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The NATALEE study showed a significant benefit in invasive disease-free survival (iDFS) for patients with HR+/HER2− early breast cancer (eBC) at intermediate and high risk of recurrence who were treated with the CDK4/6 inhibitor Ribociclib in combination with endocrine therapy (ET). This retrospective study aims to apply the NATALEE inclusion criteria to a representative real-world cohort to estimate the proportion of HR+/HER2− breast cancer patients eligible for adjuvant Ribociclib therapy. Patients who underwent full surgical treatment for eBC between January 2018 and December 2020 at two large German university breast cancer centers (University of Ulm, University of Tuebingen) were included. Descriptive statistics were used to characterize the patient population eligible for Ribociclib treatment based on the NATALEE study's inclusion criteria. Out of 2384 enrolled patients, 1738 had HR+/HER2− eBC, of whom 43% (747/1738) met the NATALEE inclusion criteria. Of note, these patients were older, received less chemotherapy and presented with less advanced tumor stages compared to the NATALEE study cohort. Additionally, compared to the NATALEE study cohort, fewer patients had lymph node involvement (72.4% vs. 88.7%). Our analysis suggests that approximately 43% of all HR+/HER2− breast cancer patients will qualify for Ribociclib treatment. Given the numerous treatment options for patients with HR+/HER2− eBC, as well as the differences between the NATALEE cohort and patients in the real-world clinical setting, future analyses will be needed to determine which patients would benefit most from adjuvant CDK4/6 inhibitor treatment. [ABSTRACT FROM AUTHOR]

Introduction: As the numbers of young patients diagnosed with early-stage endometrial carcinoma continue to rise, the question regarding fertility-preserving therapeutic options will increasingly gain significance in the future. Case Presentation: Here, we present the case of a 21-year-old patient diagnosed with symptomatic atypical endometrial hyperplasia. After 4 months of treatment with medroxyprogesterone acetate, a follow-up dilatation and curettage revealed early-stage, well-differentiated endometrioid endometrial carcinoma. Despite national guidelines recommending hysterectomy, the nulliparous patient expressed a desire to preserve her fertility. Subsequently, she underwent polyendocrine therapy with letrozole, everolimus, metformin, and Zoladex. Forty-three months after diagnosis, the patient successfully gave birth to a healthy child, and there have been no indications of recurrence thus far. Discussion: This case suggests that triple endocrine therapy may be an option for selected patients with early endometrial cancer and a desire for fertility-sparing therapy. [ABSTRACT FROM AUTHOR]

The aggregation of amyloid- β (A β) peptides, particularly of A β 1 − 42 , has been linked to the pathogenesis of Alzheimer's disease. In this study, we focus on the conformational change of A β 1 − 42 in the presence of glycosaminoglycans (GAGs) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipids using molecular dynamics simulations. We analyze the conformational changes that occur in A β by extracting the key structural features that are then used to generate transition networks. Using the same three features per network highlights the transitions from intrinsically disordered states ubiquitous in A β 1 − 42 in solution to more compact states arising from stable β -hairpin formation when A β 1 − 42 is in the vicinity of a GAG molecule, and even more compact states characterized by a α -helix or β -sheet structures when A β 1 − 42 interacts with a POPC lipid cluster. We show that the molecular mechanisms underlying these transitions from disorder to order are different for the A β 1 − 42 /GAG and A β 1 − 42 /POPC systems. While in the latter the hydrophobicity provided by the lipid tails facilitates the folding of A β 1 − 42 , in the case of GAG there are hardly any intermolecular A β 1 − 42 –GAG interactions. Instead, GAG removes sodium ions from the peptide, allowing stronger electrostatic interactions within the peptide that stabilize a β -hairpin. Our results contribute to the growing knowledge of the role of GAGs and lipids in the conformational preferences of the A β peptide, which in turn influences its aggregation into toxic oligomers and amyloid fibrils. [ABSTRACT FROM AUTHOR]

• Transition networks built from MD simulations reveal the configurational ensemble and structural interconversions of IDPs in an easy-to-grasp manner. • The creation of transition networks with the open-source software ATRANET is explained. • The effects of molecular descriptors on transition networks is demonstrated. Intrinsically disordered proteins (IDPs) do not fold into a unique three-dimensional structure but sample different configurations of different probabilities that further change with the surrounding of the IDPs. The structural heterogeneity and dynamics of IDPs pose a challenge for the characterization of their structures by experimental techniques only. Molecular dynamics (MD) simulations provide a powerful complement to experimental approaches for that purpose. However, MD simulations on the micro- to millisecond timescale generate a lot of data of protein motions, necessitating advanced post-processing techniques to extract the relevant information. Here, we demonstrate how transition networks created from MD trajectories allow revealing the configurational ensemble and structural interconversions of IDPs, using the amyloid- β peptide as example. The construction of transition networks relies on molecular descriptors as input, and we show how the choice of descriptors influences the resulting transition network. The transition networks are generated with the open-source Python script ATRANET, and we explain the usage of ATRANET by providing a detailed workflow and exemplary analysis for amyloid- β , which can be easily generalized to other IDPs and even protein aggregation. [ABSTRACT FROM AUTHOR]

[Display omitted] Lipid nanoparticles (LNPs) employing ionizable lipids are the most advanced technology for delivery of RNA, most notably mRNA, to cells. LNPs represent well-defined core–shell particles with efficient nucleic acid encapsulation, low immunogenicity and enhanced efficacy. While much is known about the structure and activity of LNPs, less attention is given to the timing of LNP uptake, cytosolic transfer and protein expression. However, LNP kinetics is a key factor determining delivery efficiency. Hence quantitative insight into the multi-cascaded pathway of LNPs is of interest to elucidate the mechanism of delivery. Here, we review experiments as well as theoretical modeling of the timing of LNP uptake, mRNA-release and protein expression. We describe LNP delivery as a sequence of stochastic transfer processes and review a mathematical model of subsequent protein translation from mRNA. We compile probabilities and numbers obtained from time resolved microscopy. Specifically, live-cell imaging on single cell arrays (LISCA) allows for high-throughput acquisition of thousands of individual GFP reporter expression time courses. The traces yield the distribution of mRNA life-times, expression rates and expression onset. Correlation analysis reveals an inverse dependence of gene expression efficiency and transfection onset-times. Finally, we discuss why timing of mRNA release is critical in the context of codelivery of multiple nucleic acid species as in the case of mRNA co-expression or CRISPR/Cas gene editing. [ABSTRACT FROM AUTHOR]

