107 research outputs found
Tool-based Codification in Business Process Improvement and the Impact on Problem-Solving
Business process improvement (BPI) is an important task in times of quickly changing customer requirements and evolving technologies. A variety of BPI approaches were developed in recent years, however, the proper codification of results created in BPI projects has not been properly investigated yet. In this respect, the paper at hand examines the impact of tool-based codification approaches on problem-solving in BPI. Moreover, the effect of the design either as a spreadsheet-based or a conceptual model-based tool on user satisfaction is analyzed. For that purpose, we revert to two tools we developed, which both offer the identical functionality but diverge in the techniques of codifying results: spreadsheet templates on the one side and conceptual models on the other side. In our study, the form of codification tremendously affected the perceived user satisfaction whereas the results received for problem-solving did not show a clear preference. Regarding the former issue, the beneficial role of conceptual models for codifying results with the help of software tools could be demonstrated.publishedVersio
Inhibition of Inducible Nitric Oxide Synthase Prevents IL-1β-Induced Mitochondrial Dysfunction in Human Chondrocytes
Interleukin (IL)-1β is an important pro-inflammatory cytokine in the progression of osteoarthritis (OA), which impairs mitochondrial function and induces the production of nitric oxide (NO) in chondrocytes. The aim was to investigate if blockade of NO production prevents IL-1βinduced mitochondrial dysfunction in chondrocytes and whether cAMP and AMP-activated protein kinase (AMPK) affects NO production and mitochondrial function. Isolated human OA chondrocytes were stimulated with IL-1β in combination with/without forskolin, L-NIL, AMPK activator or inhibitor. The release of NO, IL-6, PGE2 , MMP3, and the expression of iNOS were measured by ELISA or Western blot. Parameters of mitochondrial respiration were measured using a seahorse analyzer. IL-1β significantly induced NO release and mitochondrial dysfunction. Inhibition of iNOS by L-NIL prevented IL-1β-induced NO release and mitochondrial dysfunction but not IL-1β-induced release of IL-6, PGE2 , and MMP3. Enhancement of cAMP by forskolin reduced IL-1β-induced NO release and prevented IL-1β-induced mitochondrial impairment. Activation of AMPK increased IL-1β-induced NO production and the negative impact of IL-1β on mitochondrial respiration, whereas inhibition of AMPK had the opposite effects. NO is critically involved in the IL-1β-induced impairment of mitochondrial respiration in human OA chondrocytes. Increased intracellular cAMP or inhibition of AMPK prevented both IL-1β-induced NO release and mitochondrial dysfunction
Osteoarthritis-Induced Metabolic Alterations of Human Hip Chondrocytes
Osteoarthritis (OA) alters chondrocyte metabolism and mitochondrial biology. We explored whether OA and non-OA chondrocytes show persistent differences in metabolism and mitochondrial function and different responsiveness to cytokines and cAMP modulators. Hip chondrocytes from patients with OA or femoral neck fracture (non-OA) were stimulated with IL-1β, TNF, forskolin and opioid peptides. Mediators released from chondrocytes were measured, and mitochondrial functions and glycolysis were determined (Seahorse Analyzer). Unstimulated OA chondrocytes exhibited significantly higher release of IL-6, PGE 2 and MMP1 and lower production of glycosaminoglycan than non-OA chondrocytes. Oxygen consumption rates (OCR) and mitochondrial ATP production were comparable in unstimulated non-OA and OA chondrocytes, although the non-mitochondrial OCR was higher in OA chondrocytes. Compared to OA chondrocytes, non-OA chondrocytes showed stronger responses to IL-1β/TNF stimulation, consisting of a larger decrease in mitochondrial ATP production and larger increases in non-mitochondrial OCR and NO production. Enhancement of cAMP by forskolin prevented IL-1β-induced mitochondrial dysfunction in OA chondrocytes but not in non-OA chondrocytes. Endogenous opioids, present in OA joints, influenced neither cytokine-induced mitochondrial dysfunction nor NO upregulation. Glycolysis was not different in non-OA and OA chondrocytes, independent of stimulation. OA induces persistent metabolic alterations, but the results suggest upregulation of cellular mechanisms protecting mitochondrial function in OA
