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Drews, Henning Johannes ; Wallot, Sebastian ; Brysch, Philip ; Berger-Johannsen, Hannah ; Weinhold, Sara Lena ; Mitkidis, Panagiotis ; Baier, Paul Christian ; Lechinger, Julia ; Roepstorff, Andreas ; Göder, Robert
Background/Objectives: Sharing the bed with a partner is common among adults and impacts sleep quality with potential implications for mental health. However, hitherto findings are contradictory and particularly polysomnographic data on co-sleeping couples are extremely rare. The present study aimed to investigate the effects of a bed partner's presence on individual and dyadic sleep neurophysiology.
Methods: Young healthy heterosexual couples underwent sleep-lab-based polysomnography of two sleeping arrangements: individual sleep and co-sleep. Individual and dyadic sleep parameters (i.e., synchronization of sleep stages) were collected. The latter were assessed using cross-recurrence quantification analysis. Additionally, subjective sleep quality, relationship characteristics, and chronotype were monitored. Data were analyzed comparing co-sleep vs. individual sleep. Interaction effects of the sleeping arrangement with gender, chronotype, or relationship characteristics were moreover tested.
Results: As compared to sleeping individually, co-sleeping was associated with about 10% more REM sleep, less fragmented REM sleep (p = 0.008), longer undisturbed REM fragments (p = 0.0006), and more limb movements (p = 0.007). None of the other sleep stages was significantly altered. Social support interacted with sleeping arrangement in a way that individuals with suboptimal social support showed the biggest impact of the sleeping arrangement on REM sleep. Sleep architectures were more synchronized between partners during co-sleep (p = 0.005) even if wake phases were excluded (p = 0.022). Moreover, sleep architectures are significantly coupled across a lag of ± 5min. Depth of relationship represented an additional significant main effect regarding synchronization, reflecting a positive association between the two. Neither REM sleep nor synchronization was influenced by gender, chronotype, or other relationship characteristics.
Conclusion: Depending on the sleeping arrangement, couple's sleep architecture and synchronization show alterations that are modified by relationship characteristics. We discuss that these alterations could be part of a self-enhancing feedback loop of REM sleep and sociality and a mechanism through which sociality prevents mental illness.
Maier, Hannes ; Lenarz, Thomas ; Agha-Mir-Salim, Parwis ; Agterberg, Martijn J. H. ; Anagiotos, Andreas ; Arndt, Susan ; Ball, Geoffrey R. ; Bance, Manohar ; Barbara, Maurizio ; Baumann, Uwe ; Baumgartner, Wolfgang ; Bernardeschi, Daniele ; Beutner, Dirk ; Bosman, Arjan ; Briggs, Robert ; Busch, Susan ; Caversaccio, Marco ; Dahm, Markus ; Dalhoff, Ernst ; Devèze, Arnaud ; Ebrahimi-Madiseh, Azadeh ; Fraysse, Bernard ; Frenzel, Henning ; Gavilán, Javier ; Ghoncheh, Mohammad ; Håkansson, Bo E. V. ; Hodgetts, William ; Hol, Myrthe Karianne Sophie ; Holland, Julian ; Holmberg, Marcus ; Huber, Alexander ; Jenkins, Herman ; Katiri, Roulla ; Kheirkhah, Kiana ; Koitschev, Assen ; Kompis, Martin ; Lanting, Cris ; Lassaletta, Luis ; Lerut, Bob ; Leuwer, Rudolf ; Linder, Thomas ; Löwenheim, Hubert Martin ; Lustig, Lawrence ; Mandavia, Rishi ; Manrique, Manuel ; Jorge Humberto, Martins ; Mertens, Griet ; Mlynski, Robert Arndt ; Mojallal, Hamidreza ; Monini, Simonetta ; Monksfield, Peter ; Müller, Alexander ; Mylanus, Emmanuel ; Nakajima, Hideko Heidi ; Neudert, Marcus ; Offeciers, Erwin ; Pfiffner, Flurin ; Pietsch, Markus ; Plontke, Stefan K.