The characteristics of solar cells in the reverse voltage direction are essential for the resilience of a photovoltaic module against partial-shading induced damage. Therefore, it is important to establish a thorough understanding of the mechanisms that lead to reverse breakdown in solar cells. This work studies thin-film solar cells based on Cu(In,Ga)Se2 (CIGS) absorber layers. Systematic material variations are investigated in order to learn more about the mechanisms governing reverse breakdown in these devices. To this end, devices with different thicknesses of the CdS buffer layer and with and without a RbF-post-deposition treatment (PDT) of the absorber layer were fabricated. The resulting current-voltage characteristics at negative voltage biases reveal that devices break down at much more negative voltages if they underwent a PDT, if the buffer layer thickness is increased, or if the buffer layer is not photoexcited. This implies that possibly a PDT may be disadvantageous for the shading tolerance of a module. The further analysis indicates that several mechanisms are involved in the reverse breakdown. Whereas tunneling currents in the buffer layer seem to play a major role for the actual breakdown, the strong effect of the PDT is probably caused by a reduction of shunt leakage currents along grain boundaries which lowers material heating. [ABSTRACT FROM AUTHOR]

The anti-inflammatory adipokine CTRP-3 might affect innate immune reactions such as NOD1. The impact of CTRP-3 on NOD1-mediated inflammation in adipocytes and monocytic cells as well as on NOD1 expression was investigated. Murine 3T3-L1 pre-adipocytes and adipocytes as well as human THP-1 monocyte-like cells were co-stimulated with the synthetic NOD1 agonist Tri-DAP and recombinant CTRP-3. Gonadal adipose tissue and primary adipocytes were obtained from a murine model carrying a knockout (KO) of CTRP-3 in adipocytes but not in stroma-vascular cells. Wildtype mice with lipopolysaccharide (LPS)-induced elevated NOD1 expression were treated with CTRP-3. Secreted inflammatory cytokines in cell supernatants were measured by ELISA and mRNA levels were quantified by RT-PCR. Pro-inflammatory chemokine and cytokine secretion (MCP-1, RANTES, TNFα) was induced by NOD1 activation in adipocytes and monocyte-like cells, and MCP-1 and RANTES release was effectively inhibited by pre-incubation of cells with CTRP-3. CTRP-3 also antagonized LPS-triggered induction of NOD1 gene expression in murine adipose tissue, whereas adipocyte CTRP-3 deficiency upregulated NOD1 expression in adipose tissue. CTRP-3 is an effective antagonist of peptidoglycan-induced, NOD1-mediated inflammation and of LPS-induced NOD1 expression. Since basal NOD1 expression is increased by adipocyte CTRP-3 deficiency, there have to be also inflammation-independent mechanisms of NOD1 expression regulation by CTRP-3. [ABSTRACT FROM AUTHOR]

Premise of research. Flowers of the genus Euphorbia are arranged in a unique type of inflorescence called cyathia, packed into more or less dense synflorescences. These synflorescences can be showy or inconspicuous, suggesting different pollination strategies. Methodology. We described and compared the morphology, color, scent, and insect guilds visiting the synflorescences of five European Euphorbia species, two with inconspicuous synflorescences and three with showy ones. Pivotal results. All five species present their reproductive structures openly, with easily accessible nectaries. In the inconspicuous E. peplus and E. dulcis , there was little color contrast between the reproductive parts and the vegetative parts. Both species attracted low numbers of insects (Diptera and Hymenoptera), and these insects carried little (E. peplus) or no (E. dulcis) pollen. We did not detect any floral scent for E. peplus. In the showy E. amygdaloides , E. virgata , and E. verrucosa , the color of the reproductive parts and of the relatively large nectaries was standing out clearly against vegetative organs. These species attracted up to 14 times more insects (Diptera, Hymenoptera, Coleoptera) than the inconspicuous species, and these insects carried larger amounts of pollen on their bodies. In E. verrucosa , nearly half of the pollinators were sawflies from the genus Tenthredo feeding and mating on the synflorescences. All Euphorbia species except E. peplus were also visited by ants. However, the role of ants as pollinators remains to be tested. Finally, E. peplus and E. dulcis can reproduce without insect pollination, whereas among the showy species, E. virgata did not produce seeds when pollinators were excluded. Conclusions. We found that all study species had similar generalist pollination systems, with the showy species attracting significantly more insects and the inconspicuous species being largely independent of insect visits for reproduction. Our study tentatively indicates that the degree of entomophily seems positively correlated with showiness and size of attractive and rewarding organs. [ABSTRACT FROM AUTHOR]

• A novel protocol for the application of isotope-dilution-LC-MS/MS in reference measurement procedures is described. • An spreadsheet file is used as an essential tool for result generation, data review and validation of series and results. • A method for the quantification of ciprofloxacin in human serum was investigated as an example. Reference measurement procedures for assigning values to calibration materials play a crucial role in the concept of metrological traceability in laboratory medicine. ISO standard 15,193 specifies the requirements for such measurement procedures, albeit in a very general terms. A standard structure of analysis series for value assignment by LC-MS/MS was developed and tested,this structure was complemented by a spreadsheet file for result calculation, metadata evaluation, and finally validation and confirmation of individual analysis runs and individual results, and measurement uncertainty evaluation. This framework was applied to a procedure for the quantification of ciprofloxacin in serum as an example. The approach of a detailed description of the analytical procedures of isotope dilution LC-MS/MS reference measurement methods together with a highly standardized spreadsheet-based method for data processing was found to be practical and efficient. The described measurement procedure for the quantification of ciprofloxacin in serum was found to be fit for purpose. A standardized, detailed procedure for the application of isotope dilution LC-MS/MS in reference measurement procedures can complement the ISO 15193 standard with respect to this particular analytical technique, which is now widely used in the context of metrological traceability in laboratory medicine. [ABSTRACT FROM AUTHOR]