Placental Syncytiotrophoblast Maintains a Specific Type of Glycocalyx at the Fetomaternal Border: The Glycocalyx at the Fetomaternal Interface in Healthy Women and Patients With HELLP Syndrome
Recent studies showed that considerable amounts of glycosaminoglycans are released into maternal blood during normal pregnancy and in hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Maternal endothelia and the syncytiotrophoblast layer have been discussed as a possible origin of these glycocalyx components. Our study aimed to visualize the glycocalyx on the syncytiotrophoblast by electron microscopy, to analyze its structure and composition by immunohistochemistry, and to determine potential differences between healthy women and women with HELLP syndrome. For electron microscopy, a cotyledon was fixed by perfusion of the intervillous space with a 2% lanthanum-nitrate glutaraldehyde solution followed by immersion fixation in the same fixative. For immunohistochemistry, sections of 16 placentas (HELLP patients/healthy women, n = 8 each) were stained with monoclonal antibodies against the main glycocalyx constituents syndecan 1, hyaluronic acid, and heparan sulfate. Semiquantitative evaluation of staining intensity focused on the apical surface of the syncytiotrophoblast and fetal intravillous endothelia as possible localizations of a placental glycocalyx. Electron microscopy revealed a glycocalyx of approximately 250nm, covering the syncytiotrophoblast layer. This was found to contain large amounts of syndecan 1, but neither hyaluronic acid nor heparan sulfate as major components. Intravillous fetal endothelium did not express any of the investigated glycosaminoglycans. Healthy women and patients with HELLP showed no differences concerning glycocalyx composition and thickness of the syncytiotrophoblast. The composition of the placental glycocalyx differs from the adult and fetal vascular glycocalyx. Obviously, the human placental syncytiotrophoblast maintains a special kind of glycocalyx at the fetomaternal interface
Placental Syncytiotrophoblast Maintains a Specific Type of Glycocalyx at the Fetomaternal Border: The Glycocalyx at the Fetomaternal Interface in Healthy Women and Patients With HELLP Syndrome
Recent studies showed that considerable amounts of glycosaminoglycans are released into maternal blood during normal pregnancy and in hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Maternal endothelia and the syncytiotrophoblast layer have been discussed as a possible origin of these glycocalyx components. Our study aimed to visualize the glycocalyx on the syncytiotrophoblast by electron microscopy, to analyze its structure and composition by immunohistochemistry, and to determine potential differences between healthy women and women with HELLP syndrome. For electron microscopy, a cotyledon was fixed by perfusion of the intervillous space with a 2% lanthanum-nitrate glutaraldehyde solution followed by immersion fixation in the same fixative. For immunohistochemistry, sections of 16 placentas (HELLP patients/healthy women, n = 8 each) were stained with monoclonal antibodies against the main glycocalyx constituents syndecan 1, hyaluronic acid, and heparan sulfate. Semiquantitative evaluation of staining intensity focused on the apical surface of the syncytiotrophoblast and fetal intravillous endothelia as possible localizations of a placental glycocalyx. Electron microscopy revealed a glycocalyx of approximately 250nm, covering the syncytiotrophoblast layer. This was found to contain large amounts of syndecan 1, but neither hyaluronic acid nor heparan sulfate as major components. Intravillous fetal endothelium did not express any of the investigated glycosaminoglycans. Healthy women and patients with HELLP showed no differences concerning glycocalyx composition and thickness of the syncytiotrophoblast. The composition of the placental glycocalyx differs from the adult and fetal vascular glycocalyx. Obviously, the human placental syncytiotrophoblast maintains a special kind of glycocalyx at the fetomaternal interface
Center and Periphery. Theological Perspectives on Church and Society
Krisenzeit – Zeit der Kirche – Zeit der Theologie?
