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Background: Culture-derived mesenchymal stromal cells (MSCs) exhibit variable characteristics when manufactured using different methods and different source materials. The purpose of this study was to assess the impact on MSC characteristics when different laboratories propagated MSCs from cultures initiated with BM aliquots derived from the same donor source material.
Methods and Methods: Five aliquots from each of three different BM donors were distributed to five independent laboratories. Three laboratories plated whole BM and two laboratories a mononuclear BM cell fraction. Four laboratories cultured in media supplemented with fetal bovine serum (FBS) and one laboratory used human platelet lysate (hPL). Initial cell seeding densities (i.e., P0) ranged from 19.7 × 103/cm2–282 × 103/cm2 and for second seeding (i.e., P1) 0.05 × 103–5.1 × 103 cells/cm2. Post-thawed MSCs from each laboratory were analyzed for cell viability, immunophenotype, tri-lineage differentiation, fibroblast colony-forming units (CFU-F), gene expression, and immunosuppressive activity.
Results: Transit times from BM collection to receipt by laboratories located in the United States ranged from 16.0–30.0 h and from 41.5–71.5 h for a laboratory in Asia. Post-thaw culture derived MSCs rom BM #1, #2, and #3 exhibited viabilities that ranged from 74–92%, 61–96%, and 23–90%, respectively. CFU activity from BM #1, #2, and #3 per 200 MSCs plated averaged 45.1 ± 21.4, 49.3 ± 26.8 and 14.9 ± 13.3, respectively. No substantial differences were observed in immunophenotype, and immunosuppressive activities. Global gene expression profiles of MSCs revealed transcriptome differences due to different inter-laboratory methods and to donor source material with the center effects showing greater molecular differences than source material.
Conclusion: Functional and molecular differences exist among MSCs produced by different centers even when the same BM starting material is used to initiate cultures. These results indicated that manufacturing of MSCs by five independent centers contributed more to MSC variability than did the source material of the BM used in this study. Thus, emphasizing the importance of establishing worldwide standards to propagate MSCs for clinical use.
Das Hauptziel dieses Artikels ist es, einen Überblick über die Entstehung eines Lehrprojekts der Stadt Rio de Janeiro zur Förderung der Mehrsprachigkeit an öffentlichen Schulen zu geben. Zu diesem Zweck stützt sich der Artikel zunächst auf einige offizielle Dokumente – wie z.B. den Text des Nationalen Rahmenlehrplans (BNCC) und die Leitprinzipien für das Programm für zweisprachige Schulen in der Stadt Rio de Janeiro, die das Lehren von Fremdsprachen in Brasilien und in der Stadt Rio de Janeiro leiten. Darüber hinaus werden in diesem Beitrag Ergebnisse einer Studie vorgestellt, die mit den Lehrkräften durchgeführt wurde, die seit Beginn des Projekts als Deutschlehrende dort arbeiten. Die Ergebnisse der Studie zeigen, dass critical literacy und interkulturelles Lernen grundlegende Prinzipien sowohl in der Wahrnehmung als auch in der Praxis der Lehrenden sind. Schließlich zeigt der vorliegende Beitrag, wie wichtig diese Lehrprojekt zur Förderung einer reicheren und pluralen Bildung von Schüler*innen ist.
Background: Tuberous sclerosis complex (TSC) is a monogenetic, multisystem disorder characterized by benign growths due to TSC1 or TSC2 mutations. This German multicenter study estimated the costs and related cost drivers associated with organ manifestations in adults with TSC.
Methods: A validated, three-month, retrospective questionnaire assessed the sociodemographic and clinical characteristics, organ manifestations, direct, indirect, out-of-pocket (OOP), and nursing care-level costs among adult individuals with TSC throughout Germany from a societal perspective (costing year: 2019).
Results: We enrolled 192 adults with TSC (mean age: 33.4 ± 12.7 years; range: 18–78 years, 51.6% [n = 99] women). Reported TSC disease manifestations included skin (94.8%) and kidney and urinary tract (74%) disorders, epilepsy (72.9%), structural brain defects (67.2%), psychiatric disorders (50.5%), heart and circulatory system disorders (50.5%), and lymphangioleiomyomatosis (11.5%). TSC1 and TSC2 mutations were reported in 16.7% and 25% of respondents, respectively. Mean direct health care costs totaled EUR 6452 (median EUR 1920; 95% confidence interval [CI] EUR 5533–7422) per patient over three months. Medication costs represented the major direct cost category (77% of total direct costs; mean EUR 4953), and mechanistic target of rapamycin (mTOR) inhibitors represented the largest share (68%, EUR 4358). Mean antiseizure drug (ASD) costs were only EUR 415 (6%). Inpatient costs (8%, EUR 518) and outpatient treatment costs (7%; EUR 467) were important further direct cost components. The mean care grade allowance as an approximator of informal nursing care costs was EUR 929 (median EUR 0; 95% CI EUR 780–1083) over three months. Mean indirect costs totaled EUR 3174 (median EUR 0; 95% CI EUR 2503–3840) among working-age individuals (< 67 years in Germany). Multiple regression analyses revealed mTOR inhibitor use and persistent seizures as independent cost-driving factors for total direct costs. Older age and disability were independent cost-driving factors for total indirect costs, whereas epilepsy, psychiatric disease, and disability were independent cost-driving factors for nursing care costs.