The extracellular metalloprotease meprin β is expressed as a homodimer and is primarily membrane bound. Meprin β can be released from the cell surface by its known sheddases ADAM10 and ADAM17. Activation of pro-meprin β at the cell surface prevents its shedding, thereby stabilizing its proteolytic activity at the plasma membrane. We show that a single amino acid exchange variant (G32R) of meprin β, identified in endometrium cancer, is more active against a peptide substrate and the IL-6 receptor than wild-typemeprin β.We demonstrate that the change to an arginine residue at position 32 represents an additional activation site used by furin-like proteases in theGolgi,which consequently leads to reduced shedding by ADAM17. We investigated this meprin β G32R variant to assess cell proliferation, invasion through a collagen IV matrix and outgrowth from tumor spheroids. We found that increased meprin β G32R activity at the cell surface reduces cell proliferation, but increases cell invasion. [ABSTRACT FROM AUTHOR]

Objective: Nucleotide‐binding oligomerization domain‐containing protein 2 (NOD2) gene mutations are known to be an important risk factor in the pathogenesis of Crohn's disease (CD). Specific disease phenotypes are associated with the presence of NOD2 gene mutation. One treatment option is to use an anti‐tumor necrosis factor (TNF)‐α agent. Therapeutic drug monitoring (TDM) is usually performed in cases of a loss of response. Our aim was to explore whether NOD2 gene mutations have an effect on the disease phenotype, vitamin D levels, and on TDM in CD patients. Methods: This was a retrospective genotype–phenotype association study on NOD2 gene mutations in 161 patients with CD. Results: Altogether 55 (34.2%) patients carried at least one mutant allele of NOD2. NOD2 gene mutations were associated with ileocecal disease, ileocecal resection, stricturing and perianal disease, and patients with NOD2 gene mutation had significantly less frequent colonic disease and received an ostomy less frequently. TDM in patients with NOD2 gene mutation showed more frequent anti‐TNF trough levels in the subtherapeutic range and lower anti‐TNF trough levels than in NOD2 wild‐type (WT) patients. Conclusions: CD patients with NOD2 gene mutation have a specific clinical phenotype and they may require higher doses of anti‐TNF agents to achieve sufficient anti‐TNF trough levels. They may therefore benefit from a proactive TDM than a reactive approach. This could be another step in the direction of personalized medicine. [ABSTRACT FROM AUTHOR]

Bile acids (BAs) in the peripheral circulation represent a specific but underestimated physiological compartment Systemic (peripheral) BAs can be regarded as specific steroidal hormones that act on white adipocytes. The term 'bilokines' ('bile hormones') is suggested for peripheral BAs subspecies acting on specific receptors on adipocytes and peripheral tissues other than gut or liver. Adipoflammation and metaflammation in visceral obesity represent the main and causal mechanisms for insulin resistance and type 2 diabetes mellitus (T2D), and can be targeted by BAs in an anti-inflammatory manner. The kinetics of systemic BA subspecies upon feeding and bariatric surgery represents a widely uncharacterized black box whose decipherment could help to identify single BAs as druggable targets in obesity, T2D, and metabolic syndrome. The effects of bile acids (BAs) on liver, enteroendocrine function, small intestine, and brown adipose tissue have been described extensively. Outside the liver, BAs in the peripheral circulation system represent a specific but underappreciated physiological compartment. We discuss how systemic BAs can be regarded as specific steroidal hormones that act on white adipocytes, and suggest the name 'bilokines' ('bile hormones') for the specific FXR/TGR5 receptor interaction in adipocytes. Some BAs and their agonists regulate adipocyte differentiation, lipid accumulation, hypoxia, autophagy, adipokine and cytokine secretion, insulin signaling, and glucose uptake. BA signaling could provide a new therapeutic avenue for adipoflammation and metaflammation in visceral obesity, the causal mechanisms underlying insulin resistance and type 2 diabetes mellitus (T2D). [ABSTRACT FROM AUTHOR]

OBJECTIVE: Dysbiosis is a common feature in the pathogenesis of inflammatory bowel diseases (IBD). Environmental factors, such as vitamin D deficiency, seem to play a role in the intestinal inflammation of IBD. The aim of this study was to investigate whether vitamin D administration has an impact on the bacterial composition in Crohn's disease (CD) compared to healthy controls (HC). METHODS: A prospective, longitudinal, controlled interventional analysis was conducted in seven patients with CD in clinical remission and 10 HC to investigate the effect of orally administrated vitamin D on the intestinal bacterial composition using 16S ribosomal RNA gene amplicon sequencing. Clinical parameters were assessed. RESULTS: In contrast to HC, microbial communities of CD patients changed significantly during early vitamin D administration. However, a further increase in vitamin D level was associated with a reversal of this effect and additionally with a decrease in the bacterial richness in the CD microbiome. Specific species with a high abundancy were found during vitamin D administration in CD, but not in HC; the abundancy of Alistipes, Barnesiella, unclassified Porphyromonadaceae (both Actinobacteria), Roseburia, Anaerotruncus, Subdoligranulum and an unclassified Ruminococaceae (all Firmicutes) increased significantly after 1‐week vitamin D administration in CD. CONCLUSIONS: Vitamin D has a specific influence on the bacterial communities in CD, but not in HC. Administration of vitamin D may have a positive effect in CD by modulating the intestinal bacterial composition and also by increasing the abundance of potential beneficial bacterial strains. [ABSTRACT FROM AUTHOR]

OBJECTIVE: There is growing evidence that vitamin D deficiency plays a role in the development and the course of inflammatory bowel disease (IBD). However, the correlation between vitamin D deficiency and clinical parameters in IBD is still not completely understood. METHODS: A retrospective study of IBD patients was performed. Vitamin D values were analyzed, regardless of vitamin D substitution administration, and correlated with clinical parameters such as medical therapy, anatomical situation, location of the disease and disease activity. Level of 25‐hydroxyvitamin D [25(OH)D] <50 nmoL/L was regarded as vitamin D deficiency and <75 nmoL/L as insufficiency. RESULTS: In total, 208 IBD patients were analyzed, including 123 with Crohn's disease (CD) and 85 with ulcerative colitis (UC). Therapy with azathioprine did not affect the vitamin D values of either disease entity. But CD patients benefited from therapy with tumor necrosis factor‐α inhibitor and exhibited significantly higher vitamin D levels than those without. Furthermore, significantly lower vitamin D levels were found if CD was located in the small bowel or if the small bowel had been resected. Moreover, significantly lower levels of vitamin D were detectable for high disease activity (reflected by high simple clinical colitis activity index values) in patients with UC. CONCLUSIONS: Vitamin D deficiency is common in patients with IBD. However, certain clinical situations lead to significantly lower vitamin D levels and may therefore require close monitoring for vitamin D deficiency. [ABSTRACT FROM AUTHOR]

