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BSTRACT Traditionally, identification of the Muskingum routing coefficients has been based on observations of the linearity of a loop formed by graphically plotting a forward and a reverse path. This graphical procedure is time-consuming and may not minimize the error of estimation. A procedure was developed to improve the drawbacks of the graphical method. This procedure calls for (a) the use of least square regression on the forward and reverse paths to determine their respective slopes, and (b) the use of statistical t-test to evaluate the hypothesis that these two slopes are equal. The computational procedure is repeated, using incremental values of the flow weighting coefficient, x. A graph of the computed t-value versus x can be constructed. The optimal value of x, as read from the graph, occurs at the minimum computed t-value. The procedure has been demonstrated superior to the graphical method for three illustrative examples, resulting in a reduction of the error squares by factors ranging from 5 to 6. [ABSTRACT FROM AUTHOR]

BSTRACT: A steady-state, one-dimensional water quality model has been formulated to evaluate spatial variations of Biochemical Oxygen Demand, ammonia nitrogen, and dissolved oxygen for nontidal, branched river systems, with point sources of treated wastes and uniform nonpoint-source loads, under aerobic and/or anaerobic stream conditions. For anaerobic conditions, the decay rate of organic matter is assumed to be limited by the rate of oxygen addition to the streams via stream reaeration and net algal photosynthesis and respiration contributions. The model is applicable to stream impact analysis under sustained wet weather conditions, during which storm-runoff loads are generated by storms of sufficiently long duration to approach steady state in the river system. [ABSTRACT FROM AUTHOR]

BSTRACT: Non-point source pollution has been characterized, in magnitude and in concentration of pollutants, by intermittent and impulse-type discharges into receiving waters, causing shock-loading problems for the ecosystems of these water bodies. The quality of storm runoff appears random and complex in nature. There are not yet universally applicable assessment tools for analysis and evaluation of the impacts and contributions of pollutant loads to receiving waters. This paper reviews and recommends methods for predicting storm runoff loads. The state-of-the-art for storm runoff runoff pollution prediction includes: zero-order, direct, statistical and descriptive methods. For transient water quality analysis of individual storm events, it is essential to have an efficient sampling is considered necessary to a detailed time history of runoff flows and loadings within a storm and for a limited number of storms. Homogeneous-land-use and statistical-synthetic approaches are recommended as accurate and practical methods for storm-runoff-load prediction. These two approaches are event-oriented, predicting time-varying runoff loads for transient water quality analysis, utilizing data collected from intensive sampling programs. [ABSTRACT FROM AUTHOR]

BSTRACT: This study was to designed to determine concentrations of selected metals, organic compounds, pesticides, and conventional pollutants in stormwater runoff from two North Carolina businesses in each of the following five general industrial groups: auto salvage, metal fabrication, scrap and recycling, vehicle maintenance, and wood preserving facilities. The sampling procedure involved collecting a first flush sample of runoff from a single storm event and both first flush and composite samples of runoff from three consecutive storm events. Analysis of samples collected during the first flush indicated that zinc and copper were the most common of the 13 metals included in the analysis. Additional analysis documented that several volatile organic, semi-volatile organic, or pesticide compounds including acrolein, methylene chloride, xylenes, toluene, tetrachloroethylene, trichloroethylene, pentachlorophenol, and aldrin were also found in the first flush samples. Concentrations of aggregate organics, nitrogen, phosphorus, and sediment were determined in both first flush and three-hour composite samples. Concentrations of pollutants in first flush samples were similar to those in corresponding composite samples. [ABSTRACT FROM AUTHOR]

21-Hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal hyperplasia, with an incidence of 1:14000 live births and equal prevalence among males and females. Newborns with the most severe "salt-wasting" form of 21-OHD are susceptible to salt-wasting crises in the first few weeks of life. This is associated with morbidity and mortality. 21-OHD newborn screening (NBS) is currently performed in many countries. Despite several prominent medical societies recommending 21-OHD NBS, no state in Australia currently screens for this condition. We report a case that illustrates the need to reconsider including 21-OHD in NBS. 21-OHD NBS can be reliable, sensitive and effective in reducing morbidity and mortality. [ABSTRACT FROM AUTHOR]

Guided by in silico analysis tools and biotransformation technology, new derivatives of natural compounds with heightened bioactivities can be explored and synthesized efficiently. In this study, in silico data mining and molecular docking analysis predicted that glucosides of skullcapflavone II (SKII) were new flavonoid compounds and had higher binding potential to oncogenic proteins than SKII. These benefits guided us to perform glycosylation of SKII by utilizing four glycoside hydrolases and five glycosyltransferases (GTs). Findings unveiled that exclusive glycosylation of SKII was achieved solely through the action of GTs, with Bacillus subtilis BsUGT489 exhibiting the highest catalytic glycosylation efficacy. Structure analysis determined the glycosylated product as a novel compound, skullcapflavone II-6'-O-β-glucoside (SKII-G). Significantly, the aqueous solubility of SKII-G exceeded its precursor, SKII, by 272-fold. Furthermore, SKII-G demonstrated noteworthy anti-melanoma activity against human A2058 cells, exhibiting an IC 50 value surpassing that of SKII by 1.4-fold. Intriguingly, no substantial cytotoxic effects were observed in a murine macrophage cell line, RAW 264.7. This promising anti-melanoma activity without adverse effects on macrophages suggests that SKII-G could be a potential candidate for further preclinical and clinical studies. The in silico tool-guided synthesis of a new, highly soluble, and potent anti-melanoma glucoside, SKII-G, provides a rational design to facilitate the future discovery of new and bioactive compounds., (© 2024 International Union of Biochemistry and Molecular Biology, Inc.)

