Heinrich-Heine-Universität Düsseldorf

Structural brain imaging parameters may successfully predict cognitive performance in neurodegenerative diseases but mostly fail to predict cognitive abilities in healthy older adults. One important aspect contributing to this might be sex differences. Behaviorally, older males and females have been found to differ in terms of cognitive profiles, which cannot be captured by examining them as one homogenous group. In the current study, we examined whether the prediction of cognitive performance from brain structure, i.e. region-wise grey matter volume (GMV), would benefit from the investigation of sex-specific cognitive profiles in a large sample of older adults (1000BRAINS; N = 634; age range 55–85 years). Prediction performance was assessed using a machine learning (ML) approach. Targets represented a) a whole-sample cognitive component solution extracted from males and females, and b) sex-specific cognitive components. Results revealed a generally low predictability of cognitive profiles from region-wise GMV. In males, low predictability was observed across both, the whole sample as well as sex-specific cognitive components. In females, however, predictability differences across sex-specific cognitive components were observed, i.e. visual working memory (WM) and executive functions showed higher predictability than fluency and verbal WM. Hence, results accentuated that addressing sex-specific cognitive profiles allowed a more fine-grained investigation of predictability differences, which may not be observable in the prediction of the whole-sample solution. The current findings not only emphasize the need to further investigate the predictive power of each cognitive component, but they also emphasize the importance of sex-specific analyses in older adults.

Insulin action in the human brain modulates eating behaviour, whole-body metabolism and body fat distribution1,2. In particular, brain insulin action increases whole-body insulin sensitivity, but these studies were mainly performed in lean men3,4. Here we investigate metabolic and hypothalamic effects of brain insulin action in women with a focus on the impact of menstrual cycle (ClinicalTrials.gov registration: NCT03929419). Eleven women underwent four hyperinsulinemic–euglycemic clamps, two in the follicular phase and two in the luteal phase. Brain insulin action was introduced using nasal insulin spray5–7 and compared to placebo spray in a fourfold crossover design with change in glucose infusion rate as the primary endpoint. Here we show that during the follicular phase, more glucose has to be infused after administration of nasal insulin than after administration of placebo. This remains significant after adjustment for blood glucose and insulin. During the luteal phase, no significant influence of brain insulin action on glucose infusion rate is detected after adjustment for blood glucose and insulin (secondary endpoint). In 15 other women, hypothalamic insulin sensitivity was assessed in a within-subject design by functional magnetic resonance imaging with intranasal insulin administration⁸. Hypothalamus responsivity is influenced by insulin in the follicular phase but not the luteal phase. Our study therefore highlights that brain insulin action improves peripheral insulin sensitivity also in women but only during the follicular phase. Thus, brain insulin resistance could contribute to whole-body insulin resistance in the luteal phase of the menstrual cycle.

Background Eosinophilic granulomatosis with polyangiitis (EGPA) is often associated with glucocorticoid-dependent asthma and/or ear, nose and throat (ENT) manifestations. When immunosuppressants and/or mepolizumab are ineffective, dupilumab could be an option. We describe the safety and efficacy of off-label use of dupilumab in relapsing and/or refractory EGPA. Patients and methods We conducted an observational multicentre study of EGPA patients treated with dupilumab. Complete response was defined by Birmingham Vasculitis Activity Score (BVAS)=0 and prednisone dose ≤4 mg/day, and partial response by BVAS=0 and prednisone dose >4 mg/day. Eosinophilia was defined as an eosinophil count >500/mm ³ . Results Fifty-one patients were included. The primary indication for dupilumab was disabling ENT symptoms in 92%. After a median follow-up of 13.1 months, 18 patients (35%) reported adverse events (AEs), including two serious AEs. Eosinophilia was reported in 34 patients (67%), with a peak of 2195/mm3 (IQR 1268–4501) occurring at 13 weeks (IQR 4–36) and was associated with relapse in 41%. Twenty-one patients (41%) achieved a complete response and 12 (24%) a partial response. Sixteen (31%) patients experienced an EGPA relapse while on dupilumab, which was associated with blood eosinophilia in 14/16 (88%) patients. The median eosinophil count at the start of dupilumab was significantly lower in relapsers than in non-relapsers, as was the median time between stopping anti-IL-5/IL-5R and switching to dupilumab. Conclusion These results suggest that dupilumab may be effective in treating patients with EGPA-related ENT manifestations. However, EGPA flares occurred in one-third of patients and were preceded by eosinophilia in 88%, suggesting that caution is required.

