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Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms. Results: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial [CHEST-2]). Conclusion: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified. © 2020 The Authors

Negative ion beam source test equipment, currently under construction at Institute of Plasma Physics, Chinese Academy of Sciences, is a prototype of a radio-frequency (RF) ion source for neutral be...

Background:Bone remodeling is a constant process maintained by the balance between osteoclast-triggered bone resorption and osteoblast-mediated bone formation. In inflammatory arthritis, such as rheumatoid arthritis (RA), the pro-inflammatory environment favors osteoclast differentiation and skews the balance towards resorption, leading to progressive bone erosion and bone loss. O-GlcNAcylation is a post-translational modification, which transfers a single N-acetylglucosamine molecule to the serine or threonine of the target protein. The modification is accomplished by a single pair of enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Unlike other glycosylation, O-GlcNAcylation occurs in multiple cellular compartments, including the nucleus. Although O-GlcNAcylation is one of the most common modifications, its role in bone homeostasis is still poorly understood.Objectives:We aimed to investigate the role of O-GlcNAcylation in osteoclastogenesis under pro-inflammatory milieus. We also focused on dissecting the signaling pathways affected by O-GlcNAcylation during osteoclast differentiation.Methods:We examined the levels of O-GlcNAc during in vitro osteoclastogenesis by western blotting. The levels of O-GlcNAc in tissue from RA patients and experimental arthritis were detected by immunofluorescence. Pharmacological inhibition and genetic knockout were used to manipulate O-GlcNAcylaiton during osteoclastogenesis. RNA sequencing was performed to study O-GlcNAc-mediated pathways.Results:We demonstrate the dynamic changes in O-GlcNAcylation during osteoclastogenesis. The elevated O-GlcNAcylation was found in the early differentiation stages, whereas its downregulation was detected in the maturation process. TNFα elaborates the dynamic changes in O-GlcNAcylation, which further intensifies osteoclast differentiation.Targeting OGT by selective inhibitor and genetic knockout restrain O-GlcNAcylation and hinder the expression of the early differentiation marker Nfatc1. Inhibition of OGA, which forces high levels of O-GlcNAcylation throughout the differentiation, reduces the formation of multinucleated mature osteoclasts. Consistent with our in vitro data, suppressing OGT and OGA both ameliorate bone loss in experimental arthritis. We detected a reduced number of TRAP-expressing precursors and mature osteoclasts in the mice subjected to OGT inhibition. While inhibiting OGA only lowers the number of TRAP+F4/80– mature osteoclasts without affecting the number of TRAP+F4/80+ precursors.Transcriptome profiling reveals that O-GlcNAcylation regulates several biological processes. Increased O-GlcNAcylation promotes cytokine signaling and oxidative phosphorylation. The downregulation of O-GlcNAcylation is essential for cytoskeleton organization and cell fusion.Conclusion:We demonstrate that the dynamic changes of O-GlcNAcylation are essential for osteoclast differentiation. These findings reveal the therapeutic potential of targeting O-GlcNAcylation in pathologic bone resorption.Disclosure of Interests:Chih-Wei Chen: None declared, Yi-Nan Li: None declared, Thuong Trinh-Minh: None declared, ZHU Honglin: None declared, Alexandru-Emil Matei: None declared, Xiao Ding: None declared, Cuong Tran Manh: None declared, Xiaohan Xu: None declared, Christoph Liebel: None declared, Ruifang Liang: None declared, Min-Chuan Huang: None declared, Neng-Yu Lin: None declared, Andreas Ramming Speakers bureau: Boehringer Ingelheim, Roche, Janssen, Consultant of: Boehringer Ingelheim, Novartis, Gilead, Pfizer, Grant/research support from: Pfizer, Novartis, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Jörg H.W. Distler Shareholder of: 4D Science, Speakers bureau: Boehringer Ingelheim, Paid instructor for: Boehringer Ingelheim, Consultant of: Actelion, Active Biotech, Anamar, ARXX, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva, JB Therapeutics, Medac, Pfizer, RuiYi and UCB, Grant/research support from: Anamar, Active Biotech, Array Biopharma, aTyr, BMS, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva, Novartis, Sanofi-Aventis, RedX, UCB, Employee of: FibroCure

A new methodology via using an adaptive fuzzy algorithm to obtain solutions of “Two-dimensional Navier-Stokes equations” (2-D NSE) is presented in this investigation. The design objective is to find two fuzzy solutions to satisfy precisely the 2-D NSE frequently encountered in practical applications. In this study, a rough fuzzy solution is formulated with adjustable parameters firstly, and then, a set of adaptive laws for optimally tuning the free parameters in the consequent parts of the proposed fuzzy solutions are derived from minimizing an error cost function which is the square summation of approximation errors of boundary conditions, continuum equation and Navier-Stokes equations. In addition, elegant approximated error bounds between the exact solution and the proposed fuzzy solution with respect to the number of fuzzy rules and solution errors have also been proven. Furthermore, the error equations in mesh points can be proven to converge to zero for the 2-D NSE with two sufficient conditions.

