TY - JOUR A1 - Kittel-Schneider, Sarah A1 - Felice, Ethel A1 - Buhagiar, Rachel A1 - Lambregtse-van den Berg, Mijke A1 - Wilson, Claire A. A1 - Banjac Baljak, Visnja A1 - Vujovic, Katarina Savic A1 - Medic, Branislava A1 - Opankovic, Ana A1 - Fonseca, Ana A1 - Lupattelli, Angela T1 - Treatment of peripartum depression with antidepressants and other psychotropic medications: a synthesis of clinical practice guidelines in Europe JF - International Journal of Environmental Research and Public Health N2 - This study examined (1) the availability and content of national CPGs for treatment of peripartum depression, including comorbid anxiety, with antidepressants and other psychotropics across Europe and (2) antidepressant and other psychotropic utilization data as an indicator of prescribers' compliance to the guidelines. We conducted a search using Medline and the Guidelines International Network database, combined with direct e-mail contact with national Riseup-PPD COST ACTION members and researchers within psychiatry. Of the 48 European countries examined, we screened 41 records and included 14 of them for full-text evaluation. After exclusion of ineligible and duplicate records, we included 12 CPGs. Multiple CPGs recommend antidepressant initiation or continuation based on maternal disease severity, non-response to first-line non-pharmacological interventions, and after risk-benefit assessment. Advice on treatment of comorbid anxiety is largely missing or unspecific. Antidepressant dispensing data suggest general prescribers' compliance with the preferred substances of the CPG, although country-specific differences were noted. To conclude, there is an urgent need for harmonized, up-to-date CPGs for pharmacological management of peripartum depression and comorbid anxiety in Europe. The recommendations need to be informed by the latest available evidence so that healthcare providers and women can make informed, evidence-based decisions about treatment choices. KW - clinical practice guideline KW - depression KW - anxiety KW - antidepressant KW - psychotropic medications KW - peripartum Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262130 SN - 1660-4601 VL - 19 IS - 4 ER - TY - JOUR A1 - Gram, Maximilian A1 - Albertova, P. A1 - Schirmer, V. A1 - Blaimer, M. A1 - Gamer, M. A1 - Herrmann, M. J. A1 - Nordbeck, P. A1 - Jakob, P. M. T1 - Towards robust in vivo quantification of oscillating biomagnetic fields using Rotary Excitation based MRI JF - Scientific Reports N2 - Spin-lock based functional magnetic resonance imaging (fMRI) has the potential for direct spatially-resolved detection of neuronal activity and thus may represent an important step for basic research in neuroscience. In this work, the corresponding fundamental effect of Rotary EXcitation (REX) is investigated both in simulations as well as in phantom and in vivo experiments. An empirical law for predicting optimal spin-lock pulse durations for maximum magnetic field sensitivity was found. Experimental conditions were established that allow robust detection of ultra-weak magnetic field oscillations with simultaneous compensation of static field inhomogeneities. Furthermore, this work presents a novel concept for the emulation of brain activity utilizing the built-in MRI gradient system, which allows REX sequences to be validated in vivo under controlled and reproducible conditions. Via transmission of Rotary EXcitation (tREX), we successfully detected magnetic field oscillations in the lower nano-Tesla range in brain tissue. Moreover, tREX paves the way for the quantification of biomagnetic fields. KW - functional magnetic resonance imaging KW - Rotary EXcitation (REX) KW - oscillating biomagnetic fields Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300862 VL - 12 IS - 1 ER - TY - JOUR A1 - Lichter, Katharina A1 - Paul, Mila Marie A1 - Pauli, Martin A1 - Schoch, Susanne A1 - Kollmannsberger, Philip A1 - Stigloher, Christian A1 - Heckmann, Manfred A1 - Sirén, Anna-Leena T1 - Ultrastructural analysis of wild-type and RIM1α knockout active zones in a large cortical synapse JF - Cell Reports N2 - Rab3A-interacting molecule (RIM) is crucial for fast Ca\(^{2+}\)-triggered synaptic vesicle (SV) release in presynaptic active zones (AZs). We investigated hippocampal giant mossy fiber bouton (MFB) AZ architecture in 3D using electron tomography of rapid cryo-immobilized acute brain slices in RIM1α\(^{−/−}\) and wild-type mice. In RIM1α\(^{−/−}\), AZs are larger with increased synaptic cleft widths and a 3-fold reduced number of tightly docked SVs (0–2 nm). The distance of tightly docked