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排序方式: 共有2167条查询结果,搜索用时 15 毫秒
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Jennifer C. Sasaki Ashley Allemang Steven M. Bryce Laura Custer Kerry L. Dearfield Yasmin Dietz Azeddine Elhajouji Patricia A. Escobar Albert J. Fornace Jr Roland Froetschl Sheila Galloway Ulrike Hemmann Giel Hendriks Heng-Hong Li Mirjam Luijten Gladys Ouedraogo Lauren Peel Stefan Pfuhler Daniel J. Roberts Véronique Thybaud Jan van Benthem Carole L. Yauk Maik Schuler 《Environmental and molecular mutagenesis》2020,61(1):114-134
In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity pathways using five example case studies. Each of these genetic toxicology AOPs proposed for further development includes the relevant molecular initiating events, key events, and adverse outcomes (AOs), identification and/or further development of the appropriate assays to link an agent to these events, and discussion regarding the biological plausibility of the proposed AOP. A key difference between these proposed genetic toxicology AOPs versus traditional AOPs is that the AO is a genetic toxicology endpoint of potential significance in risk characterization, in contrast to an adverse state of an organism or a population. The first two detailed case studies describe provisional AOPs for aurora kinase inhibition and tubulin binding, leading to the common AO of aneuploidy. The remaining three case studies highlight provisional AOPs that lead to chromosome breakage or mutation via indirect DNA interaction (inhibition of topoisomerase II, production of cellular reactive oxygen species, and inhibition of DNA synthesis). These case studies serve as starting points for genotoxicity AOPs that could ultimately be published and utilized by the broader toxicology community and illustrate the practical considerations and evidence required to formalize such AOPs so that they may be applied to genetic toxicity evaluation schemes. Environ. Mol. Mutagen. 61:114–134, 2020. © 2019 Wiley Periodicals, Inc. 相似文献
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TG Berger F Kiesewetter C Maczek N Bauer M Lueftl G Schuler M Simon Jr 《Journal of the European Academy of Dermatology and Venereology》2006,20(2):178-183
Vitiligo and psoriasis are both common skin disorders. However, psoriasis strictly confined to pre-existing vitiligo areas is rare and suggests a causal relationship. We report here on two patients with a strict anatomical colocalization of vitiligo and psoriasis. The histopathological examinations showed typical changes for both diseases together with a dense infiltrate of CD4+ and CD8+ T cells. By immunohistochemistry, intracytoplasmatic granzyme B and tumour necrosis factor alpha (TNF-alpha) were detected within the T-cell population, suggesting the functional activity of these cells and the creation of a local T helper 1 (Th1)-cytokine milieu. Additionally, in one patient we could identify anti-melanocytic T cells by tetramer staining and enzyme-linked immunospot (ELISPOT) analysis. These skin-infiltrating lymphocytes might trigger, by the local production of Th-1 cytokines such as TNF-alpha and interferon-gamma (IFN-gamma), the eruption of psoriatic plaques in patients with a genetic predisposition for psoriasis. 相似文献
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Amelie Perron RN PhD Trudy Rudge RN RMHN PhD Dave Holmes RN PhD 《Nursing philosophy》2010,11(2):100-111
The concept of citizenship is becoming more and more prominent in specific fields, such as psychiatry/mental health, where it is constituted as a solution to the issues of exclusion, discrimination, and poverty often endured by the mentally ill. We argue that such discourse of citizenship represents a break in the history of psychiatry and constitutes a powerful strategy to counter the effects of equally powerful psychiatric labelling. However, we call into question the emancipatory promise of a citizenship agenda. Foucault's concept of governmentality is helpful in understanding the production of the citizen subject, its location within the ‘art of government’, as well as the ethical and political implications of citizenship in the context of mental health. 相似文献
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Understanding the minimum clinically important difference: a review of concepts and methods. 总被引:2,自引:0,他引:2
Anne G Copay Brian R Subach Steven D Glassman David W Polly Thomas C Schuler 《The spine journal》2007,7(5):541-546
