Background and Aims
Coronavirus disease 2019 (COVID‐19), the illness caused by the SARS‐CoV‐2 virus, is rapidly spreading throughout the world. Hospitals and healthcare providers are preparing for ...the anticipated surge in critically ill patients, but few are wholly equipped to manage this new disease. The goals of this document are to provide data on what is currently known about COVID‐19, and how it may impact hepatologists and liver transplant providers and their patients. Our aim is to provide a template for the development of clinical recommendations and policies to mitigate the impact of the COVID‐19 pandemic on liver patients and healthcare providers.
Approach and Results
This article discusses what is known about COVID‐19 with a focus on its impact on hepatologists, liver transplant providers, patients with liver disease, and liver transplant recipients. We provide clinicians with guidance for how to minimize the impact of the COVID‐19 pandemic on their patients’ care.
Conclusions
The situation is evolving rapidly, and these recommendations will need to evolve as well. As we learn more about how the COVID‐19 pandemic impacts the care of patients with liver disease, we will update the online document available at https://www.aasld.org/about-aasld/covid-19-and-liver.
An era of exploring the interactions of high-intensity, hard X-rays with matter has begun with the start-up of a hard-X-ray free-electron laser, the Linac Coherent Light Source (LCLS). Understanding ...how electrons in matter respond to ultra-intense X-ray radiation is essential for all applications. Here we reveal the nature of the electronic response in a free atom to unprecedented high-intensity, short-wavelength, high-fluence radiation (respectively 10(18) W cm(-2), 1.5-0.6 nm, approximately 10(5) X-ray photons per A(2)). At this fluence, the neon target inevitably changes during the course of a single femtosecond-duration X-ray pulse-by sequentially ejecting electrons-to produce fully-stripped neon through absorption of six photons. Rapid photoejection of inner-shell electrons produces 'hollow' atoms and an intensity-induced X-ray transparency. Such transparency, due to the presence of inner-shell vacancies, can be induced in all atomic, molecular and condensed matter systems at high intensity. Quantitative comparison with theory allows us to extract LCLS fluence and pulse duration. Our successful modelling of X-ray/atom interactions using a straightforward rate equation approach augurs favourably for extension to complex systems.
This review summarises genetic studies in which calcium channel genes have been connected to the spectrum of neuropsychiatric syndromes, from bipolar disorder and schizophrenia to autism spectrum ...disorders and intellectual impairment. Among many other genes, striking numbers of the calcium channel gene superfamily have been implicated in the aetiology of these diseases by various DNA analysis techniques. We will discuss how these relate to the known monogenic disorders associated with point mutations in calcium channels. We will then examine the functional evidence for a causative link between these mutations or single nucleotide polymorphisms and the disease processes. A major challenge for the future will be to translate the expanding psychiatric genetic findings into altered physiological function, involvement in the wider pathology of the diseases, and what potential that provides for personalised and stratified treatment options for patients.
This paper investigates anaerobic co-digestion of pig manure and algae (Scenedesmus sp.) with and without extraction of intracellular algal co-products, with views towards the development of a ...biorefinery concept for lipid, protein and/or biogas production. Protein and/or lipids were extracted from Scenedesmus sp. using free nitrous acid pre-treatments and solvent-based Soxhlet extraction, respectively. Processing increased algae methane yield between 29% and 37% compared to raw algae (VS basis), but reduced the amount of algae available for digestion. Co-digestion experiments showed a synergy between pig manure and raw algae that increased raw algae methane yield from 0.163 to 0.245 m(3) CH4 kg(-1)VS. No such synergy was observed when algal residues were co-digested with pig manure. Finally, experimental results were used to develop a high-level concept for an integrated biorefinery processing pig manure and onsite cultivated algae, evaluating methane production and co-product recovery per mass of pig manure entering the refinery.
Mass spectrometry (MS)-based targeted lipidomics enables the robust quantification of selected lipids under various biological conditions but comprehensive software tools to support such analyses are ...lacking. Here we present LipidCreator, a software that fully supports targeted lipidomics assay development. LipidCreator offers a comprehensive framework to compute MS/MS fragment masses for over 60 lipid classes. LipidCreator provides all functionalities needed to define fragments, manage stable isotope labeling, optimize collision energy and generate in silico spectral libraries. We validate LipidCreator assays computationally and analytically and prove that it is capable to generate large targeted experiments to analyze blood and to dissect lipid-signaling pathways such as in human platelets.