SVs to the AZ center is increased from 110 to 195 nm, and the width of their electron-dense material between outer SV membrane and AZ membrane is reduced. Furthermore, the SV pool in RIM1α\(^{−/−}\) is more heterogeneous. Thus, RIM1α, besides its role in tight SV docking, is crucial for synaptic architecture and vesicle pool organization in MFBs. KW - active zone KW - acute brain slices KW - CA3 KW - electron tomography KW - high-pressure freezing KW - hippocampal mossy fiber bouton KW - RIM1α KW - SV pool KW - synaptic ultrastructure KW - presynaptic Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300913 VL - 40 IS - 12 ER - TY - JOUR A1 - Hebestreit, Helge A1 - Zeidler, Cornelia A1 - Schippers, Christopher A1 - de Zwaan, Martina A1 - Deckert, Jürgen A1 - Heuschmann, Peter A1 - Krauth, Christian A1 - Bullinger, Monika A1 - Berger, Alexandra A1 - Berneburg, Mark A1 - Brandstetter, Lilly A1 - Deibele, Anna A1 - Dieris-Hirche, Jan A1 - Graessner, Holm A1 - Gündel, Harald A1 - Herpertz, Stephan A1 - Heuft, Gereon A1 - Lapstich, Anne-Marie A1 - Lücke, Thomas A1 - Maisch, Tim A1 - Mundlos, Christine A1 - Petermann-Meyer, Andrea A1 - Müller, Susanne A1 - Ott, Stephan A1 - Pfister, Lisa A1 - Quitmann, Julia A1 - Romanos, Marcel A1 - Rutsch, Frank A1 - Schaubert, Kristina A1 - Schubert, Katharina A1 - Schulz, Jörg B. A1 - Schweiger, Susann A1 - Tüscher, Oliver A1 - Ungethüm, Kathrin A1 - Wagner, Thomas O. F. A1 - Haas, Kirsten T1 - Dual guidance structure for evaluation of patients with unclear diagnosis in centers for rare diseases (ZSE-DUO): study protocol for a controlled multi-center cohort study JF - Orphanet Journal of Rare Diseases N2 - Background In individuals suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis often extends over many years. Factors contributing to delayed diagnosis include health care professionals' limited knowledge of rare diseases and frequent (co-)occurrence of mental disorders that may complicate and delay the diagnostic process. The ZSE-DUO study aims to assess the benefits of a combination of a physician focusing on somatic aspects with a mental health expert working side by side as a tandem in the diagnostic process. Study design This multi-center, prospective controlled study has a two-phase cohort design. Methods Two cohorts of 682 patients each are sequentially recruited from 11 university-based German Centers for Rare Diseases (CRD): the standard care cohort (control, somatic expertise only) and the innovative care cohort (experimental, combined somatic and mental health expertise). Individuals aged 12 years and older presenting with symptoms and signs which are not explained by current diagnoses will be included. Data will be collected prior to the first visit to the CRD’s outpatient clinic (T0), at the first visit (T1) and 12 months thereafter (T2). Outcomes Primary outcome is the percentage of patients with one or more confirmed diagnoses covering the symptomatic spectrum presented. Sample size is calculated to detect a 10 percent increase from 30% in standard care to 40% in the innovative dual expert cohort. Secondary outcomes are (a) time to diagnosis/diagnoses explaining the symptomatology; (b) proportion of patients successfully referred from CRD to standard care; (c) costs of diagnosis including incremental cost effectiveness ratios; (d) predictive value of screening instruments administered at T0 to identify patients with mental disorders; (e) patients’ quality of life and evaluation of care; and f) physicians’ satisfaction with the innovative care approach. Conclusions This is the first multi-center study to investigate the effects of a mental health specialist working in tandem with a somatic expert physician in CRDs. If this innovative approach proves successful, it will be made available on a larger scale nationally and promoted internationally. In the best case, ZSE-DUO can significantly shorten the time to diagnosis for a suspected rare disease. KW - rare diseases KW - multi‑center cohort study KW - dual guidance Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300440 VL - 17 IS - 1 ER - TY - JOUR A1 - Egberts, Karin A1 - Fekete, Stefanie A1 - Häge, Alexander A1 - Hiemke, Christoph A1 - Scherf-Clavel, Maike A1 - Taurines, Regina A1 - Unterecker, Stefan A1 - Gerlach, Manfred A1 - Romanos, Marcel T1 - Therapeutisches Drug Monitoring zur Optimierung der Psychopharmakotherapie von Kindern und Jugendlichen: Update und Leitfaden für die Praxis JF - Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie N2 - Trotz verbesserter Evidenzbasis bestehen in der kinder- und jugendpsychiatrischen