Survey of methadone-drug interactions among patients of methadone maintenance treatment program in Taiwan

<p>Abstract</p> <p>Background</p> <p>Although methadone has been used for the maintenance treatment of opioid dependence for decades, it was not introduced in China or Taiwan until 2000s. Methadone-drug interactions (MDIs) have been shown to cause many adverse effects. However, such effects have not been scrutinized in the ethnic Chinese community.</p> <p>Methods</p> <p>The study was performed in two major hospitals in southern Taiwan. A total of 178 non-HIV patients aged ≥ 20 years who had participated in the Methadone Maintenance Treatment Program (MMTP) ≥ 1 month were recruited. An MDI is defined as concurrent use of drug(s) with methadone that may result in an increase or decrease of effectiveness and/or adverse effect of methadone. To determine the prevalence and clinical characteristics of MDIs, credible data sources, including the National Health Insurance (NHI) database, face-to-face interviews, medical records, and methadone computer databases, were linked for analysis. Socio-demographic and clinical factors associated with MDIs and co-medications were also examined.</p> <p>Results</p> <p>128 (72%) MMTP patients took at least one medication. Clinically significant MDIs included withdrawal symptoms, which were found among MMTP patients co-administered with buprenorphine or tramadol; severe QTc prolongation effect, which might be associated with use of haloperidol or droperidol; and additive CNS and respiratory depression, which could result from use of methadone in combination with chlorpromazine or thioridazine. Past amphetamine use, co-infection with hepatitis C, and a longer retention in the MMTP were associated with increased odds of co-medication. Among patients with co-medication use, significant correlates of MDIs included the male gender and length of co-medication in the MMTP.</p> <p>Conclusions</p> <p>The results demonstrate clinical evidence of significant MDIs among MMTP patients. Clinicians should check the past medical history of MMTP clients carefully before prescribing medicines. Because combinations of methadone with other psychotropic or opioid medications can affect treatment outcomes or precipitate withdrawal symptoms, clinicians should be cautious when prescribing these medications to MMTP patients and monitor the therapeutic effects and adverse drug reactions. Although it is difficult to interconnect medical data from different sources for the sake of privacy protection, the incumbent agency should develop pharmacovigilant measures to prevent the MDIs from occurring. Physicians are also advised to check more carefully on the medication history of their MMTP patients.</p

Comparing factors affecting commencement and cessation of betel quid chewing behavior in Taiwanese adults

<p>Abstract</p> <p>Background</p> <p>Betel quid is the fourth most common used substance in the world after tobacco, alcohol and caffeine. Although factors related to betel quid chewing or cessation of behaviors were reported previously, few studies simultaneously compared both behaviors in the same population. In addition, it is essential to consider time-to-event concept, since the chance of developing or stopping habit may vary over time. The purpose of this study was to compare the risk factors for commencement and cessation of betel quid chewing behaviors in a time-to-event setting.</p> <p>Methods</p> <p>A stratified multi-stage cluster sampling with selection probabilities proportional to size (PPS) was designed for Taiwanese adults with aged 18 years old and above. Kaplan-Meier estimates and Cox proportional hazard regression models were used to compare and calculate the hazard rate ratios for related factors to commencement or cessation of chewing habits.</p> <p>Results</p> <p>In Taiwan, men had a higher betel quid chewing rate (M: 20.9%, W: 1.2%), but woman chewers had a lower cessation rate (M: 27.5%, W: 12.7%). The hazard rate ratio (HRR) of having chewing habit changed from 4.22 (men vs women) univariately to 1.38 multivariablely, which indicated gender differences were confounded by other factors. In multivariable analysis, the risk factors of gender, education and ethnicity were significantly associated with both starting and cessation of betel quid chewing behavior. The factors of occupation, cigarette smoking and alcohol drinking were only associated with starting habit.</p> <p>Conclusion</p> <p>Commencement or cessation of chewing behavior involves a scenario of time, hence it is preferable to use a time-to-event approach for the comparison. The cessation rates of betel quid chewing were decreasingly associated with the daily consumption of betel quid. Hence, reducing of daily amount in betel quid cessation program may be associated with future stopping habit.</p

Functional characterization of cellulases identified from the cow rumen fungus Neocallimastix patriciarum W5 by transcriptomic and secretomic analyses

<p>Abstract</p> <p>Background</p> <p><it>Neocallimastix patriciarum</it> is one of the common anaerobic fungi in the digestive tracts of ruminants that can actively digest cellulosic materials, and its cellulases have great potential for hydrolyzing cellulosic feedstocks. Due to the difficulty in culture and lack of a genome database, it is not easy to gain a global understanding of the glycosyl hydrolases (<it>GHs</it>) produced by this anaerobic fungus.</p> <p>Results</p> <p>We have developed an efficient platform that uses a combination of transcriptomic and proteomic approaches to <it>N. patriciarum </it>to accelerate gene identification, enzyme classification and application in rice straw degradation. By conducting complementary studies of transcriptome (Roche 454 GS and Illumina GA IIx) and secretome (ESI-Trap LC-MS/MS), we identified 219 putative <it>GH </it>contigs and classified them into 25 <it>GH</it> families. The secretome analysis identified four major enzymes involved in rice straw degradation: β-glucosidase, endo-1,4-β-xylanase, xylanase B and Cel48A exoglucanase. From the sequences of assembled contigs, we cloned 19 putative cellulase genes, including the <it>GH1</it>, <it>GH3</it>, <it>GH5</it>, <it>GH6</it>, <it>GH9</it>, <it>GH18</it>, <it>GH43 </it>and <it>GH48 </it>gene families, which were highly expressed in <it>N. patriciarum </it>cultures grown on different feedstocks.</p> <p>Conclusions</p> <p>These <it>GH </it>genes were expressed in Pichia pastoris and/or Saccharomyces cerevisiae for functional characterization. At least five novel cellulases displayed cellulytic activity for glucose production. One β-glucosidase (W5-16143) and one exocellulase (W5-CAT26) showed strong activities and could potentially be developed into commercial enzymes.</p

