Primary Care Workforce And Continuous Medical Education In China: Lessons To Learn From A Nationwide Cross-sectional Survey

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Importance of highly selective LC–MS/MS analysis for the accurate quantification of tamoxifen and its metabolites: focus on endoxifen and 4-hydroxytamoxifen

The antiestrogenic effect of tamoxifen is mainly attributable to the active metabolites endoxifen and 4-hydroxytamoxifen. This effect is assumed to be concentration-dependent and therefore quantitative analysis of tamoxifen and metabolites for clinical studies and therapeutic drug monitoring is increasing. We investigated the large discrepancies in reported mean endoxifen and 4-hydroxytamoxifen concentrations. Two published LC–MS/MS methods are used to analyse a set of 75 serum samples from patients treated with tamoxifen. The method from Teunissen et al. (J Chrom B, 879:1677–1685, 2011) separates endoxifen and 4-hydroxytamoxifen from other tamoxifen metabolites with similar masses and fragmentation patterns. The second method, published by Gjerde et al. (J Chrom A, 1082:6–14, 2005) however lacks selectivity, resulting in a factor 2–3 overestimation of the endoxifen and 4-hydroxytamoxifen levels, respectively. We emphasize the use of highly selective LC–MS/MS methods for the quantification of tamoxifen and its metabolites in biological samples

Digenean parasites of Chinese marine fishes: a list of species, hosts and geographical distribution

In the literature, 630 species of Digenea (Trematoda) have been reported from Chinese marine fishes. These belong to 209 genera and 35 families. The names of these species, along with their hosts, geographical distribution and records, are listed in this paper

Diminished temperature and vegetation seasonality over northern high latitudes

Global temperature is increasing, especially over northern lands (>50° N), owing to positive feedbacks1. As this increase is most pronounced in winter, temperature seasonality (ST)—conventionally defined as the difference between summer and winter temperatures—is diminishing over time2, a phenomenon that is analogous to its equatorward decline at an annual scale. The initiation, termination and performance of vegetation photosynthetic activity are tied to threshold temperatures3. Trends in the timing of these thresholds and cumulative temperatures above them may alter vegetation productivity, or modify vegetation seasonality (SV), over time. The relationship between ST and SV is critically examined here with newly improved ground and satellite data sets. The observed diminishment of ST and SV is equivalent to 4° and 7° (5° and 6°) latitudinal shift equatorward during the past 30 years in the Arctic (boreal) region. Analysis of simulations from 17 state-of-the-art climate models4 indicates an additional STdiminishment equivalent to a 20° equatorward shift could occur this century. How SV will change in response to such large projected ST declines and the impact this will have on ecosystem services5 are not well understood. Hence the need for continued monitoring6 of northern lands as their seasonal temperature profiles evolve to resemble thosefurther south.Lopullinen vertaisarvioitu käsikirjoitu

Swirl Flow Bioreactor coupled with Cu-alginate beads: A system for the eradication of Coliform and Escherichia coli from biological effluents.

It is estimated that approximately 1.1 billion people globally drink unsafe water. We previously reported both a novel copper-alginate bead, which quickly reduces pathogen loading in waste streams and the incorporation of these beads into a novel swirl flow bioreactor (SFB), of low capital and running costs and of simple construction from commercially available plumbing pipes and fittings. The purpose of the present study was to trial this system for pathogen reduction in waste streams from an operating Dewats system in Hinjewadi, Pune, India and in both simulated and real waste streams in Seattle, Washington, USA. The trials in India, showed a complete inactivation of coliforms in the discharged effluent (Mean Log removal Value (MLRV) = 3.51), accompanied by a total inactivation of E. coli with a MLRV of 1.95. The secondary clarifier effluent also showed a 4.38 MLRV in viable coliforms during treatment. However, the system was slightly less effective in reducing E. coli viability, with a MLRV of 1.80. The trials in Seattle also demonstrated the efficacy of the system in the reduction of viable bacteria, with a LRV of 5.67 observed of viable Raoultella terrigena cells (100%)

Two highly divergent alcohol dehydrogenases of melon exhibit fruit ripening-specific expression and distinct biochemical characteristics

