure with reduced ejection fraction, but less is known about the association in heart failure with preserved ejection fraction.\n We examined the prevalence of elevated high-sensitivity troponin T (hs-TnT) in 298 patients with heart failure with preserved ejection fraction enrolled in the Prospective comparison of angiotensin receptor neprilysin inhibitor with angiotensin receptor blocker on Management Of heart failUre with preserved ejectioN fracTion (PARAMOUNT) trial, in which the angiotensin receptor neprilysin inhibitor LCZ696 reduced markers of heart failure severity compared with valsartan. We assessed the association between hs-TnT and cardiac structure and function, and the effect of LCZ696, compared with valsartan, on hs-TnT over 36 weeks. Elevated hs-TnT in the myocardial injury range (>0.014 μg/L) was found in 55% of patients and was associated with older age, history of diabetes mellitus, higher N-terminal pro-brain natriuretic peptide, lower estimated glomerular filtration rate, and larger left atrial size, left ventricular volume, and mass. LCZ696 treatment reduced hs-TnT to a greater extent at 12 weeks (12% reduction; P=0.05) and at 36 weeks (14% reduction; P=0.03) compared with valsartan.\n Troponin T was elevated in a substantial number of patients enrolled in a heart failure with preserved ejection fraction clinical trial and was associated with abnormalities of cardiac structure, function, and elevated baseline N-terminal pro-brain natriuretic peptide. Decreases in hs-TnT with LCZ696 in parallel with improvement in N-terminal pro-brain natriuretic peptide and left atrial size suggest that the angiotensin receptor neprilysin inhibitor LCZ696 may reduce this measure of myocardial injury in heart failure with preserved ejection fraction.\n http://www.clinicaltrials.gov. Unique identifier: NCT00887588.\n © 2014 American Heart Association, Inc.\n\n\n"
},
{
"text": "\n153259\nExecutive summary. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.\n\nHansmann, G\n\nApitz, C\n\nAbdul-Khaliq, H\n\nAlastalo, TP\n\nBeerbaum, P\n\nBonnet, D\n\nDubowy, KO\n\nGorenflo, M\n\nHager, A\n\nHilgendorff, A\n\nKaestner, M\n\nKoestenberger, M\n\nKoskenvuo, JW\n\nKozlik-Feldmann, R\n\nKuehne, T\n\nLammers, AE\n\nLatus, H\n\nMichel-Behnke, I\n\nMiera, O\n\nMoledina, S\n\nMuthurangu, V\n\nPattathu, J\n\nSchranz, D\n\nWarnecke, G\n\nZartner, P\n\nBeiträge in Fachzeitschriften\nISI:000376881300010\n27053701.0\n10.1136/heartjnl-2015-309132\nNone\n: The European Paediatric Pulmonary Vascular Disease (PVD) Network is a registered, non-profit organisation that strives to define and develop effective, innovative diagnostic methods and treatment options in all forms of paediatric pulmonary hypertensive vascular disease, including specific forms such as pulmonary arterial hypertension (PAH)-congenital heart disease, pulmonary hypertension (PH) associated with bronchopulmonary dysplasia, persistent PH of the newborn, and related cardiac dysfunction.\n The writing group members conducted searches of the PubMed/MEDLINE bibliographic database (1990-2015) and held five face-to-face meetings with votings. Clinical trials, guidelines, and reviews limited to paediatric data were searched using the terms 'pulmonary hypertensioń' and 5-10 other keywords, as outlined in the other nine articles of this special issue. Class of recommendation (COR) and level of evidence (LOE) were assigned based on European Society of Cardiology/American Heart Association definitions and on paediatric data only, or on adult studies that included >10% children.\n A total of 9 original consensus articles with graded recommendations (COR/LOE) were developed, and are summarised here. The topics included diagnosis/monitoring, genetics/biomarker, cardiac catheterisation, echocardiography, cardiac magnetic resonance/chest CT, associated forms of PH, intensive care unit/ventricular assist device/lung transplantation, and treatment of paediatric PAH.\n The multipaper expert consensus statement of the European Paediatric PVD Network provides a specific, comprehensive, detailed but practical framework for the optimal clinical care of children with PH.\n Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/\n\nKoestenberger, Martin\n\n\n"
},
{
