The human Epstein-Barr virus is associated with several human solid and hematopoietic malignancies. However, the underlying molecular mechanisms including virus-encoded microRNAs (miRs), which lead to the malignant transformation of infected cells and immune evasion of EBV-associated tumors, have not yet been characterized. The expression levels of numerous known EBV-specific miRs and their suitability as diagnostic and/or prognostic markers were determined in different human EBV-positive tissues followed by in silico analyses to identify putative EBV-miR-regulated target genes, thereby offering a suitable screening strategy to overcome the limited available data sets of EBV-miRs and their targeted gene networks. Analysis of microarray data sets from healthy human B cells and malignant-transformed EBV-positive B cells of patients with Burkitt's lymphoma revealed statistically significant (p < 0.05) deregulated genes with known functions in oncogenic properties, immune escape and anti-tumoral immune responses. Alignments of in vivo and in silico data resulted in the prediction of putative candidate EBV-miRs and their target genes. Thus, a combinatorial approach of bioinformatics, transcriptomics and in situ expression analyses is a promising tool for the identification of EBV-miRs and their potential targets as well as their eligibility as markers for EBV detection in different EBV-associated human tissue.
Background Domestic pigs have an evolutionary conserved exploratory behaviour. To comply with this requirement, the European Union aims at setting standards for appropriate enrichment materials for pigs (Council Directive 2008/120/EC). As recommended characteristics include ‘chewable’ and ‘edible’, pigs might also consume these materials (Commission Recommendation (EU) 2016/336), which are often additionally advertised to enhance lying comfort and hygienic conditions in stables. To date, a wide range of bedding, enrichment and disinfectant materials is available on the market to ensure environmental enrichment, a dry, hygienic environment or lying comfort. Previous studies revealed considerable amounts of undesirable substances in some of these materials possibly being a risk for food safety considering oral uptake by the animal. To determine interest and indicators for consumption of different types of materials by pigs during exploratory behaviour, a camera-assisted observational study with 12 female pigs (German Landrace) was conducted. We tested their preference for a disinfectant powder, peat, biochar and straw as reference material in a 4 × 6 factorial arrangement. Results Pigs manipulated and consumed all offered materials. However, longest manipulation time per pig was observed for biochar (63 min/day) and peat (50 min/day) (p < 0.05). Analyses of the bulk molecular-chemical composition and n-alkanes and acid insoluble ash as markers in the materials and in faeces clearly revealed the consumption of these materials by pigs. Conclusions Whether the consumption of considerable amounts together with certain levels of undesirable substances represents a risk for pig and consumer health could yet not be established. Future studies will address the quantitative contribution of undesirable substances by oral ingestion of bedding and enrichment materials and disinfectant powders to the daily feed ration.
Objective Mental health is a fundamental aspect in ensuring the stable and successful professional life of future physicians. Depressive symptoms can negatively affect the work-life-balance and efficiency at work of medical students. To date, there have been very few studies involving medical students that examine the association between single sleep characteristics and the outcome of the Beck Depression Inventory-II score. Therefore, the aim of the present study is to investigate this possible association. A classroom survey using socio-demographic characteristics, the Beck Depression Inventory-II, and the Pittsburgh Sleep Quality Index was conducted amongst students at a German medical school from December 2017 to September 2018. Data analysis was performed with descriptive statistics and binary logistic regression. Results Of the students surveyed, 19% showed depressive symptoms with a Beck Depression Inventory-II score over 13 and 42% of these cases were moderate or severe. The occurrence of relevant depressive symptoms was associated with lower sleep quality, higher sleep latency, and the consumption of sleeping pills. In general, female students and students from abroad had a higher risk of depressive symptoms. Addressing these relevant findings in medical school can increase awareness of mental health.
