A Hypomorphic Vasopressin Allele Prevents Anxiety-Related Behavior

To investigate neurobiological correlates of trait anxiety, CD1 mice were selectively bred for extremes in anxiety-related behavior, with high (HAB) and low (LAB) anxiety-related behavior mice additionally differing in behavioral tests reflecting depression-like behavior. promoter deletion to anxiety-related behavior. gene promoter explains gene expression differences in association with the observed phenotype, thus further strengthening the concept of the critical involvement of centrally released AVP in trait anxiety

Interoperable Metadatenmodelle und Repositories

Um elektronische Publikationen in einem größeren Kontext (international und interdisziplinär) verfügbar zu machen, ist die Vernetzung von Repositories durch übergreifende Services eine wesentliche Voraussetzung. Dabei werden i.d.R. nicht die elektronischen Publikationen ausgetauscht, sondern die standardisierten Beschreibungen derselben, also die Metadaten. Damit bekommen Interoperabilität und Standardisierung von Metadatenmodellen entscheidende Bedeutung. Die Mehrzahl der Repositorien stellt für die Nachnutzung der Metadaten das OAI-PMH zur Verfügung. Dieses Protokoll berücksichtigt die Forderung nach Metadaten-Interoperabilität, indem es Dublin Core Simple als Mindeststandard für den Austausch von Metadaten fordert, gleichzeitig aber die Erweiterung dieses Mindeststandards durch domainspezifisch und lokal benötigte Metadatenelemente erlaubt. Die Verwendung von DC Simple erweist sich jedoch dann als problematisch, wenn beim Zusammenführen der Daten verschiedener Herkunft deutlich wird, dass die Data Provider bei der Datenerfassung unterschiedliche Regeln bezüglich Syntax und Semantik anwenden. Hier gilt es Lösungen zu finden, die sowohl den Forderungen der Data Provider nach möglichst einfacher Metadatenerfassung als auch den Forderungen der Service Provider nach möglichst großer syntaktischer und semantischer Interoperabilität entgegenkommen. Der Vortrag wird beispielhaft die Probleme, die sich beim Zusammenführen von Metadaten aus unabhängigen Repositorien ergeben, deutlich machen und die aktuellen theoretischen Lösungsansätze aus der Dublin Core Community (DCAM, Singapore Framework, SWAP) vorstellen

Case report: takotsubo syndrome in infectious endocarditis

Background!#!Outcome of ischemic VT ablation may differ between patients with previous myocardial infarction (MI) in relation to infarct localization.!##!Methods!#!We analyzed procedural data, acute and long-term outcomes of 152 consecutive patients (139 men, mean age 67 ± 9 years) with previous anterior or inferior MI who underwent ischemic VT ablation at our institution between January 2010 and October 2015.!##!Results!#!More patients had a history of inferior MI (58%). Mean ejection fraction was significantly lower in anterior MI patients (28 ± 10% vs. 34 ± 10%, p < 0.001). NYHA class and presence of comorbidities were not different between the groups. Indication for the procedure was electrical storm in 43% of patients, and frequent implantable cardioverter defibrillator (ICD) therapies in 57%, and did not differ significantly between anterior and inferior MI patients. A mean of 3 ± 2 VT morphologies were inducible, with a trend towards more VT in the anterior MI group (3.1 ± 2.2 vs. 2.6 ± 1.9, p = 0.18). Procedural parameters and acute success did not differ between the groups. During a mean follow-up of 3 ± 2 years, more anterior MI patients had undergone a re-ablation (49% vs. 33%, p = 0.09, Chi-square test). There was a trend towards more ICD shocks in patients with previous anterior MI (46% vs. 34%). After adjusting for risk factors and ejection fraction, multivariable Cox regression analyses showed no significant difference in mortality (p = 0.78) and cardiovascular mortality between infarct localizations (p = 0.6).!##!Conclusion!#!Clinical characteristics of patients with anterior and inferior MI are similar except for ejection fraction. Patients with inferior MI appear to have better outcome regarding survival, ICD shocks and re-ablation, but this appears to be related to better ejection fraction when compared with anterior MI

