A Rare Case of Propofol-Induced Acute Liver Failure and Literature Review

The incidence of drug-induced acute liver failure is increasing. A number of drugs can inhibit mitochondrial functions, alter β-oxidation and cause accumulation of free fatty acids within the hepatocytes. This may result in hepatic steatosis, cell death and liver injury. In our case, propofol, an anesthetic drug commonly used in adults and children, is suspected to have induced disturbance of the mitochondrial respiratory chain, which in consequence led to insufficient energy supply and finally liver failure. We report the case of a 35-year-old Caucasian woman with acute liver failure after anesthesia for stripping of varicose veins. Liver histology, imaging and laboratory data indicate drug-induced acute liver failure, presumably due to propofol. Hepatocyte death and microvesicular fatty degeneration of 90% of the liver parenchyma were observed before treatment with steroids. Six months later, a second biopsy was performed, which revealed only minimal steatosis and minimal periportal hepatitis. We suggest that propofol led to impaired fatty acid oxidation possibly due to a genetic susceptibility. This caused free fatty acid accumulation within hepatocytes, which presented as hepatocellular fatty degeneration and cell death. Large scale hepatocyte death was followed by impaired liver function and, consecutively, progressed to acute liver failure

Production of D-Glyceric Acid by a Two-step Culture Strategy Based on Whole-cell Biocatalysis of Acetobacter tropicalis

D-Glyceric acid (D-GA) is a promising chemical for minimizing the toxic effect of acetaldehyde. It has been successfully produced by bioprocesses using glycerol as a substrate. However, high concentrations of glycerol are not beneficial for cell growth. A two-step culture strategy was employed to deal with the ambivalent culture conditions between the growth of Acetobacter tropicalis and the biosynthesis of D-GA. The first stage focuses on biomass accumulation with low initial glycerol concentration; the second stage provides D-GA accumulation through whole-cell biocatalysis. Approximately 2-fold of D-GA yield and 4.5-fold of D-GA productivity were gained by the two-step culture strategy compared to the traditional fermentation with 150 g L–1 of glycerol. Our results also showed that A. tropicalis was able to catalyze the conversion of glycerol to D-GA in the presence of up to 10 % methanol. These findings have important implications to enhance D-GA yield by strategy optimization and reduce its cost. This work is licensed under a Creative Commons Attribution 4.0 International License

Predictive preoperative clinical score for patients with liver-only oligometastatic colorectal cancer

BACKGROUND: Resection of liver metastases from colorectal cancer (CRC) in the oligometastatic stage improves survival and is a potentially curative treatment. Thus, predictive scores that reliably identify those patients who especially benefit from surgery are essential. PATIENTS AND METHODS: In this multicenter analysis, 512 patients had undergone surgery for liver metastases from CRC. We investigated distinct cancer-specific risk factors that are routinely available in clinical practice and developed a predictive preoperative score using a training cohort (TC), which was thereafter tested in a validation cohort (VC). RESULTS: Inflammatory response to the tumor, a right-sided primary tumor, multiple liver metastases, and node-positive primary tumor were significant adverse variables for overall survival (OS). Patients were stratified in five groups according to the cumulative score given by the presence of these risk factors. Median OS for patients without risk factors was 133.8 months [95% confidence interval (CI) 81.2-not reached (nr)] in the TC and was not reached in the VC. OS decreased significantly for each subsequent group with increasing number of risk factors. Median OS was significantly shorter (P < 0.0001) for patients presenting all four risk factors: 14.3 months (95% CI 10.5 months-nr) in the TC and 16.6 months (95% CI 14.6 months-nr) in the VC. CONCLUSIONS: Including easily obtainable variables, this preoperative score identifies oligometastatic CRC patients with prolonged survival rates that may be cured, and harbors potential to be implemented in daily clinical practice

Negative Refraction Angular Characterization in One-Dimensional Photonic Crystals

