Role of calcium phosphate and bioactive glass coating on in vivo bone healing of new Mg-Zn-Ca implant

Present investigation focuses on development and detailed characterization of a new Mg alloy sample (BM) with and without coating of hydroxyapatite (BMH) and bioactive glass (BMG) by air plasma spray method. After detailed mechano-physico-chemical characterization of powders and coated samples, electrochemical corrosion and SBF immersion tests were carried out. Detailed in vitro characterizations for cell viability were undertaken using MG-63 cell line followed by in vivo tests in rabbit model for studying bone healing up to 60 days. Starting current density increases from BM to BMH to BMG indicating highest resistance towards corrosion in case of BMG samples, however BMH also showed highest i(corr) value suggesting slowest rate of corrosion than BM and BMG samples. Dissolution of calcium ion in case of BMH and BMG control formation of apatite phases on surface. Ca2+ ions of coatings and from SBF solution underwent reduction reaction simultaneously with conversion of Mg to MgCl2 releasing OH- in the solution, which increases pH. Viability and propagation of human osteoblast-like cells was verified using confocal microscopy observations and from expression of bone specific genes. Alkaline phosphatase assay and ARS staining indicate cell proliferation and production of neo-osseous tissue matrix. In vivo, based on histology of heart, kidney and liver, and immune response of IL-2, IL-6 and TNF alpha, all the materials show no adverse effects in body system. The bone creation was observed to be more for BMH. Although both BMH and BMG show rays of possibilities in early new bone formation and tough bone-implant bonding at interface as compared to bare Mg alloy, however, BMG showed better well-sprayed coating covering on substrate and resistance against corrosion prior implanting in vivo. Also, better apatite formation on this sample makes it more favourable implant. GRAPHICS]

CD4<SUP>+</SUP> T Cell-derived novel peptide Thp5 induces interleukin-4 production in CD4<SUP>+</SUP> T cells to direct T helper 2 cell differentiation

The differentiation of naïve CD4+ T cells into T helper 2 (Th2) cells requires production of the cytokine IL-4 in the local microenvironment. It is evident that naïve/quiescently activated CD4+ T cells produce the IL-4 that drives Th2 cell differentiation. Because early production of IL-4 in naïve T cells leads to preferential Th2 cell differentiation, this process needs to be tightly regulated so as to avoid catastrophic and misdirected Th2 cell differentiation. Here, we show that Thp5, a novel peptide with structural similarity to vasoactive intestinal peptide, regulates production of early IL-4 in newly activated CD4+ T cells. Induction of IL-4 in CD4+ T cells by Thp5 is independent of the transcription factor STAT6 but dependent on ERK1/2 signaling. Furthermore, cytokines (IL-12 and TGF-β) that promote the differentiation of Th1 or Th17 cells inhibit Thp5 induction, thus suppressing Th2 cell differentiation. We further showed that Thp5 enhances Th2 responses and exacerbates allergic airway inflammation in mice. Taken together, our findings reveal that early activated CD4+ T cells produce Thp5, which plays a critical role as a molecular switch in the differentiation of Th cells, biasing the response toward the Th2 cell phenotype

Efficacy of nano-hydroxyapatite prepared by an aqueous solution combustion technique in healing bone defects of goat

The present study was undertaken to evaluate porous hydroxyapatite (HAp), the powder of which was prepared by a novel aqueous solution combustion technique, as a bone substitute in healing bone defects in vivo, as assessed by radiologic and histopathologic methods, oxytetracycline labeling, and angiogenic features in Bengal goat. Bone defects were created in the diaphysis of the radius and either not filled (group I) or filled with a HAp strut (group II). The radiologic study in group II showed the presence of unabsorbed implants which acted as a scaffold for new bone growth across the defect, and the quality of healing of the bone defect was almost indistinguishable from the control group, in which the defect was more or less similar, although the newly formed bony tissue was more organized when HAp was used. Histologic methods showed complete normal ossification with development of Haversian canals and well-defined osteoblasts at the periphery in group II, whereas the control group had moderate fibro-collagenization and an adequate amount of marrow material, fat cells, and blood vessels. An oxytetracycline labeling study showed moderate activity of new bone formation with crossing-over of new bone trabeculae along with the presence of resorption cavities in group II, whereas in the control group, the process of new bone formation was active from both ends and the defect site appeared as a homogenous non-fluoroscent area. Angiograms of the animals in the control group showed uniform angiogenesis in the defect site with establishment of trans-transplant angiogenesis, whereas in group II there was complete trans-transplant shunting of blood vessel communication. Porous HAp ceramic prepared by an aqueous combustion technique promoted bone formation over the defect, confirming their biologic osteoconductive property

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Acute otitis externa: Consensus definition, diagnostic criteria and core outcome set development.

