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The benchmark dose (BMD) approach is increasingly used as a preferred approach for dose-effect analysis, but standard experimental designs are generally not optimized for BMD analysis. The aim of this study was to evaluate how the use of unequally sized dose groups affects the quality of BMD estimates in toxicity testing, with special consideration of the total burden of animal distress. We generated continuous dose-effect data by Monte Carlo simulation using two dose-effect curves based on endpoints with different shape parameters. Eighty-five designs, each with four dose groups of unequal size, were examined in scenarios ranging from low- to high-dose placements and with a total number of animals set to 40, 80, or 200. For each simulation, a BMD value was estimated and compared with the "true" BMD. In general, redistribution of animals from higher to lower dose groups resulted in an improved precision of the calculated BMD value as long as dose placements were high enough to detect a significant trend in the dose-effect data with sufficient power. The improved BMD precision and the associated reduction of the number of animals exposed to the highest dose, where chemically induced distress is most likely to occur, are favorable for the reduction and refinement principles. The result thereby strengthen BMD-aligned design of experiments as a means for more accurate hazard characterization along with animal welfare improvements.
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Increasingly, dose-response data are being evaluated with the benchmark dose (BMD) approach rather than by the less precise no-observed-adverse-effect-level (NOAEL) approach. However, the basis for designing animal experiments, using equally sized dose groups, is still primed for the NOAEL approach. The major objective here was to assess the impact of using dose groups of unequal size on both the quality of the BMD and overall animal distress. We examined study designs with a total number of 200 animals distributed in four dose groups employing quantal data generated by Monte Carlo simulations. Placing more animals at doses close to the targeted BMD provided an estimate of BMD that was slightly better than the standard design with equally sized dose groups. In situations involving a clear dose-response, this translates into fewer animals receiving high doses and thus less overall animal distress. Accordingly, in connection with risk and safety assessment, animal distress can potentially be reduced by distributing the animals appropriately between dose groups without decreasing the quality of the information obtained.
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In this study, the cumulative margin of exposure (MOE) was estimated for a group of polychlorinated biphenyls (PCBs) based on reduction of hepatic retinoids as a mode-of-action relevant toxicological endpoint. The MOE was defined as the ratio between a reference dose, derived using the benchmark dose (BMD) approach, and the estimated human dietary PCB exposure. A distribution for the cumulative MOE was established, taking into account inter- and intra-individual variability as well as uncertainty in data measurements. The cumulative MOE reflected mainly the MOE for PCB 126; other PCB congeners had little contribution to the cumulative exposure and MOE. The median of the 0.1st percentile for the cumulative MOE was about 20 for women; depending on the percentile, cumulative MOE was 2-4 times higher for men compared to women. Furthermore, a relative potency factor (RPF) based approach was compared to an RPF-free approach for estimating the cumulative MOE. The RPF-free approach more completely accounts for variability and uncertainty but is more data intensive than the RPF-based approach, which can be more easily implemented in practice and allows for a use of historical data on RPFs. Consideration of the discussed approaches may contribute to improving cumulative health risk assessments.
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Exposição Ambiental/análise , Poluentes Ambientais/toxicidade , Bifenilos Policlorados/toxicidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Benchmarking , Relação Dose-Resposta a Droga , Feminino , Contaminação de Alimentos/análise , Contaminação de Alimentos/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Medição de Risco , Fatores Sexuais , Incerteza , Adulto JovemRESUMO
Objectives: This study assesses complex factors related to marital and sexual satisfaction among couples undergoing infertility treatment. Methods: This cross-sectional study was conducted with 140 couples who visited fertility centers in Iran, between September 2015 and July 2016. Data collection was done by Marital and Sexual Satisfaction Questionnaires and were analyzed by the IBM SPSS 26 software. Results: There was a significant difference between wives and husbands in the MSQ total scores (p = 0.027). However, there was no significant difference between wives and husbands in the SSQ total scores (p = 0.398). Sexual satisfaction and decision-maker in life among wives and husbands were significant predictors of MSQ. The kind of treatment, cause of infertility and BMI among wives and kinds of treatment, cause of infertility, and decision-maker among husbands were also significant predictors of SSQ. Conclusion: The findings of this study showed that there is a difference between the understanding of marital and sexual satisfaction in wives and their husbands. Healthcare providers need to pay more attention to these differences.