Common genetic variants identified in the general population have been found to increase phenotypic risks among individuals with certain genetic conditions. Up to 90% of individuals with tuberous sclerosis complex (TSC) are affected by some type of epilepsy, yet the common variants contributing to epilepsy risk in the general population have not been evaluated in the context of TSC-associated epilepsy. Such knowledge is important to help uncover the underlying pathogenesis of epilepsy in TSC which is not fully understood, and critical as uncontrolled epilepsy is a major problem in this population. To evaluate common genetic modifiers of epilepsy, our study pooled phenotypic and genotypic data from 369 individuals with TSC to evaluate known and novel epilepsy common variants. We did not find evidence of enhanced genetic penetrance for known epilepsy variants identified across the largest genome-wide association studies of epilepsy in the general population, but identified support for novel common epilepsy variants in the context of TSC. Specifically, we have identified a novel signal in SLC7A1 that may be functionally involved in pathways relevant to TSC and epilepsy. Our study highlights the need for further evaluation of genetic modifiers in TSC to aid in further understanding of epilepsy in TSC and improve outcomes., (© 2024 Wiley Periodicals LLC.)

The aim of this study was to review the intervention components of school-based oral health-related behavioural interventions using the Theoretical Domains Framework (TDF). We identified relevant papers from the review of Cooper et al., and these papers came from both the original inclusion and exclusion article lists. We also modified and updated their search strategies (2013 - April 2019). The 53 included papers reported on 79 interventions (experimental groups = 57 interventions, control groups = 22 interventions). Most of the papers used three to nine domains (average = 5.6) in their experimental interventions, and the most commonly used domains were 'knowledge,' 'skills,' 'social influences,' and 'environmental context and resources.' Considering the complexity of intervention components in one programme, there is no one specific domain or domain set that can determine the success of behavioural interventions. The design of future programmes should be guided by a complex intervention methodology. However, the best combination set might not exist, and the choice of domains should depend on local context or resources. This study can be used as a resource for identifying previous papers, which have used the same domains., (© 2021 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.)

Bone fracture is one of the most common injuries. Despite the high regenerative capacity of bones, failure of healing still occurs to near 10% of the patients. Herein, we aim to investigate the modulatory role of neurofibromatosis type I gene (NF1) to osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and new bone formation after fracture in a rat model. We studied the NF1 gene expression in normal and non-union bone fracture models. Then, we evaluated how NF1 overexpression modulated osteogenic differentiation of BMSCs, autophagy activity, mTORC1 signalling and osteoclastic bone resorption by qRT-PCR, Western blot and immunostaining assays. Finally, we injected lentivirus-NF1 (Lv-NF1) to rat non-union bone fracture model and analysed the bone formation process. The NF1 gene expression was significantly down-regulated in non-union bone fracture group, indicating NF1 is critical in bone healing process. In the NF1 overexpressing BMSCs, autophagy activity and osteogenic differentiation were significantly enhanced. Meanwhile, the NF1 overexpression inhibited mTORC1 signalling and osteoclastic bone resorption. In rat non-union bone fracture model, the NF1 overexpression significantly promoted bone formation during fracture healing. In summary, we proved the NF1 gene is critical in non-union bone healing, and NF1 overexpression promoted new bone formation after fracture by enhancing autophagy and inhibiting mTORC1 signalling. Our results may provide a novel therapeutic clue of promoting bone fracture healing., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objective: To evaluate the efficacy and safety of lesinurad for the treatment of hyperuricemia in patients with gout., Design: Systematic review and meta-analysis of randomized controlled trials (RCTs)., Patients or Participants: Five RCTs, which included 1959 patients, compared the efficacy and safety of lesinurad in patients with hyperuricemia associated with gout., Measurements and Results: Relevant studies were identified from PubMed, EMBASE, Cochrane Library databases, and the ClinicalTrials.gov registry. Two reviewers independently assessed the studies. Individual effect sizes were standardized, and a meta-analysis was conducted to calculate the pooled effect size by using a random-effect model. The primary outcomes were the proportion of patients achieving target serum uric acid (sUA) levels by month 6 and the mean sUA levels at month 6 and month 12. Gout-related outcomes were also assessed. The secondary outcome was the number of treatment-emergent adverse events (TEAEs). Compared with xanthine oxidase inhibitor (XOI) monotherapy, lesinurad 200 mg or 400 mg in combination with allopurinol or febuxostat exhibited a higher proportion of patients achieving target sUA levels of < 6.0 mg/dl or < 5.0 mg/dl, respectively, by month 6. Lesinurad-plus-XOI groups also significantly sustained lower mean sUA levels at month 6 and month 12 compared to XOI alone group. In gout-related outcomes, no significant treatment group differences favored lesinurad. The number of TEAEs was comparable between the lesinurad 200 mg-plus-XOI group and the XOI-monotherapy group. Although lesinurad 400 mg monotherapy demonstrated superior efficacy compared with placebo, significantly more TEAEs occurred., Conclusions: Although the combination of lesinurad 200 mg and XOI is effective and well tolerated for treating patients with gout who have not achieved an adequate response to XOI monotherapy, clinical gout-related outcomes were not improved. Therefore, additional studies investigating the long-term clinical implication of lesinurad are warranted., (© 2018 Pharmacotherapy Publications, Inc.)

Aims: Depression is one of the most common nonmotor symptoms in Parkinson's disease (PD). But the pathogenesis is still unclear. Studies have shown that depression in PD is closely related to the white matter abnormalities, but the number of studies is still very small and lack of whole brain white matter lesions study., Methods: In this study, we investigated whole brain white matter integrity in 31 depressed PD patients and 37 nondepressed PD patients by diffusion tensor imaging., Results: There was no difference in age, gender, age of onset, disease duration, Hoehn-Yahr scale, Unified Parkinson's Disease Rating Scale scores-III, and Mini-Mental State Examination scores between the two groups. The only difference was the Hamilton Depression Rating Scale. Depressed PD patients showed reduced fractional anisotropy values in the left anterior corona radiata, left posterior thalamic radiation, left cingulum, left superior longitudinal fasciculus, left sagittal stratum (including inferior longitudinal fasciculus and inferior fronto-occipital fasciculus), and left uncinate fasciculus. In patients with depression, the Hamilton Depression Rating Scale (HDRS) was negatively correlated with the FA value in the left cingulum (r = -0.712, P = .032) and left superior longitudinal fasciculus (r = -0.699, P = .025)., Conclusions: This study suggested depression in PD was related to impaired white matter integrity especially the long contact fibers in the left hemisphere. These findings may be helpful for further understanding the potential mechanisms underlying depression in PD., (© 2017 John Wiley & Sons Ltd.)