Recent investigation has revealed the significant role of Cathelicidin antimicrobial peptide (CAMP) in infection defense and innate immunity processes in adipose tissue. Meanwhile, knowledge of its regulation and functions in metabolic contexts as an adipokine remains sparce. The present study investigated the postprandial regulation of circulating CAMP levels during oral glucose tolerance tests (OGTTs). Eighty-six metabolically healthy volunteers participated in a standardized 75 g-2 h-OGTT setting. The effects of exogenous glucose, insulin, and incretins on CAMP expression in human adipocyte culture (cell-line SGBS) were studied in vitro. CAMP concentrations in blood serum samples were measured by ELISA techniques and adipocyte gene expression levels were quantified by real-time PCR. Of note, base-line CAMP serum quantities were negatively correlated with HDL cholesterol levels as well as with the anti-inflammatory adipokine adiponectin. During the 2 h following glucose ingestion, a significant rise in circulating CAMP concentrations was observed in considerable contrast to reduced quantities of fatty acid binding proteins (FABP) 2 and 4 and dipeptidyl peptidase 4 (DPP4). In SGBS adipocytes, neither differing glucose levels nor insulin or incretin treatment significantly induced CAMP mRNA levels. According to our data, glucose represents a positive postprandial regulator of systemic CAMP. This effect apparently is not mediated by the regulatory impact of glucose metabolism on adipocyte CAMP expression. [ABSTRACT FROM AUTHOR]

In inflammatory bowel diseases (IBD), microbial communities often become imbalanced suggesting abnormal microbial-gut interactions. In this study, we analysed the mucosa-attached gut microbiota from 26 Crohn's disease (CD) patients using 16S rRNA gene amplicon sequencing. The samples were stratified according to their disease activity (Crohn's disease activity index, CDAI). The different disease activity categories had a comparable bacterial richness. Bacterial communities of patients in remission and intermediate CDAI (0-220) were relatively similar and dominated by the genus Bacteroides (>40%). The bacterial composition of patients assigned to a high CDAI category was dominated by Pelomonas (25%) and Flavobacterium (13%) but had a low relative abundance of Bacteroidetes (4%). This indicates the presence of specific abundant bacterial taxa at different CDAI levels. In addition, bacterial communities were also significantly influenced when a tumour necrosis factor (TNF)-α inhibitor was applied or by the local mucosal inflammation level. As a consequence, a shift of the microbial composition may also indicate a change of the disease activity in CD patients. [ABSTRACT FROM AUTHOR]

The article presents a report from a March 4, 2016 conference in Munich, Germany on Bohemian history hosted by the Collegium Carolinum college. Topics of presentations delivered include the history of the Habsburg monarchy's rule over Krumlov, Czech Republic, an exhibition on Holy Roman Emperor Karl IV, and the Czech national historical research department.

Introduction: Changes in the intestinal bacterial composition seem to play a major role in the pathogenesis and in the clinical course of inflammatory bowel diseases (IBD), which consist of Crohn's disease (CD), and ulcerative colitis (UC). Mutations in the NOD2 gene are the most important genetic risk factors for the development of CD. In this study, the association between mucosal biopsies and the mucosa-associated bacterial composition from CD and UC patients regarding their genetic risk factors (mutations in the NOD2 gene), their endoscopic activity, and their medical therapy (TNF-α blocking therapy) was examined. Material and methods: Seventy biopsies from routine colonoscopies from 33 IBD patients (26 CD and 7 UC) were obtained. Disease activity and clinical characteristics were assessed. Seven different bacterial strains ( Bacteroides fragilis, Escherichia coli, Prevotella melaninogenica, Clostridium coccoides, Clostridium difficile, Bifidobacterium bifidum, and Faecalibacterium prausnitzii) were quantified using real-time PCR. NOD2 genotyping from patients with CD was performed. Results: Five of the 24 patients were positive for at least one mutation in the NOD2 gene. The bacterial composition was different in CD compared to UC, in macroscopic healthy compared to macroscopic inflamed biopsies, in NOD2 mutated compared to NOD2 wildtype patients, and in patients receiving TNF-α blocking therapy compared to patients without this treatment. Conclusion: This study further characterizes the mucosa-associated bacteria in IBD patients. Different clinical situations lead to an altered mucosa-associated bacterial composition. The analyzed bacteria could be promising targets for cost-effective surveillance or therapies in IBD patients. [ABSTRACT FROM AUTHOR]

BackgroundRecently, we demonstrated in vivo effects of acutely induced hyperglycemia, diabetes and mannitol infusions on rat mesenteric microcirculation concerning leukocyte–endothelial-cell interaction (Schäffler et al. EJCI 28: 886–893, 1998). DesignIn this study we have investigated the possible involvement of the protein kinase C (PKC) and p38 MAP kinase cascade as signal transducing elements during hyperglycemic and osmotic stress in an in vivo rat model. ResultsAcutely induced hyperglycemia resulted in a significant increase in leukocyte adhesion. This effect could be mimicked by mannitol. Both PKC and p38 MAP kinase were involved in the effects mediated by glucose and mannitol. Acutely induced hyperglycemia resulted in a significant increase in leukocyte emigration. This effect could be imitated by mannitol. However, PKC and p38 MAP kinase were only involved under osmotic stimulation. The hyperglycemia-induced reduction in leukocyte rolling velocity seemed to be a glucose-specific effect, since mannitol did not influence leukocyte rolling velocity. This glucose effect on leukocyte rolling velocity was mediated by an activation of the PKC/p38 MAP kinase cascade. Both hyperglycemia and osmotic stimuli alone were able to reduce venular shear rate without recruitment of the p38 MAP kinase cascade. The observed reduction of shear rate seems to be mediated only by the osmotic effects of glucose via activation of the PKC system. ConclusionThe observed effects of glucose on adhesion, emigration and shear rate are due to osmotic effects. The PKC/MAP kinase cascade is involved as a signal transducing component. The reduction of leukocyte rolling velocity is a glucose-specific effect, mediated by the activation of both the PKC and the p38 MAP kinase cascade. Venular shear rate and leukocyte emigration can be influenced by glucose and mannitol due to different regulation mechanisms. It is concluded, that isoform-specific inhibitors of PKC and... [ABSTRACT FROM AUTHOR]

