Förderzeitraum 2017
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Institute
- Theodor-Boveri-Institut für Biowissenschaften (23)
- Institut für Klinische Epidemiologie und Biometrie (9)
- Institut für Psychologie (9)
- Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II) (8)
- Institut für Sportwissenschaft (8)
- Institut für Virologie und Immunbiologie (8)
- Neurologische Klinik und Poliklinik (8)
- Klinik und Poliklinik für Thorax-, Herz- u. Thorakale Gefäßchirurgie (7)
- Klinik und Poliklinik für Unfall-, Hand-, Plastische und Wiederherstellungschirurgie (Chirurgische Klinik II) (7)
- Medizinische Klinik und Poliklinik I (7)
In transparent orthographies, persistent reading fluency difficulties are a major cause of poor reading skills in primary school. The purpose of the present study was to investigate effects of a syllable-based reading intervention on word reading fluency and reading comprehension among German-speaking poor readers in Grade 4. The 16-session intervention was based on analyzing the syllabic structure of words to strengthen the mental representations of syllables and words that consist of these syllables. The training materials were designed using the 500 most frequent syllables typically read by fourth graders. The 75 poor readers were randomly allocated to the treatment or the control group. Results indicate a significant and strong effect on the fluency of recognizing single words, whereas text-level reading comprehension was not significantly improved by the training. The specific treatment effect provides evidence that a short syllable-based approach works even in older poor readers at the end of primary school.
Introduction.
Tropheryma whipplei is the causative agent of Whipple’s disease. Gastrointestinal and lymphatic tissues are affected in the majority of cases, resulting in diarrhoea, malabsorption and fever. Here, we report a rare case of ocular manifestation in a patient lacking the typical Whipple symptoms.
Case presentation.
A 74-year-old Caucasian female presented with blurred vision in the right eye over a period of 1–2 months, accompanied by stinging pain and conjunctival hyperaemia for the last 2 days. Upon admission, visual acuity was hand motion in the affected eye. Ophthalmological examination showed typical signs of intraocular inflammation. Diagnostic and therapeutic pars plana vitrectomy including vitreous biopsy and intravitreal instillation of vancomycin and amikacin was performed within hours of initial presentation. Both microscopic analysis and microbial cultures of the vitreous biopsy remained negative for bacteria and fungi. The postoperative antibiotic regime included intravenous administration of ceftriaxone in combination with topical tobramycin and ofloxacin. Due to the empirical therapy the inflammation ceased and the patient was discharged after 5 days with cefpodoxime orally and local antibiotic and steroidal therapy. Meanwhile, the vitreous body had undergone testing by PCR for the eubacterial 16S rRNA gene, which was found to be positive. Analysis of the PCR product revealed a specific sequence of T. whipplei.
Conclusion.
In our patient, endophthalmitis was the first and only symptom of Morbus Whipple, while most patients with Whipple’s disease suffer from severe gastrointestinal symptoms. 16S rDNA PCR should be considered for any intraocular infection when microscopy and standard culture methods remain negative.
Many pathogenic bacteria utilize specialized secretion systems to deliver proteins called effectors into eukaryotic cells for manipulation of host pathways. The vast majority of known effector targets are host proteins, whereas a potential targeting of host nucleic acids remains little explored. There is only one family of effectors known to target DNA directly, and effectors binding host RNA are unknown. Here, we take a two-pronged approach to search for RNA-binding effectors, combining biocomputational prediction of RNA-binding domains (RBDs) in a newly assembled comprehensive dataset of bacterial secreted proteins, and experimental screening for RNA binding in mammalian cells. Only a small subset of effectors were predicted to carry an RBD, indicating that if RNA targeting was common, it would likely involve new types of RBDs. Our experimental evaluation of effectors with predicted RBDs further argues for a general paucity of RNA binding activities amongst bacterial effectors. We obtained evidence that PipB2 and Lpg2844, effector proteins of Salmonella and Legionella species, respectively, may harbor novel biochemical activities. Our study presenting the first systematic evaluation of the RNA-targeting potential of bacterial effectors offers a basis for discussion of whether or not host RNA is a prominent target of secreted bacterial proteins.
