Clinical and in vitro analysis of Osteopontin as a prognostic indicator and unveil its potential downstream targets in bladder cancer

YesOsteopontin (OPN) plays an important role in cancer progression, however its prognostic significance and its downstream factors are largely elusive. In this study, we have shown that expression of OPN was significantly higher in bladder cancer specimens with higher T-stage or tumor grades. In addition, a high level of OPN was significantly associated with poorer survival in two independent bladder cancer patient cohorts totaling 389 bladder cancer patients with available survival data. We further identified Matrix metallopeptidase 9 (MMP9) and S100 calcium-binding protein A8 (S100A8) were both downstream factors for OPN in bladder cancer specimens and bladder cancer cell lines. Expression of OPN was significantly positively associated with that of MMP9 and S100A8, while overexpression of OPN resulted in upregulation of MMP9 and S100A8, and knockdown of OPN showed consistent downregulation of MMP9 and S100A8 expression levels. Importantly, expression levels of both MMP9 and S100A8 were significantly associated with higher T-stage, higher tumor grade and a shorter survival time in the bladder cancer patients. Interestingly, OPN expression only predicted survival in MMP9-high, but not MMP9-low subgroups, and in S100A8-low but not S100A8-high subgroups. Our results suggest that OPN, MMP9 and S100A8 all play a significant role in bladder cancer progression and are potential prognostic markers and therapeutic targets in bladder cancer. The mechanistic link between these three genes and bladder cancer progression warrants further investigation.University of Macau Multi-Year Research Grant (MYRG2015-00065-FHS

Formulation and Evaluation of Ketotifen Fumarate Fast Disintegrating Sublingual Tablets

The aim of this study was to formulate KF fast disintegrating sublingual tablets (FDSLTs).  KF has an oral bioavailability of only 50%, as it undergoes first pass metabolism in liver. Sublingual dosage form bypasses the metabolism of KF in liver and offers a fast relieve of asthma also it is not swallowed thus; improve the patient compliance especially for geriatric and pediatric patients, because of swallowing difficulties. To achieve this goal, superdisintegrants and diluents were evaluated for their effect on the disintegration behavior of KF fast disintegrating sublingual tablets. In addition, of enhancing the permeability and bioavailability of selected formulae through comlexation with 2-HP-β-CD.   A 24 full factorial design was applied for a screening study in which four factors were used at two levels.  Two of these factors, were the type of disintegrants; Ac-di-sol or Explotab, and the concentration of each disintegrant (3% or 5%w/w).  10%w/w Avicel PH101 or PEG6000 was used as binder and the filler was either spray dried lactose or granular mannitol. The weight variation, content uniformity, friability, hardness, disintegration time, and in-vitro dissolution of the prepared formulae were evaluated.  The formula F9 containing 5%w/w Ac-di-sol with 10%w/wAvicel PH101and granular mannitol as diluent which has the least disintegration time (about 20 seconds) and the highest dissolution rate was selected as best formula for bioequivalence study.  The mean plasma concentration–time courses for KF following the administration of FDSLTs  F9 (contains KF without compelxation with 2HP-βCD), Fc9 (contains KF/2HP-βCD complex) and Zaditen® (Novartis-Egypt) tablets  in six healthy male volunteers were found to be different following the three treatments, expressed with  higher Cmax by about 60% and 90% for both FDSLTs of F9 and Fc9 respectively,  and earlier tmax (by 1 h) values for  both of  FDSLTs F9 and Fc9 compared with Zaditen tablets. The relative bioavailability of Fc9 was 152.45% compared to 130.304% for F9 when Zaditen® tablets were taken as reference standard. The results indicate that KF/2-HP-βCD fast disintegrating sublingual tablets may serve as a successful strategy for enhancing the bioavailability of KF

Magnetic transitions and electrical transport in Bi-doped lanthanum strontium manganites

The temperature dependence of the electrical resistivity ρ, thermoelectric power S and the magnetic susceptibility χ of La₀.₇–xBixSr₀.₃MnO₃ (x = 0.05, 0.10, and 0.15 at.%) manganites were investigated. La₀.₇–xBixSr₀.₃MnO₃ crystallizes in a single phase rhombohedral structure with parasitic phase inclusions. With increasing Bi concentration, a systematic decrease in the ferromagnetic transition temperature (TC), the metal–semiconducting transition temperature (Tms1) and also the values of activation energies Eρ and ES from ρ(T) and S(T) were observed. On the other hand, in the high-temperature (T > Tms) paramagnetic semiconductor regime, the adiabatic small polaron hopping model fit well, thereby indicating that polaron hopping might be responsible for the conduction mechanism. In addition, the thermoelectric power data at low temperatures were analyzed by considering both the magnon and the phonon drag concept, while the high-temperature data were confirmed a small polaron hopping conduction mechanism

The annealing influence onto the electrical and magnetic behavior of magnetoresistive/insulator system

This investigation is mainly concerned with the effect of annealing temperature (600, 700, 800, and 900 °C) in air for (La₀.₇Ba₀.₃MnO₃)₁–x/(NiO) x with x = 0 and x = 0.10 samples. It was shown that the annealing temperature does not affect the structure and parameters of rhombohedral lattice of the samples. However, it is observed that the annealing treatment has a notable effect on the electrical resistivity and the metal-semiconductor transition temperature Tms. Temperature dependent magnetization measurements showed a decrease in Curie temperature TC with annealing temperature. In the same time, annealing process decreases the magnetoresistance of La₀.₇Ba₀.₃MnO₃, in contrast to (La₀.₇Ba₀.₃MnO₃)₀.₉/(NiO)₀.₁ composite

Differential Metabolite Profiles during Fruit Development in High-Yielding Oil Palm Mesocarp

10.1371/journal.pone.0061344PLoS ONE84

Experimental investigation of mechanically laminated straight or curved-and-tapered bamboo-concrete T-beams

This study echoes the rising demand for bio-based material in concrete composite structures in the race to accelerate carbon neutrality in construction. Noticing that most previous studies are focused on straight timber or engineered bamboo-to-concrete composite beams, this study developed straight or curved-and-tapered mechanically laminated bamboo-concrete (LBC) T-beams. Six layers of 26mm thick laminated bamboo panels were glue laminated together to form the bamboo beams. The curved bamboo beams have three different rises of arch: 50mm, 100mm and 150mm. All specimen beams were tested by four-point bending tests to evaluate their structural performances of the curved and straight LBC T-beams. To monitor the flange-to-web interface shear transfer, a novel interface shear slip calibration method that captures the longitudinal after-slip strain redistribution was developed and validated by strain gauge measurements. This study also highlights the interlayer shear bonding strength of laminated bamboo as the thresholding parameter that determines the composite beams' overall flexural strength, evidenced by detailed failure mode analysis. The proposed interface shear slip calibration method can be extended to the other types of shear connectors such as screws, nails, shear plates and notched connections

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369