Einfluss von multimodaler sportlicher Aktivität auf Kognition und Alltagskompetenz bei früher Alzheimer-Demenz (Sport&Kog) - Ennen, J C; Müller, Bernhard; Bibl, M; Esselmann, H; Rütten, Alfred; Platen, P; Trampisch, H J; Abu-Omar, Karim; Schade-Brittinger, C; Freese, J; Juckel, G; Meier, W; et al. (Zeitschrift für Gerontopsychologie und -psychiatrie, 2008)
Der vorliegende Bericht beschreibt ein vom Bundesministerium für Gesundheit gefördertes Vorhaben zum «Leucht- turmprojekt Demenz» im Themenfeld 1 «Therapie und Pflegemaßnahmen: Wirksamkeit unter Alltagsbedingungen». Hierbei handelt es sich um eine multizentrische randomisierte Interventionsstudie, die den Einfluss von Sport (multimodale sportliche Aktivität) unter kontrollierten Bedingungen auf die kognitive Entwicklung von Alzheimer-Patienten im frühen Stadium prüft. In einem zweiarmigen Design werden je 150 Patienten mit früher AD unter Verum- bzw. Kontroll-Bedingungen untersucht. Die Verum-Gruppe erhält ein spezifisches sportliches Trainingsprogramm. In der Kontrollgruppe werden lediglich Dehnungsübungen durchgeführt. Primäre Endpunkte der Studie sind die kognitive Leistung der Patienten sowie deren Alltagskompetenz im Verlauf. Die gesundheitsbezogene Lebensqualität der Patienten sowie etwaige Verhaltensstörungen und depressive Symptome werden als sekundäre Endpunkte erfasst. Darüber hinaus werden die Angehörigen zur krankheitsbezogenen Belastung befragt und auf depressive Symptome untersucht. Angelehnt an die Hypo- thesen der «Initiative Demenzversorgung in der Allgemeinmedizin» (IDA) sollen entsprechende nicht-medikamentöse Versorgungsan- gebote dazu beitragen, dass Patienten länger in ihrem gewohnten häuslichen Umfeld leben. Im Sinne der Nachhaltigkeit der zu erwar- tenden Ergebnisse wird ein «Do it yourself»-Manual erstellt, mit dem das Trainingsprogramm auch ohne professionelle Anleitung, z. B. im Rahmen von Selbsthilfegruppen durchgeführt werden kann. Die weitere Implementierung (z. B. in Internetforen und weiteren Medien) wird durch einen Beirat der lokalen Krankenkassen, Gesundheitsämter und der Deutschen Alzheimer-Gesellschaft unterstützt.
UnivIS-Import:2015-03-09:Pub.2008.phil.dps.iss.lsw.einflu
Keywords: Torbus Alzheimer; Alzheimer-Erkrankung; Sport; Kognition; kognitive Defizite; körperliche Aktivität; körperliches Training; randomisiert-kontrollierte Studie

E-Learning Is Not Inferior to On-Site Teaching in a Psychiatric Examination Course - Rauch, Christoph; Utz, Janine; Rauch, Miriam; Kornhuber, Johannes; Spitzer, Philipp (Frontiers in Psychiatry, 2021)
Background: Implementing e-learning into medical education is a growing field of research. Researchers have had positive experiences so far, and evidence suggests it to be no less effective than offline teaching. However, there are a few findings concerning psychiatric education and the use of simulated patients online. Methods: We developed an online workshop for medical students at our psychiatric clinic, including group work exercises, lectures, and interviews with simulated patients. To compare the learning outcome, a cohort of students learning online was compared with a previous cohort that learned on-site. The same objective structured clinical examination (OSCE) was used in both cases. Evaluation questionnaires were gathered from students and lecturers and were compared with the former semesters along with the exam results. Results: The exam grades did not significantly differ between on-site and online teaching, even though students rated their own communication skills better with online teaching. We also found that the connection experienced between students and teachers was impaired without on-site contact. Discussion: We conclude that an online course may be an effective alternative to on-site teaching but requires further improvement to maintain a dependable student–teacher relationship.
CRIS-Team Scopus Importer:2021-05-14
Keywords: communication skills; digital teaching; medical education; on-site teaching; online learning; practical course; psychiatry; simulated patients

Electroconvulsive therapy and adiposity-related parameters in treatment-resistant depressed patients - Maier, Hannah Benedictine; Pollak, Christoph; Moschny, Nicole; Toto, Sermin; Schlatt, Colin; Eberlein, Christian K.; Sperling, Wolfgang; Kornhuber, Johannes; Kahl, Kai G.; Bleich, Stefan; Neyazi, Alexandra; Frieling, Helge (Journal of Neural Transmission, 2022)
Obesity is often accompanied by major depressive disorder (MDD), and vice versa. Latest research findings suggest the body mass index (BMI) to play a role in antidepressant treatment response in general. Our study aims to examine whether adiposity-related parameters such as BMI, glucose homeostasis, or serum lipids are associated with remission to electroconvulsive therapy (ECT). A pilot study (PS, n = 9) and a glucose study (GS, n = 29) were conducted. Blood was withdrawn directly before and 15 min (GS) as well as 1 h (PS) after the first ECT and directly before the last one (usually an ECT series comprised up to twelve sessions). BMI was associated with remission in the PS (remitters: M = 28, SD = 2.5; non-remitters: M = 22, SD = 2.08; t(7) = 3.325, p < 0.001, d = 0.24) but not in the GS or when pooled together. Glucose and insulin levels increased significantly after a single ECT session (GS: glucose: F (2,25.66) = 39.04, p < 0.001; insulin: PS: F (2,83) = 25.8, p < 0.001; GS: F (2,25.87) = 3.97, p < 0.05) but no chronic effect was detectable. Serum lipids were neither significantly altered after a single ECT session nor during a whole course of ECT. There was no difference between remitters and non-remitters in insulin, glucose, or serum lipid levels. Our study is lacking the differentiation between abdominal and peripheral fat distribution, and the sample size is small. Unexpectedly, BMI, glucose homeostasis, and lipid serum levels did not differ in patients remitting during ECT. In contrast to recently published studies, we cannot confirm the hypothesis that BMI may have an impact on ECT response.
CRIS-Team Scopus Importer:2022-03-04
Keywords: BMI; Depression; ECT; Glucose; HDL; HOMA; Insulin; LDL; Serum lipids; Triglyceride

Electroconvulsive Therapy Hasn't Negative Effects on Short-Term Memory Function, as Assessed Using a Bedside Hand-Held Device - Mueller, Helge H. O.; Reike, Mareen; Grosse-Holz, Simon; Röther, Mareike; Likke, Caroline; Philipsen, Alexandra; Kornhuber, Johannes; Groemer, Teja W. (Mental Illness, 2017)
Electroconvulsive therapy (ECT) is effective in the treatment of treatment-resistant major depression. The fear of cognitive impairment after ECT often deters patients from choosing this treatment option. There is little reliable information regarding the effects of ECT on overall cognitive performance, while short-term memory deficits are well known but not easy to measure within clinical routines. In this pilot study, we examined ECT recipients' pre- and post-treatment performances on a digital ascending number tapping test. We found that cognitive performance measures exhibited good reproducibility in individual patients and that ECT did not significantly alter cognitive performance up to 2 hours after this therapy was applied. Our results can help patients and physicians make decisions regarding the administration of ECT. Digital measurements are recommended, especially when screening for the most common side effects on cognitive performance and short-term memory.
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Elevated Insulin Levels Engage the Salience Network during Multisensory Perception - Schumann, Katja; Rodriguez-Raecke, Rea; Sijben, Rik; Freiherr, Jessica (Neuroendocrinology, 2024)
INTRODUCTION: Brain insulin reactivity has been reported in connection with systematic energy metabolism, enhancement in cognition, olfactory sensitivity, and neuroendocrine circuits. High receptor densities exist in regions important for sensory processing. The main aim of the study was to examine whether intranasal insulin would modulate the activity of areas in charge of olfactory-visual integration. METHODS: As approach, a placebo-controlled double-blind within crossover design was chosen. The experiments were conducted in a research unit of a university hospital. On separate mornings, twenty-six healthy normal-weight males aged between 19 and 31 years received either 40 IU intranasal insulin or placebo vehicle. Subsequently, they underwent 65 min of functional magnetic resonance imaging whilst performing an odor identification task. Functional brain activations of olfactory, visual, and multisensory integration as well as insulin versus placebo were assessed. Regarding the odor identification task, reaction time, accuracy, pleasantness, and intensity measurements were taken to examine the role of integration and treatment. Blood samples were drawn to control for peripheral hormone concentrations. RESULTS: Intranasal insulin administration during olfactory-visual stimulation revealed strong bilateral engagement of frontoinsular cortices, anterior cingulate, prefrontal cortex, mediodorsal thalamus, striatal, and hippocampal regions (p ≤ 0.001 familywise error [FWE] corrected). In addition, the integration contrast showed increased activity in left intraparietal sulcus, left inferior frontal gyrus, left superior frontal gyrus, and left middle frontal gyrus (p ≤ 0.013 FWE corrected). CONCLUSIONS: Intranasal insulin application in lean men led to enhanced activation in multisensory olfactory-visual integration sites and salience hubs which indicates stimuli valuation modulation. This effect can serve as a basis for understanding the connection of intracerebral insulin and olfactory-visual processing.
CRIS-Team Scopus Importer:2024-01-26
Keywords: Brain imaging; Intranasal insulin; Multisensory; Neuropeptides

Elevated Oxytocin Receptor Blood Concentrations Predict Higher Risk for, More, and Earlier 24-Month Hospital Readmissions after In-Patient Detoxification in Males with Alcohol Use Disorder - Mühle, Christiane; Mazza, Massimiliano; Weinland, Christian; von Zimmermann, Claudia; Bach, Patrick; Kiefer, Falk; Grinevich, Valery; Zoicas, Iulia; Kornhuber, Johannes; Lenz, Bernd (International Journal of Molecular Sciences, 2022)
Alcohol use disorder (AUD) is a major global mental health challenge. Knowledge concerning mechanisms underlying AUD and predictive biomarkers of AUD progression and relapse are insufficient. Recently, addiction research is focusing attention on the oxytocin system. However, to our knowledge, blood concentrations of the oxytocin receptor (OXTR) have not yet been studied in AUD. Here, in sex-separated analyses, OXTR serum concentrations were compared between early-abstinent in-patients with AUD (113 men, 87 women) and age-matched healthy controls (133 men, 107 women). The OXTR concentrations were correlated with sex hormone and oxytocin concentrations and alcohol-related hospital readmissions during a 24-month follow-up. In male patients with AUD, higher OXTR concentrations were found in those with an alcohol-related readmission than in those without (143%; p = 0.004), and they correlated with more prospective readmissions (rho = 0.249; p = 0.008) and fewer days to the first readmission (rho = -0.268; p = 0.004). In men and women, OXTR concentrations did not significantly differ between patients with AUD and controls. We found lower OXTR concentrations in smokers versus non-smokers in female patients (61%; p = 0.001) and controls (51%; p = 0.003). In controls, OXTR concentrations correlated with dihydrotestosterone (men, rho = 0.189; p = 0.030) and testosterone concentrations (women, rho = 0.281; p = 0.003). This clinical study provides novel insight into the role of serum OXTR levels in AUD. Future studies are encouraged to add to the available knowledge and investigate clinical implications of OXTR blood concentrations.
CRIS-Team WoS Importer:2022-09-23

Elterliche Belastung und die Zuverlässigkeit von Elternangaben in der Diagnostik psychisch und verhaltensauffälliger Kinder und Jugendlicher - Irlbauer-Müller, Viktoria; Eichler, Anna; Stemmler, Mark; Moll, Gunther; Kratz, Oliver (Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie, 2016)

Embedded QRS Detection for Noisy ECG Sensor Data Using a Matched Filter and Directed Graph Search - Eskofier, Björn; Kornhuber, Johannes; Hornegger, Joachim (Russian-Bavarian Conference on Biomedical Engineering, 2008)

Emotional stress and health-related quality of life of patients on the waiting list for a liver transplant - Can personal resources reduce the stress? - Erim, Yesim; Beckmann, M. B.; Senf, W. (Transplantationsmedizin, 2009)

Enhanced Acid Sphingomyelinase Activity Drives Immune Evasion and Tumor Growth in Non-Small Cell Lung Carcinoma - Kachler, Katerina; Bailer, Maximilian; Heim, Lisanne; Schumacher, Fabian; Reichel, Martin; Holzinger, Corinna D.; Trump, Sonja; Mittler, Susanne; Monti, Juliana; Trufa, Denis; Rieker, Ralf; Hartmann, Arndt; et al. (Cancer Research, 2017)
The lipid hydrolase enzyme acid sphingomyelinase (ASM) is required for the conversion of the lipid cell membrane component sphingomyelin into ceramide. In cancer cells, ASM-mediated ceramide production is important for apoptosis, cell proliferation, and immune modulation, highlighting ASM as a potential multimodal therapeutic target. In this study, we demonstrate elevated ASM activity in the lung tumor environment and blood serum of patients with non-small cell lung cancer (NSCLC). RNAi-mediated attenuation of SMPD1 in human NSCLC cells rendered them resistant to serum starvation-induced apoptosis. In a murine model of lung adenocarcinoma, ASM deficiency reduced tumor development in a manner associated with significant enhancement of Th1-mediated and cytotoxic T-cell-mediated antitumor immunity. Our findings indicate that targeting ASM in NSCLC can act by tumor cell-intrinsic and -extrinsic mechanisms to suppress tumor cell growth, most notably by enabling an effective antitumor immune response by the host. Cancer Res; 77(21); 5963-76. ©2017 AACR.
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Enhanced Alcohol Preference and Anxiolytic Alcohol Effects in Niemann-Pick Disease Model in Mice - Kalinichenko, Liubov; Mühle, Christiane; Eulenburg, Volker; Praetner, Marc; Reiche, Martin; Gulbins, Erich; Kornhuber, Johannes; Müller, Christian P. (Frontiers in Neurology, 2019)
Major depression and alcohol use disorder are severe psychiatric diseases affecting the world's population with high comorbidity level. However, the pathogenesis of this comorbidity remains unclear, and no selective treatment for this condition is available. A pathogenic pathway and a possible therapeutic target for the treatment of depression-alcoholism comorbidity based on the hyperfunction of acid sphingomyelinase (Asm) were recently suggested. Here we analyzed the effects of alcohol on the depression/anxiety state of homozygous Asm-knockout mice (Asm-/-), which can be considered as a model of an early stage of Niemann-Pick disease, as well as their drinking pattern under normal and stress conditions. It was observed that forced treatment with alcohol (2 g/kg, i.p.) reduces the anxiety level of Asm-/- mice as measured in the elevated plus maze (EPM) test, but enhances the depression level in the forced swim test (FST). The analysis of drinking pattern of these animals in a free-choice alcohol drinking paradigm revealed higher alcohol intake and preference in Asm-/- mice compared to wild type (wt) littermates. However, this difference was overwritten by the stress exposure. Stronger sedating effects of alcohol were observed in Asm-/- mice compared to wt animals in the loss of righting reflex test after single and repeated alcohol injections (3 g/kg, i.p.). Altogether, the present findings might indicate an Asm involvement in the mechanisms of comorbidity between alcoholism and anxiety/depression.
CRIS-Team WoS Importer:2019-07-19

Entwicklung und Validierung eines Fragebogens zur Patientenkompetenz im Umgang mit einer Krebserkrankung (PUK) - Aderhold, Caroline; Morawa, Eva; Paslakis, Georgios; Erim, Yesim (Zeitschrift für Psychosomatische Medizin und Psychotherapie, 2019)
Objectives: The aim of the study was the development and evaluation of the psychometric properties of a self-assessment questionnaire for resource-orientated coping with cancer (Patient Competence Questionnaire, PCQ). Methods: In 420 patients and members of cancer support-groups item selection and evaluation of item properties, reliability (Cronbach's Alpha), validity (convergent and divergent) and factorial structure were performed in two studies. Results: The final version of the PCQ (18 items) demonstrated a Cronbach's Alpha between 0.71 and 0.91 for five subscales identified with exploratory factor analysis (religious/spiritual coping, coping competence, healthy lifestyle, information seeking, adaptability) and 0.85 for the total score. The PCQ shows a high convergent validity (r = 0.46) with the Freiburg Questionnaire on Coping with Illness (FKV) and significant correlations with depression (r = -0.23), posttraumatic growth (r = 0.65) and religiosity (r = 0.59). Conclusions: First analyses underline that the PCQ can be regarded as a valid and reliable instrument for assessing patients' resources in dealing with cancer.
CRIS-Team Scopus Importer:2020-02-21
Keywords: Cancer; Development; Patient Competence; Questionnaire; Validation

Environmental enrichment recruits activin A to recalibrate neural activity in mouse hippocampus - Dahlmanns, Marc; Dahlmanns, Jana; Schmidt, Carla C.; Valero Aracama, Maria Jesus; Zheng, Fang; Alzheimer, Christian (Cerebral Cortex, 2022)
The TGF-beta family member activin A modulates neural underpinnings of cognitive and affective functions in an activity-dependent fashion. We have previously shown that exploration of a novel and enriched environment (EE) strongly enhanced activin signaling. Whereas the many beneficial effects of EE are amply documented, the underlying mechanisms remain largely elusive. Here, we examined the hypothesis that EE recruits activin to regulate synaptic plasticity in a coordinated, cognition-promoting manner. Elevated activin levels after EE enhanced CA1 pyramidal cell excitability, facilitated synaptic transmission, and promoted long-term potentiation. These EE-induced changes were largely absent in mice expressing a dominant-negative mutant of activin receptor IB. We then interrogated the impact of activin on network oscillations and functional connectivity, using high-speed Ca (2+) imaging to study spike routing within networks formed by dissociated primary hippocampal cultures. Activin facilitated Ca2+ signaling, enhanced the network strength, and shortened the weighted characteristic path length. In the slice preparation, activin promoted theta oscillations during cholinergic stimulation. Thus, we advance activin as an activity-dependent and very early molecular effector that translates behavioral stimuli experienced during EE exposure into a set of synchronized changes in neuronal excitability, synaptic plasticity, and network activity that are all tuned to improve cognitive functions.
CRIS-Team WoS Importer:2022-03-25
Keywords: brain slice; hippocampal culture; network oscillations; neuronal connectivity; synaptic plasticity

Epigenetic control of epilepsy target genes contributes to a cellular memory of epileptogenesis in cultured rat hippocampal neurons - Kiese, Katharina; Jablonski, J.; Hackenbracht, J.; Wrosch, Jana Katharina; Groemer, Teja W.; Kornhuber, Johannes; Blümcke, Ingmar; Kobow, K. (Acta Neuropathologica Communications, 2017)
Hypersynchronous neuronal excitation manifests clinically as seizure (ictogenesis), and may recur spontaneously and repetitively after a variable latency period (epileptogenesis). Despite tremendous research efforts to describe molecular pathways and signatures of epileptogenesis, molecular pathomechanisms leading to chronic epilepsy remain to be clarified. We hypothesized that epigenetic modifications may form the basis for a cellular memory of epileptogenesis, and used a primary neuronal cell culture model of the rat hippocampus to study the translation of massive neuronal excitation into persisting changes of epigenetic signatures and pro-epileptogenic target gene expression. Increased spontaneous activation of cultured neurons was detected 3 and 7 days after stimulation with 10 ?M glutamate when compared to sham-treated time-matched controls using calcium-imaging in vitro. Chromatin-immunoprecipitation experiments revealed short-term (3 h, 7 h, and 24 h) and long-term (3 d and 2 weeks) changes in histone modifications, which were directly linked to decreased expression of two selected epilepsy target genes, e.g. excitatory glutamate receptor genes Gria2 and Grin2a. Increased promoter methylation observed 4 weeks after glutamate stimulation at respective genes suggested long-term repression of Gria2 and Grin2a genes. Inhibition of glutamatergic activation or blocking the propagation of action potentials in cultured neurons rescued altered gene expression and regulatory epigenetic modifications. Our data support the concept of a cellular memory of epileptogenesis and persisting epigenetic modifications of epilepsy target genes, which are able to turn normal into pro-epileptic neurons and circuits.
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Epigenetic modifications in children associated with maternal emotional stress during pregnancy - Stonawski, Valeska; Frey, Silke; Golub, Yulia; Moll, Gunther; Heinrich, Hartmut; Eichler, Anna (Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie, 2018)
Besides typical physical and hormonal changes during pregnancy, this life period is often associated with an increased emotional and mental stress for women. For the child, the time in utero is regarded as a critical developmental period since adverse stimuli during pregnancy can have lasting consequences for the fetal and postnatal health and development. Thus, prenatal depression, anxiety and stress are considered as risk factors for developmental delay, emotional and behavioral problems. Epigenetic modifications, especially modifications in DNA methylation, are discussed as a possible biological mechanism that could explain the association between prenatal emotional stress and altered developmental and health outcomes of the child. This review summarizes evidence for DNA methylation changes related to prenatal emotional stress from studies with a candidate-gene approach as well as epigenome-wide association studies. Problematic issues are discussed and recommendations for future research are presented.
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Erlangen Score as a tool to predict progression from mild cognitive impairment to dementia in Alzheimer's disease - Baldeiras, Ines; Santana, Isabel; Leitao, Maria Joao; Vieira, Daniela; Duro, Diana; Mroczko, Barbara; Kornhuber, Johannes; Lewczuk, Piotr (Alzheimer's Research and Therapy, 2019)
Background: The previously described and validated Erlangen Score (ES) algorithm enables interpretation of the cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD), ordering them on an ordinal scale: From neurochemically normal (ES = 0) through improbable AD (ES = 1), possible AD (ES = 2 or 3), to probable AD (ES = 4). Here we assess the accuracy of the ES in predicting hazards of progression from the mild cognitive impairment (MCI) stage of AD to the dementia stage of the disease (Alzheimer's disease dementia (ADD)) in a novel, single-center cohort. Methods: Baseline CSF biomarkers (amyloid beta (Aβ) 1-42, Aβ42/40, Tau, and pTau181), interpreted according to the ES, were used to estimate time to progression from the MCI stage of AD to ADD, conditional on age, gender, APOE ϵ4 genotype, and Mini Mental State Examination score in 144 MCI subjects, using the Extended Cox Model; the subjects were followed-up until they developed dementia or until they had been cognitively stable for at least 2 years. In addition, ES distributions were studied in 168 ADD cases and 66 neurologic controls. Further, we stratified MCI patients into those who progressed to ADD faster (within 3 years, n = 47) and those who progressed slower (n = 74). Results: The distributions of the ES categories across the four diagnostic groups (Controls, MCI-Stable, MCI-AD, and ADD) were highly significantly different (Kruskal-Wallis χ 2 (df = 3) = 151.4, p < 0.001), with significant contrasts between each pair (p < 0.005), except between the ADD and the MCI-AD groups (p = 1.0). MCI patients with ES = 2 or 3 had 6-8 times higher hazards to progress to ADD compared to patients with ES = 0 or 1 in the first 3 follow-up years, and then their hazards decreased to those of the group with ES = 0 or 1. Patients with ES = 4 had hazards 8-12 times higher compared to the ES = 0 or 1 group. Faster progressors with ES = 2 or 3 had, in comparison to slower progressors, significantly lower Aβ1-42, Aβ1-40, and Aβ42/40, but comparable Tau and pTau181. A highly significant difference of the ES distributions between these two groups was observed (p < 0.001). Conclusions: Our current results reconfirm and extend the conclusions of the previously published report that the Erlangen Score is a useful tool facilitating interpretation of a complex pattern of the CSF AD biomarkers.
CRIS-Team Scopus Importer:2019-05-02
Keywords: Alzheimer's disease; Biomarker; Cerebrospinal fluid; Mild cognitive impairment-progression

Erlangen Score Predicts Cognitive and Neuroimaging Progression in Mild Cognitive Impairment Stage of Alzheimer's Disease - Skillbäck, Tobias; Kornhuber, Johannes; Blennow, Kaj; Zetterberg, Henrik; Lewczuk, Piotr (Journal of Alzheimer's Disease, 2019)
Background: To alleviate the interpretation of the core Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers, amyloid β 1-42 (Aβ 42), total tau (T-tau), and phosphorylated tau (P-tau), the Erlangen Score (ES) interpretation algorithm has been proposed. Objective: In this study, we aim to assess the predictive properties of the ES algorithm on cognitive and neuroimaging outcomes in mild cognitive impairment (MCI). Methods: All MCI subjects with an available baseline CSF sample from ADNI-1 were included (n=193), and assigned an ES between 0 and 4 based on their baseline CSF biomarker profile. Structural magnetic resonance imaging brain scans and MMSE and ADAS-Cog scores were collected at up to 7 times in follow-up examinations. Results: We observed strong and significant correlations between the ES at baseline and neuroimaging and cognitive results with patients with neurochemically probable AD (ES=4) progressing significantly (p≤0.01) faster than those with a neurochemically improbable AD (ES=0 or 1), and the subjects with neurochemically possible AD (ES=2 or 3) in-between these two groups. Conclusion: This study further demonstrates the utility of the ES algorithm as a as a tool in predicting cognitive and imaging progression in MCI patients.
CRIS-Team Scopus Importer:2019-06-18
Keywords: Alzheimer's disease; Aβ 1-42; biomarkers; cerebrospinal fluid; Erlangen score; P -tau; T -tau

Erratum: Author Correction: Common variants in Alzheimer's disease and risk stratification by polygenic risk scores (Nature communications (2021) 12 1 (3417)) - de Rojas, Itziar; Moreno-Grau, Sonia; Tesi, Niccolo; Grenier-Boley, Benjamin; Andrade, Victor; Jansen, Iris E.; Pedersen, Nancy L.; Stringa, Najada; Zettergren, Anna; Hernández, Isabel; Montrreal, Laura; Antúnez, Carmen; et al. (Nature Communications, 2023)
CRIS-Team Scopus Importer:2023-02-17

Erratum to: The Antidepressant Fluoxetine Mobilizes Vesicles to the Recycling Pool of Rat Hippocampal Synapses During High Activity - Jung, Jasmin; Loy, Kristina; Schilling, Eva-Maria; Röther, Mareike; Brauner, Jan M.; Huth, Tobias; Schlötzer-Schrehardt, Ursula; Alzheimer, Christian; Kornhuber, Johannes; Welzel, Oliver; Groemer, Teja W. (Molecular Neurobiology, 2017)
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Essener Leitlinien zur interkulturellen Psychotherapie Interkulturalität in psychotherapeutischer Praxis, Aus- und Fortbildung, Forschung und in der Öffnung von Institutionen - Erim, Yesim; Toker, Mehmet; Aygün, Sanem; Özdemir, Zeki; Renz, Meral; Gün, Ali Kemal (Psychotherapie im Dialog, 2010)

Estrogen receptor 1 gene variants and estradiol activities in alcohol dependence - Mühle, Christiane; Barry, Brianna; Weinland, Christian; Kornhuber, Johannes; Lenz, Bernd (Progress in Neuro-Psychopharmacology & Biological Psychiatry, 2019)
Objective: Alcohol use disorders inflict a great individual and societal burden. Although sex hormone effects have been implicated in alcohol dependence, research has mostly neglected estrogen activities and female alcohol- dependent patients. Here, we investigated associations of estrogen receptor 1 (ESR1) genetics and serum estradiol activities with aspects of alcohol dependence.
CRIS-Team WoS Importer:2019-05-24

Eucalyptol Masks the Olfactory But Not the Trigeminal Sensation of Ammonia - Müschenich, Franziska S.; Sijben, Rik; Gallenmüller, Felix; Singer, Marco; Rodriguez-Raecke, Rea; Di Francesco, Maria Elisa; Wiesmann, Martin; Freiherr, Jessica (Chemical Senses, 2019)
Eucalyptol is a substance with rather pleasant olfactory and trigeminal characteristics and is thus suggested as an efficient tool for malodor coverage. In this study ammonia would be the malodor substance such as is found in cat litter or hair coloration. We investigated the potential of eucalyptol to inhibit both the olfactory as well as the trigeminal sensation of ammonia. For this purpose, we mixed eucalyptol and ammonia and compared odor component intensities. After being presented with either the pure odors or a binary mixture thereof, 21 young and healthy participants had to lateralize the odors and rate component (eucalyptol and ammonia) and total intensity. Analysis of intensity ratings revealed hypoadditivity (total mixture intensity was less than the sum of the total intensity of the single components). Significant interaction effects verified that mixing eucalyptol and ammonia only affected the perceived intensity of ammonia. Comparing the odor components within the pure and mixed stimuli, the ammonia component was rated as significantly less intense in the mixture compared to pure ammonia whereas the eucalyptol component was rated equal in the pure and mixed condition. On the basis of lateralization scores, we observed trigeminal mixture enhancement. We conclude that eucalyptol is a suitable masking agent to cover the unpleasant smell of ammonia; however, it fails to serve as an ammonia counterirritant because it lacks the ability to mask the trigeminal sensation of ammonia.
CRIS-Team Scopus Importer:2019-11-08
Keywords: counteraction; masking; olfactometer; olfactory receptor; trigeminal receptor

Evaluating the hematological and clinical-chemistry parameters of kratom (Mitragyna speciosa) users in Malaysia - Singh, Darshan; Müller, Christian P.; Murugaiyah, Vikneswaran; Hamid, Shahrul Bariyah Sahul; Vicknasingam, Balasingam K.; Avery, Bonnie; Chear, Nelson Jeng Yeou; Mansor, Sharif Mahsufi (Journal of Ethnopharmacology, 2018)
ETHNOPHARMACOLOGICAL RELEVANCE: Kratom (Mitragyna speciosa Korth.) from the Rubiaceae family is an indigenous tropical medicinal tree of Southeast Asia. Kratom leaves have been used for decades in Malaysia and Thailand in traditional context for its perceived vast medicinal value, and as a mild stimulant among manual labourers. Kratom consumption has been reported to cause side-effects in kratom users. AIM OF THE STUDY: To evaluate kratom's effects towards hematological and clinical-chemistry parameters among regular kratom users in Malaysia. METHODS: A total of 77 subjects (n=58 regular kratom users, and n=19 healthy controls) participated in this cross-sectional study. All the surveys were conducted through face-to-face interview to elicit subject's socio-demographic characteristics and kratom use history. A full-blood test was also administered. Laboratory analysis was conducted using GC-MS to determine mitragynine content in the acquired kratom samples in order to relate mitragynine consumption with possible alterations in the blood parameters of kratom users. RESULTS: Findings showed that there were no significant differences in the hematological and clinical-chemistry parameters of traditional kratom users and healthy controls, except for HDL and LDL cholesterol values; these were found to be above the normal reference range for the former. Similarly, long-term kratom consumption (>5 years), and quantity of daily kratom use (≥3 ½ glasses; mitragynine content 76.3-114.8mg) did not appear to alter the hematological and biochemical parameters of kratom users. CONCLUSION: These data suggest that even long-term and heavy kratom consumption did not significantly alter the hematological and clinical-chemistry parameters of kratom users in a traditional setting.
EVALuna2:36549

Evaluation of a Group Therapy for Work-Related Mental Disorders - Hondong, Sinja; Morawa, Eva; Kastel-Hoffmann, Silke; Kandler, Anja; Erim, Yesim (International Journal of Environmental Research and Public Health, 2023)
Objectives: Work-related mental distress is one of the most dominant reasons for sick leave and early retirement. Specialized therapy programs for work-related mental health problems are rare, especially in a group setting. This study evaluates the severity of depression, anxiety, somatization and burnout symptoms before and after a work-related group therapy program. Methods: Patients of a psychosomatic outpatient clinic with work-related mental disorders completed 12 sessions of a manual-based group training with reference to the workplace. Data were collected using the Patient Health Questionnaire-9 (PHQ-9), Patient Health Questionnaire-15 (PHQ-15), General Anxiety Disorder Scale-7 (GAD-7) and the Maslach Burnout Inventory (MBI) before (T1) and directly after the intervention (T2). Results: Overall, 48 participants completed the intervention. The participants’ symptoms of depression (T1: M = 11.06, SD = 6.19, T2: M = 8.92, SD = 8.17; p < 0.001, d = 0.53) and anxiety (T1: M = 9.94, SD = 5.18, T2: M = 7.13, SD = 5.69; p = 0.001, d = 0.49) as well as their emotional exhaustion (T1: M = 4.63, SD = 0.95, T2: M = 4.05, SD = 1.35; p < 0.001, d = 0.55) decreased significantly, and the difference was clinically relevant at T2. For cynicism (T1: M = 3.93, SD = 0.99, T2: M = 3.70, SD = 1.32; p = 0.14, d = 0.22) and personal fulfillment at work (T1: M = 4.30, SD = 0.83, T2: M = 4.41, SD = 0.94; p = 0.24, d = 0.17), the difference between T1 and T2 was not significant. Women benefited more than men (PHQ-9: p < 0.001, d = 0.96; GAD-7: p < 0.001, d = 0.91; PHQ-15: p < 0.001, d = 0.76) from the training. Conclusions: Participants’ mental health symptoms were substantially reduced during the course of the work-related group therapy. As mental health problems account for the largest group of work disability days, the potential of group therapy should be better exploited in health care services.
CRIS-Team Scopus Importer:2023-02-24
Keywords: anxiety; burnout; depression; mental health treatment; work-related mental disorders

