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Effect of typical transcranial household power activation units and also electrode dimensions upon generator cortical excitability from the quadriceps muscles.
Since cancer cells have different mitochondrial bioenergetic requirements than non-cancerous cells, therapeutic inhibition of its mitochondrial functionality continues to be an important target for anticancer drug discovery. In this study, a series of acylhydroquinones with different acyl-chain length, and their chlorinated derivatives, in the aromatic ring, synthesized by Fries rearrangement under microwave irradiation, were evaluated for their anticancer activity in two leukemia cell lines. Findings from the primary and secondary screening of the 18 acylhydroquinones, tested at 5 µM on acute promyelocytic leukemia HL-60 and acute lymphoblastic leukemia CEM cells lines, identified an acylchlorohydroquinone (12) with a highly selective anti-proliferative effect toward HL-60 cells. This compound induced S-phase arrest in the cell cycle progression of HL-60 cells with insignificant toxicity on leukemic CEM cells and non-cancerous Hs27 cells. In HL-60 leukemic cells, 12 triggered increased mitochondrial NADH oxidation, increased respiration in presence of oligomycin (state 4o), mitochondrial depolarization, and ROS production, suggesting an uncoupling of OXPHOS. This provoked a metabolic adaptation dependent on AMPK/ACC/autophagy axis, having the mitochondrial β-oxidation a pro-survival role since the combination of 12 and etomoxir, a carnitine palmitoyl-transferase (CPT) inhibitor promoted extensive HL-60 cell death. Finally, 12-induced metabolic stress sensitized to HL-60 cells to cell death by the FDA-approved anti-leukemic drug ABT-199, a BH3 mimetic. Therefore, our results suggest that acylchlorohydroquinone is a promising scaffold in anti-promyelocytic leukemia drug research.Three novel series of triazolophthalazine derivatives bearing hydrazone moiety were designed, synthesized, and evaluated for their anticancer activity against four human cancer cell lines by MTT assay. Six derivatives demonstrated comparable activity with Doxorubicin reference drug against the selected cancer cells. Especially, compound 16 showed the most potent activity with IC50 values of 5.70, 8.04, 11.15, and 4.25, µM against HePG2, MCF-7, PC3, and HCT-116 respectively. Also, compound 26 exhibited comparable inhibitory effect with that of Doxorubicin against the selected cancer cell lines with IC50 values of 6.45, 8.63, 12.28, and 7.03 µM against HePG2, MCF-7, PC3, and HCT-116 respectively. Investigation of the apoptotic activity of the two most active compounds revealed that compounds 16 and 26 could induce both the early and the late apoptosis of HePG2. Further mechanistic study of the HePG2 cell cycle confirmed the spectacular cytotoxic and apoptotic effects of both compounds. Compounds 16 and 26 showed a pronounced increase in cells in G2/M and Pre G1 phases with a concomitant reduction of cells in G0-G1 and S phases. A follow up enzymatic assay indicated that these two compounds have comparable activities with that of bromosporine as PCAF inhibitors with IC50 values of 8.13 and 5.31 µM respectively. Moreover, molecular docking study for all the synthesized compounds was performed to predict their binding affinities toward the active site of histone acetyltransferase GCN5. Results of molecular docking were strongly correlated with that of the cytotoxicity study.Background The opening hours of drug consumption rooms could constitute a barrier to access among people who use drugs (PWUD). CAS Baluard is an outpatient substance use care center in Barcelona, which provides a drug consumption room in Barcelona among other services. The objectives of our study were to compare the client profile, the facility use, the drugs used, and the number of non-fatal overdose episodes between (1) a 15-hour opening period of a drug consumption room versus a 24-hour opening period; and (2) between daytime and nighttime during the 24-hour period. Methods Data from CAS Baluard was obtained from March-June (15-hour opening period) and July-October (24-hour opening period), 2018. The sociodemographic characteristics of clients were gathered in both periods and in the daytime and nighttime client groups in the 24-hour period. Finally, associations were estimated between facility use and period and between facility use and opening hours. Results There were 1,089 clients in the 15-hour period and 1,262 in the 24-hour period. There were no sociodemographic differences in the clients between periods. During nighttime, there was a higher proportion of women (17%) and homeless people (47%) than during daytime (12% and 30%, respectively). Injected cocaine use was more frequent during nighttime (34%) than during daytime (25%) and injected heroin use was less frequent during nighttime (17%) than during daytime (24%). There was a non-significant increase in non-fatal overdose risk during nighttime (PR 3.9 95%CI 0.98-15.64). However, when we analyzed heroin use alone, the increase in non-fatal overdose risk was significant (PR 4.69 95%CI 1.17-18.75). Conclusion During nighttime, attendance at the facility was higher