Background Pain occurs in the majority of patients with late onset Pompe disease (LOPD) and is associated with a reduced quality of life. The aim of this study was to analyse the pain characteristics and its relation to a small nerve fiber involvement in LOPD patients. Methods In 35 patients with LOPD under enzyme replacement therapy without clinical signs of polyneuropathy (19 females; 51 ± 15 years), pain characteristics as well as depressive and anxiety symptoms were assessed using the PainDetect questionnaire (PDQ) and the hospital anxiety and depression scale (HADS), respectively. Distal skin biopsies were analysed for intraepidermal nerve fiber density (IENFD) and compared to age- and gender-matched reference data. Skin biopsies from 20 healthy subjects served as controls to assure validity of the morphometric analysis. Results Pain was reported in 69% of the patients with an average intensity of 4.1 ± 1.1 on the numeric rating scale (NRS; anchors: 0–10). According to PDQ, neuropathic pain was likely in one patient, possible in 29%, and unlikely in 67%. Relevant depression and anxiety symptoms occurred in 31% and 23%, respectively, and correlated with pain intensity. Distal IENFD (3.98 ± 1.95 fibers/mm) was reduced in 57% of the patients. The degree of IENFD reduction did not correlate with the durations of symptoms to ERT or duration of ERT to biopsy. Conclusions Pain is a frequent symptom in treated LOPD on ERT, though a screening questionnaire seldom indicated neuropathic pain. The high frequency of small nerve fiber pathology in a treated LOPD cohort was found regardless of the presence of pain or comorbid risk factors for SFN and needs further exploration in terms of clinical context, exact mechanisms and when developing novel therapeutic options for LOPD.
The past three decades have witnessed the rapid development of fast scanning calorimetry (FSC), a novel calorimetric technique that employs micromachined sensors. The key advantages of this technique are the ultrahigh scanning rate, which can be as high as 10 6 K s −1 , and the ultrahigh sensitivity, with a heat capacity resolution typically better than 1 nJ K −1 . This chapter reviews the development of FSC and summarizes its applications to polymers (including proteins). FSC has attracted much attention in polymer science, where it is used for quantitative analysis of rapid phase transitions, particularly, though not throughout, on fast cooling. Another emerging field of application of FSC is the study of thermophysical properties of thermally labile compounds. Quantities like melting temperature and enthalpy as well as sublimation and vaporization enthalpies and vapor pressures of biomolecules became available. Even deeper insights into the various processes are possible by combining FSC with structural characterization techniques such as X‐ray diffraction (XRD), polarized light optical microscopy (POM), atomic force microscopy (AFM), transmission and scanning electron microscopy (TEM and SEM, respectively), and infrared spectroscopy (IR). Finally, current challenges and outlooks will be discussed. Given the unique attributes of the technique, FSC is expected to attract increasing attention, especially concerning the characterization of fast phase transitions, structural states which can only be adjusted by rapid cooling, and the evaluation of thermodynamic properties of thermally labile compounds.
This chapter presents an overview of polymer crystallization upon cooling the melt, or heating the glass. Inter‐ and intramolecular forces drive many polymers to develop ordered structures at the nanometer‐ and micrometer‐scale. These structures ultimately control bulk material properties and influence the selection of a given polymer for specific applications. Polymer crystallization proceeds via crystal nucleation and growth, and both processes are discussed and analyzed thoroughly herein. Together with these key features of polymer crystallization, the influence of crystal formation on the coupled amorphous fraction is also described. The chapter is completed with analysis of crystallization in polymer blends, and crystallization in industrial processing, with main aspects of flow‐induced crystallization detailed.
The extraction efficiency, recovery, quantification, and stability of isoflavones (daidzein, genistein and puerarin) from the wastes /by-products of kudzu roots and soy molasses were evaluated by using natural deep eutectic solvents (NADESs) coupled with ultrasound-assisted extraction. The NADES extraction was compared with the conventional Soxhlet extraction technique, and the extracted isoflavones were quantified using HPLC-UV/Vis. Results showed extractability of puerarin to be significantly increased (p < 0.0001) in proportion to the increased water concentration of NADES (9.7 ± 0.2, 12.6 ± 0.2, and 14.8 ± 0.3 mg/g in NADESs containing 10%, 20%, and 30% water, respectively). Despite having less isoflavone content, kudzu roots and soy molasses extracts obtained using NADES exhibited higher antioxidant activity when compared with methanolic extracts. Further, NADES extracts also markedly reduced the degradation degree of isoflavones. The results of this investigation support the use of green extraction techniques to obtain value-added components like isoflavones from wastes/by-products like that of kudzu roots and soy molasses, which are envisaged to find future potential applications in the food and pharmaceutical industries.