Enrichment and propagation of gonocytes or spermatogonial stem cells (SSCs) from cryopreserved testicular tissue is essential to apply SSCs-related techniques in large domestic animals. We previously reported the cryopreservation of adult bovine testicular tissue. Here, we conducted the enrichment and culture of putative gonocytes from cryopreserved testicular tissues of post-natal 1-day-old bulls. The testicular structure was well maintained after freezing and thawing. Higher mRNA levels of gonocyte/SSCs markers (PLZF, GFRα1, and UCHL-1) than those of pluripotency genes (Oct4, Sox2, and Nanog) were detected in the frozen-thawed sex cords. GFRα1 was specifically detected in the membrane and cytoplasm of gonocytes by immunostaining. Differential plating provided 40-50% enrichment of putative gonocytes. They were single, paired-, aligned-cells, or grape cluster-like colonies in minimum essential medium (MEM) containing 2.5% FBS + 2 mM glutamine + 100 IU/mL penicillin-streptomycin + 40 μg/mL gentamycin + 15 mM HEPES + 10 mM β-mercaptoethanol + 0.1 mM non-essential amino acids + 1 mM sodium pyruvate. On day 3, gonocyte progeny increased and the contaminated somatic cells spread and concurrently divided slowly. On day 5, gonocyte progeny proliferated continuously and typical intercellular bridges formed by incomplete cytokinesis in paired-cells or aligned-cysts were observed. Immunochemically, they were still GFRα1 and PLZF positive. These cells expressed significantly higher gonocyte/SSCs marker mRNAs than pluripotency gene mRNAs, concomitant with a higher level of differentiated spermatogonia marker c-kit. With time, gonocyte progeny colonies appeared in varied sizes and expanded dramatically on day 7. After cultured for 9-10 days, however, large colonies collapsed and dispersed as some single cells and small syncytial cysts. Together, MEM containing 10% dimethyl sulfoxide + 2.5% newborn calf serum provides efficient cryoprotection for the testicular tissue from 1-day-old neonatal bulls. Putative gonocytes enriched from these nascent tissues present robust proliferation capacity, conserved gonocyte/SSCs markers, and SSCs-like in vitro features., (© 2016 American Society of Andrology and European Academy of Andrology.)

Background: Ischemic stroke is a major cause of death and disability in the world. A major ischemic stroke subtype, large-vessel ischemic stroke (large artery atherosclerosis; LAA), has been shown to have some genetic components in individuals of European ancestry. However, it is not clear whether the genetic predisposition to LAA stroke varies among ethnicities. We sought to identify genetic factors that contribute to LAA stroke in 2 independent samples of Han Chinese individuals., Methods and Results: Novel genetic variants that predispose individuals to LAA stroke were identified using a genome-wide association study (GWAS) of 444 individuals with LAA stroke and 1727 controls in a Han Chinese population residing in Taiwan. The study was replicated in an independent Han Chinese population comprising an additional 319 cases and 1802 controls. We identified 5 single-nucleotide polymorphisms, including rs2415317 (P=3.10×10(-8)), rs934075 (P=4.00×10(-9)), rs944289 (P=3.57×10(-8)), rs2787417 (P=1.76×10(-8)), and rs1952706 (P=2.92×10(-8)), at one novel locus on chromosome 14q13.3 within PTCSC3 (encoding papillary thyroid carcinoma susceptibility candidate 3) that were associated with LAA stroke at genome-wide significance (P<5×10(-8))., Conclusions: Our data provide strong support for future studies on the role of PTCSC3 in the pathogenesis of LAA stroke and the association between LAA stroke development and thyroid function. In addition, these findings provide insights into the genetic basis of LAA stroke and identify a novel pathway that might be applicable for future therapeutic intervention., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Whether 10-day or 14-day sequential therapy is superior to 14-day triple therapy in the first-line treatment of Helicobacter pylori remains controversial., Aim: To compare the efficacy of 10-day or 14-day sequential therapy vs. 14-day triple therapy., Methods: Randomised controlled trials (RCTs) comparing 10-day or 14-day sequential therapy and 14-day triple therapy as first-line treatment in adults were searched from the PubMed and Cochrane databases from 2000 to October 2015. Abstracts from international annual conferences were also searched. The primary and secondary outcomes were the eradication rate according to the intention-to-treat analysis and adverse effects, respectively., Results: Of the 109 articles identified, 13 RCTs including 2749 patients in the sequential therapy group and 2424 patients in the 14-day triple therapy group were eligible. Overall, sequential therapy for 10 or 14 days was not significantly superior to 14-day triple therapy [Risk ratio (RR) 1.04, 95% confidence interval (CI) 0.99-1.08, P = 0.145]. However, there was significant heterogeneity (I(2) = 57.6%, P = 0.005). In the subgroup analysis of four trials, we found that 14-day sequential therapy was significantly more effective than 14-day triple therapy (RR: 1.09, 95% CI: 1.04-1.16, P = 0.002), and there was no significant heterogeneity (I(2) = 0%, P = 0.624) in this comparison. Sequential therapy given for 10 days was not superior to 14-day triple therapy (RR: 1.03, 95% CI: 0.98-1.09, P = 0.207). There was no significant difference in the risk of adverse effects., Conclusion: Sequential therapy given for 14 days, but not 10 days, was more effective than 14-day triple therapy as first-line treatment., (© 2015 John Wiley & Sons Ltd.)

