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IgG autoantibodies bound to surfaces of necrotic cells and complement C4 comprise the phagocytosis promoting activity for necrotic cells of systemic lupus erythaematosus sera

Objective: Accumulation of dying and dead cells is thought to be involved in the etiopathogenesis of systemic lupus erythaematosus (SLE). Clearance has been described mainly for apoptotic cells; however, the knowledge of serum factors participating in the phagocytosis of necrotic cells is limited. Patients and methods: Sera from 18 patients with SLE and 10 normal healthy donors (NHD), and macrophages from 3 NHD were included. Autoantibodies and complement were measured by ELISA and phagocytosis by flow cytometry. Binding of serum IgG to necrotic cells was assessed by flow cytometry and confocal microscopy. Results: Sera from patients with SLE and NHD generally promoted the phagocytosis of necrotic cells by macrophages isolated from NHD. Five independent experiments with macrophages from three different NHD led to similar results. The sera from healthy controls displayed a homogeneous activity, whereas sera from patients with SLE showed a dichotomic behaviour. Only sera containing autoantibodies binding to the surfaces of necrotic cells and sufficient complement showed increased phagocytosis promoting activities. In SLE sera, C4 turned out to be the critical complement component in this process. Sera de-complemented by heat treatment strongly reduced phagocytosis of necrotic cells. Conclusions: Serum components influence the uptake of necrotic cells by phagocytosis competent macrophages from NHD. Complement is required for this process and autoantibodies binding to the surfaces of necrotic cells additionally promote their phagocytosis

Students benefit from developing their own emergency medicine OSCE stations: a comparative study using the matched-pair method

Background: Students can improve the learning process by developing their own multiple choice questions. If a similar effect occurred when creating OSCE (objective structured clinical examination) stations by themselves it could be beneficial to involve them in the development of OSCE stations. This study investigates the effect of students developing emergency medicine OSCE stations on their test performance. Method: In the 2011/12 winter semester, an emergency medicine OSCE was held for the first time at the Faculty of Medicine at the University of Leipzig. When preparing for the OSCE, 13 students (the intervention group) developed and tested emergency medicine examination stations as a learning experience. Their subsequent OSCE performance was compared to that of 13 other students (the control group), who were parallelized in terms of age, gender, semester and level of previous knowledge using the matched-pair method. In addition, both groups were compared to 20 students who tested the OSCE prior to regular emergency medicine training (test OSCE group). Results: There were no differences between the three groups regarding age (24.3 +/- 2.6; 24.2 +/- 3.4 and 24 +/- 2.3 years) or previous knowledge (29.3 +/- 3.4; 29.3 +/- 3.2 and 28.9 +/- 4.7 points in the multiple choice {[} MC] exam in emergency medicine). Merely the gender distribution differed (8 female and 5 male students in the intervention and control group vs. 3 males and 17 females in the test OSCE group). In the exam OSCE, participants in the intervention group scored 233.4 +/- 6.3 points (mean +/- SD) compared to 223.8 +/- 9.2 points (p < 0.01) in the control group. Cohen's effect size was d = 1.24. The students of the test OSCE group scored 223.2 +/- 13.4 points. Conclusions: Students who actively develop OSCE stations when preparing for an emergency medicine OSCE achieve better exam results

Performance of Interleukin-6 and Interleukin-8 serum levels in pediatric oncology patients with neutropenia and fever for the assessment of low-risk

<p>Abstract</p> <p>Background</p> <p>Patients with chemotherapy-related neutropenia and fever are usually hospitalized and treated on empirical intravenous broad-spectrum antibiotic regimens. Early diagnosis of sepsis in children with febrile neutropenia remains difficult due to non-specific clinical and laboratory signs of infection. We aimed to analyze whether IL-6 and IL-8 could define a group of patients at low risk of septicemia.</p> <p>Methods</p> <p>A prospective study was performed to assess the potential value of IL-6, IL-8 and C-reactive protein serum levels to predict severe bacterial infection or bacteremia in febrile neutropenic children with cancer during chemotherapy. Statistical test used: Friedman test, Wilcoxon-Test, Kruskal-Wallis H test, Mann-Whitney U-Test and Receiver Operating Characteristics.</p> <p>Results</p> <p>The analysis of cytokine levels measured at the onset of fever indicated that IL-6 and IL-8 are useful to define a possible group of patients with low risk of sepsis. In predicting bacteremia or severe bacterial infection, IL-6 was the best predictor with the optimum IL-6 cut-off level of 42 pg/ml showing a high sensitivity (90%) and specificity (85%).</p> <p>Conclusion</p> <p>These findings may have clinical implications for risk-based antimicrobial treatment strategies.</p

Clinical relevance of molecular characteristics in Burkitt lymphoma differs according to age