Conclusions: This three-month study revealed substantial direct healthcare, indirect healthcare, and medication costs associated with TSC in Germany. This study highlights the spectrum of organ manifestations and their associated treatment needs in the German healthcare setting. Trial registration: DRKS, DRKS00016045. Registered 01 March 2019, http://www.drks.de/DRKS00016045.
We investigate the long-standing question of the effect of proton-antiproton annihilation on the (anti-)proton yield, while respecting detailed balance for the five-body back-reaction for the first time in a full microscopic description of the late stages of heavy-ion collisions. This is achieved by employing a stochastic collision criterion in a hadronic transport approach (SMASH), which is used to account for the regeneration of (anti-)protons via 5π→p¯p. We investigate Au+Au and Pb+Pb collisions from √sNN=17.3GeV−5.02 TeV in a viscous hybrid approach. Our results show that back-reactions happen for a fraction of 15%–20% of all annihilations, independent of the beam energy or centrality of the system. The inclusion of the back-reaction results in the regeneration of half of the (anti-)proton yield lost to annihilations at midrapidity. We also find that, concerning the multiplicities, treating the back-reaction as a chain of two-body reactions is equivalent to a single 5-to-2 reaction.
Previous studies in developing Xenopus and zebrafish reported that the phosphate transporter slc20a1a is expressed in pronephric kidneys. The recent identification of SLC20A1 as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role of SLC20A1 in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish ortholog slc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detected SLC20A1 in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequenced SLC20A1 in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelic de novo variants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novel de novo variant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact of SLC20A1 variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggest SLC20A1 is involved in urinary tract and urorectal development and implicate SLC20A1 as a disease-gene for BEEC.
O objetivo deste trabalho é divulgar e analisar os resultados de uma pesquisa realizada em três instituições paulistanas nas quais se ensina/aprende alemão como língua estrangeira. A pesquisa teve como objetivo geral investigar as crenças que alunos de língua alemã mantêm em relação a seu processo de aprendizagem. O corpus, coletado a partir de questionários e entrevistas, revelou muitas dessas crenças, referentes, por exemplo, à aprendizagem de gramática. Os resultados também apontam para a existência de uma relação entre as crenças e a adoção de determinadas estratégias de aprendizagem. Durante a análise, buscou-se identificar possíveis origens para as crenças detectadas, bem como os efeitos potenciais das mesmas sobre a aprendizagem da língua alemã. No presente artigo, algumas das crenças constatadas no estudo serão descritas e analisadas em relação a pressupostos teóricos e metodológicos da didática de línguas estrangeiras para o ensino de gramática.
Protein aggregation of the p63 transcription factor underlies severe skin fragility in AEC syndrome
(2018)
The p63 gene encodes a master regulator of epidermal commitment, development, and differentiation. Heterozygous mutations in the C-terminal domain of the p63 gene can cause ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, a life-threatening disorder characterized by skin fragility and severe, long-lasting skin erosions. Despite deep knowledge of p63 functions, little is known about mechanisms underlying disease pathology and possible treatments. Here, we show that multiple AEC-associated p63 mutations, but not those causative of other diseases, lead to thermodynamic protein destabilization, misfolding, and aggregation, similar to the known p53 gain-of-function mutants found in cancer. AEC mutant proteins exhibit impaired DNA binding and transcriptional activity, leading to dominant negative effects due to coaggregation with wild-type p63 and p73. Importantly, p63 aggregation occurs also in a conditional knock-in mouse model for the disorder, in which the misfolded p63 mutant protein leads to severe epidermal defects. Variants of p63 that abolish aggregation of the mutant proteins are able to rescue p63’s transcriptional function in reporter assays as well as in a human fibroblast-to-keratinocyte conversion assay. Our studies reveal that AEC syndrome is a protein aggregation disorder and opens avenues for therapeutic intervention.
Background: With increasing life expectancy the number of people affected by multimorbidity rises. Knowledge of factors associated with health-related quality of life in multimorbid people is scarce. We aimed to identify the factors that are associated with self-rated health (SRH) in aged multimorbid primary care patients.