"text": "\n159630\nCOUP-TFII gene expression is upregulated in embryonic pleuroperitoneal folds in the nitrofen-induced congenital diaphragmatic hernia rat model.\n\nDingemann, J\n\nDoi, T\n\nRuttenstock, EM\n\nGosemann, JH\n\nPuri, P\n\nBeiträge in Fachzeitschriften\nISI:000301973200006\n21879463.0\n10.1055/s-0031-1284358\nNone\nThe nitrofen model of congenital diaphragmatic hernia (CDH) creates a Bochdalek-type diaphragmatic defect and has been widely used to investigate the pathogenesis of CDH. However, the exact pathogenesis of the diaphragmatic defect in this model is still poorly understood. Chicken ovalbumin upstream promotor-transcription factor II (COUP-TFII) is expressed in the embryonic pleuroperitoneal folds (PPF) in the early stage of development and in the diaphragm in the late days of gestation. COUP-TFII is known to be a strong repressor of the retinoid signaling pathway (RSP), which plays an important role in diaphragm development. Furthermore, it has been recently shown that COUP-TFII is upregulated during early gestation in the nitrofen-induced hypoplastic lung. We designed this study to investigate the hypothesis that COUP-TFII gene expression is upregulated during early diaphragmatic development in the PPF.\n Timed pregnant rats were exposed to either olive oil (Control) or nitrofen (CDH) on day 9 of gestation (D9). Fetuses were sacrificed on D13, D18 or D21. The PPF was dissected from D13 fetuses using laser capture microdissection. Diaphragms were dissected from D18 and D21 fetuses under the dissection microscope. The relative mRNA expression levels of COUP-TFII were determined using real-time PCR. Immunohistochemistry was performed to evaluate diaphragmatic protein expression and the distribution of COUP-TFII.Results On D13, gene expression levels of COUP-TFII in the PPF were significantly increased in the CDH group (82.93 ± 11.85) compared to Controls (46.22 ± 8.09; p < 0.05), whereas there were no differences at later time points. The immunoreactivity of diaphragmatic COUP-TFII was markedly increased in the PPF in the CDH group compared to controls on D13. No difference in immunoreactivity was observed on D18 and D21.\n Upregulation of COUP-II gene expression in the PPF may contribute to the diaphragmatic defect in the nitrofen CDH model by inhibiting the RSP.\n Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.\n\n\n"
},
{
"text": "\n160415\nCharacterisation of adipocyte-derived extracellular vesicle subtypes identifies distinct protein and lipid signatures for large and small extracellular vesicles.\n\nDurcin, M\n\nFleury, A\n\nTaillebois, E\n\nHilairet, G\n\nKrupova, Z\n\nHenry, C\n\nTruchet, S\n\nTrötzmüller, M\n\nKöfeler, H\n\nMabilleau, G\n\nHue, O\n\nAndriantsitohaina, R\n\nMartin, P\n\nLe Lay, S\n\nBeiträge in Fachzeitschriften\nISI:000398663900001\n28473884.0\n10.1080/20013078.2017.1305677\nPMC5405565\nExtracellular vesicles (EVs) are biological vectors that can modulate the metabolism of target cells by conveying signalling proteins and genomic material. The level of EVs in plasma is significantly increased in cardiometabolic diseases associated with obesity, suggesting their possible participation in the development of metabolic dysfunction. With regard to the poor definition of adipocyte-derived EVs, the purpose of this study was to characterise both qualitatively and quantitatively EVs subpopulations secreted by fat cells. Adipocyte-derived EVs were isolated by differential centrifugation of conditioned media collected from 3T3-L1 adipocytes cultured for 24 h in serum-free conditions. Based on morphological and biochemical properties, as well as quantification of secreted EVs, we distinguished two subpopulations of adipocyte-derived EVs, namely small extracellular vesicles (sEVs) and large extracellular vesicles (lEVs). Proteomic analyses revealed that lEVs and sEVs exhibit specific protein signatures, allowing us not only to define novel markers of each population, but also to predict their biological functions. Despite similar phospholipid patterns, the comparative lipidomic analysis performed on these EV subclasses revealed a specific cholesterol enrichment of the sEV population, whereas lEVs were characterised by high amounts of externalised phosphatidylserine. Enhanced secretion of lEVs and sEVs