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This study is a secondary analysis of a randomized clinical trial (October 2013–April 2017) involving 150 People Who Inject Drugs (PWIDs) with hepatitis C virus (HCV) seen in opioid agonist treatment programs in the Bronx, New York, and investigates the impact of distrust in the healthcare system on adherence to Direct-Acting Antivirals (DAAs) HCV treatment therapy among PWIDs. The distrust was scaled on a 9-item instrument and the adherence to DAA medications was measured using electronic blister packs. This study demonstrated a significant inverse relationship between levels of distrust and medication adherence: 71.8 ± 2.2% (se) vs. 77.9 ± 1.8%, p = 0.024 between participants with higher and lower distrust levels. Despite the absence of significant association of distrust with sociodemographic or substance use characteristics, these findings suggest that building trust within the healthcare system is paramount for improving adherence to DAAs among PWIDs. The results call for a healthcare approach that emphasizes trust-building through patient-centered care, sensitivity training, peer support, and health system reform to effectively address the treatment needs of this marginalized population. [ABSTRACT FROM AUTHOR]

Synthesis of sodium fatty alcohol polyoxyethylene ether acetate (C12-14 alkyl chain, oxyethylene unit number of 2, AEC-3Na) through the direct reaction between fatty alcohol polyoxyethylene ether (AEO-3) and NaOH was conducted with the use of commercial ZnO and SnO2 powders as catalysts in a solvent free and anaerobic atmosphere at 180‒220 °C. When the reaction was catalyzed by the ZnO catalyst with the NaOH/AEO-3 mol ratio of 2:1 and ZnO/AEO-3 mass ratio of 1:100 at 210 °C for 15 h, the AEC-3Na yield reached 71.8% at the selectivity of 95.9%. The ZnO catalyst with a lower basicity more effectively catalyzes the reaction than the SnO2 catalyst with a higher basicity. On the ZnO catalyst, the catalytic reaction activation is 72 kJ mol‒1. The impact of NaOH concentration on reaction rate is stronger than that of catalyst dosage. [ABSTRACT FROM AUTHOR]

Keywords: adherence; DAA; drug use; HCV; PWID EN adherence DAA drug use HCV PWID 172 175 4 01/19/23 20230201 NES 230201 Abbreviations DAA direct-acting antiviral DTF daily time frame GT groups therapy HCV hepatitis C infection mDOT modified directly observed therapy OTP opioid treatment program PWID people who inject drugs SIT standard individual therapy SVR sustained virologic response INTRODUCTION Direct-acting antiviral (DAA) therapies are more effective for treating hepatitis C virus (HCV) with higher rates of sustained virologic response (SVR) and fewer side effects than older interferon-based treatments.[1] DAAs are effective even among people who inject drugs (PWID),[2] a population disproportionately infected by HCV.[3] Nonetheless, adequate adherence is crucial for PWID living with HCV to achieve SVR and reduce transmission, a public health goal which has been prioritized for global efforts to eliminate HCV by 2030.[4] How ongoing drug use interferes with HCV treatment adherence support remains unknown.[[5]] The PREVAIL study[2] was conducted in opioid treatment program (OTP) settings to test the effectiveness of three models of HCV care for PWID. Hepatitis C virus direct-acting antiviral treatment adherence patterns and sustained viral response among people who inject drugs treated in opioid agonist therapy programs. [Extracted from the article]