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Background: Infertility is an abnormal event in the life of families and can have various consequences on a personal and social level. Therefore, infertile couples need to manage their emotional responses. Social capital, as one of the social determinants of health, can affect mental health. Objective: This study was conducted to determine the relationship between social capital and emotional adjustment in infertile couples. Materials and Methods: This cross-sectional study was conducted from October 2018 to February 2019 with 170 infertile couples visiting infertility centers in Sari, Iran. The data collection instruments included the social capital integrated questionnaire, an emotional adjustment scale and a demographic-reproductive checklist. Results: All the social capital dimensions, except for the groups and networks dimension, had a score of higher than 50 (more than the mean score). Based on ANCOVA and the multiple linear regression results, the dimension of trust and solidarity had a significant negative relationship with emotional adjustment (p = 0.01), but no significant relationship was observed between the other social capital dimensions and emotional adjustment. Conclusion: The trust and solidarity dimension had a significant relationship with emotional adjustment in infertile couples. Accordingly, increasing mutual trust between neighborhood residents can strengthen social capital, and in turn, improve emotional adjustment in infertile couples.
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In this study, differences in sensitivity between Long-Evans (L-E; dioxin sensitive) and Han/Wistar (H/W; dioxin resistant) rats following long-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were statistically and quantitatively investigated. Sensitivity differences were analyzed by comparing benchmark doses (BMDs) for the two strains considering a number of toxicological endpoints including data on body and organ weights, hepatic foci, hepatic CYP1A1 induction, as well as tissue retinoid levels. Dose-response relationships for L-E and H/W rats, described by the Hill function, were assumed to be parallel, which was supported according to statistical analysis. It was concluded that L-E and H/W rats differed statistically in their response to TCDD treatment for most of the parameters investigated. Differences between the strains were most pronounced for hepatic foci; L-E rats were approximately 20-40 times more sensitive than H/W rats. For body and organ weight parameters, L-E rats were approximately 10-20 times more sensitive than H/W rats. For retinoid parameters and hepatic CYP1A1 induction, estimated differences between the strains were generally about 5-fold, and associated with a low uncertainty. In conclusion, the present study employs a dose-response modeling approach suitable for statistical evaluation of strain and species differences in sensitivity to chemical exposure. The study demonstrates quantitatively the differences in sensitivity between the L-E and H/W rat strains following long-term TCDD exposure.
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Fígado/efeitos dos fármacos , Dibenzodioxinas Policloradas/toxicidade , Testes de Toxicidade Crônica , Animais , Benchmarking , Peso Corporal/efeitos dos fármacos , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A2 , Citocromos/metabolismo , Relação Dose-Resposta a Droga , Feminino , Fígado/enzimologia , Fígado/metabolismo , Fígado/patologia , Tamanho do Órgão/efeitos dos fármacos , Especificidade de Órgãos , Ratos , Ratos Long-Evans , Ratos Wistar , Especificidade da Espécie , Fatores de Tempo , Testes de Toxicidade Crônica/métodos , Testes de Toxicidade Crônica/estatística & dados numéricos , Vitamina A/sangueRESUMO
INTRODUCTION: Several studies have shown the role of oxidative stress in pathophysiology of burn injuries. This study aimed to evaluate the changes of oxidant-antioxidant levels during the week following burn injuries and its correlation with grade of burn. METHODS: In this prospective cross-sectional study, changes of total glutathione, reduced glutathione (GSH), oxidized GSH (GSSG), GSH/GSSG ratio, as well as Pro-oxidant-antioxidant balance (PAB) were investigated on the 1st, 2nd and 7th days of admission in patients with > 15 % burns. RESULTS: 40 patients with the mean age of 21.1 ± 14.5 were studied (47.5% male). More than 50% of patients were in the 18 - 55 years age range and over 70% had 20% - 60% grade of burn. Total serum glutathione level and GSH had significant decreasing trends (P < 0.001) and GSSG and GSH/GSSG ratio had increasing trends (p < 0.001). No significant correlation was observed between serum GSH level and the total body surface area (TBSA) of burn injury (r = 0.047; p = 0.779). The evaluation of PAB and its correlation with TBSA showed a significant and direct association between them on the 1st (coefficient = 0.516; p = 0.001), 2nd (coefficient = 0.62; p <0.001), and 3rd (coefficient = 0.471; p = 0.002) day of follow up. CONCLUSION: According to this study, the redox perturbation occurred in burn injury which was measured and proved by decreased GSH/GSSG ratio as well as the shift of PAB in favour of oxidants. Besides, since PAB positively correlated with the severity of dermal damage, it might suggest the application of antioxidants as a part of therapeutic protocol for which the dosage should be proportionate to the surface area of the damaged skin.