BACKGROUND CONTEXT: The effectiveness of spinal surgery as a treatment option is currently evaluated through the assessment of patient-reported outcomes (PROs). The minimum clinically important difference (MCID) represents the smallest improvement considered worthwhile by a patient. The concept of an MCID is offered as the new standard for determining effectiveness of a given treatment and describing patient satisfaction in reference to that treatment. PURPOSE: Our goal is to review the various definitions of MCID and the methods available to determine MCID. STUDY DESIGN: The primary means of determining the MCID for a specific treatment are divided into anchor-based and distribution-based methods. Each method is further subdivided and examined in detail. METHODS: The overall limitations of the MCID concept are first identified. The basic assumptions, statistical biases, and shortcomings of each method are examined in detail. RESULTS: Each method of determining the MCID has specific shortcomings. Three general limitations in the accurate determination of an MCID have been identified: the multiplicity of MCID determinations, the loss of the patient's perspective, and the relationship between pretreatment baseline and posttreatment change scores. CONCLUSIONS: An ideal means of determining the MCID for a given intervention is yet to be determined. It is possible to develop a useful method provided that the assumptions and methodology are initially declared. Our efforts toward the establishment of a MCID will rely on the establishment of specific external criteria based on the symptoms of the patient and treatment intervention being evaluated. 相似文献
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Ralf F Schuler Frank A Roberts 《Practical procedures & aesthetic dentistry》2005,17(10):697-704; quiz 706
While less emphasis has traditionally been placed on aesthetics in order to focus on successful osseointegration, increased success rates provided by contemporary endosseous root-form dental implants have improved postoperative peri-implant hard and soft tissue structures. The criteria for the evaluation of implant success should, therefore, include lack of pain, mobility, radiolucency, bone loss, infection, or paresthesia, as well as acceptability and stable aesthetics. This article discusses surgical means to preserve or restore hard and soft tissues around dental implants to achieve ideal and predictable outcomes. 相似文献
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Postoperative analgesia: pain by choice? The influence of patient attitudes and patient education 总被引:3,自引:0,他引:3
Postoperative pain control can be unsatisfactory for a variety of reasons, including patients' attitudes towards pain treatment itself. To assess patients' expectations and their influence on postoperative analgesia, as well as the prevalence of pain following common gynaecological surgery, a prospective study was performed in 166 patients with either adbominal hysterectomy, mastectomy, laparoscopy or uterine curettage. After a first postoperative period with routine on-demand analgesia, a nurse specialised in pain treatment discussed the purposes and risks of pain treatment with the patients and cared for these patients in the second, subsequent study period. Following this discussion, 30 of 40 patients refusing analgesics in the first study period agreed to be given pain medication. In the groups with hysterectomy or mastectomy, pain control improved in the second postoperative period, even though the doses of analgesics administered were generally lower. Education of patients regarding the aims and risks of pain therapy is an essential part of pain control and can lead to an improvement of postoperative analgesia. 相似文献
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Joseph D. Borsi Thomas Revesz Dezso Schuler 《Cancer chemotherapy and pharmacology》1987,19(3):261-264
Summary Pharmacokinetic studies of methotrexate have been carried out in 21 children with acute lymphoblastic leukemia diagnosed in 1981. Children were treated with intermediate dose (500 mg/m2) methotrexate in keeping with the 1981 ALL treatment Protocol of the Hungarian Childhood Leukemia Working Group. Of the 21 children, 8 relapsed, and 13 are in continuous complete remission. In the relapsed patients significantly increased systemic clearance of methotrexate was observed at the time of the second methotrexate treatment cycle compared with the calculated value after the first administration of the drug. No such change in the clearance was found in patients who are still in remission. There was no difference between children who relapsed or who are in remission in the elimination half-time of the drug. Age, sex, WBC at diagnosis, and systemic clearance of methotrexate were found to be connected with the probability of relapse in the patients studied. The possible reasons for the prognostic role of systemic methotrexate clearance are discussed. 相似文献