Attentional Bias for Opioids in Taiwanese Heavy Smokers with Chronic Noncancer Pain.

Background and Objectives: Attentional bias (AB) for addictive substances is a feature of attention found in individuals with substance misuse or diagnosed with substance use disorders. When AB exists, the attention of the addicted individual may be quickly oriented to cues related to the addictive substance or be maintained on these cues for a longer time. AB toward opioids was found in Western samples of smokers with chronic noncancer pain. The level of AB was dose-responsive. However, similar studies in the Taiwanese population are lacking. This study compared the patterns of AB for opioid analgesics in Taiwanese participants with chronic noncancer pain to that of individuals without pain. This study aimed to investigate if AB toward opioids is presented in Taiwanese heavy smokers who are on long-term opioid therapy for pain control. Materials and Methods: Participants were grouped into chronic noncancer pain smokers, chronic pain nonsmokers, and smokers without pain, according to smoking habits and whether or not on long-term opioid therapy for pain control. Each participant completed demographic questionnaires, mood scales, and the opioid-related visual probe task. Differences in AB among the groups were compared using a three-way analysis of covariance controlling for daily cigarette consumption. Results: Chronic noncancer pain smokers (n = 17) and chronic pain nonsmokers (n = 16) displayed more severe levels of depression, anxiety, and pain, compared to smokers without pain (n = 28). Only did chronic pain nonsmokers show significant AB for opioid cues that were displayed for a short time. Analysis on reaction time found that smokers without pain consistently responded faster to the tasks. No difference in reaction time was found between the pain groups. Conclusions: The current study did not fully replicate findings from studies that were based in Western countries. Formulary availability and regulatory limitations might have affected patient's perception of prescription opioids in Taiwan. However, chronic pain nonsmokers exhibited initial orientation toward opioid-related cues when daily cigarette consumption was accounted for. According to previous research, this AB for shortly displayed opioid cues can be associated with the expectation of pain relief. The current finding also indicated general psychomotor retardation in individuals who were on long-term use of opioids.

Right femoral vein and right dorsal artery thrombosis in childhood acute myeloid leukemia: A case report.

BACKGROUND: It is rare for newly diagnosed (de novo) or newly treated acute myeloid leukemia (AML) complicated with thrombotic complications, especially combined arterial and venous thrombosis. METHODS: We reported a 13-year-old boy diagnosed with AML and leukocytosis, who developed right femoral vein and right dorsal artery thrombosis during chemotherapy. After treatment with low molecular weight heparin, diosmin, and alprostadil, symptoms were relieved. Unfortunately, the child suffered from coagulopathy afterward, which was unexpectedly caused by vitamin K deficiency. RESULTS: After supplementation with vitamin K and prothrombin complex concentrate, coagulation function recovered. CONCLUSION: For childhood AML patients with high thrombotic risks, close monitoring during anticoagulant treatment was necessary. Concomitantly, we should be alert to past medication history and combined medication use, especially those that may lead to vitamin K deficiency, secondary bleeding, and coagulation disorders. Rational use of antibiotics, anticoagulants, and antitumor drugs must be guaranteed.

Smart Nanosensitizers for Activatable Sono-Photodynamic Immunotherapy of Tumors by Redox-Controlled Disassembly.

Tumor-targeted and stimuli-activatable nanosensitizers are highly desirable for cancer theranostics. However, designing smart nanosensitizers with multiple imaging signals and synergistic therapeutic activities switched on is challenging. Herein, we report tumor-targeted and redox-activatable nanosensitizers (1-NPs) for sono-photodynamic immunotherapy of tumors by molecular co-assembly and redox-controlled disassembly. 1-NPs show a high longitudinal relaxivity (r1 =18.7±0.3 mM-1 s-1 ), but "off" dual fluorescence (FL) emission (at 547 and 672 nm), "off" sono-photodynamic therapy and indoleamine 2,3-dioxygenase 1 (IDO1) inhibition activities. Upon reduction by glutathione (GSH), 1-NPs rapidly disassemble and remotely release small molecules 2-Gd, Zn-PPA-SH and NLG919, concurrently switching on (1) dual FL emission, (2) sono-photodynamic therapy and (3) IDO1 inhibition activities. After systemic injection, 1-NPs are effective for bimodal FL and magnetic resonance (MR) imaging-guided sono-photodynamic immunotherapy of orthotropic breast and brain tumors in mice under combined ultrasound (US) and 671-nm laser irradiation.