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BACKGROUND: Infertility all around the world and in every culture is recognized as a stressful and critical experience that threatens individual, familial, marital, and social stability. Thus, in accordance with the importance of a woman's mental health and the possible impact of mental health on treatment outcome, finding a way to deal with perceived stress in women can help improve pregnancy outcomes. METHODS: This study is a systematic review on reducing perceived infertility stress in infertile women. The current study was undertaken using multiple databases such as SID, Irandoc, Magi ran, Google Scholar, PubMed, Science Direct, Scopus, Cochrane library, and CINAHL selected from articles pertinent to the study. The selection of papers was undertaken from 1990 through May 2016. The methodological quality was assessed. RESULTS: The initial search yielded a list of 725 papers, and then reviewers studied titles and abstracts. Thereafter, 68 papers were incorporated, and researchers reviewed summaries of all of the searched articles. Finally, the researchers utilized the data gained from 29 full articles so as to compile this review paper. Reviewing the studies conducted on reducing infertility perceived stress, the researchers classified related findings into two main categories: supportive and counseling intervention. CONCLUSION: Considering the fact that there is an international agreement that fertility centers need to offer counseling programs for psychological problems of the infertile, it is especially important to recognize counseling-supportive interventions for decreasing infertile women's perceived stress and to program plans for decreasing women's perceived stress. By investigating counseling-supportive stress, we hope that this study has stepped forward toward health care agent's familiarity with decreasing infertile women's perceived stress and, therefore, improving treatment consequences.
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BACKGROUND: Both industrial chemicals and environmental pollutants can interfere with bone modeling and remodeling. Recently, detailed toxicological bone studies have been performed following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which exerts most of its toxic effects through the aryl hydrocarbon receptor (AhR). OBJECTIVES: The aims of the present study were to quantitatively evaluate changes in bone geometry, mineral density and biomechanical properties following long-term exposure to TCDD, and to further investigate the role of AhR in TCDD-induced bone alterations. To this end, tissue material used in the study was derived from TCDD-exposed Long-Evans (L-E) and Han/Wistar (H/W) rats, which differ markedly in sensitivity to TCDD-induced toxicity due to a strain difference in AhR structure. METHODS: Ten weeks old female L-E and H/W rats were administered TCDD s.c. once per week for 20 weeks, at doses corresponding to calculated daily doses of 0, 1, 10, 100 and 1000ngTCDD/kgbw (H/W only). Femur, tibia and vertebra from the L-E and H/W rats were analyzed by peripheral quantitative computed tomography (pQCT) and biomechanical testing at multiple sites. Dose-response modeling was performed to establish benchmark doses for the analyzed bone parameters, and to quantify strain sensitivity differences for those parameters, which were affected by TCDD exposure in both rat strains. RESULTS: Bone geometry and bone biomechanical parameters were affected by TCDD exposure, while bone mineral density parameters were less affected. The trabecular area at proximal tibia and the endocortical circumference at tibial diaphysis were the parameters that showed the highest maximal responses. Significant strain differences in response to TCDD treatment were observed, with the L-E rat being the most sensitive strain. For the parameters that were affected in both strains, the differences in sensitivity were quantified, showing the most pronounced (about 49-fold) strain difference for cross-sectional area of proximal tibia. CONCLUSION: The study provides novel information about TCDD-induced bone alterations at doses, which are of relevance from a health risk assessment point of view. In addition, the obtained results provide further support for a distinct role of the AhR in TCDD-induced bone alterations, and suggest that the benchmark dose modeling approach is appropriate for quantitative evaluation of bone toxicity parameters.