Evaluation of neurofeedback in ADHD: the long and winding road - Arns, Martijn; Heinrich, Hartmut; Strehl, Ute (Biological Psychology, 2014)
Among the clinical applications of neurofeedback, most research has been conducted in ADHD. As an introduction a short overview of the general history of neurofeedback will be given, while the main part of the paper deals with a review of the current state of neurofeedback in ADHD. A meta-analysis on neurofeedback from 2009 found large effect sizes for inattention and impulsivity and medium effects sizes for hyperactivity. Since 2009 several new studies, including 4 placebo-controlled studies, have been published. These latest studies are reviewed and discussed in more detail. The review focuses on studies employing (1) semi-active, (2) active, and (3) placebo-control groups. The assessment of specificity of neurofeedback treatment in ADHD is discussed and it is concluded that standard protocols such as theta/beta, SMR and slow cortical potentials neurofeedback are well investigated and have demonstrated specificity. The paper ends with an outlook on future questions and tasks. It is concluded that future controlled clinical trials should, in a next step, focus on such known protocols, and be designed along the lines of learning theory.
EVALuna2:23876

Evaluation of the German biographic screening interview for fetal alcohol spectrum disorder (BSI-FASD) - Widder, Michael; Mierzwa, Luisa; Schwerg, Lina; Schecke, Henrike; Kornhuber, Johannes; Bouna-Pyrrou, Polyxeni; Bumb, Jan Malte; Richter-Schmidinger, Tanja; Lenz, Bernd (Scientific Reports, 2021)
Alcohol consumption during pregnancy may lead to permanent damage in the offspring, including fetal alcohol spectrum disorders (FASD), which have an estimated prevalence of 1–8% worldwide. In adulthood, diagnosing FASD is time-consuming and costly. This study aimed to evaluate the discriminatory power of a German screening instrument for FASD in adults—the biographic screening interview (BSI-FASD). In an open-label comparative cohort study wherein a one-time survey was administered per participant, we compared 22 subjects with confirmed FASD with control groups of 15 subjects diagnosed with attention deficit hyperactivity disorder (ADHD), 20 subjects with alcohol or opiate dependence, 18 subjects with depression, and 31 controls without prenatal alcohol exposure. The BSI-FASD was found to be resource-efficient, user-friendly, comprehensible, and easily applicable. It provided an overall good convergent and discriminant validity with a sensitivity of 0.77 (adapted 0.86) and specificities between 0.70 and 1.00. The BSI-FASD subdomains differed in their power to differentiate FASD from the groups. This study established that the BSI-FASD is an efficient instrument to screen adults with suspected FASD. The BSI-FASD may facilitate future diagnostic evaluation and thereby contribute to improved treatment of affected individuals.
CRIS-Team Scopus Importer:2021-03-19

Evaluation of visinin-like protein 1 concentrations in the cerebrospinal fluid of patients with mild cognitive impairment as a dynamic biomarker of Alzheimer's disease - Mroczko, Barbara; Groblewska, Magdalena; Zboch, Marzena; Muszynski, Pawel; Zajkowska, Agata; Borawska, Renata; Szmitkowski, Maciej; Kornhuber, Johannes; Lewczuk, Piotr (Journal of Alzheimer's Disease, 2015)
The correlations between pathology of neurodegenerative diseases, especially Alzheimer's disease (AD), and concentrations of neuronal calcium sensor proteins, such as visinin-like protein 1 (VILIP-1), in cerebrospinal fluid (CSF) have been discussed in the literature but its utility as biomarker of AD in comparison with mild cognitive impairment (MCI) has not been studied yet.Therefore, the aim of our study was to assess the clinical utility of the measurement of CSF concentrations of VILIP-1 in patients with AD, MCI subjects, and non-demented controls. The clinical and neuropsychological diagnoses were supported by CSF biomarkers of neurochemical dementia diagnostics: decreased concentrations of A?1-42 and/or A?42/40 ratio and increased concentrations of Tau and pTau181 proteins.The study included 33 AD patients, 15 subjects with MCI, and 18 elderly individuals without cognitive deficits. The CSF concentrations of biomarkers tested were determined by using the ELISA method.Concentrations of VILIP-1 in CSF were significantly higher in AD patients compared to the MCI subjects and elderly individuals without cognitive impairment. Increased concentrations of VILIP-1 correlated significantly with reduced A?42/40 ratio and higher pTau181 in AD group.Our findings suggest that VILIP-1 may play a role in the AD pathophysiology and is a good candidate for dynamic biomarker of AD, although this issue requires further investigation.
EVALuna2:23721

Everything you always wanted to know about sex and dopamine, but were afraid to ask: An Editorial for 'No basal or drug-induced sex differences in striatal dopaminergic levels: a cluster and metaanalysis of rat microdialysis studies' on page 482 - Müller, Christian P. (Journal of Neurochemistry, 2020)
Behavioral neuroscience has taken a long time to finally recognize that the largely distinct behavioral repertoires of males and females may arise from differences in brain function. This may in particular apply for the neurochemistry of the dopamine systems and their roles in the organization of emotion, learning, and reinforcement in health and in pathological conditions. The current Editorial highlights a study by Egenrieder and colleagues published in the current issue of the Journal of Neurochemistry, in which the authors have analyzed extracellular dopamine neurochemistry from females and males in a meta-analysis. Largely surprising, they report that after detailed control of methodological differences between studies, no major differences in basal or drug-induced extracellular dopamine activity emerged between sexes in rodents. The locally dissociating effects of ovariectomy in females reported in the Egenrieder et al. study, may furthermore suggest that there may be different sex effects in the distinct dopaminergic projections of the mesolimbic and nigrostriatal dopamine system. However, this may only be the beginning of a system's analysis of dopaminergic sex differences that calls for further meta-analyses of the existing studies.
EVALuna2:215141

Everything you always wanted to know about sex and dopamine, but were afraid to ask - Müller, Christian P. (Journal of Neurochemistry, 2019)
Behavioral neuroscience has taken a long time to finally recognize that the largely distinct behavioral repertoires of males and females may arise from differences in brain function. This may in particular apply for the neurochemistry of the dopamine systems and their roles in the organization of emotion, learning, and reinforcement in health and in pathological conditions. The current Editorial highlights a study by Egenrieder and colleagues published in the current issue of the Journal of Neurochemistry, in which the authors have analyzed extracellular dopamine neurochemistry from females and males in a meta-analysis. Largely surprising, they report that after detailed control of methodological differences between studies, no major differences in basal or drug-induced extracellular dopamine activity emerged between sexes in rodents. The locally dissociating effects of ovariectomy in females reported in the Egenrieder et al. study, may furthermore suggest that there may be different sex effects in the distinct dopaminergic projections of the mesolimbic and nigrostriatal dopamine system. However, this may only be the beginning of a system's analysis of dopaminergic sex differences that calls for further meta-analyses of the existing studies.
CRIS-Team WoS Importer:2019-12-10

Evidence-based health services research–a short review and implications - Grässel, Elmar; Donath, Carolin; Hollederer, A.; Drexler, Hans; Kornhuber, Johannes; Zobel, A.; Kolominsky-Rabas, Peter (Gesundheitswesen, 2015)
Health services research aims to generate knowledge about care processes of people with illnesses who access health-care services. In addition, the consequences of those processes in the care routine concerning the involved persons and the health system are analyzed. CONCEPT OF THE THEORETICAL WORK: In the first part of the manuscript, an overview concerning the current definitions and subsumptions of the concept of health services research is given. The second part of the manuscript focuses on demonstrating how evidence-based health services research can be used to enable optimization of the care system. The concept is called the "circle of care optimization". In the first step the current care situation concerning its deficits and their reasons is analyzed. In the second step a relevant care goal is defined. In the third step an improvement of an existing care process is developed to achieve the defined care goal. In the fourth step, a comparative empirical study with a high-quality study design is carried out, to assess whether the improved care process is superior to the current care as usual. A health economic evaluation will be performed if applicable. If the results show no or only small advantages, the "circle" starts again with step 3. However, if the results show a significant effect in favour of the new care process and are relevant for the delivery of care and efficient in the context of health economics, a fifth step will be performed which involves developing and testing strategies for implementation. Where relevant, the consequences of implementation are investigated in a sixth step. A "best-practice" practical example is demonstrated to illustrate the "circle of care optimization".conclusions are derived by illustrating future challenges for health services research.
EVALuna2:9737

Excessive daytime sleepiness in a patient with coexisting myotonic dystrophy type 1, myasthenia gravis and Graves' disease - Kapica-Topczewska, Katarzyna; Pogorzelski, Robert; Tarasiuk, Joanna; Drozdowski, Wieslaw; Lewczuk, Piotr; Kulakowska, Alina (Neurologia I Neurochirurgia Polska, 2017)
A 41-year-old female with history of Graves' disease, bilateral cataract, paroxysmal atrial fibrillation was admitted because of muscle weakness, daytime sleepiness, fatigability, drowsiness, bilateral eyelid ptosis, descending of head and lower jaw. On neurological examination the patient was presented with muscle weakness, muscle atrophy (in face and sternocleidomastoid muscles), features of myotonia and apocamnosis (orbicular muscles). Electromyography revealed myopathic changes, myotonic and pseudomyotonic discharges, positive repetitive nerve stimulation test in proximal muscles. Myotonic dystrophy (MD) diagnosis was confirmed by genetic testing and myasthenia gravis (MG) by a positive titer of cholinergic receptor autoantibodies. In the CSF concentration of hypocretin was significantly decreased.
EVALuna2:33561

Experience after the evaluation of 700 potential donors for living donor liver transplantation in a single center - Valentin-Gamazo, Camino; Malago, Massimo; Karliova, Marc; Lutz, Jürgen T; Frilling, Andrea; Nadalin, Silvio; Testa, Giuliano; Ruehm, Stefan G; Erim, Yesim; Paul, Andreas; Lang, Hauke; Gerken, Guido; et al. (Liver Transplantation, 2004)

Experimental epileptogenesis in a cell culture model of primary neurons from rat brain: A temporal multi‐scale study - Jablonski, Janos; Hoffmann, Lucas; Blümcke, Ingmar; Fejtová, Anna; Uebe, Steffen; Ekici, Arif Bülent; Gnatkovsky, Vadym; Kobow, Katja (Cells, 2021)
Understanding seizure development requires an integrated knowledge of different scales of organization of epileptic networks. We developed a model of “epilepsy‐in‐a‐dish” based on dissociated primary neuronal cells from neonatal rat hippocampus. We demonstrate how a single application of glutamate stimulated neurons to generate spontaneous synchronous spiking activity with further progression into spontaneous seizure‐like events after a distinct latency period. By computational analysis, we compared the observed neuronal activity in vitro with intracranial electroencephalography (EEG) data recorded from epilepsy patients and identified strong similarities, including a related sequence of events with defined onset, progression, and termination. Next, a link between the neurophysiological changes with network composition and cellular structure down to molecular changes was established. Temporal development of epileptiform network activity correlated with increased neurite outgrowth and altered branching, increased ratio of glutamatergic over GABAergic synapses, and loss of calbindin‐positive interneurons, as well as genome‐wide alterations in DNA methylation. Differentially methylated genes were engaged in various cellular activities related to cellular structure, intracellular signaling, and regulation of gene expression. Our data provide evidence that a single short‐term excess of glutamate is sufficient to induce a cascade of events covering different scales from molecule‐ to network‐level, all of which jointly contribute to seizure development.
CRIS-Team Scopus Importer:2021-11-12
Keywords: DNA methylation; Epigenetic; Epilepsy; In vitro

Explicit and implicit approach vs. avoidance tendencies towards high vs. low calorie food cues in patients with anorexia nervosa and healthy controls - Paslakis, Georgios; Kuehn, Simone; Schaubschläger, Anke; Schieber, Katharina; Roeder, Kathrin; Rauh, Elisabeth; Erim, Yesim (Appetite, 2016)
EVALuna2:24036

Explicit and Implicit Approach vs. Avoidance Tendencies towards High vs. Low Calorie Food Cues in Patients with Obesity and Active Binge Eating Disorder. - Paslakis, Georgios; Kühn, Simone; Grunert, Sebastian; Erim, Yesim (Nutrients, 2017)

Exploring Genetic Associations of Alzheimer's Disease Loci With Mild Cognitive Impairment Neurocognitive Endophenotypes - Espinosa, Ana; Hernandez-Olasagarre, Begona; Moreno-Grau, Sonia; Kleineidam, Luca; Heilmann-Heimbach, Stefanie; Hernandez, Isabel; Wolfsgruber, Steffen; Wagner, Holger; Rosende-Roca, Maitee; Mauleon, Ana; Vargas, Liliana; Lafuente, Asuncion; et al. (Frontiers in Aging Neuroscience, 2018)
The role of genetic risk markers for Alzheimer's disease (AD) in mediating the neurocognitive endophenotypes (NEs) of subjects with mild cognitive impairment (MCI) has rarely been studied. The aim of the present study was to investigate the relationship between well-known AD-associated single-nucleotide polymorphisms (SNPs) and individual NEs routinely evaluated during diagnosis of MCI, AD, and other dementias. The Fundació ACE (ACE) dataset, comprising information from 1245 patients with MCI, was analyzed, including the total sample, amnestic MCI (aMCI) (n = 811), and non-amnestic MCI (naMCI) (n = 434). As probable-MCI (Pr-MCI) patients with memory impairment have a higher risk of AD, which could influence the statistical power to detect genetic associations, the MCI phenotype was also stratified into four related conditions: Pr-aMCI (n = 262), Pr-naMCI (n = 76), possible (Pss)-aMCI (n = 549), and Pss-naMCI (n = 358). Validation analyses were performed using data from the German study on Aging, Cognition, and Dementia in primary care patients (AgeCoDe), and the German Dementia Competence Network (DCN). SNP associations with NEs were calculated in PLINK using multivariate linear regression analysis adjusted for age, gender, and education. In the total MCI sample, APOE-ε4 was significantly associated with the memory function NEs "delayed recall (DR)" (β = -0.76, p = 4.1 × 10-10), "learning" (β = -1.35, p = 2.91 × 10-6), and "recognition memory" (β = -0.58, p = 9.67 × 10-5); and with "DR" in the aMCI group (β = -0.36, p = 2.96 × 10-5). These results were confirmed by validation in the AgeCoDe (n = 503) and DCN (n = 583) datasets. APOE-ε4 was also significantly associated with the NE "learning" in individuals classified as having Pss-aMCI (β = -1.37, p = 5.82 × 10-5). Moreover, there was a near study-wide significant association between the HS3ST1 locus (rs6448799) and the "backward digits" working memory NE (β = 0.52, p = 7.57 × 10-5) among individuals with Pr-aMCI, while the AP2A2 locus (rs10751667) was significantly associated with the language NE "repetition" (β = -0.19, p = 5.34 × 10-6). Overall, our findings support specific associations of established AD-associated SNPs with MCI NEs.
EVALuna2:211616

Exploring Links Between Psychosis and Frontotemporal Dementia Using Multimodal Machine Learning Dementia Praecox Revisited - Koutsouleris, Nikolaos; Pantelis, Christos; Velakoulis, Dennis; Mcguire, Philip; Dwyer, Dominic B.; Urquijo-Castro, Maria-Fernanda; Paul, Riya; Sen Dong,; Popovic, David; Oeztuerk, Oemer; Kambeitz, Joseph; Salokangas, Raimo K. R.; et al. (JAMA Psychiatry, 2022)
IMPORTANCE The behavioral and cognitive symptoms of severe psychotic disorders overlap with those seen in dementia. However, shared brain alterations remain disputed, and their relevance for patients in at-risk disease stages has not been explored so far.
CRIS-Team WoS Importer:2022-08-26

Exploring Reference Values for Hair Cortisol: Hair Weight versus Hair Protein - Frisch, Nadine; Eichler, Anna; Plank, Anne-Christine; Golub, Yulia; Moll, Gunther; Kratz, Oliver (Therapeutic Drug Monitoring, 2020)
BACKGROUND: As a marker of cumulative cortisol activity, hair cortisol has received attention in clinical and methodological research. Currently, it is common practice to relate hair cortisol concentration (HCC) to hair weight. The present paper explores hair protein concentration (HPC) as another possible reference value for HCC. METHODS: For n = 18 hair samples cut from the posterior vertex, the HCC, HPC, and hair sample weight were determined, and the cortisol-to-weight and cortisol-to-protein ratios were calculated. Correlations were analyzed between HCC, HPC, and hair sample weight as well as between the cortisol-to-weight and cortisol-to-protein ratios. Hair sample weight and HPC were included as independent variables in a stepwise linear regression model to predict HCC. RESULTS: HCC and HPC did not correlate significantly (r = .393, p = .106); however, the correlation between HCC and hair sample weight was significant (r = .520, p = .027). HPC and hair sample weight (r = .605, p = .008) as well as the cortisol-to-weight and cortisol-to-protein ratios (r = .858, p < .000) showed a high correlation. Hair sample weight was the better predictor of HCC (β = .520, p = .027) than HPC (β = .125, p = .657). CONCLUSIONS: The results indicate that hair sample weight is the more suitable reference value for HCC. Thus, the standard cortisol-to-weight ratio should be used as the preferred expression for cumulative cortisol activity measured in scalp hair. However, calculating the cortisol-to-protein ratio can be considered as an alternative if the hair sample weight is not available.
CRIS-Team Scopus Importer:2020-06-30

Exploring Reference Values for Hair Cortisol: Hair Weight Versus Hair Protein. - Frisch, Nadine; Eichler, Anna; Plank, Anne-Christine; Golub, Yulia; Moll, Gunther; Kratz, Oliver (Therapeutic Drug Monitoring, 2020)
BACKGROUND: As a marker of cumulative cortisol activity, hair cortisol has received attention in clinical and methodological research. Currently, it is a common practice to relate the hair cortisol concentration (HCC) to hair weight. This article explores the hair protein concentration (HPC) as another possible reference value for HCC. METHODS: For n = 18 hair samples cut from the posterior vertex, the HCC, HPC, and hair sample weight were determined, and the cortisol-to-weight and cortisol-to-protein ratios were calculated. Correlations were analyzed between the HCC, HPC, and hair sample weight as well as between the cortisol-to-weight and cortisol-to-protein ratios. Hair sample weight and HPC were included as independent variables in a stepwise linear regression model to predict HCC. RESULTS: The HCC and HPC did not correlate significantly (r = 0.393, P = 0.106); however, the correlation between HCC and hair sample weight was significant (r = 0.520, P = 0.027). The HPC and hair sample weight (r = 0.605, P = 0.008) as well as the cortisol-to-weight and cortisol-to-protein ratios (r = 0.858, P < 0.000) showed a high correlation. The hair sample weight was the better predictor of the HCC (β = 0.520, P = 0.027) than HPC (β = 0.125, P = 0.657). CONCLUSIONS: The results indicate that the hair sample weight is the more suitable reference value for the HCC. Thus, the standard cortisol-to-weight ratio should be used as the preferred expression for the cumulative cortisol activity measured in the scalp hair. However, calculating the cortisol-to-protein ratio can be considered as an alternative if the hair sample weight is not available.
EVALuna2:384364
Keywords: hair cortisol; hair protein; hypothalamic-pituitary-adrenal axis; methodology; stress

Extended Multimodal Flat Detector CT Imaging in Acute Ischemic Stroke: A Pilot Study - Hölter, Philip; Lang, Stefan; Beuscher, Vanessa; Kallmünzer, Bernd; Manhart, Michael; Schwab, Stefan; Dörfler, Arnd (Journal of Digital Imaging, 2023)
By using Flat detector computed tomography (FD-CT), a one-stop-shop approach in the diagnostic workup of acute ischemic stroke (AIS) might be achieved. Although information on upstream vessels is warranted, dedicated FD-CT protocols which include the imaging of the cervical vasculature are still lacking. We aimed to prospectively evaluate the implementation of a new multimodal FD-CT protocol including cervical vessel imaging in AIS patients. In total, 16 patients were included in this study. Eight patients with AIS due to large vessel occlusion (LVO) prospectively received a fully multimodal FD-CT imaging, including non-enhanced flat detector computed tomography (NE-FDCT), dynamic perfusion flat detector computed tomography (FD-CTP) and flat detector computed tomography angiography (FD-CTA) including cervical imaging. For comparison of time metrics and image quality, eight AIS patients, which received multimodal CT imaging, were included retrospectively. Although image quality of NE-FDCT and FD-CTA was rated slightly lower than NE-CT and CTA, all FD-CT datasets were of diagnostic quality. Intracerebral hemorrhage exclusion and LVO detection was reliably possible. Median door-to-image time was comparable for the FD-CT group and the control group (CT:30 min, IQR27-58; FD-CT:44.5 min, IQR31-55, p = 0.491). Door-to-groin-puncture time (CT:79.5 min, IQR65-90; FD-CT:59.5 min, IQR51-67; p = 0.016) and image-to-groin-puncture time (CT:44 min, IQR30-50; FD-CT:14 min, IQR12-18; p < 0.001) were significantly shorter, when patients were directly transferred to the angiosuite, where FD-CT took place. Our study indicates that using a new fully multimodal FD-CT approach including imaging of cervical vessels for first-line imaging in AIS patients is feasible and comparable to multimodal CT imaging with substantial potential to streamline the stroke workflow.
CRIS-Team Scopus Importer:2023-02-03
Keywords: Flat Detector Computed Tomography; Interventional; Stroke; Workflow

Externalization Errors of Olfactory Source Monitoring in Healthy Controls-An fMRI Study - Leclerc, Marcel P.; Kellermann, Thilo; Freiherr, Jessica; Clemens, Benjamin; Habel, Ute; Regenbogen, Christina (Chemical Senses, 2019)
Using a combined approach of functional magnetic resonance imaging (fMRI) and noninvasive brain stimulation (transcranial direct current stimulation [tDCS]), the present study investigated source memory and its link to mental imagery in the olfactory domain, as well as in the auditory domain. Source memory refers to the knowledge of the origin of mental experiences, differentiating events that have occurred and memories of imagined events. Because of a confusion between internally generated and externally perceived information, patients that are prone to hallucinations show decreased source memory accuracy; also, vivid mental imagery can lead to similar results in healthy controls. We tested source memory following cathodal tDCS stimulation using a mental imagery task, which required participants to perceive or imagine a set of the same olfactory and auditory stimuli during fMRI. The supplementary motor area (SMA) is involved in mental imagery across different modalities and potentially linked to source memory. Therefore, we attempted to modulate participants' SMA activation before entering the scanner using tDCS to influence source memory accuracy in healthy participants. Our results showed the same source memory accuracy between the olfactory and auditory modalities with no effects of stimulation. Finally, we found SMA's subregions differentially involved in olfactory and auditory imagery, with activation of dorsal SMA correlated with auditory source memory.
CRIS-Team Scopus Importer:2019-10-25
Keywords: fMRI; reality monitoring; tDCS

Ex vivo assay to evaluate the efficacy of drugs targeting sphingolipids in preventing SARS-CoV-2 infection of nasal epithelial cells - Becker, Katrin Anne; Carpinteiro, Alexander; Hoffmann, Markus; Pöhlmann, Stefan; Kornhuber, Johannes; Gulbins, Erich (STAR Protocols, 2021)
This protocol enables the testing of drugs against infection of epithelial cells with SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2), using pseudo-typed replication deficient vesicular stomatitis virus particles (pp-VSV) presenting the SARS-CoV-2 spike protein. After treating human volunteers with amitriptyline, an approved antidepressant and inhibitor of the acid sphingomyelinase, freshly isolated nasal epithelial cells were infected ex vivo and infection levels were quantified. This protocol offers the possibility to rapidly test the efficacy of potential drugs in the fight against COVID-19. For complete details on the use and execution of this protocol, please refer to Carpinteiro et al. (2020).
CRIS-Team Scopus Importer:2021-04-23
Keywords: Cell isolation; Cell-based assays

Ex vivo glucocorticoid receptor-mediated IL-10 response predicts the course of depression severity - von Zimmermann, Claudia; Böhm, Lea; Richter-Schmidinger, Tanja; Kornhuber, Johannes; Lenz, Bernd; Mühle, Christiane (Journal of Neural Transmission, 2021)
Directly measuring hypothalamic pituitary adrenal (HPA) axis function, an important player in affective disorders, is intensive and invasive. A crucial component of this system, the activity of the glucocorticoid receptor (GR), can be assessed ex vivo instead. Here, we investigated GR sensitivity in patients with major depressive disorder (MDD) to determine its predictive potential. Psychometric data and blood samples were collected from patients experiencing a major depressive episode (MDE, n = 87), healthy control subjects (n = 49), and patients with remitted MDD (n = 31) at baseline and (for patients) after median 20 days of follow-up after treatment as usual. Blood cells were stimulated ex vivo with lipopolysaccharide and the effect was suppressed by increasing dexamethasone (DEX) concentrations. The resultant cytokine secretion profile (for IL-6, IL-10, and TNF-α) was considered indicative of GR activity. Higher baseline scores of the Montgomery–Åsberg Depression Rating Scale (MADRS) were associated with a stronger decrease of logIC IL-6 (indicating an increase of GR sensitivity). Higher baseline logEC IL-10 (indicating a lower GR sensitivity) and a stronger reduction of logEC IL-10 (indicating a stronger increase in GR sensitivity) were associated with a stronger decrease in the MADRS score. Patients with remitted MDD showed higher logIC TNF-α values (indicating lower GR sensitivity) in comparison to patients with a current MDD at baseline and follow-up. Initially low GR sensitivity measured ex vivo in peripheral blood cells that increases over the course of treatment could serve as a predictive marker for stronger improvement in depression severity.
CRIS-Team Scopus Importer:2021-01-22
Keywords: Cytokines; Depression; Glucocorticoid receptor; Hypothalamic–pituitary–adrenal axis

Ex vivo radiosensitivity is increased in non-cancer patients taking valproate - Stritzelberger, Jenny; Lainer, Jennifer; Gollwitzer, Stefanie; Graf, Wolfgang; Jost, Tina; Lang, Johannes; Müller, Tamara; Schwab, Stefan; Fietkau, Rainer; Hamer, Hajo; Distel, Luitpold (BMC Neurology, 2020)
Background: Valproate (VPA) is a commonly prescribed antiepileptic drug for patients experiencing epileptic seizures due to brain tumors. VPA increases radiation sensitivity in various tumor cells in vitro due to complex mechanisms. This could make tumors more vulnerable to ionizing radiation or overcome radioresistance. Yet, clinical data on possible improvement of tumor control by adding VPA to tumor therapy is controversial. Potentially radiosensitizing effects of VPA on healthy tissue remain unclear. To determine individual radiosensitivity, we analyzed blood samples of individuals taking VPA. Methods: Ex vivo irradiated blood samples of 31 adult individuals with epilepsy were studied using 3-color fluorescence in situ hybridization. Aberrations in chromosomes 1, 2 and 4 were analyzed. Radiosensitivity was determined by the mean breaks per metaphase (B/M) and compared to age-matched (2:1) healthy donors. Results: The patient cohort (n = 31; female: 38.7%) showed an increase of their average B/M value compared to healthy individuals (n = 61; female: 56.9%; B/M: 0.480 ± 0.09 vs. 0.415 ± 0.07; p =.001). The portion of radiosensitive (B/M > 0.500) and distinctly radiosensitive individuals (B/M > 0.600) was increased in the VPA group (54.9% vs. 11.3 and 9.7% vs. 0.0%; p <.001). In 3/31 patients, radiosensitivity was determined prior to and after VPA treatment and radiosensitivity was increased by VPA-treatment. Conclusions: In our study, we confirmed that patients treated with VPA had an increased radiosensitivity compared to the control group. This could be considered in patients taking VPA prior to the beginning of radiotherapy to avoid toxic side effects of VPA-treatment.
CRIS-Team Scopus Importer:2020-11-06
Keywords: 3-colour fluorescence-in-situ-hybridization; Breaks per metaphase; Individual radiosensitivity; Valproate

FDG-PET underscores the key role of the thalamus in frontotemporal lobar degeneration caused by C9ORF72 mutations - Diehl-Schmid, Janine; Licata, Abigail; Goldhardt, Oliver; Foerstl, Hans; Yakushew, Igor; Otto, Markus; Anderl-Straub, Sarah; Beer, Ambros; Ludolph, Albert Christian; Landwehrmeyer, Georg Bernhard; Levin, Johannes; Danek, Adrian; et al. (Translational Psychiatry, 2019)
C9ORF72 mutations are the most common cause of familial frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). MRI studies have investigated structural changes in C9ORF72-associated FTLD (C9FTLD) and provided first insights about a prominent involvement of the thalamus and the cerebellum. Our multicenter, F-18-fluorodeoxyglucose positron-emission tomography study of 22 mutation carriers with FTLD, 22 matched non-carriers with FTLD, and 23 cognitively healthy controls provided valuable insights into functional changes in C9FTLD: compared to non-carriers, mutation carriers showed a significant reduction of glucose metabolism in both thalami, underscoring the key role of the thalamus in C9FTLD. Thalamic metabolism did not correlate with disease severity, duration of disease, or the presence of psychotic symptoms. Against our expectations we could not demonstrate a cerebellar hypometabolism in carriers or non-carriers. Future imaging and neuropathological studies in large patient cohorts are required to further elucidate the central role of the thalamus in C9FTLD.
CRIS-Team WoS Importer:2019-03-12

Feasibility, acceptance, and impact of socially assistive robots in non-drug interventions with people with dementia: A scoping review - Wasic, Catharina; Pendergrass, Anna; Böhme, Hans Joachim; Bahrmann, Frank; Grässel, Elmar (Gerontechnology, 2020)
Background: With increasing research on robotics, socially assistive robots may broaden potential forms of non-drug interventions for the increasing numbers of people with cognitive impairments. Existing reviews have concentrated on one robot, one intervention, or one outcome only. With this paper, we attempt to gain an overarching perspective on different types of socially assistive robots in various non-drug interventions, and their feasibility, acceptance, and impact. Objective: We conducted a scoping review of research on socially assistive robots used in non-drug interventions for people with dementia (PwDs) or people with mild cognitive impairment (PwMCIs) to determine whether the use of robots is feasible, accepted, and yields a positive impact on the attendees. Methods: We used the online databases PubMed, CINAHL, and IEEE Xplore to identify relevant studies published up to the end of 2018. To be included, studies had to involve PwDs/PwMCIs and deploy a robot in a non-drug intervention. Ambient Assisted Living (AAL) structures were excluded. Results: This review included a total of 70 records with 21 different robots (12 animaloids, 4 humanoids, 5 mechanoids). The findings indicated that feasibility is a necessity for acceptance, which in turn is a necessity to generate an impact. Robots are feasible as long as they function and as long as non-cognitive symptoms (e.g. agitation) do not get in the way of conducting the intervention. Results for acceptance were mixed, but generally, PwDs and PwMCIs were interested in interacting with the robots. No coherent positive impacts other than increased communication, engagement, and pleasure were found. Neither cognitive nor other non-cognitive symptoms of PwD/PwMCI were significantly positively influenced by controlled studies. Conclusions: Firstly, more research should focus on feasibility and acceptance. Secondly, studies examining possible impacts need to be better structured and comparable.
CRIS-Team Scopus Importer:2021-04-19
Keywords: Cognitive Dysfunction [MeSH]; Dementia [MeSH]; Non-drug Intervention; Review [MeSH]; Robotics [MeSH]

Feasibility and Acceptability of an Alcohol Addiction Therapy Integrated in a Transplant Center for Patients Awaiting Liver Transplantation - Erim, Yesim; Boettcher, Michael; Schieber, Katharina; Lindner, Marion; Klein, Christian; Paul, Andreas; Beckebaum, Susanne; Mayr, Andreas; Helander, Anders (Alcohol and Alcoholism, 2016)
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Feasibility and Diagnostic Accuracy of Ischemic Stroke Territory Recognition Based on Two-Dimensional Projections of Three-Dimensional Diffusion MRI Data. - Wrosch, Jana Katharina; Volbers, Bastian; Gölitz, Philipp; Gilbert, Daniel; Schwab, Stefan; Dörfler, Arnd; Kornhuber, Johannes; Groemer, Teja W. (Frontiers in Neurology, 2015)
This study was conducted to assess the feasibility and diagnostic accuracy of brain artery territory recognition based on geoprojected two-dimensional maps of diffusion MRI data in stroke patients. In this retrospective study, multiplanar diffusion MRI data of ischemic stroke patients was used to create a two-dimensional map of the entire brain. To guarantee correct representation of the stroke, a computer-aided brain artery territory diagnosis was developed and tested for its diagnostic accuracy. The test recognized the stroke-affected brain artery territory based on the position of the stroke in the map. The performance of the test was evaluated by comparing it to the reference standard of each patient’s diagnosed stroke territory on record. This study was designed and conducted according to Standards for Reporting of Diagnostic Accuracy (STARD). The statistical analysis included diagnostic accuracy parameters, cross-validation, and Youden Index optimization. After cross-validation on a cohort of 91 patients, the sensitivity of this territory diagnosis was 81% with a specificity of 87%. With this, the projection of strokes onto a two-dimensional map is accurate for representing the affected stroke territory and can be used to provide a static and printable overview of the diffusion MRI data. The projected map is compatible with other two-dimensional data such as EEG and will serve as a useful visualization tool.
Keywords: computer-aided detection and diagnosis; diffusion-weighted imaging; dimensionality reduction; magnetic resonance imaging; stroke territories; validation; visualization