Background: Responses to height may range from indifference to minor distress to severe symptoms of fear of heights (acrophobia); visual height intolerance (vHI) denotes the whole spectrum of symptoms. Although there are options to manage vHI, only a small part of persons affected by vHI are willing to seek professional help or confront their problem. Purpose of this study was to determine if persons with vHI, specifically those who show avoidant behavior towards heights (avoiders), score lower in their general self-efficacy (GSE) than those who confront vHI (confronters). Method: Cross-sectional survey in 607 individuals living in the urban region of Munich, Germany, using a mailed questionnaire on presence or absence of vHI, confronting or avoiding behaviour, and GSE. Results: Of all participants (mean age 53.9, 50.3% female), 407 reported life-time presence of vHI. Participants with vHI had a mean GSE score of 31.8 (SD 4.3) points (participants without vHI: 32.5, SD 4.3, p  = 0.008 for difference). Among individuals with vHI, 23% reported confronting behavior. Confronters were significantly younger (p<.0001, 50.2 vs. 55.7 years), more likely to be female (p  = 0.0039, 64.3% female), and had a higher GSE score (p  = 0.0049, 32.5 vs. 31.1). Associations remained significant after multiple adjustment. Conclusions: Our study provides evidence for the association of GSE and vHI. These findings may have consequences for strategies of alleviation and therapy of vHI. [ABSTRACT FROM AUTHOR]

Background: The changing age distribution in our society inevitably also leads to an increase in age-specific injuries. As a result, the percentage of osteoporotic and fatigue fractures and the absolute number of insufficiency fractures of the pelvic ring are increasing. Causes of pelvic ring fractures: While pelvic ring injuries in younger patients are mainly caused by high velocity accidents, the reason for pelvic fractures in elderly patients is often a trivial fall to the floor or even no impact at all. These kinds of injuries are consequently assessed as insufficiency fractures. Diagnosis and therapy: Conventional x-rays of the pelvic ring are frequently not able to reveal the injury; therefore, additional diagnostic methods (e.g., CT scan or even MRI) are recommended. The established classifications for pelvic ring fractures do not sufficiently reflect the complexity of these injuries. Therapy must be chosen based on the general condition and living environment of the elderly patient. Reduced bone quality leads to problems with implants such as early loosening of conventional screws and must be considered when planning operative stabilization. [ABSTRACT FROM AUTHOR]

The distribution of most recently discovered or described lemur species remains poorly known, but many appear to have small geographical ranges, making them vulnerable to extinction. Research can contribute to future conservation actions on behalf of these species by providing accurate information on local distribution and abundance. The distribution of the world's smallest primate, the endangered Madame Berthe's mouse lemur ( Microcebus berthae), is limited to the Menabe Central region of western Madagascar. This species was discovered in the 1990s, but many fundamental aspects of its ecology remain unknown. The aims of our study were therefore to determine the actual distribution of Microcebus berthae across the forests of this region, to estimate population density, and to examine the species' response to anthropogenic activities. We established 35 1-km line transects across Menabe Central, on which we surveyed mouse lemurs by distance sampling and live trapping. Microcebus berthae does not occur in all remaining forests of this small region and its population density is highly heterogeneous, both across its geographic range and locally. Within its area of occupancy, the population of Microcebus berthae not only was distributed according to spatial heterogeneities of the habitat, but also responded to anthropogenic disturbances and varied seasonally. Our results indicate that Microcebus berthae is susceptible to habitat degradation and avoids human environments spatially. As none of the forest remnants in which the species still occurs were officially protected until recently, immediate conservation actions should focus on effectively protecting Kirindy and Ambadira forests. [ABSTRACT FROM AUTHOR]

Abstract: Nanoparticles (NP) and nanoparticulated drug delivery promise to be the breakthrough for therapy in medicine but raise concerns in terms of nanotoxicity. We present quantitative murine biokinetics assays using polyelectrolyte-multilayer-coated gold NP (AuNP, core diameter 15 and 80 nm; 198Au radio-labeled). Those were stably conjugated either with human serum albumin (alb-AuNP) or apolipoprotein E (apoE-AuNP), prior to intravenous injection. We compare the biokinetics of protein-AuNP-conjugates with citrate-stabilized AuNP (cit-AuNP). Biokinetics was complemented with histology in organs with high AuNP content using 15 nm double fluorescently-labeled alb-AuNP-conjugates. Protein conjugation massively reduced liver retention (alb-AuNP: 52%, apoE-AuNP: 72%, cit-AuNP: >95%, at 19 h and 48 h) when compared to cit-AuNP. The protein conjugates were retained in lungs (alb-AuNP (18%) and spleen (alb-AuNP (16%), apoE-AuNP (21%) at 19 h. Alb-AuNP show significantly increased fractions in lungs (factors: 60 (30 min); 111 (19 h); 235 (48 h) and brain (factors: 70 (30 min); 90 (19 h); >200 (48 h) compared to cit-AuNP (control) - or even to apoE-AuNP. The influence of protein conjugation on the biodistribution disappears for 80 nm AuNP comparing to control. Histologically, the 15 nm alb-AuNP are mainly located in the endothelium of brain, lungs, liver and kidneys after 30 min, while at 19 h they moved deeper into the parenchyma e.g. in hippocampus. Our study clearly suggests that stable conjugation of AuNP with albumin and apoE prior to intravenous administration increases specificity and efficiency of NP in diseased target-organs thus suggesting a potential role in nanomedicine and nanopharmacology. [Copyright &y& Elsevier]

Purpose: Visual height intolerance (vHI) occurs when a trigger causes the apprehension of losing balance and falling. Depending on the severity of vHI, an avoidance behavior may develop in about 50 % of the thus afflicted, and it can have considerable impact on their daily life and interpersonal interactions. It seems obvious that such experiences may be impairing and distressing, but this has not yet been examined systematically. Objective of this study was to examine the consequences of vHI for quality of life. Methods: A qualitative, phenomenological exploratory approach was chosen. Individual face-to-face interviews were conducted with individuals who had reported in a previous study that they were susceptible to vHI. The interview transcripts were segregated into distinct meaning units, which were used to create a coding guideline with meta- and subcodes. Meaning units were then systematically extracted and assigned to the appropriate codes. Weights and links were used to assign priorities for interpretation. Results: Eighteen participants were interviewed (mean age 53, range 30-73; 11 females). Data analysis resulted in 29 meta-codes and 115 subcodes. Responses indicated that vHI can be very disabling and has a relevant impact on quality of life and daily activities of the affected persons, including their family life and behavior towards partner, children and friends. Conclusion: Relevant topics for further quantitative studies were identified, for example, strategies of compensation and the influence of vHI on family life. Other quantitative studies should determine whether comorbidities and the typologies found in this study have consequences for individual therapeutic approaches. [ABSTRACT FROM AUTHOR]

