@article{JariusRuprechtWildemannetal.2012, author = {Jarius, Sven and Ruprecht, Klemens and Wildemann, Brigitte and Kuempfel, Tania and Ringelstein, Marius and Geis, Christian and Kleiter, Ingo and Kleinschnitz, Christoph and Berthele, Achim and Brettschneider, Johannes and Hellwig, Kerstin and Hemmer, Bernhard and Linker, Ralf A. and Lauda, Florian and Hayrettin, Christoph A. and Tumani, Hayrettin and Melms, Arthur and Trebst, Corinna and Stangel, Martin and Marziniak, Martin and Hoffmann, Frank and Schippling, Sven and Faiss, J{\"u}rgen H. and Neuhaus, Oliver and Ettrich, Barbara and Zentner, Christian and Guthke, Kersten and Hofstadt-van Oy, Ulrich and Reuss, Reinhard and Pellkofer, Hannah and Ziemann, Ulf and Kern, Peter and Wandinger, Klaus P. and Bergh, Florian Then and Boettcher, Tobias and Langel, Stefan and Liebetrau, Martin and Rommer, Paulus S. and Niehaus, Sabine and M{\"u}nch, Christoph and Winkelmann, Alexander and Zettl, Uwe K and Metz, Imke and Veauthier, Christian and Sieb, J{\"o}rn P. and Wilke, Christian and Hartung, Hans P. and Aktas, Orhan and Paul, Friedemann}, title = {Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients}, series = {Journal of Neuroinflammation}, volume = {9}, journal = {Journal of Neuroinflammation}, number = {14}, doi = {10.1186/1742-2094-9-14}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133636}, year = {2012}, abstract = {Background: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. Objective: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. Methods: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3\%). Results: Seropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of <= 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades <= 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions >= 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis. Both the time to relapse and the time to diagnosis was longer if the disease started with ON (p < 0.002 and p < 0.013). Motor symptoms or tetraparesis at first myelitis and > 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome.}, language = {en} } @article{LudwigSaemannAlexanderetal.2013, author = {Ludwig, K. U. and S{\"a}mann, P. and Alexander, M. and Becker, J. and Bruder, J. and Moll, K. and Spieler, D. and Czisch, M. and Warnke, A. and Docherty, S. J. and Davis, O. S. P. and Plomin, R. and N{\"o}then, M. M. and Landerl, K. and M{\"u}ller-Myhsok, B. and Hoffmann, P. and Schumacher, J. and Schulte-K{\"o}rne, G. and Czamara, D.}, title = {A common variant in Myosin-18B contributes to mathematical abilities in children with dyslexia and intraparietal sulcus variability in adults}, series = {Translational Psychiatry}, volume = {3}, journal = {Translational Psychiatry}, number = {e229}, doi = {10.1038/tp.2012.148}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131513}, year = {2013}, abstract = {The ability to perform mathematical tasks is required in everyday life. Although heritability estimates suggest a genetic contribution, no previous study has conclusively identified a genetic risk variant for mathematical performance. Research has shown that the prevalence of mathematical disabilities is increased in children with dyslexia. We therefore correlated genome-wide data of 200 German children with spelling disability, with available quantitative data on mathematic ability. Replication of the top findings in additional dyslexia samples revealed that rs133885 was a genome-wide significant marker for mathematical abilities\((P_{comb}=7.71 x 10^{-10}, n=699)\), with an effect size of 4.87\%. This association was also found in a sample from the general population (P=0.048, n=1080), albeit with a lower effect size. The identified variant encodes an amino-acid substitution in MYO18B, a protein with as yet unknown functions in the brain. As areas of the parietal cortex, in particular the intraparietal sulcus (IPS), are involved in numerical processing in humans, we investigated whether rs133885 was associated with IPS morphology using structural magnetic resonance imaging data from 79 neuropsychiatrically healthy adults. Carriers of the MYO18B risk-genotype displayed a significantly lower depth of the right IPS. This validates the identified association between rs133885 and mathematical disability at the level of a specific intermediate phenotype.}, language = {en} } @article{JarickVolckmarPuetteretal.2014, author = {Jarick, I. and Volckmar, A. L. and P{\"u}tter, C. and Pechlivanis, S. and Nguyen, T. T. and Dauvermann, M. R. and Beck, S. and Albayrak, {\"O}. and Scherag, S. and Gilsbach, S. and Cichon, S. and Hoffmann, P. and Degenhardt, F. and N{\"o}then, M. M. and Schreiber, S. and Wichmann, H. E. and J{\"o}ckel, K. H. and Heinrich, J. and Tiesler, C. M. T. and Faraone, S. V. and Walitza, S. and Sinzig, J. and Freitag, C. and Meyer, J. and Herpertz-Dahlmann, B. and Lehmkuhl, G. and Renner, T. J. and Warnke, A. and Romanos, M. and Lesch, K. P. and Reif, A. and Schimmelmann, B. G. and Hebebrand, J. and Scherag, A. and Hinney, A.