@article{ZieglerKaiserIgeletal.2021, author = {Ziegler, Mirjam and Kaiser, Anna and Igel, Christine and Geissler, Julia and Mechler, Konstantin and Holz, Nathalie E. and Becker, Katja and D{\"o}pfner, Manfred and Romanos, Marcel and Brandeis, Daniel and Hohmann, Sarah and Millenet, Sabina and Banaschewski, Tobias}, title = {Actigraphy-derived sleep profiles of children with and without attention-deficit/hyperactivity disorder (ADHD) over two weeks — comparison, precursor symptoms, and the chronotype}, series = {Brain Sciences}, volume = {11}, journal = {Brain Sciences}, number = {12}, issn = {2076-3425}, doi = {10.3390/brainsci11121564}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250084}, year = {2021}, abstract = {Although sleep problems are common in children with ADHD, their extent, preceding risk factors, and the association between neurocognitive performance and neurobiological processes in sleep and ADHD, are still largely unknown. We examined sleep variables in school-aged children with ADHD, addressing their intra-individual variability (IIV) and considering potential precursor symptoms as well as the chronotype. Additionally, in a subgroup of our sample, we investigated associations with neurobehavioral functioning (n = 44). A total of 57 children (6-12 years) with (n = 24) and without ADHD (n = 33) were recruited in one center of the large ESCAlife study to wear actigraphs for two weeks. Actigraphy-derived dependent variables, including IIV, were analyzed using linear mixed models in order to find differences between the groups. A stepwise regression model was used to investigate neuropsychological function. Overall, children with ADHD showed longer sleep onset latency (SOL), higher IIV in SOL, more movements during sleep, lower sleep efficiency, and a slightly larger sleep deficit on school days compared with free days. No group differences were observed for chronotype or sleep onset time. Sleep problems in infancy predicted later SOL and the total number of movements during sleep in children with and without ADHD. No additional effect of sleep problems, beyond ADHD symptom severity, on neuropsychological functioning was found. This study highlights the importance of screening children with ADHD for current and early childhood sleep disturbances in order to prevent long-term sleep problems and offer individualized treatments. Future studies with larger sample sizes should examine possible biological markers to improve our understanding of the underlying mechanisms.}, language = {en} } @article{WiegeringSchlegelWinkleretal.2015, author = {Wiegering, V. and Schlegel, P. G. and Winkler, B. and Lazarus, M. and Wirth, C. and Ernestus, K. and Walles, T. and Liese, J.}, title = {Persisting Cough as the Single Presenting Symptom of an Intrathoracic Tumor in a Nine-Month-Old Child with Adenovirus Airway Infection}, series = {Journal of Case Reports and Studies}, volume = {3}, journal = {Journal of Case Reports and Studies}, number = {2}, doi = {10.15744/2348-9820.2.504}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125536}, pages = {204}, year = {2015}, abstract = {We report on a nine-month-old girl who presented with persisting cough, and diminished ventilation of the left hemithorax. Viral pneumonia was suspected after Adenovirus detection by PCR, but chest X-rays showed a persistent shadowing of the left hemithorax and persistent coughing despite clinical improvement. Because of the discrepancy between clinical and radiological signs further investigations by ultrasound and CT scan were performed, which visualized an intrathroracic tumor. Histopathology confirmed diagnosis of a teratoma. This case highlights the need for careful evaluation by the treating physicians. If the chest X-ray provides a discrepancy to the clinical findings or persistent pathologies exist, differential diagnosis should be discussed and further diagnostics be performed.}, language = {en} } @article{WannagatWaizeneggerNiedling2021, author = {Wannagat, Wienke and Waizenegger, Gesine and Niedling, Gerhild}, title = {Coherence formation during narrative text processing: a comparison between auditory and audiovisual text presentation in 9- to 12-year-old children}, series = {Cognitive Processing}, volume = {22}, journal = {Cognitive Processing}, issn = {1612-4782}, doi = {10.1007/s10339-020-01008-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235744}, pages = {299-310}, year = {2021}, abstract = {In an experiment with 114 children aged 9-12 years, we compared the ability to establish local and global coherence of narrative texts between auditory and audiovisual (auditory text and pictures) presentation. The participants listened to a series of short narrative texts, in each of which a protagonist pursued a goal. Following each text, we collected the response time to a query word that was either associated with a near or a distant causal antecedent of the final sentence. Analysis of these response times indicated that audiovisual presentation has advantages over auditory presentation for accessing information relevant for establishing both local and global coherence, but there are indications that this effect may be slightly more pronounced for global coherence.}, language = {en} } @phdthesis{Wannagat2018, author = {Wannagat, Wienke Charlotte}, title = {Cognitive Processes of Discourse Comprehension in Children and Adults - Comparisons between Written, Auditory, and Audiovisual Modes of Presentation -}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-162515}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {In drei Studien wurde untersucht, wie sich unterschiedliche Darbietungsformate (schriftlich, auditiv, audiovisuell (auditiv + Bilder) auf das Verst{\"a}ndnis semantisch identischer Inhalte auswirken. Dabei interessierte insbesondere der Entwicklungsverlauf von der ersten Klasse bis zum Erwachsenenalter. Dass sich Bilder f{\"o}rderlich auf die Verst{\"a}ndnisleistung auswirken k{\"o}nnen, gilt als gut untersucht (z.B. Carney \& Levin, 2002). Anders als viele bisherige Studien erfassen wir Textverstehen mit impliziten Maßen, die differenziertere R{\"u}ckschl{\"u}sse auf die, g{\"a}ngigen Theorien zufolge, zugrundeliegenden Prozesse zulassen: Textverstehen geht mit der Konstruktion von drei Ebenen mentaler Repr{\"a}sentationen einher (vgl. Kintsch, 1998). Weiterhin bedeutet erfolgreiches