Alcohol dehydrogenases (ADH) participate in the biosynthetic pathway of aroma volatiles in fruit by interconverting aldehydes to alcohols and providing substrates for the formation of esters. Two highly divergent ADH genes (15% identity at the amino acid level) of Cantaloupe Charentais melon (Cucumis melo var. Cantalupensis) have been isolated. Cm-ADH1 belongs to the medium-chain zinc-binding type of ADHs and is highly similar to all ADH genes expressed in fruit isolated so far. Cm-ADH2 belongs to the short-chain type of ADHs. The two encoded proteins are enzymatically active upon expression in yeast. Cm-ADH1 has strong preference for NAPDH as a co-factor, whereas Cm-ADH2 preferentially uses NADH. Both Cm-ADH proteins are much more active as reductases with Kms 10–20 times lower for the conversion of aldehydes to alcohols than for the dehydrogenation of alcohols to aldehydes. They both show strong preference for aliphatic aldehydes but Cm-ADH1 is capable of reducing branched aldehydes such as 3-methylbutyraldehyde, whereas Cm-ADH2 cannot. Both Cm-ADH genes are expressed specifically in fruit and up-regulated during ripening. Gene expression as well as total ADH activity are strongly inhibited in antisense ACC oxidase melons and in melon fruit treated with the ethylene antagonist 1-methylcyclopropene (1-MCP), indicating a positive regulation by ethylene. These data suggest that each of the Cm-ADH protein plays a specific role in the regulation of aroma biosynthesis in melon fruit

Antimetastatic Effects of Norcantharidin on Hepatocellular Carcinoma by Transcriptional Inhibition of MMP-9 through Modulation of NF-kB Activity

The rate of morbidity and mortality of hepatocellular carcinoma (HCC) in Taiwan has not lessened because of difficulty in treating tumor metastasis. Norcantharidin (NCTD) is currently used as an anticancer drug for hepatoma, breast cancer, and colorectal adenocarcinoma. NCTD possesses various biological anticancer activities, including apoptosis. However, detailed effects and molecular mechanisms of NCTD on metastasis are unclear. Thus, HCC cells were subjected to treatment with NCTD and then analyzed to determine the effects of NCTD on cell metastasis.Modified Boyden chamber assays revealed that NCTD treatment inhibited cell migration and invasion capacities of HCC cells substantially. Results of zymography and western blotting showed that activities and protein levels of matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (u-PA) were inhibited by NCTD. Western blot analysis showed that NCTD inhibits phosphorylation of ERK1/2. Testing of mRNA level, quantitative real-time PCR, and promoter assays evaluated the inhibitory effects of NCTD on MMP-9 and u-PA expression in HCC cells. The chromatin immunoprecipitation (ChIP) assay for analyzing the genomic DNA sequences bound to these proteins was reactive to the transcription protein nuclear factor (NF)-kappaB, which was inhibited by NCTD. The expression of NF-kappa B was measured by western blot analysis, which revealed decreased nuclear-factor DNA-binding activity after NCTD treatment.NCTD inhibited MMP-9 and u-PA expression through the phosphorylation of ERK1/2 and NF-kappaB signaling pathway which serves as a powerful chemopreventive agent in HCC cell metastasis

The role of specific biomarkers, as predictors of post-operative complications following flexible ureterorenoscopy (FURS), for the treatment of kidney stones: a single-centre observational clinical pilot-study in 37 patients

Abstract: Background: The number of patients diagnosed and subsequently treated for kidney stones is increasing, and as such the number of post-operative complications is likely to increase. At present, little is known about the role of specific biomarkers, following flexible ureterorenoscopy (FURS) for the surgical treatment of kidney stones. The main aim of the study was to evaluate the role of kidney and infection biomarkers, in patients undergoing FURS. Methods: Included were 37 patients (24 males, 13 females), who underwent elective FURS, for the treatment of kidney stones. Venous blood samples were collected from each patient: pre-operatively, and at 30 min, 2 and 4 h post-operatively. Changes to kidney (NGAL, Cystatin-C) and infection (MPO, PCT) biomarkers was quantified by means of ELISA, Biomerieux mini-vidas and Konelab 20 analysers. Results: Four patients developed post-operative complications (3 - UTIs with urinary retention, 1 - urosepsis. NGAL concentration increased significantly following FURS (p = 0.034). Although no significant changes were seen in Cystatin C, MPO and PCT (p ≥ 0.05) some key clinical observation were noted. Limiting factors for this study were the small number of patients recruited and restriction in blood sampling beyond 4 h. Conclusions: Although not confirmative, changes seen to biomarkers such as Cystatin C, NGAL and MPO in our observational clinical pilot-study may warrant further investigation, involving larger cohorts, to fully understand the role of these biomarkers and their potential association with post-operative complications which can develop following FURS