Microbial volatile metabolite 2-methylisoborneol (2-MIB) causes odor and taste issues in drinking water, making it unappealing for human consumption. It has been suggested that 2-MIB biosynthesis consists of two main steps, namely, methylation of geranyl diphosphate into 2-methyl geranyl diphosphate by geranyl diphosphate methyl transferase (GPPMT) and subsequent cyclization into 2-MIB by 2-MIB synthase (MIBS). Pseudanabaena foetida var. intermedia is a 2-MIB-producing cyanobacterium whose GPPMT and MIBS enzymes are encoded by adjacent mtf and mtc genes . The present study identified a 2-MIB-related gene cluster composed of cnb A, mtf , mtc , and cnb B genes in P . foetida var. intermedia . The two homologous cyclic nucleotide-binding protein genes, cnb A and cnb B, were detected adjacent to the mtf and mtc genes, respectively. The nucleotide sequence of the cnb A- mtf-mtc-cnb B gene cluster showed 99.55% identity with 2-MIB synthesis-associated gene cluster of Pseudanabaena sp. dqh15. RT-PCR results revealed that mtf and mtc genes are co-expressed, while cnb A and cnb B genes are expressed independently in P . foetida var. intermedia . To investigate whether only mtf and mtc genes are sufficient for 2-MIB synthesis, the two-gene unit ( mtf-mtc ) was introduced into Escherichia coli strain JM109 via overexpression vector pYS1C. Gas chromatograph-mass spectrometry results showed that the E. coli strain transformed with mtf-mtc was able to produce 2-MIB. The intracellular 2-MIB level in P . foetida var. intermedia was higher than the extracellular 2-MIB level, while the transformed E. coli strain showed an opposite trend. Growth inhibition was observed in the 2-MIB-producing transformed E. coli strain. IMPORTANCE Contamination of drinking water with odiferous microbial metabolite 2-MIB is a worldwide concern. Removal of 2-MIB from drinking water burdens the water purification process. Therefore, it is important to search for alternative methods, such as suppressing the production of 2-MIB by aquatic microorganisms. For that, it is necessary to expand the current knowledge about the mechanism of 2-MIB synthesis at the genetic level. This study revealed that mtf and mtc genes of the 2-MIB-related gene cluster are transcribed as a single unit in P . foetida var. intermedia , and the expression of both mtf and mtc genes is essential and sufficient for 2-MIB synthesis in E. coli heterologous gene expression system.

The term Silk Road was created in the Middle Ages for a rather low spectrum of streets (roads) being used to transport goods from China to Europe and back, passing different cultures. However, not only goods had been and are still today (intensively) spread along this pathway, but also agents of (often) severe diseases. Thus, constant control systems have to be established and permanently controlled with respect to their efficacy. Today, it takes only a few days (if not hours) until persons, goods, and agents of diseases are transported from one continent to the other. The old and the present pathways are enlarged daily, thus increasing the worldwide network.

The so-called Silk Road connected during the Middle Ages regions of China of our days to Southern regions in Europe, passing countries like Iran, Iraq, Kazakhstan, etc., of our days, since European people wanted materials and products based on silk. These East-Western connections led to cultural connections as well as to the exchange and transfer of severe bacterial diseases like plague and cholera as well as viral diseases like Spring-summer-meningo-encephalitis/tick-borne encephalitis (Fig. 6.1).

Dizziness is a common symptom in medicine. The anamnesis and detection of a nystagmus is essential to distinguish a vertigo's pathogenesis. The diagnosis is complex, expensive, and not always available across the board. We present a novel location- and time-independent mobile application for videonystagmography (VNG) to support vertigo patients and medical staff. No additional hardware is necessary. The app uses artificial intelligence for eye tracking and to detect a horizontal nystagmus. A feasibility study of the mobile VNG with 13 healthy volunteers was performed. Each participant underwent a caloric vestibular testing to provoke the presence of a vestibular nystagmus. It could be shown that a smartphone-based VNG is possible.

Let F q \mathbb{F}_{q} be the finite field with 𝑞 elements and consider the 𝑛-dimensional F q \mathbb{F}_{q} -vector space V = F q n V=\mathbb{F}_{q}^{n} . In this paper, we define a closure operator on the subgroup lattice of the group G = PGL ⁢ ( V ) G=\mathrm{PGL}(V) . Let 𝜇 denote the Möbius function of this lattice. The aim is to use this closure operator to characterize subgroups 𝐻 of 𝐺 for which μ ⁢ ( H , G ) ≠ 0 \mu(H,G)\neq 0 . Moreover, we establish a polynomial bound on the number c ⁢ ( m ) c(m) of closed subgroups 𝐻 of index 𝑚 in 𝐺 for which the lattice of 𝐻-invariant subspaces of 𝑉 is isomorphic to a product of chains. This bound depends only on 𝑚 and not on the choice of 𝑛 and 𝑞. It is achieved by considering a similar closure operator for the subgroup lattice of GL ⁢ ( V ) \mathrm{GL}(V) and the same results proven for this group.