}, title = {Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder}, series = {Molecular Psychiatry}, volume = {19}, journal = {Molecular Psychiatry}, number = {19}, doi = {10.1038/mp.2012.161}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121131}, pages = {115-21}, year = {2014}, abstract = {Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder. Genetic loci have not yet been identified by genome-wide association studies. Rare copy number variations (CNVs), such as chromosomal deletions or duplications, have been implicated in ADHD and other neurodevelopmental disorders. To identify rare (frequency ≤1\%) CNVs that increase the risk of ADHD, we performed a whole-genome CNV analysis based on 489 young ADHD patients and 1285 adult population-based controls and identified one significantly associated CNV region. In tests for a global burden of large (>500 kb) rare CNVs, we observed a nonsignificant (P=0.271) 1.126-fold enriched rate of subjects carrying at least one such CNV in the group of ADHD cases. Locus-specific tests of association were used to assess if there were more rare CNVs in cases compared with controls. Detected CNVs, which were significantly enriched in the ADHD group, were validated by quantitative (q)PCR. Findings were replicated in an independent sample of 386 young patients with ADHD and 781 young population-based healthy controls. We identified rare CNVs within the parkinson protein 2 gene (PARK2) with a significantly higher prevalence in ADHD patients than in controls \((P=2.8 × 10^{-4})\) after empirical correction for genome-wide testing). In total, the PARK2 locus (chr 6: 162 659 756-162 767 019) harboured three deletions and nine duplications in the ADHD patients and two deletions and two duplications in the controls. By qPCR analysis, we validated 11 of the 12 CNVs in ADHD patients \((P=1.2 × 10^{-3})\) after empirical correction for genome-wide testing). In the replication sample, CNVs at the PARK2 locus were found in four additional ADHD patients and one additional control \((P=4.3 × 10^{-2})\). Our results suggest that copy number variants at the PARK2 locus contribute to the genetic susceptibility of ADHD. Mutations and CNVs in PARK2 are known to be associated with Parkinson disease.}, language = {en} } @article{IyengarSedorFreedmanetal.2015, author = {Iyengar, Sudha K. and Sedor, John R. and Freedman, Barry I. and Kao, W. H. Linda and Kretzler, Matthias and Keller, Benjamin J. and Abboud, Hanna E. and Adler, Sharon G. and Best, Lyle G. and Bowden, Donald W. and Burlock, Allison and Chen, Yii-Der Ida and Cole, Shelley A. and Comeau, Mary E. and Curtis, Jeffrey M. and Divers, Jasmin and Drechsler, Christiane and Duggirala, Ravi and Elston, Robert C. and Guo, Xiuqing and Huang, Huateng and Hoffmann, Michael Marcus and Howard, Barbara V. and Ipp, Eli and Kimmel, Paul L. and Klag, Michael J. and Knowler, William C. and Kohn, Orly F. and Leak, Tennille S. and Leehey, David J. and Li, Man and Malhotra, Alka and M{\"a}rz, Winfried and Nair, Viji and Nelson, Robert G. and Nicholas, Susanne B. and O'Brien, Stephen J. and Pahl, Madeleine V. and Parekh, Rulan S. and Pezzolesi, Marcus G. and Rasooly, Rebekah S. and Rotimi, Charles N. and Rotter, Jerome I. and Schelling, Jeffrey R. and Seldin, Michael F. and Shah, Vallabh O. and Smiles, Adam M. and Smith, Michael W. and Taylor, Kent D. and Thameem, Farook and Thornley-Brown, Denyse P. and Truitt, Barbara J. and Wanner, Christoph and Weil, E. Jennifer and Winkler, Cheryl A. and Zager, Philip G. and Igo, Jr, Robert P. and Hanson, Robert L. and Langefeld, Carl D.}, title = {Genome-wide association and trans-ethnic meta-analysis for advanced diabetic kidney disease: Family Investigation of Nephropathy and Diabetes (FIND)}, series = {PLoS Genetics}, volume = {11}, journal = {PLoS Genetics}, number = {8}, doi = {10.1371/journal.pgen.1005352}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180545}, pages = {e1005352}, year = {2015}, abstract = {Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45\% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10\(^{-9}\)). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10\(^{-8}\)), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.