Pharmacologic inhibition of RGD-binding integrins ameliorates fibrosis and improves function following kidney injury

Fibrosis is a final common pathway for many causes of progressive chronic kidney disease (CKD). Arginine-glycine-aspartic acid (RGD)-binding integrins are important mediators of the pro-fibrotic response by activating latent TGF-β at sites of injury and by providing myofibroblasts information about the composition and stiffness of the extracellular matrix. Therefore, blockade of RGD-binding integrins may have therapeutic potential for CKD. To test this idea, we used small-molecule peptidomimetics that potently inhibit a subset of RGD-binding integrins in a murine model of kidney fibrosis. Acute kidney injury leading to fibrosis was induced by administration of aristolochic acid. Continuous subcutaneous administration of CWHM-12, an RGD integrin antagonist, for 28 days improved kidney function as measured by serum creatinine. CWHM-12 significantly reduced Collagen 1 (Col1a1) mRNA expression and scar collagen deposition in the kidney. Protein and gene expression markers of activated myofibroblasts, a major source of extracellular matrix deposition in kidney fibrosis, were diminished by treatment. RNA sequencing revealed that inhibition of RGD integrins influenced multiple pathways that determine the outcome of the response to injury and of repair processes. A second RGD integrin antagonist, CWHM-680, administered once daily by oral gavage was also effective in ameliorating fibrosis. We conclude that targeting RGD integrins with such small-molecule antagonists is a promising therapeutic approach in fibrotic kidney disease

Constant-angle surfaces in liquid crystals

We discuss some properties of surfaces in R3 whose unit normal has constant angle with an assigned direction field. The constant angle condition can be rewritten as an Hamilton-Jacobi equation correlating the surface and the direction field. We focus on examples motivated by the physics of interfaces in liquid crystals and of layered fluids, and discuss the properties of the constant-angle surfaces when the direction field is singular along a line (disclination) or at a point (hedgehog defect

Macroporous materials: microfluidic fabrication, functionalization and applications

This article provides an up-to-date highly comprehensive overview (594 references) on the state of the art of the synthesis and design of macroporous materials using microfluidics and their applications in different fields

Decisions, Decisions: Factors that Influence a Patient\u27s Medical Tourism Choices

In the digital age, the amount of information and sources concerning Medical Tourism is overwhelming. Knowledge is power in an era of healthcare uncertainty. As health care options have grown in global proportions, it has become more difficult for potential patients to locate the material necessary to make informed decisions or to even know which factors to consider during their information search. Individual financial circumstances vary greatly. This paper suggests how medical tourism makes financial sense for many patients and payers. Proximity and culture play roles in that medical tourists may prefer locations that are not too far from home. Or at least don’t seem quite so far because of the cultural similarities such as language and food. Medical tourists want to know that they are safe not only concerning medical care but also in their travels. Legal issues are also an important consideration as medical tourists may forego some of the rights they take for granted in the U.S. Information on medical tourism is available from government sources such as the Centers for Disease Control and accrediting organizations including the Joint Commission International. Additional organizations to include the Medical Tourism Association exist for the purpose of guiding would-be medical tourists through the process

Decisions, Decisions: Factors that Influence a Patient\u27s Medical Tourism Choices

In the digital age, the amount of information and sources concerning Medical Tourism is overwhelming. Knowledge is power in an era of healthcare uncertainty. As health care options have grown in global proportions, it has become more difficult for potential patients to locate the material necessary to make informed decisions or to even know which factors to consider during their information search. Individual financial circumstances vary greatly. This paper suggests how medical tourism makes financial sense for many patients and payers. Proximity and culture play roles in that medical tourists may prefer locations that are not too far from home. Or at least don’t seem quite so far because of the cultural similarities such as language and food. Medical tourists want to know that they are safe not only concerning medical care but also in their travels. Legal issues are also an important consideration as medical tourists may forego some of the rights they take for granted in the U.S. Information on medical tourism is available from government sources such as the Centers for Disease Control and accrediting organizations including the Joint Commission International. Additional organizations to include the Medical Tourism Association exist for the purpose of guiding would-be medical tourists through the process

Medical Tourism: How Far are You Willing to Go to Save Money?