Textverstehen, eine auf lokaler und globaler Ebene koh{\"a}rente mentale Repr{\"a}sentation zu konstruieren (z.B. Schnotz \& Dutke, 2004). Mit einem Satz-Rekognitionstest (vgl. Schmalhofer \& Glavanov, 1986) untersuchten wir, ob sich das Ged{\"a}chtnis f{\"u}r die Textoberfl{\"a}che, die Textbasis und das Situationsmodell bei 103 8- und 10-J{\"a}hrigen zwischen schriftlicher, auditiver und audiovisueller (Studie 1) und bei 106 7-, 9- und 11-J{\"a}hrigen zwischen auditiver und audiovisueller Darbietung narrativer Texte (Studie 2) unterscheidet. Weiterhin (Studie 3) untersuchten wir mit 155 9- und 11-J{\"a}hrigen, inwieweit sich die F{\"a}higkeit der Inferenzbildung zur Herstellung lokaler und globaler Koh{\"a}renz zwischen schriftlicher, auditiver und audiovisueller Darbietung unterscheidet. Als Indikator dienten die Reaktionszeiten auf W{\"o}rter, die mit einem {\"u}ber (global)- oder untergeordneten (lokal) Protagonistenziel assoziiert sind. Insgesamt zeigte sich, dass Sch{\"u}ler bis zu einem Alter von 11 Jahren nicht nur die Textoberfl{\"a}che besser erinnern, sondern auch besser in der Lage sind ein Situationsmodell zu konstruieren, wenn einem Text Bilder beigef{\"u}gt sind. Dies zeigte sich sowohl im Vergleich mit auditiver als auch mit schriftlicher Darbietung. Bei Erwachsenen zeigte sich kein Effekt der Darbietungsform. Sowohl 9- als auch 11-J{\"a}hrigen gelingt außerdem die Herstellung globaler Koh{\"a}renz bei audiovisueller Darbietung besser als bei auditiver. Die schriftliche Darbietung zeigte sich im Vergleich zur auditiven sowohl im Hinblick auf lokale als auch auf globale Koh{\"a}renz {\"u}berlegen.}, subject = {Textverstehen}, language = {en} } @article{WalterReilichThieleetal.2013, author = {Walter, Maggie C. and Reilich, Peter and Thiele, Simone and Schessl, Joachim and Schreiber, Herbert and Reiners, Karlheinz and Kress, Wolfram and M{\"u}ller-Reible, Clemens and Vorgerd, Matthias and Urban, Peter and Schrank, Bertold and Deschauer, Marcus and Schlotter-Weigel, Beate and Kohnen, Ralf and Lochm{\"u}ller, Hans}, title = {Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial}, series = {Orphanet Journal of Rare Diseases}, volume = {8}, journal = {Orphanet Journal of Rare Diseases}, number = {26}, issn = {1750-1172}, doi = {10.1186/1750-1172-8-26}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125663}, year = {2013}, abstract = {Background: Dysferlinopathies are autosomal recessive disorders caused by mutations in the dysferlin (DYSF) gene encoding the dysferlin protein. DYSF mutations lead to a wide range of muscular phenotypes, with the most prominent being Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B). Methods: We assessed the one-year-natural course of dysferlinopathy, and the safety and efficacy of deflazacort treatment in a double-blind, placebo-controlled cross-over trial. After one year of natural course without intervention, 25 patients with genetically defined dysferlinopathy were randomized to receive deflazacort and placebo for six months each (1 mg/kg/day in month one, 1 mg/kg every 2nd day during months two to six) in one of two treatment sequences. Results: During one year of natural course, muscle strength declined about 2\% as measured by CIDD (Clinical Investigation of Duchenne Dystrophy) score, and 76 Newton as measured by hand-held dynamometry. Deflazacort did not improve muscle strength. In contrast, there is a trend of worsening muscle strength under deflazacort treatment, which recovers after discontinuation of the study drug. During deflazacort treatment, patients showed a broad spectrum of steroid side effects. Conclusion: Deflazacort is not an effective therapy for dysferlinopathies, and off-label use is not warranted. This is an important finding, since steroid treatment should not be administered in patients with dysferlinopathy, who may be often misdiagnosed as polymyositis.}, language = {en} } @article{vonLukowiczSchlegelHaerteletal.2021, author = {von Lukowicz, Hannah and Schlegel, Paul-Gerhardt and H{\"a}rtel, Christoph and Morbach, Henner and Haubitz, Imme and Wiegering, Verena}, title = {ESPED survey on newly diagnosed immune thrombocytopenia in childhood: how much treatment do we give?}, series = {Molecular and Cellular Pediatrics}, volume = {8}, journal = {Molecular and Cellular Pediatrics}, doi = {10.1186/s40348-021-00121-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261832}, year = {2021}, abstract = {Background Immune thrombocytopenia (ITP) is an autoimmune disease associated with isolated thrombocytopenia, which is caused by an imbalance between platelet production and platelet destruction. Petechial and mucous membrane hemorrhages are characteristic of ITP, but life-threatening bleeding rarely occurs. Depending on the bleeding symptoms, ITP can be treated with glucocorticoids (GC), intravenous immunoglobulins (IVIG), or in severe cases, platelet transfusions. Mild bleeding does not necessarily require therapy. Using the German Surveillance Unit for rare Pediatric Diseases (ESPED) we conducted a prospective survey on ITP patients in all German Children's Hospitals between September 2018 and August 2019. We collected data on ITP, including the clinical course, therapy implementation recommendations (according to the Association of German Scientific Medical Societies guidelines), outcome, and influence of treatment regimens depending on the treating physician´s experience with ITP patients. Results Of the 287 recorded cases of children with ITP, 268 questionnaires were sent to the authors. Two hundred seventeen of the questionnaires fulfilled the inclusion criteria. ITP affected boys and girls similarly, and the median age of manifestation was 3.5 years. The main reasons for hospitalization were thrombocytopenia, bleeding signs, hematomas, and/or petechiae. Bleeding scores were ≤ 3 in 96\% of children, which corresponded to a low-to-moderately low risk of bleeding. No life-threatening bleeding was documented. The most common therapies were IVIG (n = 59), GC (n = 33), or a combination of these (n = 17). Blood products (i.e., red blood cells, platelet concentrate, and fresh frozen plasma) were given to 13 patients. Compared to the established guidelines, 67 patients were over-treated, and 2 patients were under-treated. Conclusions Adherence to German ITP treatment guidelines is currently limited. To improve patient safety and medical care, better medical training and dissemination of the guidelines are required in line with targeted analyses of patients with serious bleeding events to identify potential risk constellations.