Die Problemlagen der Gegenwart stellen die wissenschaftliche Theologie vor so große Herausforderungen wie selten zuvor. Nicht allein stehen in den kommenden Jahren strukturelle Weichenstellungen an, welche die Kirche kaum unberührt lassen werden. Schon jetzt verlangt die prekäre Situation vieler Menschen und ganzer Völker nach einer tragfähigen Reflexion und Verkündigung des Glaubens. Christliche Theologie darf die notwendigen Antworten hier nicht schuldig bleiben. In der vorliegenden Festschrift haben sich Kollegen, Freunde und Schüler von Otmar Meuffels den vielfältigen Fragestellungen zugewandt, welche die Arbeit an der zeitgenössischen Heilsbedeutung des christlichen Glaubens aufwirft. Sie schreiben damit seinen prägenden Ansatz fort, der stets die aktuelle Relevanz der Rede von Gott im Blick hat. In diesem Sinn zeigen die in diesem Band versammelten Beiträge auf ganz unterschiedlichen Feldern die Anschlussfähigkeit der Theologie in den heute virulenten gesellschaftlichen Debatten.Time of Crisis – Times of Church – Time of Theology?
Academic theology has rarely faced bigger challenges than those of the present. The coming years will see structural course changes which will leave the church hardly untouched. Even today, the precarious situation of people and people’s demands for viable reflection and proclamation of Faith. Christian theology must not fail to give necessary answers in this regard. In this publication, colleagues, friends, and students of Otmar Meuffels faced these diverse questions, which are posed by working with the contemporary soteriological significance of Christian faith. With this, they continue his defining approach which always focuses on the current relevance of the speech of God. Therefore, all contributions collected in this publication show the ability to connect theology with current and relevant societal controversies in completely different fields
New insights into the prevalence of depressive symptoms and depression in rheumatoid arthritis – Implications from the prospective multicenter VADERA II study
Objectives
To investigate the prevalence of depressive symptoms in rheumatoid arthritis (RA) patients using two previously validated questionnaires in a large patient sample, and to evaluate depressive symptoms in the context of clinical characteristics (e.g. remission of disease) and patient-reported impact of disease.
Methods
In this cross-sectional study, the previously validated Patient Health Questionnaire (PHQ-9) and Beck-Depression Inventory II (BDI-II) were used to assess the extent of depressive symptoms in RA patients. Demographic background, RA disease activity score (DAS28), RA impact of disease (RAID) score, comorbidities, anti-rheumatic therapy and antidepressive treatment, were recorded. Cut-off values for depressive symptomatology were PHQ-9 ≥5 or BDI-II ≥14 for mild depressive symptoms or worse and PHQ-9 ≥ 10 or BDI-II ≥ 20 for moderate depressive symptoms or worse. Prevalence of depressive symptomatology was derived by frequency analysis while factors independently associated with depressive symptomatology were investigated by using multiple logistic regression analyses. Ethics committee approval was obtained, and all patients provided written informed consent before participation.
Results
In 1004 RA-patients (75.1% female, mean±SD age: 61.0±12.9 years, mean disease duration: 12.2±9.9 years, DAS28 (ESR): 2.5±1.2), the prevalence of depressive symptoms was 55.4% (mild or worse) and 22.8% (moderate or worse). Characteristics independently associated with depressive symptomatology were: age 2 (OR = 10.54) and presence of chronic pain (OR = 3.25). Of patients classified as having depressive symptoms, only 11.7% were receiving anti-depressive therapy.
Conclusions
Mild and moderate depressive symptoms were common in RA patients according to validated tools. In routine clinical practice, screening for depression with corresponding follow-up procedures is as relevant as incorporating these results with patient-reported outcomes (e.g. symptom state), because the mere assessment of clinical disease activity does not sufficiently reflect the prevalence of depressive symptoms.
Clinical trial registration number
This study is registered in the Deutsches Register Klinischer Studien (DRKS00003231) and ClinicalTrials.gov (NCT02485483)
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