When acid sulfate soils dry, oxidation of pyrite can cause acidification and formation of iron (Fe) oxyhydroxy sulfate phases such as jarosite. Remediation via re-establishment of reducing conditions requires submergence and addition of biodegradable organic carbon (OC) to stimulate activity of reducing bacteria. Addition of fresh plant litter has been shown to activate reducing bacteria, likely due to the release of readily available soluble organic matter. However, the effectiveness of soluble organic matter from plant residues has not been tested yet. Here, we tested the potential of wheat straw-derived dissolved OC (DOC) for remediation of a sandy sulfuric (pH < 4) soil. In a second set of experiments, we used combinations of wheat straw-derived DOC with lactate, which is a preferred substrate of sulfate reducing bacteria. All incubation experiments were conducted in the dark at 20 °C. The results showed that addition of DOC from wheat straw induces reduction reactions and rapidly increases the pH by 2–3 units after 3 weeks of incubation under submerged conditions. Mössbauer spectroscopy and X-ray diffraction revealed that jarosite was lost after 200 days of anoxic incubation. Short range-ordered FeIII oxyhydroxides were formed, most likely by FeII-catalysed transformation of jarosite. A second addition of DOC, as well as the addition of lactate, resulted in the almost complete loss of jarosite with increased proportions of FeIII oxyhydroxides in the remaining solids, but not in the formation of FeII sulfides. The formation of FeIII oxyhydroxides reduces the risk of both Fe leaching and renewed acidification in the event of future oxidation. The results suggest that deep injection of wheat straw-derived DOC is a promising approach for rapid and sustainable remediation of sandy sulfuric subsoils.
Plants show remarkable phenotypic plasticity and are able to adjust their morphology and development to diverse environmental stimuli. Morphological acclimation responses to elevated ambient temperatures are collectively termed thermomorphogenesis. In Arabidopsis thaliana, morphological changes are coordinated to a large extent by the transcription factor PHYTOCHROME-INTERACTING FACTOR 4 (PIF4), which in turn is regulated by several thermosensing mechanisms and modulators. Here, we review recent advances in the identification of factors that regulate thermomorphogenesis of Arabidopsis seedlings by affecting PIF4 expression and PIF4 activity. We summarize newly identified thermosensing mechanisms and highlight work on the emerging topic of organ- and tissue-specificity in the regulation of thermomorphogenesis.
Background Post-stroke delirium (POD) in patients on stroke units (SU) is associated with an increased risk for complications and poorer clinical outcome. The objective was to reduce the severity of POD by implementing an interprofessional delirium-management. Methods Multicentric quality-improvement project on five SU implementing a delirium-management with pre/post-comparison. Primary outcome was severity of POD, assessed with the Nursing Delirium Screening Scale (Nu-DESC). Secondary outcome parameters were POD incidence, duration, modified Rankin Scale (mRS), length of stay in SU and hospital, mortality, and others. Results Out of a total of 799 patients, 59.4% ( n = 475) could be included with 9.5% ( n = 45) being delirious. Implementation of a delirium-management led to reduced POD severity; Nu-DESC median: pre: 3.5 (interquartile range 2.6–4.7) vs. post 3.0 (2.2–4.0), albeit not significant ( p = 0.154). Other outcome parameters were not meaningful different. In the post-period, delirium-management could be delivered to 75% ( n = 18) of delirious patients, and only 24 (53.3%) of delirious patients required pharmacological treatments. Patients with a more severe stroke and POD remained on their disability levels, compared to similar affected, non-delirious patients who improved. Conclusions Implementation of delirium-management on SU is feasible and can be delivered to most patients, but with limited effects. Nursing interventions as first choice could be delivered to the majority of patients, and only the half required pharmacological treatments. Delirium-management may lead to reduced severity of POD but had only partial effects on duration of POD or length of stay. POD hampers rehabilitation, especially in patients with more severe stroke. Registry DRKS, DRKS00021436. Registered 04/17/2020, www.drks.de/DRKS00021436 .