Aim: Lactates accumulate in ischemic brains. G protein-coupled receptor 81 (GPR81) is an endogenous receptor for lactate. We aimed to explore whether lactate is involved in ischemic injury via activating GPR81., Methods: N2A cells were transfected with GFP-GPR81 plasmids 24 h previously, and then treated with GPR81 antagonist 3-hydroxy-butyrate (3-OBA) alone or cotreated with agonists lactate or 3, 5-dihydroxybenzoic acid (3, 5-DHBA) during 3 h of oxygen-glucose deprivation (OGD). Adult male C57BL/6J mice and primary cultured cortical neurons were treated with 3-OBA at the onset of middle cerebral artery occlusion (MCAO) or OGD, respectively., Results: The GPR81 overexpression increased the cell vulnerability to ischemic injury. And GPR81 antagonism by 3-OBA significantly prevented cell death and brain injury after OGD and MCAO, respectively. Furthermore, inhibition of GPR81 reversed ischemia-induced apoptosis and extracellular signal-regulated kinase (ERK) signaling may be involved in the neuroprotection., Conclusions: G protein-coupled receptor 81 (GPR81) inhibition attenuated ischemic neuronal death. Lactate may aggravate ischemic brain injury by activating GPR81. GPR81 antagonism might be a novel therapeutic strategy for the treatment of cerebral ischemia., (© 2014 John Wiley & Sons Ltd.)

In the title compound, C22H23NO2, the planes of the eth-oxy-benzene rings are oriented with respect to that of the phenyl ring at dihedral angles of 61.77 (8) and 84.77 (8)°, and they are twisted with respect to one another, with a dihedral angle of 80.37 (7)°. In the crystal, weak C-H⋯π inter-actions link the mol-ecules into supra-molecular chains propagating along [101].

In the title compound, C21H21NO3S, the planes of the two benzene rings are nearly perpendicular to one another [dihedral angle = 84.50 (10)°] and they are oriented with respect to the plane of the thio-phene ring at dihedral angles of 59.15 (9) and 66.61 (9)°. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds, forming supra-molecular chains propagating along the b-axis direction.

Background: The need for new effective Helicobacter pylori eradication therapy has focused efforts on the development and optimization of regimens with excellent eradication rates such as 14-day hybrid therapy. This study evaluated whether the duration of hybrid therapy could be reduced while maintaining a high eradication rate and to examine the effect of antibiotic resistance on outcome., Materials and Methods: Three separate multicenter pilot studies were carried out concurrently. To reduce selection bias, eligible subjects were randomized to 10-day, 12-day, or 14-day hybrid therapy consisting of esomeprazole 40 mg and amoxicillin 1 gm twice daily for 10, 12, or 14 days plus clarithromycin 500 mg, and metronidazole 500 mg twice daily for the final 7 days. The primary outcome was H. pylori eradication per-protocol assessed at least 8 weeks after therapy., Results: A total of 220 subjects were entered. The per-protocol analyses contained 60, 61, 61 subjects in the 10-, 12- and 14-day therapy studies, respectively. The eradication rates, per-protocol, were similar: 95% (95% confidence interval (CI); 89.5-100%) for 10-day, 95.1% (95% CI; 89.7-100%) for 12-day, and 93.4% (95% CI; 87.2-99.7%) for 14-day hybrid therapies. Antibiotic resistance was infrequent; however, all metronidazole or clarithromycin resistances were cured with 12- and 14-day therapies., Conclusion: These results suggest that in regions of moderate to low clarithromycin and/or metronidazole resistance it may be feasible to shorten hybrid therapy to 10 or 12 days. Further study is needed to compare hybrid and concomitant therapy in regions with moderate-to-high clarithromycin and/or metronidazole resistance., (© 2014 John Wiley & Sons Ltd.)

The asymmetric unit of the title Schiff base molecule, C25H20N2O, contains two independent mol-ecules. In each mol-ecule, the C=N bond is in an E conformation. The most significant difference between the two mol-ecules is seen for the dihedral angles between the meth-oxy-substituted benzene ring and the two phenyl rings, which are 85.5 (1) and 82.3 (1)° in the first mol-ecule, and 49.0 (1) and 40.4 (1)° in the second. This conformational difference is reflected in the central C=N-C C torsion angle, which is 28.7 (2)° in the first mol-ecule and -29.8 (3)° in the other. In each mol-ecule, there is an intra-molecular O-H⋯N hydrogen bond.

In the title mol-ecule, C22H22N2O4, the eth-oxy-phenyl rings are oriented at dihedral angles of 69.31 (13) and 75.90 (13)° to the nitro-phenyl ring and are twisted to each other, making a dihedral angle of 78.55 (13)°. In the crystal, weak C-H⋯O hydrogen bonds and C-H⋯π inter-action link the mol-ecules into a three-dimensional supra-molecular architecture.

In the title compound, C24H18N2OS, the pyridine and the two phenyl rings are oriented at dihedral angles of 10.1 (5), 71.7 (6) and 68.7 (5)°, respectively, to the central thio-phene ring. In the crystal, pairs of weak C-H⋯O hydrogen bonds link inversion-related mol-ecules, forming dimers. The dimers are linked by further weak C-H⋯O hydrogen bonds, forming chains running along the a-axis direction.

A novel supramolecular framework, catena-poly[[[aqua(2-phenylquinoline-4-carboxylato-κO)silver(I)]-μ-4,4'-bipyridine-κ(2)N:N'] dihydrate], {[Ag(C16H10NO2)(C10H8N2)(H2O)]·2H2O}n, has been synthesized and structurally characterized. The Ag(I) centres are four-coordinated and bridged by 4,4'-bipyridine (4,4'-bipy) ligands to form a one-dimensional Ag-bipy chain. The Ag-bipy chains are further linked together by intermolecular O-H···O and O-H···N hydrogen-bonding interactions between adjacent chains, resulting in a three-dimensional framework.

The prevalence of and psychosocial risks for suicide attempts was investigated in college students in Taiwan by gender, after controlling for depressive symptoms. Self-reported data were collected from a nationally representative sample of 2,835 college students; 11.90% of females and 8.87% of males reported they had attempted suicide in the preceding 12 months. After controlling for depression, suicidal ideations were associated with suicide attempts in females, whereas there were fewer positive expectations toward the future associated with suicide attempts in males. Several explanations for the high prevalence of suicide attempts among college students in Taiwan were discussed. In the future, further verification of the findings is necessary., (© 2013 The American Association of Suicidology.)

