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Serum GFAP for stroke diagnosis in regions with limited access to brain imaging (BE FAST India)
(2021)
Introduction: Despite a high burden of stroke, access to rapid brain imaging is limited in many middle- and low-income countries. Previous studies have described the astroglial protein GFAP (glial fibrillary acidic protein) as a biomarker of intracerebral hemorrhage. The aim of this study was to test the diagnostic accuracy of GFAP for ruling out intracranial hemorrhage in a prospective cohort of Indian stroke patients. Patients and methods: This study was conducted in an Indian tertiary hospital (Christian Medical College, Ludhiana). Patients with symptoms suggestive of acute stroke admitted within 12 h of symptom onset were enrolled. Blood samples were collected at hospital admission. Single Molecule Array technology was used for determining serum GFAP concentrations. Results: A total number of 155 patients were included (70 intracranial hemorrhage, 75 ischemic stroke, 10 stroke mimics). GFAP serum concentrations were elevated in intracranial hemorrhage patients compared to ischemic stroke patients [median (interquartile range) 2.36 µg/L (0.61–7.16) vs. 0.18 µg/L (0.11–0.38), p < 0.001]. Stroke mimics patients had a median GFAP serum level of 0.14 µg/L (0.09–0.26). GFAP values below the cut-off of 0.33 µg/L (area under the curve 0.871) ruled out intracranial hemorrhage with a negative predictive value of 89.7%, (at a sensitivity for detecting intracranial hemorrhage of 90.0%). Discussion: The high negative predictive value of a GFAP test system allows ruling out patients with intracranial hemorrhage. Conclusion: In settings where immediate brain imaging is not available, this would enable to implement secondary prevention (e.g., aspirin) in suspected ischemic stroke patients as soon as possible.
Activation of Notch1 signaling in neural progenitor cells (NPCs) induces self-renewal and inhibits neurogenesis. Upon neuronal differentiation, NPCs overcome this inhibition, express proneural genes to induce Notch ligands, and activate Notch1 in neighboring NPCs. The molecular mechanism that coordinates Notch1 inactivation with initiation of neurogenesis remains elusive. Here, we provide evidence that Prox1, a transcription repressor and downstream target of proneural genes, counteracts Notch1 signaling via direct suppression of Notch1 gene expression. By expression studies in the developing spinal cord of chick and mouse embryo, we showed that Prox1 is limited to neuronal precursors residing between the Notch1+ NPCs and post-mitotic neurons. Physiological levels of Prox1 in this tissue are sufficient to allow binding at Notch1 promoter and they are critical for proper Notch1 transcriptional regulation in vivo. Gain-of-function studies in the chick neural tube and mouse NPCs suggest that Prox1-mediated suppression of Notch1 relieves its inhibition on neurogenesis and allows NPCs to exit the cell cycle and differentiate. Moreover, loss-of-function in the chick neural tube shows that Prox1 is necessary for suppression of Notch1 outside the ventricular zone, inhibition of active Notch signaling, down-regulation of NPC markers, and completion of neuronal differentiation program. Together these data suggest that Prox1 inhibits Notch1 gene expression to control the balance between NPC self-renewal and neuronal differentiation.
Etwa 800 000 Bundesbürger leiden an rheumatoider Arthritis (RA), der häufigsten chronisch-entzündlichen Erkrankung der Gelenke. Obwohl die Forschung in den vergangenen Jahren erhebliche Fortschritte gemacht hat, sind die Ursachen dieser schmerzhaften, bisher unheilbaren Krankheit noch nicht im Einzelnen geklärt. In vielerlei Richtungen diskutiert wird eine Fehlsteuerung des Immunsystems, bei der körpereigene Gewebsmatrix, wie der Gelenkknorpel, von Zellen des Immunsystems angegriffen wird. Die Forschungen der Mediziner, auch der Frankfurter Gruppe, konzentrieren sich weltweit auf die entzündungsfördernden Faktoren, spezielle Zytokine, und die Hemmstoffe dieser Zytokine. Aus diesen Ansätzen resultieren die neuartigen "Biologics": gentechnisch hergestellte monoklonale Antikörper, die natürlich vorkommenden Wirkstoffen entsprechen. Sie richten sich spezifisch gegen bestimmte vom menschlichen Organismus gebildete Zytokine.