Context:
Bariatric surgery is increasingly popular but may lead to metabolic bone disease.
Objective:
The objective was to determine the rate of bone loss in the 24 months after Roux-en-Y gastric ...bypass.
Design and Setting:
This was a prospective cohort study conducted at an academic medical center.
Participants:
The participants were adults with severe obesity, including 30 adults undergoing gastric bypass and 20 nonsurgical controls.
Outcomes:
We measured bone mineral density (BMD) at the lumbar spine and proximal femur by quantitative computed tomography (QCT) and dual-energy x-ray absorptiometry at 0, 12, and 24 months. BMD and bone microarchitecture were also assessed by high-resolution peripheral QCT, and estimated bone strength was calculated using microfinite element analysis.
Results:
Weight loss plateaued 6 months after gastric bypass but remained greater than controls at 24 months (−37 ± 3 vs −5 ± 3 kg mean ± SEM; P < .001). At 24 months, BMD was 5–7% lower at the spine and 6–10% lower at the hip in subjects who underwent gastric bypass compared with nonsurgical controls, as assessed by QCT and dual-energy x-ray absorptiometry (P < .001 for all). Despite significant bone loss, average T-scores remained in the normal range 24 months after gastric bypass. Cortical and trabecular BMD and microarchitecture at the distal radius and tibia deteriorated in the gastric bypass group throughout the 24 months, such that estimated bone strength was 9% lower than controls. The decline in BMD persisted beyond the first year, with rates of bone loss exceeding controls throughout the second year at all skeletal sites. Mean serum calcium, 25(OH)-vitamin D, and PTH were maintained within the normal range in both groups.
Conclusions:
Substantial bone loss occurs throughout the 24 months after gastric bypass despite weight stability in the second year. Although the benefits of gastric bypass surgery are well established, the potential for adverse effects on skeletal integrity remains an important concern.
This work focuses on fermentation of pre-treated waste activated sludge (WAS) to generate volatile fatty acids (VFAs). Pre-treatment by high-pressure thermal hydrolysis (HPTH) was shown to aid WAS ...fermentation. Compared to fermentation of raw WAS, pre-treatment enabled a 2–5x increase in VFA yield (gVFACODgTCOD−1) and 4–6x increase in VFA production rate (gVFACODL−1d−1).
Three sludges, pre-treated in full-scale HPTH plants, were fermented. One was from a plant processing a mix of primary sludge and WAS and the other two from plants processing solely WAS. The HPTH plants solubilised suspended matter, evidenced by a 20–30% decrease in suspended solids and an increase of soluble COD : total COD from 0.04 to 0.4. Fermentation of the three sludges yielded similar VFA concentrations (15–20gVFACODL−1). The yields were largely independent of retention time (1d–6d) and temperature (42°C, 55°C). Also, the product spectrum depended mostly on the composition of the sludge rather than on operating conditions.
Ca V1 and Ca V2 voltage-gated calcium channels are associated with β and α ₂δ accessory subunits. However, examination of cell surface-associated Ca V2 channels has been hampered by the lack of ...antibodies to cell surface-accessible epitopes and of functional exofacially tagged Ca V2 channels. Here we report the development of fully functional Ca V2.2 constructs containing inserted surface-accessible exofacial tags, which allow visualization of only those channels at the plasma membrane, in both a neuronal cell line and neurons. We first examined the effect of the auxiliary subunits. Although α ₂δ subunits copurify with Ca V2 channels, it has recently been suggested that this interaction is easily disrupted and nonquantitative. We have now tested whether α ₂δ subunits are associated with these channels at the cell surface. We found that, whereas α ₂δ-1 is readily observed at the plasma membrane when expressed alone, it appears absent when coexpressed with Ca V2.2/β1b, despite our finding that α ₂δ-1 increases plasma-membrane Ca V2.2 expression. However, this was due to occlusion of the antigenic epitope by association with Ca V2.2, as revealed by antigen retrieval; thus, our data provide evidence for a tight interaction between α ₂δ-1 and the α ₁ subunit at the plasma membrane. We further show that, although Ca V2.2 cell-surface expression is reduced by gabapentin in the presence of wild-type α ₂δ-1 (but not a gabapentin-insensitive α ₂δ-1 mutant), the interaction between Ca V2.2 and α ₂δ-1 is not disrupted by gabapentin. Altogether, these results demonstrate that Ca V2.2 and α ₂δ-1 are intimately associated at the plasma membrane and allow us to infer a region of interaction.
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