Medical needs of Americans are increasing as the population is aging and struggling with obesity. The addition of new medical technology and techniques, their widespread availability, and procedural improvements have created a more open market for medical providers. Costly procedures in cardiology and orthopedics serve as examples of increasingly needed medical treatments. Individuals, businesses and insurance companies have struggled to find ways to pay for these necessary procedures. Traditionally, in the U.S. the majority of medical procedures have been performed locally. Because of the rising costs associated with these procedures individuals and some healthcare providers are now looking to foreign markets. The performance of medical procedures by foreign providers has created a whole industry referred to as Medical Tourism. The growth of the field of Medical Tourism has presented significant questions, as well as substantial risks and rewards that need to be addressed before the consumer decides what is right for their particular circumstances

The effects of guided elaboration in a CSCL programme on the learning outcomes of primary school students from Dutch and immigrant families

This study examined the effects of guided elaboration on students’ learning outcomes in a computer-supported collaborative learning (CSCL) environment. The programme provided students with feedback on their elaborations, and students reflected on this feedback. It was expected that students in the experimental (elaboration) programme would show better learning gains and that students from immigrant families would especially benefit. Two hundred primary school students of 9 different schools participated. The research can be characterized as a quasi-experimental study with a pre-test, post-test, control group design. In a multilevel regression analysis, no main effect of the intervention was found. However, there was a significant differential effect of the intervention; students from immigrant families in the experimental programme outperformed their counterparts in the control group. It can be concluded that guided elaboration in a CSCL programme through feedback and reflection is a promising approach. Keywords: CSCL; outcomes; participatio

NHI 2.1 Veranderingen in NHI

Dit document is een concept en uitsluitend bedoeld voor discussiedoeleinden. Een impuls is gegeven aan het verbeteren van het nationaal hydrologisch instrumentarium, NHI 2.0. NHI 2.0 voldeed in 2010 nog niet volledig aan de wensen van RWS. In 2010 hebben twee processen plaatsgevonden, die tot meer inzicht hebben geleid in de prestaties van het NHI. Ten eerste de regionale toetsing van het NHI, onder andere door STOWA, en ten tweede het gebruik van NHI in diverse regionale en landelijke studies voor Zoetwaterverkenning (ZWV). Als gevolg hiervan zijn in NHI 2.1, in opdracht van de RWS Waterdienst, veel verbeteringen doorgevoerd

Fluid-crystal coexistence for proteins and inorganic nanocolloids: dependence on ionic strength

We investigate theoretically the fluid-crystal coexistence of solutions of globular charged nanoparticles like proteins and inorganic colloids. The thermodynamic properties of the fluid phase are computed via the optimized Baxter model. This is done specifically for lysozyme and silicotungstates for which the bare adhesion parameters are evaluated via the experimental second virial coefficients. The electrostatic free energy of the crystal is approximated by supposing the cavities in the interstitial phase between the particles are spherical in form. In the salt-free case a Poisson-Boltzmann equation is solved to calculate the effective charge on a particle and a Donnan approximation is used to derive the chemical potential and osmotic pressure in the presence of salt. The coexistence data of lysozyme and silicotungstates are analyzed within this scheme, especially with regard to the ionic-strength dependence of the chemical potentials. The latter agree within the two phases provided some upward adjustment of the effective charge is allowed for.Comment: 15 pages, 9 figure

NHI Toetsing, Ontwikkeling en toepassing van methode voor toetsing van NHI 2.1 inclusief vergelijking met NHI 2.0.

Dit rapport beschrijft de achtergrond van de methode om NHI2.1 te toetsen aan de criteria die opgesteld zijn door Rijkswaterstaat Waterdienst geldend voor 2010 en bevat de resultaten van die toetsing en de vergelijking met resultaten van NHI2.0. Volgens de criteria is de berekende aan en afvoer van oppervlakte water verbeterd. Op enkele belangrijke meetpunten van de oppervlaktewaterverdeling zijn signifinante verbeteringen te zien