Stimulatory effect of Echinacea purpurea extract on the trafficking activity of mouse dendritic cells: revealed by genomic and proteomic analyses

<p>Abstract</p> <p>Background</p> <p>Several <it>Echinacea </it>species have been used as nutraceuticals or botanical drugs for "immunostimulation", but scientific evidence supporting their therapeutic use is still controversial. In this study, a phytocompound mixture extracted from the butanol fraction (BF) of a stem and leaf (S+L) extract of <it>E. purpurea </it>([BF/S+L/Ep]) containing stringently defined bioactive phytocompounds was obtained using standardized and published procedures. The transcriptomic and proteomic effects of this phytoextract on mouse bone marrow-derived dendritic cells (BMDCs) were analyzed using primary cultures.</p> <p>Results</p> <p>Treatment of BMDCs with [BF/S+L/Ep] did not significantly influence the phenotypic maturation activity of dendritic cells (DCs). Affymetrix DNA microarray and bioinformatics analyses of genes differentially expressed in DCs treated with [BF/S+L/Ep] for 4 or 12 h revealed that the majority of responsive genes were related to cell adhesion or motility (<it>Cdh10</it>, <it>Itga6</it>, <it>Cdh1</it>, <it>Gja1 </it>and <it>Mmp8</it>), or were chemokines (<it>Cxcl2, Cxcl7) </it>or signaling molecules (<it>Nrxn1, Pkce </it>and <it>Acss1</it>). TRANSPATH database analyses of gene expression and related signaling pathways in treated-DCs predicted the JNK, PP2C-α, AKT, ERK1/2 or MAPKAPK pathways as the putative targets of [BF/S+L/Ep]. In parallel, proteomic analysis showed that the expressions of metabolic-, cytoskeleton- or NF-κB signaling-related proteins were regulated by treatment with [BF/S+L/Ep]. <it>In vitro </it>flow cytometry analysis of chemotaxis-related receptors and <it>in vivo </it>cell trafficking assay further showed that DCs treated with [BF/S+L/Ep] were able to migrate more effectively to peripheral lymph node and spleen tissues than DCs treated as control groups.</p> <p>Conclusion</p> <p>Results from this study suggest that [BF/S+L/Ep] modulates DC mobility and related cellular physiology in the mouse immune system. Moreover, the signaling networks and molecules highlighted here are potential targets for nutritional or clinical application of <it>Echinacea </it>or other candidate medicinal plants.</p

The Dipyridamole Added to Dual Antiplatelet Therapy in Cerebral Infarction After First Acute Myocardial Infarction: A Nationwide, Case-Control Study

Background and Purpose: No previous study has compared the impact of dipyridamole-based triple antiplatelet therapy on secondary stroke prevention and long-term outcomes to that of dual antiplatelet therapy (DAPT) in patients with acute myocardial infarction (AMI) and previous stroke. This study aimed to evaluate the impact of dipyridamole added to DAPT on stroke prevention and long-term outcomes in patients with cerebral infarction after first AMI.Methods: This nationwide, case-control study included 75,789 patients with cerebral infarction after first AMI. A 1:4 propensity score matching ratio was adopted based on multiple variables. Finally, the data of 4,468 patients included in the DAPT group and 1,117 patients included in the Dipyridamole-DAPT group were analyzed. Primary outcome was overall survival. Secondary outcomes were cumulative event rate of recurrent MI or stroke, and cumulative intracerebral hemorrhage (ICH) and gastrointestinal bleeding rate.Results: Long-term survival rate was comparable between the two groups (log-rank P = 0.1117), regardless of sex analyses. However, after first year, DAPT subgroup revealed better survival over DAPT-dipyridamole subgroup (log-rank P = 0.0188). In age subgroup analysis, a lower survival rate was detected in younger patients from the Dipyridamole-DAPT group after first year (log-rank P = 0.0151), but no survival difference for older patients. No benefit of Dipyridamole-DAPT was detected for patients after AMI, regardless of the myocardial infarction type. DAPT was superior to Dipyridamole-DAPT in patients who underwent percutaneous coronary intervention (PCI) (log-rank P = 0.0153) and ST elevation myocardial infarction after first year (log-rank P = 0.0019). Dipyridamole-DAPT did not reduce cumulative event rate of recurrent MI or stroke in patients after AMI. Moreover, Dipyridamole-DAPT increased the cumulative ICH rate (log-rank P = 0.0026), but did not affect the cumulative event rate of gastrointestinal bleeding. In Cox analysis, dipyridamole did not improve long-term survival.Conclusions: This nationwide study showed that Dipyridamole-DAPT, compared with DAPT, did not improve long-term survival in patients with stroke after AMI, and was related to poor outcomes after 1 year. Dipyridamole-DAPT did not reduce recurrent rate of MI or stroke, but increased the ICH rate without impacting the incidence of gastrointestinal bleeding

Comprehensive molecular characterization of gastric adenocarcinoma

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data