Supplemental material for Corticosteroid dose and the risk of opportunistic infection in a national systemic lupus erythematosus cohort by S-C Yang, Y-Y Lai, M-C Huang, C-S Tsai and J-L Wang in Lupus

Der weltweite Bedarf an Spenderhornhauten ubersteigt die Verfugbarkeit von humanem Spendergewebe bei Weitem. Aktuelle Bemuhungen zielen deshalb auf die Identifikation und Analyse von potenziellem Ersatzgewebe, wie z. B. dezellularisierten Kollagenmatrizes. Die durchsichtige Schuppe des Tilapia-Fisches (Oreochromis mossambicus) wurde als potenzielles Ersatzgewebe fur die Hornhauttransplantation untersucht („BioCornea“). Der Beitrag stutzt sich auf eine Literaturubersicht und eigene Ergebnisse. Nach Dezellularisierung wurden die Materialeigenschaften, die potenzielle Repopulation mit Hornhautepithel- und Hornhautstromazellen, die Immunogenitat, die Durchfuhrbarkeit von Keratoplastiken sowie die Angiogenitat dieser Kollagenmatrix in Zellkultur und in verschiedenen Tiermodellen analysiert. Die Schuppe des Tilapia-Fisches besteht fast ausschlieslich aus Kollagen Typ I und zeigt einen ahnlichen Aufbau wie die Hornhaut. Eine Repopulation mit Hornhautepithel- und Hornhautstromazellen ist moglich. In verschiedenen Tiermodellen konnten Transplantationen mit dieser Matrix ohne schwerwiegende Entzundungsreaktionen durchgefuhrt werden. Weiterhin kommt es nach Transplantation dieser Matrix im Mausmodell im Vergleich zu herkommlichen allogenen Transplantaten zu einem deutlich reduzierten Blut- und Lymphgefaswachstum in die Matrix. Erste Analysen mit der dezellularisierten Kollagenmatrix aus der Schuppe des Tilapia-Fisches als Hornhautersatz („BioCornea“) zeigen vielversprechende Ergebnisse.

This study investigated satellite cells and their related molecular events adapted to light moderate endurance training in the white gastrocnemius muscle of the rat. The white gastrocnemius muscle of male Sprague-Dawley rats that had been trained for 4 weeks and 8 weeks, with control rats being analysed alongside them, was selected for analysis (n=3 per group). The training protocol consisted of treadmill running at 20 m · min -1 for 30 min on a 0% grade, for 3 days · week -1 . Immunohistochemical staining coupled with image analysis was used for quantification. To provide deeper insight into the cell layer, 40 sections per rat, corresponding to 120 values per group, were obtained as a mean value for statistical comparison. The results indicated that at week 4, training effects increased the vascular endothelial growth factor (VEGF) content and c-met positive satellite cell numbers. At week 8, the training effect was attenuated for VEGF and c-met satellite cell numbers, but it increased in the muscle fibre area. Additionally, c-met positive satellite cell numbers correlated with VEGF content (r = 0.79, p

Objective: Because of ethnic differences in metabolic syndrome (MS) criteria, this study aimed to investigate the MS prevalence among patients with schizophrenia or schizoaffective disorder in Taiwan. Method: We recruited 650 patients with schizophrenia or schizoaffective disorder from 36 psychiatric institutions. The MS prevalence was assessed based on the modified Adult Treatment Panel (ATP) III criteria for Asians. Results: The overall MS prevalence was 34.9%, with 38.9% in female and 31.5% in male patients respectively. The difference of MS prevalence between our sample and the general population was marked in male patients under 40 years of age and in female patients under 50 years old. Body mass index ≥24 and age over 40 years old are two important risk factors of MS. Female and polypharmacy had marginal significance with the presence of MS. Conclusion: Patients with schizophrenia or schizoaffective disorder in Taiwan had a high prevalence of MS, which appeared early in their lives.

Inspired by the protein folding problem, we propose a Rubik’s cube model and study its thermodynamic and kinetic behavior. We find that the energy landscape contains a tiny funnel-like region, as the dynamics towards the native state is mostly diffusive. In particular, from Monte Carlo simulations we observe exponential kinetics in the first-passage-time distribution towards the native state at all temperatures considered, while the complexity of the energy landscape is exhibited through a stretched-exponential relaxation of the energy autocorrelation function. The rollover feature in the mean first passage time, as observed in many protein-folding dynamics studies, is captured again in our model and discussed under the statistical energy landscape approach.

In this study, a simple and cheap way to solve the drift problem is presented which describes the relation of drift and gate voltage. Constant various gate voltages are biased in sensing layers with reference electrode. It obviously shows a strong relation of gate drifts and gate stress voltages. When the gate voltage is controlled as 0.5 V, the drift voltage of SiO2 gate ISFET will decrease from 56.12 to 2.94 mV in ten hours measurement. The improvement of drift voltage reaches 94.8%. When the gate voltage is controlled as -1 V, the drift voltage of ZrO2 gate ISFET will also decrease from -57.94 to 0.76 mV. The improvement of drift voltage reaches 98.7%. This may result from the gate electric field affecting the ions to diffusive into the gate insulator. By this way, we can commercialize the ISFET with a very low drift rate in a simple way.