Pharmakotherapie viele Unsicherheiten über die Wirkung und Verträglichkeit der häufig off-label oder in Kombinationstherapie verordneten Medikamente. Gerade auch vor dem Hintergrund der in vielen Fällen notwendigen mittel- bis langfristigen Einnahme sollen unerwünschte Arzneimittelwirkungen in dieser Altersstufe möglichst minimiert und eine auf die individuellen Charakteristika der Patientin oder des Patienten zugeschnittene, effektive Dosierung gefunden werden. Kinder und Jugendliche scheinen nicht nur besonders anfällig für bestimmte unerwünschte Arzneimittelwirkungen, sondern sind auch iatrogenen Risiken durch Dosierungs- oder Applikationsfehler ausgesetzt, die zu Unter- oder Überdosierungen führen können mit entsprechend negativen Auswirkungen auf den Therapieerfolg. Neben einer strengen Indikationsstellung sind daher eine präzise Dosisfindung sowie systematische Überwachung der Sicherheit der Psychopharmakotherapie unverzichtbar. In diesem Artikel wird Therapeutisches Drug Monitoring als hilfreiches klinisches Instrument vorgestellt und beschrieben, wie dessen richtige Anwendung sowohl die Wirksamkeit als auch die Sicherheit und Verträglichkeit einer Psychopharmakotherapie im Kindes- und Jugendalter zum unmittelbaren Nutzen für die Patientinnen und Patienten verbessern kann. N2 - Despite the improved evidence base, many uncertainties remain in child and adolescent psychiatric pharmacotherapy about the efficacy and tolerability of drugs, which are often prescribed off-label or in combination therapy in this age group. Because medium- to long-term use is unavoidable in many cases, clinicians should minimize adverse drug reactions as far as possible and tailor an effective dosage to the individual characteristics of the patient. Not only are children and adolescents particularly vulnerable to certain adverse drug effects, they are also exposed to iatrogenic risks from dosing or application errors, which can lead to under- or overdosing with correspondingly negative effects on the success of the therapy. In addition to determining a strict indication, it is therefore essential to establish precise dosage and systematic monitoring of the safety of the psychopharmacotherapy. This article introduces therapeutic drug monitoring as a useful clinical tool and describes how its correct application in practice can improve the efficacy as well as the safety and tolerability of psychotropic therapy in children and adolescents for the immediate benefit of patients. T2 - Therapeutic drug monitoring to optimize psychopharmacotherapy in children and adolescents - Update and guidelines for practice KW - Psychopharmakotherapie KW - unerwünschte Arzneimittelwirkungen KW - Pharmakovigilanz KW - Therapeutisches Drug Monitoring KW - Qualitätssicherung KW - psychopharmacotherapy KW - adverse drug reactions KW - pharmacovigilance KW - therapeutic drug monitoring KW - quality assurance Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262038 SN - 1422-4917 SN - 1664-2880 VL - 50 IS - 2 ER - TY - JOUR A1 - Traub, Jan A1 - Otto, Markus A1 - Sell, Roxane A1 - Göpfert, Dennis A1 - Homola, György A1 - Steinacker, Petra A1 - Oeckl, Patrick A1 - Morbach, Caroline A1 - Frantz, Stefan A1 - Pham, Mirko A1 - Störk, Stefan A1 - Stoll, Guido A1 - Frey, Anna T1 - Serum phosphorylated tau protein 181 and neurofilament light chain in cognitively impaired heart failure patients JF - Alzheimer's Research & Therapy N2 - Background Chronic heart failure (HF) is known to increase the risk of developing Alzheimer’s dementia significantly. Thus, detecting and preventing mild cognitive impairment, which is common in patients with HF, is of great importance. Serum biomarkers are increasingly used in neurological disorders for diagnostics, monitoring, and prognostication of disease course. It remains unclear if neuronal biomarkers may help detect cognitive impairment in this high-risk population. Also, the influence of chronic HF and concomitant renal dysfunction on these biomarkers is not well understood. Methods Within the monocentric Cognition.Matters-HF study, we quantified the serum levels of phosphorylated tau protein 181 (pTau) and neurofilament light chain (NfL) of 146 extensively phenotyped chronic heart failure patients (aged 32 to 85 years; 15.1% women) using ultrasensitive bead-based single-molecule immunoassays. The clinical work-up included advanced cognitive testing and cerebral magnetic resonance imaging (MRI). Results Serum concentrations of NfL ranged from 5.4 to 215.0 pg/ml (median 26.4 pg/ml) and of pTau from 0.51 to 9.22 pg/ml (median 1.57 pg/ml). We detected mild