@article{LiuHuStoerketal.2014,
  author    = {Liu, Dan and Hu, Kai and St{\"o}rk, Stefan and Herrmann, Sebastian and Kramer, Bastian and Cikes, Maja and Gaudron, Philipp Daniel and Knop, Stefan and Ertl, Georg and Bijnens, Bart and Weidemann, Frank},
  title     = {Predictive Value of Assessing Diastolic Strain Rate on Survival in Cardiac Amyloidosis Patients with Preserved Ejection Fraction},
  series = {PLOS ONE},
  volume    = {9},
  journal   = {PLOS ONE},
  number    = {12},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0115910},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-118024},
  year      = {2014},
  abstract  = {Objectives: Since diastolic abnormalities are typical findings of cardiac amyloidosis (CA), we hypothesized that speckle-tracking-imaging (STI) derived longitudinal early diastolic strain rate (LSRdias) could predict outcome in CA patients with preserved left ventricular ejection fraction (LVEF >50\%). Background: Diastolic abnormalities including altered early filling are typical findings and are related to outcome in CA patients. Reduced longitudinal systolic strain (LSsys) assessed by STI predicts increased mortality in CA patients. It remains unknown if LSRdias also related to outcome in these patients. Methods: Conventional echocardiography and STI were performed in 41 CA patients with preserved LVEF (25 male; mean age 65±9 years). Global and segmental LSsys and LSRdias were obtained in six LV segments from apical 4-chamber views. Results: Nineteen (46\%) out of 41 CA patients died during a median of 16 months (quartiles 5-35 months) follow-up. Baseline mitral annular plane systolic excursion (MAPSE, 6±2 vs. 8±3 mm), global LSRdias and basal-septal LSRdias were significantly lower in non-survivors than in survivors (all p<0.05). NYHA class, number of non-cardiac organs involved, MAPSE, mid-septal LSsys, global LSRdias, basal-septal LSRdias and E/LSRdias were the univariable predictors of all-cause death. Multivariable analysis showed that number of non-cardiac organs involved (hazard ratio [HR] = 1.96, 95\% confidence interval [CI] 1.17-3.26, P = 0.010), global LSRdias (HR = 7.30, 95\% CI 2.08-25.65, P = 0.002), and E/LSRdias (HR = 2.98, 95\% CI 1.54-5.79, P = 0.001) remained independently predictive of increased mortality risk. The prognostic performance of global LSRdias was optimal at a cutoff value of 0.85 S-1 (sensitivity 68\%, specificity 67\%). Global LSRdias <0.85 S-1 predicted a 4-fold increased mortality in CA patients with preserved LVEF. Conclusions: STI-derived early diastolic strain rate is a powerful independent predictor of survival in CA patients with preserved LVEF.},
  language  = {en}
}
@phdthesis{Samtleben2014,
  author    = {Samtleben, Samira},
  title     = {Investigation of homeostatic calcium fluxes in hippocampal neurons by means of targeted-esterase induced dye loading (TED)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-110332},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {Calcium ions can activate intracellular signalling cascades that control key functions in all types of neurons. These functions include neuronal excitability and excitation, synaptic plasticity, cell migration, transmitter release, gene transcription, and apoptosis. The major intracellular neuronal store for calcium is the endoplasmic reticulum (ER), a continuous and dynamic, membranous organelle that extends through all parts of neurons, from axons to dendrites. The calcium concentration in the ER is appr. one thousand fold higher than in the cytosol and this calcium gradient is built up by the sarco-/endoplasmic reticulum calcium ATPase (SERCA) pump that pumps calcium from the cytosol into the ER. Despite detailed knowledge about various induced calcium signals within neurons, it was still elusive, how resting neurons maintain their ER calcium content at rest. In order to shed light on the calcium homeostasis at rest, the targeted-esterase induced dye loading (TED) technique was improved. TED allows the direct and non-disruptive visualization of ER calcium in presence of extracellular calcium, thus enabling to visualize the dynamic flow of ER calcium. TED is based on the overexpression of an ER-targeted mouse carboxylesterase. Inside the ER the carboxylesterase cleaves the acetoxymethyl ester calcium dye Fluo5N, AM, thereby converting this dye into a calcium sensitive, low-affinity, cell membrane impermeable calcium indicator that is trapped in the ER. When bound to calcium ions and excited by fluorescent light, its fluorescence intensity increases one hundredfold compared to the calcium-free state. It was observed that calcium withdrawal from resting neurons led to a rapid loss of calcium from both the ER and the cytosol, which recovered upon calcium re-addition. It was concluded that a strong calcium influx and efflux must exist under resting conditions that maintain a constant calcium concentration in neurons at rest. TED calcium imaging could visualize this resting calcium influx event. When the inhibitor of store-operated calcium entry (SOCE), SKF-96365, was acutely added to neurons an immediate decline in ER calcium levels was observed, whereas cytosolic calcium levels remained constant. Based on these findings, a novel calcium homeostasis model is proposed in which a strong SOCE-like calcium influx and a corresponding calcium efflux maintain the ER calcium levels at rest. These fluxes are adapted to disturbances in order to maintain a constant calcium level in resting neurons. This study visualizes for the first time the resting calcium flow into the ER. The calcium enters the neurons via a store-operated calcium entry-like mechanism, a form of calcium influx that was thought to be induced by signalling events.},
  subject      = {Calciumhom{\"o}ostase},
  language  = {en}
}