is achievable following exposure to different biological stimuli related to the chronic low-grade inflammation state associated with obesity. Finally, we demonstrate the ability of primary murine adipocytes to secrete sEVs and lEVs, which display physical and biological characteristics similar to those described for 3T3-L1. Our study provides additional information and elements to define EV subtypes based on the characterisation of adipocyte-derived EV populations. It also underscores the need to distinguish EV subpopulations, through a combination of multiple approaches and markers, since their specific composition may cause distinct metabolic responses in recipient cells and tissues.\n\nKöfeler, Harald\n\nTrötzmüller, Martin\n\n\n"
},
{
"text": "\n160428\nmiR-196b-5p Regulates Colorectal Cancer Cell Migration and Metastases through Interaction with HOXB7 and GALNT5.\n\nStiegelbauer, V\n\nVychytilova-Faltejskova, P\n\nKarbiener, M\n\nPehserl, AM\n\nReicher, A\n\nResel, M\n\nHeitzer, E\n\nIvan, C\n\nBullock, M\n\nLing, H\n\nDeutsch, A\n\nWulf-Goldenberg, A\n\nAdiprasito, JB\n\nStoeger, H\n\nHaybaeck, J\n\nSvoboda, M\n\nStotz, M\n\nHoefler, G\n\nSlaby, O\n\nCalin, GA\n\nGerger, A\n\nPichler, M\n\nBeiträge in Fachzeitschriften\nISI:000409037300031\n28533224.0\n10.1158/1078-0432.CCR-17-0023\nNone\nPurpose: miR-196b-5p has been previously implicated in malignant transformation; however, its role in colorectal cancer has not been fully explored. In this study, we examine the clinical and biological relevance of miR-196b-5p, and the molecular pathways regulated by miR-196b-5p in colorectal cancer.Experimental Design: miR-196b-5p expression was quantitated by qRT-PCR in 2 independent cohorts composed of 292 patients with colorectal cancer in total, to explore its biomarker potential. Transient and stable gain- and loss-of-function experiments were conducted in a panel of colorectal cancer cell lines and mice, to evaluate the impact of miR-196b-5p on proliferation, chemosensitivity, migration/invasion, and metastases formation in vitro and in vivo The molecular pathways influenced by miR-196b-5p were characterized using whole transcriptome profiling, in silico target prediction tools, luciferase interaction assays, and phenocopy/rescue gene knockdown experiments.Results: Low miR-196b-5p expression was significantly associated with metastases and poor outcomes in 2 independent colorectal cancer patient cohorts (P < 0.05, log-rank test). miR-196b-5p inhibition led to significantly increased colorectal cancer cell migration/invasion and metastases formation in mice, whereas ectopic overexpression showed the opposite phenotype. Molecular profiling and target confirmation identified an interaction between miR-196b-5p and HOXB7 and GALNT5, which in turn regulated colorectal cancer cell migration.Conclusions: The association of low levels of miR-196b-5p and poor prognosis in patients with colorectal cancer can be explained by its influence on cancer cell migration and metastases formation. miR-196b-5p has an impact on colorectal cancer progression pathways through direct interaction with genes involved in cancer cell migration. Clin Cancer Res; 23(17); 5255-66. ©2017 AACR.\n ©2017 American Association for Cancer Research.\n\nDeutsch, Alexander\n\nGerger, Armin\n\nHaybäck, Johannes\n\nHeitzer, Ellen\n\nHöfler, Gerald\n\nPichler, Martin\n\nResel, Margit\n\nStoeger, Herbert\n\n\n"
},
{
"text": "\n170497\nGDF11 Decreases Pressure Overload-Induced Hypertrophy, but Can Cause Severe Cachexia and Premature Death.\n\nHarper, SC\n\nJohnson, J\n\nBorghetti, G\n\nZhao, H\n\nWang, T\n\nWallner, M\n\nKubo, H\n\nFeldsott, EA\n\nYang, Y\n\nJoo, Y\n\nGou, X\n\nSabri, AK\n\nGupta, P\n\nMyzithras, M\n\nKhalil, A\n\nFranti, M\n\nHouser, SR\n\nBeiträge in Fachzeitschriften\nISI:000449493300015\n30571461.0\n10.1161/CIRCRESAHA.118.312955\nPMC6309347\nPossible beneficial effects of GDF11 (growth differentiation factor 11) on the normal, diseased, and aging heart have been reported, including reversing aging-induced hypertrophy. These effects have not been well validated. High levels of GDF11 have also been shown to cause cardiac and skeletal muscle wasting. These controversies could be resolved if dose-dependent effects of GDF11 were defined in normal and aged animals as well as in pressure overload-induced pathological hypertrophy.