Controlling Disassembly of Paramagnetic Prodrug and Photosensitizer Nanoassemblies for On-Demand Orthotopic Glioma Theranostics.

Controlling delivery and release of therapeutic agents to accomplish on-demand synergistic therapy of orthotopic gliomas is desired but challenging. Here, we report a glioma targeting and redox activatable theranostic nanoprobe (Co-NP-RGD1/1) for magnetic resonance (MR) and fluorescence (FL) bimodal imaging-guided on-demand synergistic chemotherapy/photodynamic therapy (Chemo-PDT) of orthotopic gliomas. Co-NP-RGD1/1 is formed via molecular coassembly of two paramagnetic and fluorogenic small-molecule probes CPT-RGD and PPa-RGD at an optimized molar ratio of 1/1, which shows a high longitudinal relaxivity (r1 = 17.0 ± 0.6 mM-1 s-1, 0.5 T) but weak FL emissions and low Chemo-PDT activity. Upon reduction by endogenous glutathione (GSH), Co-NP-RGD1/1 disassemble and release small molecules 2-RGD, chemodrug camptothecin (CPT), and near-infrared (NIR) photosensitizer (PS) PPa-SH that further binds to endogenous albumin to form PPa-SH-albumin complex, allowing to turn on FL, chemotherapeutic efficacy, and PDT activity for synergistic Chemo-PDT of orthotopic U87MG or U251 gliomas in living mice. Moreover, Co-NP-RGD1/1 can also allow noninvasive detection and monitoring of orthotopic brain tumor growth via FL and MR imaging. Findings suggest the potential of cascade coassembly and stimuli-controlled intracellular disassembly strategy for constructing targeted and activatable nanoagents for improving combinational cancer theranostics.

Iron-Catalyzed Cadiot-Chodkiewicz Coupling with High Selectivity in Water under Air.

An iron-based catalytic system was developed for the cross-coupling of 1-bromoalkynes with terminal alkynes to selectively generate unsymmetrical 1,3-butadiynes in water under air. It was found that a combination of 1-bromoalkynes derived from less acidic terminal alkynes with more acidic counterparts would greatly enhance yields and selectivity for unsymmetrical 1,3-butadiynes. The reaction was also applicable for the synthesis of unsymmetrical 1,3,5-hexatriynes through coupling of 1-bromoalkynes and trimethylsilyl-protected 1,3-butadiynes in a one-pot manner.

Bioinspired large Stokes shift small molecular dyes for biomedical fluorescence imaging.

Long Stokes shift dyes that minimize cross-talk between the excitation source and fluorescent emission to improve the signal-to-background ratio are highly desired for fluorescence imaging. However, simple small molecular dyes with large Stokes shift (more than 120 nanometers) and near-infrared (NIR) emissions have been rarely reported so far. Here, inspired by the chromophore chemical structure of fluorescent proteins, we designed and synthesized a series of styrene oxazolone dyes (SODs) with simple synthetic methods, which show NIR emissions (>650 nanometers) with long Stokes shift (ranged from 136 to 198 nanometers) and small molecular weight (<450 daltons). The most promising SOD9 shows rapid renal excretion and blood-brain barrier passing properties. After functioning with the mitochondrial-targeted triphenylphosphonium (TPP) group, the resulting SOD9-TPP can be engineered for head-neck tumor imaging, fluorescence image-guided surgery, brain neuroimaging, and on-site pathologic analysis. In summary, our findings add an essential small molecular dye category to the classical dyes.