}, language = {en} } @article{TecleHackenbergScheichetal.2023, author = {Tecle, Nyat-Eyob and Hackenberg, Stephan and Scheich, Matthias and Scherzad, Agmal and Hagen, Rudolf and Gehrke, Thomas}, title = {Surgical management of lateral neck abscesses in children: a retrospective analysis of 100 cases}, series = {European Journal of Pediatrics}, volume = {182}, journal = {European Journal of Pediatrics}, number = {1}, doi = {10.1007/s00431-022-04676-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324179}, pages = {431-438}, year = {2023}, abstract = {Cervical abscesses are relatively common infections in pediatric patients. There is an ongoing debate about the necessity and time point of surgical drainage. The identification of a focus of infection might play an important role in facilitating a therapeutic decision. In a retrospective study, 100 pediatric patients aged 1-18 years who underwent incision and drainage of a lateral cervical abscess at our institution were analyzed. Patients were divided into two groups based on whether a focus of infection could be identified or not. Data collection included patient characteristics, microbiological results, antibiotic regimen, and clinical course. A focus of infection was found in 29\% (29/100) of the patients, most frequently in the tonsils. A causative microorganism was found in 75\% (75/100) of all patients, with Staphylococcus aureus and Streptococcus pyogenes being the most common pathogens. All patients received an empiric antibiotic therapy in addition to surgery. Antibiotic medication was changed in 31\% in both groups (9/29 with a focus of infection and 22/71 without a focus of infection) during therapy. Children without an identified focus of infection generally were younger and had more comorbidities reducing immune response while also showing differences in the pathogens involved. There were no complications associated to surgery or antibiotic therapy in any of the patients involved. Conclusion: Children with an identified focus of infection show several differences compared to those with isolated lateral abscesses, especially regarding the microorganisms involved. But the focus of infection seems not to have an impact on patient's outcome. What is Known: • Neck abscesses are a relatively common disease in the pediatric population and may cause serious complications. • Therapy in general consists of intravenous antibiotics with or without surgery. What is New: • The focus identification has no impact on patient's outcome. • Children with an identified focus of infection show several differences compared to those with isolated lateral abscesses, especially regarding their medical history, age, and the microorganisms involved.}, language = {en} } @article{TaurinesFeketePreussWiedenhoffetal.2022, author = {Taurines, R. and Fekete, S. and Preuss-Wiedenhoff, A. and Warnke, A. and Wewetzer, C. and Plener, P. and Burger, R. and Gerlach, M. and Romanos, M. and Egberts, K. M.}, title = {Therapeutic drug monitoring in children and adolescents with schizophrenia and other psychotic disorders using risperidone}, series = {Journal of Neural Transmission}, volume = {129}, journal = {Journal of Neural Transmission}, number = {5-6}, doi = {10.1007/s00702-022-02485-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324833}, pages = {689-701}, year = {2022}, abstract = {Risperidone is commonly used to treat different psychiatric disorders worldwide. Knowledge on dose-concentration relationships of risperidone treatment in children and adolescents with schizophrenia or other psychotic disorders is, however, scarce and no age-specific therapeutic ranges have been established yet. Multicenter data of a therapeutic drug monitoring service were analyzed to evaluate the relationship between risperidone dose and serum concentration of the active moiety (risperidone (RIS) plus its main metabolite 9-hydroxyrisperidone (9-OH-RIS)) in children and adolescents with psychotic disorders. Patient characteristics, doses, serum concentrations and therapeutic outcomes were assessed by standardized measures. The study also aimed to evaluate whether the therapeutic reference range for adults (20-60 ng/ml) is applicable for minors. In the 64 patients (aged 11-18 years) included, a positive correlation between daily dose and the active moiety (RIS\(_{am}\)) concentration was found (r\(_s\) = 0.49, p = 0.001) with variation in dose explaining 24\% (r\(_s\)\(^2\) = 0.240) of the variability in serum concentrations. While the RIS\(_{am}\) concentration showed no difference, RIS as well 9-OH-RIS concentrations and the parent to metabolite ratio varied significantly in patients with co-medication of a CYP2D6 inhibitor. Patients with extrapyramidal symptoms (EPS) had on average higher RIS\(_{am}\) concentrations than patients without (p = 0.05). Considering EPS, the upper threshold of the therapeutic range of RIS\(_{am}\) was determined to be 33 ng/ml. A rough estimation method also indicated a possibly decreased lower limit of the preliminary therapeutic range in minors compared to adults. These preliminary data may contribute to the definition of a therapeutic window in children and adolescents with schizophrenic disorders treated with risperidone. TDM is recommended in this vulnerable population to prevent concentration-related adverse drug reactions.}, language = {en} } @article{StrengPrifertWeissbrichetal.2022, author = {Streng, Andrea and Prifert, Christiane and Weissbrich, Benedikt and Sauerbrei, Andreas and Krumbholz, Andi and Schmid-Ott, Ruprecht and Liese, Johannes G.