Aims: To determine the association between rainfall rate and occurrence of enterovirus infection related to contamination of drinking water. Methods and Results: One fatality case and three cases of severe illness were observed during the enterovirus epidemic in a village in southern Taiwan from 16 September to 3 October 1998. Groundwater samples were collected from the public well in the village after heavy rainfall to test for enterovirus using the reverse transcription-polymerase chain reaction (RT-PCR) assay. The RT-PCR assay detected the enterovirus in the groundwater sample collected on 26 September 1998. The logistic regression model also revealed a statistically significant association between the rainfall rate and the observation of cases of enterovirus infection. Conclusions: According to the fitted logistic regression model, the probability of detecting cases of enterovirus infection was greater than 50% at rainfall rates >31 mm h−1. The higher the rainfall rate, the higher the probability of enterovirus epidemic. Significance and Impact of the Study: Contamination of drinking water by the enterovirus may lead to epidemics that cause deaths and severe illness, and such contamination may be caused by heavy rainfall. The major finding in this study is that the enterovirus could be flushed to groundwater in an unconfined aquifer after a heavy rainfall. This work allows for a warning level so that an action can be taken to minimize future outbreaks and so protect public health.

This is a sequel to Huang’s paper entitled ‘Wave parameters and functions in wavelet analysis’ (Ocean Engineering, 2004, 31(1), 111–125) preliminary study of wave parameters and functions in wavelet analysis. Both discrete wavelet transform and median filtering techniques are applied to remove spiky noise from wind wave data obtained from a coastal observation tower. Fourier band-pass filters are also applied to remove low frequency drift and high frequency fluctuations. The original data and processed data are then analyzed by the time-domain, frequency-domain, and Morlet wavelet transform procedures. Two non-dimensional wave parameters, wave generation index NIT and non-stationary index NIF, are calculated from the Morlet wavelet transform and normalized with respect to the number of waves in each record, and the functional dependency of these two parameter on various wave statistics is reexamined in this study. Regression results confirm the effectiveness of the normalized wave generation index in describing the wave growth and decaying phenomena. It is also found that the normalized non-stationary index is linearly correlated with the time-domain groupiness factor per wave group and therefore can be used as another basic descriptor of wind waves in wavelet analysis.

The follicles (1.8 to 7.8 mm in diameter) were recovered from the ovaries in marketed pigs and the number of granulosa cells, the diameter of oocytes obtained from different development stages of the follicles and follicular fluid levels were determined. Correlations between size measurements and cell counts as well as the diameter of antral follicles and oocytes were also investigated. The results indicated that, while expanding in size, follicle numbers decreased with a greater atretic proportion. Granulosa cells increased in numbers continuously and remained unchanged beyond the size of 200 mm 3 in non-atretic follicles, whereas a sudden drop of granulosa counts was observed in atretic follicles. Follicular fluid, on the other hand, linearly increased its volume with follicle size and differed little between those of non-atretic and atretic follicles. Diameters of oocytes in non-atretic follicles increased to its maximum when follicles expanded to 150 mm 3 and maintained its size during later follicular expansion. It is concluded that, for in vitro culture, the optimal size of porcine follicle should be between 150 to 180 mm 3 if they are collected from pre-pubertal gilts of marketing size slaughtered in an abattoir. (Asian-Aust. J. Anim. Sci. 2004. Vol 17, No. 12 : 1647-1651)

Using nystatin perforated-patch whole cell recording, we investigated the role of Cl−conductance in the modulation of outer medullary descending vasa recta (OMDVR) pericyte membrane potential (Ψm) by ANG II. ANG II (10−11 to 10−7 M) consistently depolarized OMDVR and induced Ψm oscillations at lower concentrations. The Cl− channel blockers anthracene-9-decarboxylate (1 mM) and niflumic acid (10 μM) hyperpolarized resting pericytes and repolarized ANG II-treated pericytes. In voltage-clamp experiments, ANG II-treated pericytes exhibited slowly activating currents that were nearly eliminated by treatment with niflumic acid (10 μM) or removal of extracellular Ca2+. Those currents reversed at −31 and −10 mV when extracellular Cl− concentration was 152 and 34 mM, respectively. In pericytes held at −70 mV, oscillating inward currents were sometimes observed; the reversal potential also shifted with extracellular Cl− concentration. We conclude that ANG II activates a Ca2+-dependent Cl− conductance in OMDVR pericytes to induce membrane depolarization and Ψm oscillations.

Objective To compare parental knowledge, attitudes, concerns, and first-aid practices for children experiencing febrile convulsions (FC). Subjects and methods A questionnaire was mailed to 326 FC parents from 11 emergency departments in southern Taiwan. Results A total of 109 first- and 107 recurrent-FC parents responded 1-3 months after the FC. Most incorrectly believed an electroencephalogram (EEG) or computed tomography (CT) was necessary; immunization should be postponed, and overestimated the risk of subsequent epilepsy. Parents were concerned about further attacks in the night, fever episodes, and frequently measured the child's body temperature. During the first episode, objects were inserted into the child's mouth and they were rushed to a hospital. One third lowered the child's body temperature, and 15% positioned the children on their side. For subsequent seizures, 80% anticipated rushing the child to a hospital, and 44% would put objects into the child's mouth. In comparison, although the recurrent-FC parents had higher scores in knowledge and attitudes than the first-FC parents, low knowledge scores (40% correct) were seen in both groups. No significant differences were found on parental concerns, performed/anticipated first aid for FC. Conclusion Most FC parents had inadequate knowledge, high concerns, and improper first-aid practices. This suggests that parents with either first- or recurrent-FC children need information, emotional support, and first-aid demonstrations.

