Early postoperative feeding following surgery for upper gastrointestinal cancer: A systematic review.

Nutrition post major upper gastrointestinal (UGI) cancer surgery is a significant consideration known to affect postoperative recovery and the ability to tolerate adjuvant treatment. This systematic review assessed the effect of early oral feeding (EOF), compared to traditional timing of oral feeding, following major surgery for UGI cancer on postoperative complications, postoperative length of hospital stay (LOS), nutritional status and quality of life (QOL). The literature was searched up to March 9th 2020 using CINHAL, PubMed, MEDLINE, Embase, Scopus and Web of Science databases. Quality assessment was completed using the Academy of Nutrition and Dietetics quality criteria checklist. Fifteen articles were included, consisting of seven randomised controlled trials, six cohort studies and two non-randomised trials, with a total of 2517 participants. The type and timing of EOF varied considerably across studies with limited reporting of energy and protein intakes from oral or enteral feeding. Fourteen studies assessed postoperative complications of which 13 reported no difference between EOF and standard care. Fourteen studies assessed postoperative LOS and of these, 13 reported a reduced length of stay in the EOF group. Four of 15 studies assessing nutritional status found no difference between groups. Three of 15 studies assessed QOL with inconsistent findings. This review found EOF reduced postoperative LOS and did not increase postoperative complications. However, the optimal timing for the introduction of EOF could not be established. Furthermore, the type of EOF varied considerably making comparison across studies challenging and demonstrates a need for internationally standardised definitions.

Coastal sea level rise with warming above 2 °C.

Two degrees of global warming above the preindustrial level is widely suggested as an appropriate threshold beyond which climate change risks become unacceptably high. This "2 °C" threshold is likely to be reached between 2040 and 2050 for both Representative Concentration Pathway (RCP) 8.5 and 4.5. Resulting sea level rises will not be globally uniform, due to ocean dynamical processes and changes in gravity associated with water mass redistribution. Here we provide probabilistic sea level rise projections for the global coastline with warming above the 2 °C goal. By 2040, with a 2 °C warming under the RCP8.5 scenario, more than 90% of coastal areas will experience sea level rise exceeding the global estimate of 0.2 m, with up to 0.4 m expected along the Atlantic coast of North America and Norway. With a 5 °C rise by 2100, sea level will rise rapidly, reaching 0.9 m (median), and 80% of the coastline will exceed the global sea level rise at the 95th percentile upper limit of 1.8 m. Under RCP8.5, by 2100, New York may expect rises of 1.09 m, Guangzhou may expect rises of 0.91 m, and Lagos may expect rises of 0.90 m, with the 95th percentile upper limit of 2.24 m, 1.93 m, and 1.92 m, respectively. The coastal communities of rapidly expanding cities in the developing world, and vulnerable tropical coastal ecosystems, will have a very limited time after midcentury to adapt to sea level rises unprecedented since the dawn of the Bronze Age.

A Structural, Functional, and Computational Analysis of BshA, the First Enzyme in the Bacillithiol Biosynthesis Pathway.

Bacillithiol is a compound produced by several Gram-positive bacterial species, including the human pathogens Staphylococcus aureus and Bacillus anthracis. It is involved in maintaining cellular redox balance as well as the destruction of reactive oxygen species and harmful xenobiotic agents, including the antibiotic fosfomycin. BshA, BshB, and BshC are the enzymes involved in bacillithiol biosynthesis. BshA is a retaining glycosyltransferase responsible for the first committed step in bacillithiol production, namely the addition of N-acetylglucosamine to l-malate. Retaining glycosyltransferases like BshA are proposed to utilize an SNi-like reaction mechanism in which leaving group departure and nucleophilic attack occur on the same face of the hexose. However, significant questions regarding the details of how BshA and similar enzymes accommodate their substrates and facilitate catalysis persist. Here we report X-ray crystallographic structures of BshA from Bacillus subtilis 168 bound with UMP and/or GlcNAc-mal at resolutions of 2.15 and 2.02 Å, respectively. These ligand-bound structures, along with our functional and computational studies, provide clearer insight into how BshA and other retaining GT-B glycosyltransferases operate, corroborating the substrate-assisted, SNi-like reaction mechanism. The analyses presented herein can serve as the basis for the design of inhibitors capable of preventing bacillithiol production and, subsequently, help combat resistance to fosfomycin in various pathogenic Gram-positive microorganisms.

Fever and Leukocytosis Are Poor Predictors of Bacterial Coinfection in Patients With COVID-19 and Influenza Who Are Receiving Extracorporeal Membrane Oxygenation.