Ferroptosis and PPAR-gamma in the limelight of brain tumors and edema - Yakubov, Eduard; Schmid, Sebastian; Hammer, Alexander; Chen, Daishi; Dahlmanns, Jana; Mitrovic, Ivana; Zurabashvili, Luka; Savaskan, Nicolai; Steiner, Hans Herbert; Dahlmanns, Marc (Frontiers in Oncology, 2023)
Human malignant brain tumors such as gliomas are devastating due to the induction of cerebral edema and neurodegeneration. A major contributor to glioma-induced neurodegeneration has been identified as glutamate. Glutamate promotes cell growth and proliferation in variety of tumor types. Intriguently, glutamate is also an excitatory neurotransmitter and evokes neuronal cell death at high concentrations. Even though glutamate signaling at the receptor and its downstream effectors has been extensively investigated at the molecular level, there has been little insight into how glutamate enters the tumor microenvironment and impacts on metabolic equilibration until recently. Surprisingly, the 12 transmembrane spanning tranporter xCT (SLC7A11) appeared to be a major player in this process, mediating glutamate secretion and ferroptosis. Also, PPARγ is associated with ferroptosis in neurodegeneration, thereby destroying neurons and causing brain swelling. Although these data are intriguing, tumor-associated edema has so far been quoted as of vasogenic origin. Hence, glutamate and PPARγ biology in the process of glioma-induced brain swelling is conceptually challenging. By inhibiting xCT transporter or AMPA receptors in vivo, brain swelling and peritumoral alterations can be mitigated. This review sheds light on the role of glutamate in brain tumors presenting the conceptual challenge that xCT disruption causes ferroptosis activation in malignant brain tumors. Thus, interfering with glutamate takes center stage in forming the basis of a metabolic equilibration approach.
CRIS-Team Scopus Importer:2023-08-18
Keywords: ferroptosis; glioblastoma; glutamate; peritumoral edema; SLC7A11

FGF21 Regulates Sweet and Alcohol Preference - Talukdar, Saswata; Owen, Bryn M.; Song, Parkyong; Hernandez, Genaro; Zhang, Yuan; Zhou, Yingjiang; Scott, William T.; Paratala, Bhavna; Turner, Tod; Smith, Andrew; Bernardo, Barbara; Müller, Christian P.; et al. (Cell Metabolism, 2016)
Fibroblast growth factor 21 (FGF21) is a hormone induced by various metabolic stresses, including ketogenic and high-carbohydrate diets, that regulates energy homeostasis. In humans, SNPs in and around the FGF21 gene have been associated with macronutrient preference, including carbohydrate, fat, and protein intake. Here we show that FGF21 administration markedly reduces sweet and alcohol preference in mice and sweet preference in cynomolgus monkeys. In mice, these effects require the FGF21 co-receptor ?-Klotho in the central nervous system and correlate with reductions in dopamine concentrations in the nucleus accumbens. Since analogs of FGF21 are currently undergoing clinical evaluation for the treatment of obesity and type 2 diabetes, our findings raise the possibility that FGF21 administration could affect nutrient preference and other reward behaviors in humans.
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Field Simulation for Interstitial Microwave Hyperthermia Using a Finite Integration Algorithm - Erb, J.; Engelbrecht, Rainer; Schaller, Gerd; Müller, R. G.; Sauer, R. (26. Wissenschaftliche Tagung der Deutschen Gesellschaft für Medizinische Physik (DGMP) - Röntgen Centenary Congress, 1995)
UnivIS-Import:2015-04-16:Pub.1995.tech.IE.LEH.fields_8

FINE STRUCTURE ANALYSIS OF THE INTER-RELATION BETWEEN TOPHUS DEPOSITION AND BONE LESIONS IN GOUT USING A COMBINATION OF DUAL ENERGY AND HIGH-RESOLUTION CT - Bayat, Sara; Simon, David; Pecherstorfer, Caroline; Ellmann, Hanna; Figueiredo, C.; Englbrecht, Matthias; Hueber, A.; Kleyer, Arnd; Rech, Jürgen; Schett, Georg (ANNALS OF THE RHEUMATIC DISEASES, 2020)
CRIS-Team WoS Importer:2020-08-21

First amyloid β1-42 certified reference material for re-calibrating commercial immunoassays - Boulo, Sébastien; Kuhlmann, Julia; Andreasson, Ulf; Brix, Britta; Venkataraman, Iswariya; Herbst, Victor; Rutz, Sandra; Manuilova, Ekaterina; Vandijck, Manu; Dekeyser, Filip; Bjerke, Maria; Pannee, Josef; et al. (Alzheimers & Dementia, 2020)
Introduction: Reference materials based on human cerebrospinal fluid were certified for the mass concentration of amyloid beta (Aβ)1-42 (Aβ42). They are intended to be used to calibrate diagnostic assays for Aβ42. Methods: The three certified reference materials (CRMs), ERM-DA480/IFCC, ERM-DA481/IFCC and ERM-DA482/IFCC, were prepared at three concentration levels and characterized using isotope dilution mass spectrometry methods. Roche, EUROIMMUN, and Fujirebio used the three CRMs to re-calibrate their immunoassays. Results: The certified Aβ42 mass concentrations in ERM-DA480/IFCC, ERM-DA481/IFCC, and ERM-DA482/IFCC are 0.45, 0.72, and 1.22 μg/L, respectively, with expanded uncertainties (k = 2) of 0.07, 0.11, and 0.18 μg/L, respectively. Before re-calibration, a good correlation (Pearson's r > 0.97), yet large biases, were observed between results from different commercial assays. After re-calibration the between-assay bias was reduced to < 5%. Discussion: The Aβ42 CRMs can ensure the equivalence of results between methods and across platforms for the measurement of Aβ42.
CRIS-Team Scopus Importer:2020-08-14
Keywords: Alzheimer's disease; amyloid beta peptide; certified reference material; commercial immunoassays

First comparative evaluation of a new leukapheresis technology in non-cytokine-stimulated donors - Steininger, Philipp; Strasser, Erwin; Weiss, D.; Achenbach, Susanne; Zimmermann, Rüdiger; Eckstein, Reinhold (Vox Sanguinis, 2014)
Leukapheresis is an important source for mononuclear cells (MNCs) used in adoptive immunotherapies. Differences in the apheresis technology concerning physical conditions during cell separation and the optical detection system can affect the product's cellular content.In a paired analysis, twenty healthy non-cytokine-stimulated donors underwent MNC collection at the Spectra Optia (Terumo BCT, Lakewood, CO, USA) and the COM.TEC (Fresenius Kabi, Bad Homburg, Germany) device. In twelve donors, apheresis was additionally performed with the Amicus (Fenwal Inc., Lake Zurich, IL, USA). Donor response to leukapheresis and product composition was compared.Mean yields of CD14(+) (CD3(+) ) cells were 1·64 ± 0·70x10(9) (2·36 ± 0·96 × 10(9) ) in the Spectra Optia, 1·45 ± 0·50 × 10(9) (3·03 ± 1·04 × 10(9) ) in the COM.TEC and 1·20 ± 0·37 × 10(9) (2·80 ± 1·00 × 10(9) ) in the Amicus products, respectively. The Spectra Optia collected significantly more CD14(+) monocytes than the Amicus and significantly less CD3(+) T cells than the COM.TEC (P = 0·002 and P = 0·021). Apheresis products of the Spectra Optia showed the significantly lowest red blood cell yields while the Amicus generated products with the significantly lowest platelet contents.Leukaphereses with the three devices resulted in almost equal total MNC yields. MNC products of the Spectra Optia and the Amicus could be used in preference for the monocyte enrichment by the Elutra system and the leukapheresis procedures could be also favourably applied in patients with low platelet counts. The COM.TEC is more efficient in monocyte and T-cell collection with the disadvantage of high residual non-target cell content in the products.
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Flight, Migration and Mental Health - Erim, Yesim; Braehler, Elmar (Psychotherapie Psychosomatik Medizinische Psychologie, 2016)
EVALuna2:24042

FRET probes for measuring sphingolipid metabolizing enzyme activity - Mohamed, Zainelabdeen H.; Rhein, Cosima; Saied, Essa M.; Kornhuber, Johannes; Arenz, Christoph (Chemistry and Physics of Lipids, 2018)
Förster resonance energy transfer (FRET) probes are unique tools in biology, as they allow for a non-destructive monitoring of a certain state of a biomolecule or of an artificial substrate within living cells in real time. FRET substrates indicate their relative cleavage rate and thus the in situ activity of a given enzyme. In contrast to quenched probes or turn-on probes, one of the two separate signals of the FRET probes can be used as internal reference, which makes ratio-imaging and quantitation of cleavage events independent of cellular delivery possible. In this review, we describe the first examples of sphingolipid FRET probes in comparison to different alternative probes. Finally, we give an outlook on future probes and their potential application.
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From board to bedside - training the communication competences of medical students with role plays - Luttenberger, Katharina; Grässel, Elmar; Simon, Cosima; Donath, Carolin (Bmc Medical Education, 2014)
Role plays and standardized patients are often used in medical education and have proven to be effective tools for enhancing the communication skills of medical students. Most course concepts need additional time and teaching staff, and there are only a few studies about role plays in the preclinical segment.We developed a highly consolidated concept for the curricular course of 2nd-year medical students, including ten role plays about five subjects: anamnesis, shared decision making, prevention, breaking bad news, and so-called "difficult interactions". Before the course, all students were asked about their expectations and attitudes toward the course. After the course, all students rated the course, their individual learning progress, whether their expectations had been fulfilled, and re-evaluated their attitudes. Questionnaires were self-report measures and had a quantitative and a short qualitative section and were analyzed with descriptive statistics. Group differences (sex, age, role played) were evaluated with t tests at a Bonferonni-corrected significance level of p = .03 and the non-parametric U-tests.Implementing this practical course concept is possible without incurring additional costs. This paper not only shows how that can be done but also provides 5 examples of role scripts for different training subjects. The course concept was highly appreciated by the students. More than 75% felt that they had learned important communication techniques and would be better able to handle difficult situations. Playing the doctor's role was felt to be more useful than playing the patient's role. Women admitted a higher degree of shyness in the beginning and gave higher ratings to their learning progress than men. Students' most frequent wish in the qualitative analysis was to be able to play the doctor's role at least once. The students' answers showed a differentiated pattern, thus suggesting that the influence of social desirability was minimal.Practical skills can be taught successfully in the preclinical stage of medical education even without an increase in resources. The course concept described in this article provides an effective means by which to do so.
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Functional implications of novel human acid sphingomyelinase splice variants - Rhein, Cosima; Tripal, Philipp; Seebahn, Angela; Konrad, Alice; Kramer, Marcel; Nagel, Christine; Kemper, Jonas; Bode, Jens; Mühle, Christiane; Gulbins, Erich; Reichel, Martin; Becker, Cord-Michael; et al. (PLoS ONE, 2012)
Acid sphingomyelinase (ASM) hydrolyses sphingomyelin and generates the lipid messenger ceramide, which mediates a variety of stress-related cellular processes. The pathological effects of dysregulated ASM activity are evident in several human diseases and indicate an important functional role for ASM regulation. We investigated alternative splicing as a possible mechanism for regulating cellular ASM activity.We identified three novel ASM splice variants in human cells, termed ASM-5, -6 and -7, which lack portions of the catalytic- and/or carboxy-terminal domains in comparison to full-length ASM-1. Differential expression patterns in primary blood cells indicated that ASM splicing might be subject to regulatory processes. The newly identified ASM splice variants were catalytically inactive in biochemical in vitro assays, but they decreased the relative cellular ceramide content in overexpression studies and exerted a dominant-negative effect on ASM activity in physiological cell models.These findings indicate that alternative splicing of ASM is of functional significance for the cellular stress response, possibly representing a mechanism for maintaining constant levels of cellular ASM enzyme activity.
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Functional inhibitors of acid sphingomyelinase (FIASMAS): A novel pharmacological group of drugs with broad clinical applications - Kornhuber, Johannes; Tripal, Philipp; Reichel, Martin; Mühle, Christiane; Rhein, Cosima; Muehlbacher, Markus; Groemer, Teja W.; Gulbins, Erich (Cellular Physiology and Biochemistry, 2010)
Acid sphingomyelinase (ASM) is an important lipid-metabolizing enzyme cleaving sphingomyelin to ceramide, mainly within lysosomes. Acid ceramidase (AC) further degrades ceramide to sphingosine which can then be phosphorylated to sphingosine-1-phosphate. Ceramide and its metabolite sphingosine-1-phosphate have been shown to antagonistically regulate apoptosis, cellular differentiation, proliferation and cell migration. Inhibitors of ASM or AC therefore hold promise for a number of new clinical therapies, e.g. for Alzheimer's disease and major depression on the one hand and cancer on the other. Inhibitors of ASM have been known for a long time. Cationic amphiphilic substances induce the detachment of ASM protein from inner lysosomal membranes with its consecutive inactivation, thereby working as functional inhibitors of ASM. We recently experimentally identified a large number of hitherto unknown functional inhibitors of ASM and determined specific physicochemical properties of such cationic amphiphilic substances that functionally inhibit ASM. We propose the acronym "FIASMA" (Functional Inhibitor of Acid SphingoMyelinAse) for members of this large group of compounds with a broad range of new clinical indications. FIASMAs differ markedly with respect to molecular structure and current clinical indication. Most of the available FIASMAs are licensed for medical use in humans, are minimally toxic and may therefore be applied for disease states associated with increased activity of ASM. Copyright © 2010 S. Karger AG, Basel.
Created from Fastlane, Scopus look-up
Keywords: Acid ceramidase; Acid sphingomyelinase; Acid trapping; Cationic amphiphilic drugs; Desipramine; Lysosomotropism

Functional Inhibitors of Acid Sphingomyelinase (FIASMAs) - Kornhuber, Johannes; Tripal, Philipp; Gulbins, Erich; Mühlbacher, Markus (Sphingolipids: Basic Science and Drug Development, 2013)
Sphingolipids are not only structural components of biological membranes, but also play an important role in cellular signalling and, thus, are involved in cell proliferation and differentiation but also stress and cell death. It is therefore of great clinical relevance to define inhibitors of the enzymes involved in sphingolipid metabolism. Here, we describe the state of the art of functional inhibitors of the acid sphingomyelinase. The acid sphingomyelinase converts sphingomyelin to ceramide, a compound often involved in cell stress. We describe the structural and physicochemical properties, the distribution, the pharmacokinetics, the pharmocodynamics and the clinical use of direct and functional inhibitors of the acid sphingomyelinase.<br
Keywords: Acid sphingomyelinaseö; Functional inhibitors; Ceramide; Structure–property-activity relation

Functional Viability: Measurement of Synaptic Vesicle Pool Sizes - Wrosch, Jana Katharina; Groemer, Teja W. (Methods in Molecular Biology, 2017)
Neurons and their function of conveying information across a chemical synapse are highly regulated systems. Impacts on their functional viability can occur independently from changes in morphology. Here we describe a method to assess the size of synaptic vesicle pools using live cell fluorescence imaging and a genetically encoded probe (pHluorin). Assessing functional parameters such as the size of synaptic vesicle pools can be a valuable addition to common assays of neuronal cell viability as they demonstrate that key cellular functions are intact.
EVALuna2:33744

Gaming and Religion: The Impact of Spirituality and Denomination - Braun, Birgit; Kornhuber, Johannes; Lenz, Bernd (Journal of Religion & Health, 2016)
A previous investigation from Korea indicated that religion might modulate gaming behavior (Kim and Kim in J Korean Acad Nurs 40:378-388, 2010). Our present study aimed to investigate whether a belief in God, practicing religious behavior and religious denomination affected gaming behavior. Data were derived from a Western cohort of young men (Cohort Study on Substance Use Risk Factors, n = 5990). The results showed that a stronger belief in God was associated with lower gaming frequency and smaller game addiction scale scores. In addition, practicing religiosity was related to less frequent online and offline gaming. Finally, Christians gamed less frequently and had lower game addiction scale scores than subjects without religious denomination. In the future, these results could prove useful in developing preventive and therapeutic strategies for the Internet gaming disorder.
EVALuna:34140

Gender-Dependent Crossmodal Interactions Between Olfactory and Tactile Stimulation Revealed Using the Unimodal Tactile Stimulation Device (UniTaSD) - Sijben, Rik; Hensel, Sonja M.; Rodriguez-Raecke, Rea; Freiherr, Jessica (Chemical Senses, 2021)
Due to the complex stimulation methods required, olfaction and touch are 2 relatively understudied senses in the field of perceptual (neuro-)science. In order to establish a consistent presentation method for the bimodal stimulation of these senses, we combined an olfactometer with the newly developed Unimodal Tactile Stimulation Device. This setup allowed us to study the influence of olfaction on tactile perception and opened up an unexplored field of research by examining the crossmodal influence of tactile stimuli on olfaction. Using a pseudorandomized design, we analyzed how positive or negative tactile and olfactory stimuli influenced the opposing modality's perceived intensity and pleasantness. By asking participants to rate tactile stimuli, we were able to reproduce previously reported differences indicating that bimodal presentation with an olfactory stimulus increases or reduces perceived tactile pleasantness in an odor-dependent manner while highlighting that this effect appears unique to women. Furthermore, we found the first evidence for the influence of tactile stimuli on perceived odor pleasantness, an effect that is also driven primarily by women in our study. Based on these findings we believe that future neurophysiological studies, using controlled stimulus presentation can help unravel how and why olfactory and tactile perception interact in the human brain.
CRIS-Team Scopus Importer:2021-04-19
Keywords: crossmodal interaction; olfaction; perception; tactile; touch

Gene dosage-dependent rescue of HSP neurite defects in SPG4 patients' neurons - Havlicek, Steven; Kohl, Zacharias; Mishra, Himanshu Kumar; Prots, Iryna; Eberhardt, Esther; Denguir, Naime; Wend, Holger; Ploetz, Sonja; Boyer, Leah; Marchetto, Maria C. N.; Aigner, Stefan; Sticht, Heinrich; et al. (Human Molecular Genetics, 2014)
The hereditary spastic paraplegias (HSPs) are a heterogeneous group of motorneuron diseases characterized by progressive spasticity and paresis of the lower limbs. Mutations in Spastic Gait 4 (SPG4), encoding spastin, are the most frequent cause of HSP. To understand how mutations in SPG4 affect human neurons, we generated human induced pluripotent stem cells (hiPSCs) from fibroblasts of two patients carrying a c.1684C>T nonsense mutation and from two controls. These SPG4 and control hiPSCs were able to differentiate into neurons and glia at comparable efficiency. All known spastin isoforms were reduced in SPG4 neuronal cells. The complexity of SPG4 neurites was decreased, which was paralleled by an imbalance of axonal transport with less retrograde movement. Prominent neurite swellings with disrupted microtubules were present in SPG4 neurons at an ultrastructural level. While some of these swellings contain acetylated and detyrosinated tubulin, these tubulin modifications were unchanged in total cell lysates of SPG4 neurons. Upregulation of another microtubule-severing protein, p60 katanin, may partially compensate for microtubuli dynamics in SPG4 neurons. Overexpression of the M1 or M87 spastin isoforms restored neurite length, branching, numbers of primary neurites and reduced swellings in SPG4 neuronal cells. We conclude that neurite complexity and maintenance in HSP patient-derived neurons are critically sensitive to spastin gene dosage. Our data show that elevation of single spastin isoform levels is sufficient to restore neurite complexity and reduce neurite swellings in patient cells. Furthermore, our human model offers an ideal platform for pharmacological screenings with the goal to restore physiological spastin levels in SPG4 patients.
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Gene expression imputation across multiple brain regions provides insights into schizophrenia risk - Huckins, Laura M.; Dobbyn, Amanda; Ruderfer, Douglas M.; Hoffman, Gabriel; Wang, Weiqing; Pardinas, Antonio F.; Rajagopal, Veera M.; Als, Thomas D.; Nguyen, Hoang T.; Girdhar, Kiran; Boocock, James; Roussos, Panos; et al. (Nature Genetics, 2019)
Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.
CRIS-Team WoS Importer:2019-04-12

Genetic disruption of bassoon in two mutant mouse lines causes divergent retinal phenotypes - Ryl, Miriam; Urbasik, Alexander; Gierke, Kaspar; Babai, Norbert; Joachimsthaler, Anneka; Feigenspan, Andreas; Frischknecht, Renato; Stallwitz, Nina; Fejtová, Anna; Kremers, Jan; von Wittgenstein, Julia; Brandstätter, Johann Helmut (The FASEB Journal, 2021)
Bassoon (BSN) is a presynaptic cytomatrix protein ubiquitously present at chemical synapses of the central nervous system, where it regulates synaptic vesicle replenishment and organizes voltage-gated Ca2+ channels. In sensory photoreceptor synapses, BSN additionally plays a decisive role in anchoring the synaptic ribbon, a presynaptic organelle and functional extension of the active zone, to the presynaptic membrane. In this study, we functionally and structurally analyzed two mutant mouse lines with a genetic disruption of Bsn-Bsngt and Bsnko -using electrophysiology and high-resolution microscopy. In both Bsn mutant mouse lines, full-length BSN was abolished, and photoreceptor synaptic function was similarly impaired, yet synapse structure was more severely affected in Bsngt/gt than in Bsnko/ko photoreceptors. The synaptic defects in Bsngt/gt retina coincide with remodeling of the outer retina-rod bipolar and horizontal cell sprouting, formation of ectopic ribbon synaptic sites-and death of cone photoreceptors, processes that did not occur in Bsnko/ko retina. An analysis of Bsngt/ko hybrid mice revealed that the divergent retinal phenotypes of Bsngt/gt and Bsnko/ko mice can be attributed to the expression of the Bsngt allele, which triggers cone photoreceptor death and neurite sprouting in the outer retina. These findings shed new light on the existing Bsn mutant mouse models and might help to understand mechanisms that drive photoreceptor death.
CRIS-Team Scopus Importer:2021-04-16
Keywords: active zone; bassoon; photoreceptor; photoreceptor death; ribbon synapse

Genetic interaction of PICALM and APOE is associated with brain atrophy and cognitive impairment in Alzheimer's disease - Morgen, Katrin; Ramirez, Alfredo; Frölich, Lutz; Tost, Heike; Plichta, Michael M.; Kölsch, Heike; Rakebrandt, Fabian; Rienhoff, Otto; Jessen, Frank; Peters, Oliver; Jahn, Holger; Luckhaus, Christian; et al. (Alzheimers & Dementia, 2014)
Evidence has emerged indicating that the ?4 allele of APOE and PICALM interact in conferring risk of Alzheimer's disease (AD). The biologic basis of this interaction is unclear, but it is likely to have phenotypic relevance and contribute to the structural and clinical heterogeneity of AD.The aim of this study was to investigate interaction effects of the APOE ?4 allele and the alleles at the single-nucleotide polymorphism rs3851179 located in the PICALM locus. We analyzed brain volumes and cognitive phenotypes of 165 patients with early AD dementia.There was a synergistic adverse effect of homozygosity for the PICALM risk allele G in rs3851179 and APOE ?4 on volume in prefrontal and performance on the Trail Making Test A, which is sensitive to processing speed and working memory function.The data suggest a neural mechanism for APOE-PICALM interactions in patients with manifest AD and indicate that the PICALM genotype modulates both brain atrophy and cognitive performance in APOE ?4 carriers.
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Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates A beta, tau, immunity and lipid processing - Kunkle, Brian W.; Grenier-Boley, Benjamin; Sims, Rebecca; Bis, Joshua C.; Damotte, Vincent; Naj, Adam C.; Boland, Anne; Vronskaya, Maria; Van Der Lee, Sven J.; Amlie-Wolf, Alexandre; Bellenguez, Celine; Frizatti, Aura; et al. (Nature Genetics, 2019)
Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and A beta processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 x 10(-7)), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.
CRIS-Team WoS Importer:2019-03-15

Genetics of preparation and response control in ADHD: the role of DRD4 and DAT1 - Albrecht, Bjoern; Brandeis, Daniel; Uebel-Von Sandersleben, Henrik; Valko, Lilian; Heinrich, Hartmut; Xu, Xiaohui; Drechsler, Renate; Heise, Alexander; Kuntsi, Jonna; Mueller, Ueli C.; Asherson, Philip; Steinhausen, Hans-Christoph; et al. (The journal of child psychology and psychiatry, 2014)
Difficulties with performance and brain activity related to attentional orienting (Cue-P3), cognitive or response preparation (Cue-CNV) and inhibitory response control (Nogo-P3) during tasks tapping executive functions are familial in ADHD and may represent endophenotypes. The aim of this study was to clarify the impact of dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) gene polymorphisms on these processes in ADHD and control children.Behavioural and electrophysiological parameters from cued continuous performance tests with low and high attentional load were assessed in boys with ADHD combined type (N = 94) and controls without family history of ADHD (N = 31). Both groups were split for the presence of at least one DRD4 7-repeat allele and the DAT1 10-6 haplotype.Children with ADHD showed diminished performance and lower Cue-P3, CNV and Nogo-P3 amplitudes. Children with DRD4 7R showed similar performance problems and lower Cue-P3 and CNV, but Nogo-P3 was not reduced. Children with the DAT1 10-6 haplotype had no difficulties with performance or Cue-P3 and CNV, but contrary to expectations increased Nogo-P3. There were no Genotype by ADHD interactions.This study detected specific effects of DRD4 7R on performance and brain activity related to attentional orienting and response preparation, while DAT1 10-6 was associated with elevated brain activity related to inhibitory response control, which potentially compensates increased impulsivity. As these genotype effects were additive to the impact of ADHD, the current results indicate that DRD4 and DAT1 polymorphisms are functionally relevant risk factors for ADHD and presumably other disorders sharing these endophenotypes.
EVALuna2:23878

Genetic variants in the genes of the sex steroid hormone metabolism and depressive symptoms during and after pregnancy - Schneider, Michael; Pretscher, Jutta; Goecke, Tamme; Häberle, Lothar; Engel, Anne; Kornhuber, Johannes; Eichler, Anna; Ekici, Arif Bülent; Beckmann, Matthias; Fasching, Peter; Schwenke, Eva (Archives of Gynecology and Obstetrics, 2022)
Purpose: The aim of this study was to conduct an association analysis of depressive symptoms and polymorphisms in the ESR1, PGR, CYP19A1, and COMT genes in pregnant and postpartum women. Methods: The Franconian Maternal Health Evaluation Study (FRAMES) recruited healthy pregnant women prospectively for assessment of maternal and fetal health. The German version of the 10-item Edinburgh Postnatal Depression Scale (EPDS) was completed at three time points in this prospective cohort study. Visit 1 was at study entry in the third trimester of pregnancy, visit 2 was shortly after birth, and visit 3 was 6–8 months after birth. Germline DNA and depression measurements from 361 pregnant women were available for analysis. Six single nucleotide polymorphisms (SNPs) in the above-mentioned genes were genotyped. After reconstruction of haplotypes for PGR (rs1042838 and rs10895068) and CYP19A1 (rs10046 and rs4646), a multifactorial linear mixed model was applied to the data to describe the association between haplotypes and depression values. The single SNPs for ESR1 (rs488133) and COMT (rs4680) were analyzed separately using linear mixed models analogously. Results: The mean antepartum EPDS measurement was 5.1, the mean postpartal measurement after 48–72 h was 3.5, and the mean value 6–8 months postpartum was 4.2. The SNPs in PGR were reconstructed into three haplotypes. The most common haplotype was GG, with 63.43% of patients carrying two copies and 33.52% carrying one copy. For haplotype GA, the group of carriers of two copies (0.28%) was combined with the carriers of one copy (9.70%). Haplotype reconstruction using CYP19A1 SNPs resulted in three haplotypes. The most common haplotype was TC, with 25.48% of patients carrying two copies and 51.52% one copy. None of the haplotype blocks and neither of the two single SNPs showed any significant associations with EPDS values. Conclusions: The candidate haplotypes analyzed in PGR and CYP19A1 and single SNPs in ESR1 and COMT did not show any association with depression scores as assessed by EPDS in this cohort of healthy unselected pregnant women.
CRIS-Team Scopus Importer:2022-06-17
Keywords: COMT; CYP19A1; Depression; EPDS; ESR1; PGR; Single nucleotide polymorphisms

Genetic variants in the genes of the stress hormone signalling pathway and depressive symptoms during and after pregnancy - Schneider, Michael; Engel, Anne; Fasching, Peter; Haeberle, Lothar; Binder, Elisabeth B.; Voigt, Franziska; Grimm, Jennifer; Faschingbauer, Florian; Eichler, Anna; Dammer, Ulf; Rebhan, Dirk; Amann, Manuela; et al. (BioMed Research International, 2014)
The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in genes of the stress hormone signaling pathway, specifically FKBP5, NR3C1, and CRHR1, are associated with depressive symptoms during and after pregnancy.The Franconian Maternal Health Evaluation Study (FRAMES) recruited healthy pregnant women prospectively for the assessment of maternal and fetal health including the assessment of depressiveness. The German version of the 10-item Edinburgh Postnatal Depression Scale (EPDS) was completed at three time points in this prospective cohort study. Visit 1 was at study entry in the third trimester of the pregnancy, visit 2 was shortly after birth, and visit 3 was 6-8 months after birth. Germline DNA was collected from 361 pregnant women. Nine SNPs in the above mentioned genes were genotyped. After construction of haplotypes for each gene, a multifactorial linear mixed model was performed to analyse the depression values over time.EPDS values were within expected ranges and comparable to previously published studies. Neither did the depression scores differ for comparisons among haplotypes at fixed time points nor did the change over time differ among haplotypes for the examined genes. No haplotype showed significant associations with depressive symptoms severity during pregnancy or the postpartum period.The analysed candidate haplotypes in FKBP5, NR3C1, and CRHR1 did not show an association with depression scores as assessed by EPDS in this cohort of healthy unselected pregnant women.
EVALuna2:17356

Genetic variants in the glucocorticoid pathway genes and birth weight - Schneider, Michael; Hübner, Theresa; Pretscher, Jutta; Goecke, Tamme W.; Schwitulla, Judith; Häberle, Lothar; Kornhuber, Johannes; Ekici, Arif Bülent; Beckmann, Matthias; Fasching, Peter; Schwenke, Eva (Archives of Gynecology and Obstetrics, 2020)
Purpose: The aim of this study was to examine associations between single nucleotide polymorphisms (SNPs) that tag genetic variation in the glucocorticoid pathways (particularly in maternal genes FKBP5, NR3C1, and CRHR1) and birth weight. Methods: The Franconian Maternal Health Evaluation Study (FRAMES) recruited healthy pregnant women prospectively for the assessment of maternal and fetal health. Germline DNA was collected from 375 pregnant women. Nine SNPs in the above-mentioned genes were genotyped. After reconstruction of haplotypes for each gene, a linear regression model was applied to the data to describe the association between haplotypes and birth weight. Results: Female sex in the newborn (compared to male) was associated with lower birth weight, whereas a later week of gestation, higher body mass index pre-pregnancy, and higher parity were associated with higher birth weight. No association with birthweight was shown for the haplotypes of the selected SNPs. Conclusions: In this cohort of healthy unselected pregnant women, the analyzed candidate haplotypes in FKBP5, NR3C1, and CRHR1 did not show any association with birth weight. This might be in line with several other studies that have found no influence of fetal polymorphisms in the glucocorticoid receptor gene or triggers of the maternal HPA axis such as stress and psychosocial problems on birth weight. However, the small sample size in this study and the lack of consideration of individual risk factors and levels of stress in this cohort needs to be taken into account when interpreting the results.
CRIS-Team Scopus Importer:2020-09-11
Keywords: Birth weight; CRHR1; FKBP5; NR3C1; Single nucleotide polymorphisms

Genetic variants of methionine metabolism and DNA methylation - Bleich, Stefan; Semmler, Alexander; Frieling, Helge; Thumfart, L.; Muschler, Marc; Hillemacher, Thomas; Kornhuber, Johannes; Kallweit, Ulf; Simon, Matthias; Linnebank, Michael (Epigenomics, 2014)
Altered DNA methylation is associated with important and common pathologies such as cancer. The origin of altered DNA methylation is unknown. The methyl groups for DNA methylation are provided by methionine metabolism. This metabolism is characterized by a high interindividual variability, which is in part explained by genetic variants.In a cohort of 313 individuals derived from a family-based study with index cases of cerebrovascular disease, we analyzed whether global methylation of leukocyte DNA was associated with age, gender, homocysteine plasma levels or functionally relevant genetic variants.We observed an association of the G-allele of the methionine synthase variant c.2756A>G (D919G) with global methylation (% methylation ± 1 SD, AA: 41.3 ± 14.9; AG: 36.4 ± 18.2; GG: 30.8 ± 16.9; F = 4.799; p = 0.009). The methionine synthase variant c.2756A>G is associated with various types of cancer.Our data suggest that an impact on DNA methylation may contribute to the clinical relevance of the methionine synthase variant.
EVALuna2:23687

Genome-wide analysis for genes that mediate IFN-induced depression in HCV patients - Trippler, Martin; Erim, Yesim; Bein, Sabine; Gerken, Guido; Schlaak, J. F. (Gastroenterology, 2007)

Genome-Wide DNA Methylation Patterns in Children Exposed to Nonpharmacologically Treated Prenatal Depressive Symptoms: Results From 2 Independent Cohorts - Stonawski, Valeska; Roetner, Jakob; Goecke, Tamme W.; Fasching, Peter; Beckmann, Matthias; Kornhuber, Johannes; Kratz, Oliver; Moll, Gunther; Eichler, Anna; Heinrich, Hartmut; Frey, Stefan (Epigenetics Insights, 2020)
Background: Maternal depressive symptoms are a common phenomenon during pregnancy and are related to negative outcomes for child development and health. Modifications in child DNA methylation are discussed as an underlying mechanism for the association between prenatal depressive symptoms and alterations in child outcomes. However, formerly reported genome-wide associations have yet to be replicated. Methods: In an epigenome-wide association study (EWAS), alterations of DNA methylation related to maternal prenatal depressive symptoms were investigated in buccal cell samples from 174 children (n = 52 exposed to prenatal depressive symptoms; 6-9 years old) of the German longitudinal study FRAMES-FRANCES. Whole blood samples from the independent, age-comparable ARIES subsample of the ARIES/ALSPAC study (n = 641; n = 159 exposed to prenatal depressive symptoms; 7-8 years old) were examined as a confirmation sample. Depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale. DNA methylation was analyzed with the Infinium Human Methylation 450k BeadChip. Modifications in single CpGs, regions, and biological pathways were investigated. Results were adjusted for age and birth outcomes as well as postnatal and current maternal depressive symptoms. Analyses were performed for the whole sample as well as separated for sex. Results: The EWAS yielded no differentially methylated CpG or region as well as no accordance between samples withstanding correction for multiple testing. In pathway analyses, no overlapping functional domain was found to be enriched for either sample. A comparison of current and former findings suggests some overlapping methylation modifications from infancy to childhood. Results suggest that there might be sex-specific differential methylation, which should be further investigated in additional studies. Conclusions: The current, mainly nonsignificant, results challenge the assumption of consistent modifications of DNA methylation in children exposed to prenatal depressive symptoms. Despite the relatively small sample size used in this study, this lack of significant results may reflect diverse issues of environmental epigenetic studies, which need to be addressed in future research.
CRIS-Team Scopus Importer:2020-06-26
Keywords: ALSPAC; ARIES; DNA methylation; epigenetics; FRANCES; Pregnancy; prenatal depression