Correction to: Oncogene (2017) 36, 4243–4252; doi: 10.1038/onc.2017.8; published online 6 March 2017 The authors noted an error in the bottom panel of Figure 2c. A revised version is shown below and the text of the manuscript remains unchanged. The authors would like to apologize for any inconvenience caused and confirm that the conclusions drawn from this research are not affected by this error.

The worldwide need for donor corneal tissue clearly exceeds the availability of transplantable human tissue; therefore, recent efforts aim to identify and characterize alternative tissues, such as decellularized collagen scaffolds.The transparent fish scales of tilapia (Oreochromis mossambicus) were analyzed as a potential alternative for corneal reconstruction ("BioCornea").The article gives a review of the literature and own preliminary results. After decellularization the tissue characteristics of the fish scales, the repopulation with corneal epithelium and stromal cells, immunogenicity, the feasibility of corneal transplantation and the angiogenic properties were analyzed in vitro and in various animal models.The fish scales mainly consist of collagen type I and show an architecture that is similar to the human cornea. Corneal epithelium and stromal cells are able to grow over and into the scaffold. It is possible to transplant fish scales in various animal models without severe inflammatory responses. Furthermore, in mice, less blood and lymphatic vessels grow into the xenograft when compared to conventional allogenic transplants.Preliminary results with decellularized tilapia fish scales as an alternative for corneal reconstruction ("BioCornea") are promising.

We investigated the dependence of ANG II (10−8 M)-induced constriction of outer medullary descending vasa recta (OMDVR) on membrane potential (Ψm) and chloride ion. ANG II depolarized OMDVR, as measured by fully loading them with the voltage-sensitive dye bis[1,3-dibutylbarbituric acid-(5)] trimethineoxonol [DiBAC4(3)] or selectively loading their pericytes. ANG II was also observed to depolarize pericytes from a resting value of −55.6 ± 2.6 to −26.2 ± 5.4 mV when measured with gramicidin D-perforated patches. When measured with DiBAC4(3) in unstimulated vessels, neither changing extracellular Cl− concentration ([Cl−]) nor exposure to the chloride channel blocker indanyloxyacetic acid 94 (IAA-94; 30 μM) affected Ψm. In contrast, IAA-94 repolarized OMDVR pretreated with ANG II. Neither IAA-94 (30 μM) nor niflumic acid (30 μM, 1 mM) affected the vasoactivity of unstimulated OMDVR, whereas both dilated ANG II-preconstricted vessels. Reduction of extracellular [Cl−] from 150 to 30 meq/l enhanced ANG II-induced constriction. Finally, we identified a Cl−channel in OMDVR pericytes that is activated by ANG II or by excision into extracellular buffer. We conclude that constriction of OMDVR by ANG II involves pericyte depolarization due, in part, to increased activity of chloride channels.

Objective To evaluate long-term effects of educational interventions on parental concerns for children with febrile convulsions (FC). Subjects and methods 209 FC parents were recruited from southern Taiwan, and assigned into program or pamphlet groups by their choices. A questionnaire was used to examine the parental concerns at 4 time points: prior to the interventions, 3 months, 1 year, and 2 years after the interventions. Results The concern scores were high before the interventions. Parents concerned that their child is apt to get a fever, has further seizures in the night, that FC results in potential brain damage and is life threatening. After interventions the concern scores were significantly lower for the program group than for the pamphlet group. The educational program was the most significant factor that influenced the change in parental concerns. The recurrence of FC did not significantly influence the change in the concern trajectory in the program group but showed a significant difference in the pamphlet group. Conclusion FC parental concerns decreased as time passed particularly in the program group. The educational program was the significant factor that influenced the change of concern trajectories, and the recurrent/non-recurrent factor influenced the change of concern only in pamphlet group. FC parental concerns should be assessed, and information given combined with emotional support.

The bond-percolation process is studied on periodic planar random lattices and their duals. The thresholds and critical exponents of the percolation transition are determined. The scaling functions of the percolating probability, the existence probability of the appearance of percolating clusters, and the mean cluster size are also calculated. The simulation result of the percolation threshold is pc50.333360.0001 for planar random lattices, and 0.667060.0001 for the duals of planar random lattices. We conjecture that the exact value of pc is 1/3 for a planar random lattice and 2/3 for the dual of a planar random lattice. By taking possible errors into account, the results of our critical exponents agree with the values given by the universality hypothesis. By properly adjusting the metric factors on random lattices and their duals, we demonstrate explicitly that the idea of a universal scaling function with nonuniversal metric factors in the finite-size scaling theory can be extended to random lattices and their duals for the existence probability, the percolating probability, and the mean cluster size. @S1063-651X~99!00112-9#