Use of Cardiac Biomarkers for Monitoring Improvement of Left Ventricular Function by Immunoadsorption Treatment in Dilated Cardiomyopathy

Immunoadsorption and subsequent administration of intravenous immunoglobulin (IVIG) have shown beneficial effects on cardiac function and symptoms in patients with dilated cardiomyopathy. Biomarkers play an emerging role in disease monitoring and outcome prediction of heart failure (HF) patients. We aimed to analyze cardiac biomarkers as predictor for improvement of left ventricular (LV) function after immunoadsorption treatment in dilated cardiomyopathy (DCM). Thirty-one patients with dilated cardiomyopathy on optimized HF pharmacotherapy received a single cycle of immunoadsorption for five days followed by IVIG administration. Left ventricular ejection fraction (LVEF) and heart failure biomarkers (hs troponin T, hs troponin I, NT-proBNP and sST2) were evaluated before treatment, after the last cycle of immunoadsorption and during a median follow-up of 30.5 months. We correlated HF biomarkers before immunoadsorption and acute changes of HF biomarkers by immunoadsorption with LV improvement during the long-term follow-up. LV function improved significantly after immunoadsorption from 28.0 to 42.0% during the long-term follow-up (p < 0.0001). Evaluation of biomarker levels showed a significant decrease for hs troponin I (from 9.2 to 5.5 ng/L, p < 0.05) and NT-proBNP (from 789.6 to 281.2 pg/mL, p < 0.005). Correlation of biomarker levels before immunoadsorption and LVEF at the long-term follow-up show good results for hs troponin T (r = −0.40, r2 = 0.16, p < 0.05), hs troponin I (r = −0.41, r2 = 0.17, p < 0.05) and sST2 (r = −0.46, r2 = 0.19, p < 0.05). Correlation of biomarker levels before immunoadsorption and the individual increase in LV function was significant for hs troponin T (r = −0.52, r2 = 0.27, p < 0.005) and hs troponin I (r = −0.53, r2 = 0.29, p < 0.005). To imply a tool for monitoring outcome immediately after immunoadsorption treatment, we investigated the correlation of acute changes of biomarker levels by immunoadsorption treatment and individual increase in LV function. A drop in hs troponin T (r = −0.41, r2 = 0.17, p < 0.05) and hs troponin I (r = −0.53, r2 = 0.28, p < 0.005) levels demonstrate a good correlation to improvement in LVEF during the long-term follow-up. Conclusion: Hs troponin T and I levels correlate with LV function improvement during long-term follow-up. Acute decrease of troponins by immunoadsorption treatment is paralleled by individual improvement of LVEF at the long-term follow-up. Thus, troponins could serve as a monitoring tool for the improvement of LV function after immunoadsorption treatment in dilated cardiomyopathy

Add-on Immunoadsorption Shortly-after Optimal Medical Treatment Further Significantly and Persistently Improves Cardiac Function and Symptoms in Recent-Onset Heart Failure—A Single Center Experience

Background: Immunoadsorption and intravenous immunoglobulin (IVIG) administration may have beneficial effects in patients with dilated cardiomyopathy with end-stage heart failure. We investigated the effect of immunoadsorption with subsequent IVIG administration on cardiac function and symptoms in patients on optimal medical treatment (OMT) for heart failure (HF) with recent-onset cardiomyopathy during long-term follow-up. Methods: Thirty-five patients with recent-onset of HF symptoms received intensive guideline-recommended medical HF therapy for 5.2 months. Subsequently, all patients received a single cycle of immunoadsorption for five days followed by IVIG administration. During the 29-month follow-up period, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF) and N-terminal pro brain natriuretic peptide (NT-proBNP) were evaluated. Changes in quality of life (QoL) were assessed using the Minnesota Living with HF Questionnaire. Results: Three months after immunoadsorption, NYHA functional class improved from 2.0 to 1.5 (p < 0.005) and LVEF significantly increased from 27.0% to 39.0% (p < 0.0001). Long-term follow-up of 29 months showed stable NYHA functional class and a further moderate increase in LVEF from 39.0% to 42.0% (p < 0.0001) accompanied by a significant improvement in NT-proBNP and QoL scores. Conclusion: Immunoadsorption followed by IVIG administration further enhances LVEF, HF symptoms, QoL and biomarkers in patients with recent-onset HF on OMT

Tbx20 Is an Essential Regulator of Embryonic Heart Growth in Zebrafish.