}, title = {Similar severity of influenza primary and re-infections in pre-school children requiring outpatient treatment due to febrile acute respiratory illness: prospective, multicentre surveillance study (2013-2015)}, series = {BMC Infectious Diseases}, volume = {22}, journal = {BMC Infectious Diseases}, doi = {10.1186/s12879-021-06988-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265841}, year = {2022}, abstract = {Background Influenza virus infections in immunologically na{\"i}ve children (primary infection) may be more severe than in children with re-infections who are already immunologically primed. We compared frequency and severity of influenza virus primary and re-infections in pre-school children requiring outpatient treatment. Methods Influenza-unvaccinated children 1-5 years of age presenting at pediatric practices with febrile acute respiratory infection < 48 h after symptom onset were enrolled in a prospective, cross-sectional, multicenter surveillance study (2013-2015). Influenza types/subtypes were PCR-confirmed from oropharyngeal swabs. Influenza type/subtype-specific IgG antibodies serving as surrogate markers for immunological priming were determined using ELISA/hemagglutination inhibition assays. The acute influenza disease was defined as primary infection/re-infection by the absence/presence of influenza type-specific immunoglobulin G (IgG) and, in a second approach, by the absence/presence of subtype-specific IgG. Socio-demographic and clinical data were also recorded. Results Of 217 influenza infections, 178 were due to influenza A (87 [49\%] primary infections, 91 [51\%] re-infections) and 39 were due to influenza B (38 [97\%] primary infections, one [3\%] re-infection). Children with "influenza A primary infections" showed fever with respiratory symptoms for a shorter period than children with "influenza A re-infections" (median 3 vs. 4 days; age-adjusted p = 0.03); other disease characteristics were similar. If primary infections and re-infections were defined based on influenza A subtypes, 122 (87\%) primary infections (78 "A(H3N2) primary infections", 44 "A(H1N1)pdm09 primary infections") and 18 (13\%) re-infections could be classified (14 "A(H3N2) re-infections" and 4 "A(H1N1)pdm09 re-infections"). Per subtype, primary infections and re-infections were of similar disease severity. Children with re-infections defined on the subtype level usually had non-protective IgG titers against the subtype of their acute infection (16 of 18; 89\%). Some patients infected by one of the influenza A subtypes showed protective IgG titers (≥ 1:40) against the other influenza A subtype (32/140; 23\%). Conclusions Pre-school children with acute influenza A primary infections and re-infections presented with similar frequency in pediatric practices. Contrary to expectation, severity of acute "influenza A primary infections" and "influenza A re-infections" were similar. Most "influenza A re-infections" defined on the type level turned out to be primary infections when defined based on the subtype. On the subtype level, re-infections were rare and of similar disease severity as primary infections of the same subtype. Subtype level re-infections were usually associated with low IgG levels for the specific subtype of the acute infection, suggesting only short-time humoral immunity induced by previous infection by this subtype. Overall, the results indicated recurring influenza virus infections in this age group and no or only limited heterosubtypic antibody-mediated cross-protection.}, language = {en} } @article{StrengPrifertWeissbrichetal.2015, author = {Streng, Andrea and Prifert, Christiane and Weissbrich, Benedikt and Liese, Johannes G.}, title = {Continued high incidence of children with severe influenza A(H1N1)pdm09 admitted to paediatric intensive care units in Germany during the first three post-pandemic influenza seasons, 2010/11-2012/13}, series = {BMC Infectious Diseases}, volume = {15}, journal = {BMC Infectious Diseases}, number = {573}, organization = {Bavarian PICU Study Group on Influenza and Other Viral ARI}, doi = {10.1186/s12879-015-1293-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125280}, year = {2015}, abstract = {Background Previous influenza surveillance at paediatric intensive care units (PICUs) in Germany indicated increased incidence of PICU admissions for the pandemic influenza subtype A(H1N1)pdm09. We investigated incidence and clinical characteristics of influenza in children admitted to PICUs during the first three post-pandemic influenza seasons, using active screening. Methods We conducted a prospective surveillance study in 24 PICUs in Bavaria (Germany) from October 2010 to September 2013. Influenza cases among children between 1 month and 16 years of age admitted to these PICUs with acute respiratory infection were confirmed by PCR analysis of respiratory secretions. Results A total of 24/7/20 influenza-associated PICU admissions were recorded in the post-pandemic seasons 1/2/3; incidence estimates per 100,000 children were 1.72/0.76/1.80, respectively. Of all 51 patients, 80 \% had influenza A, including 65 \% with A(H1N1)pdm09. Influenza A(H1N1)pdm09 was almost absent in season 2 (incidence 0.11), but dominated PICU admissions in seasons 1 (incidence 1.35) and 3 (incidence 1.17). Clinical data was available for 47 influenza patients; median age was 4.8 years (IQR 1.6-11.0). The most frequent diagnoses were influenza-associated pneumonia (62 \%), bronchitis/bronchiolitis (32 \%), secondary bacterial pneumonia (26 \%), and ARDS (21 \%). Thirty-six patients (77 \%) had underlying medical conditions. Median duration of PICU stay was 3 days (IQR 1-11). Forty-seven per cent of patients received mechanical ventilation, and one patient (2 \%) extracorporeal membrane oxygenation; 19 \% were treated with oseltamivir. Five children (11 \%) had pulmonary sequelae. Five children (11 \%) died; all had underlying chronic conditions and were infected with A(H1N1)pdm09. In season 3, patients with A(H1N1)pdm09 were younger than in season 1 (p = 0.020), were diagnosed more often with bronchitis/bronchiolitis (p = 0.004), and were admitted to a PICU later after the onset of influenza symptoms (p = 0.041). Conclusions Active screening showed a continued high incidence of A(H1N1)pdm09-associated PICU admissions in the post-pandemic seasons 1 and 3, and indicated possible underestimation of incidence in previous German studies. The age shift of severe A(H1N1)pdm09 towards younger children may be explained by increasing immunity in the older paediatric population. The high proportion of patients with underlying chronic conditions indicates the importance of consistent implementation of the current influenza vaccination recommendations for risk groups in Germany.