Phosphorus (P) fertilizer recommendations of individual countries may differ in many aspects, but often the main principle is to reach or maintain a target range of plant-available P in soil. Within this target P fertility class, the soil is expected to supply enough P to the crop, while P fertilization replaces what is exported by the harvested crop. However, the threshold values of the target P fertility classes are based on a multitude of different soil test P (STP) methods and vary by a factor of up to three, even for countries using the same STP method. This study aimed to provide a comparison of the thresholds of target P fertility classes of different European countries and critical soil test P values (Pcrit; STP below which the average relative yield falls below 95% due to P insufficiency) derived from the analysis of data from 55 long-term field experiments in eight European countries. To overcome the issue of diverging STP methods, all values were converted to Olsen-P using empirically based conversion equations from the literature. Converted threshold values varied by a factor of up to five. For the experimental data, we fitted multi-level Mitscherlich-type models to determine Pcrit values of unfertilized soils corresponding to 95% of maximum yield. We found an average Olsen-Pcrit value of 15 mg P kg⁻¹ (adj. R² = 0.37; RMSE = 14.1% relative yield; n = 2368; 55 experiments), which lies far below several country-specific thresholds of target P fertility classes. Crop-specific analyses resulted in higher Olsen-Pcrit values for sugar beet (22 mg P kg⁻¹), potato (19 mg P kg⁻¹) and winter rapeseed (18 mg P kg⁻¹). Among the texture classes (loam, sand, silt and clay), sandy soils exhibited the highest average Olsen-Pcrit value (22 mg P kg⁻¹). We consider a reevaluation of extraordinarily high country-specific thresholds as well as an inclusion of crop type and soil texture (where not already implemented) to be a reasonable measure towards more cost-effective and environment-friendly P fertilization.
B cells are central for the adaptive immune system to mount successful immune responses not only as antibody producers but also as regulators of cellular immunity. These multifaceted features are also reflected in autoimmunity where autoreactive B cells can fuel disease by production of cytotoxic autoantibodies, presentation of autoantigens to autoreactive T cells, and secretion of cytokines and chemokines that either promote detrimental immune activation or impair regulatory T and B cells. The role of B cells and autoantibodies in autoimmune hepatitis (AIH) have been controversially discussed, with typical autoantibodies and hypergammaglobulinemia indicating a key role, while strong HLA class II association suggests T cells as key players. In this review, we summarize current knowledge on B cells in AIH and how different B cell subpopulations may drive AIH progression beyond autoantibodies. We also discuss recent findings of B cell-directed therapies in AIH.
The beneficiation process of bauxite (Al-ore) generates over 10 mi tons of waste clay disposed of in tailing ponds. The purpose of this work was to test this material to produce CSA–based cements. Raw mixtures with the clay were formulated to maximize ye’elimite contents in the clinkers. A CSA-belite clinker composed of 46% of ye’elimite, 40% of belite, and minor amounts of Fe-perovskite and brownmillerite was produced. Cement pastes using clinker to gypsum ratios of 90:10, 85:15, and 75:25 developed compressive strength higher than a Portland cement. The pastes have major contents of ettringite and kuzelite depending on the sulfate additions, besides straetlingite, aluminium hydroxide and hemicarboaluminate. The waste clay is as a potential raw material for CSA-belite low-CO2 cements.