cognitive impairment (i.e., T-score < 40 in at least one cognitive domain) in 60% of heart failure patients. pTau (p = 0.014), but not NfL, was elevated in this group. Both NfL (ρ = − 0.21; p = 0.013) and pTau (ρ = − 0.25; p = 0.002) related to the cognitive domain visual/verbal memory, as well as white matter hyperintensity volume and cerebral and hippocampal atrophy. In multivariable analysis, both biomarkers were independently influenced by age (T = 4.6 for pTau; T = 5.9 for NfL) and glomerular filtration rate (T = − 2.4 for pTau; T = − 3.4 for NfL). Markers of chronic heart failure, left atrial volume index (T = 4.6) and NT-proBNP (T = 2.8), were further cardiological determinants of pTau and NfL, respectively. In addition, pTau was also strongly affected by serum creatine kinase levels (T = 6.5) and ferritin (T = − 3.1). Conclusions pTau and NfL serum levels are strongly influenced by age-dependent renal and cardiac dysfunction. These findings point towards the need for longitudinal examinations and consideration of frequent comorbidities when using neuronal serum biomarkers. KW - Alzheimer’s dementia KW - heart failure KW - cognitive impairment KW - neurofilament light chain KW - phosphorylated tau protein KW - renal function KW - age Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300515 VL - 14 ER - TY - JOUR A1 - Dannhäuser, Sven A1 - Mrestani, Achmed A1 - Gundelach, Florian A1 - Pauli, Martin A1 - Komma, Fabian A1 - Kollmannsberger, Philip A1 - Sauer, Markus A1 - Heckmann, Manfred A1 - Paul, Mila M. T1 - Endogenous tagging of Unc-13 reveals nanoscale reorganization at active zones during presynaptic homeostatic potentiation JF - Frontiers in Cellular Neuroscience N2 - Introduction Neurotransmitter release at presynaptic active zones (AZs) requires concerted protein interactions within a dense 3D nano-hemisphere. Among the complex protein meshwork the (M)unc-13 family member Unc-13 of Drosophila melanogaster is essential for docking of synaptic vesicles and transmitter release. Methods We employ minos-mediated integration cassette (MiMIC)-based gene editing using GFSTF (EGFP-FlAsH-StrepII-TEV-3xFlag) to endogenously tag all annotated Drosophila Unc-13 isoforms enabling visualization of endogenous Unc-13 expression within the central and peripheral nervous system. Results and discussion Electrophysiological characterization using two-electrode voltage clamp (TEVC) reveals that evoked and spontaneous synaptic transmission remain unaffected in unc-13\(^{GFSTF}\) 3rd instar larvae and acute presynaptic homeostatic potentiation (PHP) can be induced at control levels. Furthermore, multi-color structured-illumination shows precise co-localization of Unc-13\(^{GFSTF}\), Bruchpilot, and GluRIIA-receptor subunits within the synaptic mesoscale. Localization microscopy in combination with HDBSCAN algorithms detect Unc-13\(^{GFSTF}\) subclusters that move toward the AZ center during PHP with unaltered Unc-13\(^{GFSTF}\) protein levels. KW - active zone KW - Unc-13 KW - MiMIC KW - presynaptic homeostasis KW - nanoarchitecture KW - localization microscopy KW - STORM KW - HDBSCAN Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-299440 SN - 1662-5102 VL - 16 ER - TY - JOUR A1 - Hübner, Theresa A1 - Wolfgang, Tanja A1 - Theis, Ann-Catrin A1 - Steber, Magdalena A1 - Wiedenmann, Lea A1 - Wöckel, Achim A1 - Diessner, Joachim A1 - Hein, Grit A1 - Gründahl, Marthe A1 - Kämmerer, Ulrike A1 - Kittel-Schneider, Sarah A1 - Bartmann, Catharina T1 - The impact of the COVID-19 pandemic on stress and other psychological factors in pregnant women giving birth during the first wave of the pandemic JF - Reproductive Health N2 - Background The onset of mental illness such as depression and anxiety disorders in pregnancy and postpartum period is common. The coronavirus induced disease 2019 (COVID-19) pandemic and the resulting public policy responses represent an exceptional situation worldwide and there are hints for adverse psychosocial impact, hence, the study of psychological effects of the pandemic in women during hospitalization for delivery and in the postpartum period is highly relevant. Methods Patients who gave birth during the first wave of the COVID-19 pandemic in Germany (March to June 2020) at the Department of Obstetrics and Gynecology, University of Würzburg, Germany, were recruited at hospital admission for delivery. Biosamples were collected for analysis of SARS-CoV-2 infection and various stress hormones and interleukin-6 (IL-6). In addition to sociodemographic and medical obstetric data, survey questionnaires in relation to concerns about and