\n To determine dose-dependent effects of GDF11 on normal hearts and those with pressure overload-induced cardiac hypertrophy.\n Twelve- to 13-week-old C57BL/6 mice underwent transverse aortic constriction (TAC) surgery. One-week post-TAC, these mice received rGDF11 (recombinant GDF11) at 1 of 3 doses: 0.5, 1.0, or 5.0 mg/kg for up to 14 days. Treatment with GDF11 increased plasma concentrations of GDF11 and p-SMAD2 in the heart. There were no significant differences in the peak pressure gradients across the aortic constriction between treatment groups at 1 week post-TAC. Two weeks of GDF11 treatment caused dose-dependent decreases in cardiac hypertrophy as measured by heart weight/tibia length ratio, myocyte cross-sectional area, and left ventricular mass. GDF11 improved cardiac pump function while preventing TAC-induced ventricular dilation and caused a dose-dependent decrease in interstitial fibrosis (in vivo), despite increasing markers of fibroblast activation and myofibroblast transdifferentiation (in vitro). Treatment with the highest dose (5.0 mg/kg) of GDF11 caused severe body weight loss, with significant decreases in both muscle and organ weights and death in both sham and TAC mice.\n Although GDF11 treatment can reduce pathological cardiac hypertrophy and associated fibrosis while improving cardiac pump function in pressure overload, high doses of GDF11 cause severe cachexia and death. Use of GDF11 as a therapy could have potentially devastating actions on the heart and other tissues.\n\nWallner, Markus\n\n\n"
},
{
"text": "\n178397\nIn vitro elimination of epidermal growth factor receptor-overexpressing cancer cells by CD32A-chimeric receptor T cells in combination with cetuximab or panitumumab.\n\nCaratelli, S\n\nArriga, R\n\nSconocchia, T\n\nOttaviani, A\n\nLanzilli, G\n\nPastore, D\n\nCenciarelli, C\n\nVenditti, A\n\nDel Principe, MI\n\nLauro, D\n\nLandoni, E\n\nDu, H\n\nSavoldo, B\n\nFerrone, S\n\nDotti, G\n\nSconocchia, G\n\nBeiträge in Fachzeitschriften\nISI:000495546500025\n31479522.0\n10.1002/ijc.32663\nNone\nCetuximab and panitumumab bind the human epidermal growth factor receptor (EGFR). Although the chimeric cetuximab (IgG1) triggers antibody-dependent-cellular-cytotoxicity (ADCC) of EGFR positive target cells, panitumumab (a human IgG2) does not. The inability of panitumumab to trigger ADCC reflects the poor binding affinity of human IgG2 Fc for the FcγRIII (CD16) on natural killer (NK) cells. However, both human IgG1 and IgG2 bind the FcγRII (CD32A) to a similar extent. Our study compares the ability of T cells, engineered with a novel low-affinity CD32A131R -chimeric receptor (CR), and those engineered with the low-affinity CD16158F -CR T cells, in eliminating EGFR positive epithelial cancer cells (ECCs) in combination with cetuximab or panitumumab. After T-cell transduction, the percentage of CD32A131R -CR T cells was 74 ± 10%, whereas the percentage of CD16158F -CR T cells was 46 ± 15%. Only CD32A131R -CR T cells bound panitumumab. CD32A131R -CR T cells combined with the mAb 8.26 (anti-CD32) and CD16158F -CR T cells combined with the mAb 3g8 (anti-CD16) eliminated colorectal carcinoma (CRC), HCT116FcγR+ cells, in a reverse ADCC assay in vitro. Crosslinking of CD32A131R -CR on T cells by cetuximab or panitumumab and CD16158F -CR T cells by cetuximab induced elimination of triple negative breast cancer (TNBC) MDA-MB-468 cells, and the secretion of interferon gamma and tumor necrosis factor alpha. Neither cetuximab nor panitumumab induced Fcγ-CR T antitumor activity against Kirsten rat sarcoma (KRAS)-mutated HCT116, nonsmall-cell-lung-cancer, A549 and TNBC, MDA-MB-231 cells. The ADCC of Fcγ-CR T cells was associated with the overexpression of EGFR on ECCs. In conclusion, CD32A131R -CR T cells are efficiently redirected by cetuximab or panitumumab against breast cancer cells overexpressing EGFR.\n © 2019 UICC.\n\nSconocchia, Tommaso\n\n\n"
},
{