}, language = {en} } @article{SonnenscheinvanderVoortArendsdeJongsteetal.2014, author = {Sonnenschein-van der Voort, Agnes M. M. and Arends, Lidia R. and de Jongste, Johan C. and Annesi-Maesano, Isabella and Arshad, S. Hasan and Barros, Henrique and Basterrechea, Mikel and Bisgaard, Hans and Chatzi, Leda and Corpeleijn, Eva and Correia, Sofia and Craig, Leone C. and Devereux, Graham and Dogaru, Cristian and Dostal, Miroslav and Duchen, Karel and Eggesb{\o}, Merete and van der Ent, C. Kors and Fantini, Maria P. and Forastiere, Francesco and Frey, Urs and Gehring, Ulrike and Gori, Davide and van der Gugten, Anne C. and Hanke, Wojciech and Henderson, A. John and Heude, Barbara and I{\~n}iguez, Carmen and Inskip, Hazel M. and Keil, Thomas and Kelleher, Cecily C. and Kogevinas, Manolis and Kreiner-M{\o}ller, Eskil and Kuehni, Claudia E. and K{\"u}pers, Leanne K. and Lancz, Kinga and Larsen, Pernille S. and Lau, Susanne and Ludvigsson, Johnny and Mommers, Monique and Andersen, Anne-Marie Nybo and Palkovicova, Lubica and Pike, Katherine C. and Pizzi, Constanza and Polanska, Kinga and Porta, Daniela and Richiardi, Lorenzo and Roberts, Graham and Schmidt, Anne and Sram, Radim J. and Sunyer, Jordi and Thijs, Carel and Torrent, Maties and Viljoen, Karien and Wijga, Alet H. and Vrijheid, Martine and Jaddoe, Vincent W. V. and Duijts, Liesbeth}, title = {Preterm birth, infant weight gain, and childhood asthma risk: A meta-analysis of 147,000 European children}, series = {The Journal of Allergy and Clinical Immunology}, volume = {133}, journal = {The Journal of Allergy and Clinical Immunology}, number = {5}, doi = {10.1016/j.jaci.2013.12.1082}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120714}, pages = {1317-29}, year = {2014}, abstract = {Background Preterm birth, low birth weight, and infant catch-up growth seem associated with an increased risk of respiratory diseases in later life, but individual studies showed conflicting results. Objectives We performed an individual participant data meta-analysis for 147,252 children of 31 birth cohort studies to determine the associations of birth and infant growth characteristics with the risks of preschool wheezing (1-4 years) and school-age asthma (5-10 years). Methods First, we performed an adjusted 1-stage random-effect meta-analysis to assess the combined associations of gestational age, birth weight, and infant weight gain with childhood asthma. Second, we performed an adjusted 2-stage random-effect meta-analysis to assess the associations of preterm birth (gestational age <37 weeks) and low birth weight (<2500 g) with childhood asthma outcomes. Results Younger gestational age at birth and higher infant weight gain were independently associated with higher risks of preschool wheezing and school-age asthma (P < .05). The inverse associations of birth weight with childhood asthma were explained by gestational age at birth. Compared with term-born children with normal infant weight gain, we observed the highest risks of school-age asthma in children born preterm with high infant weight gain (odds ratio [OR], 4.47; 95\% CI, 2.58-7.76). Preterm birth was positively associated with an increased risk of preschool wheezing (pooled odds ratio [pOR], 1.34; 95\% CI, 1.25-1.43) and school-age asthma (pOR, 1.40; 95\% CI, 1.18-1.67) independent of birth weight. Weaker effect estimates were observed for the associations of low birth weight adjusted for gestational age at birth with preschool wheezing (pOR, 1.10; 95\% CI, 1.00-1.21) and school-age asthma (pOR, 1.13; 95\% CI, 1.01-1.27). Conclusion Younger gestational age at birth and higher infant weight gain were associated with childhood asthma outcomes. The associations of lower birth weight with childhood asthma were largely explained by gestational age at birth."}, language = {en} } @phdthesis{Slyschak2022, author = {Slyschak, Anna}, title = {Fear conditioning, its generalization and extinction in children and adolescents under consideration of trait anxiety and anxiety sensitivity}, doi = {10.25972/OPUS-26780}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267806}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {The propounded thesis investigated fear learning including fear conditioning, its generalization as well as its extinction in 133 healthy children and adolescents aged 8 to 17 years. The main goal was to analyze these processes also in the course of childhood and adolescence due to far less research in this age span compared to adults. Of note, childhood is the typical period for the onset of anxiety disorders. To achieve this, an aversive discriminative fear conditioning, generalization and extinction paradigm, which based on the "screaming lady paradigm" from Lau et al. (2008) and was adapted by Schiele \& Reinhard et al. (2016), was applied. All probands traversed the pre-acquisition (4 x CS-, 4 x CS+, no US), the acquisition (12 x CS-, 12 x CS+, reinforcement rate: 83\%), the generalization (12 x CS-, 12 x GS4, 12 x GS3, 12 x GS2, 12 x GS1, 12 x CS+, reinforcement rate: 50\%) and the extinction (18 x CS-, 18 x CS+, no US). The generalization stimuli, i.e. GS1-GS4, were built out of CS- and CS+ in different mixtures on a percentage basis in steps of 20\% from CS- to CS+. Pictures of faces of two actresses with a neutral expression were used for the discriminative conditioning, whereby the CS+ was paired with a 95-dB loud female scream at the same time together with a fearful facial expression (US). CS- and GS1-GS4 were never followed by the US. Subjective ratings (arousal, valence and US expectancy) were collected and further the psychophysiological measure of the skin conductance response (SCR). The hypotheses were 1) that underage probands show a negative correlation between age and overgeneralization and 2) that anxiety is positively correlated with overgeneralization in the same sample. ANOVAs with repeated measures were conducted for all four dependent variables with phase (pre-acquisition phase, 1. + 2. acquisition phase, 1. + 2. generalization phase, 1. - 3. extinction phase) and stimulus type (CS-, CS+, GS1-GS4) as within-subject factors. For the analyses of the modulatory effects of age and anxiety in additional separate ANCOVAs were conducted including a) age, b) the STAIC score for trait anxiety and c) the CASI score for anxiety sensitivity as covariates. Sex was always included as covariate of no interest. On the one hand, findings indicated that the general extent of the reactions (arousal, valence and US expectancy ratings and the SCR) decreased with growing age, i.e. the