Objective: To systematically review evidence of the accuracy of the procalcitonin test for diagnosis of bacterial infection in patients with autoimmune disease., Methods: The major databases Medline, EMBase, and the Cochrane Library were searched for studies published between January 1966 and October 2011 that evaluated procalcitonin, alone or in comparison with other laboratory markers such as C-reactive protein (CRP), as a diagnostic marker for bacterial infection in patients with autoimmune disease and provided sufficient data to permit construction of 2 × 2 tables., Results: Nine studies were included in the final meta-analysis. The area under the summary receiver operating characteristic curve values were 0.91 (95% confidence interval [95% CI] 0.88-0.93) for procalcitonin and 0.81 (95% CI 0.78-0.84) for CRP. In general, testing for procalcitonin was highly specific for identifying infectious complications, although it was not as sensitive as testing for CRP. Pooled sensitivity was 0.75 (95% CI 0.63-0.84) for procalcitonin tests and 0.77 (95% CI 0.67-0.85) for CRP tests. Pooled specificity was 0.90 (95% CI 0.85-0.93) for procalcitonin tests and 0.56 (95% CI 0.25-0.83) for CRP tests. The positive likelihood ratio for procalcitonin (7.28 [95% CI 5.10-10.38]) was sufficiently high to qualify procalcitonin testing as a rule-in diagnostic tool, while the negative likelihood ratio (0.28 [95% CI 0.18-0.40]) was not sufficiently low to qualify procalcitonin testing as a reliable rule-out diagnostic tool., Conclusion: Procalcitonin has higher diagnostic value than CRP for the detection of bacterial sepsis in patients with autoimmune disease, and the test for procalcitonin is more specific than sensitive. A procalcitonin test is not recommended to be used in isolation as a rule-out tool., (Copyright © 2012 by the American College of Rheumatology.)

The asymmetric unit of the title compound, C(9)H(9)NO(2)·2H(2)O, comprises two independent organic mol-ecules and four water mol-ecules of crystallization. The heterocyclic rings are not planar: in one mol-ecule, the C atom bearing the O atom and the adjacent methyl-ene C atom are displaced by 0.320 (3) and 0.677 (3) Å, respectively, from the other eight atoms of the fused ring system. Equivalent values of 0.243 (3) and 0.659 (3) Å apply to the second mol-ecule. In the crystal, the components are linked by N-H⋯O and O-H⋯O hydrogen bonds, forming a three-dimensional network.

Cortical oscillations arise during behavioral and mental tasks, and all temporal oscillations have particular spatial patterns. Studying the mechanisms that generate and modulate the spatiotemporal characteristics of oscillations is important for understanding neural information processing and the signs and symptoms of dynamical diseases of the brain. Nevertheless, it remains unclear how GABAergic inhibition modulates these oscillation dynamics. Using voltage-sensitive dye imaging, pharmacological methods, and tangentially cut occipital neocortical brain slices (including layers 3-5) of Sprague-Dawley rat, we found that GABAa disinhibition with bicuculline can progressively simplify oscillation dynamics in the presence of carbachol in a concentration-dependent manner. Additionally, GABAb disinhibition can further simplify oscillation dynamics after GABAa receptors are blocked. Both GABAa and GABAb disinhibition increase the synchronization of the neural network. Theta frequency (5-15-Hz) oscillations are reliably generated by using a combination of GABAa and GABAb antagonists alone. These theta oscillations have basic spatiotemporal patterns similar to those generated by carbachol/bicuculline. These results are illustrative of how GABAergic inhibition increases the complexity of patterns of activity and contributes to the regulation of the cortex., (© 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)

In the triaryl-amine group of the title compound, C(26)H(20)N(2)O(2), the N atom adopts an approximately trigonal-planar geometry, lying 0.046 (5) Å from the plane P defined by its three neighbouring C atoms; the benzene and two terminal phenyl rings are twisted by 37.4 (1), 31.4 (1) and 47.8 (1)°, respectively from plane P. In the trans-stilbene fragment, the two benzene rings form a dihedral angle of 31.3 (1)°. In the crystal, weak inter-molecular C-H⋯O inter-actions link the mol-ecules into ribbons in [100].

Trop-2, a cell surface glycoprotein, contains both extracellular epidermal growth factor-like and thyroglobulin type-1 repeat domains. Low TROP2 expression was observed in lung adenocarcinoma tissues as compared with their normal counterparts. The lack of expression could be due to either the loss of heterozygosity (LOH) or hypermethylation of the CpG island DNA of TROP2 upstream promoter region as confirmed by bisulphite sequencing and methylation-specific (MS) polymerase chain reaction (PCR). 5-Aza-2'-deoxycytidine treatment on lung cancer cell (CL) lines, CL1-5 and A549, reversed the hypermethylation status and elevated both TROP2 mRNA and protein expression levels. Enforced expression of TROP2 in the lung CL line H1299 reduced AKT as well as ERK activation and suppressed cell proliferation and colony formation. Conversely, silencing TROP2 with shRNA transfection in the less efficiently tumour-forming cell line H322M enhanced AKT activation and increased tumour growth. Trop-2 could attenuate IGF-1R signalling-mediated AKT/β-catenin and ERK activation through a direct binding of IGF1. In conclusion, inactivation of TROP2 due to LOH or by DNA methylation may play an important role in lung cancer tumourigenicity through losing its suppressive effect on IGF-1R signalling and tumour growth., (Copyright © 2012 EMBO Molecular Medicine.)

In the title compound, C(26)H(24)Br(2)N(2)O(2), the central naphthalene system carries two Br atoms and two -CH(2)CH(2)NHC(6)H(5) substituents. The phenyl rings of the latter residues are inclined at 74.17 (17) and 51.4 (2)° with respect to the naphthalene ring system. Each alkyl chain adopts a fully extended all-cis conformation with respect to the naphthalene and phenyl rings [N-C-C-O torsion angles = 68.6 (4) and 60.5 (4)°]. In the crystal, one of the N-H groups forms bifurcated N-H⋯(Br,O) hydrogen bonds, which link the mol-ecules into inversion-related dimers. The centrosymmetric dimers are aggregated via pairs of C-H⋯π inter-actions into sheets parallel to (110).