"text": "\n179676\n[Biliary complications following orthotopic liver transplantation. The Hungarian experience].\n\nNemes, B\n\nZádori, G\n\nHartmann, E\n\nNémeth, A\n\nFehérvári, I\n\nGörög, D\n\nMáthé, Z\n\nDávid, A\n\nJakab, K\n\nSárváry, E\n\nPiros, L\n\nTóth, S\n\nFazakas, J\n\nGerlei, Z\n\nJáray, J\n\nDoros, A\n\nBeiträge in Fachzeitschriften\nNone\n18487111.0\n10.1556/OH.2008.28363\nNone\nThe authors summarize the characteristics of biliary complications following liver transplantation in the Hungarian liver transplant program. Aims were to analyze the frequency and the types of biliary complications as well as their effect on the patient and graft survival. The authors observed the known risk factors in the Hungarian practice, and they also try to find unknown risk factors for biliary complications. They review the therapy of biliary complications.\n In the retrospective study, patients were divided into two groups, with and without biliary complication after liver transplantation. These two groups were compared with many factors, and with the survivals. The biliary complication group was divided into two parts: those who had an early and those with a late biliary complication. These two new groups were also compared with the controls. The results are summarized in tables and statistical figures. Categorical variables are evaluated by chi 2 -test, continuous ones are with Levine Test (for homogenicity of means), Student T test and Mann-Whitney U-test. Cumulative survivals are computed with Kaplan-Meier log rank analysis.\n Biliary complication appeared in 25% of the patients. The most frequent complications were stenosis (18%), biliary leakage (9%), biliary necrosis (6%), and ischaemic type of biliary lesions (3%). The 5-year survival is worse when biliary complications were diagnosed (55%) than without such a complication (66%). In the biliary complication group the retransplantation rate was higher (15%). The most frequent treatments were interventional radiologic methods (69%), surgical methods (17%), and the ERCP.\n The rate of biliary complications met the international reviews. Risk factors for biliary complications were cholangitis, hepatic artery thrombosis and stenosis, high rate of intraoperative blood transfusions, and acute rejection. Biliary complications frequently associated with the initial poor function of the transplanted graft. Early biliary complications have a negative impact on patient survival, while late complications influence a decreased quality of life. Biliary complications were treated mostly by interventional radiologic procedures.\n\n\n"
},
{
"text": "\n182866\nPredictors of recurrence of atrial fibrillation within the first 3 months after ablation.\n\nZink, MD\n\nChua, W\n\nZeemering, S\n\ndi Biase, L\n\nAntoni, BL\n\nDavid, C\n\nHindricks, G\n\nHaeusler, KG\n\nAl-Khalidi, HR\n\nPiccini, JP\n\nMont, L\n\nNielsen, JC\n\nEscobar, LA\n\nde Bono, J\n\nVan Gelder, IC\n\nde Potter, T\n\nScherr, D\n\nThemistoclakis, S\n\nTodd, D\n\nKirchhof, P\n\nSchotten, U\n\nBeiträge in Fachzeitschriften\nISI:000581004800006\n32725107.0\n10.1093/europace/euaa132\nPMC7478316\nFreedom from atrial fibrillation (AF) at 1 year can be achieved in 50-70% of patients undergoing catheter ablation. Recurrent AF early after ablation most commonly terminates spontaneously without further interventional treatment but is associated with later recurrent AF. The aim of this investigation is to identify clinical and procedural factors associated with recurrence of AF early after ablation.\n We retrospectively analysed data for recurrence of AF within the first 3 months after catheter ablation from the randomized controlled AXAFA-AFNET 5 trial, which demonstrated that continuous anticoagulation with apixaban is as safe and as effective compared to vitamin K antagonists in 678 patients undergoing first AF ablation. The primary outcome of first recurrent AF within 90 days was observed in 163 (28%) patients, in which 78 (48%) patients experienced an event within the first 14 days post-ablation. After multivariable adjustment, a history of stroke/transient ischaemic attack [hazard ratio (HR) 1.54, 95% confidence interval (CI) 0.93-2.6; P = 0.11], coronary artery disease (HR 1.85, 95% CI 1.20-2.86; P = 0.005), cardioversion during ablation (HR 1.78, 95% CI 1.26-2.49; P = 0.001), and an age:sex interaction for older women (HR 1.01, 95% CI 1.00-1.01; P = 0.04) were associated with recurrent AF. The P-wave duration at follow-up was significantly longer for patients with AF recurrence (129 ± 31 ms vs. 122 ± 22 ms in patients without AF, P = 0.03).\n Half of all early AF recurrences within the first 3 months post-ablation occurred within the first 14 days post-ablation. Vascular disease and cardioversion during the procedure are strong predictors of recurrent AF. P-wave duration at follow-up was longer in patients with recurrent AF.\n Clinicaltrials.gov identifier NCT02227550.\n © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.\n\nScherr, Daniel\n\n\n"
