Risk stratification for the development of chronic postsurgical pain

Chronic postsurgical pain (CPSP) is a common complication of surgery with important consequences for the individual patient and society as a whole. Risk stratification is best defined as the grouping of patients based on factors measured at baseline (in this context before surgery), to determine an individual's risk of suffering a particular condition and thereby the likely level of need for preventive interventions. Risk factors for CPSP have been identified in the preoperative, intraoperative, and postoperative periods and cover 6 broad domains: genetic, demographic, psychosocial, pain, clinical, and surgical factors. Risk stratification for CPSP enables clinicians to address these risk factors before surgery, to discuss the necessity of surgery or to change the surgical and anaesthetic/analgesic planning

Assessment of chronic postsurgical pain after knee replacement : a systematic review

Objective: Approximately 20% of patients experience chronic pain after total knee replacement (TKR), yet there is no consensus about how best to assess such pain. This systematic review aimed to identify measures used to characterise chronic pain after TKR. Methods: MEDLINE, Embase, PsycINFO, Cochrane Library and CINAHL databases were searched for research articles published in all languages from January 2002- November 2011. Articles were eligible for inclusion if they assessed knee pain at a minimum of 3-months after TKR, yielding a total of 1,164 articles. Data extracted included study design, country, timings of assessments, and outcome measures containing pain items. Outcome measures were compared with domains recommended by IMMPACT for inclusion in assessment of chronic pain related outcomes within clinical trials. Temporal trends were also explored. Results: The review found use of a wide variety of composite and single-item measures, with the American Knee Society Score most common. Many measures used in published studies do not capture the multi-dimensional nature of pain recommended by IMMPACT; of those commonly used, the WOMAC and Oxford Knee Score are most comprehensive. Geographical trends were evident, with nation-specific preferences for particular measures. A recent reduction in use of some clinically-administered tools was accompanied by increased use of patient-reported outcome measures. Conclusion: There was wide variation in methods of pain assessment alongside nation-specific preferences and changing temporal trends in pain assessment after TKR. Standardisation and improvements in assessment is needed to enhance the quality of research and facilitate the establishment of a core outcome set

Native structure-based modeling and simulation of biomolecular systems per mouse click

Background Molecular dynamics (MD) simulations provide valuable insight into biomolecular systems at the atomic level. Notwithstanding the ever-increasing power of high performance computers current MD simulations face several challenges: the fastest atomic movements require time steps of a few femtoseconds which are small compared to biomolecular relevant timescales of milliseconds or even seconds for large conformational motions. At the same time, scalability to a large number of cores is limited mostly due to long-range interactions. An appealing alternative to atomic-level simulations is coarse-graining the resolution of the system or reducing the complexity of the Hamiltonian to improve sampling while decreasing computational costs. Native structure-based models, also called Gō-type models, are based on energy landscape theory and the principle of minimal frustration. They have been tremendously successful in explaining fundamental questions of, e.g., protein folding, RNA folding or protein function. At the same time, they are computationally sufficiently inexpensive to run complex simulations on smaller computing systems or even commodity hardware. Still, their setup and evaluation is quite complex even though sophisticated software packages support their realization. Results Here, we establish an efficient infrastructure for native structure-based models to support the community and enable high-throughput simulations on remote computing resources via GridBeans and UNICORE middleware. This infrastructure organizes the setup of such simulations resulting in increased comparability of simulation results. At the same time, complete workflows for advanced simulation protocols can be established and managed on remote resources by a graphical interface which increases reusability of protocols and additionally lowers the entry barrier into such simulations for, e.g., experimental scientists who want to compare their results against simulations. We demonstrate the power of this approach by illustrating it for protein folding simulations for a range of proteins. Conclusions We present software enhancing the entire workflow for native structure-based simulations including exception-handling and evaluations. Extending the capability and improving the accessibility of existing simulation packages the software goes beyond the state of the art in the domain of biomolecular simulations. Thus we expect that it will stimulate more individuals from the community to employ more confidently modeling in their research

The association between conditioned pain modulation and manipulation induced analgesia in people with lateral epicondylalgia

Objectives: Conditioned Pain Modulation (CPM) and Manipulation Induced Analgesia (MIA) may activate similar neurophysiological mechanisms to mediate their analgesic effects. This study assessed the association between CPM and MIA responses in people with lateral epicondylalgia (LE). Methods: Seventy participants with LE were assessed for CPM followed by MIA. A single assessor measured pressure pain thresholds (PPT) before, during, and after cold water immersion (10°C) of the asymptomatic hand and contralateral lateral glide (CLG) mobilization of the neck. For analyses, linear mixed models evaluated differences in CPM and MIA responses. Pearson partial correlations and regression analyses evaluated the association between CPM and MIA PPT. Results: There was a significant increase (CPM and MIA p<0.001) in PPT from baseline during the interventions (CPM mean 195.84 kPa elbow and 201.87 kPa wrist. MIA mean 123.01 kPa elbow 126.06 kPa wrist) and post the interventions (CPM mean 126.06 kPa elbow, 114.24 kPa wrist, MIA mean 123.50 kPa elbow, 122.16 kPa wrist). There were also significant moderate and positive partial linear correlations (r: 0.40–0.54, p<0.001) between CPM and MIA measures, controlling for baseline measures. Regression analyses showed that CPM PPT was a significant predictor of MIA PPT (p<0.001) and the models explained between 73% and 85% of the variance in MIA PPT. Discussion: This study showed that CPM and MIA responses were significantly correlated and that the CPM response was a significant predictor of MIA response