Dichterhäuser produzieren Mythen. Dies ist bei Hofmannsthals barockem Wohnhaus in Rodaun bei Wien nicht anders. Als Vorbesitzer seines Hauses erwähnt Hofmannsthal in einem Brief an Eberhard von Bodenhausen vom 16. März 1901 beiläufig einen Fürsten Trautson: das Haus sei "zur Zeit der Kaiserin Maria Theresia von einem Fürsten Trautsohn, der ein Schwarzkünstler gewesen sein soll, für seine Geliebte gebaut worden". Das gemeinhin als 'Schlösschen Fuchs' oder 'Fuchs-Schlössel' bezeichnete Anwesen wurde von Hofmannsthal von 1901 bis zu seinem Tod 1929 bewohnt und von seiner Familie noch bis 1937 gemietet. Das Landhaus aus dem 17./18. Jahrhundert, dessen Erbauungs- oder Umgestaltungsdatum nicht belegbar ist, wird in der Forschungsliteratur zu Hofmannsthal, in Zeitungsartikeln und in der Lokalgeschichtsschreibung kaum mit Trautsohn, sondern vielmehr mit einer anderen Vorbesitzerin in Verbindung gebracht: mit einer der Kaiserin Maria Theresia nahestehenden Gräfin Fuchs.
In the absence of an active prophylactic vaccine against HIV-1, passively administered, broadly neutralizing antibodies (bnAbs) identified in some chronically infected persons were shown to prevent HIV-1 infection in animal models. However, passive administration of bnAbs may not be suited to prevent sexual HIV-1 transmission in high-risk cohorts, as a continuous high level of active bnAbs may be difficult to achieve at the primary site of sexual transmission, the human vagina with its acidic pH. Therefore, we used Lactobacillus, a natural commensal in the healthy vaginal microbiome, to express bn nanobodies (VHH) against HIV-1 that we reported previously. After demonstrating that recombinant VHHA6 expressed in E. coli was able to protect humanized mice from mucosal infection by HIV-1Bal, we expressed VHHA6 in a soluble or in a cell-wall-anchored form in Lactobacillus rhamnosus DSM14870. This strain is already clinically applied for treatment of bacterial vaginosis. Both forms of VHHA6 neutralized a set of primary epidemiologically relevant HIV-1 strains in vitro. Furthermore, VHHA6 was still active at an acidic pH. Thus, lactobacilli expressing bn VHH potentially represent an attractive vector for the passive immunization of women in cohorts at high risk of HIV-1 transmission.
Taking blood via venipuncture is part of the necessary surveillance before and after liver transplantation. The spectrum of response from children and their parents is variable, ranging from a short and limited aversion to paralyzing phobia. The aim of this retrospective, cross-sectional study was to determine the level of anxiety amongst children during venipuncture, to compare the anxiety reported by children and parents, and to identify the factors affecting the children’s and parents’ anxiety in order to develop therapeutic strategies. In total, 147 children (aged 0–17 years, 78 female) and their parents completed questionnaires. Statistical analysis was performed using qualitative and quantitative methods. Results showed that the majority of children reported anxiety and pain during venipuncture. Younger children had more anxiety (self-reported or assessed by parents). Children and parental reports of anxiety were highly correlated. However, the child’s anxiety was often reported as higher by parents than by the children themselves. The child’s general anxiety as well as the parents’ perceived stress from surgical interventions (but not the number of surgical interventions) prompted parental report of child anxiety. For children, the main stressors that correlated with anxiety and pain were factors during the blood collection itself (e.g., feeling the puncture, seeing the syringe). Parental anxiety was mainly related to circumstances before the blood collection (e.g., approaching the clinic, sitting in the waiting room). The main stressors mentioned by parents were the child’s discomfort and their inability to calm the child. Results indicate that the children’s fear of factors during the blood collection, along with the parents’ perceived stress and helplessness as well as their anticipatory anxiety are important starting points for facilitating the drawing of blood from children before and after liver transplantation, thereby supporting a better disease course in the future.