We apply Plechko’s Grassmann path-integral method to Ising cylinders of rectangular, triangular, and hexagonal lattices to obtain the analytic solutions of free energies for the periodic and antiperiodic boundary conditions in the joined circumferences of the cylinders. These analytic solutions are used to analyze the scaling functions of the interfacial tensions for isotropic and anisotropic couplings. The finite-size corrections to the scaling functions are also discussed. @S0163-1829~99!12141-6#

Summary Sequence polymorphism of the displacement loop (D-loop) region in mitochondrial DNA (mtDNA) is a cytoplasmic DNA marker. Since the analysis of single-strand conformation polymorphism (SSCP) has been used for detection of substitutions in nucleotide sequence, this technique was employed to investigate the porcine sequence polymorphism in the D-loop region. The primers were prepared to amplify the most polymorphic site with 392-bp in the D-loop region from whole blood of pigs. The PCR-SSCP patterns were identical in European breeds Landrace and Duroc, but were different in Yorkshire and in Taiwanese breeds Lanyu and Taoyuan. Nucleotide sequence analysis in the 392-bp PCR products were completely in accordance with the PCR-SSCP patterns. There was only a single nucleotide substitution between Yorkshire and Landrace/Duroc pig and 2–3 nucleotide substitutions (dependent on the breed and individual) between Taiwanese Lanyu and Taoyuan. As many as 10–11 nucleotides were different between European and Taiwanese breeds in which most differences clustered within a certain region in the D-loop. The results suggest that PCR-SSCP analysis may be used for detecting single nucleotide substitution in the porcine mtDNA D-loop region and show the diversified sequence in this region between European and Asian origins. Zusammenfassung SSCP Analyse in der D-Schleifen-Region porciner mitochondrialer DNA bestatigt durch Sequenz Diversitat Da Einzelstrang Konformationspolymorphismus (SSCP) zur Entdeckung von Substitutionen in der Nukleotidesequenz benutzt wird, haben wir diese Technik zur Untersuchung der D-Schleifen Region angewendet. Es wurden Primers zur Amplifikation der am starksten polymorphen 392 bp konstruiert. Die PCR-SSCP Muster waren zwischen Landrasse und Duroc identisch, unterschieden sich aber bei Yorkshire und den Taiwanesichen Rassen Lanyu und Taoyuan. Die Analyse der Nukleotidsequenzen im 392 bp PCR Produkt ergaben ein identisches Bild. Yorkshire unterschied sich von Landrasse/Duroc nur in einer Substitution und die Taiwanesichen Rassen voneinander um 2 bis 3. Von den europaischen unterschieden sich diese aber in 10 bis 11 Nukleotiden, wobei die Unterschiede in einer bestimmten D-Schleifen Region gehauft sind. Die Ergebnisse zeigen, das PCR-SSCP Analyse zu Entdeckung einzelner Nukleotid Substitutionen geeignet ist und diesbezuglishe Unterschiede zwischen Rassen europaischer und asiatischer Herkunft aufzeigt.

In our previous cDNA microarray study, we found that the carbonic anhydrase II (CA2) gene is one of the differentially expressed transcripts in the duck isthmus epithelium during egg formation period. The aim of this study was to identify the single-nucleotide polymorphisms (SNPs) in the CA2 gene of Tsaiya ducks. The relationship of SNP genotype with egg production and reproduction traits was also investigated. A total of 317 ducks from two lines, a control line with no selection and a selected line, were employed for testing. Three SNPs (C37T, A62G and A65G) in the 3'-untranslated region of the CA2 gene were found. SNP-trait association analysis showed that SNP C37T and A62G were associated with duck egg weight besides fertility. The ducks with the CT and AG genotypes had a 1.46 and 1.62 g/egg lower egg weight as compared with ducks with the CC and AA genotypes, respectively (p0.05). But the ducks with CT and AG genotypes had 5.20% and 4.22% higher fertility than those with CC and AA genotypes, respectively (p0.05). Diplotype constructed on these three SNPs was associated with duck fertility, and the diplotype H1H4 was dominant for duck fertility. These findings might provide the basis for balanced selection and may be used in marker-assisted selection to improve egg weight and fertility simultaneously in the Tsaiya ducks.

Extravillus trophoblast (EVT) invasion plays a critical role in placental development. Integrins bind to extracellular matrix (ECM) proteins to mediate EVT cell adhesion, migration, and invasion. Changes in O-glycans on β1-integrin have been found to regulate cancer cell behavior. We hypothesize that O-glycosyltransferases can regulate EVT invasion through modulating the glycosylation and function of β1-integrin. Here, we found that the GALNT1 and GALNT2 mRNA were highly expressed in HTR8/SVneo and first trimester EVT cells. Immunohistochemstry and immunofluorescence staining showed that GALNT2 was expressed in subpopulations of EVT cells in deciduas, but not in syncytiotrophoblasts and cytotrophoblasts of placental villi. The percentage of GALNT2-positive EVT cells increased with gestational ages. Overexpression of GALNT2 in HTR8/SVneo cells significantly enhanced cell-collagen IV adhesion, but suppressed cell migration and invasion. Notably, we found that GALNT2 increased the expression of Tn antigen (GalNAc-Ser/Thr) on β1-integrin as revealed by Vicia Villosa agglutinin (VVA) binding. Furthermore, GALNT2 suppressed the phosphorylation of focal adhesion kinase (FAK), a crucial downstream signaling molecule of β1-integrin. Our findings suggest that GALNT2 is a critical initiating enzyme of O-glycosylation for regulating EVT invasion.

