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31.
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
32.
Imre W.K. Kouw Bart B.L. Groen Joey S.J. Smeets Irene Fleur Kramer Janneau M.X. van Kranenburg Rachél Nilwik Jan A.P. Geurts René H.M. ten Broeke Martijn Poeze Luc J.C. van Loon Lex B. Verdijk 《Journal of the American Medical Directors Association》2019,20(1):35-42
Objectives
Short successive periods of skeletal muscle disuse have been suggested to substantially contribute to the observed loss of skeletal muscle mass over the life span. Hospitalization of older individuals due to acute illness, injury, or major surgery generally results in a mean hospital stay of 5 to 7 days, during which the level of physical activity is strongly reduced. We hypothesized that hospitalization following elective total hip arthroplasty is accompanied by substantial leg muscle atrophy in older men and women.Design and participants
Twenty-six older patients (75 ± 1 years) undergoing elective total hip arthroplasty participated in this observational study.Measurements
On hospital admission and on the day of discharge, computed tomographic (CT) scans were performed to assess muscle cross-sectional area (CSA) of both legs. During surgery and on the day of hospital discharge, a skeletal muscle biopsy was taken from the m. vastus lateralis of the operated leg to assess muscle fiber type–specific CSA.Results
An average of 5.6 ± 0.3 days of hospitalization resulted in a significant decline in quadriceps (?3.4% ± 1.0%) and thigh muscle CSA (?4.2% ± 1.1%) in the nonoperated leg (P < .05). Edema resulted in a 10.3% ± 1.7% increase in leg CSA in the operated leg (P < .05). At hospital admission, muscle fiber CSA was smaller in the type II vs type I fibers (3326 ± 253 μm2 vs 4075 ± 279 μm2, respectively; P < .05). During hospitalization, type I and II muscle fiber CSA tended to increase, likely due to edema in the operated leg (P = .10).Conclusions
Six days of hospitalization following elective total hip arthroplasty leads to substantial leg muscle atrophy in older patients. Effective intervention strategies are warranted to prevent the loss of muscle mass induced by short periods of muscle disuse during hospitalization. 相似文献33.
34.
Konrad Matyja Anna Małachowska-Jutsz Anna K. Mazur Kazimierz Grabas 《Ecotoxicology (London, England)》2016,25(5):924-939
Dehydrogenase activity is frequently used to assess the general condition of microorganisms in soil and activated sludge. Many studies have investigated the inhibition of dehydrogenase activity by various compounds, including heavy metal ions. However, the time after which the measurements are carried out is often chosen arbitrarily. Thus, it can be difficult to estimate how the toxic effects of compounds vary during the reaction and when the maximum of the effect would be reached. Hence, the aim of this study was to create simple and useful mathematical model describing changes in dehydrogenase activity during exposure to substances that inactivate enzymes. Our model is based on the Lagergrens pseudo-first-order equation, the rate of chemical reactions, enzyme activity, and inactivation and was created to describe short-term changes in dehydrogenase activity. The main assumption of our model is that toxic substances cause irreversible inactivation of enzyme units. The model is able to predict the maximum direct toxic effect (MDTE) and the time to reach this maximum (TMDTE). In order to validate our model, we present two examples: inactivation of dehydrogenase in microorganisms in soil and activated sludge. The model was applied successfully for cadmium and copper ions. Our results indicate that the predicted MDTE and TMDTE are more appropriate than EC50 and IC50 for toxicity assessments, except for long exposure times. 相似文献
35.
36.
Contraceptive use is an important strategy for the prevention of unwanted pregnancy and avoidance of induced abortion. Of all the contraception methods, emergency contraceptive (EC) offers the last chance to achieve this. However, few studies have documented the use of EC among young people in Ghana. This study explored knowledge and usage of EC as well as the factors associated with it among University of Cape Coast students. Data were obtained on the knowledge and usage of ECs among University of Cape Coast students in 2013. Logistic regression analysis was used to investigate the association between students’ socio-demographic characteristics and EC knowledge and use. More male students (72 %) than females (59 %) were sexually active. Fifty-seven percent of the respondents had ever heard of EC and 36 % had ever used EC. Although males were more likely to be sexually active, females were more likely to have knowledge of EC use compared to males. The study underscores the need to increase awareness regarding EC among University students in order to offer them the opportunity that EC provides if other forms of contraceptives are missed. 相似文献
37.