-R. ; Prenzler, Nils Kristian ; Profant, Milan ; Rahne, Torsten ; Rajan, Gunesh ; Ratuszniak, Anna ; Raufer, Stefan ; Ray, Jaydip ; Reinfeldt, Sabine ; Röösli, Christof ; Rosenbom, Tove ; Salcher, Rolf Benedikt ; Schönermark, Matthias ; Schwab, Burkard ; Skarżyński, Henryk ; Skarżyński, Piotr H. ; Snapp, Hillary ; Sprinzl, Georg ; Spearman, Michael ; Stenfelt, Stefan ; Stieger, Christof ; Tringali, Stephane ; Truy, Eric ; Tysome, James ; Van de Heyning, Paul ; Verhaert, Nicolas ; Wesarg, Thomas ; Westerkull, Patrik ; Wollenberg, Barbara ; Zahnert, Thomas ; Zarowski, Andrzej ; Snik, Ad
Nowadays, several options are available to treat patients with conductive or mixed hearing loss. Whenever surgical intervention is not possible or contra-indicated, and amplification by a conventional hearing device (e.g., behind-the-ear device) is not feasible, then implantable hearing devices are an indispensable next option. Implantable bone-conduction devices and middle-ear implants have advantages but also limitations concerning complexity/invasiveness of the surgery, medical complications, and effectiveness. To counsel the patient, the clinician should have a good overview of the options with regard to safety and reliability as well as unequivocal technical performance data. The present consensus document is the outcome of an extensive iterative process including ENT specialists, audiologists, health-policy scientists, and representatives/technicians of the main companies in this field. This document should provide a first framework for procedures and technical characterization to enhance effective communication between these stakeholders, improving health care.
Pedretti, Roberto F. E. ; Iliou, Marie-Christine ; Israel, Carsten Walter ; Abreu, Ana ; Miljoen, Hielko ; Corrà, Ugo ; Stellbrink, Christoph ; Gevaert, Andreas B. ; Theuns, Dominic A. M. J. ; Piepoli, Massimo F. ; Reibis, Rona Katharina ; Schmid, Jean Paul ; Wilhelm, Matthias ; Heidbuchel, Hein ; Völler, Heinz ; Ambrosetti, Marco ; Deneke, Thomas ; Cornelissen, Veronique ; Heinzel, Frank ; Davos, Constantinos H. ; Kudaiberdieva, Gulmira ; Frederix, Ines ; Svendsen, Jesper Hastrup ; Hansen, Dominique
Cardiac rehabilitation (CR) is a multidisciplinary intervention including patient assessment and medical actions to promote stabilization, management of cardiovascular risk factors, vocational support, psychosocial management, physical activity counselling, and prescription of exercise training. Millions of people with cardiac implantable electronic devices live in Europe and their numbers are progressively increasing, therefore, large subsets of patients admitted in CR facilities have a cardiac implantable electronic device. Patients who are cardiac implantable electronic devices recipients are considered eligible for a CR programme. This is not only related to the underlying heart disease but also to specific issues, such as psychological adaptation to living with an implanted device and, in implantable cardioverter-defibrillator patients, the risk of arrhythmia, syncope, and sudden cardiac death. Therefore, these patients should receive special attention, as their needs may differ from other patients participating in CR. As evidence from studies of CR in patients with cardiac implantable electronic devices is sparse, detailed clinical practice guidelines are lacking. Here, we aim to provide practical recommendations for CR in cardiac implantable electronic devices recipients in order to increase CR implementation, efficacy, and safety in this subset of patients.