Background Large Impella systems (5.0 or 5.5; i.e., Impella 5+) (Abiomed Inc., Danvers, MA, USA) help achieve better clinical outcomes through relevant left ventricular unloading in acute cardiogenic shock (CS). Here, we report our experience with Impella 5+, while focusing on the clinical outcomes depending on individual case scenarios in patients with acute CS. Methods This single‐center retrospective observational study included 100 Impella 5+ implantations conducted on patients with acute CS from November 2018 to October 2021. After excluding 10 reimplantation cases, 90 cases were enrolled for further analysis. Results In‐hospital and 30‐day mortality rates were 56.7% ( n = 51) and 48.9% ( n = 44), respectively. In‐hospital mortality was lower in patients with acute myocardial infarction (AMI) than in non‐AMI patients ( p = 0.07). Young age and low lactate levels were the independent predictors of successful transition and survival after permanent mechanical circulatory support/heart transplantation (pMCS/HTX) (age, p = 0.03; lactate level, p = 0.04; survived after pMCS/HTX, n = 11; died on Impella, n = 41). During simultaneous utilization of venoarterial extracorporeal membrane oxygenation therapy and Impella 5+, termed ECMELLA therapy, high dose of noradrenaline was a predictive factor for in‐hospital mortality by multivariate analysis ( n = 0.02). Conclusions Our results suggest that enhanced Impella support might have better clinical outcomes among acute CS patients supported with large Impella, those with AMI than those with no AMI. Young age and low lactate levels were predictors of successful bridging to pMCS/HTX and favorable clinical outcomes thereafter. The clinical outcomes of ECMELLA therapy might depend on noradrenaline dose at the time of Impella 5+ implantation.

Specialized psychotherapeutic treatments like dialectical behavioral therapy (DBT) are recommended as first treatment for borderline personality disorder (BPD). In recent years, studies have emerged that focus on repetitive transcranial magnetic stimulation (rTMS) in BPD. Both have independently demonstrated efficacy in the treatment of BPD. Intermitted theta burst stimulation (iTBS), a modified design of rTMS, is thought to increase the excitability of neurons and could be a supplement to psychotherapy in addition to being a standalone treatment. However, no studies to date have investigated the combination of DBT and rTMS/iTBS. This study protocol describes the methods and design of a randomized, single-blinded, sham-controlled clinical pilot study in which BPD patients will be randomly assigned to either iTBS or sham during four consecutive weeks (20 sessions in total) in addition to standardized DBT treatment. The stimulation will focus on the unilateral stimulation of the left dorsolateral prefrontal cortex (DLPFC), which plays an important role in the control of impulsivity and risk-taking. Primary outcome is the difference in borderline symptomatology, while secondary target criteria are depressive symptoms, general functional level, impulsivity and self-compassion. Statistical analysis of therapy response will be conducted by Mixed Model Repeated Measurement using a 2 × 2-factorial between-subjects design with the between-subject factor stimulation (TMS vs. Sham) and the within-subject factor time (T0 vs. T1). Furthermore, structural magnetic resonance imaging (MRI) will be conducted and analyzed. The study will provide evidence and insight on whether iTBS has an enhancing effect as add-on to DBT in BPD. Trial registration: drks.de (DRKS00020413) registered 13/01/2020.

Atrial tachycardias (AT) occurring in patients after previous atrial fibrillation (AF) ablation are increasingly observed in clinical practice. Catheter ablation is the treatment of choice but an optimal workflow to improve patient outcome has not been defined. The purpose of this study was to assess procedural and clinical outcome depending on baseline rhythm at the beginning of AT ablation. A total of 380 patients (69 (61–75) years, 56.6% male) who underwent catheter ablation for consecutive AT after previous AF ablation were studied. At the beginning of the procedure, 140 patients (36.8%) presented in sinus rhythm (SR), 208 (54.7%) with AT and 32 (8.4%) with AF. Patients in SR or with AT underwent shorter procedures (173 (132–213) minutes vs. 161 (120–203) minutes vs. 226 (154–249) minutes; p = 0.002) with more frequent termination to SR (87.9% vs. 81.3% vs. 56.3%; p < 0.001) than patients with AF. Acute procedural success did not differ between patients in SR or with AT but was higher compared to those with AF (96.4% vs. 97.1% vs. 87.5%; p = 0.033). During a follow-up of 290 (181–680) days, patients in baseline SR experienced arrhythmia recurrences less often (36.4% vs. 49.5% vs. 68.8%; p = 0.002) than patients with AT or AF. Baseline rhythm during AT ablation predicts procedural and clinical outcome. Whereas acute procedural success does not differ between patients in SR or with AT, patients presenting in SR have a more favorable mid-term success rate.

