Plasma protein binding in uremia: Extraction and characterization of an inhibitor

Plasma protein binding in uremia: Extraction and characterization of an inhibitor. The impairment of binding of drugs and other substances to serum albumin in patients with uremia can be restored to normal or near normal levels by adsorption with charcoal or synthetic polymers at pH 3. We used a nonionic poly-styrene-divinylbenzene copolymer to treat uremic plasma at pH 3. We observed a marked improvement of binding. Subsequent elution of this resin with ethanol produced a substance that, when dried and recombined with normal plasma, caused dose-dependent impairment of phenytoin and tryptophan binding. Restoration of normal binding affinity occurred after retreatment of this abnormalized plasma with resin at pH 3. Plasma and pleural fluid exudate from patients with uremia yielded, after extraction by the above technique, an inhibitor(s) of phenytoin binding in amounts averaging five times that extracted from equal volumes of normal plasma. This inhibitor (Ix) is water soluble, heat stable, and dialyzable across cellophane membranes. Unlike fatty acids, which can also interfere with binding, Ix partitions primarily in the water phase in solvent partition studies but undergoes a sharp transition in the pH 4 to 5 range, suggesting the presence of a carboxyl group. These findings lend further support to the hypothesis that a retained ligand(s) is responsible for impaired plasma binding associated with uremia and suggests a role for organic acids known to accumulate in renal failure.Liaison aux protéines plasmatiques dans l'urémie: Extraction et caractérisation d'un inhibiteur. L'altération de la liaison de drogues et d'autres substances à l'albumine sérique au cours de l'urémie peut être complètement ou presque complètement supprimée par l'adsorption sur du charbon ou des polymères synthétiques à pH 3. Nous avons utilisé un co-polymère non ionique polystyrènedivinylbenzène pour traiter le plasma urémique à pH 3 et observé une amélioration importante de la liaison. L'élution ultérieure de cette résine par l'éthanol produit une substance qui, lorsqu'elle est séchée et recombinée avec du plasma normal, détermine une altération dose dépendante de la liaison de la diphényl-hydantoïne et du tryptophane. La récupération d'une affinité de liaison normale a été obtenue après un nouveau traitement du plasma par la résine à pH 3. Le plasma et le liquide pleural de malades urémiques a donné, après extraction par la technique ci-dessus, un inhibiteur(s) de la liaison de la phénylhydantoïne en quantité cinq fois plus grande que celle extraite devolumes identiques de plasma normal. Cet inhibiteur (Ix) est soluble dans l'eau, thermostable et dialysable à travers des membranes de cellophane. A la différence des acides gras, qui peuvent aussi interférer avec la liaison, Ix passe dans la phase aqueuse au cours des études de partition dans des solvants, mais subit une transition brusque dans la gamme de pH 4 à 5, ce qui suggère la présence d'un groupe carboxyle. Ces constatations apportent des arguments supplémentaires à l'hypothèse selon laquelle un ligand (ou des ligands) retenus au cours de l'urémie est responsable de l'altération de la liaison plasmatique et suggère un rôle des acides organiques dont l'accumulation est connue dans l'insuffisance rénale

Mean curvature flow with triple junctions in higher space dimensions

We consider mean curvature flow of n-dimensional surface clusters. At (n-1)-dimensional triple junctions an angle condition is required which in the symmetric case reduces to the well-known 120 degree angle condition. Using a novel parametrization of evolving surface clusters and a new existence and regularity approach for parabolic equations on surface clusters we show local well-posedness by a contraction argument in parabolic Hoelder spaces.Comment: 31 pages, 2 figure

I-care-an interaction system for the individual activation of people with dementia

I-CARE is a hand-held activation system that allows professional and informal caregivers to cognitively and socially activate people with dementia in joint activation sessions without special training or expertise. I-CARE consists of an easy-to-use tablet application that presents activation content and a server-based backend system that securely manages the contents and events of activation sessions. It tracks various sources of explicit and implicit feedback from user interactions and different sensors to estimate which content is successful in activating individual users. Over the course of use, I-CARE’s recommendation system learns about the individual needs and resources of its users and automatically personalizes the activation content. In addition, information about past sessions can be retrieved such that activations seamlessly build on previous sessions while eligible stakeholders are informed about the current state of care and daily form of their protegees. In addition, caregivers can connect with supervisors and professionals through the I-CARE remote calling feature, to get activation sessions tracked in real time via audio and video support. In this way, I-CARE provides technical support for a decentralized and spontaneous formation of ad hoc activation groups and fosters tight engagement of the social network and caring community. By these means, I-CARE promotes new care infrastructures in the community and the neighborhood as well as relieves professional and informal caregivers