Hildebrandt-Einfeldt, Lars ; Yap, Kenrick ; Paul, Mandy H. ; Stoffer, Carolin ; Zahn, Nadine ; Drakew, Alexander ; Lenz, Maximilian ; Vlachos, Andreas ; Deller, Thomas
The entorhino-dentate projection, i.e., the perforant pathway, terminates in a highly ordered and laminated fashion in the rodent dentate gyrus (DG): fibers arising from the medial entorhinal cortex (MEC) terminate in the middle molecular layer, whereas fibers arising from the lateral entorhinal cortex (LEC) terminate in the outer molecular layer of the DG. In rats and rabbits, a crossed entorhino-dentate projection exists, which originates from the entorhinal cortex (EC) and terminates in the contralateral DG. In contrast, in mice, such a crossed projection is reportedly absent. Using single and double mouse organotypic entorhino-hippocampal slice cultures, we studied the ipsi- and crossed entorhino-dentate projections. Viral tracing revealed that entorhino-dentate projections terminate with a high degree of lamina-specificity in single as well as in double cultures. Furthermore, in double cultures, entorhinal axons arising from one slice freely intermingled with entorhinal axons originating from the other slice. In single as well as in double cultures, entorhinal axons exhibited a correct topographical projection to the DG: medial entorhinal axons terminated in the middle and lateral entorhinal axons terminated in the outer molecular layer. Finally, entorhinal neurons were virally transduced with Channelrhodopsin2-YFP and stimulated with light, revealing functional connections between the EC and dentate granule cells. We conclude from our findings that entorhino-dentate projections form bilaterally in the mouse hippocampus in vitro and that the mouse DG provides a permissive environment for crossed entorhinal fibers.
Alber, Thomas ; Bartke, Jerzy ; Białkowska, Helena ; Bloomer, Matthew A. ; Bock, Rudolf ; Braithwaite, Wilfred J. ; Brinkmann, Dittmar ; Brockmann, Robert ; Bunčić, Predrag ; Chan, Phaikying ; Chase, S. I. ; Cramer, Pauline B. ; Cramer, John G. ; Derado, Ivan ; Eberlein, Björn ; Eckardt, Volker ; Eschke, Jürgen ; Ferenc, Daniel ; Fleischmann, B. ; Foka, Panagiota ; Freund, Peter ; Fuchs, Michael ; Gładysz-Dziaduś, Ewa ; Harris, John W. ; Hoffmann, Matthias ; Jacobs, Peter Martin ; Kabana, Sonia ; Kadija, Krešo ; Kosiec, Jacek ; Kowalski, Marek ; Lahanas, Michael ; Lee, Jae-Yun ; Ljubicic, Ante Jr. ; Margetis, Spyridon ; Mitchell, Jeffery Thomas ; Morse, Richard J. ; Nappi, Eugenio ; Odyniec, Grazyna Janina ; Paic, Guy ; Panagiotou, Apostolos D. ; Petridis, Athanasios ; Piper, Andreas ; Posa, Francesco ; Poskanzer, Arthur M. ; Pugh, Howel G. ; Rai, Gulshan ; Rauch, Wolfgang Hans ; Renfordt, Rainer Arno Ernst ; Retyk, Waldemar ; Roland, Gunther ; Rothard, Hermann ; Runge, Kay ; Sandoval, Andres ; Schambach, Joachim ; Schmitz, Norbert ; Schmoetten, Emile ; Schneider, Ingo ; Sendelbach, Ralf ; Seyboth, Peter ; Seyerlein, Jürgen ; Skrzypczak, Ewa ; Stefansky, Piotr ; Teitelbaum, Lawrence Paul ; Tonse, Shaheen ; Trainor, Thomas A. ; Vasileiadis, Georgios ; Vassiliou, Maria ; Wenig, Siegfried ; Wensveen, Martinus ; Wosiek, Barbara
We present the measured correlation functions for pi+ pi-, pi- pi- and pi+ pi+ pairs in central S+Ag collisions at 200 GeV per nucleon. The Gamov function, which has been traditionally used to correct the correlation functions of charged pions for the Coulomb interaction, is found to be inconsistent with all measured correlation functions. Certain problems which have been dominating the systematic uncertainty of the correlation analysis are related to this inconsistency. It is demonstrated that a new Coulomb correction method, based exclusively on the measured correlation function for pi+ pi- pairs, may solve the problem.
