In inner ear development, phosphatase and tensin homolog (PTEN) is necessary for neuronal maintenance, such as neuronal survival and accurate nerve innervations of hair cells. We previously reported ...that Pten conditional knockout (cKO) mice exhibited disorganized fasciculus with neuronal apoptosis in spiral ganglion neurons (SGNs). To better understand the genes and signaling networks related to auditory neuron maintenance, we compared the profiles of differentially expressed genes (DEGs) using microarray analysis of the inner ear in E14.5 Pten cKO and wild-type mice. We identified 46 statistically significant transcripts using significance analysis of microarrays, with the false-discovery rate set at 0%. Among the DEGs, expression levels of candidate genes and expression domains were validated by quantitative real-time RT-PCR and in situ hybridization, respectively. Ingenuity pathway analysis using DEGs identified significant signaling networks associated with apoptosis, cellular movement, and axon guidance (i.e., secreted phosphoprotein 1 (Spp1)-mediated cellular movement and regulator of G-protein signaling 4 (Rgs4)-mediated axon guidance). This result was consistent with the phenotypic defects of SGNs in Pten cKO mice (e.g., neuronal apoptosis, abnormal migration, and irregular nerve fiber patterns of SGNs). From this study, we suggest two key regulatory signaling networks mediated by Spp1 and Rgs4, which may play potential roles in neuronal differentiation of developing auditory neurons.
The purpose of this study was to determine whether predicting maturation of the midpalatal suture is possible by classifying its morphology on cone-beam computed tomography (CBCT) images and to ...investigate relationships with other developmental age indices.
The morphology of the midpalatal suture was assessed by using CBCT images of 99 patients. Axial plane images of the midpalatal suture were classified into five stages according to the classification scheme. To make the assessment more accurate, the morphology and fusion of the midpalatal suture were additionally investigated on coronal cross-sectional planar images and volume-rendered images. Bone age was evaluated using the hand and wrist method (HWM) and cervical vertebrae method (CVM); dental age (Hellman's index), sex, and chronological age were also assessed. To evaluate relationships among variables, Spearman's rho rank test was performed along with crosstabs using contingency coefficients.
The HWM and CVM showed strong correlations with the maturation stage of the midpalatal suture, while other indices showed relatively weak correlations (
< 0.01). Through crosstabs, the HWM and CVM showed high association values with CBCT stage; the HWM demonstrated slightly higher values (
< 0.0001). Based on the HWM, the midpalatal suture was not fused until stage 6 in both sexes.
Among developmental age indices, the HWM and CVM showed strong correlations and high associations, suggesting that they can be useful in assessing maturation of the midpalatal suture.
Doxazosin mesylate (DXM) sustained release pellets were prepared by an extrusion-spheronization and fluid-bed coating technique. The core pellets containing DXM were prepared by ...extrusion-spheronization technique, and coated by a fluid-bed coater to control the release of DXM. The factors affecting to properties of pellets, such as diluent content, type and coating level of coating agents and plasticizers were studied in the present study. Polymethacrylate derivatives (Eudragit® RS PO and RL PO) were used for coating agents, and polyethylene glycol 6000 (PEG 6000), triethyl citrate (TEC) and castor oil were as plasticizers. To evaluate the properties of prepared pellets, the size of prepared pellets was investigated by sieve analysis technique and the morphology of pellets was evaluated by scanning electron microscopy. Through the dissolution test, factors that have an effect on the dissolution of the drug were evaluated. As the content ratio of microcrystalline cellulose (MCC) had increased, the dissolution was proportionally sustained. Eudragit® RS PO had more marked sustaining effect on the dissolution rate than Eudragit® RL PO, and the effect was more pronounced with the increased coating level. PEG 6000 was an appropriate plasticizer for DXM pellets, and increasing the content of PEG 6000, was also slightly decreasing the dissolution rate.