Introduction Mutations in the NOD2 gene are a significant risk factor to acquire intestinal failure requiring home parenteral nutrition. Tuberculous lymphadenitis is the main manifestation of extrapulmonary tuberculosis. Defects in the innate immunity, including NOD2 mutations, may increase the risk for acquiring infections caused by M. tuberculosis. An association of intestinal failure, mutations in the NOD2 gene and tuberculous lymphadenitis has not been described before. Case presentation We report of two patients with intestinal failure secondary to mesenteric ischemia. Both patients presented with fever and weight loss while receiving long term home parenteral nutrition. Both of them were found to have mutations in the NOD2 gene. Catheter related infections were ruled out. FDG-PET-CT scans initially obtained in search for another infectious focus that would explain the symptoms unexpectedly showed high FDG uptake in mediastinal lymph nodes. Direct or indirect evidence proved or was highly suggestive for tuberculous lymphadenitis. Intravenous tuberculostatic therapy was started and led to a reversal of symptoms and to resolution of the lesions by FDG-PET-CT. Conclusion Mutations in the NOD2 gene may put patients both at an increased risk for acquiring M. tuberculosis infections as well as at an increased risk of intestinal failure after extensive intestinal resection. Thus we suggest to specifically include reactivated and opportunistic infections in the differential diagnosis of suspected catheter related infection in patients with intestinal failure who carry mutations in their NOD2 gene. [ABSTRACT FROM AUTHOR]

The largest remaining tract of western dry deciduous forest in Madagascar is located in the region of Menabe Central and harbors a species-rich lemur community. The distribution and abundance of lemur species have never been assessed across the forests of the Menabe Central. We therefore surveyed populations of three species of the family Cheirogaleidae (Cheirogaleus medius, Mirza coquereli, Phaner pallescens) via distance sampling on 35 1-km line transects to estimate overall population densities and to investigate the regional distribution against the backdrop of anthropogenic activities. Corresponding to species-specific ecological demands, we documented divergent spatial population structures for the three species across Menabe Central. Cheirogaleus medius occurred in comparably high population densities in all forest regions, whereas the abundance of M. coquereli and P. pallescens was substantially lower and their distribution more heterogeneous. Moreover, regional distribution patterns revealed differential susceptibilities to human impact: C. medius largely relies on non-degraded habitat and both C. medius and P. pallescens avoid human environments spatially. In contrast to results of earlier studies, M. coquereli appeared to be fairly resilient to disturbances. Thus, this cheirogaleid assemblage varied in composition across heterogeneous habitats and was deprived where anthropogenic pressure was particularly intense. In order to prevent biodiversity loss in Menabe Central, effective protection of Kirindy and Ambadira Forests, and the narrow remaining forest corridor connecting them, will be crucial. [ABSTRACT FROM AUTHOR]

Background Patient-reported outcome measurements ( PROMS) have been proposed sensitive outcome parameters in multiple sclerosis ( MS). In this study, we assessed a German version of the Multiple Sclerosis Impact Scale ( MSIS-29) and a revised version of the Hamburg Quality of Life Questionnaire in Multiple Sclerosis ( HAQUAMS) in comparison with rater- and physician-based tools. Methods Consecutive MS patients ( n = 117) of the MS outpatient unit were included. In addition to MSIS-29 and HAQUAMS, the following parameters were obtained: Expanded Disability Status Scale ( EDSS) and modified Multiple Sclerosis Functional Composite ( MSFC) [9-hole peg test (9 HPT), 25-foot walk test and symbol digit modalities test]. We investigated validity, internal consistency and test-retest reliability as well as correlation between these measures. Results Internal consistency (Cronbach's α ≤ 0.96) and test-retest coefficients ( ICC ≤ 0.87) of both scales were high and satisfied psychometric standards. Convergent and discriminant validity was supported by direction, magnitude and pattern of correlation with other rater-based measures depending on the functional subdomain. Both MSIS-29 and HAQUAMS correlated with EDSS (ρ = 0.55 vs 0.62), but stronger correlation was found between MSIS-29 and HAQUAMS total score (ρ = 0.90). Both scales distinguished between patient groups of varied disease severity and cognitive impairment. Conclusion Patient-reported outcome measurements as MSIS-29 and HAQUAMS seem to be valid instruments to detect different impairment levels in comparison with traditional rater-based instruments like EDSS or MSFC. [ABSTRACT FROM AUTHOR]

When nanoparticles (NP) enter the body they come into contact with body fluids containing proteins which can adsorb to their surface. These proteins may influence the NP interactions with the biological vicinity, eventually determining their biological fate inside the body. Adsorption of the most abundantly binding proteins was studied after an in vitro 24 hr incubation of monodisperse, negatively charged 5, 15 and 80 nm gold spheres (AuNP) in mouse serum by a two-step analysis: proteomic protein identification and quantitative protein biochemistry. The adsorbed proteins were separated from non-adsorbed proteins by centrifugation and gel electrophoresis and identified using a MALDI-TOF-MS-Proteomics- Analyzer. Quantitative analysis of proteins in gel bands by protein densitometry, required the focus on predominantly binding serum proteins. Numerous proteins adsorbed to the AuNP depending on their size, e.g. apolipoproteins or complement C3. The qualitative and quantitative amount of adsorbed proteins differed between 5, 15 and 80 nm AuNP. Band intensities of adsorbed proteins decreased with increasing AuNP sizes based not only on their mass but also on their surface area. Summarizing, the AuNP surface is covered with serum proteins containing transport and immune related proteins among others. Hence, protein binding depends on the size, surface area and curvature of the AuNP. [ABSTRACT FROM AUTHOR]