The central pyridine ring of the 2,2':6',2''-terpyridine fragment of the title compound, C(35)H(24)N(4)O(2), forms dihedral angles of 8.3 (2), 10.6 (3) and 39.4 (3)°, respectively, with the two outer pyridine rings and the attached benzene ring. In the crystal, weak C-H⋯O inter-actions link the mol-ecules into chains in [010].

The title compound, C(54)H(48)N(2)O(2), lies about an inversion centre. The carbazole ring system makes dihedral angles of 58.43 (7) and 88.96 (7)°, respectively, with the adjacent and central benzene rings. The dihedral angle between the two benzene rings is 52.01 (8)°. In the crystal, mol-ecules are linked by pairs of C-H⋯O inter-actions, forming a tape along the a axis. The methyl group is disordered over two sets of sites with occupancies of 0.63 (3) and 0.37 (3).

The asymmetric unit of the title compound, C(9)H(10)N(4), consists of two mol-ecules in which the dihedral angles between the planes of the imidazole and pyrimidine rings are 4.8 (1) and 2.1 (1)°.

We performed a genome-wide linkage analysis to identify susceptibility loci in a large six-generation extended family previously reported with early-onset osteoarthritis (OA) DNA sequencing was performed to investigate involvement of the COMP (Cartilage oligomeric matrix protein) gene in this family. The region covering D19S884, D19S226, and D19S414 on chromosome 19p following genome-wide scan from 70 individuals of this kindred showed significant linkage, with a maximum point LOD (logarithm of the odds ratio) score of 2.51 at D19S226. Direct sequencing of the COMP gene, the most plausible candidate gene in the region, identified a c.2152C>T substitution in exon 18 which resulted in a substitution of tryptophan for arginine at position 718 located in the C terminal globular domain of the gene product. A total of 26 individuals were identified with this mutation of which 21 affected individuals had the mutation, and the other five younger individuals (18.6 ± 11.3 years of age) carried the mutation without symptoms. The results indicate that COMP is the disease susceptibility gene and the c.2152C>T mutation in exon 18 could cause early-onset OA phenotypes in this kindred, which is compatible with a previous report that this mutation also causes a mild form of multiple epiphyseal dysplasia (MED)., (© 2011 The Authors Annals of Human Genetics © 2011 Blackwell Publishing Ltd/University College London.)

Background: Ten-day sequential therapy with a proton pump inhibitor (PPI) and amoxicillin followed by a PPI, clarithromycin, and an imidazole typically achieves Helicobacter pylori eradication rates of 90-94% (Grade B success)., Aims: We tested whether prolonging treatment and continuing amoxicillin throughout the 14-day treatment period would produce a ≥ 95% result., Methods: This was a multicenter pilot study in which H. pylori-infected patients received a 14-day sequential-concomitant hybrid therapy (esomeprazole and amoxicillin for 7 days followed by esomeprazole, amoxicillin clarithromycin, and metronidazole for 7 days). H. pylori status was examined 8 weeks after therapy. Success was defined as achieving ≥ 95% eradication by per-protocol analysis., Results: One hundred and seventeen subjects received hybrid therapy. The eradication rate was 99.1% (95% confidence interval (CI), 97.3-100.0%) by per-protocol analysis and 97.4% by intention-to-treat analysis (95% CI, 94.5-100.0%). Adverse events were seen in 14.5%; drug compliance was 94.9%., Conclusions: Fourteen-day hybrid sequential-concomitant therapy achieved > 95%H. pylori eradication (Grade A result). Further studies are needed 1, in regions with different patterns and frequencies of resistance to confirm these findings, and 2, to examine whether Grade A success is maintained with hybrid therapy shorter than 14 days., (© 2011 Blackwell Publishing Ltd.)

Background and Aims:  Ten-day sequential therapy with a proton-pump inhibitor (PPI) and amoxicillin followed by a PPI, clarithromycin, and an imidazole typically achieves Helicobacter pylori (H. pylori) eradication rates between 90 and 94% (i.e., Grade B success). It has been suggested that prolonging the duration of therapy might improve the treatment success. We tested whether prolonging treatment duration to 14-days would improve the results to 95% or greater eradication., Methods:  This was a multi-center, single site, pilot study in which H. pylori-infected patients received a 14-day sequential therapy (esomeprazole and amoxicillin for 7 days followed by esomeprazole, clarithromycin, and metronidazole for 7 days). H. pylori status was assessed 8 weeks after therapy. Success was defined as achieving 95% or greater eradication by per-protocol (PP) analysis., Results:   One hundred and twenty-three subjects received the 14-day sequential therapy. The eradication rate was 93.9% (95% confidence interval [CI], 89.5-98.3%) by PP and 91.9% (95% CI, 87.1-96.7%) by intention-to-treat analysis. Adverse events were experienced by 21.1%; compliance of 90% or greater was 95.9%., Conclusions:  Extending sequential therapy to 14 days did not result in improving the treatment outcome to 95% or greater., (© 2011 Blackwell Publishing Ltd.)

Interstitial deletion of 16q has emerged into a recognizable pattern of congenital malformation. We report on a 9-year-old boy with short stature, psychomotor retardation, high forehead, broad flat nasal bridge, hypertelorism, cup-shaped ears, short neck, and a normal karyotype. Using high-density oligonucleotide array chip (Affymetrix 6.0) to perform parental and proband samples concurrently on three chips and interpreted as a trio set, a de novo 3.2 Mb deletion from bands q12.2 to q13 on chromosome 16 (from 52.08 to 55.3 Mb) of paternal origin was identified. The deletion was confirmed by quantitative genomic PCR and the break points were defined by junction PCR. Our study demonstrated the power of high-density oligonucleotide array chip in identifying novel submicroscopic deletions that were not detectable using G-banding cytogenetic technology. Furthermore, our result narrowed down the critical region for craniofacial features in interstitial 16q11.2-q13 deletion syndrome. In patients who have high forehead, broad flat nasal bridge, hypertelorism, cup-shaped ears, short neck and short stature, high-density array should be included in initial work up.