fear of COVID-19, depression, stress, anxiety, loneliness, maternal self-efficacy and the mother–child bonding were administered at T1 (delivery stay) and T2 (3–6 months postpartum). Results In total, all 94 recruited patients had a moderate concern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at T1 with a significant rise at T2. This concern correlated with low to low-medium general psychosocial stress levels and stress symptoms, and the women showed a significant increase of active coping from T1 to T2. Anxiety levels were low and the Edinburgh Postnatal Depression Scale showed a medium score of 5 with a significant (T1), but only week correlation with the concerns about SARS-CoV-2. In contrast to the overall good maternal bonding without correlation to SARS-CoV-2 concern, the maternal self-efficiency correlated negatively with the obstetric impairment caused by the COVID-19 pandemic. Conclusion Obstetric patients` concerns regarding SARS-CoV-2 and the accompanying pandemic increased during the course of the pandemic correlating positively with stress and depression. Of note is the increase in active coping over time and the overall good mother–child-bonding. Maternal self-efficacy was affected in part by the restrictions of the pandemic. KW - Covid-19 KW - stress KW - pregnancy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300189 VL - 19 IS - 1 ER - TY - JOUR A1 - Helaß, Madeleine A1 - Greinacher, Anja A1 - Götz, Sebastian A1 - Müller, Andreas A1 - Gündel, Harald A1 - Junne, Florian A1 - Nikendei, Christoph A1 - Maatouk, Imad T1 - Age stereotypes towards younger and older colleagues in registered nurses and supervisors in a university hospital: A generic qualitative study JF - Journal of Advanced Nursing N2 - Aim This study aimed to identify and compare age stereotypes of registered nurses and supervisors in clinical inpatient settings. Design Generic qualitative study using half‐standardized interviews. Method Nineteen face‐to‐face interviews and five focus groups (N = 50) were conducted with nurses of varying levels at a hospital of maximum medical care in Germany between August and November 2018 and were subjected to structured qualitative content analysis. Results Reflecting the ageing process and cooperation in mixed‐age teams, nursing staff and supervisors defined similar age stereotypes towards older and younger nurses reminiscent of common generational labels ‘Baby Boomers’ and Generations X. Their evaluation created an inconsistent and contradictory pattern differing to the respective work context and goals. Age stereotypes were described as both potentially beneficial and detrimental for the individual and the cooperation in the team. If a successfully implemented diversity management focuses age stereotypes, negative assumptions can be reduced and cooperation in mixed‐age teams can be considered beneficial. Conclusion Diversity management as measures against age stereotypes and for mutual acceptance and understanding should include staff from various hierarchical levels of the inpatient setting. KW - age stereotypes KW - nurses KW - older employees KW - qualitative approaches KW - supervisors KW - younger employees Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262751 VL - 78 IS - 2 SP - 471 EP - 485 ER - TY - JOUR A1 - Klenk, Christoph A1 - Hommers, Leif A1 - Lohse, Martin J. T1 - Proteolytic cleavage of the extracellular domain affects signaling of parathyroid hormone 1 receptor JF - Frontiers in Endocrinology N2 - Parathyroid hormone 1 receptor (PTH1R) is a member of the class B family of G protein-coupled receptors, which are characterized by a large extracellular domain required for ligand binding. We have previously shown that the extracellular domain of PTH1R is subject to metalloproteinase cleavage in vivo that is regulated by ligand-induced receptor trafficking and leads to impaired stability of PTH1R. In this work, we localize the cleavage site in the first loop of the extracellular domain using amino-terminal protein sequencing of purified receptor and by mutagenesis studies. We further show, that a receptor mutant not susceptible to proteolytic cleavage exhibits reduced signaling to G\(_s\) and increased activation of G\(_q\) compared to wild-type PTH1R. These findings indicate that the extracellular domain modulates PTH1R signaling specificity, and that its cleavage affects receptor signaling. KW - GPCRs KW - parathyroid hormone 1 receptor KW - matrix metalloproteinase KW - ectodomain cleavage KW - biased signaling Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262055 SN - 1664-2392 VL - 13 ER -