The implications of telework are discussed controversially and research on its positive and negative effects has produced contradictory results. We explore voluntariness of employee telework as a boundary condition which may underpin these contradictory findings. Under normal circumstances, individuals who do more telework should perceive fewer disadvantages. However, during the COVID-19 pandemic, employees could no longer voluntarily choose to telecommute, as many organizations were forced to introduce telework by governmental regulations. In two studies, we examine whether the voluntary nature of telework moderates the association between the amount of telework and perceptions of disadvantage. In Study 1, we collected data before and during the COVID-19 pandemic (N = 327). Results show that pre-pandemic participants (who were more likely to voluntarily choose this form of work) reported fewer disadvantages the more telework they did, but this was not the case for employees during the COVID-19 pandemic. To validate these findings, we measured employees’ voluntariness of telework in Study 2 (N = 220). Results support the importance of voluntariness: Individuals who experience a high degree of voluntariness in choosing telework perceive fewer disadvantages the more they telework. However, the amount of telework was not related to reduced perceptions of disadvantages for those who experienced low voluntariness regarding the telecommuting arrangement. Our findings help to understand when telework is related to the perception of disadvantages and they can provide organizations with starting points for practical interventions to reduce the negative effects of telework.
The implications of telework are discussed controversially and research on its positive and negative effects has produced contradictory results. We explore voluntariness of employee telework as a boundary condition which may underpin these contradictory findings. Under normal circumstances, individuals who do more telework should perceive fewer disadvantages. However, during the COVID-19 pandemic, employees could no longer voluntarily choose to telecommute, as many organizations were forced to introduce telework by governmental regulations. In two studies, we examine whether the voluntary nature of telework moderates the association between the amount of telework and perceptions of disadvantage. In Study 1, we collected data before and during the COVID-19 pandemic (N = 327). Results show that pre-pandemic participants (who were more likely to voluntarily choose this form of work) reported fewer disadvantages the more telework they did, but this was not the case for employees during the COVID-19 pandemic. To validate these findings, we measured employees’ voluntariness of telework in Study 2 (N = 220). Results support the importance of voluntariness: Individuals who experience a high degree of voluntariness in choosing telework perceive fewer disadvantages the more they telework. However, the amount of telework was not related to reduced perceptions of disadvantages for those who experienced low voluntariness regarding the telecommuting arrangement. Our findings help to understand when telework is related to the perception of disadvantages and they can provide organizations with starting points for practical interventions to reduce the negative effects of telework.
The ability to respond appropriately to employees' work-related well-being requires leaders to pay attention to their employees' well-being in the first place. We propose that leaders' stress mindset, that is, the belief that stress is enhancing versus debilitating, may bias their perception of employees' well-being. We further propose that this judgment then influences leaders' intention to engage in or refrain from health-oriented leadership behavior, to express higher performance expectations, or to promote their employees. We expect this process to be stronger if leaders strongly identify with their team, increasing their perceived similarity with their employees. In three experiments (N1 = 198, N2 = 292, N3 = 250), we tested the effect of participants' stress mindset on their intention to show certain leadership behaviors, mediated by their perception of employee well-being (emotional exhaustion, somatic symptoms, work engagement) and moderated by their team identification. Our findings largely support the association between stress mindset and the perception of well-being. The results for the proposed mediation and the moderating function of identification were mixed. Overall, the results emphasize the critical role of leaders' stress mindset and may, thus, improve health promotion in organizations by helping leaders to adequately recognize employees' well-being and respond appropriately.