}, language = {en} } @article{HoffmannJanssenKannoetal.2020, author = {Hoffmann, Jan V. and Janssen, Jan P. and Kanno, Takayuki and Shibutani, Takayuki and Onoguchi, Masahisa and Lapa, Constantin and Grunz, Jan-Peter and Buck, Andreas K. and Higuchi, Takahiro}, title = {Performance evaluation of fifth-generation ultra-high-resolution SPECT system with two stationary detectors and multi-pinhole imaging}, series = {EJNMMI Physics}, volume = {7}, journal = {EJNMMI Physics}, doi = {10.1186/s40658-020-00335-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230361}, year = {2020}, abstract = {Background Small-animal single-photon emission computed tomography (SPECT) systems with multi-pinhole collimation and large stationary detectors have advantages compared to systems with moving small detectors. These systems benefit from less labour-intensive maintenance and quality control as fewer prone parts are moving, higher accuracy for focused scans and maintaining high resolution with increased sensitivity due to focused pinholes on the field of view. This study aims to investigate the performance of a novel ultra-high-resolution scanner with two-detector configuration (U-SPECT5-E) and to compare its image quality to a conventional micro-SPECT system with three stationary detectors (U-SPECT\(^+\)). Methods The new U-SPECT5-E with two stationary detectors was used for acquiring data with \(^{99m}\)Tc-filled point source, hot-rod and uniformity phantoms to analyse sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR). Three dedicated multi-pinhole mouse collimators with 75 pinholes each and 0.25-, 0.60- and 1.00-mm pinholes for extra ultra-high resolution (XUHR-M), general-purpose (GP-M) and ultra-high sensitivity (UHS-M) imaging were examined. For CNR analysis, four different activity ranges representing low- and high-count settings were investigated for all three collimators. The experiments for the performance assessment were repeated with the same GP-M collimator in the three-detector U-SPECT\(^+\) for comparison. Results Peak sensitivity was 237 cps/MBq (XUHR-M), 847 cps/MBq (GP-M), 2054 cps/MBq (UHS-M) for U-SPECT5-E and 1710 cps/MBq (GP-M) for U-SPECT\(^+\). In the visually analysed sections of the reconstructed mini Derenzo phantoms, rods as small as 0.35 mm (XUHR-M), 0.50 mm (GP-M) for the two-detector as well as the three-detector SPECT and 0.75 mm (UHS-M) were resolved. Uniformity for maximum resolution recorded 40.7\% (XUHR-M), 29.1\% (GP-M, U-SPECT5-E), 16.3\% (GP-M, U-SPECT\(^+\)) and 23.0\% (UHS-M), respectively. UHS-M reached highest CNR values for low-count images; for rods smaller than 0.45 mm, acceptable CNR was only achieved by XUHR-M. GP-M was superior for imaging rods sized from 0.60 to 1.50 mm for intermediate activity concentrations. U-SPECT5-E and U-SPECT+ both provided comparable CNR. Conclusions While uniformity and sensitivity are negatively affected by the absence of a third detector, the investigated U-SPECT5-E system with two stationary detectors delivers excellent spatial resolution and CNR comparable to the performance of an established three-detector-setup.}, language = {en} } @article{JanssenHoffmannKannoetal.2020, author = {Janssen, Jan P. and Hoffmann, Jan V. and Kanno, Takayuki and Nose, Naoko and Grunz, Jan-Peter and Onoguchi, Masahisa and Chen, Xinyu and Lapa, Constantin and Buck, Andreas K. and Higuchi, Takahiro}, title = {Capabilities of multi-pinhole SPECT with two stationary detectors for in vivo rat imaging}, series = {Scientific Reports}, volume = {10}, journal = {Scientific Reports}, doi = {10.1038/s41598-020-75696-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230616}, year = {2020}, abstract = {We aimed to investigate the image quality of the U-SPECT5/CT E-Class a micro single-photon emission computed tomography (SPECT) system with two large stationary detectors for visualization of rat hearts and bones using clinically available \(^{99m}\)Tc-labelled tracers. Sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR) of the small-animal SPECT scanner were investigated in phantom studies using an ultra-high-resolution rat and mouse multi-pinhole collimator (UHR-RM). Point source, hot-rod, and uniform phantoms with \(^{99m}\)Tc-solution were scanned for high-count performance assessment and count levels equal to animal scans, respectively. Reconstruction was performed using the similarity-regulated ordered-subsets expectation maximization (SROSEM) algorithm with Gaussian smoothing. Rats were injected with similar to 100 MBq [\(^{99m}\)TcTc-MIBI or similar to 150 MBq [\(^{99m}\)Tc]Tc-HMDP and received multi-frame micro-SPECT imaging after tracer distribution. Animal scans were reconstructed for three different acquisition times and post-processed with different sized Gaussian filters. Following reconstruction, CNR was calculated and image quality evaluated by three independent readers on a five-point scale from 1="very poor" to 5="very good". Point source sensitivity was 567 cps/MBq and radioactive rods as small as 1.2 mm were resolved with the UHR-RM collimator. Collimator-dependent uniformity was 55.5\%. Phantom CNR improved with increasing rod size, filter size and activity concentration. Left ventricle and bone structures were successfully visualized in rat experiments. Image quality was strongly affected by the extent of post-filtering, whereas scan time did not have substantial influence on visual assessment. Good image quality was achieved for resolution range greater than 1.8 mm in bone and 2.8 mm in heart. The recently introduced small animal SPECT system with two stationary detectors and UHR-RM collimator is capable to provide excellent image quality in heart and bone scans in a rat using standardized reconstruction parameters and appropriate post-filtering. However, there are still challenges in achieving maximum system resolution in the sub-millimeter range with in vivo settings under limited injection dose and acquisition time.