Background: Photonic crystals are artificial structures that have periodic dielectric components with different refractive indices. Under certain conditions, they abnormally refract the light, a phenomenon called negative refraction. Here we experimentally characterize negative refraction in a one dimensional photonic crystal structure; near the low frequency edge of the fourth photonic bandgap. We compare the experimental results with current theory and a theory based on the group velocity developed here. We also analytically derived the negative refraction correctness condition that gives the angular region where negative refraction occurs. Methodology/Principal Findings: By using standard photonic techniques we experimentally determined the relationship between incidence and negative refraction angles and found the negative refraction range by applying the correctness condition. In order to compare both theories with experimental results an output refraction correction was utilized. The correction uses Snell’s law and an effective refractive index based on two effective dielectric constants. We found good agreement between experiment and both theories in the negative refraction zone. Conclusions/Significance: Since both theories and the experimental observations agreed well in the negative refraction region, we can use both negative refraction theories plus the output correction to predict negative refraction angles. This can be very useful from a practical point of view for space filtering applications such as a photonic demultiplexer or fo

Interferon alfa for chronic hepatitis B infection: Increased efficacy of prolonged treatment

Interferon alfa (IFN-a) is the primary treatment for chronic hepatitis B. The standard duration of IFN-a therapy is considered 16 weeks; however, the optimal treatment length is still poorly defined. We evaluated the efficacy and acceptability of prolonged IFN-a treatment in patients with chronic hepatitis B. To investigate whether treatment prolongation could enhance the rate of hepatitis B e antigen (HBeAg) seroconversion, we conducted a prospective, controlled, multicenter trial in wh

Reviews and syntheses : Turning the challenges of partitioning ecosystem evaporation and transpiration into opportunities

Evaporation (E) and transpiration (T) respond differently to ongoing changes in climate, atmospheric composition, and land use. It is difficult to partition ecosystem-scale evapotranspiration (ET) measurements into E and T, which makes it difficult to validate satellite data and land surface models. Here, we review current progress in partitioning E and T and provide a prospectus for how to improve theory and observations going forward. Recent advancements in analytical techniques create new opportunities for partitioning E and T at the ecosystem scale, but their assumptions have yet to be fully tested. For example, many approaches to partition E and T rely on the notion that plant canopy conductance and ecosystem water use efficiency exhibit optimal responses to atmospheric vapor pressure deficit (D). We use observations from 240 eddy covariance flux towers to demonstrate that optimal ecosystem response to D is a reasonable assumption, in agreement with recent studies, but more analysis is necessary to determine the conditions for which this assumption holds. Another critical assumption for many partitioning approaches is that ET can be approximated as T during ideal transpiring conditions, which has been challenged by observational studies. We demonstrate that T can exceed 95% of ET from certain ecosystems, but other ecosystems do not appear to reach this value, which suggests that this assumption is ecosystem-dependent with implications for partitioning. It is important to further improve approaches for partitioning E and T, yet few multi-method comparisons have been undertaken to date. Advances in our understanding of carbon-water coupling at the stomatal, leaf, and canopy level open new perspectives on how to quantify T via its strong coupling with photosynthesis. Photosynthesis can be constrained at the ecosystem and global scales with emerging data sources including solar-induced fluorescence, carbonyl sulfide flux measurements, thermography, and more. Such comparisons would improve our mechanistic understanding of ecosystem water fluxes and provide the observations necessary to validate remote sensing algorithms and land surface models to understand the changing global water cycle.Peer reviewe

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Crystal structure of the CusBA heavy-metal efflux complex of Escherichia coli

Gram-negative bacteria, such as Escherichia coli, expel toxic chemicals via tripartite efflux pumps spanning both the inner and outer membranes. The three parts are: 1) a membrane fusion protein connecting 2) a substrate-binding inner membrane transporter to 3) an outer membrane-anchored channel in the periplasmic space. A crystallographic model of this tripartite efflux complex has been unavailable simply because co-crystallization of different components of the system has proven to be extremely difficult. We previously described the crystal structures of both the inner membrane transporter CusA1 and membrane fusion protein CusB2 of the CusCBA efflux system3,4 from E. coli. We here report the co-crystal structure of the CusBA efflux complex, revealing the trimeric CusA efflux pump interacts with six CusB protomers at the upper half of the periplasmic domain. These six CusB molecules form a channel extending contiguously from the top of the pump. The affinity of the CusA and CusB interaction was found to be in the micromolar range. Finally, we predicted a three-dimensional structure of the trimeric CusC outer membrane channel, and develop a model of the tripartite efflux assemblage. This CusC3-CusB6-CusA3 model presents a 750 kDa efflux complex spanning the entire bacterial cell envelope to export Cu(I)/Ag(I) ions