},
{
"text": "\n183252\nMolecular and Cellular Mechanisms of Arthritis in Children and Adults: New Perspectives on Applied Photobiomodulation.\n\nAilioaie, LM\n\nLitscher, G\n\nBeiträge in Fachzeitschriften\nISI:000581474600001\n32911717.0\n10.3390/ijms21186565\nPMC7554967\nJuvenile idiopathic arthritis and adult rheumatoid arthritis are two major groups with chronic joint pain and inflammation, extra-articular manifestations, and high risk of comorbidities, which can cause physical and ocular disability, as well as create great socio-economic pressure worldwide. The pathogenesis of arthritis manifested in childhood and adulthood is multifactorial, unclear, and overly complex, in which immunity plays an important role. Although there are more and more biological agents with different mechanisms of action for the treatment of arthritis, the results are not as expected, because there are partial responses or non-responsive patients to these compounds, high therapeutic costs, side effects, and so on; therefore, we must turn our attention to other therapeutic modalities. Updating knowledge on molecular and cellular mechanisms in the comparative pathogenesis of chronic arthritis in both children and adults is necessary in the early and correct approach to treatment. Photobiomodulation (PBM) represents a good option, offering cost-effective advantages over drug therapy, with a quicker, more positive response to treatment and no side effects. The successful management of PBM in arthritis is based on the clinician's ability to evaluate correctly the inflammatory status of the patient, to seek the optimal solution, to choose the best technology with the best physical parameters, and to select the mode of action to target very precisely the immune system and the molecular signaling pathways at the molecular level with the exact amount of quantum light energy in order to obtain the desired immune modulation and the remission of the disease. Light is a very powerful tool in medicine because it can simultaneously target many cascades of immune system activation in comparison with drugs, so PBM can perform very delicate tasks inside our cells to modulate cellular dysfunctions, helping to initiate self-organization phenomena and finally, healing the disease. Interdisciplinary teams should work diligently to meet these needs by also using single-cell imaging devices for multispectral laser photobiomodulation on immune cells.\n\nLitscher, Gerhard\n\n\n"
},
{
"text": "\n187598\nA Framework for the generation of digital twins of cardiac electrophysiology from clinical 12-leads ECGs.\n\nGillette, K\n\nGsell, MAF\n\nPrassl, AJ\n\nKarabelas, E\n\nReiter, U\n\nReiter, G\n\nGrandits, T\n\nPayer, C\n\nŠtern, D\n\nUrschler, M\n\nBayer, JD\n\nAugustin, CM\n\nNeic, A\n\nPock, T\n\nVigmond, EJ\n\nPlank, G\n\nBeiträge in Fachzeitschriften\nNone\n33975097.0\n10.1016/j.media.2021.102080\nNone\nCardiac digital twins (Cardiac Digital Twin (CDT)s) of human electrophysiology (Electrophysiology (EP)) are digital replicas of patient hearts derived from clinical data that match like-for-like all available clinical observations. Due to their inherent predictive potential, CDTs show high promise as a complementary modality aiding in clinical decision making and also in the cost-effective, safe and ethical testing of novel EP device therapies. However, current workflows for both the anatomical and functional twinning phases within CDT generation, referring to the inference of model anatomy and parameters from clinical data, are not sufficiently efficient, robust and accurate for advanced clinical and industrial applications. Our study addresses three primary limitations impeding the routine generation of high-fidelity CDTs by introducing; a comprehensive parameter vector encapsulating