A novel strip-based disposable amperometric proton sensor that can selectively detect organophosphate neurotoxins (
i.e., paraoxon) is described. The detection methodology is based on measuring the ...current change involved in the assisted proton transfer by a proton selective ligand (
e.g., ETH 1778) across a microelliptic hole interface between the aqueous and polyvinylchloride-2-nitrophenyloctylether gel phase. The selective detection of paraoxon is achieved by measuring protons released by the specific hydrolysis of paraoxon with the organophosphorus hydrolase enzyme. A two-step process involving the hydrolysis and proton transfer reaction was characterized using cyclic voltammetry and differential pulse stripping voltammetry. A strip-based sensor fabricated using a simple polydimethylsiloxane (PDMS) mold with the resulting device was found to exhibit a linear response over a wide range of paraoxon concentrations (0.5
μM–100
μM) present in aqueous samples. In addition to the excellent detection limit and a wide dynamic range, a superb selectivity in the presence of common interfering agents in agricultural samples is achieved.
► Amperometric proton sensor for paraoxon with ion transfer reaction across an ITIES. ► Disposable strip-sensors are prepared via a simple PDMS microfabrication method. ► Paraoxon selective detection via hydrolysis followed by assisted proton transfer. ► Extended linear response over a wide dynamic range of paraoxon concentrations. ► Good detection limit with excellent selectivity over other electrochemical methods.
The aim of the study was to identify factors influencing the health-related quality of life (HR-QOL) for Korean RA patients and factors associated with each dimension of the EQ-5D. Two hundred and ...twenty-five RA patients were recruited from one University Hospital in Seoul, South Korea. Their clinical and socio-demographic data were widely collected by means of interviews, self-administered questionnaires, and clinical examinations. Multiple logistic regression analyses were performed to determine the factors influencing QOL and factors associated with each dimension of the EQ-5D. The mean EQ-5D utility observed for Korean RA patients was 0.60 (−0.29 to 1.0). Functional disability measured with Health Assessment Questionnaire (OR = 10.0, CI 2.8–34.5), disease activity score (DAS) 28 (OR = 2.6, CI 1.4–4.9), and pain VAS (OR = 2.2, CI 1.2–4.1) was three main factors influencing on QOL of RA patients. Although the functional disability consistently showed significant associations with all dimensions, various factors were associated with the each five specific dimension of EQ-5D. Pain (OR = 2.5, CI 1.4–4.6), history of hospitalization (OR = 2.1, CI 1.0–4.3), and men (OR = 2.6, CI 1.0–6.8) were associated with lower QOL in mobility. Use of alternative medicine (OR = 2.0, CI 1.1–3.7) and disease activity (OR = 3.1, CI 1.7–5.7) were associated with lower self-care QOL. For the patients with discomfort in usual activity, pain (OR = 4.7, CI 2.4–9.2) and the presence of anemia (OR = 2.3, CI 1.2–4.5) were major influencing factors. Higher disease activity (OR = 4.5, CI 1.0–21.2) and pain (OR = 3.3, CI 1.9–5.8) were associated with the pain/discomfort dimension of EQ-5D, and the pain (OR = 3.3, CI 1.9–5.8) was an independent associating factor of anxiety/depression. The strongest determinants of lower QOL in Korean RA patients were functional disability, higher disease activity, and subjective pain. However, various factors are influencing on the QOL for RA patients according to aspects of QOL. It suggested that clinicians should pay more attention to other factors of RA patients as well as clinical remission to improve their QOL.
Consider directed acyclic graph (DAG) scheduling for a large heterogeneous system, which consists of processors with varying processing capabilities and network links with varying bandwidths. The ...search space of possible task schedules for this problem is immense. One possible approach for this optimization problem, which is NP-hard, is to start with the best task schedule found by a fast deterministic task scheduling algorithm and then iteratively attempt to improve the task schedule by employing a general random guided search method. However, such an approach can lead to extremely long search times, and the solutions found are sometimes not significantly better than those found by the original deterministic task scheduling algorithm. In this paper, we propose an alternative strategy, termed Push-Pull, which starts with the best task schedule found by a fast deterministic task scheduling algorithm and then iteratively attempts to improve the current best solution using a deterministic guided search method. Our simulation results show that given similar runtimes, the Push-Pull algorithm performs well, achieving results similar to or better than all of the other algorithms being compared.