Genome-wide significant risk factors for Alzheimer's disease: role in progression to dementia due to Alzheimer's disease among subjects with mild cognitive impairment - Lacour, Andre; Espinosa, Ana; Louwersheimer, E.; Heilmann, S.; Hernandez, I.; Wolfsgruber, S.; Fernandez, V.; Wagner, H.; Rosende-Roca, M.; Mauleon, A.; Moreno-Grau, S.; Vargas, Liliana; et al. (Molecular Psychiatry, 2017)
Few data are available concerning the role of risk markers for Alzheimer's disease (AD) in progression to AD dementia among subjects with mild cognitive impairment (MCI). We therefore investigated the role of well-known AD-associated single-nucleotide polymorphism (SNP) in the progression from MCI to AD dementia. Four independent MCI data sets were included in the analysis: (a) the German study on Aging, Cognition and Dementia in primary care patients (n=853); (b) the German Dementia Competence Network (n=812); (c) the Fundació ACE from Barcelona, Spain (n=1245); and (d) the MCI data set of the Amsterdam Dementia Cohort (n=306). The effects of single markers and combined polygenic scores were measured using Cox proportional hazards models and meta-analyses. The clusterin (CLU) locus was an independent genetic risk factor for MCI to AD progression (CLU rs9331888: hazard ratio (HR)=1.187 (1.054-1.32); P=0.0035). A polygenic score (PGS1) comprising nine established genome-wide AD risk loci predicted a small effect on the risk of MCI to AD progression in APOE-ɛ4 (apolipoprotein E-ɛ4) carriers (HR=1.746 (1.029-2.965); P=0.038). The novel AD loci reported by the International Genomics of Alzheimer's Project were not implicated in MCI to AD dementia progression. SNP-based polygenic risk scores comprising currently available AD genetic markers did not predict MCI to AD progression. We conclude that SNPs in CLU are potential markers for MCI to AD progression.
EVALuna2:33562

GESTALT – ein bewegungstherapeutisches Interventionskonzept gegen die Alzheimer-Krankheit - Rütten, Alfred; Abu-Omar, Karim; Hoffmann, Martina; Schuster, Matthias; Bracher, Birgit; Gelius, Peter; Wiltfang, Jens (Bewegungstherapie und Gesundheitssport, 2009)

Gesundheitsbezogene Lebensqualität und Krankheitsbewältigung Laryngektomierter mit funktionierenden Provox-Stimmventilprothesen - Rosanowski, Frank; Grässel, Elmar; Haderlein, Tino; Schuster, Maria (Aktuelle phoniatrisch-pädaudiologische Aspekte 2007, 2007)

Glial Fibrillary Acidic Protein in Serum is Increased in Alzheimer's Disease and Correlates with Cognitive Impairment - Oeckl, Patrick; Halbgebauer, Steffen; Anderl-Straub, Sarah; Steinacker, Petra; Huss, Andre M.; Neugebauer, Hermann; Von Arnim, Christine A. F.; Diehl-Schmid, Janine; Grimmer, Timo; Kornhuber, Johannes; Lewczuk, Piotr; Danek, Adrian; et al. (Journal of Alzheimer's Disease, 2019)
Reliable blood biomarkers for Alzheimer's disease (AD) are missing. We measured astroglial GFAP in patients with AD (n = 28), frontotemporal dementia (bvFTD, n = 35), Parkinson's disease (n = 11), Lewy body dementias (n = 19), and controls (n = 34). Serum GFAP was increased in AD (p < 0.001) and DLB/PDD (p < 0.01), and cerebrospinal fluid GFAP was increased in all neurodegenerative diseases (p < 0.001). Serum GFAP correlated with the Mini-Mental State Examination score (r = -0.42, p < 0.001) and might be a follow-up marker in clinical trials. Sensitivity and specificity of serum GFAP for AD versus bvFTD was 89% and 79% and might be the first blood biomarker in the differential diagnosis of AD and bvFTD.
CRIS-Team WoS Importer:2019-02-21

Glial Glutamate Transporter-Mediated Plasticity: System xc -/xCT/SLC7A11 and EAAT1/2 in Brain Diseases - Dahlmanns, Marc; Dahlmanns, Jana; Savaskan, Nicolai; Steiner, Hans Herbert; Yakubov, Eduard (Frontiers in Bioscience - Landmark, 2023)
Glial cells play an essential role in the complex function of the nervous system. In particular, astrocytes provide nutritive support for neuronal cells and are involved in regulating synaptic transmission. Oligodendrocytes ensheath axons and support information transfer over long distances. Microglial cells constitute part of the innate immune system in the brain. Glial cells are equipped with the glutamatecystine- exchanger xCT (SLC7A11), the catalytic subunit of system xc -, and the excitatory amino acid transporter 1 (EAAT1, GLAST) and EAAT2 (GLT-1). Thereby, glial cells maintain balanced extracellular glutamate levels that enable synaptic transmission and prevent excitotoxic states. Expression levels of these transporters, however, are not fixed. Instead, expression of glial glutamate transporters are highly regulated in reaction to the external situations. Interestingly, such regulation and homeostasis is lost in diseases such as glioma, (tumor-associated) epilepsy, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis or multiple sclerosis. Upregulation of system xc - (xCT or SLC7A11) increases glutamate export from the cell, while a downregulation of EAATs decreases intracellular glutamate import. Occurring simultaneously, these reactions entail excitotoxicity and thus harm neuronal function. The release of glutamate via the antiporter system xc - is accompanied by the import of cystine-an amino acid essential in the antioxidant glutathione. This homeostasis between excitotoxicity and intracellular antioxidant response is plastic and off-balance in central nervous system (CNS) diseases. System xc - is highly expressed on glioma cells and sensitizes them to ferroptotic cell death. Hence, system xc - is a potential target for chemotherapeutic add-on therapy. Recent research reveals a pivotal role of system xc - and EAAT1/2 in tumor-associated and other types of epilepsy. Numerous studies show that in Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease, these glutamate transporters are dysregulated-and disease mechanisms could be interposed by targeting system xc - and EAAT1/2. Interestingly, in neuroinflammatory diseases such as multiple sclerosis, there is growing evidence for glutamate transporter involvement. Here, we propose that the current knowledge strongly suggest a benefit from rebalancing glial transporters during treatment.
CRIS-Team Scopus Importer:2023-04-14
Keywords: Alzheimer's disease; amyotrophic lateral sclerosis; GLAST; glioma; GLT-1; neuroinflammation; Parkinson's disease; SLC7A11

Glucocorticoid modulation of synaptic plasticity in the human temporal cortex of epilepsy patients: Does chronic stress contribute to memory impairment? - Brandner, Sebastian; Schröter, Sarah; Çalışkan, Gürsel; Salar, Seda; Kobow, Katja; Coras, Roland; Blümcke, Ingmar; Hamer, Hajo; Schwarz, Michael; Buchfelder, Michael; Maslarova, Anna (Epilepsia, 2021)
Objective: Memory impairment is common in patients with temporal lobe epilepsy and seriously affects life quality. Chronic stress is a recognized cofactor in epilepsy and can also impair memory function. Furthermore, increased cortisol levels have been reported in epilepsy patients. Animal models have suggested that aggravating effects of stress on memory and synaptic plasticity were mediated via glucocorticoids. The aim of this study was, therefore, to investigate the effect of glucocorticoid receptor (GR) modulation on synaptic plasticity in the human cortex of epilepsy patients. Methods: We performed field potential recordings in acute slices from the temporal neocortex of patients who underwent surgery for drug-resistant temporal lobe epilepsy. Synaptic plasticity was investigated by a theta-burst stimulation (TBS) protocol for induction of long-term potentiation (LTP) in the presence of GR modulators. Results: LTP was impaired in temporal cortex from epilepsy patients. Pretreatment of the slices with the GR antagonist mifepristone (RU486) improved LTP induction, suggesting that LTP impairment was due to baseline GR activation in the human cortex. The highly potent GR agonist dexamethasone additionally weakened synaptic strength in an activity-dependent manner when applied after TBS. Significance: Our results show a direct negative glucocorticoid effect on synaptic potentiation in the human cortex and imply chronic activation of GRs. Chronic stress may therefore contribute to memory impairment in patients with temporal lobe epilepsy. Furthermore, the activity-dependent acute inhibitory effect of dexamethasone suggests a mechanism of synaptic downscaling by which postictally increased cortisol levels may prevent pathologic plasticity upon seizures.
CRIS-Team Scopus Importer:2021-10-29
Keywords: dexamethasone; epilepsy; human cortex; long-term potentiation; stress

Glutamic acid decarboxylase antibody-associated neurological syndromes: Clinical and antibody characteristics and therapy response - Madlener, Marie; Strippel, Christine; Thaler, Franziska S.; Doppler, Kathrin; Wandinger, Klaus P.; Lewerenz, Jan; Ringelstein, Marius; Roessling, Rosa; Menge, Til; Wickel, Jonathan; Kellingshaus, Christoph; Mues, Sigrid; et al. (Journal of the Neurological Sciences, 2023)
Background: Antibodies against glutamic acid decarboxylase (GAD-abs) at high serum levels are associated with diverse autoimmune neurological syndromes (AINS), including cerebellar ataxia, epilepsy, limbic encephalitis and stiff-person syndrome. The impact of low serum GAD-ab levels in patients with suspected AINS remains controversial. Specific intrathecal GAD-ab synthesis may serve as a marker for GAD-ab-associated nervous system autoimmunity. We present characteristics of a multicentric patient cohort with suspected AINS associated with GAD antibodies (SAINS-GAD+) and explore the relevance of serum GAD-ab levels and intrathecal GAD-ab synthesis. Methods: All patients with SAINS-GAD+ included in the registry of the German Network for Research on Autoimmune Encephalitis (GENERATE) from 2011 to 2019 were analyzed. High serum GAD-ab levels were defined as RIA>2000 U/mL, ELISA>1000 U/mL, or as a positive staining pattern on cell-based assays. Results: One-hundred-one patients were analyzed. In descending order they presented with epilepsy/limbic encephalitis (39%), cerebellar ataxia (28%), stiff person syndrome (22%), and overlap syndrome (12%). Immunotherapy was administered in 89% of cases with improvements in 46%. 35% of SAINS-GAD+ patients had low GAD-ab serum levels. Notably, unmatched oligoclonal bands in CSF but not in serum were more frequent in patients with low GAD-ab serum levels. GAD-ab-levels (high/low) and intrathecal GAD-ab synthesis (present or not) did not impact clinical characteristics and outcome. Conclusions: Overall, immunotherapy in SAINS-GAD+ was moderately effective. Serum GAD-ab levels and the absence or presence of intrathecal GAD-ab synthesis did not predict clinical characteristics or outcomes in SAINS-GAD+. The detection of unmatched oligoclonal bands might outweigh low GAD-ab serum levels.
CRIS-Team Scopus Importer:2023-01-13
Keywords: Autoantibodies; Autoimmune encephalitis; GAD; GENERATE; Glutamic acid decarboxylase

Going Beyond the Cookie Theft Picture Test: Detecting Cognitive Impairments Using Acoustic Features - Braun, Franziska; Erzigkeit, Andreas; Lehfeld, Hartmut; Hillemacher, Thomas; Riedhammer, Korbinian; Bayerl, Sebastian P. (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), 2022)
Standardized tests play a crucial role in the detection of cognitive impairment. Previous work demonstrated that automatic detection of cognitive impairment is possible using audio data from a standardized picture description task. The presented study goes beyond that, evaluating our methods on data taken from two standardized neuropsychological tests, namely the German SKT and a German version of the CERAD-NB, and a semi-structured clinical interview between a patient and a psychologist. For the tests, we focus on speech recordings of three sub-tests: reading numbers (SKT 3), interference (SKT 7), and verbal fluency (CERAD-NB 1). We show that acoustic features from standardized tests can be used to reliably discriminate cognitively impaired individuals from non-impaired ones. Furthermore, we provide evidence that even features extracted from random speech samples of the interview can be a discriminator of cognitive impairment. In our baseline experiments, we use OpenSMILE features and Support Vector Machine classifiers. In an improved setup, we show that using wav2vec 2.0 features instead, we can achieve an accuracy of up to 85%.
CRIS-Team Scopus Importer:2022-10-14
Keywords: dementia screening; neuropsychological tests; paralinguistics; pathological speech

Grehlin concentrations correlate with hunger and craving ratings following oral ingestion of macronutrients - Thürauf, Norbert; Bachlechner, Stephan; Denzer-Lippmann, Melanie; Wielopolski, Jan; Fischer, Marie; Büttner, Andrea; Dörfler, Arnd; Schöfl, Christof; Muench, Gerald; Kornhuber, Johannes (CHEMICAL SENSES, 2019)
CRIS-Team WoS Importer:2019-03-26

Guidelines for the psychosomatic evaluation of living liver donors: Analysis of donor exclusion - Erim, Yesim; Malago, Massimo; Valentin-Gamazo, Camino; Senf, Wolfgang; Broelsch, Christoph E. (Transplantation Proceedings, 2003)

Guidelines for the standardized collection of blood-based biomarkers in psychiatry: Steps for laboratory validity - a consensus of the Biomarkers Task Force from the WFSBP - Andreazza, Ana C.; Laksono, Isabelle; Fernandes, Brisa S.; Toben, Catherine; Lewczuk, Piotr; Riederer, Peter; Kennedy, Sidney H.; Kapogiannis, Dimitrios; Thibaut, Florence; Gerlach, Manfred; Gallo, Carla; Kim, Yong-Ku; et al. (World Journal of Biological Psychiatry, 2019)
Recently, there has been a major shift in the field of psychiatry towards the exploration of complex relationships between blood-based biomarkers and the pathophysiology of psychiatric and neuropsychiatric disorders. However, issues with study reproducibility, validity and reliability have hindered progress towards the identification of clinically relevant biomarkers for psychiatry. The achievement of laboratory validity is a crucial first step for the posterior development of clinical validity. There is evidence that the variability observed in blood-based research studies may be minimised with the implementation of standardised pre-analytical methods and uniform clinical protocols (i.e., pre-venipuncture). It has been documented that errors made in the pre-analytical phase account for 46-68.2% of laboratory testing errors. Thus, standardising clinical assessment, ethical procedures and pre-analytical phase of clinical research is essential for the reproducibility, validity and reliability of blood marker assessment, and reducing the risk of invalid test results. Various other areas of research have already moved towards guidelines for the standardised collection of blood-based biomarkers. Here we aim to provide a set of guidelines that we believe would improve biomarker research: (1) pre-venipuncture information and documentation, (2) ethics of participant consent and (3) pre-analytical methods. Ultimately, we hope this will assist study planning and will improve data comparison across studies allowing for the discovery of biomarkers in psychiatry with both laboratorial and clinical validity.
CRIS-Team WoS Importer:2019-04-25

Gustav Nikolaus Specht (1860–1940): His impact on Kraepelin’s nosology and approaches to his position in National Socialism Gustav Nikolaus Specht (1860–1940): Sein Einfluss auf die Nosologie Kraepelins und Annäherungen an seine Position im Nationalsozialismus - Braun, Birgit; Kornhuber, Johannes (Der Nervenarzt, 2021)
Introduction: Gustav Specht (1860–1940) represents the beginning of the university psychiatry in Erlangen. 80 years after his death, this article focuses on Specht’s role in the psychopathologic nosological discussion initiated by Kraepelin. Despite the sparse data situation, the authors approach for the first time Specht’s position within psychiatry under National Socialism. Methods: The relevant primary and secondary literature as well as archival sources were evaluated. Results: In 1897 Specht was appointed supernumerary professor and in 1903 the first full professor for psychiatry in Erlangen. Specht elaborated the role of the manic element in paranoia. Specht added the depressive reaction to Bonhoeffers “exogenic reaction type” in 1913; Specht himself was in the view of some colleagues suspected of having a cyclothyme temperament and twice suffered from exogenous depressive reaction. Discussion: Specht’s research studies on the pathological affect in chronic paranoia influenced the contemporary psychopathological discussion in a sustainable manner. Specht’s change of attitude towards eugenic measures can be interpreted as an adaptation to the National Socialist regime. Conclusion: The work of Gustav Specht can stimulate the cultivation of an interdisciplinary psychopathological discourse.
CRIS-Team Scopus Importer:2021-08-06
Keywords: Chronic mania; Contemporary psychopathological discussion; Exogenous depressive reaction; Hereditary health; Paranoia

Gustav Nikolaus Specht (1860-1940): psychiatric practice, research and teaching during a change of psychiatric paradigm before and after Kraepelin - Braun, Birgit; Kornhuber, Johannes (History of Psychiatry, 2022)
Gustav Specht (1860-1940) developed academic psychiatry in Erlangen. After studying medicine in Wurzburg, Munich and Berlin, he became assistant medical director in the mental asylum of Erlangen. In 1897 he was appointed extraordinary, and in 1903 ordinary, Professor of Psychiatry. A good clinician and teacher, Specht worked during a time of paradigm change in psychiatry. He was an expert in chronic mania, and introduced the concept of the 'grumbler's delusion'. Paranoia he believed to be the core problem of psychopathology and considered the depressive syndrome as an 'exogenous-type' of reaction. For him, trauma was important in the genesis of mental illness, and his 'hystero-melancholy' anticipated the concept of borderline personality disorder.
CRIS-Team WoS Importer:2022-06-24
Keywords: Borderline personality disorder; chronic mania; exogenous depressive reaction; general psychopathology; paranoia; traumatic genesis of mental illness

Gut microbiota-brain interaction: An emerging immunotherapy for traumatic brain injury - Zhang, Yuxuan; Wang, Zhaoyang; Peng, Jianhua; Gerner, Stefan; Yin, Shigang; Jiang, Yong (Experimental Neurology, 2021)
Individuals suffering from traumatic brain injury (TBI) often experience the activation of the immune system, resulting in declines in cognitive and neurological function after brain injury. Despite decades of efforts, approaches for clinically effective treatment are sparse. Evidence on the association between current therapeutic strategies and clinical outcomes after TBI is limited to poorly understood mechanisms. For decades, an increasing number of studies suggest that the gut-brain axis (GBA), a bidirectional communication system between the central nervous system (CNS) and the gastrointestinal tract, plays a critical role in systemic immune response following neurological diseases. In this review, we detail current knowledge of the immune pathologies of GBA after TBI. These processes may provide a new therapeutic target and rehabilitation strategy developed and used in clinical treatment of TBI patients.
CRIS-Team Scopus Importer:2021-01-15
Keywords: CNS; GBA; Immune response; Immunotherapy; TBI

Handbook of the Behavioral Neurobiology of Serotonin, Volume 31, 2nd edition, preface - Müller, Christian P.; Cunningham, Kathryn A. (Handbook of the Behavioral Neurobiology of Serotonin, 2020)
CRIS-Team WoS Importer:2021-03-12

Health-Related Lifestyle Behavior and Religiosity among First-Generation Immigrants of Polish Origin in Germany. - Morawa, Eva; Erim, Yesim (International Journal of Environmental Research and Public Health, 2018)

Health-related quality of life and sense of coherence among Polish immigrants in Germany and indigenous Poles - Morawa, Eva; Erim, Yesim (Transcultural Psychiatry, 2015)
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Health-related quality of life, anxiety and depression in thyroid cancer patients under short-term hypothyroidism and TSH-suppressive levothyroxine treatment - Tagay, Sefik; Herpertz, Stephan; Langkafel, Mathias; Erim, Yesim; Freudenberg, Lutz; Schöpper, Nicole; Bockisch, Andreas; Senf, Wolfgang; Görges, Rainer (European Journal of Endocrinology, 2005)

Health-related quality of life, depression and anxiety in thyroid cancer patients - Tagay, Sefik; Herpertz, Stephan; Langkafel, Mathias; Erim, Yesim; Bockisch, Andreas; Senf, Wolfgang; Görges, Rainer (Quality of life research, 2006)
Keywords: differentiated thyroid cancer; hypothyroidism; health-related quality of life; anxiety; depression

Heart Rate as a Correlate for the Emotional Processing of Body Stimuli in Anorexia Nervosa - Horndasch, Stefanie; Sharon, Elisabeth; Eichler, Anna; Graap, Holmer; Moll, Gunther; Kratz, Oliver (Behavioral Sciences, 2023)
In anorexia nervosa, aberrant emotional reactions toward body stimuli have been discussed. We investigated heart rate as a physiological marker when viewing body stimuli and hypothesized altered HR reactions toward those highly significant and emotional stimuli in anorexia nervosa. In total, 37 anorexia nervosa patients and 43 control participants viewed pictures of women of five different weight categories, while their cardiac activity was recorded. R-R intervals following picture onset were determined, and means were calculated for three distinct time periods. The overall change in HR relative to baseline across all picture categories was greater in the patient group than in the control group (significant effect of “group”, p = 0.002, partial η2 = 0.120). A significant decrease in HR 2 to 8 s after picture presentation was found for pictures of women of extreme weight in both participant groups (significant “category ∗ time segment interaction”, p = 0.01, partial η2 = 0.037) and correlated with scores of sociocultural attitudes toward the appearance for the extremely underweight category (r = −0.33, p = 0.005). Therefore, differential HR reactions for anorexia nervosa patients and control participants were found for body stimuli in general. The highest HR decelerations in response to pictures of strongly underweight and overweight women may reflect emotional processes such as anxiety due to social comparison.
CRIS-Team Scopus Importer:2023-04-07
Keywords: adolescents; anorexia nervosa; body stimuli; heart rate

Hematoma Expansion and Clinical Outcomes in Patients With Factor-Xa Inhibitor-Related Atraumatic Intracereoral Hemorrhage Treated Within the ANNEXA-4 Trial Versus Real-World Usual Care - Huttner, Hagen; Gerner, Stefan; Kuramatsu, Joji; Connolly, Stuart J.; Beyer-Westendorf, Jan; Demchuk, Andrew M.; Middeldorp, Saskia; Zotova, Elena; Altevers, Julia; Andersohn, Frank; Christoph, Mary J.; Yue, Patrick; et al. (Stroke, 2022)
BACKGROUND AND PURPOSE: It is unestablished whether andexanet alfa, compared with guideline-based usual care including prothrombin complex concentrates, is associated with reduced hematoma expansion (HE) and mortality in patients with factor-Xa inhibitor-related intracerebral hemorrhage (ICH). We compared the occurrence of HE and clinical outcomes in patients treated either with andexanet alfa or with usual care during the acute phase of factor-Xa inhibitor-related ICH.
CRIS-Team WoS Importer:2022-02-04

"Herbal seizures" - atypical symptoms after ibogaine intoxication: a case report - Breuer, Lorenz; Kasper, Burkhard S.; Schwarze, Bernd; Gschossmann, Jürgen; Kornhuber, Johannes; Müller, Helge H. (Journal of Medical Case Reports, 2015)
Misuse of various new psychotropic substances such as ibogaine is increasing rapidly. Knowledge of their negative side effects is sparse.We present a case of intoxication with the herbal substance ibogaine in a 22-year-old white man. After taking a cumulative dose of 38 g (taken in two doses), he developed visual memories, nausea and vomiting. He developed a generalized tonic-clonic seizure with additional grand mal seizures. He was treated with midazolam and levetiracetam. Extended drug screenings and computed tomography and magnetic resonance imaging findings were all negative.Knowledge of the side effects of ibogaine has mainly come from reports of cardiovascular complications; seizures are rarely mentioned and experimental findings are inconsistent. It seems that ibogaine acts like a proconvulsive drug at high doses.
EVALuna2:22429

High Manifestations of Mental Distress in Arabic Asylum Seekers Accommodated in Collective Centers for Refugees in Germany - Georgiadou, Ekaterini; Morawa, Eva; Erim, Yesim (International Journal of Environmental Research and Public Health, 2017)

High Rejection Sensitivity in Patients With Somatoform Pain Disorder - Nacak, Yeliz; Morawa, Eva; Erim, Yesim (Frontiers in Psychiatry, 2021)
Objective: Rejection sensitivity (RS) is often associated with mental disorders but as yet has not been investigated in patients with somatoform pain disorder (SPD). The aim of the study was to explore the degree of RS in patients with SPD compared to healthy controls. In addition, we examined factors associated with RS and the moderator effect of SPD. Methods: A total of 65 patients with SPD (confirmed by Structured Clinical Interview, SCID-I) and 65 age- and gender-matched healthy controls participated. Rejection Sensitivity Questionnaire (RSQ), Patient Health Questionnaire (PHQ-9, PHQ-15), Relationship Scale (ReSQ), Essen Trauma Inventory (ETI) and the Childhood Trauma Questionnaire (CTQ) were applied. Multiple linear regression analysis was performed. Results: The level of RS was significantly higher in patients with SPD compared to healthy controls (M = 10.30, SD = 5.64; M = 6.13, SD = 2.50; p < 0.001; d = 0.95). Higher levels of depressive symptoms (p < 0.001), childhood adversities (p < 0.001) and the insecure attachment style (p = 0.007) were related to higher levels of RS. No significant moderation effect was detected. Conclusions: Patients with SPD are highly sensitive to social rejection. In addition, insecure attachment styles as well as depressive symptoms and childhood adversities are strongly associated with RS. Further studies are needed to figure out how RS is connected to SPD over lifetime.
CRIS-Team Scopus Importer:2021-04-19
Keywords: adverse life events; attachment; childhood adversities; chronic pain; rejection sensitivity; somatoform (pain) disorder

High-resolution magnetic resonance imaging in isolated, traumatic oculomotor nerve palsy: A case report - Eisenhut, Felix; Gerner, Stefan; Gölitz, Philipp; Dörfler, Arnd; Seifert, Frank (Radiology Case Reports, 2021)
Traumatic, isolated oculomotor nerve palsy is a rare clinical finding and only few reports demonstrate associated magnetic resonance imaging (MRI) findings. Here, we present the case of a 70-year-old woman with left-sided oculomotor nerve palsy following a mild head trauma due to an e-bike accident. Post-traumatic cerebral computed tomography revealed punctiform hemorrhage in the left interpeduncular cistern and the following MRI confirmed an intraneural hemorrhage of the left oculomotor nerve. Nine weeks later, the follow-up MRI showed progressive atrophy and contrast-enhancement of the left oculomotor nerve. To support functional recovery, a treatment with intravenous corticosteroids was started. Six months later, the patient presented with improved oculomotor nerve function and partial recovery of ptosis and diplopia. In accordance, MRI demonstrated recurrent contrast-enhancement of the atrophic nerve. In conclusion, high-resolution MRI allows the reliable delineation of the oculomotor nerve and can support diagnosis in trauma patients with isolated oculomotor nerve palsy.
CRIS-Team Scopus Importer:2020-12-25
Keywords: Case report; Magnetic resonance imaging; Oculomotor nerve; Traumatic nerve palsy

Hippocampal structure and function are maintained despite severe innate peripheral inflammation - Süß, Patrick; Kalinichenko, Liubov; Baum, Wolfgang; Reichel, Martin; Kornhuber, Johannes; Loskam, Sandra; Ettle, Benjamin; Distler, Jörg; Schett, Georg; Winkler, Jürgen; Müller, Christian P.; Schlachetzki, Johannes (Brain Behavior and Immunity, 2015)
Chronic peripheral inflammation mediated by cytokines such as TNF?, IL-1?, and IL-6 is associated with psychiatric disorders like depression and anxiety. However, it remains elusive which distinct type of peripheral inflammation triggers neuroinflammation and affects hippocampal plasticity resulting in depressive-like behavior. We hypothesized that chronic peripheral inflammation in the human TNF-? transgenic (TNFtg) mouse model of rheumatoid arthritis spreads into the central nervous system and induces depressive state manifested in specific behavioral pattern and impaired adult hippocampal neurogenesis. TNFtg mice showed severe erosive arthritis with increased IL-1? and IL-6 expression in tarsal joints with highly elevated human TNF-? levels in the serum. Intriguingly, IL-1? and IL-6 mRNA levels were not altered in the hippocampus of TNFtg mice. In contrast to the pronounced monocytosis in joints and spleen of TNFtg mice, signs of hippocampal microgliosis or astrocytosis were lacking. Furthermore, locomotion was impaired, but there was no locomotion-independent depressive behavior in TNFtg mice. Proliferation and maturation of hippocampal neural precursor cells as well as survival of newly generated neurons were preserved in the dentate gyrus of TNFtg mice despite reduced motor activity and peripheral inflammatory signature. We conclude that peripheral inflammation in TNFtg mice is mediated by chronic activation of the innate immune system. However, severe peripheral inflammation, though impairing locomotor activity, does not elicit depressive-like behavior. These structural and functional findings indicate the maintenance of hippocampal immunity, cellular plasticity, and behavior despite peripheral innate inflammation.
EVALuna2:12865

Homocysteine metabolism is associated with cerebrospinal fluid levels of soluble amyloid precursor protein and amyloid beta - Oikonomidi, Aikaterini; Lewczuk, Piotr; Kornhuber, Johannes; Smulders, Yvo; Linnebank, Michael; Semmler, Alexander; Popp, Julius (Journal of Neurochemistry, 2016)
Disturbed homocysteine metabolism may contribute to amyloidogenesis by modulating the amyloid precursor protein (APP) production and processing. The objective of this study was to investigate the relationships between cerebral amyloid production and both blood and cerebrospinal fluid (CSF) markers of the homocysteine metabolism. We assessed CSF concentrations of soluble APP?, soluble APP?, and amyloid ?1-42 (A?1-42), as well as plasma levels of homocysteine (Hcys), total vitamin B12, and folate, and CSF concentrations of homocysteine (Hcys-CSF), 5-methyltetrahydrofolate (5-MTHF), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) in 59 subjects with normal cognition. Linear regression analyses were performed to assess associations between homocysteine metabolism parameters and amyloid production. The study was approved by the Ethical Committee of the University of Bonn. After controlling for age, gender, APOEe4 status, and albumin ratio (Qalb), higher A?1-42 CSF levels were associated with high Hcys and low vitamin B12 plasma levels as well as with high Hcys, high SAH, and low 5-MTHF CSF levels. Higher CSF concentrations of sAPP? and sAPP? were associated with high SAH levels. The results suggest that disturbed homocysteine metabolism is related to increased CSF levels of sAPP forms and A?1-42, and may contribute to the accumulation of amyloid pathology in the brain. Disturbed homocysteine metabolism may contribute to amyloidogenesis by modulating the amyloid precursor protein (APP) production and processing. We found associations between CSF levels of soluble APP forms and A?1-42, and markers of the homocysteine metabolism in both plasma and CSF in adults with normal cognition. Disturbed homocysteine metabolism may represent a target for preventive and early disease-modifying interventions in Alzheimer's disease.
EVALuna2:23769

Human beings live longer self-determined Fit4Life - Hornegger, Joachim; Nöth, Elmar; Kornhuber, Johannes (2008)

Human Machine Interface for Elderly People - Kollorz, Eva Nicole Karin; Penne, Jochen; Hornegger, Joachim; Kornhuber, Johannes (Tagungsband zum 1. deutschen AAL-Kongress, 2008)

Human Neutrophil Alloantigen Genotype Frequencies Among Syrian Population - Hauck-Dlimi, Barbara; Damrah, Mohammed; Achenbach, Susanne; Ott, Stephan; Zimmermann, Robert; Zingsem, Jürgen; Strobel, Julian (Clinical Laboratory, 2018)
BACKGROUND: Human neutrophil antigens (HNA) are able to provoke allo- and autoimmune antibodies which lead to reactions like autoimmune and neonatal neutropenia. However, until now no data about HNA genotype distribution in Syrian population exists. The aim of this study was to determine the HNA allele frequencies in the largest group asking for asylum in Germany since 2015. Allele frequencies were compared to data from German blood donors. Therefore, we calculated the risk of alloimmunization and associated transfusion reactions, as well as the risk of developing neonatal neutropenia for newborns of mixed race couples. METHODS: We isolated DNA from blood samples of 100 Syrian volunteers and typed them for HNA-1, -3, -4, and -5 by using a commercial polymerase chain reaction kit with sequence-specific primers (SSP-PCR). Then, we compared the HNA genotype distribution with data from Germans and different populations from literature. RESULTS: In Syrian population the gene frequencies for HNA-1a, HNA-1b, and HNA-1c were 0.375, 0.580, and 0.040, for HNA-3a and -3b 0.742 and 0.258, for HNA-4a and -4b 0.860 and 0.140, and for HNA-5a and -5bw 0.660 and 0.340, respectively. No statistically significant differences between Syrian and German gene frequencies were found. CONCLUSIONS: This study is the first to report HNA gene frequencies in Syrian population. There is no significant difference of HNA genotype frequencies compared to the German population. Therefore, no elevated alloimmunization risks in transfusion of blood and blood components and in pregnancy of mixed race couples exist.
EVALuna2:36010