Transcriptome analysis using a cDNA microarray was performed to identify differentially expressed genes that are correlated with hatchability, and a new PCR-RFLP marker of high hatchability among the identified genes was observed. We used the cDNA microarray technique for gene expression profiling of the magnum epithelium of laying Tsaiya ducks, and several regulated genes associated with hatchability were found. The results of real-time PCR and Western blotting analysis confirmed that the mRNA and protein levels of ovomucoid in the magnum epithelium of animals in the low-hatchability group were significantly higher than the levels in the high-hatchability group (P0.05). Primers TovF1 and TovR1, designed according to the ovomucoid EST sequence, were used to amplify genomic DNA samples of different individual Tsaiya ducks, and sequence analysis of the amplified DNA products showed deletion among the ducks from the low-hatchability group. Primers TovF2 and TovR2 were used to perform PCR-RFLP analysis on the amplified DNA products to classify the ducks into +/+, +/- and -/- genotypes. The animals of +/+ and +/- genotypes were identified as having significantly higher hatchability than those of the -/- genotype (P0.05). In contrast, no differences were observed between genotypes in terms of fertility, duration of fertility, egg weight or total number of eggs. Our results indicated that a novel PCR-RFLP marker of high hatchability, an ovomucoid gene polymorphism, can be used as a genetic marker for marker-assisted selection to improve hatchability in Tsaiya ducks.

The combined treatment of peripheral nerve (PN) graft and fibroblast growth factor (FGF)-1 for spinal cord injury produces functional recovery, but how it affects injury events is still unknown. This project studied the effect of PN graft and FGF-1 on white matter degeneration following spinal cord injury.Rats were divided into four groups: (i) complete spinal cord transection and T8 segment removed; the remaining three groups underwent transection followed by (ii) PN grafting; (iii) supply of exogenous FGF-1; and (iv) PN grafting plus FGF-1 treatment. Chondroitin sulphate proteoglycan (CSPG) deposition, astrocytes and macrophage activation, cavity size, and calcitonin gene-related peptide and synaptophysin immunoreactivity were compared.Peripheral nerve grafting increased CSPG levels compared to transection surgery alone. This CSPG was associated with the proximity to the PN graft. FGF-1 reduced CSPG deposition in grafted animals regardless of the proximity to the graft. The CSPG reduction was accompanied by reduced GFAP expression and macrophage activation. The amount of CSPG with dissociated glycosaminoglycan did not differ between groups. FGF-1 in Schwann cell-astrocyte coculture did not reduce CSPG deposition. Furthermore, the PN graft increased the calcitonin gene-related peptide immunoreactivity and altered the distribution of synaptophysin-positive axons.Peripheral nerve graft supported sensory re-innervation and partial protection of the grey matter, but up-regulated CSPG in the graft-stump junction compared to non-grafted rats. The reduction of CSPG was caused by FGF-1-PN synergy, and did not involve dissociation of CSPG or the suppression of a general immune response.

Because of ethnic differences in metabolic syndrome (MS) criteria, this study aimed to investigate the MS prevalence among patients with schizophrenia or schizoaffective disorder in Taiwan.We recruited 650 patients with schizophrenia or schizoaffective disorder from 36 psychiatric institutions. The MS prevalence was assessed based on the modified Adult Treatment Panel (ATP) III criteria for Asians.The overall MS prevalence was 34.9%, with 38.9% in female and 31.5% in male patients respectively. The difference of MS prevalence between our sample and the general population was marked in male patients under 40 years of age and in female patients under 50 years old. Body mass indexor =24 and age over 40 years old are two important risk factors of MS. Female and polypharmacy had marginal significance with the presence of MS.Patients with schizophrenia or schizoaffective disorder in Taiwan had a high prevalence of MS, which appeared early in their lives.

The health of the corneal endothelium is essential in maintaining the clarity of the transplanted human cornea. Immune-mediated endothelial rejection is a complex series of events, which may culminate in the decompensation of the donor button. It is the commonest instigator of failure in penetrating corneal transplantation.Methods This retrospective case note review of 203 penetrating keratoplasties with adequate follow-up data during a 5-year study period from 1 January 2000 to 31 December 2003 at Manchester Royal Eye Hospital, were used for analysis.Results Forty-three of the 203 donor grafts underwent at least one single episode of immune-mediated endothelial rejection, an incidence of 21% over a 5-year follow-up. Recipient's age was inversely associated with the risk of rejection. The average age for the cohort of 58.7 years and average age for rejecting patients of 47.6 years were strongly significantly different (P=0.009). Rejection in keratoconic patients accounted for 30% of cases. Death to enucleation time (P=0.03) was also associated with an increased risk of rejection.Conclusion Although penetrating keratoplasty is an effective long-term treatment option for improving visual function, the endothelial rejection rate in our study was 21% over a mean follow-up of over 5 years. Host vascularisation, regrafts, younger recipient age group, and donor factors were found to be significantly associated with a risk of rejection. Rejection in keratoconic recipients was more common than expected.Eye advance online publication, 17 April 2009; doi:10.1038/eye.2009.72.