This article considers the importance of robust planning for green infrastructure in fast changing Southern African cities. A key theme is the extent to which ecosystem services are valued publicly, and the opportunity costs of not investing in the green infrastructure. We explore green infrastructure through pairing insights of social–ecological resilience with perspectives on urban infrastructure transitions. By converging these views, we show how green infrastructure can be viewed as an innovative response to challenged urban environments. Through a Johannesburg case study, a number of ecosystem services constitute sources of resilience for an otherwise constrained city. While this is positive and to be valorised, many South African cities are in the midst of service delivery protests, so that resilient ecosystems, and the citizen networks that sustain these, are largely overlooked in planning processes. This article offers three key conclusions. First, a proper understanding of green infrastructure requires blending insights from social–ecological system thinking and infrastructure transition scholarship. Second, there is a paucity of knowledge around ecosystem services in Johannesburg, and that the planning to facilitate ecosystem service valuation is largely inadequate. Third, addressing this requires ecosystem valuations relevant to the unique conditions in developing world cities such as Johannesburg. [Copyright &y& Elsevier]

The article looks into the impact, specific forms and perspectives of Open Access in the humanities. It focuses on different varieties of secondary and primary Open Access publishing, i.e. granting free access after the initial publication in a traditional format vs. a genuine Open Access model. Specific examples will illustrate different variations and put them into the larger framework of electronic publishing in the humanities. [ABSTRACT FROM AUTHOR]

Background and Aims Unrelated plants pollinated by the same group or guild of animals typically evolve similar floral cues due to pollinator-mediated selection. Related plant species, however, may possess similar cues either as a result of pollinator-mediated selection or as a result of sharing a common ancestor that possessed the same cues or traits. In this study, visual and olfactory floral cues in Lysimachia species exhibiting different pollination strategies were analysed and compared, and the importance of pollinators and phylogeny on the evolution of these floral cues was determined. For comparison, cues of vegetative material were examined where pollinator selection would not be expected. Methods Floral and vegetative scents and colours in floral oil- and non-floral oil-secreting Lysimachia species were studied by chemical and spectrophotometric analyses, respectively, compared between oil- and non-oil-secreting species, and analysed by phylogenetically controlled methods. Key Results Vegetative and floral scent was species specific, and variability in floral but not vegetative scent was lower in oil compared with non-oil species. Overall, oil species did not differ in their floral or vegetative scent from non-oil species. However, a correlation was found between oil secretion and six floral scent constituents specific to oil species, whereas the presence of four other floral compounds can be explained by phylogeny. Four of the five analysed oil species had bee-green flowers and the pattern of occurrence of this colour correlated with oil secretion. Non-oil species had different floral colours. The colour of leaves was similar among all species studied. Conclusions Evidence was found for correlated evolution between secretion of floral oils and floral but not vegetative visual and olfactory cues. The cues correlating with oil secretion were probably selected by Macropis bees, the specialized pollinators of oil-secreting Lysimachia species, and may have evolved in order to attract these bees. [ABSTRACT FROM PUBLISHER]

It is well known that infectious and inflammatory diseases such as sepsis and severe inflammatory response syndrome are accompanied by metabolic alterations such as insulin resistance. Conversely, metabolic diseases such as visceral obesity and type 2 diabetes are characterized by high levels of proinflammatory cytokines. Metabolism and immunity are linked by proteins of dual function. Adiponectin, a member of the C1q/TNF-related protein (CTRP) family, has attracted much interest because of its anti-inflammatory and insulin-sensitizing effects. To date, 15 additional CTRP family members have been identified that might also play a role in metabolism and immunity. This review focuses on the biochemistry and pleiotropic physiological functions of CTRPs as new molecular mediators connecting inflammatory and metabolic diseases. [ABSTRACT FROM AUTHOR]

Abstract: The progression of acute pancreatitis to necrotizing pancreatitis which often results in high morbidity and mortality is difficult to predict. Here we report that serum concentrations of sCD137 are increased in patients with acute pancreatitis. Admission levels and 10-day median sCD137 levels positively correlate with markers of biliary pancreatitis and the 10-day sCD137 median is significantly higher in metabolic than in alcoholic pancreatitis. Serum concentrations of sCD137 at time of admission and the 10-day median of sCD137 correlate with the Ranson and APACHE II disease scores but not with the radiological Balthazar and Schroeder scores that reflect pancreatic and peripancreatic necrosis. Further, sCD137 levels correlate with the probability of complications and lethality. The association of sCD137, a product of activated T cells, with the severity of acute pancreatitis suggests that T cells contribute to the pathogenesis of acute pancreatitis. [Copyright &y& Elsevier]

