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ObjectivesThe aim of this study was to develop the Remote Health Value Framework to evaluate the models of healthcare provision for workers in the oil and gas sector, predominantly situated in rural and remote areas.MethodsThe framework was co-designed with the leadership team in one global oil and gas company using a multi-criteria decision analysis approach with a conjoint analysis component. This was used to elicit and understand preferences and trade-offs among different value domains that were important to the stakeholders with respect to the provision of healthcare for its workers. Preference elicitation and interviews were conducted with a mix of health, safety, and environment (HSE) team and non-HSE managers and leaders.ResultsOut of five presented value domains, participants considered the attribute 'Improving health outcomes of employees' the most important aspect for the model of healthcare which accounted for 37.3% of the total utility score. Alternatively, the 'Program cost' attribute was least important to the participants, accounting for only 11.0% of the total utility score. The marginal willingness-to-pay analysis found that participants would be willing to pay A$9090 per utile for an improvement in a particular value attribute.ConclusionsThis is the first value framework for healthcare delivery in the oil and gas industry, contextualised by its delivery within rural and remote locations. It provides a systematic and transparent method for creating value-based healthcare models. This approach facilitates the evaluation of healthcare investments, ensuring they align with value domains prioritised by the HSE and leadership teams.

In cells, the breakdown of arginine to ornithine and ammonium ion plus carbon dioxide is coupled to the generation of metabolic energy in the form of ATP. The arginine breakdown pathway is minimally composed of arginine deiminase, ornithine transcarbamoylase, carbamate kinase, and an arginine/ornithine antiporter; ammonia and carbon dioxide most likely diffuse passively across the membrane. The genes for the enzymes and transporter have been cloned and expressed, and the proteins have been purified from Lactococcus lactis IL1403 and incorporated into lipid vesicles for sustained production of ATP. Here, we study the kinetic parameters and biochemical properties of the individual enzymes and the antiporter, and we determine how the physicochemical conditions, effector composition, and effector concentration affect the enzymes. We report the K M and V MAX values for catalysis and the native oligomeric state of all proteins, and we measured the effect of pathway intermediates, pH, temperature, freeze-thaw cycles, and salts on the activity of the cytosolic enzymes. We also present data on the protein-to-lipid ratio and lipid composition dependence of the antiporter., (© 2020 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

We are aiming for a blue print for synthesizing (moderately complex) subcellular systems from molecular components and ultimately for constructing life. However, without comprehensive instructions and design principles, we rely on simple reaction routes to operate the essential functions of life. The first forms of synthetic life will not make every building block for polymers de novo according to complex pathways, rather they will be fed with amino acids, fatty acids and nucleotides. Controlled energy supply is crucial for any synthetic cell, no matter how complex. Herein, we describe the simplest pathways for the efficient generation of ATP and electrochemical ion gradients. We have estimated the demand for ATP by polymer synthesis and maintenance processes in small cell-like systems, and we describe circuits to control the need for ATP. We also present fluorescence-based sensors for pH, ionic strength, excluded volume, ATP/ADP, and viscosity, which allow the major physicochemical conditions inside cells to be monitored and tuned., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

One of the grand challenges in chemistry is the construction of functional out-of-equilibrium networks, which are typical of living cells. Building such a system from molecular components requires control over the formation and degradation of the interacting chemicals and homeostasis of the internal physical-chemical conditions. The provision and consumption of ATP lies at the heart of this challenge. Here we report the in vitro construction of a pathway in vesicles for sustained ATP production that is maintained away from equilibrium by control of energy dissipation. We maintain a constant level of ATP with varying load on the system. The pathway enables us to control the transmembrane fluxes of osmolytes and to demonstrate basic physicochemical homeostasis. Our work demonstrates metabolic energy conservation and cell volume regulatory mechanisms in a cell-like system at a level of complexity minimally needed for life.

Niosomes are used in studies for drug delivery or gene transfer. However, their physical properties and features relative to liposomes are not well documented. To characterize and more rationally optimize niosome formulations, the properties of these vesicle systems are compared to those of liposomes composed of phosphatidylcholine and phosphatidylethanolamine lipids plus cholesterol. Niosomes are highly stable and only slightly more leaky than liposomes as assayed by calcein leakage; the permeability for ions (KCl) is higher than that of liposomes. Contrary to liposomes, the size of niosomes decreases substantially upon freezing in liquid nitrogen and subsequent thawing, as shown by cryo-EM and dynamic light scattering. The packing of niosomal membranes was determined by laurdan fluorescence and is slightly lower than that of liposomes. We did not succeed in the functional reconstitution of the L-arginine/L-ornithine antiporter ArcD2 in niosomes, which we attribute to the non-ionic nature of the surfactants. The antimicrobial peptides alamethicin and melittin act similarly on niosomes and liposomes composed of unsaturated components, whereas both niosomes and liposomes are unaffected when saturated amphiphiles are used. In conclusion, in terms of stability and permeability for drug-size molecules niosomes are comparable to liposomes and they may offer an excellent, inexpensive alternative for delivery purposes.