Background: Processed extracts from toad skin and parotoid gland have long been used to treat various illnesses including cancer in many Asian countries. Recent studies have uncovered a family of bufadienolides as the responsible pharmacological compounds, and the two major molecules, cinobufagin and bufalin, have been shown to possess robust antitumor activity; however, the underlying mechanisms remain poorly understood. Methods: Intracellular reactive oxygen species (ROS) were measured by DCFH-DA staining and flow cytometry, and DNA damage was analyzed by immunofluorescent staining and the alkaline comet assay. Cytotoxicity was measured by MTT as well as colony formation assays, and cell cycle and apoptosis were analyzed by flow cytometry. In addition, apoptosis was further characterized by TUNEL and mitochondrial membrane potential assays. Results: Here we showed that sublethal doses of cinobufagin suppressed the viability of many cancer but not noncancerous cell lines. This tumor-selective cytotoxicity was preceded by a rapid, cancer-specific increase in cellular ROS and was significantly reduced by the ROS inhibitor N-acetyl cysteine (NAC), indicating oxidative stress as the primary source of cinobufagin-induced cancer cell toxicity. Sublethal cinobufagin-induced ROS overload resulted in oxidative DNA damage and intense replication stress in cancer cells, leading to strong DNA damage response (DDR) signaling. Subsequent phosphorylation of CDC25C and stabilization of p53 downstream of DDR resulted in activation of the G2/M checkpoint followed by induction of apoptosis. These data indicate that cinobufagin suppresses cancer cell viability via DDR-mediated G2 arrest and apoptosis. Conclusion: As elevated oxidative pressure is shared by most cancer cells that renders them sensitive to further oxidative insult, these studies suggest that nontoxic doses of cinobufagin can be used to exploit a cancer vulnerability for induction of cancer-specific cytotoxicity. [ABSTRACT FROM AUTHOR]

Inhibition of the nucleotide pool sanitizing enzyme MTH1 causes extensive oxidative DNA damages and apoptosis in cancer cells and hence may be used as an anticancer strategy. As natural products have been a rich source of medicinal chemicals, in the present study, we used the MTH1-catalyzed enzymatic reaction as a high-throughput in vitro screening assay to search for natural compounds capable of inhibiting MTH1. Echinacoside, a compound derived from the medicinal plants Cistanche and Echinacea, effectively inhibited the catalytic activity of MTH1 in an in vitro assay. Treatment of various human cancer cell lines with Echinacoside resulted in a significant increase in the cellular level of oxidized guanine (8-oxoguanine), while cellular reactive oxygen species level remained unchanged, indicating that Echinacoside also inhibited the activity of cellular MTH1. Consequently, Echinacoside treatment induced an immediate and dramatic increase in DNA damage markers and upregulation of the G1/S-CDK inhibitor p21, which were followed by marked apoptotic cell death and cell cycle arrest in cancer but not in noncancer cells. Taken together, these studies identified a natural compound as an MTH1 inhibitor and suggest that natural products can be an important source of anticancer agents.

Objective: To study the effect of gemini fluorocarbon, sodium p-perfluorous nonenoxybenzene sulfonate and sodium dodecyl sulfate on the chlorine dioxide solution sterilization to object surface., Methods: Pure chlorine dioxide solution as the reference disinfectant, carrier quantitative bactericidal test and simulated test on-site were used to carry out laboratory observation according to The disinfection technical specifications (2002)., Results: Carrier quantitative bactericidal test showed that the addition dosage of gemini fluoronates, sodium dodecyl sulfate surfactant and perfluorinated the nonene oxy benzene sulfonate in disinfectant solution were 60, 60 and 40 mg/L respectively, the killing log value of Staphylococcus aureus exposed to the disinfectant solution containing chlorine dioxide 50 mg/L for 10 mm were all more than 3; and the addition dosage of gemini fluorinates, sodium dodecyl sulfate and perfluorinated the nonene oxy benzene sulfonate in disinfectant solution were 60 mg/L, the killing log value of Escherichia coli exposed to the disinfectant solution containing chlorine dixoxide 20 mg/L for 10 min were all more than 3. The bactericidal effect of the mixture use of surfactant and chlorine dioxide was better than the single use of chlorine dioxide. The simulated test on-site showed that the killing log value of Escherichia coli exposed to the disinfectant solution containing perfluorinated the nonene oxy benzene sulfonate 40 mg/L and chlorine dioxide 20 mg/L for 15 min was more than 3., Conclusion: Surface active agent on germicidal efficacy of chlorine dioxide solution had synergistic action.