Schäffler N, Köpke S, Winkler L, Schippling S, Inglese M, Fischer K, Heesen C. Accuracy of diagnostic tests in multiple sclerosis - a systematic review. Acta Neurol Scand: 2011: 124: 151-164. © 2010 John Wiley & Sons A/S. New diagnostic criteria for multiple sclerosis (MS) have been recently proposed and further updates are upcoming. This systematic literature review summarizes diagnostic studies in suspected MS to clarify the value of diagnostic tests. We included studies of at least 40 patients followed up for 2 years. All studies are limited by the fact that no gold standard to validate diagnostic tests is available. A second relapse is used as a surrogate in relapsing-remitting MS, but long follow-up of at least 5 years is necessary to detect all cases. Many studies showed selection bias, partly because of the vague definition of a clinically isolated syndrome. Based on these limitations, sensitivity of magnetic resonance imaging (MRI) criteria was between 35% and 100%, and specificity was between 36% and 92%. Cerebrospinal fluid (CSF) oligoclonal banding showed sensitivities between 69% and 91% with specificities between 59% and 94%. Combination studies of MRI and CSF indicate enhanced sensitivity (56-100%) and specificity (53-96%). Studies on evoked potentials did not justify conclusions about their value. A combination of simplified MRI criteria with CSF might be the best approach for an early MS diagnosis. However, the value of a very early diagnosis stays questionable as patients' benefit of new diagnostic criteria has never been addressed. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Adipocytes of peripancreatic and intrapancreatic adipose tissue secret adipocytokines such as leptin, adiponectin, and resistin. For resistin, a role as an early predictor of peripancreatic necrosis and clinical severity in acute pancreatitis has been reported. It was the aim of this study to investigate whether the adipocytokine visfatin is able to serve as an early marker predicting peripancreatic necrosis and clinical severity.METHODS:A total of 50 patients (20 females and 30 males) with acute pancreatitis were included in this noninterventional, prospective, and monocentric cohort study on diagnostic accuracy. Clinical severity was classified by the Ranson score and APACHE-II (Acute Physiology and Chronic Health Evaluation II) score. Pancreatic and peripancreatic necrosis were quantified by the computed tomography-based Balthazar score, the Schroeder score, and the pancreatic necrosis score. Visfatin was measured at admission and daily for 10 days by enzyme-linked immunosorbent assay (ELISA).RESULTS:Visfatin values were significantly and positively correlated with clinical severity (APACHE-II score and Ranson score) and with clinical end points such as death and need for interventions. Admission visfatin levels were significantly elevated in patients with higher pancreatic and extrapancreatic necrosis scores. It was shown by receiver operator characteristics that admission visfatin concentration provides a positive predictive value of 93.3% in predicting the extent of peripancreatic necrosis (area under the curve (AUC): 0.89, P<0.001, sensitivity: 93.3%, specificity: 81.8%, likelihood ratio: 5.1, post-test probability: 93%) by using a cutoff value of 1.8 ng/ml.CONCLUSIONS:Admission visfatin concentration serves as an early predictive marker of peripancreatic necrosis and clinical severity in acute pancreatitis. Visfatin may have potential for clinical use as a new and diagnostic serum marker. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Peripancreatic necrosis determines clinical severity in acute pancreatitis. Early markers predicting peripancreatic necrosis and clinical severity are lacking. Because adipocytes of peripancreatic adipose tissue secret highly active adipocytokines, the aim of the study was to investigate whether adipocytokines are able to serve as early markers predicting peripancreatic necrosis and clinical severity.METHODS:A total of 50 patients (20 women, 30 men) with acute pancreatitis were included in this noninterventional, prospective, and monocentric cohort study on diagnostic accuracy. Clinical severity was classified by the Ranson score and the APACHE (Acute Physiology And Chronic Health Evaluation) II score. Pancreatic and peripancreatic necrosis were quantified by using the computed tomography-based Balthazar score, the Schroeder score, and the pancreatic necrosis score. Adiponectin, leptin, and resistin were measured at admission and daily for at least 10 days by enzyme-linked immunosorbent assay.RESULTS:In contrast to admission C-reactive protein values, admission resistin values were significantly correlated with clinical severity and even with clinical end points such as death and need for interventions. Admission resistin levels were significantly elevated in patients with higher pancreatic and extrapancreatic necrosis scores. It was shown by receiver-operator characteristics that admission resistin concentration provides a positive predictive value of 89% in predicting the extent of peripancreatic necrosis (area under the curve, 0.8; P=0.002; sensitivity, 80%; specificity, 70%) by using a cutoff value of 11.9 ng/ml.CONCLUSIONS:Admission resistin concentration serves as an early predictive marker of peripancreatic necrosis and clinical severity in acute pancreatitis. Resistin may have potential for clinical use as a new and diagnostic serum marker. [ABSTRACT FROM AUTHOR]

The understanding of the role of adipose tissue has changed from a lipid storage organ to an endocrine and immunologically active organ. Here, we summarize the evidence for an important role of adipose tissue in innate immunity. The review focuses on the expression and function of Toll-like receptors (TLRs) in adipocytes and on the role of adipose tissue macrophages. The dual activation of TLR4 in adipocytes by lipopolysaccharide and fatty acids represents a molecular gate that connects innate immunity with metabolism. Dichotomic molecules derived from ancient precursor molecules control metabolism and immune function. Visceral adipose tissue is infiltrated by macrophages in obesity, and there is local crosstalk between these two types of cells, leading to an inflammatory transformation of adipose tissue. [Copyright &y& Elsevier]

Background Parallel to the establishment of early treatments in multiple sclerosis (MS), new diagnostic criteria have made an earlier diagnosis possible. While there is ongoing discussion about possible benign courses and only partial effective treatments, there have been no attempts today to facilitate shared decision making on diagnostic testing between patients with suspected MS and their physicians. Objective This study describes the development and validation process of a leaflet to be presented to people with suspected MS to engage them in a diagnostic decision-making process. Methods After a qualitative study showing acceptability among five patients, the leaflet was presented to a retrospective cohort (n = 87 of which 70 replied)) of patients being diagnosed within the last 2 years as well to a prospective cohort of n = 51 patients with symptoms suggestive of MS. Results Approximately 70% of patients in the prospective as well as in the retrospective cohort wanted to be informed about a possible MS before testing, whereas 10% did not. The leaflet did not seem to elicit anxieties. The attitude to undergo diagnostic testing was not influenced by the leaflet, which can be explained by the nonexperimental design of the study. Conclusion Taken together, our findings demonstrate that early information about possible MS is warranted by patients and does not show negative side effects. Further studies on evidence-based patient information in early MS seem necessary. [ABSTRACT FROM AUTHOR]

Background: Adiponectin is a circulating protein with hepatoprotective effects. Aims: To study the relationship of excessive alcohol consumption and serum adiponectin levels (SAL). Patients and Methods: The SAL were determined in (i) heavy drinkers without advanced liver damage during the course of alcohol withdrawal, (ii) patients with chronic hepatitis C virus (HCV) infection, (iii) patients with alcohol-associated cirrhosis, and (iv) healthy volunteers that consumed excessive amounts of alcohol for only a short period of time. Further, primary human hepatocytes (PHH) and adipocytes were incubated in vitro with alcohol or serum of patients. Results: Patients with chronic alcohol consumption had significantly higher SAL than HCV-patients with comparable degrees of liver damage. In alcoholics, but not in HCV patients, SAL positively correlated with serum levels of aminotransferases. Further, SAL correlated with the amount of alcohol consumption but declined during the course of alcohol abstinence. After short-term excessive alcohol consumption SAL were not elevated in healthy individuals. Adiponectin mRNA was detectable in adipocytes but not in hepatocytes, and alcohol failed to induce adiponectin in both cell types. In contrast, serum of active drinkers induced adiponectin expression in adipocytes while serum from the same individuals collected after alcohol withdrawal had no effect. Conclusions: Alcohol exhibits a specific effect on SAL that is dose and time dependent, and correlates with the degree of hepatic damage. Alcohol does not seem to affect adiponectin expression directly in adipocytes but potentially via mediators systemically released as a result of the chronic alcohol intake. [ABSTRACT FROM AUTHOR]

The article discusses the creation of a checklist on eBook standards developed by the Working Group on eBooks, composed of various professionals from Bavaria, Germany, with the list accessible at http://ebookstandards.ub.uni-muenchen.de. Particularly addressed are licensing issues and selection criteria for electronic textbooks and scientific monographs.