Although researchers and practitioners increasingly focus on health promotion in organizations, research has been mainly fragmented and fails to integrate different organizational levels in terms of their effects on employee health. Drawing on organizational climate and social identity research, we present a cascading model of organizational health climate and demonstrate how and when leaders' perceptions of organizational health climate are linked to employee well‐being. We tested our model in two multisource studies (NStudy 1 = 65 leaders and 291 employees; NStudy 2 = 401 leader–employee dyads). Results showed that leaders' perceptions of organizational health climate were positively related to their health mindsets (i.e., their health awareness). These in turn were positively associated with their health‐promoting leadership behavior, which ultimately went along with better employee well‐being. Additionally, in Study 1, the relationship between perceived organizational health climate and leaders' health mindsets was moderated by their organizational identification. High leader identification strengthened the relationship between perceived organizational health climate and leaders' health mindsets. These findings have important implications for theory and practice as they show how the dynamics of an organizational health climate can unfold in organizations and how it is related to employee well‐being via the novel concept of health‐promoting leadership.
Although researchers and practitioners increasingly focus on health promotion in organizations, research has been mainly fragmented and fails to integrate different organizational levels in terms of their effects on employee health. Drawing on organizational climate and social identity research, we present a cascading model of organizational health climate and demonstrate how and when leaders' perceptions of organizational health climate are linked to employee well-being. We tested our model in two multisource studies (NStudy 1 = 65 leaders and 291 employees; NStudy 2 = 401 leader–employee dyads). Results showed that leaders' perceptions of organizational health climate were positively related to their health mindsets (i.e., their health awareness). These in turn were positively associated with their health-promoting leadership behavior, which ultimately went along with better employee well-being. Additionally, in Study 1, the relationship between perceived organizational health climate and leaders' health mindsets was moderated by their organizational identification. High leader identification strengthened the relationship between perceived organizational health climate and leaders' health mindsets. These findings have important implications for theory and practice as they show how the dynamics of an organizational health climate can unfold in organizations and how it is related to employee well-being via the novel concept of health-promoting leadership.
Despite the increasing interest in leaders’ health-promoting behavior, the employees’ role in the effectiveness of such behavior and the mechanisms underlying how such leadership behavior affects their well-being have largely been ignored. Drawing on implicit leadership theories, we advance the health-oriented leadership literature by examining employees’ ideals, that is, their expectations regarding such leader behavior, as a moderating factor. We propose that higher expectations increase the association between actual health-oriented leader behavior and employee-rated leader-member relationships (LMX) and health-oriented behaviors by employees, which, in turn, positively relate to their well-being (here: exhaustion and work engagement). We tested our theoretical model in three studies, using a cross-sectional design (Study 1, N = 307), a two-wave time-lagged design (Study 2, N = 144) and an experimental design (Study 3, N = 173). We found that the effect of actual health-oriented leader behavior on LMX is contingent on employees’ ideal health-oriented leader behavior. Yet, for employees’ self-care behavior, the proposed moderation was only significant in Study 1. High expectations strengthened the relationship between actual health-oriented leader behavior with LMX and self-care behavior, which, in turn, were associated with less exhaustion and more work engagement (only LMX), supporting most of our mediation hypotheses. Our results highlight the pivotal role of employees’ expectations regarding leaders’ health support and help in building practical interventions with regard to leaders’ health promotion.
Recent studies have proven that Dimethylfumarate (DMF) has a marked anti-proliferative impact on diverse cancer entities e.g., on malignant melanoma. To explore its anti-tumorigenic potential, we examined the effects of DMF on human colon carcinoma cell lines and the underlying mechanisms of action. Human colon cancer cell line HT-29 and human colorectal carcinoma cell line T84 were treated with or without DMF. Effects of DMF on proliferation, cell cycle progression, and apoptosis were analyzed mainly by Bromodeoxyuridine (BrdU)- and Lactatdehydrogenase (LDH)-assays, caspase activation, flowcytometry, immunofluorescence, and immunoblotting. In addition, combinational treatments with radiation and chemotherapy were performed. DMF inhibits cell proliferation in both cell lines. It was shown that DMF induces a cell cycle arrest in G0/G1 phase, which is accompanied by upregulation of p21 and downregulation of cyclin D1 and Cyclin dependent kinase (CDK)4. Furthermore, upregulation of autophagy associated proteins suggests that autophagy is involved. In addition, the activation of apoptotic markers provides evidence that apoptosis is involved. Our results show that DMF supports the action of oxaliplatin in a synergetic manner and failed synergy with radiation. We demonstrated that DMF has distinct anti-tumorigenic, cell dependent effects on colon cancer cells by arresting cell cycle in G0/G1 phase as well as activating both the autophagic and apoptotic pathways and synergizes with chemotherapy.
