/st> The most reliable independent predictors of PONV were female gender, history of PONV or motion sickness, non-smoker, younger age, duration of anaesthesia with volatile anaesthetics, and postoperative opioids. There is no or insufficient evidence for a number of commonly held factors, such as preoperative fasting, menstrual cycle, and surgery type, and using these factors may be counterproductive in assessing a patient's risk for PONV.

Paclitaxel (Taxol) is a well established chemotherapeutic agent for the treatment of solid tumors, but it is limited in its usefulness by the frequent induction of peripheral neuropathy. We found that prolonged exposure of a neuroblastoma cell line and primary rat dorsal root ganglia with therapeutic concentrations of Taxol leads to a reduction in inositol trisphosphate (InsP 3)-mediated Ca 2؉ signaling. We also observed a Taxol-specific reduction in neuronal calcium sensor 1 (NCS-1) protein levels, a known modulator of InsP 3 receptor (InsP3R) activity. This reduction was also found in peripheral neuronal tissue from Taxol treated animals. We further observed that short hairpin RNA-mediated NCS-1 knockdown had a similar effect on phosphoinositide-mediated Ca 2؉ signaling. When NCS-1 protein levels recovered, so did InsP 3-mediated Ca 2؉ signaling. Inhibition of the Ca 2؉ -activated protease -calpain prevented alterations in phosphoinositide-mediated Ca 2؉ signaling and NCS-1 protein levels. We also found that NCS-1 is readily degraded by -calpain in vitro and that -calpain activity is increased in Taxol but not vehicle-treated cells. From these results, we conclude that prolonged exposure to Taxol activates -calpain, which leads to the degradation of NCS-1, which, in turn, attenuates InsP 3-mediated Ca 2؉ signaling. These findings provide a previously undescribed approach to understanding and treating Taxolinduced peripheral neuropathy.calcium imaging ͉ dorsal root ganglia ͉ endoplasmic reticulum ͉ polyneuropathy ͉ inositol 1,4,5-trisphosphate receptor

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Altered regulation of signaling pathways can lead to pathologies including cardiac hypertrophy and heart failure (HF). We report that neonatal and adult cardiomyocytes express chromogranin B (CGB), a calcium (Ca 2+ ) binding protein which modulates Ca 2+ release by the inositol 1,4,5-trisphosphate receptor (InsP 3 R). Using fluorescent Ca 2+ -indicator dyes, we found that CGB regulates InsP 3 -dependent Ca 2+ release in response to angiotensin-II (ANG-II), an octapeptide hormone that promotes cardiac hypertrophy. ELISA experiments and luciferase reporter assays identified ANG-II as a potent inducer of brain natriuretic peptide (BNP), a hormone that recently emerged as an important biomarker in cardiovascular disease. CGB was found to regulate ANG-II stimulated and basal secretion, expression and promoter activity of BNP that depend on the InsP 3 R. Moreover, we provide evidence that CGB acts via the transcription factor nuclear factor-kappa B (NF-κB) in an InsP 3 /Ca 2+ -dependent manner, but independent of nuclear factor of activated T-cells (NFAT). Invivo experiments further showed that cardiac hypertrophy induced by ANG-II, a condition characterized by increased ventricular BNP production, is associated with up-regulation of ventricular CGB expression. Over-expression of CGB in cardiomyocytes, in turn, induced the BNP promoter. The evidence presented in this study identifies CGB as a novel regulator of cardiomyocyte InsP 3 /Ca 2+ -dependent signaling, NF-κB activity and BNP production. KeywordsChromogranin B (CGB); calcium (Ca 2+ ); inositol 1,4,5-trisphosphate receptor (InsP 3 R); nuclear factor-kappa B (NF-κB); brain natriuretic peptide (BNP)