Hydroxynorketamine, but not ketamine, acts via α7 nicotinic acetylcholine receptor to control presynaptic function and gene expression - Guhathakurta, Debarpan; Petrušková, Aneta; Akdas, Enes Yagiz; Perelló Amorós, Bartomeu; Frischknecht, Renato; Anni, Daniela; Weiss, Eva-Maria; Walter, Martin; Fejtová, Anna (Translational Psychiatry, 2024)
Ketamine is clinically used fast-acting antidepressant. Its metabolite hydroxynorketamine (HNK) shows a robust antidepressant effect in animal studies. It is unclear, how these chemically distinct compounds converge on similar neuronal effects. While KET acts mostly as N-methyl-d-aspartate receptor (NMDAR) antagonist, the molecular target of HNK remains enigmatic. Here, we show that KET and HNK converge on rapid inhibition of glutamate release by reducing the release competence of synaptic vesicles and induce nuclear translocation of pCREB that controls expression of neuroplasticity genes connected to KET- and HNK-mediated antidepressant action. Ro25-6981, a selective antagonist of GluN2B, mimics effect of KET indicating that GluN2B-containing NMDAR might mediate the presynaptic effect of KET. Selective antagonist of α7 nicotinic acetylcholine receptors (α7nAChRs) or genetic deletion of Chrna7, its pore-forming subunit, fully abolishes HNK-induced synaptic and nuclear regulations, but leaves KET-dependent cellular effects unaffected. Thus, KET or HNK-induced modulation of synaptic transmission and nuclear translocation of pCREB can be mediated by selective signaling via NMDAR or α7nAChRs, respectively. Due to the rapid metabolism of KET to HNK, it is conceivable that subsequent modulation of glutamatergic and cholinergic neurotransmission affects circuits in a cell-type-specific manner and contributes to the therapeutic potency of KET. This finding promotes further exploration of new combined medications for mood disorders.
CRIS-Team Scopus Importer:2024-01-26

Hyponatremia is an independent predictor of in-hospital mortality in spontaneous intracerebral hemorrhage - Kuramatsu, Joji; Bobinger, Tobias; Volbers, Bastian; Staykov, Dimitre; Lücking, Hannes; Kloska, Stephan; Köhrmann, Martin; Huttner, Hagen (Stroke, 2014)
Hyponatremia is the most frequent electrolyte disturbance in critical care. Across various disciplines, hyponatremia is associated with increased mortality and longer hospital stay, yet in intracerebral hemorrhage (ICH) no data are available. This the first study that investigated the prevalence and clinical associations of hyponatremia in patients with ICH.This observational study included all consecutive spontaneous ICH patients (n=464) admitted during a 5-year period to the Department of Neurology. Patient characteristics, in-hospital measures, mortality, and functional outcome (90 days and 1 year) were analyzed to determine the effects of hyponatremia (Na<135 mEq/L). Multivariable regression analyses were calculated for factors associated with hyponatremia and predictors of in-hospital mortality.The prevalence of hyponatremia on hospital admission was 15.6% (n=66). Normonatremia was achieved and maintained in almost all hyponatremia patients<48 hours. In-hospital mortality was roughly doubled in hyponatremia compared with nonhyponatremia patients (40.9%; n=27 versus 21.1%; n=75), translating into a 2.5-fold increased odds ratio (P<0.001). Multivariable analyses identified hyponatremia as an independent predictor of in-hospital mortality (odds ratio, 2.2; 95% confidence interval, 1.05-4.62; P=0.037). Within 90 days after ICH, hyponatremia patients surviving hospital stay were also at greater risk of death (odds ratio, 4.8; 95% confidence interval, 2.1-10.6; P<0.001); thereafter, mortality rates were similar.Hyponatremia was identified as an independent predictor of in-hospital mortality with a fairly high prevalence in spontaneous ICH patients. The presence of hyponatremia at hospital admission is related to an increased short-term mortality in patients surviving acute care, possibly reflecting a preexisting condition that is linked to worse outcome due to greater comorbidity. Correction of hyponatremia does not seem to compensate its influence on mortality, which strongly warrants future research.
EVALuna2:22304

Ich habe noch vier Embryos in Istanbul: Muttersprachliche Gruppenpsychotherapie - Erim, Yesim; Kahraman, Sevgi (Psychotherapie im Dialog, 2010)

Identification of a Cascade of Changes in Activities of Daily Living Preceding Short-Term Clinical Deterioration in Mild Alzheimer's Disease Dementia via Lead-Lag Analysis - Fuentes, Manuel; Klostermann, Arne; Kleineidam, Luca; Bauer, Chris; Schuchhardt, Johannes; Maier, Wolfgang; Jessen, Frank; Frölich, Lutz; Wiltfang, Jens; Kornhuber, Johannes; Klöppel, Stefan; Schieting, Vera; et al. (Journal of Alzheimer's Disease, 2020)
BACKGROUND: Cognitive functions and activities of daily living (ADL) become increasingly impaired with progressing Alzheimer's disease. However, the temporal dynamics of this decline are inconsistent. OBJECTIVE: To gain insight into the classical temporal cascade of specific cognitive and ADL changes, which may aid in improving detection of an impending clinical deterioration in patients, and to select ADL items and tests most sensitive to change in a specific disease stage. METHODS: Patients with mild Alzheimer's dementia (AD; MMSE = 23.9±2.88) were followed at 12 and 24 months. Lead-lag analysis of changes in cognitive and functional outcome measures (CDR-SOB, 12 neuropsychological subtest scores from the CERAD + test battery, 25 Bayer-ADL items) was applied to rank the temporal sequence of changes on an ordinal scale. RESULTS: Of 164 patients with mild AD, moderate disease progression was identified in 84 patients over 24 months (ΔMMSE 5.8±8.64; ΔCDR-SOB 4.32±4.03). Ten Bayer-ADL item measures were altered early in moderate progressors and included in a new ADL composite score. Accordingly, the new ADL score surpassed all neuropsychological measures in repeated lead-lag analysis. The Bayer-ADL total score, TMT-A, and MMSE were lagging variables in all lead-lag analyses. CONCLUSION: Short-term clinical deterioration in mild AD is initially preceded by changes (i.e., decline) in a well-defined set of ADL and not in classical cognitive measures.
CRIS-Team Scopus Importer:2020-08-21
Keywords: Alzheimer’s disease; bayer activities of daily living scale; cognitive changes; disease progression; functional changes; lead and lag analysis

Identification of an acid sphingomyelinase ceramide kinase pathway in the regulation of the chemokine CCL5 - Newcomb, Benjamin; Rhein, Cosima; Mileva, Izolda; Ahmad, Rasheed; Clarke, Christopher J.; Snider, Justin; Obeid, Lina M.; Hannun, Yusuf A. (Journal of Lipid Research, 2018)
Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to produce the biologically active lipid ceramide. Previous studies have implicated ASM in the induction of the chemokine CCL5 in response to TNF-α however, the lipid mediator of this effect was not established. In the present study, we identified a novel pathway connecting ASM and ceramide kinase (CERK). The results show that TNF-α induces the formation of ceramide 1-phosphate (C-1-P) in a CERK-dependent manner. Silencing of CERK blocks CCL5 production in response to TNF-α. Interestingly, cells lacking ASM have decreased C-1-P production following TNF-α treatment, suggesting that ASM may be acting upstream of CERK. Functionally, ASM and CERK induce a highly concordant program of cytokine production and both are required for migration of breast cancer cells. Taken together, these data suggest ASM can produce ceramide which is then converted to C-1-P by CERK, and that C-1-P is required for production of CCL5 and several cytokines and chemokines, with roles in cell migration. These results highlight the diversity in action of ASM through more than one bioactive sphingolipid.
EVALuna2:211706

Identification of candidate genes for IFN-mediated depression in HCV patients - Trippler, Martin; Erim, Yesim; Bein, Sabine; Gerken, Guido; Schlaak, Joerg F. (Journal of Hepatology, 2007)

Identification of Drugs Inducing Phospholipidosis by Novel in vitro Data - Muehlbacher, Markus; Tripal, Philipp; Roas, Florian; Kornhuber, Johannes (ChemMedChem, 2012)
Drug-induced phospholipidosis (PLD) is a lysosomal storage disorder characterized by the accumulation of phospholipids within the lysosome. This adverse drug effect can occur in various tissues and is suspected to impact cellular viability. Therefore, it is important to test chemical compounds for their potential to induce PLD during the drug design process. PLD has been reported to be a side effect of many commonly used drugs, especially those with cationic amphiphilic properties. To predict drug-induced PLD in silico, we established a high-throughput cell-culture-based method to quantitatively determine the induction of PLD by chemical compounds. Using this assay, we tested 297 drug-like compounds at two different concentrations (2.5μM and 5.0μM). We were able to identify 28 previously unknown PLD-inducing agents. Furthermore, our experimental results enabled the development of a binary classification model to predict PLD-inducing agents based on their molecular properties. This random forest prediction system yields a bootstrapped validated accuracy of 86%. PLD-inducing agents overlap with those that target similar biological processes; a high degree of concordance with PLD-inducing agents was identified for cationic amphiphilic compounds, small molecules that inhibit acid sphingomyelinase, compounds that cross the blood-brain barrier, and compounds that violate Lipinski's rule of five. Furthermore, we were able to show that PLD-inducing compounds applied in combination additively induce PLD. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Keywords: Cationic amphiphilic drugs; Lysosomal storage disorders; Phospholipidosis; Phospholipids; Toxicology

Identification of new functional inhibitors of acid sphingomyelinase using a structure-property-activity relation model - Kornhuber, Johannes; Tripal, Philipp; Reichel, Martin; Terfloth, Lothar; Bleich, Stefan; Wiftfang, Jens; Gulbins, Erich (Journal of Medicinal Chemistry, 2008)
Some organic weak bases induce a detachment from inner lysosomal membranes and subsequent inactivation of acid sphingomyelinase (ASM) and thus work as functional ASM inhibitors. The aim of the present investigation was to develop a structure-property-activity relation (SPAR) model in order to specify the structural and physicochemical characteristics of probes capable of functionally inhibiting ASM. High pKa and high log P values are necessary but not sufficient preconditions for functional inhibition of ASM. The experimental data supported the requirement of an additional factor, which is necessary for functional inhibition of ASM. This factor k is related to the steric hindrance of the most basic nitrogen atom and presumably modulates the free presentation of a protonated nitrogen atom at the inner lysosomal surface. During the course of the study, we characterized 26 new functional ASM inhibitors, including doxepine 63, fluoxetine 104, maprotiline 109, nortriptyline 114, paroxetine 118, sertraline 124, suloctidil 125, and terfenadine 127. © 2008 American Chemical Society.
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Identification of novel functional inhibitors of acid sphingomyelinase - Kornhuber, Johannes; Muehlbacher, Markus; Trapp, Stefan; Pechmann, Stefanie; Friedl, Astrid; Reichel, Martin; Mühle, Christiane; Terfloth, Lothar; Groemer, Teja W.; Spitzer, Gudrun M.; Liedl, Klaus R.; Gulbins, Erich; et al. (PLoS ONE, 2011)
We describe a hitherto unknown feature for 27 small drug-like molecules, namely functional inhibition of acid sphingomyelinase (ASM). These entities named FIASMAs (Functional Inhibitors of Acid SphingoMyelinAse), therefore, can be potentially used to treat diseases associated with enhanced activity of ASM, such as Alzheimer's disease, major depression, radiation- and chemotherapy-induced apoptosis and endotoxic shock syndrome. Residual activity of ASM measured in the presence of 10 μM drug concentration shows a bimodal distribution; thus the tested drugs can be classified into two groups with lower and higher inhibitory activity. All FIASMAs share distinct physicochemical properties in showing lipophilic and weakly basic properties. Hierarchical clustering of Tanimoto coefficients revealed that FIASMAs occur among drugs of various chemical scaffolds. Moreover, FIASMAs more frequently violate Lipinski's Rule-of-Five than compounds without effect on ASM. Inhibition of ASM appears to be associated with good permeability across the blood-brain barrier. In the present investigation, we developed a novel structure-property-activity relationship by using a random forest-based binary classification learner. Virtual screening revealed that only six out of 768 (0.78%) compounds of natural products functionally inhibit ASM, whereas this inhibitory activity occurs in 135 out of 2028 (6.66%) drugs licensed for medical use in humans. © 2011 Kornhuber et al.
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IL-6 Quotient (The Ratio of Cerebrospinal Fluid IL-6 to Serum IL-6) as a Biomarker of an Unruptured Intracranial Aneurysm - Kaminska, Joanna; Dymicka-Piekarska, Violetta; Chrzanowski, Robert; Sawicki, Karol; Milewska, Anna J.; Zinczuk, Justyna; Tylicka, Marzena; Jadeszko, Marek; Mariak, Zenon; Kratz, Ewa M.; Matowicka-Karna, Joanna; Kornhuber, Johannes; et al. (Journal of Inflammation Research, 2021)
Background: Studies conducted so far have focused mainly on the assessment of IL-6 levels in patients with ruptured brain aneurysms. Carrying out detailed studies in patients with un-ruptured brain aneurysms (UIA) would be extremely important, as it would answer the question of whether IL-6 plays also a role in primary aneurysm formation and growth. Methods: IL-6, S100, NSE, and albumin concentrations in 67 UIA patients and 17 individuals without vascular lesions in the brain were tested using in vitro diagnostic immunoassays according to the manufacturers' instructions. IL-6 Quotient was calculated by dividing cerebrospinal fluid (CSF) IL-6 by serum IL-6. Results: We showed that IL-6 Quotient was significantly higher in UIA patients (1.78) compared to the control group (0.87; p<0.001). Multivariate logistic regression analysis demonstrated that a growth in IL-6 Quotient increases the probability of UIA diagnosis. In UIA patients CSF IL-6 concentration was significantly higher (4.55 pg/ml) compared to the serum concentration (2.39 pg/ml; p<0.001). In both the study and control group, the bloodbrain barrier was intact, thus the CSF-blood gradient of the IL-6 concentration in UIA patients was likely to be the expression of local synthesis of the cytokine within the central nervous system. Patients with multiple brain aneurysms had significantly higher CSF IL-6 levels (5.08 pg/ml) compared to individuals with a single aneurysm (4.14 pg/ml; p=0.0227). Conclusion: This totality of the may suggest IL-6 as a biomarker for UIA formation; however, further studies are needed to unequivocally confirm clinical application of IL-6 concentration evaluation.
CRIS-Team WoS Importer:2021-12-03

Imbalance of Circulating Th17 and Regulatory T Cells in Alzheimer's Disease: A Case Control Study - Oberstein, Timo; Taha, Lava; Spitzer, Philipp; Hellstern, Janina; Herrmann, Martin; Kornhuber, Johannes; Maler, Juan Manuel (Frontiers in Immunology, 2018)
The neuropathological hallmarks of Alzheimer's disease (AD), i.e., neuritic plaques and neurofibrillary tangles, consist of beta amyloid peptides (Aβ) and hyperphosphorylated Tau. These are accompanied by reactive microglia and astrocytes in the vicinity of the neuritic plaques and by changes to the peripheral immune system, e.g., an increase of the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α in the peripheral blood. To address a potential involvement of peripheral T helper cell (Th) subsets in AD, we conducted a case control study with 54 individuals with AD dementia (n = 14), with mild cognitive impairment (MCI) due to AD (MCIAD, n = 14), with MCI unlikely due to AD (MCIother, n = 13), and controls without cognitive impairment (controls, n = 13). The proportions of CD3+CD8-IL-17A+IFNγ- Th17 cells, CD3+CD8-IL-17A-IFNγ+ Th1 cells, and CD4+CD127lowCD25+ regulatory T cells (Tregs) were assessed by flow cytometry. In addition, the correlations of the proportions of Th subsets to cerebrospinal fluid biomarkers were studied. CD3+CD8-IL-17A+IFNγ- Th17 cells were significantly increased in subjects with MCIAD compared to age- and sex-matched subjects with MCIother and controls (MCIAD mean = 1.13, SD = 0.77; MCIother mean = 0.58, SD = 0.28; and controls mean = 0.52, SD = 0.22; p = 0.008). The proportion of CD4+CD127lowCD25+ Tregs was not altered between the different groups, but it significantly positively related with the levels of total Tau and pTau181 (rTreg|totalTau = 0.43, p = 0.021, n = 28; rTreg|pTau181 = 0.46; p = 0.024, n = 28) in subjects with AD but not in nonAD controls (rTreg|totalTau = -0.51, p = 0.007, n = 26). The increase of circulating CD3+CD8-IL-17A+IFNγ- Th17 cells in the early stages of AD and the association of CD4+CD127lowCD25+ Tregs with neurodegeneration marker Tau may indicate that the adaptive immune system relates to neuropathological changes in AD.
EVALuna2:211630

Immediate Intervention Effects of Standardized Multicomponent Group Interventions on People with Cognitive Impairment: A Systematic Review - Özbe, Dominik; Grässel, Elmar; Donath, Carolin; Pendergrass, Anna (Journal of Alzheimer's Disease, 2019)
Background: There is no curative medical treatment for dementia. Therefore, researchers turned their attention to nonpharmacological treatment approaches. Many reviews analyzed the efficacy of single-component interventions, but there has been no systematic review of multicomponent interventions so far.
CRIS-Team WoS Importer:2019-02-22

Immersive Painting - Soutschek, Stefan; Hönig, Florian Thomas; Maier, Andreas; Steidl, Stefan; Stürmer, Michael; Erzigkeit, Helmut; Hornegger, Joachim; Kornhuber, Johannes (Proceedings of the ArtsIT 2009, 2009)

Immunoregulatory role of acid sphingomyelinase in allergic asthma - Sopel, Nina; Kölle, Julia; Dumendiak, Sonja; Koch, Sonja; Reichel, Martin; Rhein, Cosima; Kornhuber, Johannes; Finotto, Susetta (Immunology, 2019)
Acid sphingomyelinase (ASM) is one of the enzymes that catalyzes the breakdown of sphingomyelin to ceramide and phosphorylcholine. In this study, we aimed at elucidating the role of ASM in allergic asthma. We used an ovalbumin-induced murine model of asthma where we compared wild-type and ASM-deficient mice. In wild-type mice, secretory ASM activity in the bronchoalveolar lavage fluid was increased in the acute ovalbumin model, but not in a tolerogenic model. Furthermore, in the absence of ASM, the serum IgE level was reduced, compared with wild-type mice, while an accumulation of interstitial macrophages and foreign antigen-induced regulatory T cells along with exhausted CD4(+) PD1(+) T cells was observed in the lungs of ASM(-/-) mice. In conclusion, in the absence of ASM, we observed an accumulation of immunosuppressive antigen-induced regulatory T cells expressing Foxp3 and CTLA4 in the lung as well as multinucleated interstitial macrophages and exhausted CD4(+) PD1(+) T cells associated with inhibition of serum IgE in asthma.
CRIS-Team WoS Importer:2019-04-09

Immunotherapy targeting plasma ASM is protective in a mouse model of Alzheimer’s disease - Choi, Byung Jo; Park, Min Hee; Park, Kang Ho; Han, Wan Hui; Yoon, Hee Ji; Jung, Hye Yoon; Hong, Ju Yeon; Chowdhury, Md Riad; Kim, Kyung Yeol; Lee, Jihoon; Song, Im Sook; Pang, Minyeong; et al. (Nature Communications, 2023)
Acid sphingomyelinase (ASM) has been implicated in neurodegenerative disease pathology, including Alzheimer’s disease (AD). However, the specific role of plasma ASM in promoting these pathologies is poorly understood. Herein, we explore plasma ASM as a circulating factor that accelerates neuropathological features in AD by exposing young APP/PS1 mice to the blood of mice overexpressing ASM, through parabiotic surgery. Elevated plasma ASM was found to enhance several neuropathological features in the young APP/PS1 mice by mediating the differentiation of blood-derived, pathogenic Th17 cells. Antibody-based immunotherapy targeting plasma ASM showed efficient inhibition of ASM activity in the blood of APP/PS1 mice and, interestingly, led to prophylactic effects on neuropathological features by suppressing pathogenic Th17 cells. Our data reveals insights into the potential pathogenic mechanisms underlying AD and highlights ASM-targeting immunotherapy as a potential strategy for further investigation.
CRIS-Team Scopus Importer:2023-04-07

Impact of Hypothermia Initiation and Duration on Perihemorrhagic Edema Evolution After Intracerebral Hemorrhage - Volbers, Bastian; Herrmann, Sabrina; Willfarth, Wolfgang; Lücking, Hannes; Kloska, Stephan; Dörfler, Arnd; Huttner, Hagen; Kuramatsu, Joji; Schwab, Stefan; Staykov, Dimitre (Stroke, 2016)
Intracerebral hemorrhage (ICH) causes high morbidity and mortality. Recently, perihemorrhagic edema (PHE) has been suggested as an important prognostic factor. Therapeutic hypothermia may be a promising therapeutic option to treat PHE. However, no data exist about the optimal timing and duration of therapeutic hypothermia in ICH. We examined the impact of therapeutic hypothermia timing and duration on PHE evolution.In this retrospective, single-center, case-control study, we identified patients with ICH treated with mild endovascular hypothermia (target temperature 35°C) from our institutional database. Patients were grouped according to hypothermia initiation (early: days 1-2 and late: days 4-5 after admission) and hypothermia duration (short: 4-8 days and long: 9-15 days). Patients with ICH matched for ICH volume, age, ICH localization, and intraventricular hemorrhage were identified as controls. Relative PHE, temperature, and intracranial pressure course were analyzed. Clinical outcome on day 90 was assessed using the modified Rankin scale (0-3=favorable and 4-6=poor).Thirty-three patients with ICH treated with hypothermia and 37 control patients were included. Early hypothermia initiation led to relative PHE decrease between admission and day 3, whereas median relative PHE increased in control patients (-0.05 [interquartile range, -0.4 to 0.07] and 0.07 [interquartile range, -0.07 to 0.26], respectively; P=0.007) and patients with late hypothermia initiation (0.22 [interquartile range 0.12-0.27]; P=0.037). After day 3, relative PHE increased in all groups without difference. Outcome was not different between patients treated with hypothermia and controls.Early hypothermia initiation after ICH onset seems to have an important impact on PHE evolution, whereas our data suggest only limited impact later than day 3 after onset.
EVALuna2:22477

Impact of Perihemorrhagic Edema on Short-Term Outcome After Intracerebral Hemorrhage - Volbers, Bastian; Willfarth, Wolfgang; Schwab, Sibylle; Kuramatsu, J. B.; Huttner, Hagen; Struffert, Tobias; Dörfler, Arnd; Staykov, S. (Neurocritical Care, 2016)
Intracerebral hemorrhage (ICH) is a devastating disease with ICH volume being the main predictor of poor outcome. The prognostic role of perihemorrhagic edema (PHE) is still unclear; however, available data are mainly derived from analyses during the first days after symptom onset. As PHE growth may continue up to 14 days after ICH, we evaluated PHE over a longer period of time and investigated its impact on short-term clinical outcome.In this monocentric retrospective cohort study, patients with spontaneous supratentorial ICH were identified from our institutional data base. Different time points of CT scans were merged to time clusters for better comparison (day 1, 2-3, 4-6, 7-9, 10-12). Absolute volumes of ICH and PHE were obtained using a validated semiautomatic volumetric algorithm. Clinical outcome at discharge was assessed using the modified Rankin Scale (0-3 = favorable, 4-6 = poor).220 patients (83 with favorable, 137 with poor outcome) were included in the final analysis. Mean ICH volume on admission was 22.8 [standard deviation (SD) 24.6] cm(3). Mean absolute PHE volume on admission was 22.5 (SD 20.8) cm(3) and increased to a mean peak volume of 38.1 (SD 31.4) cm(3) during 6.7 (SD 4.1) days on average. Besides GCS on admission, functional status before ICH, peak hematoma volume, lobar localization and fever burden, and high peak PHE volume predicted poor outcome at discharge [OR 0.977 (95 % CI 0.957-0.998)] in the multivariable analysis.PHE may have a negative impact on short-term functional outcome after ICH and therefore represent a possible treatment target.
EVALuna2:22273

Impact of social support on psychosocial symptoms and quality of life in cancer patients: results of a multilevel model approach from a longitudinal multicenter study - Sauer, Christina; Weis, Joachim; Faller, Hermann; Junne, Florian; Honig, Klaus; Bergelt, Corinna; Hornemann, Beate; Stein, Barbara; Teufel, Martin; Goerling, Ute; Erim, Yesim; Geiser, Franziska; et al. (Acta Oncologica, 2019)
Background: This prospective multicenter study aimed to investigate the courses of positive support (PS) and detrimental interaction (DI), two different aspects of social support, and the relation between social support and psychosocial distress and/or health-related quality of life (HRQOL) in a large sample of patients with different cancers. Methods: For this observational study, we enrolled adult patients with cancer from 13 comprehensive cancer centers (CCCs) in Germany. We included a total of 1087 patients in our analysis. We assessed the outcomes via standardized self-report questionnaires at three measurement points: at admission for acute care (T1), 6 (T2) and 12 months (T3) thereafter. Our outcome variables included PS and DI, depression and anxiety symptoms, distress, mental quality of life (MQoL) and physical QoL (PQoL). Data were analyzed using three-level hierarchical linear modeling (HLM) and group-based trajectory modeling. Results: During the first year after the cancer diagnosis, both PS and DI decreased in our sample. Baseline depression symptom severity was a significant predictor of PS and DI. Further analyses revealed significant associations between PS, DI and the course of depression and anxiety symptoms, and MQoL. PS buffered the negative effects of DI with regards to these variables. Low DI was associated with better PQoL, whereas PS was not. In general, the impact of social support on psychosocial outcomes was weak to moderate. Conclusions: Our findings provide evidence for the influence of PS and DI on psychosocial symptoms and HRQOL, and emphasize the importance of psycho-oncological interventions that strengthen PS and prevent or reduce DI for patients with cancer and their relatives.
CRIS-Team WoS Importer:2019-08-13

IMPACT OF STATINS ON HEMATOMA CHARACTERISTICS, PERIHEMORRHAGIC EDEMA, SEIZURES AND FUNCTIONAL RECOVERY AFTER INTRACEREBRAL HEMORRHAGE - Sprügel, Maximilian; Kuramatsu, Joji; Volbers, Bastian; Sembill, Jochen; Saam, Justina; Gerner, Stefan; Balk, Stefanie; Hamer, Hajo; Lücking, Hannes; Hölter, Philip; Nolte, C.; Scheitz, J.; et al. (INTERNATIONAL JOURNAL OF STROKE, 2020)
CRIS-Team WoS Importer:2021-01-22

Impact of telmisartan on the inflammatory state in patients with coronary atherosclerosis - Influence on IP-10, TNF-α and MCP-1 - Klinghammer, Lutz; Urschel, Katharina; Cicha, Iwona; Lewczuk, Piotr; Raaz-Schrauder, Dorette; Achenbach, Stephan; Garlichs, Christoph (Cytokine, 2013)
Background: Hypertension is one of the most prominent risk factors for coronary artery disease (CAD). Treatment of hypertension is therefore important for reducing cardiovascular events and the progression of atherosclerosis. Several treatment strategies are common in clinical practice for example the use of ACE-blockers or angiotensin receptor II blockers (ARBs), so called sartans. Telmisartan, belonging to the class of ARBs, was shown to exert anti-inflammatory effects besides the blood pressure lowering. Methods: In this work, two separate substudy groups of hypertensives were compared. 16 patients with arterial hypertension have been treated with telmisartan (initial 40. mg Kinzalmono®) for 7.3±4.4 months. The telmisartan group was compared to a matched control group including 31 hypertensive patients without telmisartan treatment with a follow up period of 1.9±0.5 years. Serum samples from the beginning and the end of follow up were analyzed with Luminex® technology for 26 cytokines and chemokines. The baseline scores of coronary artery calcification (CAC) were gathered by multislice detector computer tomography. Results: After 7. months of telmisartan treatment and 2. years in control patients most of the measured analytes did not change significantly. MCP-1 (P=0.001; P<0.001) was increased significantly in both telmisartan and control group. The relative decrease in IP-10 and TNF-α levels was observed in telmisartan group, as opposed to the increase in control (telmisartan vs. control P=0.048; P=0.01). No linear rank-correlation between measured analytes and the initial CAC was found. Conclusion: Telmisartan reduced blood pressure in patients with atherosclerosis and arterial hypertension within a short time period, whereas the inflammatory status of these patients remained largely unchanged. An involvement of telmisartan in the regulation of inflammatory and anti-inflammatory mediators in the context of CAD and CAC is possible, but cannot clearly be assumed based on the present findings. © 2013.
CRIS-Team Scopus Importer:2023-03-08
Keywords: %Δa; Δ; Δa; Atherosclerosis; CAC; Chemokines; Cytokines; Risk factors; Telmisartan

Impaired Regulation of ALDH2 Protein Expression Revealing a Yet Unknown Epigenetic Impact of rs886205 on Specific Methylation of a Negative Regulatory Promoter Region in Alcohol-Dependent Patients - Nassab, Mani Haschemi; Rhein, Mathias; Hagemeier, Lars; Kaeser, Marius; Muschler, Marc; Glahn, Alexander; Pich, Andreas; Heberlein, Annemarie; Kornhuber, Johannes; Bleich, Stefan; Frieling, Helge; Hillemacher, Thomas (European Addiction Research, 2016)
Acetaldehyde, the carcinogenic metabolite of ethanol known to provoke aversive symptoms of alcohol consumption, is predominantly eliminated by aldehyde dehydrogenase 2 (ALDH2). Reduced ALDH2 activity correlates with low alcohol tolerance and low risk for alcohol dependence. The ALDH2 promoter polymorphism rs886205 (A>G) is associated with decreased promoter activity, but a molecular mechanism and allele-dependent ALDH2 protein expression has not been described yet. On the basis of allele-dependent epigenetic effects, we analyzed the rs886205 genotype, methylation rates of cytosine-phosphatidyl-guanine (CpG)-sites within a regulatory promoter region and ALDH2 protein levels in 82 alcohol-dependent patients during a 2-week withdrawal and compared them to 34 matched controls. Patients without the G-allele of rs886205 showed higher methylation of the promoter region than controls and readily adapted epigenetically as well as on protein level during withdrawal, while patients with the G-allele displayed retarded methylation readjustment and no change in ALDH2 protein levels. Our data provide novel insights into an unknown genetic-epigenetic interaction, revealing impaired ALDH2 protein expression in patients with the G-allele of rs886205. Additionally, we checked for an association between rs886205 and protection against alcohol dependence and found a trend association between the G-allele and protection against alcohol dependence that needs replication in a larger Caucasian cohort.
EVALuna2:23783

Impaired sleep quality and sleep duration in smokers-results from the German Multicenter Study on Nicotine Dependence - Cohrs, Stefan; Rodenbeck, Andrea; Riemann, Dieter; Szagun, Bertram; Jaehne, Andreas; Brinkmeyer, Juergen; Gruender, Gerhard; Wienker, Thomas; Diaz-Lacava, Amalia; Mobascher, Arian; Dahmen, Norbert; Thürauf, Norbert; et al. (Addiction Biology, 2014)
Cigarette smoking is a severe health burden being related to a number of chronic diseases. Frequently, smokers report about sleep problems. Sleep disturbance, in turn, has been demonstrated to be involved in the pathophysiology of several disorders related to smoking and may be relevant for the pathophysiology of nicotine dependence. Therefore, determining the frequency of sleep disturbance in otherwise healthy smokers and its association with degree of nicotine dependence is highly relevant. In a population-based case-control study, 1071 smokers and 1243 non-smokers without lifetime Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis I disorder were investigated. Sleep quality (SQ) of participants was determined by the Pittsburgh Sleep Quality Index. As possible confounders, age, sex and level of education and income, as well as depressiveness, anxiety, attention deficit hyperactivity, alcohol drinking behaviour and perceived stress, were included into multiple regression analyses. Significantly more smokers than non-smokers (28.1% versus 19.1%; P < 0.0001) demonstrated a disturbed global SQ. After controlling for the confounders, impaired scores in the component scores of sleep latency, sleep duration and global SQ were found significantly more often in smokers than non-smokers. Consistently, higher degrees of nicotine dependence and intensity of smoking were associated with shorter sleep duration. This study demonstrates for the first time an elevated prevalence of sleep disturbance in smokers compared with non-smokers in a population without lifetime history of psychiatric disorders even after controlling for potentially relevant risk factors. It appears likely that smoking is a behaviourally modifiable risk factor for the occurrence of impaired SQ and short sleep duration.
EVALuna2:23615

Implementation and Effect of the Multimodal Psychosocial MAKS Intervention in Day Care Centers for People with Cognitive Impairment: Follow-up Results After the End of the RCT - Grässel, Elmar; Donath, Carolin; Pendergrass, Anna; Luttenberger, Katharina (Gesundheitswesen, 2021)
Zusammenfassung
CRIS-Team WoS Importer:2021-11-12