The molecular mechanisms that regulate cardiomyocyte proliferation during embryonic heart growth are not completely deciphered yet. In a forward genetic N-ethyl-N-nitrosourea (ENU) mutagenesis screen, we identified the recessive embryonic-lethal zebrafish mutant line weiches herz (whz). Homozygous mutant whz embryos display impaired heart growth due to diminished embryonic cardiomyocyte proliferation resulting in cardiac hypoplasia and weak cardiac contraction. By positional cloning, we found in whz mutant zebrafish a missense mutation within the T-box 20 (Tbx20) transcription factor gene leading to destabilization of Tbx20 protein. Morpholino-mediated knock-down of Tbx20 in wild-type zebrafish embryos phenocopies whz, indicating that the whz phenotype is due to loss of Tbx20 function, thereby leading to significantly reduced cardiomyocyte numbers by impaired proliferation of heart muscle cells. Ectopic overexpression of wild-type Tbx20 in whz mutant embryos restored cardiomyocyte proliferation and heart growth. Interestingly, ectopic overexpression of Tbx20 in wild-type zebrafish embryos resulted, similar to the situation in the embryonic mouse heart, in significantly reduced proliferation rates of ventricular cardiomyocytes, suggesting that Tbx20 activity needs to be tightly fine-tuned to guarantee regular cardiomyocyte proliferation and embryonic heart growth in vivo

Atrial Fibrillation Predicts Long-Term Outcome after Transcatheter Edge-to-Edge Mitral Valve Repair by MitraClip Implantation

Background: Atrial fibrillation is common in patients with mitral regurgitation (MR) and has a negative impact on the clinical outcome of patients with valvular heart disease. We aimed to evaluate the impact of pre-procedural atrial fibrillation on the long-term clinical outcomes of patients with MR undergoing transcatheter mitral valve repair by MitraClip implantation. Methods: We analysed 355 consecutive patients with and without atrial fibrillation with symptomatic, severe MR and inoperability or high surgical risk undergoing MitraClip implantation in a three-year follow-up. Results: In patients with pre-procedural atrial fibrillation undergoing MitraClip implantation, we found advanced age, higher baseline NT-pro-BNP levels, increased left atrial diameter, and higher rate of severe tricuspid regurgitation, compared to patients with sinus rhythm. In the three-year follow-up after MitraClip implantation, mortality and major adverse cardiovascular and cerebral events (MACCE) occur significantly more often in patients with atrial fibrillation, compared to patients without atrial fibrillation. Multivariate regression analysis confirmed atrial fibrillation (hazard ratio 2.39, 95%-confidence interval 1.06⁻5.41, p = 0.036) as an independent predictor for three-year-mortality after MitraClip implantation. Conclusions: Atrial fibrillation is an independent predictor for long-term mortality after MitraClip implantation. We demonstrate the association of atrial fibrillation with mortality and MACCE in the long-term follow-up of patients undergoing MitraClip implantation

Epidemiological Trends in Patients Undergoing Mitral Valve Transcatheter Edge-to-Edge Repair over the Last Decade: Functional vs. Structural Mitral Regurgitation