all factors relating to the ventricular EP; an abstract reference frame within the model allowing the unattended manipulation of model parameter fields; a novel fast-forward electrocardiogram (Electrocardiogram (ECG)) model for efficient and bio-physically-detailed simulation required for parameter inference. A novel workflow for the generation of CDTs is then introduced as an initial proof of concept. Anatomical twinning was performed within a reasonable time compatible with clinical workflows (<4h) for 12 subjects from clinically-attained magnetic resonance images. After assessment of the underlying fast forward ECG model against a gold standard bidomain ECG model, functional twinning of optimal parameters according to a clinically-attained 12 lead ECG was then performed using a forward Saltelli sampling approach for a single subject. The achieved results in terms of efficiency and fidelity demonstrate that our workflow is well-suited and viable for generating biophysically-detailed CDTs at scale.\n Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.\n\nAugustin, Christoph\n\nGillette, Karli\n\nGsell, Matthias\n\nKarabelas, Elias\n\nNeic, Aurel-Vasile\n\nPlank, Gernot\n\nPrassl, Anton\n\nReiter, Ursula\n\nStern, Darko\n\n\n"
},
{
"text": "\n2705\nTransfer of phospholipase A-resistant pyrene-dialkyl-glycerophosphocholine to plasma lipoproteins: differences between Lpa and LDL.\n\nGorges, R\n\nHofer, G\n\nSommer, A\n\nStütz, H\n\nGrillhofer, H\n\nKostner, GM\n\nPaltauf, F\n\nHermetter, A\n\nBeiträge in Fachzeitschriften\nISI:A1995QH01400004\n7751812.0\nNone\nNone\n1-O-Hexadecyl-2-O-pyrenedecanyl-sn-glycero-3-phosphocholine, a non-hydrolyzable fluorescent diether analog of phosphatidylcholine (PC), was synthesized as a probe for studying phospholipid transfer to different lipoprotein classes with potential phospholipase activities. After incubation of total human plasma with the new probe at 37 degrees C for 4.5 h, a characteristic partition between the main lipoprotein fractions was observed. The fluorescent lipid was not degraded under these conditions and, therefore, served as a measure for choline glycerophospholipid distribution between plasma lipoproteins. In low density lipoprotein (LDL) and high density lipoprotein-3 (HDL3) the fluorescent PC analog showed only monomer fluorescence, whereas in Lp[a] and HDL2 monomer and excimer fluorescence were observed, indicating that the fluorescent phosphatidylcholine analog was incorporated into the respective lipoproteins to a different extent. According to the increased pyrene excimer fluorescence in Lp[a] compared with LDL the labeled phosphatidylcholine must be enriched and/or clustered in Lp[a]. Data from phospholipid and total fluorescence analyses are compatible with the assumption of higher label concentration in Lp[a]. On the other hand, transfer rates for serum protein-catalyzed lipid transport into isolated Lp[a] were slower as compared to LDL. It is suggested that slower lipid transfer to Lp[a] under these conditions is due to the decreased lipid mobility in the Lp[a] surface, whereas the higher extent of label partition into Lp[a] as observed in total plasma might be due to the higher affinity of apolipoproteins for phosphatidylcholine in Lp[a] (Sommer, A., et al. 1992. J. Biol. Chem. 267: 24217-24222). The use of a fluorescent dialkyl- instead of diacyl-glycerophosphocholine for transfer studies was mandatory, as we found that lipoproteins contained phospholipase A2 activity toward long-chain phosphatidylcholine. The lipoprotein-associated phospholipase A2 was three times more active in Lp[a] than in LDL. The degradation products formed by the phospholipase, fatty acids, and lyso-PC may add to the high atherogenic potential of Lp[a].\n\nKostner, Gerhard\n\n\n"
},
{
