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Calcium channel blockers and clinical outcomes in patients with continuous-flow left ventricular assist devices
No full textAims: Current guidelines suggest calcium channel blockers (CCBs) as the second or third option for blood pressure management in patients with left ventricular assist device (LVAD). However, the clinical outcomes of patients with LVAD who receive CCBs remain unclear. Our study aims to analyse the association of CCBs with clinical outcomes in patients after LVAD implantation. Methods and results:
This is a retrospective analysis based on the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) from 2006 to 2017, and adult patients who were alive with LVAD and CCB treatment information at 6 months after implantation were included. Among 10 717 patients, 1369 received CCBs 6 months after implantation, and there was an increasing trend of CCB use after LVAD. Patients receiving CCB therapy at 6 months had a similar 5 year survival rate to those not receiving CCB [49.6%, 95% confidence interval (CI): 47.5–51.7% vs. 51.1%, 95% CI: 45.3–56.7%]. In both Cox and competing risk regressions after adjusting for confounding factors, CCB treatment at 6 months after implantation was not associated with long-term mortality [hazard ratio (HR): 1.03, 95% CI: 0.91–1.17, P = 0.624 and subdistribution HR (SHR): 1.07, 95% CI: 0.95–1.22, P = 0.260]. Consistently, in time-varying models, CCB treatment was not linked to long-term mortality (HR: 0.97, 95% CI: 0.87–1.09, P = 0.682 and SHR: 1.05, 95% CI: 0.94–1.18, P = 0.359). This null association remained in subgroup analysis according to device strategy and propensity-matching analyses. Neurological dysfunction, stroke, bleeding, rehospitalization, and renal dysfunction were more likely to occur among those with CCB when compared with those without CCB treatment. Conclusions: In patients with LVAD, CCB therapy fails to show benefits in long-term survival and is associated with increased incidences of neurological dysfunction, bleeding, renal dysfunction, and rehospitalization
Cortisol and periodontitis: Prospective observational and Mendelian randomization studies
No full textPurpose: Cortisol has obesogenic, hyperglycemic and immunomodulating effects. Preclinical and observational research suggested that it is associated with periodontitis but the evidence for potential causality in humans is sparse. We triangulated results from prospective observational and Mendelian randomization (MR) analyses to further explore this. Methods: Using pooled data from 3,388 participants of two population cohort studies embedded in the Study of Health in Pomerania (SHIP) project, we associated serum cortisol levels with periodontal outcomes measured after a median follow-up time of 6.9 years, adjusting for confounding and selection bias using propensity score weighting and multiple imputation. We further examined the effect of genetically proxied plasma morning cortisol levels on periodontitis using two-sample MR of 17,353 cases and 28,210 controls. Results: In SHIP, we found that cortisol levels were positively associated with follow-up levels of mean clinical attachment level (CAL), deep interdental CAL and bleeding on probing but were unrelated to mean probing pocket depth and deep periodontal pockets. In MR analysis, cortisol was not associated with periodontitis.
Conclusion: The observational study revealed a prospective association of spot cortisol with makers of periodontitis. Contrary to observational studies, genetically instrumented, long-term cortisol was unrelated to periodontitis. Our results find no univocal evidence that cortisol plays a role in periodontitis pathology, casting doubt on cortisol-related pathways
Der Glaubenssinn:Begründung – Beschreibung – Beurteilung – Beziehungen
No full textWas ist die Rolle der Gläubigen in der Kirche und welchen Beitrag können sie zum Glaubensverständnis leisten? In der Diskussion dazu wird häufig auf den Glaubenssinn (sensus fidei) der Gläubigen verwiesen, der jedoch kein eindeutig geklärter Ausdruck ist. Darum wird in der Studie dessen Profil geschärft, indem ein systematisch-theologisches Gesamtkonzept des Glaubenssinns herausgearbeitet wird. Es entsteht ein strukturiertes Bild und ein klareres Verständnis des Glaubenssinns, indem der Glaubenssinn vom Wirken des Heiligen Geistes her konturiert, in seinem praktischen Vollzug ausführlich beschrieben, seine inhaltliche Ausrichtung bestimmt, die Bedeutung der Glaubensverständnisse der einzelnen Gläubigen begründet, die Erhebung des Glaubenssinns besprochen, das Konsensverständnis zur Feststellung des gemeinsamen, unfehlbaren Glaubens korrigiert sowie Kriterien dafür aufgezeigt werden. Es wird konsequent von der Offenbarung her argumentiert, die als Grund, Gehalt und Kriterium des Glaubens und somit auch des Glaubenssinns erwiesen und angewendet wird. Dadurch können offene Fragen geklärt, verschiedene Einseitigkeiten korrigiert und ein ausgewogenes sowie realitätsnahes und realisierbares Konzept gezeichnet werden
Dissociating different temporal stages of emotional word processing by feature-based attention