PURPOSE: Allograft rejection is the main cause of graft failure in human corneal transplantation, for which underlying pathomechanism is not yet clear. We compared gene expression in the peripheral blood of patients who after undergoing corneal transplantation experienced graft rejection with those patients who accepted grafts. METHODS: Sixty-six patients who underwent corneal transplantation were studied including 18 patients who suffered subsequent graft rejection. cDNA array technology was used to survey and quantify transcript expression. A semiquantitative reverse transcriptase-PCR (RT-PCR) was used to confirm the gene expression pattern measured by a cDNA array of selected genes. RESULTS: Among 265 genes present on the array, eight genes were found to be differentially expressed. Four genes (Rac 2, RhoA, paxillin, and CD18) were further analysed by semiquantitative RT-PCR, and significant differences in mRNA expression levels in the rejection group were confirmed. CONCLUSIONS: Our study demonstrated that the expression of Rac2 mRNA was upregulated in the peripheral blood of patients experiencing corneal transplantation rejection compared to those patients who had no rejection episodes. In addition, three genes, RhoA, paxillin, and CD18, showed decreased expression in rejecting patients. cDNA array technology provides a potentially useful approach to identify novel genes that might participate in pathogenic pathways during corneal graft rejection.

In this paper, the equations of motion of a swinging roller-follower cam for rise-dwell-fall-dwell (RDFD) case are derived by applying Hamilton’s principle and the assumed mode method. The cycloidal displacement (sinusoidal acceleration) motion is used to describe the rise and the fall motions of the follower. The corresponding cam profile is determined using theory of envelopes. The follower rod is considered to be flexible and modeled as a Rayleigh beam including axial and transverse deflections. The roller rolls in the cam groove. The contact point between the cam and the roller is an unknown point though it is restrained in the cam groove. The contact point position depends not only on the rigid-body motions of the cam system but also the flexible vibrations of the follower rod. Two geometric constraints are formulated to restrict the roller motion and added to the Hamilton’s principle with Lagrange multipliers. The numerical integration method is applied to solve the non-linear differential-algebraic equations to obtain the vibration responses of the cam system. The numerical results for the studied cases show that the follower vibrates significantly especially for the case of high rotation speed of cam. The follower still vibrates during the dwell interval. The parameter effects including the cam rotation speed, the follower length and cross-sectional radius, and the total rise on the vibration behavior have been investigated.Copyright © 2008 by ASME

The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding1,2,3,4,5,6 and conserved non-coding4,6,7 regions, including regulatory elements8,9,10, and provide insight into the forces that have rendered modern-day genomes6. As a complement to whole-genome sequencing efforts3,5,6, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.

To compare parental knowledge, attitudes, concerns, and first-aid practices for children experiencing febrile convulsions (FC).A questionnaire was mailed to 326 FC parents from 11 emergency departments in southern Taiwan.A total of 109 first- and 107 recurrent-FC parents responded 1-3 months after the FC. Most incorrectly believed an electroencephalogram (EEG) or computed tomography (CT) was necessary; immunization should be postponed, and overestimated the risk of subsequent epilepsy. Parents were concerned about further attacks in the night, fever episodes, and frequently measured the child's body temperature. During the first episode, objects were inserted into the child's mouth and they were rushed to a hospital. One third lowered the child's body temperature, and 15% positioned the children on their side. For subsequent seizures, 80% anticipated rushing the child to a hospital, and 44% would put objects into the child's mouth. In comparison, although the recurrent-FC parents had higher scores in knowledge and attitudes than the first-FC parents, low knowledge scores (40% correct) were seen in both groups. No significant differences were found on parental concerns, performed/anticipated first aid for FC.Most FC parents had inadequate knowledge, high concerns, and improper first-aid practices. This suggests that parents with either first- or recurrent-FC children need information, emotional support, and first-aid demonstrations.

Intracranial metastasis occurs in a certain number of patients with carcinoid tumor. However, carcinoid tumor with metastasis to the pituitary gland is extremely rare. Up to the present, no effective treatment for either a metastatic intracranial carcinoid tumor or a metastatic pituitary lesion of any origin has been documented. We have treated a case of metastatic carcinoid tumor of the pituitary gland with transsphenoidal tumor resection followed by gamma knife radiosurgery. A 59-year-old man presented with headache and left oculomotor palsy. He was treated at the same hospital for bronchial atypical carcinoid tumor one and a half years ago. Magnetic resonance image of the brain showed a pituitary tumor. There were no signs of recurrent or metastatic lesion elsewhere despite thorough investigation. Transsphenoidal approach for removal of tumor was done and the pathology turned out to be a metastatic carcinoid tumor. Subsequent gamma knife radiosurgery was given for residual tumor. The oculomotor palsy improved after radiosurgery. No neurological deficit occurred. Follow-up CT scan of the brain showed complete resolution of the tumor. We concluded that gamma knife radiosurgery could be used to treat a metastatic intracranial carcinoid tumor. It can also be used to treat a metastatic lesion of the pituitary gland without causing neurological deficit.