38.
Gastroesophageal reflux is the most common benign disorder of the esophagus and laparoscopic Nissen fundoplication has become the standard surgical treatment for its treatment. In our area, where the use of bougie calibration is debatable, postoperative dysphagia is encountered often after this surgery although it is usually not permanent. The aim of this study was to investigate the effect of using a soft silicone tube 39 F in diameter for esophageal calibration during laparoscopic Nissen fundoplication on the incidence of postoperative dysphagia. We divided cases scheduled to undergo laparoscopic Nissen fundoplication between January 2009 and November 2010 into two groups, each consisting 25 patients. Esophageal calibration with a 39 F silicone orogastric tube was used for the first group while there was no operative calibration in the second group. The surgical duration was recorded; the presence and severity of the postoperative dysphagia was calculated by using a dysphagia severity scoring system during the 1-year postoperative follow-up. The dysphagia severity scores were significantly lower in group 1 than group 2 on the postoperative second day and at the end of the first week and first month. We did not find a significant difference at the end of the 6-month and first year. There was also no significant difference regarding surgery duration. The use of a soft orogastric tube 39 F in diameter for esophagus calibration during laparoscopic Nissen fundoplication has significantly decreased the incidence of postoperative transient dysphagia without affecting the duration of surgery. Although dysphagia gradually resolves in the majority of patients, a safe and easy calibration method for its prevention is worth developing, and we believe that the use of our method in larger series could be beneficial. 相似文献
39.
Anna C. Rienmüller Sandro M. Krieg Franziska A. Schmidt Elias L. Meyer Bernhard Meyer 《The spine journal》2019,19(1):113-120
Background Context
The concept of dynamic stabilization (DS) of the lumbar spine for treatment of degenerative instability has been introduced almost two decades ago. Dynamic stabilization follows the principle of controlling movement in the coronal plane by providing load transfer of the spinal segment without fusion and, at the same time, reducing side effects such as adjacent segment disease (ASD). So far, only little is known about revision rates after DS due to ASD and screw loosening (SL).Purpose
The present study aimed to evaluate the longitudinal revision rates following dynamic pedicle screw stabilization in the lumbar spine and to determine specific risk factors predictive for ASD, SL, and overall reoperation in a large cohort with considerable follow-up.Design
We carried out a post hoc analysis of a prospectively collected database in a level I spine center.Patients Example
The patient sample comprised 283 (151 female/132 male) consecutive patients suffering from painful degenerative lumbar segmental instability with or without spinal stenosis who underwent DS of the lumbar spine (Ulrich Cosmic, Ulrich Medical, Ulm, Germany) between January 2008 and December 2011.Outcome Measures
Longitudinal reoperation rate and risk factors predictive for revision surgery were evaluated.Methods
We analyzed the longitudinal reoperation rate due to ASD and SL and overall reoperation. Risk factors such as age, gender, body mass index, lumbar lordosis (LL), number of segments, and number of previous surgeries were taken into account. Regular and mixed model logistic regressions were performed to determine risk factors for revision surgery on a patient and on a screw level.Results
The mean age was 65.7±10.2 years (range 31–88). One hundred thirty-two patients were stabilized in 1 segment, 134 in 2 segments, 15 in 3 segments, and 2 patients in 4 segments. Reoperation rate for ASD and SL after 1 year was 7.4 %, after 2 years was 15.0%, and after a mean follow-up of 51.4±15 months was 22.6%. Reasons for revision were SL in 19 cases (6.6%), ASD in 39 cases (13.7%), SL and ASD in 6 cases, hematoma in 2 cases (0.7%), cerebrospinal fluid fistulae in 3 cases (1.1%), infection in 6 cases (2.1%), and implant failure in 1 case (0.4%). The patients' age, the number of stabilized segments, and the number of previous surgeries and postoperative LL had a significant influence on the probability for revision surgery.Conclusions
Reoperation rates after DS of the lumbar spine are comparable with rigid fixations. The younger the patient and the more segments are involved, the lower the LL and the more previous surgeries were found, the higher was the risk of revision. Risk of revision was almost twice as high in men compared with women. We therefore conclude that for clear clinical indication and careful evaluation of preoperative imaging data, DS using the Cosmic system seems to be a possible option. The presented data will help to further tailor indication and patient selection. 相似文献40.