Background: Fever and leukocytosis are 2 parameters commonly cited in clinical practice as indications to perform an infectious workup in patients receiving extracorporeal membrane oxygenation (ECMO), but their utility is unknown. Methods: All patients who received ECMO between December 2014 and December 2020 with influenza or COVID-19 were included in this retrospective cohort study. Cultures were included if they were drawn from patients without signs of decompensation. Maximum temperature and white blood cell count were recorded on the day of culture collection. Workups with infections were compared with those that were negative. Results: Of the 137 infectious workups in this 45-patient cohort, 86 (63%) were performed in patients with no signs of decompensation, totaling 165 cultures. These workups yielded 10 (12%) true infections. There were no differences in median (IQR) temperature (100.4 °F [100.2-100.8] vs 100.4 °F [99.3-100.9], P = .90) or white blood cell count (18.6 cells/mL [16.8-20.1] vs 16.7 cells/mL [12.8-22.3], P = .90) between those with and without infections. Conclusions: In patients with influenza or COVID-19 who require ECMO, fever and leukocytosis were common indications for infectious workups, yet results were frequently negative. Despite their use in clinical practice, fever and leukocytosis are not reliable indicators of infection in patients who are hemodynamically stable and receiving ECMO.

Use of multimodality imaging, histology, and treatment feasibility to characterize a transgenic Rag2-null rat model of glioblastoma.

Many drugs that show potential in animal models of glioblastoma (GBM) fail to translate to the clinic, contributing to a paucity of new therapeutic options. In addition, animal model development often includes histologic assessment, but multiparametric/multimodality imaging is rarely included despite increasing utilization in patient cancer management. This study developed an intracranial recurrent, drug-resistant, human-derived glioblastoma tumor in Sprague-Dawley Rag2-Rag2 tm1Hera knockout rat and was characterized both histologically and using multiparametric/multimodality neuroimaging. Hybrid 18F-fluoroethyltyrosine positron emission tomography and magnetic resonance imaging, including chemical exchange saturation transfer (18F-FET PET/CEST MRI), was performed for full tumor viability determination and characterization. Histological analysis demonstrated human-like GBM features of the intracranially implanted tumor, with rapid tumor cell proliferation (Ki67 positivity: 30.5 ± 7.8%) and neovascular heterogeneity (von Willebrand factor VIII:1.8 to 5.0% positivity). Early serial MRI followed by simultaneous 18F-FET PET/CEST MRI demonstrated consistent, predictable tumor growth, with exponential tumor growth most evident between days 35 and 49 post-implantation. In a second, larger cohort of rats, 18F-FET PET/CEST MRI was performed in mature tumors (day 49 post-implantation) for biomarker determination, followed by evaluation of single and combination therapy as part of the model development and validation. The mean percentage of the injected dose per mL of 18F-FET PET correlated with the mean %CEST (r = 0.67, P < 0.05), but there was also a qualitative difference in hot spot location within the tumor, indicating complementary information regarding the tumor cell demand for amino acids and tumor intracellular mobile phase protein levels. Finally, the use of this glioblastoma animal model for therapy assessment was validated by its increased overall survival after treatment with combination therapy (temozolomide and idasanutlin) (P < 0.001). Our findings hold promise for a more accurate tumor viability determination and novel therapy assessment in vivo in a recently developed, reproducible, intracranial, PDX GBM.

Engineered microbial biofuel production and recovery under supercritical carbon dioxide.

Culture contamination, end-product toxicity, and energy efficient product recovery are long-standing bioprocess challenges. To solve these problems, we propose a high-pressure fermentation strategy, coupled with in situ extraction using the abundant and renewable solvent supercritical carbon dioxide (scCO2), which is also known for its broad microbial lethality. Towards this goal, we report the domestication and engineering of a scCO2-tolerant strain of Bacillus megaterium, previously isolated from formation waters from the McElmo Dome CO2 field, to produce branched alcohols that have potential use as biofuels. After establishing induced-expression under scCO2, isobutanol production from 2-ketoisovalerate is observed with greater than 40% yield with co-produced isopentanol. Finally, we present a process model to compare the energy required for our process to other in situ extraction methods, such as gas stripping, finding scCO2 extraction to be potentially competitive, if not superior.

Global probabilistic projections of extreme sea levels show intensification of coastal flood hazard.

Global warming is expected to drive increasing extreme sea levels (ESLs) and flood risk along the world's coastlines. In this work we present probabilistic projections of ESLs for the present century taking into consideration changes in mean sea level, tides, wind-waves, and storm surges. Between the year 2000 and 2100 we project a very likely increase of the global average 100-year ESL of 34-76 cm under a moderate-emission-mitigation-policy scenario and of 58-172 cm under a business as usual scenario. Rising ESLs are mostly driven by thermal expansion, followed by contributions from ice mass-loss from glaciers, and ice-sheets in Greenland and Antarctica. Under these scenarios ESL rise would render a large part of the tropics exposed annually to the present-day 100-year event from 2050. By the end of this century this applies to most coastlines around the world, implying unprecedented flood risk levels unless timely adaptation measures are taken.