The import of basic amino acids in Saccharomyces cerevisiae has been reported to be unidirectional, which is not typical of how secondary transporters work. Since studies of energy coupling and transport kinetics are complicated in vivo, we purified the major lysine transporter (Lyp1) of yeast and reconstituted the protein into lipid vesicles. We show that the Michaelis constant (KM) of transport from out-to-in is well in the millimolar range and at least 3 to 4-orders of magnitude higher than that of transport in the opposite direction, disfavoring the efflux of solute via Lyp1. We also find that at low values of the proton motive force, the transport by Lyp1 is comparatively slow. We benchmarked the properties of eukaryotic Lyp1 to that of the prokaryotic homologue LysP and find that LysP has a similar KM for transport from in-to-out and out-to-in, consistent with rapid influx and efflux. We thus explain the previously described unidirectional nature of lysine transport in S. cerevisiae by the extraordinary kinetics of Lyp1 and provide a mechanism and rationale for previous observations. The high asymmetry in transport together with secondary storage in the vacuole allow the cell to accumulate basic amino acids to very high levels.

Background: (HSV) infection in neonates is rare. This infection is generally considered when there is a history of contact with a person who has a cold sore or when the mother has active genital herpes., Case Description: A 7-day-old female was admitted to hospital on suspicion of sepsis. Aciclovir was considered, but ultimately not given due to low suspicion of herpes infection. Her clinical situation deteriorated within a couple of days. Due to the advanced liver damage, the disease had a fulminant course and the patient died., Conclusion: Even without evidence of contact with HSV in the history, it is important to start acyclovir early in neonates with fever of unknown origin. A rare clinical presentation is acute liver failure. HSV infection can run a serious course in neonates; therefore, aciclovir should be started immediately if there is any suspicion.

Incretin-based therapies have shown promise in the treatment of type 2 diabetes. Here we review our current understanding of TGR5 as a target to induce glucagon-like peptide-1 (GLP-1) secretion. These new observations suggest that TGR5 agonists may constitute a novel approach to treat type 2 diabetes, as well as complications of diabetes, such as non-alcoholic fatty liver disease., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Objective: To establish the prevalence of voiding symptoms in CPP patients., Study Design: Sixty women with chronic pelvic pain (CPP), aged 23-79 (mean: 48) years completed a questionnaire mainly addressing lower abdominal pain and voiding symptoms. Symptoms occurring often, almost always, or always for more than 6 months were considered present and serious. A group of 31 consecutive cases of non-CPP women aged 18-77 (mean: 49) years were selected to serve as controls., Results: The following symptoms were found in the CPP group: incontinence: 43%; inadequate voluntary control of the urethral sphincter: 50%; inability to postpone: 37%; urge: 37%; nocturia > or =2X: 18%; dysuria: 12%; cystitis: 37%; urge-induced pain: 20%; pain-induced urge: 18%; strain to initiate voiding: 6%; strain to continue voiding: 17%; incomplete voiding: 37%. Two or more voiding symptoms were present in 63% of the CPP group. All urinary symptoms were more often present in the CPP group than in the controls., Conclusion: A substantial subgroup of CPP patients has voiding symptoms., (Copyright 2002 Elsevier Science Ireland Ltd.)

Objectives: No standard screening instrument is available enabling physicians to assign the diagnosis chronic pelvic pain (CPP) to women with lower abdominal pain. Therefore, our aim was to evaluate an easy-to-use questionnaire, which can be applied as a validated primary screening test for diagnosing CPP., Study Design: From the general female population, 577 women completed a questionnaire addressing chronic symptoms in the pelvic region. Included were (amongst others) questions on lower abdominal pain, low back pain, voiding symptoms, dyspareunia, pelveo-perineal dysesthetic feelings and evacuation problems. Serious chronic lower abdominal pain of unknown origin was considered as CPP. Three criteria were applied to validate the questionnaire: construct validity, comparison with results of a previous study and content validity. In addition, the internal consistency was checked to ascertain the reliability of the questionnaire., Results: All items, with the exception of those concerning voiding symptoms and dyspareunia, withstood the validity tests applied, were interrelated and occurred significantly more often in women with CPP than those without. There were no significant differences in the frequency of the occurrence of low back pain, dyspareunia and evacuation problems between CPP women in the current community study and outpatients diagnosed with CPP in an earlier study performed at the University Hospital Rotterdam. Compared to our current study group, pelveo-perineal dysesthesia (PPD) and voiding symptoms were significantly more often reported by the CPP outpatients., Conclusion: The CPP questionnaire can be considered as a validated tool for primary screening of CPP.