Non-Contrast-Enhancing Glioma Mimicking Acute Ischemic Stroke Within Three Hours of Onset.

Intravenous thrombolytic therapy is recommended within 3 hours of onset of acute ischemic stroke. However, stroke mimics create challenges because of time pressures. We describe a case of an undiagnosed glioma, a rarely reported condition, that was nearly treated with thrombolytic therapy. A 71-year-old man presented to the emergency department with sudden left gaze preference, right-sided hemiplegia, and global aphasia, which suggested a large infarction in the left hemisphere. The thrombolytic protocol was started at once. However, noncontrast computed tomography (CT) of the brain, CT angiography, and CT perfusion were essentially normal. Later, magnetic resonance imaging of the brain demonstrated a diffuse intracerebral lesion. The patient was found to have an undiagnosed diffuse glioma, whose initial neurologic symptoms mimicked acute stroke within 3 hours of onset. Cerebral neoplasms are an absolute contraindication for thrombolysis therapy. Several brain tumors are rarely seen on a brain CT scan. The mismatch between neurologic examination and brain perfusion imaging may suggest a stroke mimic in some cases.

Efficacy and safety of prophylactic abdominal aortic balloon occlusion versus internal iliac arterial balloon occlusion for placenta accreta spectrum disorder: A systematic review and meta-analysis.

PURPOSE: To assess the efficacy and safety of abdominal aortic (AA) balloon occlusion versus internal iliac arteries (IIA) balloon occlusion in patients with placenta accreta spectrum (PAS) disorders. METHODS: Databases of Embase, PubMed, Web of Science and Cochrane Library were systematically searched from inception to May 2020. The relevant literature was screened and the quality was assessed. RevMan software 5.3 was used to analyze the data. RESULTS: Six studies involving 239 patients in AA occlusion and 281 patients in IIA occlusion were included. The results demonstrated that the intraoperative hemorrhage volume (MD - 410.61 ml, 95% CI -779.74 to -41.47 ml, p < 0.001), balloon dilatation duration (MD -5.34 min, 95% CI -9.91 to -0.77 min, p = 0.02) and fetus radiation dose (MD-20.81 mGy, 95% CI -31.84 to -9.78 mGy, p < 0.001) were significantly less in AA occlusion compared to IIA occlusion. There was no significant difference in the rate of lower extremity thrombosis between AA occlusion and IIA occlusion (OR 0.21, 95% CI 0.02 to 2.21, p = 0.19); similarly, no significant differences were found in blood transfusion volume (MD -344.50 ml, 95% CI -735.74 to 46.74 ml, p = 0.08), the rate of hysterectomy (OR 0.99, 95% CI 0.22 to 4.44, p = 0.99) and other outcome variables. CONCLUSION: The available data demonstrated AA occlusion was more effective in reducing intraoperative hemorrhage volume and fetus radiation dose compared with IIA occlusion in patients with PAS disorders. Larger studies or randomized controlled trials are needed to further assert this evidence.

Attentional bias to betel quid cues: An eye tracking study.

The World Health Organization regards betel quid as a human carcinogen, and DSM-IV and ICD-10 dependence symptoms may develop with heavy use. This study, conducted in central Taiwan, investigated whether betel quid chewers can exhibit overt orienting to selectively respond to the betel quid cues. Twenty-four male chewers' and 23 male nonchewers' eye movements to betel-quid-related pictures and matched pictures were assessed during a visual probe task. The eye movement index showed that betel quid chewers were more likely to initially direct their gaze to the betel quid cues, t(23) = 3.70, p < .01, d = .75, and spent more time, F(1, 23) = 4.58, p < .05, η2 = .17, and were more fixated, F(1, 23) = 5.18, p < .05, η2 = .18, on them. The visual probe index (response time) failed to detect the chewers' attentional bias. The current study provided the first eye movement evidence of betel quid chewers' attentional bias. The results demonstrated that the betel quid chewers (but not the nonchewers) were more likely to initially direct their gaze to the betel quid cues, and spent more time and were more fixated on them. These findings suggested that when attention is directly measured through the eye tracking technique, this methodology may be more sensitive to detecting attentional biases in betel quid chewers. (PsycINFO Database Record

Stent-grafts for the treatment of TIPS dysfunction: fluency stent vs Wallgraft stent.