The aim of this pilot study was to analyze the off-training physical activity (PA) profile in national elite German U23 rowers during 31 days of their preparation period. The hours spent in each PA category (i.e., sedentary: <1.5 metabolic equivalents (MET); light physical activity: 1.5–3 MET; moderate physical activity: 3–6 MET and vigorous intense physical activity: >6 MET) were calculated for every valid day (i.e., >480 min of wear time). The off-training PA during 21 weekdays and 10 weekend days of the final 11-week preparation period was assessed by the wrist-worn multisensory device Microsoft Band II (MSBII). A total of 11 rowers provided valid data (i.e., >480 min/day) for 11.6 week days and 4.8 weekend days during the 31 days observation period. The average sedentary time was 11.63 ± 1.25 h per day during the week and 12.49 ± 1.10 h per day on the weekend, with a tendency to be higher on the weekend compared to weekdays (p = 0.06; d = 0.73). The average time in light, moderate and vigorous PA during the weekdays was 1.27 ± 1.15, 0.76 ± 0.37, 0.51 ± 0.44 h per day, and 0.67 ± 0.43, 0.59 ± 0.37, 0.53 ± 0.32 h per weekend day. Light physical activity was higher during weekdays compared to the weekend (p = 0.04; d = 0.69). Based on our pilot study of 11 national elite rowers we conclude that rowers display a considerable sedentary off-training behavior of more than 11.5 h/day.
Background:
While data from primary care suggest an insufficient control of vascular risk factors, little is known about vascular risk factor control in the general population. We therefore aimed to investigate the adoption of adequate risk factor control and its determinants in the general population free of cardiovascular disease (CVD).
Methods:
Data from the Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) Cohort Study, a population-based study of inhabitants aged 30 to 79 years from the general population of Würzburg (Germany), were used. Proportions of participants without established CVD meeting targets for risk factor control recommended by 2016 ESC guideline were identified. Determinants of the accumulation of insufficiently controlled vascular risk factors (three or more) were assessed.
Results:
Between December 2013 and April 2015, 1379 participants without CVD were included; mean age was 53.1 ± 11.9 years and 52.9% were female; 30.8% were physically inactive, 55.2% overweight, 19.3% current smokers. Hypertension, dyslipidemia, and diabetes mellitus were prevalent in 31.8%, 57.6%, and 3.9%, respectively. Treatment goals were not reached despite medication in 52.7% of hypertensive, in 37.3% of hyperlipidemic and in 44.0% of diabetic subjects. Insufficiently controlled risk was associated with male sex (OR 1.94, 95%CI 1.44–2.61), higher age (OR for 30–39 years vs. 70–79 years 4.01, 95%CI 1.94–8.31) and lower level of education (OR for primary vs. tertiary 2.15, 95%CI 1.48–3.11).
Conclusions:
In the general population, prevalence of vascular risk factors was high. We found insufficient identification and control of vascular risk factors and a considerable potential to improve adherence to cardiovascular guidelines for primary prevention. Further studies are needed to identify and overcome patient- and physician-related barriers impeding successful control of vascular risk factors in the general population.
Dendritic cells (DCs) and macrophages (Mph) share many characteristics as components of the innate immune system. The criteria to classify the multitude of subsets within the mononuclear phagocyte system are currently phenotype, ontogeny, transcription patterns, epigenetic adaptations, and function. More recently, ontogenetic, transcriptional, and proteomic research approaches uncovered major developmental differences between Flt3L-dependent conventional DCs as compared with Mphs and monocyte-derived DCs (MoDCs), the latter mainly generated in vitro from murine bone marrow-derived DCs (BM-DCs) or human CD14\(^{+}\) peripheral blood monocytes. Conversely, in vitro GM-CSF-dependent monocyte-derived Mphs largely resemble MoDCs whereas tissue-resident Mphs show a common embryonic origin from yolk sac and fetal liver with Langerhans cells (LCs). The novel ontogenetic findings opened discussions on the terminology of DCs versus Mphs. Here, we bring forward arguments to facilitate definitions of BM-DCs, MoDCs, and LCs. We propose a group model of terminology for all DC subsets that attempts to encompass both ontogeny and function.