}, language = {en} } @article{KaussnerKuraszkiewiczSchochetal.2020, author = {Kaussner, Y. and Kuraszkiewicz, A. M. and Schoch, S. and Markel, Petra and Hoffmann, S. and Baur-Streubel, R. and Kenntner-Mabiala, R. and Pauli, P.}, title = {Treating patients with driving phobia by virtual reality exposure therapy - a pilot study}, series = {PLoS ONE}, volume = {15}, journal = {PLoS ONE}, number = {1}, doi = {10.1371/journal.pone.0226937}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201051}, pages = {e0226937}, year = {2020}, abstract = {Objectives Virtual reality exposure therapy (VRET) is a promising treatment for patients with fear of driving. The present pilot study is the first one focusing on behavioral effects of VRET on patients with fear of driving as measured by a post-treatment driving test in real traffic. Methods The therapy followed a standardized manual including psychotherapeutic and medical examination, two preparative psychotherapy sessions, five virtual reality exposure sessions, a final behavioral avoidance test (BAT) in real traffic, a closing session, and two follow-up phone assessments after six and twelve weeks. VRE was conducted in a driving simulator with a fully equipped mockup. The exposure scenarios were individually tailored to the patients' anxiety hierarchy. A total of 14 patients were treated. Parameters on the verbal, behavioral and physiological level were assessed. Results The treatment was helpful to overcome driving fear and avoidance. In the final BAT, all patients mastered driving tasks they had avoided before, 71\% showed an adequate driving behavior as assessed by the driving instructor, and 93\% could maintain their treatment success until the second follow-up phone call. Further analyses suggest that treatment reduces avoidance behavior as well as symptoms of posttraumatic stress disorder as measured by standardized questionnaires (Avoidance and Fusion Questionnaire: p < .10, PTSD Symptom Scale-Self Report: p < .05). Conclusions VRET in driving simulation is very promising to treat driving fear. Further research with randomized controlled trials is needed to verify efficacy. Moreover, simulators with lower configuration stages should be tested for a broad availability in psychotherapy.}, language = {en} } @article{BuhlBeissertGaffaletal.2020, author = {Buhl, Timo and Beissert, Stefan and Gaffal, Evelyn and Goebeler, Matthias and Hertl, Michael and Mauch, Cornelia and Reich, Kristian and Schmidt, Enno and Sch{\"o}n, Michael P. and Sticherling, Michael and Sunderk{\"o}tter, Cord and Traidl-Hoffmann, Claudia and Werfel, Thomas and Wilsman-Theis, Dagmar and Worm, Margitta}, title = {COVID-19 and implications for dermatological and allergological diseases}, series = {JDDG: Journal der Deutschen Dermatologischen Gesellschaft}, volume = {18}, journal = {JDDG: Journal der Deutschen Dermatologischen Gesellschaft}, number = {8}, doi = {10.1111/ddg.14195}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217860}, pages = {815 -- 824}, year = {2020}, abstract = {COVID-19, caused by the coronavirus SARS-CoV-2, has become pandemic. A further level of complexity opens up as soon as we look at diseases whose pathogenesis and therapy involve different immunological signaling pathways, which are potentially affected by COVID-19. Medical treatments must often be reassessed and questioned in connection with this infection. This article summarizes the current knowledge of COVID-19 in the light of major dermatological and allergological diseases. It identifies medical areas lacking sufficient data and draws conclusions for the management of our patients during the pandemic. We focus on common chronic inflammatory skin diseases with complex immunological pathogenesis: psoriasis, eczema including atopic dermatitis, type I allergies, autoimmune blistering and inflammatory connective tissue diseases, vasculitis, and skin cancers. Since several other inflammatory skin diseases display related or comparable immunological reactions, clustering of the various inflammatory dermatoses into different disease patterns may help with therapeutic decisions. Thus, following these patterns of skin inflammation, our review may supply treatment recommendations and thoughtful considerations for disease management even beyond the most frequent diseases discussed here.}, language = {en} }