No full textNegative emotional content is prioritized across different stages of information processing as reflected by different components of the event-related potential (ERP). In this preregistered study (N = 40), we investigated how varying the attentional focus allows us to dissociate the involvement of specific ERP components in the processing of negative and neutral words. Participants had to discriminate the orientation of lines overlaid onto the words, the word type (adjective/noun), or the emotional content (negative/neutral). Thus, attention was either not focused on words (distraction task), non-emotional aspects, or the emotional relevance of words. Regardless of the task, there were no significant differences between negative and neutral words for the P1, N1, or P2 components. In contrast, interactions between emotion and task were observed for the early posterior negativity (EPN) and late positive potential (LPP). EPN differences were absent during the distraction task but were present in the other two tasks. LPP emotion differences were found only when attention was directed to the emotional content of words. Our study adds to the evidence that early ERP components do not reliably separate negative and neutral words. However, results show that mid-latency and late stages of emotion processing are separable by different attention tasks. The EPN represents a stage of attentional enhancement of negative words given sufficient attentional resources. Differential activations during the LPP stage are associated with more elaborative processing of the emotional meaning of words
Hoffnung auf Deep Empathy? Ärztliche Empathie im Zeitalter Künstlicher Intelligenz:Begriffsklärungen und mögliche Auswirkungen
No full textIm Kontext der Implementierung von KI-Anwendungen in der Medizin wird behauptet, dass KI zu mehr ärztlicher Empathie führen wird. Diese Arbeit hinterfragt diese These, die durch Eric Topol in "Deep Medicine" (2019) populär wurde. Es fehlt ihr an Definitionen, empirischen Grundlagen und komplexeren Analysen. Ziel dieser Arbeit ist es deshalb, den Begriff der (ärztlichen) Empathie zu schärfen, und zu untersuchen, wie KI-Medizin darauf Einfluss nehmen kann. Im Rahmen der Analyse werden drei Veränderungen im klinischen Alltag der KI-Medizin untersucht: Erfassung von Patientendaten, Zunahme technologischer Präsenz und Effizienzsteigerung. In Anbetracht der aktuellen Effizienzanforderungen ans Gesundheitssystem, kommt die Arbeit zum Ergebnis, dass eine Zunahme KI-basierter Behandlungsmethoden keineswegs einen Automatismus hin zu mehr ärztlicher Empathie bedeutet. Vielmehr wirbt diese Arbeit für einen differenzierten Blick auf die Einflussfaktoren von Empathie, die im KI-Zeitalter sogar noch mehr in den Blick genommen werden müssen.In the context of the implementation of AI applications in medicine, it is claimed that AI will lead to greater physician empathy. This paper questions this assumption, which was popularized by Eric Topol in "Deep Medicine" (2019). It lacks definitions, empirical foundations, and more complex analyses. Therefore, the aim of this paper is to refine the concept of (physicians) empathy and to examine how AI in medicine can influence it. The analysis investigates three changes in the clinical everyday life of AI medicine: the collection of patient data, the increase in technological presence, and efficiency enhancement. Considering the current efficiency demands on the healthcare system, the study concludes that an increase in AI-based treatment methods does not automatically lead to greater physician empathy. Rather, this paper advocates for a nuanced view of the factors influencing empathy, which need to be even more closely examined in the age of AI
Reversible photoregulation of cell-cell adhesions with opto-E-cadherin
No full textE-cadherin-based cell-cell adhesions are dynamically and locally regulated in many essential processes, including embryogenesis, wound healing and tissue organization, with dysregulation manifesting as tumorigenesis and metastasis. However, the lack of tools that would provide control of the high spatiotemporal precision observed with E-cadherin adhesions hampers investigation of the underlying mechanisms. Here, we present an optogenetic tool, opto-E-cadherin, that allows reversible control of E-cadherin-mediated cell-cell adhesions with blue light. With opto-E-cadherin, functionally essential calcium binding is photoregulated such that cells expressing opto-E-cadherin at their surface adhere to each other in the dark but not upon illumination. Consequently, opto-E-cadherin provides remote control over multicellular aggregation, E-cadherin-associated intracellular signalling and F-actin organization in 2D and 3D cell cultures. Opto-E-cadherin also allows switching of multicellular behaviour between single and collective cell migration, as well as of cell invasiveness in vitro and in vivo. Overall, opto-E-cadherin is a powerful optogenetic tool capable of controlling cell-cell adhesions at the molecular, cellular and behavioural level that opens up perspectives for the study of dynamics and spatiotemporal control of E-cadherin in biological processes
Tamm–Horsfall protein in humane urine: sex-dependent differences in the excretion and N-glycosylation pattern
No full textTamm–Horsfall protein (THP) is a highly N-glycosylated protein from epithelial cells of the ascending limb of Henle loop. It is secreted into the urine as part of the innate immune response against uropathogenic pathogens. As women are more likely to suffer from urinary tract infections, biomedical studies were conducted to investigate sex-differences in THP excretion, as well as differences in the THP N-glycosylation pattern. A total of 238 volunteers (92 men, 146 women, 69 with hormonal contraceptives) participated in this study, providing urine samples. Women showed a clear tendency to have higher THP concentration and excretion rates than men (p < 0.16). Regular intake of hormonal contraceptives had no significant influence on urinary THP concentration compared to no regular intake. The individual N-glycosylation pattern of THP in urine samples from randomly selected individuals (10 female, 10 male) was investigated after enzymatic release and MS analysis of the oligosaccharides. Female subjects tended to have an increased proportion of oligomannose type N-glycans and non-fucosylated glycans, whereas men had an increased proportion of fucosylated complex-type glycans. The higher level of oligomannose-type glycans in THP from women might be explained by a self-defence mechanism to overcome the higher infections pressure by the female anatomical properties