219 HIV-negative adults ≤70 years with primary CNS lymphoma (PCNSL) were enrolled in the randomized IELSG32 trial. Enrolled patients were randomly assigned to receive methotrexate-cytarabine (arm A), or methotrexate-cytarabine-rituximab (B), or methotrexate-cytarabine-thiotepa-rituximab (MATRix; arm C). A second randomization allocated patients with responsive/stable disease to whole-brain irradiation (WBRT) or carmustine-thiotepa-conditioned autologous transplantation (ASCT). First results, after a median follow-up of 30 months, showed that MATRix significantly improves outcome, with both WBRT and ASCT being similarly effective. However, sound assessment of overall survival (OS), efficacy of salvage therapy, late complications, secondary tumors, and cognitive impairment requires longer follow-up. Herein, we report the results of this trial at a median follow-up of 88 months. As main findings, MATRix was associated with excellent long-lasting outcome, with a 7-year OS of 21%, 37%, and 56% respectively for arms A, B, and C. Notably, patients treated with MATRix and consolidation had a 7-year OS of 70%. The superiority of arm B on arm A suggests a benefit from the addition of rituximab. Comparable efficacy of WBRT and ASCT was confirmed. Salvage therapy was ineffective; benefit was recorded only in patients with late relapse re-treated with methotrexate. Eight (4%) patients developed a second cancer. Importantly, MATRix and ASCT did not result in higher non-relapse mortality or second tumors incidence. Patients who received WBRT experienced impairment in attentiveness and executive functions, whereas patients undergoing ASCT experienced improvement in these functions as well as in memory and quality of life.
Although there is evidence that language skills and executive functions (EF) are highly intercorrelated, so far underlying mechanisms are not clear. Using the Tower of London task as a measure of complex EF performance, the present study examined self-directed speech as one possible mechanism underlying these associations by using three approaches: analyzing quantity and quality of self-directed speech, articulatory suppression, and triggering self-directed speech. Participants were N = 73 preschool children from Germany. Results confirm the relation between language skills and EF albeit it cannot be explained by self-directed speech. While quantity and quality of self-directed speech was related to language skills, the use of self-directed speech with planning function was positively related to performance. Findings suggest that the use of self-directed speech with planning function might be an important factor in explaining cognitive advantages. Moreover, results indicated that self-directed speech is helpful in children with lower non-verbal IQ.
Purpose To assess the symptoms, quality of life and sexual well-being in patients with lower urinary tract symptoms due to benign prostatic hyperplasia LUTS/BPH treated with pumpkin seed soft extract (PSE) in routine practice. Methods This noninterventional study included 130 men treated for up to 24 months. The International Prostate Symptom Score (IPSS) and related quality of life, Aging Males’ Symptoms Scale (AMS), and International Index of Erectile Function (IIEF-5) were recorded. Descriptive statistical methods were applied. The mean with 95% confidence interval (CI) was calculated for the primary end point (change in IPSS after 12-month treatment). Results Analysis at 12 months included 83 patients [mean (SD) age 65.2 (8.7) years and IPSS (15.6 (3.4), IPSS-QoL 3.4 (0.9)]. AMS and IIEF-5 indicated mild or mild to moderate disorder regarding sexual well-being and erectile dysfunction, respectively. After 12 months, the mean IPSS change from baseline was − 4.7 (95% CI − 5.4 to − 3.9), with 83% (95% CI 65.3 to 84.1) and 53% (95% CI 42.3 to 63.7) of the patients achieving reductions by at least 3 and 5 points, respectively. The proportion of patients with IPSS-QoL below 3 points (mostly satisfied) was 11% (9/83) at baseline and rose to 62% (51/83) and 73% (40/55) at 12 and 24 months, respectively. AMS and IIEF-5 scores did not indicate a negative impact on sexual function during treatment. Conclusion In men with a moderate LUTS suggestive of BPH, a low progression risk and an active sex life, treatment with pumpkin seed soft extract provided symptomatic relief, improved IPSS-QoL, and maintained sexual well-being. Trial registration DRKS00010729, June 22, 2016.
The documentary method is increasingly applied in classroom research. This article aims at presenting an approach of how the meta-theoretical categories of the praxeological sociology of knowledge, the basic theory of the documentary method, can be used to reconstruct the classroom actions of the participants in controversial classroom interactions as a power structure. This is illustrated by a teaching sequence in which students argue about how to deal with their income differences within a village foundation simulation. The power structure of the teaching milieu offers insights into the politics of the school class and perspectives of civic education to the school class as a socialization context between peers and school.
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