The centrosymmetric title mol-ecule, C(28)H(32)N(2)O(2), has a central benzene ring subsituted in the 1- and 4-positions by (ethene-2,1-di-yl)pyridine groups, and in the 2- and 5-positions by but-oxy groups. The whole mol-ecule is X-shaped and relatively flat, the dihedral angle between the pyridine and the central benzene ring being 11.29 (10)°. In the crystal, neighboring mol-ecules are linked by weak C-H⋯N inter-actions, forming a two-dimensional undulating network.

1. UbcH10 is the cancer-related E2 ubiquitin-conjugating enzyme, and its overexpression has been demonstrated in a variety of malignancies. The aim of the present study is to silence UbcH10 gene by RNA interference (RNAi) and to observe its inhibitory effect on the colorectal cancer cell growth in vitro and in vivo. 2. We constructed the expression vector pGPU6/GFP/Neo/UbcH10-RNAi (pUbcH10-RNAi), which contained a UbcH10 short hairpin RNA expression cassette. Then the UbcH10 gene silencing cell lines LoVo/UbcH10-RNAi and HT-29/UbcH10-RNAi were established. Reverse transcription-polymerase chain reaction and western blot analysis were used to evaluate the expression of the UbcH10 gene. Cell Counting Kit-8 was used to assess properties of tumour cell growth in vitro. Flow cytometry was used to detect the effect of pUbcH10-RNAi on the cell cycle of colorectal cancer cells. Furthermore, the anti-tumour effects of pUbcH10-RNAi were evaluated in vivo in a nude mouse xenografts model. 3. Results demonstrated that UbcH10 gene expression was significantly decreased in pUbcH10-RNAi treated cells. Colorectal cancer cells growth was markedly suppressed in the pUbcH10-RNAi group compared with control conditions and colorectal cancer cells were arrested in the G2-M phase. In vivo, the downregulation of UbcH10 gene expression by pUbcH10-RNAi also inhibited tumour growth in a nude mice xenograft model. 4. Our study suggests that RNA interference-mediated silencing of UbcH10 gene has anti-tumour activity on colorectal cancer and might have therapeutic potential for the treatment of colorectal cancer.

The mol-ecule of the title compound, C(12)H(11)N(3)O(2), is approximately planar with an r.m.s. deviation of 0.0814 Å from the plane through all the non-H atoms. The dihedral angle formed by the benzene and isoxazole rings is 6.88 (16)°. The mol-ecular conformation is stabilized by an intra-molecular C-H⋯N hydrogen bond, forming an S(6) ring, and the mol-ecule displays an E configuration with respect to the C=N double bond. In the crystal structure, inter-molecular N-H⋯O hydrogen bonds form centrosymmetric dimers which are further linked by weak C-H⋯N inter-actions augmented by very weak C-H⋯π contacts, forming layers parallel to (120).

Background: Several studies have suggested that the serotonin receptor 1B gene (5HT1B) may be important in the pathogenesis of alcohol dependence (alcoholism; ALC; AD). We examined whether 5HT1B gene A-161T polymorphisms (rs130058) are a susceptibility factor for total AD and subgroups of AD. We further explored correlation of this 5HT1B gene variant between anxiety-depression alcoholism (ANX/DEP ALC) and antisocial alcoholism (antisocial ALC) subgroups because of the high comorbidity of anxiety-depression, antisocial personality disorder, and AD., Methods: We recruited 522 Han Chinese in Taiwan for this study: 322 AD patients and 200 controls. The patient group was recruited primarily from medical teaching hospitals; patients with antisocial alcoholism were recruited from Taiwanese prisons. Individuals with AD were classified into 3 homogeneous clinical subgroups -- pure alcoholism (pure ALC), ANX/DEP ALC, and antisocial ALC -- using DSM-IV diagnosis. The 5HT1B gene A-161T polymorphism was determined using PCR-RFLP., Results: No significant differences in genotypic and allelic frequencies were found between controls and the total AD group or between controls and the 3 AD subgroups. However, there were significant differences in the 5HT1B gene A-161T polymorphism at both the genotype and allelic levels between the ANX/DEP ALC and antisocial ALC subgroups., Conclusions: This study suggests that the 5HT1B gene A-161T polymorphism alone is not a risk factor for increasing susceptibility to either AD or its subtypes. However, 5HT1B gene A-161T polymorphisms might be one of the common genetic factors between the ANX/DEP ALC and antisocial ALC subgroups.

In the title compound, C(14)H(13)N(3)O(3), the pyrazoline ring assumes an envelope conformation with the furanyl-bearing C atom at the flap position. The dihedral angle between the furan and nitrobenzene rings is 84.40 (9)°. Weak inter-molecular C-H⋯O hydrogen bonding is present in the crystal structure.

In the title compound, C(16)H(15)N(3)O(2), the planar [maximum deviation 0.156 (2) Å] pyrazoline ring is nearly coplanar with the 3-nitro-phenyl group and is approximately perpendicular to the phenyl ring, making dihedral angles of 3.80 (8) and 80.58 (10)°, respectively. Weak inter-molecular C-H⋯O hydrogen bonding is present in the crystal structure.

Objective: Kawasaki disease (KD) is a pediatric systemic vasculitis of unknown cause for which a genetic influence is supposed. The purpose of this study was to identify possible genetic variants in the major histocompatibility complex (MHC) region that are associated with KD and the development of coronary artery aneurysms (CAAs) in a Taiwanese population., Methods: The 168 genetic variants covering the MHC locus were analyzed in an association study of a Taiwanese cohort of 93 KD patients and 680 unrelated healthy children matched for sex and age with the study patients., Results: Eleven single-nucleotide polymorphisms (SNPs) were associated with the occurrence of KD. The SNP located at the 3'-untranslated region of HLA-E (rs2844724) was highly associated (P < 1 x 10(-7)). In addition, the frequency of the C allele was higher in KD patients without CAAs than in controls (P < 0.001) due to a significantly increased frequency of the CC and CT genotypes. Plasma levels of soluble HLA-E were significantly higher in KD patients than in controls regardless of the presence of CAAs. Furthermore, there was a trend toward higher plasma levels of soluble HLA-E in KD patients with the CT and TT genotypes of the HLA-E gene polymorphism., Conclusion: Our results suggest that the HLA-E gene polymorphism may play a role in the pathogenesis of KD.