The aims of this study were to examine the phase behavior of itraconazole–phenol mixtures and assess the feasibility of topical formulations of itraconazole using eutectic mixture systems. ...Itraconazole–phenol eutectic mixtures were characterized using differential scanning calorimetry, Fourier transform infrared spectroscopy, 1H-nuclear magnetic resonance, and powder X-ray diffractometry. The skin permeation rates of itraconazole–phenol eutectic formulations were determined using Franz diffusion cells fitted with excised hairless mouse skins. Itraconazole can form eutectic compounds with phenol, and the hydrogen-bonding interactions between the carbonyl group in the itraconazole and hydroxyl group in phenol play a major role in itraconazole–phenol eutectic formation. Despite its high molecular weight and hydrophobicity, the drug (i.e., itraconazole) can be permeated through excised hairless mouse skins from itraconazole–phenol eutectic formulations. The findings of this study emphasize the capabilities of the topical application of itraconazole via external preparations.
Tissue engineering requires functional polymeric membrane for adequate space for cell migration and attachment within the nanostructure. Therefore, biocompatible propolis loaded polyurethane ...(propolis/PU) nanofibers were successfully prepared using electrospinning of propolis/PU blend solution. Here, composite nanofibers were subjected to detailed analysis using electron microscopy, FT-IR spectroscopy, thermal gravimetric analysis (TGA), and mechanical properties and water contact angle measurement. FE-SEM images revealed that the composite nanofibers became point-bonded with increasing amounts of propolis in the blend due to its adhesive properties. Incorporation of small amount of propolis through PU matrix could improve the hydrophilicity and mechanical strength of the fibrous membrane. In order to assay the cytocompatibility and cell behavior on the composite scaffolds, fibroblast cells were seeded on the matrix. Results suggest that the incorporation of propolis into PU fibers could increase its cell compatibility. Moreover, composite nanofibers have effective antibacterial activity. Therefore, as-synthesized nanocomposite fibrous mat has great potentiality in wound dressing and skin tissue engineering.
•Sufficient amount of propolis is simply loaded through PU fibers.•Propolis increases the hydrophilicity and mechanical properties of PU fibers.•Composite mat shows excellent antibacterial activity.•Small amount of propolis can enhance the cell compatibility of PU fibers.
Let P be a finitely generated projective module over a commutative ring R with identity. If P has finite rank, then it will be shown that the map φ : Aut R (P) → U(R) defined by φ(α) = det(α) is ...locally surjective and Ker(φ) = SL R (P).
The present study identified the molecular progression risk score (MoPRS) as an independent prognostic factor for identifying patients at high risk of invasive bladder cancer (BC) in patients with ...pathologic T1 high-grade BC (pT1HG BC). The MoPRS could be applied to improve clinical decision-making and for counseling patients with pT1HG BC.
Pathologic T1 high-grade (pT1HG) bladder cancer (BC) is characterized by a high progression rate and constitutes an important clinical challenge; however, there is no consensus on the prediction of progression in pT1HG BC. The purpose of this study was to validate previously published molecular progression risk score (MoPRS) for predicting muscle-invasive disease in pT1HG BC.
The expression of an 8-gene progression-related classifier identified from microarray data was analyzed by real-time PCR, and the MoPRS was calculated in 121 newly recruited patients with pT1HG BC. Progression was defined as muscle invasion or metastasis.
Overall, the disease of 28 patients (23.1%) progressed to muscle-invasive BC during the median follow-up of 63.7 (interquartile range, 17.6-96.4) months. The MoPRS was significantly higher in 1973 World Health Organization grade 3 than grade 2 tumors (P = .004). Early development of invasive BC was more prevalent in the highest quartile MoPRS group than in the lowest to 75th percentile MoPRS groups according to Kaplan-Meier analysis. Multivariate Cox regression analysis revealed that the MoPRS was an independent predictor of invasive BC, either as a continuous variable (hazard ratio, 1.624; 95% confidence interval, 1.266-2.082; P < .001) or as a categorical variable (hazard ratio, 3.089; 95% confidence interval, 1.335-7.150; P = .008).
The MoPRS was an independent prognostic factor for identifying patients at high risk of invasive BC in patients with pT1HG BC. This scale may help identify patients who could benefit from more aggressive therapeutic intervention such as early cystectomy.
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