While survival has improved for Burkitt lymphoma patients, potential differences in outcome between pediatric and adult patients remain unclear. In both age groups, survival remains poor at relapse. Therefore, we conducted a comparative study in a large pediatric cohort, including 191 cases and 97 samples from adults. While TP53 and CCND3 mutation frequencies are not age related, samples from pediatric patients showed a higher frequency of mutations in ID3, DDX3X, ARID1A and SMARCA4, while several genes such as BCL2 and YY1AP1 are almost exclusively mutated in adult patients. An unbiased analysis reveals a transition of the mutational profile between 25 and 40 years of age. Survival analysis in the pediatric cohort confirms that TP53 mutations are significantly associated with higher incidence of relapse (25 ± 4% versus 6 ± 2%, p-value 0.0002). This identifies a promising molecular marker for relapse incidence in pediatric BL which will be used in future clinical trials

Multiple star systems in the Orion nebula

This is the author accepted manuscript. The final fersion is available from EDP Sciences via the DOI in this record.This work presents an interferometric study of the massive-binary fraction in the Orion Trapezium cluster with the recently comissioned GRAVITY instrument. We observed a total of 16 stars of mainly OB spectral type. We find three previously unknown companions for θ1 Ori B, θ2 Ori B, and θ2 Ori C. We determined a separation for the previously suspected companion of NU Ori. We confirm four companions for θ1 Ori A, θ1 Ori C, θ1 Ori D, and θ2 Ori A, all with substantially improved astrometry and photometric mass estimates. We refined the orbit of the eccentric high-mass binary θ1 Ori C and we are able to derive a new orbit for θ1 Ori D. We find a system mass of 21.7 M⊙ and a period of 53 days. Together with other previously detected companions seen in spectroscopy or direct imaging, eleven of the 16 high-mass stars are multiple systems. We obtain a total number of 22 companions with separations up to 600 AU. The companion fraction of the early B and O stars in our sample is about two, significantly higher than in earlier studies of mostly OB associations. The separation distribution hints toward a bimodality. Such a bimodality has been previously found in A stars, but rarely in OB binaries, which up to this point have been assumed to be mostly compact with a tail of wider companions. We also do not find a substantial population of equal-mass binaries. The observed distribution of mass ratios declines steeply with mass, and like the direct star counts, indicates that our companions follow a standard power law initial mass function. Again, this is in contrast to earlier findings of flat mass ratio distributions in OB associations. We excluded collision as a dominant formation mechanism but find no clear preference for core accretion or competitive accretion.Marie Skłodowska-Curie Grant AgreementFCT-PortugalERC Starting Gran

The cross-sectional GRAS sample: A comprehensive phenotypical data collection of schizophrenic patients

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is the collective term for an exclusively clinically diagnosed, heterogeneous group of mental disorders with still obscure biological roots. Based on the assumption that valuable information about relevant genetic and environmental disease mechanisms can be obtained by association studies on patient cohorts of ≥ 1000 patients, if performed on detailed clinical datasets and quantifiable biological readouts, we generated a new schizophrenia data base, the GRAS (Göttingen Research Association for Schizophrenia) data collection. GRAS is the necessary ground to study genetic causes of the schizophrenic phenotype in a 'phenotype-based genetic association study' (PGAS). This approach is different from and complementary to the genome-wide association studies (GWAS) on schizophrenia.</p> <p>Methods</p> <p>For this purpose, 1085 patients were recruited between 2005 and 2010 by an invariable team of traveling investigators in a cross-sectional field study that comprised 23 German psychiatric hospitals. Additionally, chart records and discharge letters of all patients were collected.</p> <p>Results</p> <p>The corresponding dataset extracted and presented in form of an overview here, comprises biographic information, disease history, medication including side effects, and results of comprehensive cross-sectional psychopathological, neuropsychological, and neurological examinations. With >3000 data points per schizophrenic subject, this data base of living patients, who are also accessible for follow-up studies, provides a wide-ranging and standardized phenotype characterization of as yet unprecedented detail.</p> <p>Conclusions</p> <p>The GRAS data base will serve as prerequisite for PGAS, a novel approach to better understanding 'the schizophrenias' through exploring the contribution of genetic variation to the schizophrenic phenotypes.</p

Assessment of Vascular Dysfunction in Patients Without Obstructive Coronary Artery Disease: Why, How, and When.

Ischemic heart disease secondary to coronary vascular dysfunction causes angina and impairs quality of life and prognosis. About one-half of patients with symptoms and signs of ischemia turn out not to have obstructive coronary artery disease, and coronary vascular dysfunction may be relevant. Adjunctive tests of coronary vasomotion include guidewire-based techniques with adenosine and reactivity testing, typically by intracoronary infusion of acetylcholine. The CorMicA (Coronary Microvascular Angina) trial provided evidence that routine management guided by an interventional diagnostic procedure and stratified therapy improves angina and quality of life in patients with angina but no obstructive coronary artery disease. In this paper, the COVADIS study group provide a comprehensive review of why, how, and when coronary vascular dysfunction should be assessed invasively. They discuss the rationale through a shared understanding of vascular pathophysiology and clinical evidence. They propose a consensus approach to how an interventional diagnostic procedure is performed with focus on practical aspects. Finally, the authors discuss the clinical scenarios in patients with stable and acute coronary syndromes in which measurement of coronary vascular function may be helpful for patient care