Implicit bias to food and body cues in eating disorders: a systematic review - Paslakis, Georgios; Scholz-Hehn, Anne Deborah; Sommer, Laura Marie; Kühn, Simone (Eating and Weight Disorders-Studies on Anorexia Bulimia and Obesity, 2020)
Background: Rigid, restrictive eating patterns, fear of gaining weight, body image concerns, but also binge eating episodes with loss of control leading to overweight, at times followed by compensatory measures to control weight, are typical symptoms in eating disorders (EDs). The regulation of food intake in EDs may underlie explicit processes that require cognitive insight and conscious control or be steered by implicit mechanisms that are mostly automatic, rapid, and associated with affective—rather than cognitive—processing. While introspection is not capable of assessing implicit responses, so-called indirect experimental tasks can assess implicit responses underlying a specific behavior by-passing the participant’s consciousness. Here, we aimed to present the current evidence regarding studies on implicit biases to food and body cues in patients with EDs. Methods: We performed a systematic review (PRISMA guidelines). We included controlled studies performed in clinical ED cohorts (vs. healthy control subjects or another control condition, e.g., restrictive vs. binge/purge AN) and using at least one indirect assessment method of interest. Results: Out of 115 screened publications, we identified 29 studies fulfilling the eligibility criteria, and present a synthesis of the essential findings and future directions. Conclusion: In this emerging field of research, the present work provides cornerstones of evidence highlighting aspects of implicit regulation in eating disorders. Applying both direct (e.g., self-reports) and indirect measures for the assessment of both explicit and implicit responses is necessary for a comprehensive investigation of the interplay between these different regulatory mechanisms and eating behavior. Targeted training of implicit reactions is already in use and represents a useful future tool as an add-on to standard psychotherapeutic treatments in the battle against eating disorders. Evidence level: 1 (systematic review).
CRIS-Team Scopus Importer:2020-08-14
Keywords: Anorexia nervosa; Approach avoidance task; Bias; Binge eating disorder; Bulimia nervosa; Implicit

Increased acid sphingomyelinase activity in peripheral blood cells of acutely intoxicated patients with alcohol dependence - Reichel, Martin; Greiner, Elisabeth; Richter-Schmidinger, Tanja; Yedibela, Oezlem; Tripal, Philipp; Jacobi, Andrea; Bleich, Stefan; Gulbins, Erich; Kornhuber, Johannes (Alcoholism-Clinical and Experimental Research, 2010)
Background: Acid sphingomyelinase (ASM; EC 3.1.4.12) hydrolyses membrane sphingomyelin into the bioactive lipid ceramide and is thus involved in different cellular processes such as differentiation, immunity, or cell death. Activation of ASM has been reported in particular in conjunction with the cellular stress response to several external stimuli, and increased ASM activity was observed in a variety of human diseases. Ethanol-induced activation of ASM has been observed in different cell culture systems, thus raising the question about the effect of alcohol intoxication in human subjects on ASM activity in vivo. Methods: We determined ASM activity in peripheral blood mononucleated cells of 27 patients suffering from alcohol dependence. Patients were classified according to their blood alcohol concentration at admission, and ASM activity was determined repeatedly from all patients during alcohol withdrawal. Results: Acutely intoxicated patients displayed significantly higher ASM activity than patients in early abstinence (Mann-Whitney U test: Z = - 2.6, p = 0.009). ASM activity declined in acutely intoxicated patients to normal values with the transition from the intoxicated state to early abstinence (Wilcoxon test: Z = -2.7, p = 0.007). At the end of withdrawal, ASM activity was significantly increased again compared to the early phase of abstinence in both patient groups (Wilcoxon test: Z = -2.691, p = 0.007 and Z = -2.275, p = 0.023, respectively). Conclusions: Alcohol-induced activation of ASM occurs in human subjects and might be responsible for deleterious effects of ethanol intoxication. Chronic alcohol abuse may induce deregulation of sphingomyelin metabolism in general, and this impairment may cause side effects during withdrawal from alcohol. © 2009 by the Research Society on Alcoholism.
Created from Fastlane, Scopus look-up
Keywords: Alcohol Dependence; Ceramide; Sphingomyelin; Sphingomyelin Phosphodiesterase; Sphingomyelinase

Individual activation of dementia sufferers in a home setting: A randomized controlled study Einzelaktivierung von Menschen mit Demenz im häuslichen Setting: Eine randomisierte kontrollierte Studie - Stemmer, Renate; Grässel, Elmar; Schmid, Martin (Zeitschrift für Gerontologie und Geriatrie, 2019)
Background and objectives: The present project investigated the hypothesis that a multimodal individual activation of people with mild to moderate dementia in the home setting during a 6-month intervention period leads to improved everyday practice and cognitive abilities compared to the control group. Material and methods: Intervention: a practical activation was performed by relatives 6 days per week. Cognitive stimulation took place once a week and was done by an external person. The relatives were trained and counselled by project staff. Evaluation: a multicentric randomized controlled trial (RCT) with total sample size of 72 participants suffering from dementia with a mini-mental state test (MMST) ≤24 and ≥12. Of the participants 36 were in the intervention group and 36 in the control group: intervention and follow-up periods each took 6 months. Primary outcome variables: activities of daily living (ADL) abilities (E-ADL test) and cognitive abilities (ADAS-Cog); secondary outcome variables: care dependency scale (PAS) and geriatric symptoms including instrumental abilities (NOSGER scale incl. IADL-test), quality of life (WHOQOL-BREF) and stress for the informal caregivers scale (HPS). The evaluation was carried out as a pre-post analysis (t 0 /t 1 /t 2 ) using comparison of means for the differences between the pretest and posttest values. Results: After the end of the 6‑month intervention period (t 1 ), there were positive effects on the ADL skills of people with mild dementia (Cohens d = 0.37) but no effects on the ADL skills of people with moderate dementia (Cohens d = 0.00). In terms of cognitive abilities, mild effects (Cohens d = 0.26) were found in people with moderate dementia but not in mild dementia (Cohens d = 0.04). The results are not significant. Caring dependency results in a non-significant effect in mild dementia (Cohens d = 0.33) and a significant effect in moderate dementia (Cohens d = 0.87, p = 0.025, Mann-Whitney U‑test). The NOSGER subscale social behavior showed a strong significant effect in moderately severe dementia (Cohens d = 1.03, p = 0.013) but 6 months after the end of the intervention (t 2 ) these effects were no longer detectable. With respect to the activating relatives no effects could be detected. Conclusion: The hypothesis could not be confirmed. Since the target sample size was not reached, significant results were not expected. Nevertheless, the calculation of the effect sizes provides indications of possible effects of multimodal activation.
CRIS-Team Scopus Importer:2019-05-21
Keywords: Activities of daily living; Cognitive dysfunction; Informal care; Multimodal activation; Quality of life

Individual differences in inflammatory and oxidative mechanisms of stress-related mood disorders - Kalinichenko, Liubov; Kornhuber, Johannes; Müller, Christian P. (Frontiers in Neuroendocrinology, 2019)
Emotional stress leads to the development of peripheral disorders and is recognized as a modifiable risk factor for psychiatric disorders, particularly depression and anxiety. However, not all individuals develop the negative consequences of emotional stress due to different stress coping strategies and resilience to stressful stimuli. In this review, we discuss individual differences in coping styles and the potential mechanisms that contribute to individual vulnerability to stress, such as parameters of the immune system and oxidative state. Initial differences in inflammatory and oxidative processes determine resistance to stress and stress-related disorders via the alteration of neurotransmitter content in the brain and biological fluids. Differences in coping styles may serve as possible predictors of resistance to stress and stress-related disorders, even before stressful conditions. The investigation of natural variabilities in stress resilience may allow the development of new methods for preventive medicine and the personalized treatment of stress-related conditions.
CRIS-Team Scopus Importer:2019-08-20
Keywords: Coping style; Cytokines; Depression; Immune system; Individual differences; Oxidative stress; Stress; Stress resistance; Translational medicine; Vulnerability

Individualised computerised cognitive training for community-dwelling people with mild cognitive impairment: study protocol of a completely virtual, randomised, controlled trial - Book, Stephanie; Jank, Michael; Pendergrass, Anna; Grässel, Elmar (Trials, 2022)
Background: People with mild cognitive impairment (MCI) are at increased risk of converting to dementia. Cognitive training can improve the cognitive abilities of people with MCI. Computerised cognitive training (CCT) offers several advantages over traditional paper-and-pencil cognitive training and has the potential to be more individualised by matching task difficulty with individual performance. Recent systematic reviews have reported promising effects of CCT on improving the cognitive capacities of people with MCI. However, the quality of existing studies has been limited, and it is still unclear whether CCT can influence the progression to dementia. We developed an ‘individualised’ CCT (MAKSCog) specialised for people with MCI that automatically matches task difficulty with individual performance and an active control training (‘basic’ CCT). The aims of the present study are (a) to evaluate MAKSCog and (b) to investigate whether it can be applied to maintain the cognitive abilities of people with MCI. Methods: The present study investigates the effects of CCT on cognition in a randomised controlled intervention study in Germany. Participants are community-dwelling people with a psychometric diagnosis of MCI based on the Montreal Cognitive Assessment (MoCA) and Mini-Mental Status Test (MMSE). Screening and baseline testing are conducted via a videoconferencing assessment and telephone. Participants are randomly allocated. The treatment phase is 6 months with an open phase in which participants can freely decide to continue to use the CCTs. Additionally, both CCTs contain a monthly computerised cognitive assessment that measures different cognitive abilities: information processing speed, memory span, short term memory, and logical reasoning. Discussion: This is the first study to investigate the effect of MAKSCog, an individualised CCT, specifically developed for people with different subtypes of MCI. A methodological strength is the double-blind, randomised, controlled design and the use of basic CCT as an active control group. The study is conducted entirely virtually with valid telehealth assessments for cognitive function. Methodological limitations might include a restriction to participants who feel comfortable with the use of technology and who own a computer, laptop, or tablet. Trial registration: ISRCTN ISRCTN14437015. Prospectively registered on 27 February 2020.
CRIS-Team Scopus Importer:2022-05-20
Keywords: Community-dwelling; Computerised cognitive training; Mild cognitive impairment; Non-pharmacological intervention; Randomised controlled trial

Individual Stress Burden and Mental Health in Health Care Workers during the COVID-19 Pandemic: Moderating and Mediating Effects of Resilience - Schmuck, Jonas; Hiebel, Nina; Kriegsmann-Rabe, Milena; Schneider, Juliane; Matthias, Julia-Katharina; Erim, Yesim; Morawa, Eva; Jerg-Bretzke, Lucia; Beschoner, Petra; Albus, Christian; Weidner, Kerstin; Radbruch, Lukas; et al. (International Journal of Environmental Research and Public Health, 2022)
Introduction: The COVID-19 pandemic generated a significant burden on the German health care system, affecting the mental health of health care workers (HCW) in particular. Resilience may serve as an essential protective factor for individuals' well-being. Objective: Our objective was to identify demographic and work-related correlates of individual resilience and to investigate the association between pandemic-related stress, resilience and mental health using different resilience models. Methods: Our sample comprised 1034 German HCW in different medical professions who completed an online survey from 20 April to 1 July 2020. Resilience was assessed using the Resilience Scale-5 (RS-5). The pandemic-related self-reported stress burden was captured by a single item, while depression and anxiety symptoms were measured with the PHQ-2 and GAD-2, respectively. Additionally, various sociodemographic and work-related factors were assessed. Results: Overall, we found high levels of resilience in the sample compared to a German sample before the pandemic, which were significantly associated only with the older age of participants and having children in both univariate and multivariate analyses. Regarding mechanisms of resilience, moderation analysis revealed that low individual resilience and high pandemic-related stress burden independently contributed to both anxiety and depression symptoms while resilience additionally moderated the relationship between stress burden and anxiety symptoms. The link between self-reported stress burden and mental health symptoms was also partially mediated by individual resilience. Conclusion: Taken together, the findings based on the present sample during the COVID-19 pandemic suggest that resilience plays a central role in the mental health of healthcare workers and that resilience-building interventions should be expanded, especially with a focus on younger employees.
CRIS-Team WoS Importer:2022-06-24

Indoor rock climbing (bouldering) as a new treatment for depression: study design of a waitlist-controlled randomized group pilot study and the first results - Luttenberger, Katharina; Stelzer, Eva-Maria; Foerst, Stefan; Schopper, Matthias; Kornhuber, Johannes; Book, Stephanie (BMC Psychiatry, 2015)
Depression is one of the most common diseases in industrialised nations. Physical activity is regarded as an important part of therapeutic intervention. Rock climbing or bouldering (rock climbing to moderate heights without rope) comprises many aspects that are considered useful, but until now, there has been hardly any research on the effects of a bouldering group intervention on people with depression. The purpose of this controlled pilot study was twofold: first, to develop a manual for an eight-week interventional program that integrates psychotherapeutic interventions in a bouldering group setting and second, to assess the effects of a bouldering intervention on people with depression.The intervention took place once a week for three hours across a period of eight weeks. Participants were randomly assigned to the two groups (intervention vs. waitlist). The intervention group began the bouldering therapy immediately after a baseline measurement was taken; the waitlist participants began after an eight-week period of treatment as usual. On four measurement dates at eight-week intervals, participants completed the Beck Depression Inventory II (BDI-II), the symptom checklist-90-R (SCL-90), the questionnaire on resources and self-management skills (FERUS), and the attention test d2-R. A total of 47 participants completed the study, and the data were analysed with descriptive statistics. Cohen's d was calculated as a measure of the effect size. For the primary hypothesis, a regression analysis and the Number Needed to Treat (NNT) (improvement of at least 6 points on the BDI-II) were calculated.After eight weeks of intervention, results indicated positive effects on the measures of depression (primary hypothesis: BDI-II: Cohen's d = 0.77), this was supported by the regression analysis with "group" as the only significant predictor of a change in depression (p = .007). The NNT was four.These findings provide the first evidence that therapeutic bouldering may offer an effective treatment for depression. Further research is required.Current controlled trials, ISRCTN17623318 , registered on July 15(th) 2015.
EVALuna2:23684

Influence of antithrombotic pre-treatment and time window on hemorrhagic complications of ivt in ischemic stroke - Macha, Kosmas; Hölter, Philip; Sembill, Jochen; Hock, Stefan; Siedler, Gabriela; Mühlen, Iris; Haupenthal, David; Schwab, Stefan; Kallmünzer, Bernd; Dörfler, Arnd (EUROPEAN JOURNAL OF NEUROLOGY, 2022)
CRIS-Team WoS Importer:2022-07-22

Influence of Early Enteral Nutrition on Clinical Outcomes in Neurocritical Care Patients With Intracerebral Hemorrhage - Peng, Jianhua; Volbers, Bastian; Sprugel, Maximilian I.; Hölter, Philip; Engelhorn, Tobias; Jiang, Yong; Kuramatsu, Joji; Huttner, Hagen; Dörfler, Arnd; Schwab, Stefan; Gerner, Stefan (Frontiers in Neurology, 2021)
Objective: Early enteral nutrition (EEN) represents the current standard of care for patients treated in general intensive care units (ICU). Specific nutritional recommendations for patients receiving dedicated neurocritical care are not established. This study investigated associations of EEN with clinical outcomes for patients suffering from intracerebral hemorrhage treated at a neurological ICU (NICU).
CRIS-Team WoS Importer:2021-05-14

Influence of early irradiation on in vitro red blood cell (RBC) storage variables of leucoreduced RBCs in additive solution SAG-M - Hauck-Dlimi, Barbara; Braun, Timm; Eckstein, Reinhold; Strobel, Joachim; Zimmermann, Rüdiger (Vox Sanguinis, 2016)
The only accepted way to avoid transfusion-associated graft-versus-host disease is irradiation of blood components. With respect to irradiation and associated storage time, different recommendations exist. We examined early irradiated (day +3) leucoreduced red blood cell units for irradiation-associated damages during storage.We studied 80 leucoreduced units from two manufacturers. All RBCs were stored in the additive solution saline-adenine-glucose-mannitol (SAG-M) and leucoreduced on collection day. Forty components were irradiated on day +3 with 30 Gy, 40 served as non-irradiated controls. Samples were drawn and analysed from these 80 units on days +3, +7, +14, +21, +28, +35 and +42.From day +14, there was a significant difference in the in vitro haemolysis rate between the non-irradiated and the irradiated components. Two of the irradiated units showed a haemolysis rate over the recommended limit of 0·8% on day +42. Potassium and lactate dehydrogenase activity increased faster in irradiated groups during storage.Our findings show that leucoreduced RBCs which are irradiated early after collection show an obvious radiation damage over storage period. Interestingly, on days +28, +35 and +42 the quality of RBCs which were irradiated on day +3 was nearly identical to the quality of RBCs which were irradiated on day +14 in a former series. Early irradiation does not cause more damage of RBCs during subsequent storage than irradiation on day +14. The maximum storage period of irradiated RBCs should remain restricted to 28 days from collection, however independently from the day of irradiation within this period.
EVALuna2:15994

Influence of genetic variants in SORL1 gene on the manifestation of Alzheimer's disease - Louwersheimer, Eva; Ramirez, Alfredo; Cruchaga, Carlos; Becker, Tim; Kornhuber, Johannes; Peters, Oliver; Heilmann, Stefanie; Wiltfang, Jens; Jessen, Frank; Visser, Pieter Jelle; Scheltens, Philip; Pijnenburg, Yolande A. L.; et al. (Neurobiology of Aging, 2015)
We studied the association of SORL1 single-nucleotide polymorphisms genotypes with measures of pathology in patients with probable Alzheimer's disease (AD) using an endophenotype approach. We included (1) 133 patients from the German Dementia Competence Network (71 ± 8 years; 50% females; Mini Mental State Examination [MMSE], 24 ± 3); (2) 83 patients from the Alzheimer's Disease Neuroimaging Initiative (75 ± 8 years; 45% females; MMSE, 24 ± 2); and (3) 452 patients from the Amsterdam Dementia Cohort 66 ± 8 years; 47% females; MMSE, 20 ± 5). As endophenotype markers we used cognitive tests, cerebrospinal fluid (CSF) biomarkers amyloid-beta, total tau (tau), tau phosphorylated at threonine 181, and hippocampal atrophy. We measured 19 SORL1 SNP alleles. Genotype-endophenotype associations were determined by linear regression analyses. There was an association between rs2070045-G allele and increased CSF-tau and more hippocampal atrophy. Additionally, haplotype-based analyses revealed an association between haplotype rs11218340-A/rs3824966-G/rs3824968-A and higher CSF-tau and CSF-tau phosphorylated at threonine 181. In conclusion, we found that SORL1 SNP rs2070045-G allele was related to CSF-tau and hippocampal atrophy, 2 endophenotype markers of AD, suggesting that SORL1 may be implicated in the downstream pathology in AD.
EVALuna:32725

Influence of kinship on donors' mental burden in living donor liver transplantation - Erim, Yesim; Beckmann, Mingo; Kroencke, Sylvia; Sotiropoulos, Georgios C.; Paul, Andreas; Senf, Wolfgang; Schulz, Karl-Heinz (Liver Transplantation, 2012)

Influence of the fat/carbohydrate component of snack food on energy intake pattern and reinforcing properties in rodents - Heß, Andreas; Kreß, Stefanie; Rakete, Stefan; Muench, Gerald; Kornhuber, Johannes; Pischetsrieder, Monika; Müller, Christian P. (Behavioural Brain Research, 2019)
Hedonic intake of strongly rewarding foods is independent from biological needs and, thus, a common cause of obesity. The effect of potato chips on energy intake in a snacking model could be explained by their fat/carbohydrate content (FCHc). The present study investigated if the FCHc shapes energy intake patterns and reward processing of satiated rodents. Modulation of energy intake patterns was studied in an established snacking model offering FCHc rich food for 3 x 10 min/day to satiated rats. Reward processing was analyzed by a previously established conditioned place preference tests in satiated mice. The limited access to FCHc rich food led to higher daily energy intake compared to days without access (110 +/- 10 vs. 96 +/- 5 kcal/day) indicating that fat/carbohydrate intake was not fully compensated by reducing standard chow intake during the rest of the day. Furthermore, fat/carbohydrate snacking led to binge eating episodes with up to 55% of the daily energy intake consumed during limited access. Forced withdrawal from fat/carbohydrate snacking opportunities for six weeks increased the total daily energy intake and the relative amount of energy consumed by FCHc after reintroducing fat/carbohydrate snacking. Snack food and fat/carbohydrate food were powerful food reinforcers in satiated mice in contrast to standard chow. Altogether, these data suggest that the FCHc of snack food has strong reinforcing properties, which are probably responsible for the significant modulation of the amount and pattern of food intake in ad libitum fed animals.
CRIS-Team WoS Importer:2019-04-16

Information needs in cancer patients across the disease trajectory. A prospective study - Goerling, Ute; Faller, Hermann; Hornemann, Beate; Hoenig, Klaus; Bergelt, Corinna; Maatouk, Imad; Stein, Barbara; Teufel, Martin; Erim, Yesim; Geiser, Franziska; Niecke, Alexander; Senf, Bianca; et al. (Patient Education and Counseling, 2020)
Objective: As satisfaction with information received is an important precondition of adherence to treatment in cancer patients, we aimed to examine the level of perceived information, information satisfaction and information needs, and examine the prospective association between information satisfaction and anxiety. Methods: In a multicenter study in Germany, 1398 cancer patients were evaluated in terms of this at baseline, after 6 and 12 months. Results: At baseline, the majority of patients reported to feel well-informed. Nevertheless, a considerable proportion reported to wish more information. The proportion of patients reporting unmet information needs declined over time (p < 0.001). Anxiety at baseline is negatively associated with information satisfaction after 6 months (β = −0.10, p < 0.01). Conversely, information satisfaction at baseline is negatively associated with anxiety after 6 months (β = −0.10, p < 0.01). At 12 months, only the negative path leading from anxiety to information satisfaction was significant (β = −0.12, p < 0.01). Conclusion: We found high levels of information received and high information satisfaction. Nevertheless, there was a considerable quantity of unmet information needs. A bidirectional relationship between information satisfaction and anxiety symptoms emerged after 6 months. Practice implications: These results underline the priority of providing information and emotional support to cancer patients to improve satisfaction with information.
CRIS-Team Scopus Importer:2019-09-03
Keywords: Anxiety; Cancer; Information needs; Oncology; Satisfaction with information

Inhibition of acid sphingomyelinase by ambroxol prevents SARS-CoV-2 entry into epithelial cells. - Carpinteiro, Alexander; Gripp, Barbara; Hoffmann, Markus; Poehlmann, Stefan; Hoertel, Nicolas; Edwards, Michael J.; Kamler, Markus; Kornhuber, Johannes; Becker, Katrin Anne; Gulbins, Erich (Journal of Biological Chemistry, 2021)
The acid sphingomyelinase/ceramide system has been shown to be important for cellular infection with at least some viruses, for instance, rhinovirus or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Functional inhibition of the acid sphingomyelinase using tricyclic antidepressants prevented infection of epithelial cells, for instance with SARS-CoV-2. The structure of ambroxol, that is, trans-4-[(2,4-dibromanilin-6-yl)-methyamino]-cyclohexanol, a mucolytic drug applied by inhalation, suggests that the drug might inhibit the acid sphingomyelinase and thereby infection with SARS-CoV-2. To test this, we used vesicular stomatitis virus pseudoviral particles presenting SARS-CoV-2 spike protein on their surface (pp-VSV-SARS-CoV-2 spike), a bona fide system for mimicking SARS-CoV-2 entry into cells. Viral uptake and formation of ceramide localization were determined by fluorescence microscopy, activity of the acid sphingomyelinase by consumption of [14C]sphingomyelin and ceramide was quantified by a kinase method. We found that entry of pp-VSV-SARS-CoV-2 spike required activation of acid sphingomyelinase and release of ceramide, events that were all prevented by pretreatment with ambroxol. We also obtained nasal epithelial cells from human volunteers prior to and after inhalation of ambroxol. Inhalation of ambroxol reduced acid sphingomyelinase activity in nasal epithelial cells and prevented pp-VSV-SARS-CoV-2 spike-induced acid sphingomyelinase activation, ceramide release, and entry of pp-VSV-SARS-CoV-2 spike ex vivo. The addition of purified acid sphingomyelinase or C16 ceramide restored entry of pp-VSV-SARS-CoV-2 spike into ambroxol-treated epithelial cells. We propose that ambroxol might be suitable for clinical studies to prevent coronavirus disease 2019.
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Inhibition of Acid Sphingomyelinase by Antidepressants Counteracts Stress-Induced Activation of P38-Kinase in Major Depression - Grassmé, Heike; Jernigan, Peter L.; Hoehn, Richard S.; Wilker, Barbara; Soddemann, Matthias; Edwards, Michael J.; Müller, Christian P.; Kornhuber, Johannes; Gulbins, Erich (Neurosignals, 2015)
Major depressive disorder is a common disease with serious morbidity, including increased risk of death from suicide. Major depressive disorder is treated with antidepressants. However, the molecular targets of antidepressants remained ill-defined and require further elucidation.Mice were treated with corticosterone to induce stress, amitriptyline and the p38-kinase (p38K) inhibitor SB239063 or a combination of these drugs. Phosphorylation of p38K in hippocampal neurons was determined by immunostaining with a phospho-specific antibody, neuronal proliferation using BrdU-labelling and behaviour employing a set of behavioural tests.Corticosterone induced phosphorylation/activation of p38K in the hippocampus in vivo. Antidepressants reversed the effect of corticosterone on p38K activation in wildtype mice, but had no effect in acid sphingomyelinase-deficient animals. Corticosterone also reduced neurogenesis and triggered depression-like behavioural changes, effects that were prevented by pharmacological inhibition of p38K.Stress induces p38K phosphorylation/activation in the hippocampus and thereby reduces neurogenesis and induces depression-like symptoms, events that are prevented by antidepressants via inhibition of the acid sphingomyelinase/ceramide system.
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Innovative Treatment Based on Historical Roots - Mueller, Helge H.; Linde, Otfried K.; Demling, Joachim (Biological Psychiatry, 2017)
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Insecure attachment style and cumulative traumatic life events in patients with somatoform pain disorder: A cross-sectional study - Nacak, Yeliz; Morawa, Eva; Tuffner, Daniela; Erim, Yesim (Journal of psychosomatic research, 2017)

Insights into the neuropathology of cerebral ischemia and its mechanisms - Ahad, Mohamad Anuar; Kumaran, Kesevan Rajah; Ning, Tiang; Mansor, Nur Izzati; Effendy, Mohamad Azmeer; Damodaran, Thenmoly; Lingam, Kamilla; Wahab, Habibah Abdul; Nordin, Norshariza; Liao, Ping; Müller, Christian P.; Hassan, Zurina (Reviews in the Neurosciences, 2020)
Cerebral ischemia is a result of insufficient blood flow to the brain. It leads to limited supply of oxygen and other nutrients to meet metabolic demands. These phenomena lead to brain damage. There are two types of cerebral ischemia: focal and global ischemia. This condition has significant impact on patient's health and health care system requirements. Animal models such as transient occlusion of the middle cerebral artery and permanent occlusion of extracranial vessels have been established to mimic the conditions of the respective type of cerebral ischemia and to further understand pathophysiological mechanisms of these ischemic conditions. It is important to understand the pathophysiology of cerebral ischemia in order to identify therapeutic strategies for prevention and treatment. Here, we review the neuropathologies that are caused by cerebral ischemia and discuss the mechanisms that occur in cerebral ischemia such as reduction of cerebral blood flow, hippocampal damage, white matter lesions, neuronal cell death, cholinergic dysfunction, excitotoxicity, calcium overload, cytotoxic oedema, a decline in adenosine triphosphate (ATP), malfunctioning of Na+/K+-ATPase, and the blood-brain barrier breakdown. Altogether, the information provided can be used to guide therapeutic strategies for cerebral ischemia.
CRIS-Team Scopus Importer:2020-03-31
Keywords: cerebral ischemia; excitotoxicity; neuropathology mechanisms; stroke

Insights into the Pathophysiology of Alzheimer's Disease and Potential Therapeutic Targets: A Current Perspective - Kumaran, Kesevan Rajah; Yunusa, Suleiman; Perimal, Enoch; Wahab, Habibah; Müller, Christian P.; Hassan, Zurina (Journal of Alzheimer's Disease, 2023)
The aging population increases steadily because of a healthy lifestyle and medical advancements in healthcare. However, Alzheimer's disease (AD) is becoming more common and problematic among older adults. AD-related cases show an increasing trend annually, and the younger age population may also be at risk of developing this disorder. AD constitutes a primary form of dementia, an irreversible and progressive brain disorder that steadily damages cognitive functions and the ability to perform daily tasks. Later in life, AD leads to death as a result of the degeneration of specific brain areas. Currently, the cause of AD is poorly understood, and there is no safe and effective therapeutic agent to cure or slow down its progression. The condition is entirely preventable, and no study has yet demonstrated encouraging findings in terms of treatment. Identifying this disease's pathophysiology can help researchers develop safe and efficient therapeutic strategies to treat this ailment. This review outlines and discusses the pathophysiology that resulted in the development of AD including amyloid-beta plaques, tau neurofibrillary tangles, neuroinflammation, oxidative stress, cholinergic dysfunction, glutamate excitotoxicity, and changes in neurotrophins level may sound better based on the literature search from Scopus, PubMed, ScienceDirect, and Google Scholar. Potential therapeutic strategies are discussed to provide more insights into AD mechanisms by developing some possible pharmacological agents for its treatment.
CRIS-Team WoS Importer:2023-02-17

Insular Cortical Thickness in Patients With Somatoform Pain Disorder: Are There Associations With Symptom Severity and Childhood Trauma? - Meyer, Elisabeth; Morawa, Eva; Nacak, Yeliz; Rösch, Julie; Dörfler, Arnd; Forster, Clemens; Erim, Yesim (Frontiers in Psychiatry, 2020)
Background: Studies show significant alterations in insular cortical thickness in patients with somatoform pain disorder (SPD). Additionally, associations between childhood maltreatment and morphometric alterations in insular cortex have been observed. Since patients with SPD often report about adverse childhood experiences, we were interested in the interrelationship of exposure to childhood maltreatment and insular cortical thickness in patients with SPD. Methods: Fifteen adult patients with SPD (ICD-10 F 45.40/41, DSM-Code 307.80) and thirteen healthy adult controls underwent T1-weighted MR brain imaging. In the voxel-based morphometry (VBM) analysis we compared whole brain cortical thickness between patients and controls using a Student’s two-sampled t-test (p <.05). Then we performed a secondary analysis to detect differences in cortical thickness levels in the insular cortex between both groups. For further analysis of differences in insular cortical thickness we used gender, age, depressive symptoms [Patient Health Questionnaire (PHQ)-9], and whole brain cortical thickness as nuisance covariates. Subsequently we explored associations between insular cortical thickness, symptom severity (PHQ-15) and past experiences of childhood maltreatment (CTQ) in both groups. Results: Patients showed reduced insular cortical thickness in a subregion of right Brodmann area (BA) 13 (anterior part of the insular cortex), whereas whole brain cortical thickness did not differ between groups. The between-group difference in the identified insular subregion of right BA 13 was not diminished by any of the covariates. This implies that the reduction in cortical thickness in the identified insular subregion might be due to a specific group effect. The effect sizes indicate that the group of patients experienced more childhood maltreatment than the control group. Nonetheless, significant correlations of insular cortical thickness with symptom severity and childhood maltreatment in the total collective could not be demonstrated for the group of patients. Conclusions: Our data suggest that alterations in the identified insular subregion of right BA 13 are associated with somatoform pain, independent of gender, age, or coincident depression levels. To identify significant associations of insular cortical thickness and experiences of childhood maltreatment in patients with SPD investigations within larger samples are highly recommended.
CRIS-Team Scopus Importer:2020-10-02
Keywords: childhood maltreatment; cortical thickness; insula; somatoform pain; voxel-based morphometry

Insulin resistance is associated with reduced food odor sensitivity across a wide range of body weights - Poessel, Maria; Freiherr, Jessica; Wiencke, Kathleen; Villringer, Arno; Horstmann, Annette (Nutrients, 2020)
The worldwide obesity epidemic is a major health problem driven by the modern food environment. Recently, it has been shown that smell perception plays a key role in eating behavior and is altered in obesity. However, the underlying mechanisms of this phenomenon are not well understood yet. Since the olfactory system is closely linked to the endocrine system, we hypothesized that hormonal shifts in obesity might explain this relationship. In a within-subject, repeated-measures design, we investigated sensitivity to a food and a non-food odor in the hungry and sated state in 75 young healthy (26 normal weight, 25 overweight, and 24 obese) participants (37 women). To determine metabolic health status and hormonal reactivity in response to food intake, we assessed pre-and postprandial levels of insulin, leptin, glucose, and ghrelin. Odor sensitivity did not directly depend on body weight status/body mass index (BMI) or hunger state. However, we could establish a strong negative mediating effect of insulin resistance on the relationship between BMI/waist-hip ratio and olfactory sensitivity for the food odor. These findings indicate an impact of metabolic health status on sensitivity to food odors. Our results contribute to a better understanding of the mechanisms behind altered smell perception in obesity.
CRIS-Team Scopus Importer:2020-08-07
Keywords: HOMA-IR; Insulin resistance; Obesity; Odor sensitivity; Olfaction

Integration of Clinical Examination, Self-Report, and Hair Ethyl Glucuronide Analysis for Evaluation of Patients With Alcoholic Liver Disease Prior to Liver Transplantation - Beckmann, Mingo; Paslakis, Georgios; Boettcher, Michael; Helander, Anders; Erim, Yesim (Progress in Transplantation, 2016)
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Intensive care therapy of space-occupying large hemispheric infarction. Summary of the NCS/DGNI guidelines - Boesell, J.; Schoenenberger, S.; Dohmen, C.; Juettler, E.; Staykov, D.; Zweckberger, K.; Hacke, W.; Schwab, Sibylle; Torbey, M. T.; Huttner, Hagen (Der Nervenarzt, 2015)
Large hemispheric infarction (LHI), synonymously called malignant middle cerebral artery (MCA) infarction, is a severe neurological disease with a high mortality and morbidity. Treating physicians as well as relatives are often faced with few and low quality data when attempting to apply optimal treatment to these patients and make decisions. While current stroke treatment guidelines focus on risk factors, prevention and acute management, they include only limited recommendations concerning intensive care management of LHI. The Neurocritical Care Society (NCS) and the German Society for Neurocritical and Emergency Medicine (DGNI) organized an interdisciplinary consensus conference on intensive care management of LHI to meet this demand. European and American experts in neurology, neurocritical care, neurosurgery, neuroradiology and neuroanesthesiology were selected based on their expertise and research focus. Subgroups for several main topics elaborated a number of central clinical questions concerning this topic and evaluated the quality of the currently available data according to the grading of recommendation assessment, development and evaluation (GRADE) guideline system. Subsequently, evidence-based recommendations were compiled after weighing the advantages against the disadvantages of certain management options. This is a commented abridged version of the results of the consensus conference.
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Intercultural opening on the example of the LVR joint project migration - Erim, Yesim; Morawa, Eva; Gün, Ali Kemal (Ärztliche Psychotherapie und Psychosomatische Medizin, 2014)

