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Objective: To assess the causal effect of systemic iron status by using four biomarkers (serum iron; transferrin saturation; ferritin; total iron-binding capacity) on knee osteoarthritis (OA), hip OA, total knee replacement, and total hip replacement using 2-sample Mendelian randomization (MR) design. Methods: Three instrument sets were used to construct the genetic instruments for the iron status: Liberal instruments (variants associated with one of the iron biomarkers), sensitivity instruments (liberal instruments exclude variants associated with potential confounders), and conservative instruments (variants associatedwith all four iron biomarkers). Summary-level data for four OA phenotypes, including knee OA, hip OA, total knee replacement, and total hip replacement were obtained from the largest genome-wide meta-analysis with 826,690 individuals. Inverse-variance weighted based on the random-effect model as the main approach was conducted. Weighted median, MR-Egger, and Mendelian randomization pleiotropy residual sum and outlier methods were used as sensitivity MR approaches. Results: Based on liberal instruments, genetically predicted serumiron and transferrin saturationwere significantly associated with hipOA and total hip replacement, but not with kneeOA and total knee replacement. Statistical evidence of heterogeneity across the MR estimates indicated that mutation rs1800562 was the SNP significantly associated with hip OA in serum iron (odds ratio, OR = 1.48), transferrin saturation (OR = 1.57), ferritin (OR = 2.24), and total-iron binding capacity (OR = 0.79), and hip replacement in serum iron (OR = 1.45), transferrin saturation (OR = 1.25), ferritin (OR = 1.37), and total-iron binding capacity (OR = 0.80). Conclusion: Our study suggests that high iron status might be a causal factor of hip OA and total hip replacement where rs1800562 is the main contributor. [ABSTRACT FROM AUTHOR]

In the last decades, an exceptional global warming trend was observed. Along with the temperature increase, modifications in the humidity and wind regime amplify the regional and local impacts on livestock husbandry. Direct impacts include the occurrence of climatic stress conditions. In Europe, cows are economically highly relevant and are mainly kept in naturally ventilated buildings that are most susceptible to climate change. The high-yielding cows are particularly vulnerable to heat stress. Modifications in housing management are the main measures taken to improve the ability of livestock to cope with these conditions. Measures are, however, typically taken in direct reaction to uncomfortable conditions instead of in anticipation of a long term risk for climatic stress. Moreover, measures that balance welfare, environmental and economic issues are barely investigated in the context of climate change and are thus almost not available for commercial farms. Quantitative analysis of the climate change impacts on the animal welfare and linked economic and environmental factors are rare. Therefore, we used a numerical modeling approach to estimate the future heat stress risk in such dairy cattle husbandry systems. The indoor climate was monitored inside three reference barns in Central Europe and in the Mediterranean region. An artificial neuronal network (ANN) was trained to relate the outdoor weather conditions provided by official meteorological weather stations to the measured indoor microclimate. Subsequently, this ANN model was driven by an ensemble of regional climate model projections with three different greenhouse gas concentration scenarios. For the evaluation of the heat stress risk, we considered the amount and duration of heat stress events. Based on the changes of the heat stress events various economic and environmental impacts were estimated. We found that the impacts of the projected increase of heat stress risk vary dependent on the region respectively the barn, the climate model and the assumed greenhouse gas concentration. There was an overall increasing trend in number and duration of heat stress events. At the end of the century, the number of annual stress events can be expected to increase by up to 2000 hours while the average duration of the events increases by up to 22 h compared to the end of the last century. This implies strong impacts on economics, environment and animal welfare and an urgent need for mid-term adaptation strategies. We anticipated that up to one tenth of all hours of a year respectively one third of all days will be classified as critical heat stress conditions. Due to heat stress, milk yield may decrease by about 3.5 % relative to the present European milk yield and farmers may expect financial losses in the summer season of about 6.6 % of their monthly income. In addition, an increasing demand for emission reduction measures must be expected, as an emission increase of about 16 Gg ammonia and 0.1 Gg methane per year can be expected under the anticipated heat stress conditions. The cattle respiration rate increases by up to 60 % and the standing time may be prolonged by 1 h. This promotes health issues and increases the probability of medical treatments. The various impacts imply feedback loops in the climate system which are presently underexplored. Hence, future in-depth studies on the different impacts and adaptation options at different stress levels are highly recommended. [ABSTRACT FROM AUTHOR]