older the probands the lower their reactions towards the stimuli regardless of the type of dependent variable. On the other hand, ratings of US expectancy, i.e. the likelihood that a stimulus is followed by a US (here: female scream coupled with a fearful facial expression), showed better discrimination skills the older the probands were, resulting in a smaller overgeneralization within older probands. It must be emphasized very clearly that no causality can be derived. Thus, it was only an association revealed between 15 age and generalization of conditioned fear, which is negative. Furthermore, no obvious impact of trait anxiety could be detected on the different processes of fear learning. Especially, no overgeneralization was expressed by the probands linked to higher trait anxiety. In contrast to trait anxiety, for anxiety sensitivity there was an association between its extent and the level of fear reactions. This could be described best with a kind of parallel shifts: the higher the anxiety sensitivity, the stronger the fear reactions. Likewise, for anxiety sensitivity no overgeneralization due to a stronger extent of anxiety sensitivity could be observed. Longitudinal follow-up examinations and, furthermore, neurobiological investigations are needed for replication purposes and purposes of gaining more supporting or opposing insights, but also for the profound exploration of the impact of hormonal changes during puberty and of the maturation processes of different brain structures. Finally, the question whether enhanced generalization of conditioned fear facilitates the development of anxiety disorders or vice versa remains unsolved yet.}, subject = {Furcht}, language = {en} } @article{SegerWannagatNieding2021, author = {Seger, Benedikt T. and Wannagat, Wienke and Nieding, Gerhild}, title = {Children's surface, textbase, and situation model representations of written and illustrated written narrative text}, series = {Reading and Writing}, volume = {34}, journal = {Reading and Writing}, number = {6}, issn = {1573-0905}, doi = {10.1007/s11145-020-10118-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-269813}, pages = {1415-1440}, year = {2021}, abstract = {According to the tripartite model of text representation (van Dijk \& Kintsch, 1983), readers form representations of the text surface and textbase, and construct a situation model. In this study, an experiment was conducted to investigate whether these levels of representation would be affected by adding illustrations to narrative text and whether the order of text and illustrations would make a difference. Students aged between 7 and 13 years (N = 146) read 12 narrative texts, 4 of them with illustrations presented before their corresponding sentences, 4 with illustrations presented after, and 4 without any illustration. A sentence recognition task was used to assess the accuracy for text surface, textbase, and situation model. For the text surface and situation model, neither the presence of illustrations nor the order of text and illustrations influenced accuracy. However, the textbase was negatively affected by illustrations when they followed their corresponding sentences. We suggest that illustrations can initiate model inspection after situation model construction (Schnotz, 2014), a process that can make substantial changes to the textbase representation.}, language = {en} } @article{SchwerdtleKanisKahletal.2012, author = {Schwerdtle, Barbara and Kanis, Julia and Kahl, Lena and K{\"u}bler, Andrea and Schlarb, Angelika A.}, title = {Children's Sleep Comic: development of a new diagnostic tool for children with sleep disorders [original research]}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75722}, year = {2012}, abstract = {Background: A solid diagnosis of sleep disorders in children should include both self-ratings and parent ratings. However, there are few standardized self-assessment instruments to meet this need. The Children's Sleep Comic is an adapted version of the unpublished German questionnaire "Freiburger Kinderschlafcomic" and provides pictures for items and responses. Because the drawings were outdated and allowed only for qualitative analysis, we revised the comic, tested its applicability in a target sample, and suggest a procedure for quantitative analysis. Methods: All items were updated and pictures were newly drawn. We used a sample of 201 children aged 5-10 years to test the applicability of the Children's Sleep Comic in young children and to run a preliminary analysis. Results: The Children's Sleep Comic comprises 37 items covering relevant aspects of sleep disorders in children. Application took on average 30 minutes. The procedure was well accepted by the children, as reflected by the absence of any dropouts. First comparisons with established questionnaires indicated moderate correlations. Conclusion: The Children's Sleep Comic is appropriate for screening sleep behavior and sleep problems in children. The interactive procedure can foster a good relationship between the investigator and the child, and thus establish the basis for successful intervention if necessary.}, subject = {Psychologie}, language = {en} } @article{SalzmannManriqueBremmHueneckeetal.2018, author = {Salzmann-Manrique, Emilia and Bremm, Melanie and Huenecke, Sabine and Stech, Milena and Orth, Andreas and Eyrich, Matthias and Schulz, Ansgar and Esser, Ruth and Klingebiel, Thomas and Bader, Peter and Herrmann, Eva and Koehl, Ulrike}, title = {Joint Modeling of Immune Reconstitution Post Haploidentical Stem Cell Transplantation in Pediatric Patients With Acute Leukemia Comparing CD34(+)-Selected to CD3/CD19-Depleted Grafts in a Retrospective Multicenter Study}, series = {frontiers in Immunology}, volume = {9}, journal = {frontiers in Immunology}, doi = {10.3389/fimmu.2018.01841}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227302}, pages = {1841, 1-12}, year = {2018}, abstract = {Rapid immune reconstitution (IR) following stem cell transplantation (SCT) is essential for a favorable outcome. The optimization of graft composition should not only enable a sufficient IR but also improve graft vs. leukemia/tumor effects, overcome infectious complications and, finally, improve patient survival. Especially in haploidentical SCT, the optimization of graft composition is controversial. Therefore, we analyzed the influence of graft