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1.
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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Biomechanical comparison of stimulated and nonstimulated skeletal muscle pulled to failure 总被引:1,自引:0,他引:1
W E Garrett M R Safran A V Seaber R R Glisson B M Ribbeck 《The American journal of sports medicine》1987,15(5):448-454
We compared the biomechanical properties of passive and stimulated muscle rapidly lengthened to failure in an experimental animal model. The mechanical parameters compared were force to tear, change in length to tear, site of failure, and energy absorbed by the muscle-tendon unit before failure. Paired comparisons were made between 1) muscles stimulated at 64 Hz (tetanic stimulation) and passive (no stimulation) muscles, 2) muscles stimulated at 16 Hz (wave-summated stimulation) and passive muscles, and 3) muscles stimulated at 64 Hz and at 16 Hz. Both tetanically stimulated and wave-summation contracted muscles required a greater force to tear (at 64 Hz, 12.86 N more, P less than 0.0004; and at 16 Hz, 17.79 N more, P less than 0.003) than their nonstimulated controls, while there was no statistical difference in failure force between muscles stimulated at 16 Hz and 64 Hz. The energy absorbed was statistically greater for the stimulated muscles than for the passive muscles in Groups 1 and 2 (at 64 Hz, 100% more, P less than 0.0003; and 16 Hz, 88% more, P less than 0.0002). In Group 3, the tetanically contracted muscle-tendon units absorbed 18% more energy than the wave-summated stimulated muscles (P less than 0.01). All muscles tore at the distal musculotendinous junction, and there was no difference in the length increase at tear between muscles in each group. These findings may lead to enhanced understanding of the mechanism and physiology of muscle strain injuries. 相似文献
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J A Garrett J L Stewart 《Asia-Pacific journal of public health / Asia-Pacific Academic Consortium for Public Health》1989,3(3):213-218
In less than two decades, there has been a dramatic reduction in the prevalence of otitis media and perforations among Guam's school-aged children. In addition, hearing loss due to chronic middle ear disease as a cause of disqualification from military service has dropped from a first rank order cause to next-to-last. However, there has been no reduction in the prevalence of otitis media in the preschool population. The reduction in chronic ear disease is the result of improved access to primary care, intensive hearing screening, wide availability of audiologic diagnostic and follow-up services, and comprehensive otologic care. It is essential that these services continue to be available to Guam's children to avoid a reversal of these dramatic gains. Attention must now focus on how to achieve similar gains for Micronesian children who remain restricted in their access to these resources. 相似文献
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Kelly Garrett Allison Butler Wayne R Cohen 《The journal of maternal-fetal & neonatal medicine》2005,17(1):49-53
OBJECTIVE: To characterize dysfunctional labors that lead to cesarean delivery in the second stage and to assess the accuracy of diagnoses of abnormal fetal descent. METHODS: Thirty-one patients delivered by cesarean during the second stage because of abnormal labor or presumed cephalopelvic disproportion were studied and compared to 62 control cesarean cases delivered for the same indications in the first stage. The clinical diagnosis of dysfunctional labor that led to the cesarean was compared to the diagnosis made by retrospective analysis of the labor curves. RESULTS: Cases did not differ from controls delivered in the first stage in maternal age, race, parity, gestational age, weight gain, or the frequency of associated medical complications. The newborns were not significantly different in birth weight,ponderal index, sex, or the incidence of low Apgar scores. Among study patients, 94% had a second stage labor dysfunction determined by graphic labor analysis, predominantly arrest of descent (69%) and failure of descent (28%). In 79% of cases a dysfunctional first stage preceded the abnormal second stage. Among these first stage labor abnormalities, 68% were not recognized during the labor. CONCLUSION: Characteristics of patients delivered by cesarean during the second stage were similar to those delivered before full cervical dilatation. Second stage labor abnormalities were usually preceded by an abnormal first stage. There was considerable inaccuracy in the diagnosis of second stage labor dysfunction. 相似文献
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Many people die in emergency departments (EDs) across the United States from sudden illnesses or injuries, an exacerbation of a chronic disease, or a terminal illness. Frequently, patients and families come to the ED seeking lifesaving or life-prolonging treatment. In addition, the ED is a place of transition-patients usually are transferred to an inpatient unit, transferred to another hospital, or discharged home. Rarely are patients supposed to remain in the ED. Currently, there is an increasing amount of literature related to end-of-life care. However, these end-of-life care models are based on chronic disease trajectories and have difficulty accommodating sudden-death trajectories common in the ED. There is very little information about end-of-life care in the ED. This article explores ED culture and characteristics, and examines the applicability of current end-of-life care models. 相似文献
10.
Background - A case of primary thyroid T cell lymphoma leading to lethal tracheal perforation during chemotherapy is described. 相似文献