OBJECTIVE: Evidence for the management of acute otitis externa (AOE) is limited, with unclear diagnostic criteria and variably reported outcome measures that may not reflect key stakeholder priorities. We aimed to develop 1) a definition, 2) diagnostic criteria and 3) a core outcome set (COS) for AOE. STUDY DESIGN: COS development according to Core Outcome Measures in Effectiveness Trials (COMET) methodology and parallel consensus selection of diagnostic criteria/definition. SETTING: Stakeholders from the United Kingdom. SUBJECTS AND METHODS: Comprehensive literature review identified candidate items for the COS, definition and diagnostic criteria. Nine individuals with past AOE generated further patient-centred candidate items. Candidate items were rated for importance by patient and professional (ENT doctors, general practitioners, microbiologists, nurses, audiologists) stakeholders in a three-round online Delphi exercise. Consensus items were grouped to form the COS, diagnostic criteria, and definition. RESULTS: Candidate COS items from patients (n = 28) and literature (n = 25) were deduplicated and amalgamated to a final candidate list (n = 46). Patients emphasised quality-of-life and the impact on daily activities/work. Via the Delphi process, stakeholders agreed on 31 candidate items. The final COS covered six outcomes: pain; disease severity; impact on quality-of-life and daily activities; patient satisfaction; treatment-related outcome; and microbiology. 14 candidate diagnostic criteria were identified, 8 reaching inclusion consensus. The final definition for AOE was 'diffuse inflammation of the ear canal skin of less than 6 weeks duration'. CONCLUSION: The development and adoption of a consensus definition, diagnostic criteria and a COS will help to standardise future research in AOE, facilitating meta-analysis. Consulting former patients throughout development highlighted deficiencies in the outcomes adopted previously, in particular concerning the impact of AOE on daily life

PREPARATION OF NANOPARTICLES FROM CORN COBS BY CHEMICAL TREATMENT METHODS

In order to prepare nanoparticles, corn cobs were treated with sodium hydroxide in the range 0-6 mole/litre (0-24% of sodium hydroxide on oven dry basis) at 165 oC for 1.5 h at a liquor to solid ratio of 4.5:1. The sample obtained at the optimised condition (4.5 mole/litre) was washed with deionised water, disintegrated, and filtered through 80 mesh screens. Powder thus obtained was delignified by acidified sodium chlorite and dried in a vacuum oven to constant weight. Dried powder was further separated by 270 mesh screens. An average particle size approximately equal to 22 nm was observed by Transmission Electron Microscopy (TEM). Its crystallinity was determined by XRD analysis. The aggregated particle size was observed in the micron range by Scanning Electron Microscopy (SEM)

Tumor suppressor SMAR1 represses IκBα expression and inhibits p65 transactivation through matrix attachment regions

Aberrant NF-κB activity promotes tumorigenesis. However, NF-κB also inhibits tumor growth where tumor suppressor pathways remain unaltered. Thus, its role in tumorigenesis depends upon the function of other cellular factors. Tumor suppressor SMAR1 down-modulated in high grade breast cancers is regulated by p53 and is reported to interact and stabilize p53. Because both SMAR1 and NF-κB are involved in tumorigenesis, we investigated the effect of SMAR1 upon NF-κB activity. We show that SMAR1 induction by doxorubicin or overexpression produces functional NF-κB complexes that are competent for binding to NF-κB consensus sequence. However, SMAR1 induced p65-p50 complex is phosphorylation- and transactivation-deficient. Induction of functional NF-κB complexes stems from down-regulation of IκBα transcription through direct binding of SMAR1 to the matrix attachment region site present in IκBα promoter and recruitment of corepressor complex. Real time PCR array for NF-κB target genes revealed that SMAR1 down-regulates a subset of NF-κB target genes that are involved in tumorigenesis. We also show that SMAR1 inhibits tumor necrosis factor α-induced induction of NF-κB suggesting that activation of NF-κB by SMAR1 is independent and different from classical pathway. Thus, for the first time we report that a tumor suppressor protein SMAR1 can modulate NF-κB transactivation and inhibit tumorigenesis by regulating NF-κB target genes

Stereochemical control in the structures of linear δ,α-hybrid tripeptides containing tetrahydrofuran amino acids

Structural and electronic properties of diastereomers of tetrahydrofuran amino acids (TAA) derived tripeptide, Boc-TAA-Leu-Val-OMe, are studied using density functional theory. Predicted secondary folding patterns with hydrogen bonded pseudocycles of different sizes in peptides containing (2R,5S)-cis-TAA and (2S,5R)-cis-TAA are confirmed by detailed NMR studies of both, and single crystal X-ray analysis of the former. A novel unusual folding pattern emanating from three-centered hydrogen bond is found in peptide with (2R,5S)-cis relationship. Stereochemical control on the orientation of interacting sites is substantiated by structural analysis of the peptides. Using natural bonding orbital and atoms in molecules analyses, charge transfer interactions are analyzed

Macro-to-micro porous special bioactive glass and ceftriaxone-sulbactam composite drug delivery system for treatment of chronic osteomyelitis: an investigation through in vitro and in vivo animal trial

A systematic and extensive approach incorporating in vitro and in vivo experimentation to treat chronic osteomyelitis in animal model were made using antibiotic loaded special bioactive glass porous scaffolds. After thorough characterization for porosity, distribution, surface charge, a novel drug composite were infiltrated by using vacuum infiltration and freeze-drying method which was subsequently analyzed by SEM-EDAX and studied for in vitro drug elution in PBS and SBF. Osteomyelitis in rabbit was induced by inoculation of Staphylococcus aureus and optimum drug-scaffold were checked for its efficacy over control and parenteral treated animals in terms of histopathology, radiology, in vivo drug concentration in bone and serum and implant-bone interface by SEM. It was optimized that 60P samples with 60-65% porosity (bimodal distribution of macro- to micropore) with average pore size similar to 60 mu m and higher interconnectivity, moderately high antibiotic adsorption efficiency (similar to 49%) was ideal. Results after 42 days showed antibiotic released higher than MIC against S. aureus compared to parenteral treatment (2 injections a day for 6 weeks). In vivo drug pharmacokinetics and SEM on bone-defect interface proved superiority of CFS loaded porous bioactive glass implants over parenteral group based on infection eradication and new bone formation