Interkulturelle Aspekte der psychotherapeutischen Beziehung Kollektive Übertragungsbereitschaften - Erim, Yesim (Psychotherapie im Dialog, 2004)

Interlaboratory proficiency processing scheme in CSF aliquoting: implementation and assessment based on biomarkers of Alzheimer's disease - Lewczuk, Piotr; Gaignaux, Amelie; Kofanova, Olga; Ermann, Natalia; Betsou, Fay; Brandner, Sebastian; Mroczko, Barbara; Blennow, Kaj; Strapagiel, Dominik; Paciotti, Silvia; Vogelgsang, Jonathan; Roehrl, Michael H.; et al. (Alzheimer's Research and Therapy, 2018)
BACKGROUND: In this study, we tested to which extent possible between-center differences in standardized operating procedures (SOPs) for biobanking of cerebrospinal fluid (CSF) samples influence the homogeneity of the resulting aliquots and, consequently, the concentrations of the centrally analyzed selected Alzheimer's disease biomarkers. METHODS: Proficiency processing samples (PPSs), prepared by pooling of four individual CSF samples, were sent to 10 participating centers, which were asked to perform aliquoting of the PPSs into two secondary aliquots (SAs) under their local SOPs. The resulting SAs were shipped to the central laboratory, where the concentrations of amyloid beta (Aβ) 1-42, pTau181, and albumin were measured in one run with validated routine analytical methods. Total variability of the concentrations, and its within-center and between-center components, were analyzed with hierarchical regression models. RESULTS: We observed neglectable variability in the concentrations of pTau181 and albumin across the centers and the aliquots. In contrast, the variability of the Aβ1-42 concentrations was much larger (overall coefficient of variation 31%), with 28% of the between-laboratory component and 10% of the within-laboratory (i.e., between-aliquot) component. We identified duration of the preparation of the aliquots and the centrifugation force as two potential confounders influencing within-center variability and biomarker concentrations, respectively. CONCLUSIONS: Proficiency processing schemes provide objective evidence for the most critical preanalytical variables. Standardization of these variables may significantly enhance the quality of the collected biospecimens. Studies utilizing retrospective samples collected under different local SOPs need to consider such differences in the statistical evaluations of the data.
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Interleukin-6 secretion upon acute psychosocial stress as a potential predictor of psychotherapy outcome in posttraumatic stress disorder - Rhein, Cosima; Hepp, Tobias; Kraus, Olga; von Majewski, Kristin; Lieb, Marietta; Rohleder, Nicolas; Erim, Yesim (Journal of Neural Transmission, 2021)
Posttraumatic stress disorder (PTSD) is a severe mental disorder that can develop after a traumatic event. PTSD has been reported to be associated with activation of the innate immune system, as measured by increased levels of pro-inflammatory cytokines. While it is well known that PTSD patients display increased levels of interleukin 6 (IL-6) when compared with healthy controls, the relationship between cytokine secretion and treatment outcome has been hardly investigated yet. The aim of this study was to assess the potential association of inflammatory activation and therapy outcome in PTSD. Before therapeutic intervention, we applied the Trier Social Stress Test (TSST) as a method to elicit psychosocial stress and an acute inflammatory response. IL-6 levels were measured in blood plasma of PTSD patients at different time points before and after the TSST. Severity of depressive, trauma-related, and somatic symptoms was assessed before and 8 weeks after trauma-focused treatment in a multimodal day clinic setting. We showed that high reactivity of IL-6 to psychosocial stress at the beginning of the therapy was associated with a negative therapy outcome in PTSD, especially regarding depressive symptoms. This study suggests plasma IL-6 reactivity as a potential molecular marker to predict treatment outcome in PTSD.
CRIS-Team Scopus Importer:2021-05-28
Keywords: BDI-II; Interleukin 6; Posttraumatic stress disorder; Psychotherapy; Therapy outcome; Trier Social Stress Test

Internet gaming disorder, social network disorder and laterality: handedness relates to pathological use of social networks - Bouna-Pyrrou, Polyxeni; Mühle, Christiane; Kornhuber, Johannes; Lenz, Bernd (Journal of Neural Transmission, 2015)
The internet age bears new challenges that include health risks. It is agreed that excessive internet use may reach pathological levels. However, the concept of internet addiction lacks specificity and, therefore, warrants studies on its diagnostic and etiologic classification. This study was conducted to characterize the novel DSM-5 criteria for internet gaming disorder and the adapted criteria for the "social network disorder". Based on the established association of handedness and substance use disorders, we also explored whether internet use related to laterality. For this study, 3,287 volunteers participated in the online survey and gave particulars concerning their internet use in general, internet gaming and use of social networks, laterality markers (hand, foot, eye, ear, rotational preference in gymnastics, and head turning asymmetry) and health status. Of the participants, 1.1 % fulfilled the criteria for internet gaming disorder, and 1.8 % fulfilled the criteria for social network disorder. The applied criteria were highly correlated with the time spent on the respective internet activities (p < 4 × 10(-56)). The analyses of comorbidity and working hours support the thresholds of 5/9 criteria and >=30 h/week spent on the internet for the classification as pathological (p < 5 × 10(-2)). Moreover, we found that left-handedness related to more affirmed criteria and longer times spent on social networks (p <= 4 × 10(-2)). The provided criteria proved to be user-friendly, comprehensible and well accepted. The results contribute to a better understanding of pathological internet gaming and social network use and provide evidence that biological markers of substance use disorders are involved in internet addiction.
EVALuna2:23695

Intravenous theophylline is the most effective intervention to prolong EEG seizure duration in patients undergoing electroconvulsive therapy - Tzabazis, Alexander; Wiernik, Michaela; Wielopolski, Jan; Sperling, Wolfgang; Ihmsen, Harald; Schmitt, Hubert J.; Münster, Tino (BMC Anesthesiology, 2017)
BACKGROUND: Seizure duration in electroconvulsive therapy (ECT) is positively related with patients' outcome. This study sought to investigate the impact of anesthetic management on seizure duration, and the impact of selected drugs (theophylline, remifentanil, S-ketamine) on seizure duration. METHODS: Retrospective analysis of all patients undergoing ECT at our institution from January 2011 to April 2012 was performed based on electronic medical chart and review of existing quality improvement data. Patient data (N = 78), including gender, age, height, weight, and administered drugs, energy levels, and electroencephalic seizure duration were analyzed. Statistical analysis was performed using a generalized linear model. RESULTS: A total of 78 patients (male = 39, female = 39, age 51 ± 12 years) were included. Average number of session was 10 ± 6 (1-30). In our patient population, theophylline administration was the only parameter, which significantly prolonged seizure duration, whereas S-ketamine, remifentanil, thiopental, age, sex, session or energy level had no significant effect. CONCLUSION: Theophylline can be a useful adjunct for patients with inadequate seizure duration. If there is a concomitant beneficial effect on patients' outcome needs to be investigated in further studies.
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Invasive neurology in focus - Schwab, Sibylle; Huttner, Hagen (Der Nervenarzt, 2016)
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Invasive stroke treatment - Study results and clinical routine : Lost in translation? - Breuer, L.; Schwab, Sibylle; Köhrmann, Martin (Der Nervenarzt, 2016)
How can the overwhelmingly positive results of the five randomized thrombectomy trials published in 2015 be transferred to the clinical routine?Analysis of trial-specific characteristics with regard to implementation of mechanical thrombectomy into clinical routine.Stroke patients with symptomatic proximal artery occlusion are principally eligible for mechanical thrombectomy; however, the stroke patients included in the thrombectomy trials are not representative of all stroke patients. They were carefully selected according to clinical and imaging criteria as well as to the time window from symptom onset. Furthermore, they were treated in highly selected specialized stroke centers. Analysis of the five trials and the Catalan population-based SONIIA registry revealed that the observed number needed to treat (NNT) of 5 to reach a modified Rankin scale (mRS) score of 0-2 only applies to approximately 1 % of all stroke patients. The NNT for the remaining patients who are principally eligible for thrombectomy requires further study. Currently, centralization seems to be useful to facilitate mechanical thrombectomy in routine care leading to several problems that have to be dealt with in particular regions. Secondary transport to thrombectomy centers plays a major role in this context and has to be provided with highest priority.Only careful analysis of study results and the background circumstances will enable adequate organization and successful practical implementation of this highly effective therapy in the clinical routine. Regional conditions have to be considered and will be crucial in this context.
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Inverse effects of lipopolysaccharides on anxiety in pregnant mice and their offspring - Solati, Jalal; Kleehaupt, Eva; Kratz, Oliver; Moll, Gunther; Golub, Yulia (Physiology & behavior, 2015)
This study aimed to evaluate the effects of the bacterial lipopolysaccharide (LPS) exposure during early pregnancy on anxiety-related behaviour of both pregnant female mice and their male offspring. Pregnant NMRI mice were treated with subcutaneous injections of LPS (30, 60, 120, 240 and 480?g/kg) on the tenth gestational day of pregnancy. Pro-inflammatory cytokines, such as TNF-?, IL-1?, IL-6 and corticosterone levels, were measured in maternal serum 1.5h following the LPS injections. Baseline anxiety levels of pregnant mice (1.5h after LPS administration) and their male offspring (at postnatal days 60-70) were investigated with the elevated plus maze (EPM) test. In addition, anxiety levels in the offspring were measured after 2h restraint stress or TNF-? (10?g/kg) administration. Our results demonstrate that LPS administration induces anxiety-like behaviour and a significant increase in cytokines and corticosterone levels in maternal serum. However, in male offspring, prenatal LPS administration has no significant effects on serum cytokines and corticosterone secretion with an exception of the lowest LPS dose that slightly reduced corticosterone levels. Interestingly, prenatal LPS treatment seemed to decrease the baseline anxiety levels, while pretreatment with restraint stress or TNF-? abolished this anxiolytic effects. In summary, our results suggest that prenatal exposure to LPS during early pregnancy may result in reduced baseline anxiety in adult male offspring.
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Investigation of Inertial Cavitation Induced by Modulated Focused Ultrasound Stimuli - George, Benedikt; Savsek, Ula; Fischer, Dagmar; Ermert, Helmut; Rupitsch, Stefan Johann (Current Directions in Biomedical Engineering, 2022)
A passive cavitation detection setup is used to assess and verify the capability of frequency- and amplitude-modulated ultrasound burst signals on the generation of inertial cavitation. The measurements were conducted with a flow-through tissue-mimicking phantom with a canal of dc = 1 mm in diameter simulating a fine blood vessel. By means of a flow velocity of vf = 50 mm/s circulating blood in the cardiovascular system is imitated. Applying signal frequencies from f = 550 − 950 kHz and peak rarefaction pressures in a range from pPRFP ≈ 0.17 − 1.81 MPa, various ultrasound stimuli with alternating signal parameters were investigated in the absence and presence of a talcum-water mixture acting as cavitation nuclei. By evaluating the broadband emissions in the frequency domain and calculating the voltage spectral density Srm, the results can be compared. The findings of the present study demonstrate that each ultrasound stimulus triggers a similar strength of cavitation noise at the same Mechanical Index, representing a certain pressure. Over the whole frequency and Mechanical Index (pressure) range, each ultrasound signal type generates a voltage spectral density from Srm = 0.25 − 2.25 V/√Hz.
CRIS-Team Scopus Importer:2022-09-30
Keywords: Focused ultrasound; Inertial cavitation; Modulated signals

Investigation of the role of rare TREM2 variants in frontotemporal dementia subtypes - Thelen, Mathias; Razquin, Cristina; Hernandez, Isabel; Gorostidi, Ana; Sanchez-Valle, Raquel; Ortega-Cubero, Sara; Wolfsgruber, Steffen; Drichel, Dmitriy; Fliessbach, Klaus; Duenkel, Tanja; Damian, Marinella; Heilmann, Stefanie; et al. (Neurobiology of Aging, 2014)
Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. Rare TREM2 variants have been recently identified in families affected by FTD-like phenotype. However, genetic studies of the role of rare TREM2 variants in FTD have generated conflicting results possibly because of difficulties on diagnostic accuracy. The aim of the present study was to investigate associations between rare TREM2 variants and specific FTD subtypes (FTD-S). The entire coding sequence of TREM2 was sequenced in FTD-S patients of Spanish (n = 539) and German (n = 63) origin. Genetic association was calculated using Fisher exact test. The minor allele frequency for controls was derived from in-house genotyping data and publicly available databases. Seven previously reported rare coding variants (p.A28V, p.W44X, p.R47H, p.R62H, p.T66M, p.T96K, and p.L211P) and 1 novel missense variant (p.A105T) were identified. The p.R47H variant was found in 4 patients with FTD-S. Two of these patients showed cerebrospinal fluid pattern of amyloid beta, tau, and phosphorylated-tau suggesting underlying Alzheimer's disease (AD) pathology. No association was found between p.R47H and FTD-S. A genetic association was found between p.T96K and FTD-S (p = 0.013, odds ratio = 4.23, 95% Confidence Interval [1.17-14.77]). All 6 p.T96K patients also carried the TREM2 variant p.L211P, suggesting linkage disequilibrium. The remaining TREM2 variants were found in 1 patient, respectively, and were absent in controls. The present findings provide evidence that p.T96K is associated with FTD-S and that p.L211P may contribute to its pathogenic effect. The data also suggest that p.R47H is associated with an FTD phenotype that is characterized by the presence of underlying AD pathology.
EVALuna2:23660

iPads in Breast Imaging - A Phantom Study - Hammon, Matthias; Schlechtweg, Philipp; Schulz-Wendtland, Rüdiger; Uder, Michael; Schwab, Sibylle (Geburtshilfe und Frauenheilkunde, 2014)
Introduction: Modern tablet PCs as the iPad are becoming more and more integrated into medicine. The aim of this study was to evaluate the display quality of iPads regarding digital mammography. Materials and Methods: Three experienced readers compared the display quality of the iPad 2 and 3 with a dedicated 10 megapixel (MP) mammography liquid crystal display (LCD) screen in consensus using the standardized Contrast Detail Mammography (CDMAM) phantom. Phantom fields without agreement between the readers were classified as "uncertain", correct 2 : 1 decisions were classified as "uncertain/readable". In a second step display quality of the three reading devices was judged subjectively in a side by side comparison. Results: The 10 MP screen was superior to both iPads in 4 (phantom-)fields and inferior in 2 fields. Comparing the iPads, version 3 was superior in 4 fields and version 2 was superior in 1 field. However these differences were not significant. Total number of "uncertain" fields did not show significant differences. The number of "uncertain" fields was 15 with the 10 MP screen, 16 with the iPad 2 and 17 with the iPad 3 (p > 0.05), the number of "uncertain/readable" fields was 4, 7 and 8, respectively. Subjective image quality of the iPad 3 and the 10 MP screen was rated superior to the iPad 2. Conclusion: The evaluated iPads, especially in version 3, seem to be adequate to display mammograms in a diagnostic quality and thus could be useful e.g. for patient consultation, clinical demonstration or educational and teaching purposes. However primary mammogram reading should still be performed on dedicated large sized reading screens.
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Iranian and German Patients in an Urban Psychiatric Practice: Are they Different Concerning Frequency and Severity of Mental Illness? - Leidinger, Rezvan; Morawa, Eva; Erim, Yesim (Psychiatrische Praxis, 2016)
EVALuna2:24028

Is bouldering-psychotherapy a cost-effective way to treat depression when compared to group cognitive behavioral therapy - results from a randomized controlled trial - Schwarzkopf, Larissa; Dorscht, Lisa; Kraus, Ludwig; Luttenberger, Katharina (BMC Health Services Research, 2021)
Background Bouldering-Psychotherapy (BPT) has proven to effectively reduce depressive symptoms, but evidence on its cost-effectiveness is lacking. Corresponding information is paramount to support health policy decision making on a potential implementation of BPT in routine care. Methods Using data from the German KuS trial BPT was compared with group Cognitive Behavioral Therapy (CBT). Severity of depression symptoms at end of the intervention was operationalized via Montgomery-Asberg Depression Rating Scale (MADRS) and Patient Health Questionnaire (PHQ-9). Adopting a societal perspective, direct medical costs and productivity loss were calculated based on standardized unit costs. To determine incremental cost-effectiveness ratios (ICER) and cost-effectiveness-acceptance curves (CEAC), adjusted mean differences (AMD) in costs (gamma-distributed model) and both effect parameters (Gaussian-distributed model) were obtained from 1000 simultaneous bootstrap replications. Results BPT was related to improved effects (AMDs: MADRS -2.58; PHQ-9: - 1.35) at higher costs (AMD: +euro 754). No AMD was significant. ICERs amounted to euro288 per MADRS-point and euro550 per PHQ-9-point. For both effect parameters about 20% of bootstrap replications indicated dominance of BPT, and about 75% larger effects at higher costs. At hypothetical willingness to pay (WTP) thresholds of euro241 (MADRS) and euro615 (PHQ-9) per unit of change BPT had a 50% probability of being cost-effective. Conclusion BPT is a promising alternate treatment strategy which - in absence of established WTP thresholds for improving symptoms of depression - cannot unambiguously be claimed cost-effective. Further studies defining subgroups that particularly benefit from BPT appear paramount to delineate recommendations for an efficient prospective roll-out to routine care.
CRIS-Team WoS Importer:2021-11-05

Is Instillational Topical Negative Pressure Wound Therapy in Peri-Prosthetic Infections of the Breast Effective? A Pilot Study - Grüner, Johanna; Horch, Raymund E.; Geierlehner, Alexander; Müller-Seubert, Wibke; Cai, Aijia; Arkudas, Andreas; Ludolph, Ingo (Journal of Personalized Medicine, 2022)
Peri-prosthetic breast infections pose a risk of severe complications after breast implant surgery. The need to remove the breast implant, control the infection and perform additional surgical procedures are the consequences. Reimplantation of an alloplastic implant is only appropriate after an infection-free interval. In this retrospective cohort study, we investigated the effectiveness of negative pressure wound treatment with instillation and dwell time (NPWTi-d) on peri-prosthetic breast infections in combination with implant removal and antibiotic therapy. Twelve patients treated with NPWTi-d due to breast implant infection were included in the study. The bacterial burden was analyzed using wound swabs before and after NPWTi-d. Additionally, laboratory values were determined before NPWTi-d and immediately before wound closure. A total of 13 peri-prosthetic breast infections in 12 patients were treated using implant removal and NPWTi-d. In 76.9% (n = 10) of the cases, the patients had undergone alloplastic breast reconstruction following cancer-related mastectomy, whereas 23.1% (n = 3) of the patients had undergone breast augmentation for cosmetic reasons. The bacterial burden in the breast pocket decreased statistically significant after implant removal and NPWTi-d. No shift from Gram-positive to Gram-negative bacteria was observed. Inflammatory markers rapidly decreased following treatment. NPWTi-d had a positive impact on the healing process after peri-prosthetic breast infections, leading to a decrease in bacterial burden within the wounds and contributing to uneventful healing. Therefore, secondary reimplantation of breast prostheses might be positively influenced when compared to conventional implant removal and simple secondary closure. Further studies are required to conclusively establish the beneficial long-term effects of using NPWTi-d for the treatment of peri-prosthetic breast infections.
CRIS-Team WoS Importer:2023-01-06

Isoflurane in (Super-) Refractory Status Epilepticus: A Multicenter Evaluation - Stetefeld, Henning R.; Schaal, Alexander; Scheibe, Franziska; Nichtweiss, Julia; Lehmann, Felix; Mueller, Marcus; Gerner, Stefan; Huttner, Hagen; Luger, Sebastian; Fuhrer, Hannah; Boesel, Julian; Schoenenberger, Silvia; et al. (Neurocritical Care, 2021)
Background: We aimed to determine the association between seizure termination and side effects of isoflurane for the treatment of refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE) in neurointensive care units (neuro-ICUs). Methods: This was a multicenter retrospective study of patients with RSE/SRSE treated with isoflurane for status epilepticus termination admitted to the neuro-ICUs of nine German university centers during 2011–2018. Results: We identified 45 patients who received isoflurane for the treatment of RSE/SRSE. During isoflurane treatment, electroencephalograms showed no epileptiform discharges in 33 of 41 (80%) patients, and burst suppression pattern was achieved in 29 of 41 patients (71%). RSE/SRSE was finally terminated after treatment with isoflurane in 23 of 45 patients (51%) for the entire group and in 13 of 45 patients (29%) without additional therapy. Lengths of stay in the hospital and in the neuro-ICU were significantly extended in cases of ongoing status epilepticus under isoflurane treatment (p = 0.01 for length of stay in the hospital, p = 0.049 for length in the neuro-ICU). During isoflurane treatment, side effects were reported in 40 of 45 patients (89%) and mainly included hypotension (n = 40, 89%) and/or infection (n = 20, 44%). Whether side effects occurred did not affect the outcome at discharge. Of 22 patients with follow-up magnetic resonance imaging, 2 patients (9%) showed progressive magnetic resonance imaging alterations that were considered to be potentially associated with RSE/SRSE itself or with isoflurane therapy. Conclusions: Isoflurane was associated with a good effect in stopping RSE/SRSE. Nevertheless, establishing remission remained difficult. Side effects were common but without effect on the outcome at discharge.
CRIS-Team Scopus Importer:2021-08-06
Keywords: Epilepsy; Isoflurane; Status epilepticus

Isolated meningomyeloradiculitis following infection with tick borne encephalitis virus - Racz, Attila; Schaller, Gerd; Lunkenheimer, Jens; Engelhorn, Tobias; Dörfler, Arnd; Sperling, Wolfgang; Schwab, Stefan; Maihöfner, Christian (Clinical Neurology and Neurosurgery, 2012)
CRIS-Team Scopus Importer:2022-08-05
Keywords: Meningomyeloradiculitis; Myelitis; Polyradiculitis; Tick borne encephalitis virus

Joint Effects of the Epigenetic Alteration of Neurotrophins and Cytokine Signaling: A Possible Exploratory Model of Affective Symptoms in Alcohol-Dependent Patients? - Heberlein, Annemarie; Schuster, Rilana; Kleimann, Alexandra; Groh, Adrian; Kordon, Andreas; Opfermann, Birgitt; Lichtinghagen, Ralf; Groschl, Michael; Kornhuber, Johannes; Bleich, Stefan; Frieling, Helge; Hillemacher, Thomas (Alcohol and Alcoholism, 2017)
Aims: Neurotrophins have been linked to the symptomatology of alcohol dependence. We aimed to investigate a possible association between the methylation of the promoters of both neurotrophins, the serum levels of the cytokines and core symptoms of alcohol dependence as withdrawal severity and anxiety. Methods: In this study we investigated a possible association between alterations in the methylation of the BDNF IV/NGF I gene promoter and the cytokines tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in 55 male alcohol-dependent patients. Results: Mean methylation of the promoter of the BDNF gene was significantly associated with the TNF-α serum levels and the CIWA-score during withdrawal (P < 0.001). Moreover, mean methylation of the NGF I promoter was significantly associated with the IL-6 serum levels and STAI-I score during withdrawal (P < 0.001). Conclusion: Our results suggest an association between the epigenetic regulation of both neurotrophins, BDNF and NGF, cytokine release and the symptomatology of alcohol dependence. They imply that changes in the methylation of neurotrophins may contribute to the symptomatology of alcohol dependence by affecting relevant downstream signaling cascades.
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Kdm6b and Pmepa1 as Targets of Bioelectrically and Behaviorally Induced Activin A Signaling - Link, Andrea; Kurinna, Svitlana; Havlicek, Steven; Lehnert, Sandra; Reichel, Martin; Kornhuber, Johannes; Winner, Beate; Huth, Tobias; Zheng, Fang; Werner, Sabine; Alzheimer, Christian (Molecular Neurobiology, 2016)
The transforming growth factor-? (TGF-?) family member activin A exerts multiple neurotrophic and protective effects in the brain. Activin also modulates cognitive functions and affective behavior and is a presumed target of antidepressant therapy. Despite its important role in the injured and intact brain, the mechanisms underlying activin effects in the CNS are still largely unknown. Our goal was to identify the first target genes of activin signaling in the hippocampus in vivo. Electroconvulsive seizures, a rodent model of electroconvulsive therapy in humans, were applied to C57BL/6J mice to elicit a strong increase in activin A signaling. Chromatin immunoprecipitation experiments with hippocampal lysates subsequently revealed that binding of SMAD2/3, the intracellular effectors of activin signaling, was significantly enriched at the Pmepa1 gene, which encodes a negative feedback regulator of TGF-? signaling in cancer cells, and at the Kdm6b gene, which encodes an epigenetic regulator promoting transcriptional plasticity. Underlining the significance of these findings, activin treatment also induced PMEPA1 and KDM6B expression in human forebrain neurons generated from embryonic stem cells suggesting interspecies conservation of activin effects in mammalian neurons. Importantly, physiological stimuli such as provided by environmental enrichment proved already sufficient to engender a rapid and significant induction of activin signaling concomitant with an upregulation of Pmepa1 and Kdm6b expression. Taken together, our study identified the first target genes of activin signaling in the brain. With the induction of Kdm6b expression, activin is likely to gain impact on a presumed epigenetic regulator of activity-dependent neuronal plasticity.
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Kidney-transplant patients receiving living- or dead-donor organs have similar psychological outcomes (findings from the PI-KT study) - Müller, Helge H.O.; Lücke, Caroline; Englbrecht, Matthias; Wiesener, Michael S.; Siller, Teresa; Eckardt, Kai-Uwe; Kornhuber, Johannes; Maler, Juan Manuel (Mental Illness, 2020)
Purpose: Kidney transplantation (KT) is the treatment of choice for end-stage chronic kidney disease (CKD) and is well known to improve the clinical outcome of patients. However, the impact of KT on comorbid psychological symptoms, particularly depression and anxiety, is less clear, and recipients of living-donor (LD) organs may have a different psychological outcome from recipients of dead-donor (DD) organs. Design/methodology/approach: In total, 152 patients were included and analyzed using a cross-sectional design. Of these patients, 25 were pre-KT, 13 were post-KT with a LD transplant and 114 were post-KT with a DD transplant. The patients were tested for a variety of psychometric outcomes using the Hospital Anxiety and Depression Scale, the 12-Item Short Form Health Survey (assessing physical and mental health-related quality of life), the Resilience Scale, the Coping Self-Questionnaire and the Social Support Questionnaire. Findings: The mean age of the patients was 51.25 years and 40 per cent of the patients were female. As expected, the post-KT patients had significantly better scores on the physical component of the Short Form Health Survey than the pre-KT patients, and there were no significant differences between the two post-KT groups. There were no significant differences among the groups in any of the other psychometric outcome parameters tested, including anxiety, depression and the mental component of health-related quality of life. Research limitations/implications: KT and the origin of the donor organ do not appear to have a significant impact on the psychological well-being of transplant patients with CKD. Although the diagnosis and early treatment of psychological symptoms, such as depression and anxiety, remain important for these patients, decisions regarding KT, including the mode of transplantation, should not be fundamentally influenced by concerns about psychological impairments at the population level. Originality/value: CKD is a serious condition involving profound impairment of the physical and psychological well-being of patients. KT is considered the treatment of choice for most of these patients. KT has notable advantages over dialysis with regard to the long-term physical functioning of the renal and cardiovascular system and increases the life expectancy of patients. However, the data on the improvement of psychological impairments after KT are less conclusive.
CRIS-Team Scopus Importer:2020-06-16
Keywords: Coping; Kidney transplantation

KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference - Schumann, Gunter; Liu, Chunyu; O'Reilly, Paul; Gao, He; Song, Parkyong; Xu, Bing; Ruggeri, Barbara; Amin, Najaf; Jia, Tianye; Preis, Sarah; Lepe, Marcelo Segura; Akira, Shizuo; et al. (Proceedings of the National Academy of Sciences of the United States of America, 2016)
Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified ?-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 × 10(-12)). ?-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific ?-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.
EVALuna2:23756

Klinische Interkulturelle Psychotherapie Ein Lehr- und Praxisbuch - Erim, Yesim (Kohlhammer, 2009)

Kontroverse um die Alzheimer-Frühdiagnostik – eine literaturbasierte Übersicht über die Vor- und Nachteile - Grässel, Elmar; Lauer, Natascha (Zeitschrift für Evidenz, Fortbildung und Qualitat im Gesundheitswesen, 2023)
Background: The continuum of Alzheimer's disease (AD) comprises three stages: the pre-clinical stage (with few to no subjective symptoms), the prodromal stage (measurable mild cognitive impairment) and the final stage of clinically manifest (AD) dementia. Neuropathological correlates in accordance with these stages have been found with varying frequency. The aim of early AD diagnosis is to determine such correlates in these preclinical and prodromal stages and to determine the probability of the manifestation of a later AD dementia. In this regard, the prognostic validity is of vital importance. From the perspective of those affected, the issue of early diagnosis cannot be reduced to AD, although Alzheimer's dementia is by far the most common form of dementia. The aim of this review is to provide a literature-based overview of the advantages and disadvantages of early AD diagnosis in contrast to other types of dementia. Based on this, recommendations will be formulated for the prioritisation of early diagnostic advantages and disadvantages in the patient counselling situation in clinical practice. Methods: Three databases were searched for current reviews addressing the advantages, disadvantages and ethical aspects of early AD diagnosis. The search was limited to current German or English reviews published between January 1, 2018 to November 30, 2022. The systematic search strategy was based on the PICO model and included both a Boolean and a focus-expanding keyword search using previously defined search terms. In addition, snowballing was used as a search strategy. Qualitative synoptic content analysis in accordance with Mayring was used to analyse both advantages and disadvantages. Similar arguments were combined into single statements. The resulting statements were categorized into three main groups: social, individual or clinical aspects. To emphasize the aforementioned aims, arguments were additionally distinguished into “only valid for early AD diagnosis” and ”valid for early diagnosis of all types of dementia“. Results: Overall, seven reviews with suitable content were included. Social aspects of early AD diagnosis comprise the protection of the affected person and the society as well as potential stigmatisation of the affected and their family members. Individual arguments range from the right to a “rational suicide”, including the avoidance of financial and caregiving burdens on family members, to the right not to know the diagnosis. Clinical arguments include, for example, the scientific research context (facilitating the identification of suitable clinical trial participants) and various negative effects of a false positive or false negative early diagnosis. Conclusion: Early diagnosis of AD as well as of other forms of dementia are characterised by numerous advantages and disadvantages of a social, individual and clinical nature. The decision for or against early diagnosis should always be made by weighing the current advantages against the disadvantages in a specific case. In particular, the desires of the person affected, the validity of the diagnostic procedures available and, above all, the availability of effective preventive or therapeutic measures must be taken into account.
CRIS-Team Scopus Importer:2023-06-09
Keywords: Advantages and disadvantages; Alzheimeŕs disease; Biomarkers; Dementia; Early diagnosis; Ethical issues

Körperliche Aktivität und Prävention der Alzheimerdemenz: Übersicht über aktuelle Evidenz und Überlegungen zur Machbarkeit einer Interventionsstudie - Weih, Markus; Abu-Omar, Karim; Esselmann, H; Gelbrich, Götz; Lewczuk, Piotr; Rütten, Alfred; Wiltfang, Jens; Kornhuber, Johannes (Fortschritte der Neurologie - Psychiatrie, 2009)

Korrelate der Depressivität von Müttern von Grundschulkindern - Zalan, Vera; Ziegler, Clara; Eichler, Anna; Heinrich, Hartmut; Moll, Gunther; Fasching, Peter; Beckmann, Matthias; Kornhuber, Johannes; Lenz, Bernd; Spangler, Gottfried (50. Jahreskongress der Deutschen Gesellschaft für Psychologie, 2016)

Kosteneffektivitätsmodell eines ambulanten Hilfeangebots für pflegende Angehörige von Demenzkranken - Dietl, Markus; Kornhuber, Johannes; Schöffski, Oliver; Grässel, Elmar (Gesundheitswesen, 2010)
Ziel der Studie Die Kosteneffektivitätsanalyse vergleicht ein ambulantes Hilfeangebot für pflegende Angehörige mit Standardpflege. Methodik Durch Literaturrecherchen wurden die Daten für das Kosteneffektivitätsmodell bezüglich der qualitätsadjustierten Lebensjahre (QALYs) und Kosten ermittelt. Die Evaluierung erfolgte durch ein Entscheidungsbaumverfahren. Die Überprüfung der Basisfallanalyse in Bezug auf Stabilität geschah mithilfe von Sensitivitätsanalysen und durch eine Monte-Carlo-Simulation (MCS). Ergebnisse Nach Einführung des ambulanten Hilfeangebotes wurden über einen einjährigen Zeithorizont € 750 eingespart und 0,07 QALYs gewonnen. Die Ergebnisse der Basisfallanalyse erwiesen sich in der Sensitivitätsanalyse als stabil. Schlussfolgerungen Durch die angewandten ambulanten Hilfeangebote lassen sich Kosten einsparen und QALYs bei den pflegenden Angehörigen gewinnen. Damit steht im Zusammenhang, dass pflegende Angehörige von Demenzkranken eher weniger depressiv sind und den Demenzkranken wahrscheinlich länger zu Hause betreuen.
Keywords: Demenz; Kosteneffektivität; pflegende Angehörige; ambulante Hilfeangebote; ökonomische Evaluation