"text": "\n53775\nAdjuvant treatment of osteo arthritis of the knee with weak pulsing magnetic fields - Results of a prospective, placebo controlled trial\n\nFischer, G\n\nPelka, RB\n\nBarovic, J\n\nBeiträge in Fachzeitschriften\nISI:000240946300006\nNone\n10.1055/s-2006-927051\nNone\nPurpose: The aim of this study was the objective control of the therapeutic effect of weak pulsing magnetic fields (series of periodically repeating square pulses increasing according to an e-function, frequencies of 10, 20, 30, and 200-300 Hz) by means of a double-blind study on osteoarthritis of the knee. Measured parameters were the Knee Society score, pain sensation, blood count and cardiocirculatory values. Methods: 36 placebo and 35 verum test persons (all with a knee gap smaller than 3 mm) were exposed daily for 16 minutes over 6 weeks to a low frequency magnetic field (flux densities increasing gradually from 3.4 up to 13.6 mu T) encompassing the whole body. The last data collection was made 4 weeks after the end of treatment. Results: Principally, the statistically ensured results exclusively favour the used magnetic field therapy; by far the greatest number of at least significant differences was found at the end of the whole treatment, lasting 6 weeks. In particular, it is striking that all 4 questioned pain scales showed at least significant improvements in favour of the verum collective; also the walking distance was increased. As another confirmed fact, even after 4 weeks without therapy the persistence of several functional and analgesic effects could be documented. Conclusions: Predominantly, on the one hand, pain relief in osteoarthritis patients was confirmed by a double-blind trial, on the other hand, increases in mobility could be proven. Furthermore, we describe mainly the modes of action of low frequency magnetic energy and 3 physical concepts that are seen as the connecting link between electromagnetic fields coupled into connective tissue and biochemical repair and growth processes in bones and cartilage. Proceeding from the results of this and preceding studies, one has to consider seriously whether this kind of magnetic field application should not be employed as cost-effective and side effect-free alternative or adjuvant form of therapy in the field of orthopaeclic disorders.\n\n\n"
},
{
"text": "\n67970\nReversed-phase high-performance liquid chromatography of polyethers - Comparison with a theory for flexible-chain macromolecules\n\nGorbunov, A\n\nSkvortsov, A\n\nTrathnigg, B\n\nKollroser, M\n\nParth, M\n\nBeiträge in Fachzeitschriften\nISI:000072695800023\nNone\n10.1016/S0021-9673(97)01196-5\nNone\nReversed-phase adsorption chromatography retention modes of polyethylene glycol (PEG), its mono and dimethyl ethers (MME and DME) and polypropylene glycol (PPG) are studied both experimentally and theoretically. The experimental conditions were: narrow-and wide-pore Spherisorb C-18 adsorbents and two mixed-solvent systems (methanol-water and acetone-water) as mobile phases. At varying compositions of the mobile phase, fully-resolved chromatograms of polyether samples were obtained, in which all peaks could be identified, and the dependencies of the distribution coefficient on the degree of polymerization for PEG and PPG molecules were extracted by processing these chromatograms. The data were interpreted by using a theory of homopolymers based on a continuum Gaussian chain model of flexible macromolecules and a slit-like model of pens of the stationary phase. Two regimes of an adsorption chromatography of macromolecules are examined in relation to the well-known Martin rule, the role of pore size and the end-group effects being discussed. The theory proved to describe the experimental data on both polymers well, in the whole range of molecular masses studied, and thermodynamic parameters characterizing interactions of ethylene oxide and propylene oxide (PO) repeating units in polyether molecules with the adsorbent pore walls have been determined from a comparison of the theory with the experimental data. The conditions corresponding to the critical chromatography mode are estimated from the thermodynamic data for PEG and methanol-water system as being at about 76% of methanol, while for the PPG and acetone-water system, it is shown that such critical conditions at the given temperature are not attainable. Additionally, the mean thickness H of adsorbed PEG and PPG macromolecules was estimated as being equal to about 3-10 Angstrom. The parameter H proved to be a decreasing function of the water content in the mixed solvent. The same estimate of thickness H approximate to 2.6 Angstrom is obtained for both polymers in purl water. (C) 1998 Elsevier Science B.V.\n\nKollroser, Manfred\n\n\n"
}
]
}