Effect of iodothyronine hormone status on doxorubicin related cardiotoxicity

The anthracycline anticancer agent doxorubicin has been recognised to induce a dose-dependent cardiotoxicity. The chronic form of such complication is characterized by an irreversible cardiac damage and congestive heart failure. Although the pathogenesis of anthracycline cardiotoxicity seems to be multifactorial, the pivotal role has been attributed to reactive oxygen species formation. Because redox equilibrium in cardiomyocytes may be regulated via iodothyronine hormones, the aim of the study was to appraise the effect of hypothyroidism on heart damages induced by doxorubicin. The rats received methimazole in drinking water (0.001 and 0.025%) after doxorubicin administration (2.0, 5.0 and 15 mg/kg). The cardiac morphology and blood biochemical markers of heart damage were assessed. Decreased levels of iodothyronine hormones had not significant impact on cardiac morphological changes and no effect on the level of B-type natriuretic peptide in rats receiving doxorubicin. Lower hormonal levels had sporadic, diverse effect on blood transaminases, lactate dehydrogenase and creatine kinase levels, but any relation to time, doxorubicin doses and hypothyroid status was found. Hypothyreosis leads to increase in fatty acid binding protein in rats receiving higher dose of doxorubicin. Hypothyreosis had no effect on heart stretching and on necrosis at morphological level, but caused biochemical symptoms of cardiomyocyte necrosis in rats receiving doxorubicin

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. METHODS: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. FINDINGS: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2-11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75-1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58-1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91-1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70-1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11-0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50-0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38-0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45-0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. INTERPRETATION: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. FUNDING: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Social needs and preferences in the field of leisure in protected areas – 'Nad Tanwia' nature reserve case study

Forests covered by various forms of nature protection are a popular resting place for the society. The choice of a certain place for the leisure depends not the attractiveness of the area, but also on its availability, the condition of the infrastructure, and on the preferences of tourists. The aim of the research was to determine the significance of the ‘Nad Tanwią’ nature reserve (‘NT’ NR) for tourism and recreational purposes. The following aspects were considered: the motives of arrival, forms of spending free time, frequency of visits and length of stay. The ‘NT’ NR is a landscape reserve with an area of 41.33 ha located in the Józefów Forest District (SE Poland). The research material consisted of the data from questionnaires collected in the survey conducted from May to September 2017 in the ‘NT’ NR. The research covered a group of 341 respondents. For statistical analysis we used Friedman ANOVA (with Davenport’s modification), chi−square function in the logarithmic form (so−called G function), Mann−Whitney and Kruskal−Wallis tests. The visitors most often came to the ‘NT’ NR mainly due to the need to rest (61% of respondents), interesting landscape (57%) and the proximity of the reserve from their place of residence (39%). Most tourists spent time on walks (50% of the time), trips (21%) and cycling (17%). The respondents visited the examined area on average over 11 times, and the average length of their stay was 3 days. Statistically significant differences in the needs and preferences depending on the social characteristics of the respondents were obtained. Inhabitants of the cities declare a greater need for tourism and recreation comparing to the rural residents. The ‘Nad Tanwią’ nature reserve is frequented by local population, therefore their needs in this area should be met. Hence the need for further research is to learn about their preferences in terms of necessary of infrastructure and tourist information. These factors contribute to the greater development of tourism and recreation, and ‘NT’ NR could be an example of a sylvatouristic product of this region

Applications Use Standardized Work Purpose of Increase the Production Capacity – a Case Study

The article presents the results of research carried out in the company of the foundry industry. Actions taken in the company were to analyze the losses occurring at selected positions and the implementation of standardized work procedures to improving the production process. Describes the state of the current position and manner of operations by the employee, taking into account the distances driven during the execution of the various treatments. The article presents the objectives of the program TWI (Training Within Industry), with special emphasis of the program on the improvement of working methods (MP). The proposed solutions are designed to improve working conditions in the enterprise, and shortening the distances that overcomes the operator also contributes to increased safety. The main effect introduced in the enterprise improvement activities is to increase employee productivity by reducing the execution time of repeated treatments with the introduction of standardized work rules

Valuation of non-wood forest functions by a contingent method on the example of a tourist function

The perception of forests has changed in recent years. The non−wood services of forests gain more and more importance. Society pays more attention to the protective and social aspects of forestry. Hence, there is the need for their valuation. The aim of the research was to determine the economic value of the tourist function of the ‘Nad Tanwią’ nature reserve (south−eastern Poland) using a contingent valuation method (CVM). The objective reserve is a strict reserve with an area of 41.3 hectares. In order to determine its tourist value we conducted a survey that included a group of 341 tourists resting in this area. The research was carried out from May to September 2017. The CVM method uses a questionnaire as a tool to show respondents’ Willingness−To−Pay (WTP). The research used a variant of the CVM method in the form of a Payment Card. We used classification and regression trees for the statistical analysis. The method compiled data on the amount of hypothetical contributions for reserve protection (WTP) and the amount of contributions in the case of doubling the respondents’ income (WTP2). As a result of data analysis, the WTP model was built. The respondents reported the need of 14 types of visits in terms of their duration, most often they preferred short visits of up to 3 days. The demand for recreation in the reserve was determined using the regression equation: Sd=(29.87679/N)–0.12102. Hypothetical propensity to pay contributions for the protection of the ‘Nad Tanwią’ nature reserve was confirmed by 46% of respondents, while the remaining ones were against paying fees for this purpose. The average fee for all visits was PLN 27.51. The value of non−market benefits per person was PLN 340/year, and for the group of respondents it was around PLN 116,000. The valuation of all functions of forests is important from a practical point of view, as it supports foresters in making decisions about the right direction of forest management. In addition, forest areas covered by various forms of nature conservation are an important place of recreation for tourists