manipulation on IR in 40 patients with acute leukemia in remission. We examined the cell recovery post haploidentical SCT in patients receiving a CD34(+)-selected or CD3/CD19-depleted graft, considering the applied conditioning regimen. We used joint model analysis for overall survival (OS) and analyzed the dynamics of age-adjusted leukocytes; lymphocytes; monocytes; CD3(+), CD3(+) CD4(+), and CD3(+) CD8(+) T cells; natural killer (NK) cells; and B cells over the course of time after SCT. Lymphocytes, NK cells, and B cells expanded more rapidly after SCT with CD34(+)-selected grafts (P = 0.036, P = 0.002, and P < 0.001, respectively). Contrarily, CD3(+) CD4(+) helper T cells recovered delayer in the CD34 selected group (P = 0.026). Furthermore, reduced intensity conditioning facilitated faster immune recovery of lymphocytes and T cells and their subsets (P < 0.001). However, the immune recovery for NK cells and B cells was comparable for patients who received reduced-intensity or full preparative regimens. Dynamics of all cell types had a significant influence on OS, which did not differ between patients receiving CD34(+)-selected and those receiving CD3/CD19-depleted grafts. In conclusion, cell reconstitution dynamics showed complex diversity with regard to the graft manufacturing procedure and conditioning regimen.}, language = {en} } @article{RoseDammGreineretal.2014, author = {Rose, Markus A. and Damm, Oliver and Greiner, Wolfgang and Knuf, Markus and Wutzler, Peter and Liese, Johannes G. and Kr{\"u}ger, Hagen and Wahn, Ulrich and Schaberg, Tom and Schwehm, Markus and Kochmann, Thomas F. and Eichner, Martin}, title = {The epidemiological impact of childhood influenza vaccination using live-attenuated influenza vaccine (LAIV) in Germany: predictions of a simulation study}, series = {BMC Infectious Diseases}, volume = {14}, journal = {BMC Infectious Diseases}, number = {40}, issn = {1471-2334}, doi = {10.1186/1471-2334-14-40}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117563}, year = {2014}, abstract = {Background: Routine annual influenza vaccination is primarily recommended for all persons aged 60 and above and for people with underlying chronic conditions in Germany. Other countries have already adopted additional childhood influenza immunisation programmes. The objective of this study is to determine the potential epidemiological impact of implementing paediatric influenza vaccination using intranasally administered live-attenuated influenza vaccine (LAIV) in Germany. Methods: A deterministic age-structured model is used to simulate the population-level impact of different vaccination strategies on the transmission dynamics of seasonal influenza in Germany. In our base-case analysis, we estimate the effects of adding a LAIV-based immunisation programme targeting children 2 to 17 years of age to the existing influenza vaccination policy. The data used in the model is based on published evidence complemented by expert opinion. Results: In our model, additional vaccination of children 2 to 17 years of age with LAIV leads to the prevention of 23.9 million influenza infections and nearly 16 million symptomatic influenza cases within 10 years. This reduction in burden of disease is not restricted to children. About one third of all adult cases can indirectly be prevented by LAIV immunisation of children. Conclusions: Our results demonstrate that vaccinating children 2-17 years of age is likely associated with a significant reduction in the burden of paediatric influenza. Furthermore, annual routine childhood vaccination against seasonal influenza is expected to decrease the incidence of influenza among adults and older people due to indirect effects of herd protection. In summary, our model provides data supporting the introduction of a paediatric influenza immunisation programme in Germany.}, language = {en} } @article{Reiners2011, author = {Reiners, Christoph}, title = {Clinical Experiences with Radiation Induced Thyroid Cancer after Chernobyl}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75475}, year = {2011}, abstract = {The risk of developing thyroid cancer increases considerably after exposure to external or internal radiation, especially in children below the age of 10. After the Chernobyl reactor accident, the yearly incidence of childhood thyroid cancer in Belarus increased to approximately 40 per 1.000.000 in girls and to roughly 20 per 1.000.000 in boys compared to approximately 0.5 cases per 1.000.000 prior to the accident. Typically, young children with thyroid cancer after radiation exposure present in ≈95\% of the cases as papillary cancers, in ≈50\% as invasive tumors growing outside the thyroid capsule, in ≈65\% with lymph node metastases and in ≈15\% with distant metastases. A joint Belarusian-German project starting in April 1993 that combined treatment with surgery and radioiodine was organized in 237 selected children from Belarus who were exposed to the Chernobyl fallout and had advanced stages of thyroid cancer. The study group included 141 girls and 96 boys. Their median age at the time of the accident was 1.7 years; whereas the median age at the time of diagnosis was 12.4 years. With the exception of two cases with follicular histology, the majority of the patients had been diagnosed with papillary thyroid cancers. In 63\%, the tumor had grown outside the thyroid capsule and invaded the tissue of the neck (pT4). Nearly all of the selected cases (96\%) showed-up with lymph node metastases (pN1) and 43\% of the patients with distant metastases mainly to the lungs (pM1). In 58\% of the children, complete remissions of thyroid cancer could be achieved until December 31st 2010 and in 34\% of the children, stable partial remissions; in the remaining 8\% of the patients, partial remissions were observed. The risk of radiation-induced thyroid cancer increased considerably in children and adolescents who were affected by the Chernobyl reactor accident. In spite of the fact, that thyroid cancers in young children seem to behave more aggressively than in older patients, the results of combined treatment with thyroidectomy, radioiodine therapy and thyroid hormone replacement are excellent.