Salvia miltiorrhiza Bunge (Chinese sage; Lamiaceae) is a valuable Chinese herbal plant, and its rhizome, known as Danshen in Chinese because of its characteristic red pigment, is the part of the plant used in herbal medicine. The red pigment in S. miltiorrhiza roots is mainly composed of numerous diterpenoid tanshinones, as the major bioactive ingredients of the herb. In plants, diterpenes are synthesized through the MEP (2-C-methyl-D-erythritol 4-phosphate) pathway in the plastids, and DXR [DXP (1-deoxy-D-xylulose 5-phosphate) reductoisomerase] is an enzyme catalysing the first step of the MEP pathway. In the present study, a full-length cDNA encoding DXR (GenBank Nucleotide Sequence Database accession no. DQ991431) was cloned from the hairy roots of S. miltiorrhiza in culture. The enzyme activity of DXR protein was verified by complementation of an Escherichia coli mutant deficient in dxr. The transcription level of the dxr gene in the hairy roots was up-regulated after exposure to hyperosmotic stress and a yeast elicitor in parallel with increased tanshinone accumulation in the hairy roots. This is the first report, to our knowledge, of elicitor-induced dxr transcription and its correlation with the accumulation of diterpenoid tanshinones in S. miltiorrhiza roots.

As activated microglia (MG) is an early sign that often precedes and triggers neuronal death, inhibition of microglial activation and reduction of subsequent neurotoxicity may offer therapeutic benefit. The present study demonstrates that rat primary cultured MG expressed Kir6.1 and SUR2 subunits of K(ATP) channel, which was identical to that expressed in BV-2 microglial cell line. The classic K(ATP) channel opener pinacidil and selective mitochondrial K(ATP) (mito-K(ATP)) channel opener diazoxide prevented rotenone-induced microglial activation and production of pro-inflammatory factors (tumour necrosis factor[TNF]-alpha and prostaglandin E(2)[PGE(2)]). And the effects of pinacidil and diazoxide were reversed by mito-K(ATP) blocker 5-hydroxydecanoate (5-HD), indicating that mito-K(ATP) channels participate in the regulation of microglial activation. Moreover, the underlying mechanisms involved the stabilization of mitochodrial membrane potential and inhibition of p38/c-Jun-N-terminal kinase (JNK) activation in microglia. Furthermore, the in vivo study confirmed that diazoxide exhibited neuroprotective effects against rotenone along with the inhibition of microglial activation and neuroinflammation. Thus, microglial mito-K(ATP) channel might be a novel prospective target for the treatment of neuroinflammation-related degenerative disorders such as Parkinson's disease.

Background: Different kinds of proton pump inhibitor-based triple therapies could result in different Helicobacter pylori eradication rates., Aim: The aims of this study were to compare the efficacy and safety of rabeprazole- and esomeprazole-based triple therapy in primary treatment of H. pylori infection in Taiwan., Patients and Methods: From June 2005 to March 2007, 420 H. pylori-infected patients were randomly assigned to receive a 7-day eradication therapy with either esomeprazole 40 mg daily (EAC group, n = 209) or rabeprazole 20 mg b.i.d. (RAC group, n = 211) in combination with amoxicillin 1 g b.i.d. and clarithromycin 500 mg b.i.d.. Follow-up endoscopy with biopsy was done 12-16 weeks after completion of eradication therapy. Those who refused endoscopic exams underwent (13)C-urea breath test to assess the treatment response., Results: Intention-to-treat analysis revealed that the eradication rate was 89.4% in the EAC group and 90.5% in RAC groups (p-value = .72). All of the subjects returned for assessment of compliance (100% in EAC group vs. 99.5% in RAC group, p-value = .32) and adverse events (3.83% in EAC group vs. 6.16% in RAC group, p-value = .27). Sixty (28.7%) and 37 (17.6%) patients in EAC and RAC group, respectively, refused endoscopy and underwent a (13)C-urea breath test to determine the treatment effect., Conclusion: In conclusion, rabeprazole- and esomeprazole-based primary therapies for H. pylori infection are comparable in efficacy and safety.

The present study was designed to examine whether age, gender, and depression level may moderate the effect of exposure to suicide news on the suicidality of college students in Taiwan. A representative sample of 3,222 college students were recruited from Southern Taiwan with a total of 2,602 useable surveys returned. Results showed that only depression level reached a significant moderating effect and further examination showed that the exposure to suicide news significantly predicted suicidality solely in the severely depressed group.

The present study evaluates the use of hyperosmotic stress and a biotic elicitor YE (yeast elicitor; polysaccharide fraction of yeast extract) to stimulate diterpenoid tanshinone production in hairy-root culture of Salvia miltiorrhiza Bunge (Lamiaceae). Sorbitol was applied as an osmoticum at various concentrations (30-100 g/l) to the hairy-root culture in MS (Murashige and Skoog) medium [Murashige and Skoog (1962) Physiol. Plant. 15, 473-497] containing 30 g/l sucrose, and it increased the TT (total tanshinone) content of roots most dramatically at 50-70 g/l (medium osmolality 410-500 mmol/kg; 1 mol/kg approximately 1 osmol/kg), to 4.5-fold of that in the control. The hairy roots showed strong tolerance to hyperosmotic stress, retaining a stable or higher dry weight of roots at osmolality up to 500 mmol/kg. Most remarkably, the combined use of sorbitol (50 g/l) and YE (100 mg/l) increased the TT content 10-fold (1481.6 versus 146.4 microg/g dry root) and the volumetric tanshinone yield 9-fold (16.3 versus 1.77 mg/l) compared with the control. The results suggest that the combined use of hyperosmotic stress and a biotic elicitor can effectively enhance secondary metabolite production in hairy-root cultures.