Design considerations for a superconducting linac as an option for the ESS

An approach for a superconducting high-current proton linac for the ESS has been discussed as an option in the "Proposal for a Next Generation Neutron Source for Europe-the European Spallation Source (ESS)". The following work studies the technical and economic conditions for a superconducting linac at the high-energy end of the proposed accelerator system. The use of superconducting elliptical cavities for the acceleration of high-energetic particles beta =v/c-1 is certainly state of the art. This is documented by many activities (TJNAF, TESLA, LEP, LHC, and KEK). A design study for the cavities is described in another paper on this conference. For low energy particles ( beta <<1) quarter wave type cavities and spoke-type cavities have been discussed. The main motivation for this study is the expectation of significant cost reduction in terms of operational and possibly investment cost. (5 refs)

Monte Carlo Methods for Rough Free Energy Landscapes: Population Annealing and Parallel Tempering

Parallel tempering and population annealing are both effective methods for simulating equilibrium systems with rough free energy landscapes. Parallel tempering, also known as replica exchange Monte Carlo, is a Markov chain Monte Carlo method while population annealing is a sequential Monte Carlo method. Both methods overcome the exponential slowing associated with high free energy barriers. The convergence properties and efficiency of the two methods are compared. For large systems, population annealing initially converges to equilibrium more rapidly than parallel tempering for the same amount of computational work. However, parallel tempering converges exponentially and population annealing inversely in the computational work so that ultimately parallel tempering approaches equilibrium more rapidly than population annealing.Comment: 10 pages, 3 figure

Pcdh18a regulates endocytosis of E-cadherin during axial mesoderm development in zebrafish

The notochord defines the axial structure of all vertebrates during development. Notogenesis is a result of major cell reorganization in the mesoderm, the convergence and the extension of the axial cells. However, it is currently not fully understood how these processes act together in a coordinated way during notochord formation. The prechordal plate is an actively migrating cell population in the central mesoderm anterior to the trailing notochordal plate cells. We show that prechordal plate cells express Protocadherin 18a (Pcdh18a), a member of the cadherin superfamily. We find that Pcdh18a-mediated recycling of E-cadherin adhesion complexes transforms prechordal plate cells into a cohesive and fast migrating cell group. In turn, the prechordal plate cells subsequently instruct the trailing mesoderm. We simulated cell migration during early mesoderm formation using a lattice-based mathematical framework and predicted that the requirement for an anterior, local motile cell cluster could guide the intercalation and extension of the posterior, axial cells. Indeed, a grafting experiment validated the prediction and local Pcdh18a expression induced an ectopic prechordal plate-like cell group migrating towards the animal pole. Our findings indicate that the Pcdh18a is important for prechordal plate formation, which influences the trailing mesodermal cell sheet by orchestrating the morphogenesis of the notochord

3D Growth of Cancer Cells Elicits Sensitivity to Kinase Inhibitors but Not Lipid Metabolism Modifiers

Tumor cells exhibit altered lipid metabolism compared with normal cells. Cell signaling kinases are important for regulating lipid synthesis and energy storage. How upstream kinases regulate lipid content, versus direct targeting of lipid-metabolizing enzymes, is currently unexplored. We evaluated intracellular lipid concentrations in prostate and breast tumor spheroids, treated with drugs directly inhibiting metabolic enzymes fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), diacylglyceride acyltransferase (DGAT), and pyruvate dehydrogenase kinase (PDHK), or cell signaling kinase enzymes PI3K, AKT, and mTOR with lipidomic analysis. We assessed whether baseline lipid profiles corresponded to inhibitors' effectiveness in modulating lipid profiles in three-dimensional (3D) growth and their relationship to therapeutic activity. Inhibitors against PI3K, AKT, and mTOR significantly inhibited MDA-MB-468 and PC3 cell growth in two-dimensional (2D) and 3D spheroid growth, while moderately altering lipid content. Conversely, metabolism inhibitors against FASN and DGAT altered lipid content most effectively, while only moderately inhibiting growth compared with kinase inhibitors. The FASN and ACC inhibitors' effectiveness in MDA-MB-468, versus PC3, suggested the former depended more on synthesis, whereas the latter may salvage lipids. Although baseline lipid profiles did not predict growth effects, lipid changes on therapy matched the growth effects of FASN and DGAT inhibitors. Several phospholipids, including phosphatidylcholine, were also upregulated following treatment, possibly via the Kennedy pathway. As this promotes tumor growth, combination studies should include drugs targeting it. Two-dimensional drug screening may miss important metabolism inhibitors or underestimate their potency. Clinical studies should consider serial measurements of tumor lipids to prove target modulation. Pretherapy tumor classification by de novo lipid synthesis versus uptake may help demonstrate efficacy

MALDI-TOF MS for the identification of cultivable organic-degrading bacteria in contaminated groundwater near unconventional natural gas extraction sites

Groundwater quality and quantity is of extreme importance as it is a source of drinking water in the United States. One major concern has emerged due to the possible contamination of groundwater from unconventional oil and natural gas extraction activities. Recent studies have been performed to understand if these activities are causing groundwater contamination, particularly with respect to exogenous hydrocarbons and volatile organic compounds. The impact of contaminants on microbial ecology is an area to be explored as alternatives for water treatment are necessary. In this work, we identified cultivable organic-degrading bacteria in groundwater in close proximity to unconventional natural gas extraction. Pseudomonas stutzeri and Acinetobacter haemolyticus were identified using matrix-assisted laser desorption/ionization-time-of-flight-mass spectrometry (MALDI-TOF MS), which proved to be a simple, fast, and reliable method. Additionally, the potential use of the identified bacteria in water and/or wastewater bioremediation was studied by determining the ability of these microorganisms to degrade toluene and chloroform. In fact, these bacteria can be potentially applied for in situ bioremediation of contaminated water and wastewater treatment, as they were able to degrade both compounds.info:eu-repo/semantics/publishedVersio