Mixed Bed Ion-exchange Modeling for Divalent Ions in a Ternary System

Film controlled mixed bed simulations for divalent ions in a ternary system were studied in this work. The presence of divalent ions influences the electric field produced as a result of difference in ionic mobilities of the ions. Flux expressions, particle rates, and column material balances are combined and appropriate numerical methods applied to analyze the column effluent concentrations for all the ionic impurities. The model is tested for wide range of conditions. Mathematical modeling was complex and a generalized theoretical model was developed with assumptions where necessary

Novel triple therapy in osteoarthritis of knee joint

Background: Regenerative medicine may be defined as the process of replacing or regenerating human tissues or cells of humans to restore or to get very near to normal function of human life. Biological tissues found in humans such as blood, fat, bone marrow are the main resources of regenerative medicine which help in natural process of healing of soft tissue. Extracorporeal shock wave therapy (ESWT) is a physical modality that helps in enhancing healing process of soft tissues. Osteoarthritis of the knee joint is a gradually progressive degenerative condition with the loss of articular cartilage. The early stages of disease are managed conservatively with the aim of retarding the rate of cartilage destruction. Methods: A total of 80 patients underwent the novel triple therapy. The objective is to find out the potential of combination therapy in early degenerative disease of knee with the aim of reduction of inflammation. A protocol was developed which involved three injections of platelet rich plasma (PRP), six sessions of combined ESWT and physiotherapy. Results: Evaluation was mainly based on WOMAC/KSS/VAS scores. Patients in stage 1 and 2 (55+15=70) had excellent results for 36 months, patients in stage 3 (10 cases) had satisfactory outcome at 24 months. Conclusions: Triple therapy is an alternative treatment or in few cases a definitive treatment in degenerative disease of knee joint where medical and surgical management has minimal or no role. Triple therapy in mild to moderate osteoarthritis of knee joint has better outcome

The H3K27M mutation alters stem cell growth, epigenetic regulation, and differentiation potential

BACKGROUND: Neurodevelopmental disorders increase brain tumor risk, suggesting that normal brain development may have protective properties. Mutations in epigenetic regulators are common in pediatric brain tumors, highlighting a potentially central role for disrupted epigenetic regulation of normal brain development in tumorigenesis. For example, lysine 27 to methionine mutation (H3K27M) in the H3F3A gene occurs frequently in Diffuse Intrinsic Pontine Gliomas (DIPGs), the most aggressive pediatric glioma. As H3K27M mutation is necessary but insufficient to cause DIPGs, it is accompanied by additional mutations in tumors. However, how H3K27M alone increases vulnerability to DIPG tumorigenesis remains unclear. RESULTS: Here, we used human embryonic stem cell models with this mutation, in the absence of other DIPG contributory mutations, to investigate how H3K27M alters cellular proliferation and differentiation. We found that H3K27M increased stem cell proliferation and stem cell properties. It interfered with differentiation, promoting anomalous mesodermal and ectodermal gene expression during both multi-lineage and germ layer-specific cell specification, and blocking normal differentiation into neuroectoderm. H3K27M mutant clones exhibited transcriptomic diversity relative to the more homogeneous wildtype population, suggesting reduced fidelity of gene regulation, with aberrant expression of genes involved in stem cell regulation, differentiation, and tumorigenesis. These phenomena were associated with global loss of H3K27me3 and concordant loss of DNA methylation at specific genes in H3K27M-expressing cells. CONCLUSIONS: Together, these data suggest that H3K27M mutation disrupts normal differentiation, maintaining a partially differentiated state with elevated clonogenicity during early development. This disrupted response to early developmental cues could promote tissue properties that enable acquisition of additional mutations that cooperate with H3K27M mutation in genesis of DMG/DIPG. Therefore, this work demonstrates for the first time that H3K27M mutation confers vulnerability to gliomagenesis through persistent clonogenicity and aberrant differentiation and defines associated alterations of histone and DNA methylation

A Phosphomimetic Mutation at Threonine-57 Abolishes Transactivation Activity and Alters Nuclear Localization Pattern of Human Pregnane X Receptor

The pregnane X receptor (PXR) plays crucial roles in multiple physiological processes. However, the signaling mechanisms responsible are not well defined; it is most likely that multiple functions of PXR are modulated by its phosphorylation. Therefore, we sought to determine whether mutation at a highly conserved Thr57 affects human PXR (hPXR) function. Site-directed mutagenesis was performed to generate phosphorylation-deficient (hPXRT57A) and phosphomimetic (hPXRT57D) mutants. Gene reporter, Western blotting, immunocytochemistry, mammalian two-hybrid, and electrophoretic mobility shift assays were used to study cytochrome P450 3A4 (CYP3A4) promoter activation, protein levels, localization, cofactor interaction, and CYP3A4 promoter binding of the hPXR mutants, respectively. hPXRT57D, but not hPXRT57A, lost its transcriptional activity. Neither mutation altered hPXR's protein levels and interaction with steroid receptor coactivator-1. hPXR and hPXRT57A exhibited a homogenous nuclear distribution, whereas hPXRT57D exhibited a distinctive punctate nuclear localization pattern similar to that of hPXR mutants with impaired function that colocalize with silencing mediator of retinoid and thyroid receptors (SMRT), although silencing of SMRT did not rescue the altered function of hPXRT57D. However, hPXRT57D, but not hPXRT57A, impaired hPXR's ability to bind to the CYP3A4 promoter, consistent with the mutant's transactivation function. Furthermore, the 70-kDa form of ribosomal protein S6 kinase (p70 S6K) phosphorylated hPXR in vitro and inhibited its transcriptional activity, whereas hPXRT57A partially resisted the inhibitory effect of p70 S6K. Our studies identify a functionally significant phosphomimetic mutant (hPXRT57D) and show p70 S6K phosphorylation and regulation of hPXR transactivation to support the notion that phosphorylation plays important roles in regulating hPXR function

Observer agreement in the assessment of narrowband imaging system surface patterns in Barrett's esophagus: a multicenter study

Item does not contain fulltextBackground and study aims: The clinical utility of narrow-band imaging (NBI) for Barrett's esophagus is limited by the multiplicity of classification schemes. We evaluated the interobserver agreement and accuracy of a new consensus-driven simplified binary classification of NBI surface patterns

Electrogenic transport and K+ ion channel expression by the human endolymphatic sac epithelium

The endolymphatic sac (ES) is a cystic organ that is a part of the inner ear and is connected to the cochlea and vestibule. The ES is thought to be involved in inner ear ion homeostasis and fluid volume regulation for the maintenance of hearing and balance function. Many ion channels, transporters, and exchangers have been identified in the ES luminal epithelium, mainly in animal studies, but there has been no functional study investigating ion transport using human ES tissue. We designed the first functional experiments on electrogenic transport in human ES and investigated the contribution of K(+) channels in the electrogenic transport, which has been rarely identified, even in animal studies, using electrophysiological/pharmacological and molecular biological methods. As a result, we identified functional and molecular evidence for the essential participation of K(+) channels in the electrogenic transport of human ES epithelium. The identified K(+) channels involved in the electrogenic transport were KCNN2, KCNJ14, KCNK2, and KCNK6, and the K(+) transports via those channels are thought to play an important role in the maintenance of the unique ionic milieu of the inner ear fluid