Methods: Cross-sectional study with 3,189 multimorbid primary care patients aged from 65 to 85 years recruited in 158 general practices in 8 study centers in Germany. Information about morbidity, risk factors, resources, functional status and socio-economic data were collected in face-to-face interviews. Factors associated with SRH were identified by multivariable regression analyses.
Results: Depression, somatization, pain, limitations of instrumental activities (iADL), age, distress and Body Mass Index (BMI) were inversely related with SRH. Higher levels of physical activity, income and self-efficacy expectation had a positive association with SRH. The only chronic diseases remaining in the final model were Parkinson's disease and neuropathies. The final model accounted for 35% variance of SRH. Separate analyses for men and women detected some similarities; however, gender specific variation existed for several factors.
Conclusion: In multimorbid patients symptoms and consequences of diseases such as pain and activity limitations, as well as depression, seem to be far stronger associated with SRH than the diseases themselves. High income and self-efficacy expectation are independently associated with better SRH and high BMI and age with low SRH.
Rezensionen [2017]
(2017)
156 Ansari, Christine (Hrsg.): Adoleszenz in Medienkontexten. Literaturrezeption, Medienwirkung und Jugendmedienschutz (judith mathez)
158 Bachmann, Christian A. / Emans, Laura / Schmitz-Emans, Monika (Hrsg.): Bewegungsbücher. Spielformen, Poetiken, Konstellationen (gundel mattenklott)
160 Ballis, Anja /Schlachter, Birgit (Hrsg.): Schätze der Kinder- und Jugendliteratur wiederentdeckt. Frühe Lektüreerfahrung und Kanonbildung im akademischen Kontext (ernst seibert)
162 Benner, Julia: Federkrieg. Kinder- und Jugendliteratur gegen den Nationalsozialismus 1933 – 1945 (linde storm)
164 Born, Stefan: Allgemeinliterarische Adoleszenzromane. Untersuchungen zu Herrndorf, Regener, Strunk, Kehlmann und anderen (lena hoffmann)
166 Börnchen, Stefan: Poetik der Linie. Wilhelm Busch, Max und Moritz und die Tradition (lukas sarvari)
168 Burwitz-Melzer, Eva /O’Sullivan, Emer (Hrsg.): Einfachheit in der Kinder- und Jugendliteratur. Ein Gewinn für den Fremdsprachenunterricht (roland alexander issler)
169 Emde, Oliver /Möller, Lukas /Wicke, Andreas (Hrsg.): Von »Bibi Blocksberg« bis »TKKG«. Kinderhörspiele aus gesellschafts- und kulturwissenschaftlicher Perspektive (anika ullmann)
171 Ferstl, Paul /Walach, Thomas / Zahlmann, Stefan (Hrsg.): Fantasy Studies (maren bonacker)
173 Giesa, Felix: Graphisches Erzählen von Adoleszenz. Deutschsprachige Autorencomics nach 2000 (michael staiger)
175 Hahn, Heidi / Laudenberg, Beate / Rösch, Heidi (Hrsg.): »Wörter raus!?« Zur Debatte um eine diskriminierungsfreie Sprache im Kinderbuch (julia benner)
177 Haug, Christine / Frimmel, Johannes (Hrsg.): Schulbücher um 1800. Ein Spezialmarkt zwischen staatlichem, volksaufklärerischem und konfessionellem Auftrag (ortwin beisbart)
179 Hollerweger, Elisabeth /Stemmann, Anna (Hrsg.): Narrative Delikatessen. Kulturelle Dimensionen von Ernährung (sonja loidl)
180 Hopp, Margarete: Sterben, Tod und Trauer im Bilderbuch seit 1945 (iris schäfer)
182 Huemer, Georg: Mira Lobe. Doyenne der österreichischen Kinder- und Jugendliteratur (andreas schumann)
183 Josting, Petra (Hrsg.): Andreas Steinhöfel, Bielefelder Poet in Residence 2014 (heinke kilian)
185 Josting, Petra /Roeder, Caroline /Dettmar, Ute (Hrsg.): Immer Trouble mit Gender. Genderperspektiven in Kinder- und Jugendliteraturforschung und -medien (jana mikota)
187 Kurwinkel, Tobias /Schmerheim, Philipp /Sevi, Annika (Hrsg.): Michael Ende intermedial. Von Lokomotivführern, Glücksdrachen und dem (phantastischen) Spiel mit Mediengrenzen (michael stierstorfer)
188 Mikota, Jana / Pecher, Claudia Maria / von Glasenapp, Gabriele (Hrsg.): Literarisch-kulturelle Begegnungen mit dem Judentum. Beiträge zur kinderliterarischen Fachöffentlichkeit (susanne blumesberger)