}, subject = {Chernobyl}, language = {en} } @article{OkoroBarquistConnoretal.2015, author = {Okoro, Chinyere K. and Barquist, Lars and Connor, Thomas R. and Harris, Simon R. and Clare, Simon and Stevens, Mark P. and Arends, Mark J. and Hale, Christine and Kane, Leanne and Pickard, Derek J. and Hill, Jennifer and Harcourt, Katherine and Parkhill, Julian and Dougan, Gordon and Kingsley, Robert A.}, title = {Signatures of adaptation in human invasive Salmonella Typhimurium ST313 populations from sub-Saharan Africa}, series = {PLoS Neglected Tropical Diseases}, volume = {9}, journal = {PLoS Neglected Tropical Diseases}, number = {3}, doi = {10.1371/journal.pntd.0003611}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143779}, pages = {e0003611}, year = {2015}, abstract = {Two lineages of Salmonella enterica serovar Typhimurium (S. Typhimurium) of multi-locus sequence type ST313 have been linked with the emergence of invasive Salmonella disease across sub-Saharan Africa. The expansion of these lineages has a temporal association with the HIV pandemic and antibiotic usage. We analysed the whole genome sequence of 129 ST313 isolates representative of the two lineages and found evidence of lineage-specific genome degradation, with some similarities to that observed in S. Typhi. Individual ST313 S. Typhimurium isolates exhibit a distinct metabolic signature and modified enteropathogenesis in both a murine and cattle model of colitis, compared to S. Typhimurium outside of the ST313 lineages. These data define phenotypes that distinguish ST313 isolates from other S. Typhimurium and may represent adaptation to a distinct pathogenesis and lifestyle linked to an-immuno-compromised human population.}, language = {en} } @article{NothhaftKlepperKneitzetal.2019, author = {Nothhaft, Matthias and Klepper, Joerg and Kneitz, Hermann and Meyer, Thomas and Hamm, Henning and Morbach, Henner}, title = {Hemorrhagic bullous Henoch-Sch{\"o}nlein Purpura: case report and review of the literature}, series = {Frontiers in Pediatrics}, volume = {6}, journal = {Frontiers in Pediatrics}, doi = {10.3389/fped.2018.00413}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201435}, pages = {413}, year = {2019}, abstract = {Henoch-Sch{\"o}nlein Purpura (HSP) or IgA vasculitis is the most common systemic vasculitis of childhood and may affect skin, joints, gastrointestinal tract, and kidneys. Skin manifestations of HSP are characteristic and include a non-thrombocytopenic palpable purpura of the lower extremities and buttocks. Rarely, HSP may initially present as or evolve into hemorrhagic vesicles and bullae. We present an otherwise healthy 5-year-old boy with an acute papulovesicular rash of both legs and intermittent abdominal pain. After a few days the skin lesions rapidly evolved into palpable purpura and hemorrhagic bullous lesions of variable size and severe hemorrhagic HSP was suspected. A histological examination of a skin biopsy showed signs of a small vessel leukocytoclastic vasculitis limited to the upper dermis and direct immunofluorescence analysis revealed IgA deposits in vessel walls, compatible with HSP. To further characterize the clinical picture and treatment options of bullous HSP we performed an extensive literature research and identified 41 additional pediatric patients with bullous HSP. Two thirds of the reported patients were treated with systemic corticosteroids, however, up to 25\% of the reported patients developed skin sequelae such as hyperpigmentation and/or scarring. The early use of systemic corticosteroids has been discussed controversially and suggested in some case series to be beneficial by reducing the extent of lesions and minimizing sequelae of disease. Our patient was treated with systemic corticosteroids tapered over 5 weeks. Fading of inflammation resulted in healing of most erosions, however, a deep necrosis developing from a large blister at the dorsum of the right foot persisted so that autologous skin transplantation was performed. Re-examination 11 months after disease onset showed complete clinical remission with re-epithelialization but also scarring of some affected areas.}, language = {en} } @article{NeuhoffBruderBartlingetal.2012, author = {Neuhoff, Nina and Bruder, Jennifer and Bartling, J{\"u}rgen and Warnke, Andreas and Remschmidt, Helmut and M{\"u}ller-Myhsok, Bertram and Schulte-K{\"o}rne, Gerd}, title = {Evidence for the Late MMN as a Neurophysiological Endophenotype for Dyslexia}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {5}, doi = {10.1371/journal.pone.0034909}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133686}, pages = {e34909}, year = {2012}, abstract = {Dyslexia affects 5-10\% of school-aged children and is therefore one of the most common learning disorders. Research on auditory event related potentials (AERP), particularly the mismatch negativity (MMN) component, has revealed anomalies in individuals with dyslexia to speech stimuli. Furthermore, candidate genes for this disorder were found through molecular genetic studies. A current challenge for dyslexia research is to understand the interaction between molecular genetics and brain function, and to promote the identification of relevant endophenotypes for dyslexia. The present study examines MMN, a neurophysiological correlate of speech perception, and its potential as an endophenotype for dyslexia in three groups of children. The first group of children was clinically diagnosed with dyslexia, whereas the second group of children was comprised of their siblings who had average reading and spelling skills and were therefore "unaffected'' despite having a genetic risk for dyslexia. The third group consisted of control children who were not related to the other groups and were also unaffected. In total, 225 children were included in the study. All children showed clear MMN activity to/da/-/ba/ contrasts that could be separated into three distinct MMN components. Whilst the first two MMN components did not differentiate the groups, the late MMN component (300-700 ms) revealed significant group differences. The mean area of the late MMN was attenuated in both the dyslexic children and their unaffected siblings in comparison to the control children. This finding is indicative of analogous alterations of neurophysiological processes in children with dyslexia and those with a genetic risk for dyslexia, without a manifestation of the disorder. The present results therefore further suggest that the late MMN might be a potential endophenotype for dyslexia.}, language = {en} }