Gutwein, Paul ; Schramme, Anja ; Abdel-Bakky, Mohamed Sadek ; Doberstein, Kai ; Hauser, Ingeborg A. ; Ludwig, Andreas ; Altevogt, Peter ; Gauer, Stefan ; Hillmann, Anja ; Weide, Thomas ; Jespersen, Christine ; Eberhardt, Wolfgang ; Pfeilschifter, Josef
Background: The importance of the Notch signaling in the development of glomerular diseases has been recently described. Therefore we analyzed in podocytes the expression and activity of ADAM10, one important component of the Notch signaling complex. Methods: By Western blot, immunofluorescence and immunohistochemistry analysis we characterized the expression of ADAM10 in human podocytes, human urine and human renal tissue. Results: We present evidence, that differentiated human podocytes possessed increased amounts of mature ADAM10 and released elevated levels of L1 adhesion molecule, one well known substrate of ADAM10. By using specific siRNA and metalloproteinase inhibitors we demonstrate that ADAM10 is involved in the cleavage of L1 in human podocytes. Injury of podocytes enhanced the ADAM10 mediated cleavage of L1. In addition, we detected ADAM10 in urinary podocytes from patients with kidney diseases and in tissue sections of normal human kidney. Finally, we found elevated levels of ADAM10 in urinary vesicles of patients with glomerular kidney diseases. Conclusions: The activity of ADAM10 in human podocytes may play an important role in the development of glomerular kidney diseases.
Depta, Paul Frederik ; Halsch, Andreas Mario ; Hütig, Janine ; Mendizabal Cofré, Sebastian ; Philipsen, Owe
Thermal leptogenesis, in the framework of the standard model with three additional heavy Majorana neutrinos, provides an attractive scenario to explain the observed baryon asymmetry in the universe. It is based on the out-of-equilibrium decay of Majorana neutrinos in a thermal bath of standard model particles, which in a fully quantum field theoretical formalism is obtained by solving Kadanoff-Baym equations. So far, the leading two-loop contributions from leptons and Higgs particles are included, but not yet gauge corrections. These enter at three-loop level but, in certain kinematical regimes, require a resummation to infinite loop order for a result to leading order in the gauge coupling. In this work, we apply such a resummation to the calculation of the lepton number density. The full result for the simplest “vanilla leptogenesis” scenario is by O(1) increased compared to that of quantum Boltzmann equations, and for the first time permits an estimate of all theoretical uncertainties. This step completes the quantum theory of leptogenesis and forms the basis for quantitative evaluations, as well as extensions to other scenarios.
Berkner, Hanna ; Seutter von Loetzen, Christian ; Hartl, Maximilian ; Randow, Stefanie ; Gubesch, Michaela ; Vogel, Lothar ; Husslik, Felix ; Reuter, Andreas ; Lidholm, Jonas ; Ballmer-Weber, Barbara ; Vieths, Stefan ; Rösch, Paul ; Schiller, Dirk
Background: Birch pollen-allergic subjects produce polyclonal cross-reactive IgE antibodies that mediate pollen-associated food allergies. The major allergen Bet v 1 and its homologs in plant foods bind IgE in their native protein conformation. Information on location, number and clinical relevance of IgE epitopes is limited. We addressed the use of an allergen-related protein model to identify amino acids critical for IgE binding of PR-10 allergens.
Method: Norcoclaurine synthase (NCS) from meadow rue is structurally homologous to Bet v 1 but does not bind Bet v 1-reactive IgE. NCS was used as the template for epitope grafting. NCS variants were tested with sera from 70 birch pollen allergic subjects and with monoclonal antibody BV16 reported to compete with IgE binding to Bet v 1.
Results: We generated an NCS variant (Δ29NCSN57/I58E/D60N/V63P/D68K) harboring an IgE epitope of Bet v 1. Bet v 1-type protein folding of the NCS variant was evaluated by 1H-15N-HSQC NMR spectroscopy. BV16 bound the NCS variant and 71% (50/70 sera) of our study population showed significant IgE binding. We observed IgE and BV16 cross-reactivity to the epitope presented by the NCS variant in a subgroup of Bet v 1-related allergens. Moreover BV16 blocked IgE binding to the NCS variant. Antibody cross-reactivity depended on a defined orientation of amino acids within the Bet v 1-type conformation.
Conclusion: Our system allows the evaluation of patient-specific epitope profiles and will facilitate both the identification of clinically relevant epitopes as biomarkers and the monitoring of therapeutic outcomes to improve diagnosis, prognosis, and therapy of allergies caused by PR-10 proteins.