Objective: We aimed to investigate the demographic, clinical and hemodynamic characteristics of patients who underwent percutaneous mitral valve (MV) repair over the last decade, as well as to determine the potential changes in trends of these parameters among patients with structural and functional MR (SMR and FMR). Methodology: We analyzed all patients who underwent interventional MV repair in our institution between January 2010 and March 2021. Our study included both SMR and FMR patients. All data were obtained from a local registry. Results: Nine hundred and seventeen patients (357 SMR patients and 563 FMR patients) were involved in this study. We did not find significant differences in demographical, clinical and hemodynamic characteristics among SMR and FMR patients. Left ventricular remodeling and systolic dysfunction were more pronounced in FMR patients. Systemic vascular resistance was the only hemodynamic parameter that differed between SMR and FMR patients; it was higher in SMR group. An evaluation of the trend between the first and last five years of our experience revealed that the number of patients treated with this technique is constantly increasing, but that this is more pronounced in SMR patients. It was also found that the operative risk of SMR and FMR patients was significantly higher in the first five years. Additionally, our results showed change in medical therapy in MR patients over the last decade in terms of increased use of angiotensin II receptor blockers and the introduction of angiotensin receptor II blocker-neprilysin inhibitor. Conclusion: SMR and FMR patients who underwent interventional MV repair have similar clinical and hemodynamic characteristics. The percentage of SMR patients increased more significantly than FMR patients over the last five years

Effects of the <i>whz</i> mutation on embryonic heart morphology and growth.

<p><b>(A-D)</b> Lateral view of wild-type (wt; <b>A, C</b>) and <i>whz</i> mutant (<b>B, D</b>) embryos at 72 hours post fertilization (hpf). <i>Whz</i> mutants show pericardial edema, blood congestion at the cardiac inflow tract and stretched heart chambers. <b>(E, F)</b> Hematoxylin and Eosin staining of sagittal histological sections of wt <b>(E)</b> and <i>whz</i> mutant <b>(F)</b> hearts at 72 hpf. Similar to wild-types, in <i>whz</i> atria and ventricles, myocardial (myo) and endocardial (endo) cell layers are clearly defined and separated by an atrio-ventricular canal (AVC). In contrast to wild-type hearts, <i>whz</i> mutant ventricles appear small and the myocardium monolayered. <b>(G-I)</b> Dissected wt <b>(G)</b> and <i>whz</i> mutant <b>(H)</b> hearts at 72 hpf, stained with a cardiomyocyte-specific MEF-2 antibody (nuclei; red) and co-stained with S46, exclusively marking atrial cardiomyocytes (green)<b>. (I)</b> <i>whz</i> mutant hearts show significantly reduced ventricular cardiomyocytes at 72 hpf (sib: 144.2±10 SD and <i>whz</i>: 94.9±10 SD, n = 10; p<0.0001), whereas cardiomyocyte numbers are comparable between wt and <i>whz</i> ventricles at 48 hpf (wt: 93.4±10 SD and <i>whz</i>: 88.2±10 SD, n = 10; p>0.05).</p

Overexpression of <i>tbx20</i> in wild-type zebrafish embryos results in reduced ventricular cardiomyocyte proliferation.

<p><b>(A, B)</b> Dissected wild-type hearts injected with KCl <b>(A)</b> and <i>tbx20</i> mRNA <b>(B)</b> at 72 hpf, stained against MEF-2 (red) after incorporation of 5-ethynyl-2'-deoxyuridine (EdU; green) to visualize the effect of <i>tbx20</i> overexpression on cardiomyocyte proliferation. <b>(C)</b> Wild-type zebrafish hearts injected with wild-type <i>tbx20</i> mRNA show significantly reduced numbers of ventricular cardiomyocytes at 72 hpf compared to control injected hearts (wt+KCl: 148.6±2.9; wt + <i>tbx20</i> mRNA: 64.0±2.017, n = 10, p< 0.0002). <b>(D)</b> Ventricular cardiomyocyte proliferation in wild-type embryos injected with <i>tbx20</i> mRNA is significantly reduced compared to control injected embryos at 72 hpf (wt+KCl: 8.9 ± 0.38; wt+<i>tbx20</i> mRNA: 1.1±0.28, n = 10, p = 0.0001).</p