AIM: To evaluate the clinical efficacy of an expanded polytetrafluoro-ethylene-covered Fluency stent compared with that of a polyethylene terephthalate-covered Wallgraft stent for the management of transjugular intrahepatic portosystemic shunt (TIPS) dysfunction. METHODS: A retrospective review of patients who underwent TIPS revision with stent-grafts between May 2007 and June 2011 was conducted. The patients were divided into two groups according to the stent-grafts implanted: the Fluency stent (Bard Incorporated, Karlsruhe, Germany) and the Wallgraft stent (Boston Scientific, Galway, Ireland). The primary patency rates were calculated and compared using the Kaplan-Meier method. RESULTS: A total of 73 patients were evaluated in this study: 33 with Fluency stents and 40 with Wallgraft stents. The primary patency rates at 12 and 24 mo were 91% and 85%, respectively, in the Fluency stent group and 78% and 63%, respectively, in the Wallgraft stent group. The primary shunt patency rates after TIPS revision were significantly better with the Fluency stent than with the Wallgraft stent (P = 0.033). CONCLUSION: TIPS revision with the Fluency stent has higher medium-term patency rates than that with the Wallgraft stent.

Hepatic arterial administration of ginsenoside Rg3 and transcatheter arterial embolization for the treatment of VX2 liver carcinomas.

Ginsenoside Rg3 has been demonstrated to inhibit tumor cell proliferation and angiogenesis. However, its effect on liver tumors when administered via the hepatic artery has not been investigated. The purpose of this study was to evaluate the therapeutic effect of hepatic artery administration of Rg3 combined with transcatheter arterial embolization (TAE) in the treatment of liver tumors. A total of 48 rabbits with VX2 liver tumors were randomly divided into four groups: Group 1, Rg3; Group 2, TAE; Group 3, Rg3 and TAE; and Group 4, control. Abdominal contrast computed tomography (CT) scans were performed 2 weeks before and after intervention to assess tumor growth. Immunohistochemical staining was used to detect the expression of the angiogenesis biomarkers CD31 and VEGF, and the cell apoptosis marker caspase-3. Semi-quantitative RT-PCR and western blotting were employed to detect the expression of the caspase-3, Bax and Bcl-2 apoptosis-related genes and proteins. In addition, HepG2 cells were treated with Rg3 at different concentrations (0, 25, 50, 75 and 100 mg/l) in vitro. An MTT assay and western blot analysis were used to analyze the cell proliferation and VEGF expression. Compared with the other experimental groups, the Rg3 and TAE group expressed significantly lower levels of CD31 and VEGF (P<0.05), significantly increased levels of the pro-apoptotic genes caspase-3 and Bax (P<0.05), and significantly reduced levels of anti-apoptotic Bcl-2 at the mRNA and protein levels (P<0.05). In vitro, Rg3 inhibited HepG2 cell proliferation and downregulated VEGF expression significantly. These results indicated that ginsenoside Rg3 combined with TAE may effectively inhibit tumor growth by inhibiting tumor angiogenesis and inducing cancer cell apoptosis.

Antitumor effects of ginsenoside Rg3 on human hepatocellular carcinoma cells.