To evaluate long-term effects of educational interventions on parental concerns for children with febrile convulsions (FC).209 FC parents were recruited from southern Taiwan, and assigned into program or pamphlet groups by their choices. A questionnaire was used to examine the parental concerns at 4 time points: prior to the interventions, 3 months, 1 year, and 2 years after the interventions.The concern scores were high before the interventions. Parents concerned that their child is apt to get a fever, has further seizures in the night, that FC results in potential brain damage and is life threatening. After interventions the concern scores were significantly lower for the program group than for the pamphlet group. The educational program was the most significant factor that influenced the change in parental concerns. The recurrence of FC did not significantly influence the change in the concern trajectory in the program group but showed a significant difference in the pamphlet group.FC parental concerns decreased as time passed particularly in the program group. The educational program was the significant factor that influenced the change of concern trajectories, and the recurrent/non-recurrent factor influenced the change of concern only in pamphlet group. FC parental concerns should be assessed, and information given combined with emotional support.

Meckel's diverticulum is the most common anomaly of the gastrointestinal tract and usually produces no symptoms, although the classic symptom is painless rectal bleeding in a child. Because most symptomatic diverticula in children contain ectopic gastric tissue, radionuclide imaging using a technetium 99m pertechnetate scan is considered to be the method of choice. However, a bleeding Meckel's diverticulum may not be detected by pertechnetate imaging despite the presence of ectopic gastric mucosa. When the scan is negative, visceral angiography is an alternative procedure for detecting Meckel's diverticulum. We encountered a case of pathology-proven Meckel's diverticulum whose angiography result was diagnostic, while upper gastrointestinal panendoscopy, colonofibroscopy, barium enema studies, and repeated radionuclide scans were all negative. We report on this case to emphasize the potential role for angiographic detection of Meckel's diverticulum.

A total of 65 blood samples collected from Holstein cattle were employed for DNA extraction. Genomic DNA were amplified by means of random amplified polymorphic DNA (RAPD). One hundred and one random primers (Operon kits OPAA, OPAO, OPAV, OPC, OPE and OPA-06) were used for polymerase chain reactions (PCR). The PCR products were size fractionated by means of electrophoresis in agarose gel, transferred to a nylon membrane, and then hybridized with a alpha-32P-labeled microsatellite probe for random amplified microsatellite polymorphism (RAMPO) analysis. All the primers produced many amplification patterns in RAMPO fingerprints, but only OPE-01 (5'-CCCAAGGTCC-3') yielded a male-specific strong signal. Among the 65 cases, the specific band could be observed in the RAMPO fingerprints of the 24 male samples but not in the 41 female samples. Therefore, this specific band is peculiar to male cattle.

There are various classification systems for pituitary adenomas based on whether mammosomatotroph cells, which simultaneously express both prolactin (PRL) and growth hormone (GH), can be found. Until the present, the identification of such cells required special techniques and could not be performed in paraffin-embedded specimens. This hindered large-scale studies for detection of mammosomatotrophs in various pituitary adenomas and, as a result, such classification has remained controversial. To establish a methodology for the detection of mammosomatotrophs in paraffin-embedded specimens and to propose a more logical classification for pituitary adenomas, the authors conducted this retrospective study.We performed double immunofluorescence staining of PRL and GH in paraffin-embedded specimens of various pituitary adenomas with subsequent observation with a confocal laser-scanning microscope.Mammosomatotrophs were found in four of the 10 GH-secreting adenomas and one of the 10 clinically nonfunctioning adenomas. However, mammosomatotrophs were not identified in all 10 cases of prolactinoma.This is the first report in the literature that successfully demonstrates the presence of mammosomatotrophs in routine paraffin-embedded pituitary adenomas. The new methodology is important for future study of the function and role of these cells. A large-scale study for mammosomatotrophs in various pituitary adenomas with this method and a more logical classification of pituitary adenomas are proposed.

We report structure determination of an octaene fatty acid, 4,7,10, 13,16,19,22,25-octacosaoctaenoic acid (28:8n-3). The molecular weight and double bond locations were determined using acetonitrile chemical ionization mass spectrometry (MS) and MS/MS and were confirmed by MS of hydrogenated and deuterogenated 28:8 and by argentation thin-layer chromatography. 28:8n-3 was 1.2 +/- 0.1%, in oil derived from the heterotrophic dinoflagellate Crypthecodinium cohnii and a commercial polyunsaturated fatty acid concentrate derived from fish oils (0.16 +/- 0.01%), both components of human dietary supplements. It was not found in whole bovine retina, cultured Y79 human retinoblastoma cells, or neonate baboon cerebral cortex. The long chain polyunsaturates present in the C. cohnii oil suggest a possible route for 28:8n-3 biosynthesis similar to that for biosynthesis of 22:6n-3.