190 Müller, Karla / Decker, Jan-Oliver / Krah, Hans / Schilcher, Anita (Hrsg.): Genderkompetenz mit Kinder- und Jugendliteratur entwickeln: Grundlagen – Analysen – Modelle (annette kliewer)
192 Nikolajeva, Maria: Reading for Learning. Cognitive Approaches to Children’s Literature (sabine fuchs)
194 Paul, Lissa / Johnston, Rosemary R. / Short, Emma (Hrsg.):Children’s Literature and Culture of the First World War.(julia benner)
195 Payrhuber, Franz-Josef / Meier, Bernhard(Hrsg.): Franz, Kurt: Kinderlyrik. Geschichte, Formen, Rezeption(ludger scherer)
197 Payrhuber, Franz-Josef:Gedichte entdecken. Wege zu Gedichten in der ersten bis sechsten Klasse (andreas schumann)
198 Pohlmann, Carola (Hrsg): Kinder- und Jugendliteratur. Sammeln und Erwerben (wolfgang wangerin)
200 Pompe, Anja (Hrsg): Kind und Gedicht. Wie wir lesen lernen (heinz-jürgen kliewer)
202 Preindl, Nadia:Russische Kinderliteratur im europäischen Exil der Zwischenkriegszeit (verena rutschmann)
204 Richter, Karin: Die Kinder- und Jugend-literatur der DDR. Entwicklungslinien – Themen und Genres. Autorenporträts und Textanalysen (maria becker)
206 Riemhofer, Andra:Interkulturelle Kinder- und Jugendliteratur in Deutschland. Lesen auf eigene Gefahr (roger meyer)
208Roeder, Caroline (Hrsg.): Himmel und Hölle. Raumerkundungen – interdisziplinär & in schulischer Praxis (claudia blei-hoch)
210 Ruzicka Kenfel, Vejka (Hrsg.): New Trends in Children’s Literature Research. Twenty-first Century Approaches (2000–2012) from the University of Vigo (Spain) (susanne blumesberger)
212 Schäfer, Iris:Von der Hysterie zur Magersucht. Adoleszenz und Krankheit in Romanen und Erzählungen der Jahrhundert- und der Jahrtausendwende (philipp schmerheim)
214 Scherer, Gabriela / Volz, Steffen (Hrsg.): Im Bildungsfokus: Bilderbuchrezeptions-forschung (margarete hopp)
216 Schmitt, Susann Sophie:Nachwuchs für die Literatur. Kinder- und Jugendprogramme ausgewählter Literaturhäuser Deutschlands, Österreichs und der Schweiz (renate grubert)
217 Seelinger Trites, Roberta:Literary Conceptu-alizations of Growth. Metaphors and Cogni-tion in Adolescent Literature (iris schäfer)
219 Seifert, Martina:Die Bilderfalle. Kanada in der deutschsprachigen Kinder- und Jugend-literatur: Produktion und Rezeption (sabine planka)
222 Stein, Daniel / Thon, Jan-Noël (Hrsg.): From Comic Strips to Graphic Novels. Contributions to the Theory and History of Graphic Narrative (anna stemmann)
223 Tomberg, Markus (Hrsg.): Alle wichtigen Bücher handeln von Gott. Religiöse Spuren in aktueller Kinder- und Jugendliteratur (martin anker)
Purpose: The role of obesity in glioblastoma remains unclear, as previous analyses have reported contradicting results. Here, we evaluate the prognostic impact of obesity in two trial populations; CeTeG/NOA-09 (n = 129) for MGMT methylated glioblastoma patients comparing temozolomide (TMZ) to lomustine/TMZ, and GLARIUS (n = 170) for MGMT unmethylated glioblastoma patients comparing TMZ to bevacizumab/irinotecan, both in addition to surgery and radiotherapy.
Methods: The impact of obesity (BMI ≥ 30 kg/m2) on overall survival (OS) and progression-free survival (PFS) was investigated with Kaplan–Meier analysis and log-rank tests. A multivariable Cox regression analysis was performed including known prognostic factors as covariables.
Results: Overall, 22.6% of patients (67 of 297) were obese. Obesity was associated with shorter survival in patients with MGMT methylated glioblastoma (median OS 22.9 (95% CI 17.7–30.8) vs. 43.2 (32.5–54.4) months for obese and non-obese patients respectively, p = 0.001), but not in MGMT unmethylated glioblastoma (median OS 17.1 (15.8–18.9) vs 17.6 (14.7–20.8) months, p = 0.26). The prognostic impact of obesity in MGMT methylated glioblastoma was confirmed in a multivariable Cox regression (adjusted odds ratio: 2.57 (95% CI 1.53–4.31), p < 0.001) adjusted for age, sex, extent of resection, baseline steroids, Karnofsky performance score, and treatment arm.
Conclusion: Obesity was associated with shorter survival in MGMT methylated, but not in MGMT unmethylated glioblastoma patients.