Part regarding acetylation throughout doxorubicininduced cardiotoxicity

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Earthquakes are one of the most unpredictable natural disasters. A series of secondary and derived disaster events may occur afterwards and lead to even more consequences. In such situations, a seismic risk analysis that takes into account secondary and derived disaster events is vital in reducing the risks of such disasters. The absence of a holistic seismic risk analysis model-one that takes into account the derived disaster events-may mean that the serious consequences of the disaster chains set off by earthquakes are neglected. This article proposes a comprehensive seismic risk analysis that enables a better understanding of seismic disaster chains and rescue scenarios. The approach is based on a Bayesian network constructed using scenario-based methods. The final network structure is achieved by learning parameters. To determine the critical secondary disasters and the key emergency-response measures, probability adaptation and updating using the Bayesian model were performed. The practical application of the model is illustrated using the Wenchuan earthquake and the Jiuzhaigou earthquake in China. check details The two examples show that the model can be used to predict the potential effects of secondary disasters and the final seismic losses. The results of the model can help decisionmakers gain a comprehensive understanding of seismic risk and implement practical emergency-rescue measures to reduce risk and losses.Therapeutic drug monitoring (TDM) opens the door to personalized medicine, yet it is infrequently applied to β-lactam antibiotics, one of the most commonly prescribed drug classes in the hospital setting. As we continue to understand more about β-lactam pharmacodynamics (PD) and wide inter- and intra-patient variability in pharmacokinetics (PK), the utility of TDM has become increasingly apparent. For β-lactams, the time that free concentrations remain above the minimum inhibitory concentration (MIC) as a function of the dosing interval (%fT>MIC) has been shown to best predict antibacterial effect. Many studies have shown that β-lactam %fT>MIC exposures are often suboptimal across a wide variety of disease states and clinical settings. A limitation to implementing this practice is the general lack of understanding on how to best operationalize this intervention and interpret the results. The instrumentation and expertise needed to quantify β-lactams for TDM is rarely available locally, but certain laboratories advertise these services and perform them regularly. Familiarity with the modalities and nuances of antimicrobial susceptibility testing is crucial to establishing β-lactam concentration targets that meet the relevant exposure thresholds. Evaluation of these concentrations is best accomplished using population PK software and Bayesian modeling, for which a multitude of programs are available. While TDM of β-lactams has shown an ability to increase the rate of target attainment, there is currently limited evidence to suggest that it leads to improved clinical outcomes. Although consensus guidelines for β-lactam TDM do not exist in the United States, guidance would help to promote this important practice and better standardize the approach across institutions. Herein, we discuss the basis for β-lactam TDM, review supporting evidence, and provide guidance for implementation in specific patient populations.Biological response and DNA damage following irradiation with shorter wavelengths in the UV-C range were evaluated to investigate the safety at three wavelengths because of the recent emergence of germicidal equipment emitting short-wavelength UV-C for various purposes, including medical uses. To estimate an acceptable safety dose for human skin in the UV-C range, especially short UV-C, we studied the biological effects of 207, 222 and 235 nm UV-C using albino hairless mice and evaluated the inflammatory reactions in the skin. To explore an appropriate indicator to evaluate the biological response, we employed determination of the minimal perceptible response dose (MPRD), by which any subtle cutaneous response; erythema, edema and scale could be observed by visual inspection. Erythema was rarely observed, but edema and scale formation were evident for short UV-C wavelengths. The MPRD at 207, 222 and 235 nm was determined to be > 15, 15 and 2.0 kJ m-2 , respectively. These values could be thresholds and indicators for possible safety assessments. Our data suggest that the current human exposure limits for short UV-C wavelengths below 254 nm are overly restrictive and should be reconsidered for future disinfection lamps with short UV-C wavelengths.Progranulin (PGRN) is a secreted glycoprotein with multiple biological functions in early embryogenesis, anti-inflammation, and neurodegeneration. A good model for the functional study of PGRN is the zebrafish with knockdown or knockout of grn, the gene encoding PGRN. Morpholino oligonucleotides (MOs) and zinc finger nucleases have been used to generate zebrafish grn models, yet they have shown inconsistent phenotypes due to either the neurotoxicity of the MOs or possible genetic compensation responses during gene editing. In this study, we generated stable grna (one of the major grn homologues of zebrafish) knockout zebrafish by using CRISPR/Cas9-mediated genome editing. A grna sgRNA was designed to target the similar repeated sequence shared by exon 13, exon 15, and exon 19 in zebrafish. The F1 generation with the frameshift mutation of + 4 bp (the addition of 4 bp to exon15), which causes a premature termination, was obtained and subjected to morphological and behavioral evaluation. The grna knockout zebrafish showed neurodevelopmental defects, including spinal motor neurons with shorter axons, decreased sensory hair cells, thinning of the outer nuclear layer and thickening of the inner nuclear layer of the retina, decreased expression of rhodopsin in the cone cells, and motor behavior changes. Moreover, the phenotypes of grna knockout zebrafish could be rescued with the Tol2 system carrying the grna gene. The grna knockout zebrafish model generated in this study provides a useful tool to study PGRN function and has potential for high-throughput drug screening for disease therapy.