Paclitaxel (Taxol) is a microtubule-stabilizing compound that is used for cancer chemotherapy. However, Taxol administration is limited by serious side effects including cardiac arrhythmia, which cannot be explained by its microtubule-stabilizing effect. Recently, neuronal calcium sensor 1 (NCS-1), a calcium binding protein that modulates the inositol-1,4,5-trisphosphate receptor (InsP 3 R), was described as a binding partner of Taxol and as a substrate of calpain. We examined calcium signaling processes in cardiomyocytes after treatment with Taxol to investigate the basis of Taxol-induced cardiac arrhythmia. After treating isolated neonatal rat ventricular myocytes with a therapeutic concentration of Taxol for several hours live cell imaging experiments showed that the frequency of spontaneous calcium oscillations significantly increased. This effect was not mimicked by other tubulin-stabilizing agents. However, it was prevented by inhibiting the InsP 3 R. Taxol treated cells had increased expression of NCS-1, an effect also detectable after Taxol administration in vivo. Short hairpin RNA mediated knock down of NCS-1 decreased InsP 3 R dependent intracellular calcium release, whereas Taxol treatment, that increased NCS-1 levels, increased InsP 3 R dependent calcium release. The effects of Taxol were ryanodine receptor independent. At the single channel level Taxol and NCS-1 mediated an increase in InsP 3 R activity. Calpain activity was not affected by Taxol in cardiomyocytes suggesting a calpain independent signaling pathway. In short, our study shows that Taxol impacts calcium signaling and calcium oscillations in cardiomyocytes through NCS-1 and the InsP 3 R.

This article presents an integrated, automatic home-monitoring, and assist system for patients suffering from end-stage heart failure, particularly patients with implanted mechanical circulatory support devices, such as ventricular assist devices and total artificial hearts. The system incorporates various biosensors to monitor the vital parameters of the patient unobtrusively in the home environment. Recorded data can be accessed online and in real time by a supervising physician, and these data serve as a means for immediate diagnosis of emergency events. The retrieved information can also be continuously analyzed to generate suggestions for medication, nutrition, and exercise for the patient to optimize their rehabilitation and overall health. An experimental environment (the Future Care Lab) was set up at RWTH Aachen University to serve as a testing environment for the development and evaluation of this novel integrated system. The Future Care Lab was not only used as a platform for technically testing the monitoring system, but also more concretely demonstrating to users the integration of these new medical technologies in a home. Thus, the Future Care Lab provides a unique environment for an interdisciplinary research approach consisting of iterative cycles of system development and evaluation of user acceptance.

BackgroundThe clinical effect of copper accumulation on the heart of patients suffering from Wilson’s disease (WD) is not completely understood. We aimed to determine if patients with WD show signs of cardiac involvement, structural heart disease or autonomic dysfunction. In this prospective trial, we studied 61 patients (mean age 44.3 ± 15.2 years, 51% males) with WD and compared them to 61 age- and gender-matched healthy controls. All subjects underwent clinical examination, blood tests, echocardiography and 24 h electrocardiographic (ECG) recording.ResultsLeft- and right ventricular systolic function did not differ significantly between WD patients and controls. However, 5 of the 61 patients had a reduced left ventricular ejection fraction (LVEF). Furthermore, diastolic dysfunction was more prevalent in WD patients (9 of 61 vs. 0 of 61, p = 0.001).The severity of WD based on the Unified Wilson’s Disease Rating Scale was significantly correlated to NT-pro BNP (r = 0.34, P = 0.013). Patients with an exacerbation of WD in medical history had higher troponin levels compared to those without (11.3 ± 4.7 vs 4.6 ± 1.2).The autonomic function assessed by triangular index (TI) and SDNN-index was significantly reduced in WD patients compared to controls in most in almost every age category (p-value TI and SDNN: age 20–29, p < 0.001 and 0.05; age 30–39, p < 0.01 and not significant (ns); age 40–49, p < 0,01 and 0.001; age 50–59, p = ns and < 0.001, age 60–70, p < 0.05 and ns).ConclusionOur data demonstrate that cardiac involvement and autonomic dysfunction in WD is possible, however the underlying cause is still not known. We suggest that patients with signs and symptoms of structural heart disease should be examined by a cardiologist in addition to the interdisciplinary treatment team of WD.Electronic supplementary materialThe online version of this article (10.1186/s13023-019-1007-7) contains supplementary material, which is available to authorized users.

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