Background: Peritonitis is responsible for thousands of deaths annually in Germany alone. Even source control (SC) and antibiotic treatment often fail to prevent severe sepsis or septic shock, and this situation has hardly improved in the past two decades. Most experimental immunomodulatory therapeutics for sepsis have been aimed at blocking or dampening a specific pro-inflammatory immunological mediator. However, the patient collective is large and heterogeneous. There are therefore grounds for investigating the possibility of developing personalized therapies by classifying patients into groups according to biomarkers. This study aims to combine an assessment of the efficacy of treatment with a preparation of human immunoglobulins G, A, and M (IgGAM) with individual status of various biomarkers (immunoglobulin level, procalcitonin, interleukin 6, antigen D-related human leucocyte antigen (HLA-DR), transcription factor NF-κB1, adrenomedullin, and pathogen spectrum).
Methods/design: A total of 200 patients with sepsis or septic shock will receive standard-of-care treatment (SoC). Of these, 133 patients (selected by 1:2 randomization) will in addition receive infusions of IgGAM for 5 days. All patients will be followed for approximately 90 days and assessed by the multiple-organ failure (MOF) score, by the EQ QLQ 5D quality-of-life scale, and by measurement of vital signs, biomarkers (as above), and survival.
Discussion: This study is intended to provide further information on the efficacy and safety of treatment with IgGAM and to offer the possibility of correlating these with the biomarkers to be studied. Specifically, it will test (at a descriptive level) the hypothesis that patients receiving IgGAM who have higher inflammation status (IL-6) and poorer immune status (low HLA-DR, low immunoglobulin levels) have a better outcome than patients who do not receive IgGAM. It is expected to provide information that will help to close the knowledge gap concerning the association between the effect of IgGAM and the presence of various biomarkers, thus possibly opening the way to a personalized medicine.
Trial registration: EudraCT, 2016–001788-34; ClinicalTrials.gov, NCT03334006. Registered on 17 Nov 2017.
Trial sponsor: RWTH Aachen University, represented by the Center for Translational & Clinical Research Aachen (contact Dr. S. Isfort).
Es wird über ein mindestens seit dem Jahre 2009 bestehendes Vorkommen des Neophyten Persicaria nepalensis (MEISN.) H. GROSS (Polygonaceae) im Waldgebiet "Die Haard" (Haltern am See, Kreis Recklinghausen) berichtet. Die Art stammt ursprünglich aus den gemäßigten und tropischen Zonen Asiens. Vorkommen in NRW waren bereits aus dem Sauerland und der Wahner Heide bekannt. Die Art stammt aus Wildacker-Ansaaten und ist in der Haard entlang schattiger Waldwege eingebürgert.
Es wird über Vorkommen des Rauen Straußgrases Agrostis scabra WILLD. (Poaceae) in Essen und in Nordrhein-Westfalen berichtet. Die Art stammt ursprünglich aus Nordamerika und Ostasien. Sie ist im Ruhrgebiet mindestens seit 1992 eingebürgert und besiedelt offene Standorte auf Zechenbrachen und an Talsperren.
Das Laerholz an der Grenze zwischen den Bochumer Stadtteilen Querenburg und Laer ist ein strukturreicher Laubmischwald mit Eichen und Buchen hohen Alters. Es wird von der Asbecke durchflossen. Trotz des hohen Bebauungsdrucks im letzten Jahrhundert durch das aufstrebende Universitätsviertel wurde das Laerholz erhalten, sodass der ehemals zum Haus Laer gehörende Forst heute rege zur Naherholung genutzt wird. Nachdem wir das Gebiet von West nach Ost fast komplett durchlaufen hatten, erreichten wir den evangelischen Friedhof an der Schattbachstr. und die Obstwiese des BUND Bochum. Sie wird nach Methoden des