The antitumor effects of ginsenoside Rg3 have been reported in several kinds of human malignant tumors. The purpose of this study was to investigate whether ginsenoside Rg3 can inhibit the growth of human hepatocellular carcinoma cell lines and to discuss the possible molecular mechanism(s). We cultured the human hepatocellular carcinoma cell lines, SMMC-7721 and HepG2. The cells were treated with different concentrations of ginsenoside Rg3 (0, 25, 50, 75 and 100 µg/ml), and the cell proliferation was detected by MTT assay at the 12, 24, 36 and 48 h time-points. Flow cytometry experiments were carried out to investigate the effect of Rg3 on cell apoptosis after the cells had been treated with Rg3 (50 and 100 µg/ml) for 24 and 48 h. The expression levels of caspase-3, bax and bcl-2 in Rg3-treated cells (100 µg/ml, 48 h), as well as normal cells were detected through real-time PCR experiments. MTT assay showed that the inhibition rate of cell proliferation in the Rg3 groups was significantly higher compared to the control groups in both the SMMC-7721 and HepG2 cell lines, and the inhibition rate increased with increasing Rg3 concentrations and duration of treatment. Flow cytometry analysis demonstrated that the Rg3 groups had a significantly higher cell apoptotic rate compared to the control groups in both the SMMC-7721 and HepG2 cell lines, and that the effect of Rg3 on cell apoptosis occurred in a concentration- and time-dependent manner, as was also shown by the MTT assay. Real-time PCR analysis showed that the gene expression levels of caspase-3 and bax were significantly enhanced in the Rg3 groups compared to the control groups in both the SMMC-7721 and HepG2 cell lines, but the gene expression level of bcl-2 was significantly inhibited. These results indicate that ginsenoside Rg3 can effectively inhibit the growth of human hepatocellular carcinoma cell lines by inhibiting cancer cell proliferation and promoting cancer cell apoptosis, and it may promote cancer cell apoptosis via the endogenous mitochondrial-mediated caspase-dependent apoptotic pathway.

Study of a new derivatizing reagent that improves the analysis of amino acids by HPLC with fluorescence detection: application to hydrolyzed rape bee pollen.

A simple and sensitive method for evaluating the chemical compositions of protein amino acids, including cystine (Cys)(2) and tryptophane (Try) has been developed, based on the use of a sensitive labeling reagent 2-(11H-benzo[alpha]-carbazol-11-yl) ethyl chloroformate (BCEC-Cl) along with fluorescence detection. The chromophore of the 1,2-benzo-3,4-dihydrocarbazole-ethyl chloroformate (BCEOC-Cl) molecule was replaced with the 2-(11H-benzo[alpha]-carbazol-11-yl) ethyl functional group, yielding the sensitive fluorescence molecule BCEC-Cl. The new reagent BCEC-Cl could then be substituted for labeling reagents commonly used in amino acid derivatization. The BCEC-amino acid derivatives exhibited very high detection sensitivities, particularly in the cases of (Cys)(2) and Try, which cannot be determined using traditional labeling reagents such as 9-fluorenyl methylchloroformate (FMOC-Cl) and ortho-phthaldialdehyde (OPA). The fluorescence detection intensities for the BCEC derivatives were compared to those obtained when using FMOC-Cl and BCEOC-Cl as labeling reagents. The ratios I (BCEC)/I (BCEOC) = 1.17-3.57, I (BCEC)/I (FMOC) = 1.13-8.21, and UV(BCEC)/UV(BCEOC) = 1.67-4.90 (where I is the fluorescence intensity and UV is the ultraviolet absorbance). Derivative separation was optimized on a Hypersil BDS C(18) column. The detection limits calculated from 1.0 pmol injections, at a signal-to-noise ratio of 3, ranged from 7.2 fmol for Try to 8.4 fmol for (Cys)(2). Excellent linear responses were observed, with coefficients of >0.9994. When coupled with high-performance liquid chromatography, the method established here allowed the development of a highly sensitive and specific method for the quantitative analysis of trace levels of amino acids including (Cys)(2) and Try from bee-collected pollen (bee pollen) samples.