8, 30.3 and 41.2, respectively. The PK/PD-based population dose prediction indicated a probability of target attainment (PTA) for the current marketed dose (6 mg/kg) of 88.9% against H. parasuis. The calculated gamithromycin dose for a PTA ≥ 90% was 6.55 mg/kg. Based on Monte Carlo simulations, the PK/PD cutoff (COPD) was determined to be 0.25 mg/L. CONCLUSION The determined cutoffs and PK/PD-based dose prediction will be of great importance in gamithromycin resistance surveillance and serve as an important step in the establishment of optimum dose regimen and clinical breakpoints.BACKGROUND Obesity can significantly reduce health-related quality of life (HRQoL) and may lead to numerous health problems even in youths. This study aimed to investigate whether HRQoL varies among youths with obesity depending on grade of obesity and other factors. METHODS For the Youths with Extreme obesity Study (YES) (2012-2014), a prospective multicenter cohort study, a baseline sample of 431 obese and extremely obese adolescents and young adults (age 14 to 24 years, BMI ≥30 kg/m2) was recruited at four German university medical centers and one job center. Obesity grade groups (OGG) were defined according to BMI (OGG I 30-34.9 kg/m2, OGG II 35-39.9 kg/m2, OGG III (extreme obesity) ≥40 kg/m2). HRQoL was measured with the Euroqol-5D-3 L (EQ-5D-3 L), DISABKIDS chronic generic (DCGM-31) and the KINDLR obesity module. Differences between OGGs were assessed with logistic and linear regression models, adjusting for age, sex, and study center in the base model. In a second regression analysis, we included otherextreme obesity is particularly affected. Larger and longitudinal studies are necessary to understand the relation of extreme obesity and HRQoL, and the impact of other lifestyle or socioeconomic factors. TRIAL REGISTRATION Clinicaltrials.gov NCT01625325; German Clinical Trials Register (DRKS) DRKS00004172.BACKGROUND Clinical prediction tasks such as patient mortality, length of hospital stay, and disease diagnosis are highly important in critical care research. The existing studies for clinical prediction mainly used simple summary statistics to summarize information from physiological time series. However, this lack of statistics leads to a lack of information. In addition, using only maximum and minimum statistics to indicate patient features fails to provide an adequate explanation. Few studies have evaluated which summary statistics best represent physiological time series. METHODS In this paper, we summarize 14 statistics describing the characteristics of physiological time series, including the central tendency, dispersion tendency, and distribution shape. Then, we evaluate the use of summary statistics of physiological time series as features for three clinical prediction tasks. To find the combinations of statistics that yield the best performances under different tasks, we use a cross-validation-baseday prediction tasks, and they also provide information for short-term mortality prediction. Mean and quantiles that reflect the central tendency of physiological time series are more suitable for mortality and disease prediction. Skewness and kurtosis perform poorly when used separately for prediction but can be used as supplementary statistics to improve the overall prediction effect.BACKGROUND The present study aimed to verify whether long noncoding RNA (lncRNA) MALAT1 is involved in brain tissue damage induced by ischemia-reperfusion injury, and to explore the mechanism by which MALAT1 regulates aquaporin 4 (AQP4). METHODS In this study, we established glucose deprivation (OGD)/reoxygenation (RX) astrocyte cell model and middle cerebral artery occlusion (MCAO)/reperfusion mouse model in vitro and in vivo.  https://www.selleckchem.com/products/gf109203x.html  Then cell counting kit-8 assay, flow cytometry analysis, Triphenyltetrazolium chloride (TTC) staining, and western blotting were used to determine cell viability, cell apoptosis, cerebral infarction volume, and the abundance of AQP4, respectively. RESULTS We found that the level of MALAT1 was significantly upregulated in both the MCAO/reperfusion model and OGD/RX model. Knockdown of MALAT1 increased cell viability and reduced cell apoptosis in MA-C cells, while an AQP4 siRNA combined with a siRNA targeting MALAT1 could not enhance this effect. Further experiments showed that MALAT1 positively regulated AQP4 expression via miR-145. The MALAT1 siRNA did not alleviate the exacerbation of damage after miR-145 inhibitor action. However, an miR-145 inhibitor reversed the protection effects of MALAT1, indicating that MALAT1 silencing protects against cerebral ischemia-reperfusion injury through miR-145. TTC staining showed that the infracted area of whole brain was significantly attenuated in treated with sh-MALAT1 group in vivo. CONCLUSION Taken together, our study confirmed that MALAT1 promotes cerebral ischemia-reperfusion injury by affecting AQP4 expression through competitively binding miR-145, indicating that MALAT1 might be a new therapeutic target for treatment cerebral ischemic stroke.BACKGROUND In this systematic review we investigate which instrumented measurements are available to assess motor impairments, related activity limitations and participation restrictions in children and young adults with dyskinetic cerebral palsy. We aim to classify these instrumented measurements using the categories of the international classification of functioning, disability and health for children and youth (ICF-CY) and provide an overview of the outcome parameters. METHODS A systematic literature search was performed in November 2019. We electronically searched Pubmed, Embase and Scopus databases. Search blocks included (a) cerebral palsy, (b) athetosis, dystonia and/or dyskinesia, (c) age 2-24 years and (d) instrumented measurements (using keywords such as biomechanics, sensors, smartphone, and robot). RESULTS Our search yielded 4537 articles. After inspection of titles and abstracts, a full text of 245 of those articles were included and assessed for further eligibility. A total of 49 articles met ourometers). CONCLUSION Although the current review shows the potential of several instrumented methods to be used as objective outcome measures in dyskinetic cerebral palsy, their methodological quality is still unknown. Future development should focus on evaluating clinimetrics, including validating against clinical meaningfulness. New technological developments should aim for measurements that can be applied outside the laboratory.