New Insights on the Management of Wildlife Diseases Using Multi-State Recapture Models: The Case of Classical Swine Fever in Wild Boar

The understanding of host-parasite systems in wildlife is of increasing interest in relation to the risk of emerging diseases in livestock and humans. In this respect, many efforts have been dedicated to controlling classical swine fever (CSF) in the European Wild Boar. But CSF eradication has not always been achieved even though vaccination has been implemented at a large-scale. Piglets have been assumed to be the main cause of CSF persistence in the wild since they appeared to be more often infected and less often immune than older animals. However, this assumption emerged from laboratory trials or cross-sectional surveys based on the hunting bags.In the present paper we conducted a capture-mark-recapture study in free-ranging wild boar piglets that experienced both CSF infection and vaccination under natural conditions. We used multi-state capture recapture models to estimate the immunization and infection rates, and their variations according to the periods with or without vaccination. According to the model prediction, 80% of the infected piglets did not survive more than two weeks, while the other 20% quickly recovered. The probability of becoming immune did not increase significantly during the summer vaccination sessions, and the proportion of immune piglets was not higher after the autumn vaccination.Given the high lethality of CSF in piglets highlighted in our study, we consider unlikely that piglets could maintain the chain of CSF virus transmission. Our study also revealed the low efficacy of vaccination in piglets in summer and autumn, possibly due to the low palatability of baits to that age class, but also to the competition between baits and alternative food sources. Based on this new information, we discuss the prospects for the improvement of CSF control and the interest of the capture-recapture approach for improving the understanding of wildlife diseases

Existence of Weak Solutions for a Diffuse Interface Model for Two-Phase Flows of Incompressible Fluids with Different Densities

We prove existence of weak solutions for a diffuse interface model for the flow of two viscous incompressible Newtonian fluids in a bounded domain in two and three space dimensions. In contrast to previous works, we study a new model recently developed by Abels, Garcke, and Gr\"un for fluids with different densities, which leads to a solenoidal velocity field. The model is given by a non-homogeneous Navier-Stokes system with a modified convective term coupled to a Cahn-Hilliard system. The density of the mixture depends on an order parameter.Comment: 33 page

Distinguishing Asthma Phenotypes Using Machine Learning Approaches.

Asthma is not a single disease, but an umbrella term for a number of distinct diseases, each of which are caused by a distinct underlying pathophysiological mechanism. These discrete disease entities are often labelled as asthma endotypes. The discovery of different asthma subtypes has moved from subjective approaches in which putative phenotypes are assigned by experts to data-driven ones which incorporate machine learning. This review focuses on the methodological developments of one such machine learning technique-latent class analysis-and how it has contributed to distinguishing asthma and wheezing subtypes in childhood. It also gives a clinical perspective, presenting the findings of studies from the past 5 years that used this approach. The identification of true asthma endotypes may be a crucial step towards understanding their distinct pathophysiological mechanisms, which could ultimately lead to more precise prevention strategies, identification of novel therapeutic targets and the development of effective personalized therapies

Clinical outcomes in pediatric hemodialysis patients in the USA: lessons from CMS’ ESRD CPM Project

Although prospective randomized trials have provided important information and allowed the development of evidence-based guidelines in adult hemodialysis (HD) patients, with approximately 800 prevalent pediatric HD patients in the United States, such studies are difficult to perform in this population. Observational data obtained through the Center for Medicare & Medicaid Services’ (CMS’) End Stage Renal Disease (ESRD) Clinical Performance Measures (CPM) Project have allowed description of the clinical care provided to pediatric HD patients as well as identification of risk factors for failure to reach adult targets for clinical parameters such as hemoglobin, single-pool Kt/V (spKt/V) and serum albumin. In addition, studies linking data from the ESRD CPM Project and the United States Renal Data System have allowed evaluation of associations between achievement of those targets and the outcomes of hospitalization and death. The results of those studies, while unable to prove cause and effect, suggest that the adult ESRD CPM targets may assist in identifying pediatric HD patients at risk for poor outcomes