Paul, Puneet ; Simm, Stefan ; Blaumeiser, Andreas ; Scharf, Klaus-Dieter ; Fragkostefanakis, Sotirios ; Mirus, Oliver ; Schleiff, Enrico
Background: Protein translocation across membranes is a central process in all cells. In the past decades the molecular composition of the translocation systems in the membranes of the endoplasmic reticulum, peroxisomes, mitochondria and chloroplasts have been established based on the analysis of model organisms. Today, these results have to be transferred to other plant species. We bioinformatically determined the inventory of putative translocation factors in tomato (Solanum lycopersicum) by orthologue search and domain architecture analyses. In addition, we investigated the diversity of such systems by comparing our findings to the model organisms Saccharomyces cerevisiae, Arabidopsis thaliana and 12 other plant species.
Results: The literature search end up in a total of 130 translocation components in yeast and A. thaliana, which are either experimentally confirmed or homologous to experimentally confirmed factors. From our bioinformatic analysis (PGAP and OrthoMCL), we identified (co-)orthologues in plants, which in combination yielded 148 and 143 orthologues in A. thaliana and S. lycopersicum, respectively. Interestingly, we traced 82% overlap in findings from both approaches though we did not find any orthologues for 27% of the factors by either procedure. In turn, 29% of the factors displayed the presence of more than one (co-)orthologue in tomato. Moreover, our analysis revealed that the genomic composition of the translocation machineries in the bryophyte Physcomitrella patens resemble more to higher plants than to single celled green algae. The monocots (Z. mays and O. sativa) follow more or less a similar conservation pattern for encoding the translocon components. In contrast, a diverse pattern was observed in different eudicots.
Conclusions: The orthologue search shows in most cases a clear conservation of components of the translocation pathways/machineries. Only the Get-dependent integration of tail-anchored proteins seems to be distinct. Further, the complexity of the translocation pathway in terms of existing orthologues seems to vary among plant species. This might be the consequence of palaeoploidisation during evolution in plants; lineage specific whole genome duplications in Arabidopsis thaliana and triplications in Solanum lycopersicum.
Günther, Andreas ; Krauss, Ekaterina ; Tello, Silke ; Wagner, Jasmin ; Paul, Bettina ; Kuhn, Stefan ; Maurer, Olga ; Heinemann, Sabine ; Costabel, Ulrich ; Nieto Barbero, María Asunción ; Müller, Veronika ; Bonniaud, Philippe ; Vancheri, Carlo ; Wells, Athol ; Vasakova, Martina ; Pesci, Alberto ; Sofia, Matteo ; Klepetko, Walter ; Seeger, Werner ; Drakopanagiotakis, Fotios ; Crestani, Bruno
Background: Since 2009, IPF patients across Europe are recruited into the eurIPFreg, providing epidemiological data and biomaterials for translational research.
Methods: The registry data are based on patient and physician baseline and follow-up questionnaires, comprising 1700 parameters. The mid- to long-term objectives of the registry are to provide clues for a better understanding of IPF phenotype sub-clusters, triggering factors and aggravating conditions, regional and environmental characteristics, and of disease behavior and management.
Results: This paper describes baseline data of 525 IPF subjects recruited from 11/2009 until 10/2016. IPF patients had a mean age of 68.1 years, and seeked medical advice due to insidious dyspnea (90.1%), fatigue (69.2%), and dry coughing (53.2%). A surgical lung biopsy was performed in 32% in 2009, but in only 8% of the cases in 2016, possibly due to increased numbers of cryobiopsy. At the time of inclusion in the eurIPFreg, FVC was 68.4% ± 22.6% of predicted value, DLco ranged at 42.1% ± 17.8% of predicted value (mean value ± SD). Signs of pulmonary hypertension were found in 16.8%. Steroids, immunosuppressants and N-Acetylcysteine declined since 2009, and were replaced by antifibrotics, under which patients showed improved survival (p = 0.001).
Conclusions: Our data provide important insights into baseline characteristics, diagnostic and management changes as well as outcome data in European IPF patients over time.
Trial registration: The eurIPFreg and eurIPFbank are listed in ClinicalTrials.gov(NCT02951416).