The abundance of high-quality genotype and phenotype data for the model organism Arabidopsis thaliana enables scientists to study the genetic architecture of many complex traits at an unprecedented level of detail using genome-wide association studies (GWAS). GWAS have been a great success in A. thaliana and many SNP-trait associations have been published. With the AraGWAS Catalog (https://aragwas.1001genomes.org) we provide a publicly available, manually curated and standardized GWAS catalog for all publicly available phenotypes from the central A. thaliana phenotype repository, AraPheno. All GWAS have been recomputed on the latest imputed genotype release of the 1001 Genomes Consortium using a standardized GWAS pipeline to ensure comparability between results. The catalog includes currently 167 phenotypes and more than 222 000 SNP-trait associations with P < 10\(^{-4}\), of which 3887 are significantly associated using permutation-based thresholds. The AraGWAS Catalog can be accessed via a modern web-interface and provides various features to easily access, download and visualize the results and summary statistics across GWAS.
Background:
The aim of this work is to validate the Dynamic Planning Module in terms of usability and acceptance in the treatment planning workflow.
Methods:
The Dynamic Planning Module was used for decision making whether a plan adaptation was necessary within one course of radiation therapy. The Module was also used for patients scheduled for re-irradiation to estimate the dose in the pretreated region and calculate the accumulated dose to critical organs at risk. During one year, 370 patients were scheduled for plan adaptation or re-irradiation. All patient cases were classified according to their treated body region. For a sub-group of 20 patients treated with RT for lung cancer, the dosimetric effect of plan adaptation during the main treatment course was evaluated in detail. Changes in tumor volume, frequency of re-planning and the time interval between treatment start and plan adaptation were assessed.
Results:
The Dynamic Planning Tool was used in 20% of treated patients per year for both approaches nearly equally (42% plan adaptation and 58% re-irradiation). Most cases were assessed for the thoracic body region (51%) followed by pelvis (21%) and head and neck cases (10%). The sub-group evaluation showed that unintended plan adaptation was performed in 38% of the scheduled cases. A median time span between first day of treatment and necessity of adaptation of 17 days (range 4–35 days) was observed. PTV changed by 12 ± 12% on average (maximum change 42%). PTV decreased in 18 of 20 cases due to tumor shrinkage and increased in 2 of 20 cases. Re-planning resulted in a reduction of the mean lung dose of the ipsilateral side in 15 of 20 cases.
Conclusion:
The experience of one year showed high acceptance of the Dynamic Planning Module in our department for both physicians and medical physicists. The re-planning can potentially reduce the accumulated dose to the organs at risk and ensure a better target volume coverage. In the re-irradiation situation, the Dynamic Planning Tool was used to consider the pretreatment dose, to adapt the actual treatment schema more specifically and to review the accumulated dose.
Background:
According to only a handful of historical sources, Osmunda regalis, the royal fern, has been used already in the middle age as an anti-cancer remedy. To examine this ancient cancer cure, an ethanolic extract of the roots was prepared and analysed in vitro on its effectiveness against head and neck cancer cell lines.
Methods:
Proliferation inhibition was measured with the MTT assay. Invasion inhibition was tested in a spheroid-based 3-D migration assay on different extracellular matrix surfaces. Corresponding changes in gene expression were analysed by qRT-PCR array. Induction of apoptosis was measured by fluorescence activated cell sorting (FACS) with the Annexin V binding method. The plant extract was analysed by preliminary phytochemical tests, liquid chromatography/mass spectroscopy (LC-MS) and thin layer chromatography (TLC). Anti-angiogenetic activity was determined by the tube formation assay.
Results:
O. regalis extract revealed a growth inhibiting effect on the head and neck carcinoma cell lines HLaC78 and FaDu. The toxic effect seems to be partially modulated by p-glycoprotein, as the MDR-1 expressing HLaC79-Tax cells were less sensitive. O. regalis extract inhibited the invasion of cell lines on diverse extracellular matrix substrates significantly. Especially the dispersion of the highly motile cell line HlaC78 on laminin was almost completely abrogated. Motility inhibition on laminin was accompanied by differential gene regulation of a variety of genes involved in cell adhesion and metastasis. Furthermore, O. regalis extract triggered apoptosis in HNSCC cell lines and inhibited tube formation of endothelial cells. Preliminary phytochemical analysis proved the presence of tannins, glycosides, steroids and saponins. Liquid chromatography/mass spectroscopy (LC-MS) revealed a major peak of an unknown substance with a molecular mass of 864.15 Da, comprising about 50% of the total extract. Thin layer chromatography identified ferulic acid to be present in the extract.
Conclusion:
The presented results justify the use of royal fern extracts as an anti-cancer remedy in history and imply a further analysis of ingredients.