The Influence of Polyethylene Oxide Degradation in Polymer-Based Electrolytes for NMC and Lithium Metal Batteries
No full textA multilayered ternary solid polymer electrolyte (TSPE) is presented. First, the influence of polyethylene oxide degradation on cell failure, development of subsequent volatile degradation products, and cell impedance is analyzed. The low electrochemical stability window/oxidative stability (≥3.8 V) results in side-chain oxidation and loss of active material. Subsequently, electrolyte stability is improved and a thin-film (≤50 μm) TSPE with three functional layers is developed to match the wide-ranging electrolyte requirements toward Li metal anodes and different cathode materials like LiNi0.6Mn0.2Co0.2O2 and LiFePO4 (NCM622, LFP). The high-voltage stability of ≥4.75 V makes the TSPE a promising candidate in high-voltage applications. Because of high Coulombic efficiencies in NMC622‖Li metal (99.7%) and LFP‖Li metal (99.9%) cells, the presented electrolyte enables stable long-term cycling with great capacity retention of 86% and 94%, respectively. The temperature stability of >300 °C and the capability to prevent high surface area Li and dendrite formation (even at an areal capacity utilization of >40 mAh cm−2) contribute to high safety under a wide range of conditions
A systematic review: facial, dental and orthodontic findings and orofacial diagnostics in patients with FASD
No full textBackground: The fetal alcohol spectrum disorder is a group of developmental disorders caused by maternal alcohol consumption. Patients with fetal alcohol syndrome show abnormal orofacial features. This review presents an overview over the facial, oral, dental or orthodontic findings and diagnostic tools concerning these features. Methods: For this systematic review Cochrane, Medline and Embase databases were considered and the review was performed according to the PRISMA checklist. Two independent reviewers evaluated all studies and recorded results in a summary of findings table. Risk of bias was analyzed via Quadas-2 checklist. Results: 61 studies were eligible for inclusion. All included studies were clinical studies. Methods and results of the studies were not comparable, guidelines or methods for the detection of FASD varied across studies. Facial features most often measured or found as distinguishing parameter were: palpebral fissure length, interpupillary or innercanthal distance, philtrum, upper lip, midfacial hypoplasia or head circumference. Conclusions: This review shows that to date a multitude of heterogeneous guidelines exists for the diagnosis of FASD. Uniform, objective diagnostic criteria and parameters for the orofacial region in FASD diagnosis are needed. A bio database with values and parameters for different ethnicities and age groups should be made available for diagnosis
Changing Antiarrhythmic Drug Regimen in Patients with Amiodarone and Ablation Refractory Ventricular Tachyarrhythmias Is Associated with Increased Implantable Cardioverter Defibrillator Shocks—A Retrospective Analysis from a Large Tertiary Center
No full textBackground and Objective: Implantable Cardioverter Defibrillators (ICDs) are crucial in treating ventricular tachyarrhythmias (VTs) and preventing sudden cardiac death. However, ICD shocks are linked to higher mortality and a lower quality of life. Many patients suffer from recurrent VTs despite concomitant antiarrhythmic drug (AAD) therapy with amiodarone, and it is unclear if changing the AAD while on chronic amiodarone therapy is beneficial. Hence, we investigated the impact of changing the AAD on the incidence of appropriate ICD shocks in patients on chronic amiodarone, impaired LV function, and at least one previous VT ablation. Methods and Results: We retrospectively analyzed 131 ICD patients (LVEF < 40%) from a single-center registry. All were on chronic amiodarone and had undergone VT ablation. The mean age was 66.0 ± 12.8 years; 82.4% were male; and the follow-up period averaged 5.8 ± 0.6 years. Ischemic cardiomyopathy was present in 52.7% of patients. AAD therapy was changed in 49 patients (37.4%), primarily due to inefficacy (40.8%), intolerance (16.3%), or other reasons (42.9%). Of those, 8 received flecainide (≥200 mg) and 41 sotalol (≥240 mg); 82 (62.6%) continued amiodarone. VT re-ablation was performed in 23.7%. During follow-up, 11 patients (8.4%) died and 18 (13.7%) received appropriate ICD shocks—17 with changed AAD vs. 1 with continued amiodarone (p ≤ 0.01). A multivariate regression showed that switching from amiodarone to flecainide or sotalol was significantly associated with increased ICD shock risk (OR 34.9; 95% CI 4.3–283.8; p < 0.01). Conclusions: In patients on chronic amiodarone with severely impaired LV function and at least one previous VT ablation, changing AAD therapy to flecainide or sotalol is associated with an increased incidence of appropriate ICD shocks