Impact of FTO genotypes on BMI and weight in polycystic ovary syndrome : a systematic review and meta-analysis

Aims/hypothesis FTO gene single nucleotide polymorphisms (SNPs) have been shown to be associated with obesity-related traits and type 2 diabetes. Several small studies have suggested a greater than expected effect of the FTO rs9939609 SNP on weight in polycystic ovary syndrome (PCOS). We therefore aimed to examine the impact of FTO genotype on BMI and weight in PCOS. Methods A systematic search of medical databases (PubMed, EMBASE and Cochrane CENTRAL) was conducted up to the end of April 2011. Seven studies describing eight distinct PCOS cohorts were retrieved; seven were genotyped for SNP rs9939609 and one for SNP rs1421085. The per allele effect on BMI and body weight increase was calculated and subjected to meta-analysis. Results A total of 2,548 women with PCOS were included in the study; 762 were TT homozygotes, 1,253 had an AT/CT genotype, and 533 were AA/CC homozygotes. Each additional copy of the effect allele (A/C) increased the BMI by a mean of 0.19 z score units (95% CI 0.13, 0.24; p = 2.26 × 10−11) and body weight by a mean of 0.20 z score units (95% CI 0.14, 0.26; p = 1.02 × 10−10). This translated into an approximately 3.3 kg/m2 increase in BMI and an approximately 9.6 kg gain in body weight between TT and AA/CC homozygotes. The association between FTO genotypes and BMI was stronger in the cohorts with PCOS than in the general female populations from large genome-wide association studies. Deviation from an additive genetic model was observed in heavier populations. Conclusions/interpretation The effect of FTO SNPs on obesity-related traits in PCOS seems to be more than two times greater than the effect found in large population-based studies. This suggests an interaction between FTO and the metabolic context or polygenic background of PCOS

Incorporating Distant Sequence Features and Radial Basis Function Networks to Identify Ubiquitin Conjugation Sites

Ubiquitin (Ub) is a small protein that consists of 76 amino acids about 8.5 kDa. In ubiquitin conjugation, the ubiquitin is majorly conjugated on the lysine residue of protein by Ub-ligating (E3) enzymes. Three major enzymes participate in ubiquitin conjugation. They are – E1, E2 and E3 which are responsible for activating, conjugating and ligating ubiquitin, respectively. Ubiquitin conjugation in eukaryotes is an important mechanism of the proteasome-mediated degradation of a protein and regulating the activity of transcription factors. Motivated by the importance of ubiquitin conjugation in biological processes, this investigation develops a method, UbSite, which uses utilizes an efficient radial basis function (RBF) network to identify protein ubiquitin conjugation (ubiquitylation) sites. This work not only investigates the amino acid composition but also the structural characteristics, physicochemical properties, and evolutionary information of amino acids around ubiquitylation (Ub) sites. With reference to the pathway of ubiquitin conjugation, the substrate sites for E3 recognition, which are distant from ubiquitylation sites, are investigated. The measurement of F-score in a large window size (−20∼+20) revealed a statistically significant amino acid composition and position-specific scoring matrix (evolutionary information), which are mainly located distant from Ub sites. The distant information can be used effectively to differentiate Ub sites from non-Ub sites. As determined by five-fold cross-validation, the model that was trained using the combination of amino acid composition and evolutionary information performs best in identifying ubiquitin conjugation sites. The prediction sensitivity, specificity, and accuracy are 65.5%, 74.8%, and 74.5%, respectively. Although the amino acid sequences around the ubiquitin conjugation sites do not contain conserved motifs, the cross-validation result indicates that the integration of distant sequence features of Ub sites can improve predictive performance. Additionally, the independent test demonstrates that the proposed method can outperform other ubiquitylation prediction tools