Background The SARS-CoV-2 pandemic and its influence on peripartum processes worldwide led to issues in breastfeeding support. Research Aim The aim of this study was to describe breastfeeding behavior and peripartum in-hospital management during the pandemic in Germany and Austria. Methods This study was a descriptive study using a combination of secondary longitudinal data and a cross-sectional online survey. Registry data from the prospective multicenter COVID-19 Related Obstetric and Neonatal Outcome Study (CRONOS) cohort study (longitudinal, medical records of 1,815 parent-neonate pairs with confirmed SARS-CoV-2 infection during pregnancy) and a cross-sectional online survey of CRONOS hospitals’ physicians ( N = 67) were used for a descriptive comparison of feeding outcomes and postpartum management. Results In 93.7% (n = 1700) of the cases in which information on the neonate's diet was provided, feeding was with the mother’s own milk. Among neonates not receiving their mother’s own milk, 24.3% ( n = 26) reported SARS-CoV-2 infection as the reason. Peripartum maternal SARS-CoV-2 infection, severe maternal COVID-19 including the need for intensive care unit (ICU) treatment or invasive ventilation, preterm birth, mandatory delivery due to COVID-19, and neonatal ICU admission were associated with lower rates of breastfeeding. Rooming-in positively influenced breastfeeding without affecting neonatal SARS-CoV-2 frequency (4.2% vs. 5.6%). CRONOS hospitals reported that feeding an infant their mother’s own milk continued to be supported during the pandemic. In cases of severe COVID-19, four of five hospitals encouraged breastfeeding. Conclusion Maintaining rooming-in and breastfeeding support services in the CRONOS hospitals during the pandemic resulted in high breastfeeding rates.

Patients with potential or proven cardiovascular diseases represent a relevant proportion of the total spectrum in the emergency department. Their monitoring for cardiovascular surveillance until the diagnostics and acute treatment are initiated, often poses an interdisciplinary and interprofessional challenge, because resources are limited, nevertheless a high level of patient safety has to be ensured and the correct procedure has a major prognostic significance. This consensus paper provides an overview of the practical implementation, the modalities of monitoring and the application in a selection of cardiovascular diagnoses. The article provides specific comments on the clinical presentations of acute coronary syndrome, acute heart failure, cardiogenic shock, hypertensive emergency events, syncope, acute pulmonary embolism and cardiac arrhythmia. The level of evidence is generally low as no randomized trials are available on this topic. The recommendations are intended to supplement or establish local standards and to assist all physicians, nursing personnel and the patients to be treated in making decisions about monitoring in the emergency department.

Herein, we report two new isotypic semiconductive metal phosphonate frameworks Co2[1,4‐NDPA] and Zn2[1,4‐NDPA] (1,4‐NDPA4– is 1,4‑naphthalenediphosphonate). Co2[1,4‐NDPA] and Zn2[1,4‐NDPA] have optical bandgaps of 1.7 eV and 2.5 eV respectively, which are within the semiconductive regime. The electrocatalyst derived from Co2[1,4‐NPDA] as a precatalyst generated a lower overpotential of 374 mV in the oxygen evolution reaction (OER) with a Tafel slope of 43 mV dec–1 at a current density of 10 mA cm–2 in alkaline electrolyte (1 mol L–1 KOH), which is indicative of remarkably superior reaction kinetics. Benchmarking of the oxygen evolution reaction, OER of Co2[1,4‐NPDA] materials as precatalyst coupled with nickel foam (NF) showed exceptional long‐term stability at a current density of 50 mA cm–2for water splitting compared to the state‐of‐the‐art Pt/C/RuO2@NF after 30 h in 1 mol L‐1 KOH. In order to further understand the OER mechanism, the transformation of Co2[1,4‐NPDA] into its electrocatalytically active species was investigated.

Patients with potential or proven cardiovascular diseases represent a relevant proportion of the total spectrum in the emergency department. Their monitoring for cardiovascular surveillance until the diagnostics and acute treatment are initiated, often poses an interdisciplinary and interprofessional challenge, because resources are limited, nevertheless a high level of patient safety has to be ensured and the correct procedure has a major prognostic significance. This consensus paper provides an overview of the practical implementation, the modalities of monitoring and the application in a selection of cardiovascular diagnoses. The article provides specific comments on the clinical presentations of acute coronary syndrome, acute heart failure, cardiogenic shock, hypertensive emergency events, syncope, acute pulmonary embolism and cardiac arrhythmia. The level of evidence is generally low as no randomized trials are available on this topic. The recommendations are intended to supplement or establish local standards and to assist all physicians, nursing personnel and the patients to be treated in making decisions about monitoring in the emergency department.