Kratom instrumentalization for severe pain self-treatment resulting in addiction – A case report of acute and chronic subjective effects - Müller, Elisabeth; Hillemacher, Thomas; Müller, Christian P. (Heliyon, 2020)
Background: Kratom is a Southeast Asian plant, which is widely used in this region, and making an increasing appearance in Europe and the US. Case report: We present the case of a 26-year-old man in Substitol-assisted treatment of excessive Kratom and Tilidin use expressing the wish for a drug-free management of a chronic pain condition. After an accidental calcaneus impression fracture, the patient was suffering from severe chronic pain and anxiety of further accidents. This was managed initially with Tilidin. Resulting from the wish to self-manage the pain condition in a way that permitted continuation of a job, the patient searched for a ‘natural’ treatment alternative obtained from an Internet vendor. He successfully instrumentalized Kratom for 3 years with daily consumption intermixed with occasional Tilidin for pain management. However, the dose of Kratom was increased considerably up to a level of effect reversal, when no analgesic and behaviorally activating effects occurred any more, but only intense drowsiness. The patient was treatment seeking and subsequently detoxified from Kratom and Tilidin. Pain management was shifted to retarded morphine. Conclusion: Kratom instrumentalization for pain management might appear to be more problematic for addiction development than when its use is established for other consumption motives.
CRIS-Team Scopus Importer:2020-07-31
Keywords: Clinical psychology; Drug instrumentalization; Kratom; Opiate withdrawal; Pain management; Pharmaceutical science; Pharmacology; Psychiatry; Public health; Toxicology

Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users - Singh, Darshan; Müller, Christian P.; Vicknasingam, Balasingam K. (Drug and Alcohol Dependence, 2014)
Kratom (Mitragyna speciosa) preparations have been traditionally used in Southeast Asia for its medicinal properties. Lately, Kratom use has spread to Europe and the US, where abuse potential and health hazards increasingly emerge. This study is the first to measure systematically Kratom dependence, withdrawal symptoms, and drug craving in regular Kratom users in Malaysia.A cross-sectional survey of 293 regular Kratom users was conducted in the community across three northern peninsular states of Malaysia. The Leeds Dependence Questionnaire, Marijuana Withdrawal Checklist, and Marijuana Craving Questionnaire-Short Form were used to measure Kratom dependence, withdrawal and craving.More than half of the regular users (>6 month of use) developed severe Kratom dependence problems, while 45% showed a moderate Kratom dependence. Physical withdrawal symptoms commonly experienced include muscle spasms and pain, sleeping difficulty, watery eyes/nose, hot flashes, fever, decreased appetite, and diarrhoea. Psychological withdrawal symptoms commonly reported were restlessness, tension, anger, sadness, and nervousness. The average amount of the psychoactive compound, mitragynine, in a single dose of a Kratom drink was 79mg, suggesting an average daily intake of 276.5mg. Regular users who consumed >=3 glasses Kratom per day, had higher odds of developing severe Kratom dependence, withdrawal symptoms, and inability to control Kratom craving.The findings from this study show that regular Kratom use is associated with drug dependency, development of withdrawal symptoms, and craving. These symptoms become more severe with prolonged use and suggest a stronger control of the drug.
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Kratom use for depression/anxiety self-management: challenges during the COVID-19 pandemic – A case report - Müller, Elisabeth; Hillemacher, Thomas; Müller, Christian P. (Heliyon, 2021)
Background: Kratom is a psychoactive plant preparation originating from Southeast Asia. It has been used as a recreational and performance drug in Southeast Asia, and is now increasingly used in Europe and the U.S. Case report: We describe the case of a 63-year-old man who presented for treatment after his long-term Kratom use failed as a self-management for persistent major depression (ICD 10: F33.2) and a generalized anxiety disorder (ICD-10: F41.1). The failure coincided with emerging stress at the beginning of the COVID-19 pandemic. The patient suffered from childhood on from ruminative thinking and depressive mood, which was treated in several settings during his life. He started to use alcohol to control his depression, but developed an alcohol addiction. This was successfully treated and the patient remained abstinent for more than 25 years afterwards. About 7 years ago, he started to use Kratom 3–4 times daily on a regular, but constant rate. Kratom use worked efficiently as a self-management of his depression with no escalation of dosing. It was also very effective in reducing Morbus Menière symptoms of tinnitus and sudden hearing loss, which eventually allowed regular performance as a caregiver in a demanding job on shift-work. During recently increased stress load in the work environment and the COVID-19 pandemic, the established Kratom doses failed to control hyperarousal and mental nervousness. The patient was treatment seeking and subsequently detoxified from Kratom. Anxiety- and depression management was shifted to treatment attempts with Lorazepam, Venlafaxine, Opipramol, Mirtazapine and psychotherapy. Conclusion: Kratom instrumentalization for self-management of depression and anxiety may effectively work without causing escalation of drug use and addiction, but may be limited by a temporary increase in psychological stress load and a relapse into major depression and generalized anxiety disorder.
CRIS-Team Scopus Importer:2021-05-21
Keywords: Depression management; Drug instrumentalization; Kratom; Stress; Sudden hearing loss; Tinnitus

LAP proteins are localized at the post-synaptic membrane of neuromuscular junctions and appear to modulate synaptic morphology and transmission - Kravic, Bojana; Huraskin, Danyil; Frick, Alexander; Jung, Jasmin; Redai, Veronika; Palmisano, Ralf; Marchetto, Sylvie; Borg, Jean-Paul; Mei, Lin; Hashemolhosseini, Said (Journal of Neurochemistry, 2016)
Erbin, Lano, Scribble, and Densin-180 belong to LAP (leucine-rich repeats and PDZ domain) adaptor proteins involved in cell signaling pathways. Previously, we identified Erbin, Lano, and Scribble, but not Densin-180, in muscle cells, where they are involved in regulating the aggregation of nicotinic acetylcholine receptors in vitro. Here, we analyzed their cellular localization at the neuromuscular junction (NMJ) in skeletal muscles of mice. Erbin, Lano, and Scribble were significantly accumulated at NMJs and localized in different synaptic cells. Moreover, we used mouse mutants to analyze the role of Erbin at the NMJ. We used two Erbin mutant mouse strains that either completely lack Erbin protein (Erbin(null/null) ) or express a truncated Erbin mutant where the carboxy-terminal PDZ domain is replaced by ?-galactosidase (Erbin(?C/?C) ) thereby abolishing its interaction with ErbB receptor tyrosine kinases. Neither the lack of the PDZ domain of Erbin, nor its complete absence interfered with the general localization of LAP proteins at NMJs, but Lano and Scribble transcript levels were up-regulated in homozygous Erbin-null muscles. Furthermore, grip strength was reduced and neural transmission impaired in homozygous aged Erbin-null but not Erbin-?C mice. Erbin-null skeletal muscles did not reveal any conspicuous impairment of the muscle fiber. Localization of other NMJ marker proteins was not affected either. Quantitative 3D morphometry showed that NMJs of Erbin-null muscles were significantly smaller and fragmented in the soleus. We speculate that Erbin, Lano, and Scribble act at the post-synaptic membrane of NMJs in a concerted fashion to regulate nicotinic acetylcholine receptors cluster morphology and neural transmission. Cover Image for this issue: doi: 10.1111/jnc.13340.
EVALuna2:4995

Lasting translation: how to improve animal models for addiction treatment - Müller, Christian P. (Addiction, 2019)
CRIS-Team Scopus Importer:2019-11-01
Keywords: Addiction; animal models; drug abuse; translation

Layer-specific axonal degeneration of serotonergic fibers in the prefrontal cortex of aged A53T α-synuclein–expressing mice - Wihan, Jeanette; Grosch, Janina; Kalinichenko, Liubov; Müller, Christian P.; Winkler, Jürgen; Kohl, Zacharias (Neurobiology of Aging, 2019)
Axonal pathology precedes dopaminergic cell loss in Parkinson's disease (PD), indicating a dying back axonopathy of nigrostriatal projections. Although most attention focused on the dopaminergic system, increasing evidence implies a compromised serotonergic system in PD as well. By combining immunohistological and biochemical approaches, a profound layer-specific reduction of the serotonergic input to the prefrontal cortex (PFC)layers II and V/VI in aged mutant A53T α-synuclein–expressing mice (A53T mice)was detected. In addition, the altered fiber network was characterized by swollen axons and enlarged axonal varicosities within all PFC layers, but most pronounced in PFC layer I. Although prefrontal serotonin levels and synaptic protein expression were preserved, aged A53T mice showed increased levels of kinesin family member 1a and vesicular monoamine transporter 2. Together with increased tryptophan hydroxylase 2 mRNA levels in the raphe nuclei and an elevated serotonin receptor 1b expression in the PFC, these findings point to compensatory mechanisms within the serotonergic system to overcome the reduced neuritic input to the PFC in this transgenic animal model for PD.
CRIS-Team Scopus Importer:2019-05-16
Keywords: Alpha-synuclein; Parkinson's disease; Prefrontal cortex; Serotonin; Serotonin transporter

Laying the foundation for a core set of the International Classification of Functioning, Disability and Health for community-dwelling adults aged 75 years and above in general practice: a study protocol - Tomandl, Johanna; Book, Stephanie; Gotthardt, Susann; Heinmüller, Stefan; Grässel, Elmar; Freiberger, Ellen; Kühlein, Thomas; Hueber, Susann; Hoyer, Stefanie (BMJ Open, 2018)
Introduction With the medical focus on disease, the problem of overdiagnosis inevitably increases with ageing. Considering the functional health of patients might help to discriminate between necessary and unnecessary medicine. The International Classification of Functioning, Disability and Health (ICF) is an internationally recognised tool for describing functional health. However, it is too detailed to be used in primary care practices. Consequently, the aim of this study is to identify relevant codes for an ICF core set for community-dwelling older adults (75 years and above) in primary care. Methods and analysis The study will follow the methodology proposed by the ICF Research Branch to identify relevant concepts from different perspectives: (1) Research perspective: A systematic review of studies focusing on functional health in old age will be conducted in different databases. Relevant concepts will be extracted from the publications. (2) Patients' perspective: Relevant areas of functioning and disability will be identified conducting qualitative interviews and focus groups with community-dwelling older persons. The interviews will be transcribed verbatim and analysed using the documentary method of interpretation. (3) Experts' perspective: An online survey with open-ended questions will be conducted. Answers will be analysed using the qualitative content analysis of Mayring. (4) Clinical perspective: A cross-sectional empirical study will be performed to assess the health status of community-dwelling older adults using the extended ICF checklist and other measurement tools. Relevant concepts identified in each study will be linked to ICF categories resulting in four preliminary core sets. Ethics and dissemination Ethical approval for the study was obtained (90_17B). All participants will provide written informed consent. Data will be pseudonymised for analysis. Results will be disseminated by conference presentations and journal publications. Trial registration number Projektdatenbank Versorgungsforschung Deutschland: VfD_17_003833, Clinicaltrials.gov: NCT03384732 and PROSPERO: CRD42017067784.
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Laying the foundation for a Core Set of the International Classification of Functioning, Disability and Health for community-dwelling older adults in primary care: Relevant categories of their functioning from the research perspective, a scoping review - Tomandl, Johanna; Heinmüller, Stefan; Selb, Melissa; Grässel, Elmar; Freiberger, Ellen; Kühlein, Thomas; Hueber, Susann; Book, Stephanie; Gotthardt, Susann (BMJ Open, 2021)
Objectives The objective of this study was to find relevant concepts of functioning in community-dwelling older adults within frequently used assessment instruments published in the scientific literature. This was part of a larger project to develop an International Classification of Functioning, Disability and Health (ICF) Core Set for use in primary care. Design A scoping review was conducted. Articles dealing with functioning in older adults were searched and assessed for eligibility. The study population included community-dwelling adults (≥75 years) without dementia, living in high-resource countries. Relevant concepts were extracted from assessment instruments and linked to the ICF using standardised linking rules. Finally, a frequency analysis was conducted. Setting Home, primary care. Participants Community-dwelling adults aged 75 years and above. Results From 5060 identified publications, 68 were included and 30 assessment instruments extracted. Overall, 1182 concepts were retrieved. Most were linked to the â € activities and participation' component. The most frequently identified categories were â € memory functions', â € dressing' and â € changing basic body position'. Conclusions This review provides a list of relevant ICF categories from the research perspective that will be used for developing an ICF Core Set for older primary care patients.
CRIS-Team Scopus Importer:2021-03-05
Keywords: general medicine (see internal medicine); geriatric medicine; primary care

Laying the foundation for an International Classification of Functioning, Disability and Health Core Set for community-dwelling elderly adults in primary care: the clinical perspective identified in a cross-sectional study - Book, Stephanie; Ulbrecht, Gudrun; Tomandl, Johanna; Kühlein, Thomas; Gotthardt, Susann; Freiberger, Ellen; Grässel, Elmar (BMJ Open, 2020)
OBJECTIVES: Having more information about the biopsychosocial functioning of their geriatric patients might help physicians better balance medical interventions according to patients' needs. For this reason, we aimed to develop an easy-to-handle International Classification of Functioning, Disability and Health (ICF) Core Set for community-dwelling geriatric patients aged 75 and older in primary care. In this empirical study, we describe the functioning and health of community-dwelling patients aged 75 and older in primary care in Germany and identify the most common problems encountered by these individuals when using the ICF. DESIGN: In this exploratory, cross-sectional study, a health professional conducted semi-structured interviews. SETTING: Community-dwelling older adults aged 75 and older in Germany. PARTICIPANTS: 65 participants (mean age=80.2, SD=3.6). OUTCOME MEASURES: Extended ICF Checklist V.2.1a, patients prioritised chapters of the 'activities and participation' component. RESULTS: The three most common impairments for 'body functions' were visual system functions (ICF-code b210; 89%), blood pressure functions (b420; 80%) and sensations associated with hearing and vestibular functions (b240; 59%). For 'body structures', they were eyes, ears and related structures (s2; 81%), structure of mouth (s320; 74%) and structures related to the digestive, metabolic and endocrine systems (s5; 49%). For the 'activities and participation' component, adequate aids compensated for activity limitations to a certain degree. Still, after having adequate aids, the category in which the participants had the most difficulty was walking (d450; 35%). Participants rated the 'mobility' chapter as the most important of all chapters. 'Environmental factors' were facilitators of participants' functioning. CONCLUSIONS: This empirical study provides a list of ICF categories relevant to older adults from the clinical perspective. Along with lists from the other three preparatory studies, it will form the basis for the development of an ICF Core Set for community-dwelling older adults in primary care. TRIAL REGISTRATION DETAILS: The trial is registered in ClinicalTrials.gov (NCT03384732).
CRIS-Team Scopus Importer:2020-12-04
Keywords: aging; community-dwelling older people; core set; functioning; general practice; ICF

Laying the foundation for a primary care core set of the international classification of functioning, disability and health (icf) for community-dwelling older adults: A qualitative study - Tomandl, Johanna; Book, Stephanie; Höfle, Anina; Grässel, Elmar; Sieber, Cornel; Freiberger, Ellen; Kühlein, Thomas; Hueber, Susann; Gotthardt, Susann (Journal of Rehabilitation Medicine, 2021)
Objective: To explore relevant areas of functioning from the perspective of community-dwelling adults aged 75 years and over, in order to develop a Core Set of the International Classification of Functioning, Disability and Health (ICF) for community-dwelling older adults for use in primary care. Design: Qualitative study using semi-structured interviews and focus groups. Participants: A total of 27 community-dwelling older adults participated in the interviews and 24 of them in the focus groups. Methods: Following the proposed methodology of the ICF Research Branch, this is 1 of 4 preparatory studies in the Core Set development process. Within the transcripts, concepts of functioning were identified, based on Mayring s qualitative content analysis using deductive category assignment with the ICF being the category system. Results: Overall 6,667 concepts were identified. Most were linked to the Activities and Participation component. The most frequently identified categories were "recreation and leisure" and "family relationships". Conclusion: Categories from all ICF chapters were identified, demonstrating the complexity and multidimensionality of the ageing process, with a special emphasis on the component Activities and Participation. This qualitative study provides a list of relevant categories from the perspective of community-dwelling elderly people, which will be used to develop a Core Set for older primary care patients.
CRIS-Team Scopus Importer:2021-03-26
Keywords: aged; cross-sectional study; Disability and Health; focus group; general practice/methods.; geriatric assessment/ methods; independent living; International Classification of Functioning; interviews as topic

LDL cholesterol relates to depression, its severity, and the prospective course - Wagner, Claudia; Musenbichler, Cornelia; Böhm, Lea; Färber, Katharina; Fischer, Anna-Isabell; von Nippold, Felicitas; Winkelmann, Merle; Richter-Schmidinger, Tanja; Mühle, Christiane; Kornhuber, Johannes; Lenz, Bernd (Progress in Neuro-Psychopharmacology & Biological Psychiatry, 2019)
Background: Major depressive disorder (MDD) is a highly prevalent and burdening mental illness. Approximately 30% of the major depressive episodes (MDE) are classified as therapy-refractory. Further knowledge of the pathophysiological mechanisms underlying MDD and predictive biomarkers are needed to improve treatment options. Methods: Serum lipid levels were compared between patients with a current MDE (n = 130) or remitted MDD (n = 39) and healthy control subjects (n = 61) and associated with the severity (17-item Hamilton Depression Rating Scale [HAMD] scores) and the prospective course of depression (direct follow-up of at median 20 days post-inclusion). Results: We found higher levels of LDL cholesterol (152.5 vs. 134.0 mg/dl, U = 3021, P = 0.008) and LDL/HDL ratio (2.82 vs. 2.21, U = 2912, P = 0.003) in patients with a current MDE than in healthy control subjects. In patients with a current MDE, higher HAMD scores correlated also with higher values of triglycerides (ρ = 0.213, P = 0.015), total cholesterol (ρ = 0.199, P = 0.023), LDL cholesterol (ρ = 0.224, P = 0.010), and LDL/HDL ratio (ρ = 0.196, P = 0.026). Moreover, higher total cholesterol (ρ = −0.233, P = 0.010), LDL cholesterol (ρ = 0.235, P = 0.010), and LDL/HDL ratio (ρ = −0.199, P = 0.029) were associated with a stronger decline in HAMD score between study inclusion and direct follow-up. Limitations: We employed an associational study design, performed only a short-term follow-up, and excluded suicidal study subjects. Conclusions: Serum lipid levels are associated with depression per se, the depression severity, and the prospective 3-week course. These observations build the basis for future investigations on individualized lipid metabolism-related treatment strategies in depressed patients.
CRIS-Team Scopus Importer:2019-05-02
Keywords: Cholesterol; Depression; LDL cholesterol; Serum lipids; Triglycerides

Linking epileptic phenotypes and neural extracellular matrix remodeling signatures in mouse models of epilepsy - Blondiaux, Armand; Jia, Shaobo; Annamneedi, Anil; Çalışkan, Gürsel; Nebel, Jana; Montenegro-Venegas, Carolina; Wykes, Robert C.; Fejtová, Anna; Walker, Matthew C.; Stork, Oliver; Gundelfinger, Eckart D.; Dityatev, Alexander; et al. (Neurobiology of Disease, 2023)
Epilepsies are multifaceted neurological disorders characterized by abnormal brain activity, e.g. caused by imbalanced synaptic excitation and inhibition. The neural extracellular matrix (ECM) is dynamically modulated by physiological and pathophysiological activity and critically involved in controlling the brain's excitability. We used different epilepsy models, i.e. mice lacking the presynaptic scaffolding protein Bassoon at excitatory, inhibitory or all synapse types as genetic models for rapidly generalizing early-onset epilepsy, and intra-hippocampal kainate injection, a model for acquired temporal lobe epilepsy, to study the relationship between epileptic seizures and ECM composition. Electroencephalogram recordings revealed Bassoon deletion at excitatory or inhibitory synapses having diverse effects on epilepsy-related phenotypes. While constitutive Bsn mutants and to a lesser extent GABAergic neuron-specific knockouts (BsnDlx5/6cKO) displayed severe epilepsy with more and stronger seizures than kainate-injected animals, mutants lacking Bassoon solely in excitatory forebrain neurons (BsnEmx1cKO) showed only mild impairments. By semiquantitative immunoblotting and immunohistochemistry we show model-specific patterns of neural ECM remodeling, and we also demonstrate significant upregulation of the ECM receptor CD44 in null and BsnDlx5/6cKO mutants. ECM-associated WFA-binding chondroitin sulfates were strongly augmented in seizure models. Strikingly, Brevican, Neurocan, Aggrecan and link proteins Hapln1 and Hapln4 levels reliably predicted seizure properties across models, suggesting a link between ECM state and epileptic phenotype.
CRIS-Team Scopus Importer:2023-12-15
Keywords: Bassoon (Bsn) mouse mutants; Brevican; CD44; Hapln4; Intra-hippocampal kainate model; Wisteria floribunda agglutinin (WFA)

Lipids in psychiatric disorders and preventive medicine - Schneider, Miriam; Levant, Beth; Reichel, Martin; Gulbins, Erich; Kornhuber, Johannes; Müller, Christian P. (Neuroscience and Biobehavioral Reviews, 2017)
Psychiatric disorders like mood disorders, schizophrenia, or drug addiction affect a sizeable proportion of the human population and severely compromise quality of life. Therefore, measures to prevent the manifestation, and treatments to ameliorate the symptoms, of these disorders are in high demand. Brain lipids determine the localization and function of proteins in the cell membrane of neurons. Lipids may also act as neurotransmitters or other signalling molecules. The lipid composition of the brain can be influenced by nutrition, environmental factors, and by behavioural activity. Thus, lipids represent a target for preventive medicine of psychiatric disorders. Here we review how brain lipids contribute to normal behaviour and to major psychiatric disorders with the focus on phospholipids/fatty acids, sphingolipids, and endocannabinoids. Accumulating evidence suggests a crucial role for membrane forming and signalling lipids in the brain in the etiopathologies of depression, bipolar disorders, schizophrenia, and drug addiction. Lipids also represent potential preventive interventions for these psychiatric disorders by either targeted dietary supplementation or pharmacological manipulation of lipid regulating enzymes.
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Lipophilic cationic drugs increase the permeability of lysosomal membranes in a cell culture system - Kornhuber, Johannes; Henkel, Andreas W.; Groemer, Teja W.; Städtler, Sven; Welzel, Oliver; Tripal, Philipp; Rotter, Andrea; Bleich, Stefan; Trapp, Stefan (Journal of Cellular Physiology, 2010)
Lysosomes accumulate many drugs several fold higher compared to their extracellular concentration. This mechanism is believed to be responsible for many pharmacological effects. So far, uptake and release kinetics are largely unknown and interactions between concomitantly administered drugs often provoke mutual interference. In this study, we addressed these questions in a cell culture model. The molecular mechanism for lysosomal uptake kinetics was analyzed by live cell fluorescence microscopy in SY5Y cells using four drugs (amantadine, amitriptyline, cinnarizine, flavoxate) with different physicochemical properties. Drugs with higher lipophilicity accumulated more extensively within lysosomes, whereas a higher pKa value was associated with a more rapid uptake. The drug-induced displacement of LysoTracker was neither caused by elevation of intra-lysosomal pH, nor by increased lysosomal volume. We extended our previously developed numerical single cell model by introducing a dynamic feedback mechanism. The empirical data were in good agreement with the results obtained from the numerical model. The experimental data and results from the numerical model lead to the conclusion that intra-lysosomal accumulation of lipophilic xenobiotics enhances lysosomal membrane permeability. Manipulation of lysosomal membrane permeability might be useful to overcome, for example, multi-drug resistance by altering subcellular drug distribution. © 2010 Wiley-Liss, Inc.
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Long-term Associations of an Early Corrected Ventricular Septal Defect and Stress Systems of Child and Mother at Primary School Age - Stonawski, Valeska; Vollmer, Laura; Köhler-Jonas, Janna Nicola; Rohleder, Nicolas; Golub, Yulia; Purbojo, Ariawan; Moll, Gunther; Heinrich, Hartmut; Cesnjevar, Robert; Kratz, Oliver; Eichler, Anna (Frontiers in Pediatrics, 2017)
Introduction: Ventricular septal defect (VSD) is the most common congenital heart defect, with larger VSDs typically being corrected with an open-heart surgery during infancy. Long-term consequences of a VSD-corrective surgery on stress systems of child and mother are still unknown. The aim of the present study is to investigate the associations of an early corrected VSD and diurnal cortisol release of child and mother. Methods: 26 children (12 boys) between 6 and 9 years old, who underwent surgery for an isolated VSD within the first 3 years of life, and their mothers participated in the study. Their diurnal cortisol profiles were compared to a sex-, age-, and socioeconomic status-matched healthy control group. Within the VSD group, associations between cortisol and characteristics of surgery and hospitalization were investigated. Child and mother psychopathological symptoms were considered as a possible interfering mechanism of altered cortisol profiles. Results: Diurnal cortisol profiles of children with an early corrected VSD did not differ from those of controls. However, mothers of affected children exhibited higher cortisol levels in the morning (p < 0.001, [Formula: see text]) and a steeper diurnal cortisol slope (p = 0.016, [Formula: see text]) than mothers of healthy children. Conclusion: Results indicate a favorable development of children with an early corrected VSD, in terms of comparable diurnal cortisol profiles with healthy controls, according to a comparable mother-rated psychopathology. Mothers of affected children reveal altered diurnal cortisol levels, without differences in self-rated psychopathology. This divergence should be clarified in future research.
EVALuna2:33491

Long-Term Associations of an Early Corrected Ventricular Septal Defect and Stress Systems of Child and Mother at Primary School-Age - Stonawski, Valeska; Vollmer, Laura; Köhler-Jonas, Janna Nicola; Rohleder, Nicolas; Golub, Yulia; Purbojo, Ariawan; Moll, Gunther; Heinrich, Hartmut; Cesnjevar, Robert; Kratz, Oliver; Eichler, Anna (Frontiers in Pediatrics, 2018)

Long-Term Cognitive Effects of Kratom (Mitragyna speciosa Korth.) Use - Singh, Darshan; Narayanan, Suresh; Müller, Christian P.; Vicknasingam, Balasingam; Yuecel, Murat; Ho, Eric Tatt Wei; Hassan, Zurina; Mansor, Sharif Mahsufi (Journal of Psychoactive Drugs, 2019)
Kratom or Mitragyna speciosa (Korth.) is a medicinal plant of Southeast Asia. As a result of its opioid-like effects, it remains unknown whether consumption of kratom tea is associated with impaired cognitive function. We assessed the cognitive function of 70 regular kratom users and 25 control participants using the Cambridge Neuropsychological Test Automated Battery. Participants performed six neuropsychological tasks that assessed motor, learning and memory, attention and executive function. Relative to control participants, higher consumption (>3 glasses daily or mitragynine doses between 72.5 mg and 74.9 mg) of kratom tea was selectively associated with impaired performance on the Paired Associates Learning task, reflecting deficits in visual episodic memory and new learning. Overall, the performance of kratom users compared to control participants, and the performance of high (>3 glasses per day) as well as low (3 glasses per day) kratom using groups, were comparable on all neuropsychological domains. Higher intake of kratom juice (>3 glasses daily) did not appear to impair motor, memory, attention or executive function of regular kratom users.
CRIS-Team WoS Importer:2019-03-15

Long-term effects of bouldering psychotherapy on depression: benefits can be maintained across a 12-month follow-up - Schwarz, Laura; Dorscht, Lisa; Book, Stephanie; Stelzer, Eva Maria; Kornhuber, Johannes; Luttenberger, Katharina (Heliyon, 2019)
Background: Previous studies have identified positive effects of Bouldering Psychotherapy (BPT) on symptoms of depression. The aim of the present study was to investigate the short- and long-term effects of BPT on 97 participants with depression. Methods: BPT took place once a week over a period of 8 weeks. In a waitlist control group design, participants were assessed at baseline and after 8 weeks (end of BPT for the intervention group; start of BPT for the waitlist group), 16 weeks, and 12 months. The main outcome was severity of depression measured with the Beck Depression Inventory II (BDI-II). Results: Depression scores dropped by 7.21 on the BDI-II during the first intervention period with a Cohen's d of 0.59. A regression analysis at t1 showed that group allocation (p < .001) was the only significant predictor besides the baseline depression score (p < .001). A 12-month (after t0) follow-up measurement showed that the decrease in depression severity remained stable during that time, with values of d = 0.37 for the intervention group and d = 0.43 for the waitlist group. Limitations: Limitations of the study are the assessment of symptoms via only self-report, the lack of a control group during follow-up, and different durations of the follow-up period in the two groups. Conclusion: Our results augment the findings of previous studies regarding the short-term effects of BPT and provide initial evidence that the positive effects of BPT on depression severity can be maintained across a period of 12 months.
CRIS-Team Scopus Importer:2019-12-17
Keywords: Bouldering; Depression; Exercise; Long-term effect; Psychiatry; Psychology

Long-term follow-up of a multimodal day clinic, group-based treatment program for patients with very high risk for complex posttraumatic stress disorder, and for patients with non-complex trauma-related disorders - Bever-Philipps, Anke; Silbermann, Andrea; Morawa, Eva; Schäflein, Eva; Stemmler, Mark; Erim, Yesim (Frontiers in Psychiatry, 2023)
Objective: The present study examined the follow-up of a multimodal day clinic group-based therapy program for patients with trauma-related disorders and investigated potential differences for patients with classic PTSD versus cPTSD. Method: Sixty-six patients were contacted 6 and 12 months after discharge of our 8-week program and completed various questionnaires (Essen Trauma Inventory (ETI), Beck Depression Inventory-Revised (BDI-II), Screening scale of complex PTSD (SkPTBS), Patient Health Questionnaire (PHQ)-Somatization, as well as single items to therapy utilization and life events in the interim period). Due to organizational reasons a control group could not be included. Statistical analyses included repeated-measures ANOVA with cPTSD as between-subject factor. Results: The reduction of depressive symptoms at discharge was persistent at 6 and 12 months follow-up. Somatization symptoms were increased at discharge, but were leveled out at 6 months follow-up. The same effect was found for cPTSD symptoms in those patients with non-complex trauma-related disorders: Their increase of cPTSD symptoms was flattened at 6 months follow-up. Patients with a very high risk for cPTSD showed a strong linear reduction of cPTSD symptoms from admission to discharge and 6 months follow-up. cPTSD patients had a higher symptom load compared to patients without cPTSD on all time points and scales. Conclusion: Multimodal, day clinic trauma-focused treatment is associated with positive changes even after 6 and 12 months. Positive therapy outcomes (reduced depression, reduced cPTSD symptoms for patients with a very high risk for cPTSD) could be maintained. However, PTSD symptomatology was not significantly reduced. Increases in somatoform symptoms were leveled out and can therefore be regarded as side effects of treatment, which may be connected with actualization of trauma in the intensive psychotherapeutic treatment. Further analyses should be applied in larger samples and a control group.
CRIS-Team Scopus Importer:2023-07-21
Keywords: CPTSD; day clinic; follow-up; group therapy; psychotherapy; PTSD; trauma

Long-term positive and negative psychosocial outcomes in young childhood cancer survivors, type 1 diabetics and their healthy peers - Kremer, Anna-Lena; Schieber, Katharina; Metzler, Markus; Schuster, Sonja; Erim, Yesim (International Journal of Adolescent Medicine and Health, 2016)
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Long-term prognostic factors in stroke patients for living at home up to 7.5 years after initial inpatient rehablititation - Schupp, W.; Schmidt, R.; Grässel, Elmar (EUROPEAN JOURNAL OF NEUROLOGY, 2019)
CRIS-Team WoS Importer:2019-07-30

Long-Term Results after Fallot Repair - Kleinöder, Jonas; Purbojo, Ariawan; Blumauer, Robert; Cuomo, Michela; Alkassar, Muhannad; Dittrich, Sven; Cesnjevar, Robert (Thoracic and Cardiovascular Surgeon, 2022)
Background The aim of this study was to evaluate the long-term outcome and freedom from pulmonary valve replacement (PVR) after initial repair of tetralogy of Fallot (TOF). Patients and Methods The cohort of 306 patients treated between 1980 and 2017 was divided into anatomical subgroups according to the diagnosis of TOF-pulmonary stenosis, TOF-pulmonary atresia and TOF-double outlet right ventricle. Patients were treated with transannular patch (TAP), valve sparing repair (VSR), or conduits from the right ventricle to the pulmonary arteries (RVPA conduits). Results There were 21 deaths (6.9%), 14 being hospital deaths (4.6%) after primary correction and four deaths (1.3%) occurred after PVR. One patient died after a non-cardiac operation (0.3%). There were two late deaths (0.7%). During the past 12 years no early mortality has been observed. Ninety-one patients (30.4%) received PVR after a median of 12.1 +/- 7.0 years with an early mortality of 4.4% ( n = 4) and no late mortality. A significant difference in freedom from reoperation after TAP, VSR, and RVPA-conduits could be identified. Multivariate analysis displayed transannular repair ( p = 0.016), primary palliation ( p <0.001), the presence of major aortopulmonary collateral arteries (MAPCA; p = 0.023), and pulmonary valve Z -scores < - 4.0 ( p = 0.040) as significant risk factors for PVR. Conclusion TOF repair has a beneficial long-term prognosis with low morbidity and mortality. Pulmonary valve Z -scores < - 4.0, transannular repair, and presence of MAPCAs are associated with earlier PVR. Non-VSRs and TOF-pulmonary atresia lead to earlier reoperation but have no negative impact on survival.
CRIS-Team WoS Importer:2022-07-29