among women, homeless people, and people who used stimulants. Our results point to a possible increase in overdose risk during nighttime, when most drug consumption rooms are closed.Background Social networks determine the availability of drugs, which in turn affects use patterns. Yet, there is some limited evidence that as frequency of drug use increases, people who use drugs increasingly utilize drug dealers. Further, females more often report receiving drugs for free. find more Studies on these two phenomena are limited by the substances they examine and the countries in which they have been conducted, and they have not been considered together. We examine whether gender differences in sources is moderated by increased frequency of use across four different substances in a web survey of sixteen European countries. Methods The European Web Survey on Drugs was collected from 2016-2018 among the national partners of the European Monitoring Centre for Drugs and Drug Addiction. Individuals who use drugs in sixteen European countries completed an online survey. For herbal cannabis, cannabis resin, cocaine, and MDMA, we examine drug acquisition sources by gender and frequency of use. Sources include through dealers and sharing or free, as well as growing and online markets for cannabis. We model each source with logistic regression with chained multiple imputation and a country fixed-effect and clustered standard errors. Results Across all substances, females who use drugs at low frequencies had significantly lower probabilities than males in using dealers; however, females were equally likely to use dealers when use is frequent. The probability of acquiring drugs for free was higher for females except among those who use most frequently, where the difference became non-significant except for herbal cannabis. Conclusions Females and males use dealers to acquire illicit drugs at similar rates when use is more frequent. Except for highest frequency use, females are typically more likely than males to acquire drugs for free. Examinations of supply should consider these gendered differences in acquisition.Background Although emerging evidence demonstrates increased risk of secondary bladder cancer following pelvic radiotherapy, the aggressiveness of these tumors is not well-characterized. Materials and methods A search of the Surveillance, Epidemiology, and End Results (SEER) 18 Database, identified 25,734 patients diagnosed with bladder cancer following definitive therapy for previous pelvic malignancy. Kaplan-Meier curve analyses were utilized to determine overall survival with significance set at p less then 0.05. Results Of the 25,734 patients, 11,376 (44.2%) received radiation treatment for their first cancer. Overall survival of bladder cancer was found to be 80%, 69.5%, and 49.2% at 1,2 and 5 years, respectively. There was no significant survival difference between groups whose first cancer was treated with or without radiation (p=0.8). A survival advantage was seen for the bladder cancer patients not treated with radiation for cervical (p=0.004), uterine (p=0.0006), and vaginal cancers (p less then 0.0 no significant survival difference between groups whose first cancer was treated with or without radiation. Second primary bladder cancer following pelvic radiotherapy has similar biologic aggressiveness to urothelial carcinoma developing without a history of radiotherapy.Introduction Microglandular adenosis (MGA) is a rare benign proliferative lesion lacking a myoepithelial cell layer; 27% of all reported cases have progressed to invasive carcinoma. Salivary gland-type carcinomas of the breast are also uncommon, representing 2% of all breast cancers. This wide spectrum of neoplasms tends to be triple negative and generally has an excellent prognosis. Given the rarity of salivary gland-type carcinomas of the breast arising from MGA, there are few reports of these cases in literature. As such, there is uncertainty regarding their diagnosis and treatment strategies. Presentation of case We report the rare case of a 66-year-old woman who presented with a triple negative, invasive carcinoma with salivary gland-type features, arising from MGA. The patient underwent mastectomy with sentinel lymph node biopsy, followed by Taxotere and Cyclophosphamide (TC) chemotherapy and 50 Gy in 25 fractions of radiation to her chest wall. We reviewed the available literature on salivary gland-type breast carcinomas arising from MGA. Discussion Despite the generally unfavourable characteristics associated with carcinoma arising in microglandular adenosis (MGACA), most patients with MGACA have favourable outcomes. Conclusions The findings of the present case and reviewed cases are consistent with the literature on MGA, atypical MGA (AMGA), and MGACA. Future study of this rare entity is warranted to establish a consensus surrounding its clinical significance and treatment methods.Background Impaired phagocytic function has been established in uremic patients. Chemotaxis, particle ingestion, and free radical and metabolic activity were all found to be disturbed in dialysis patients. Malnutrition is common among hemodialysis (HD) patients, with an estimated prevalence of 40% to 70%. Malnutrition-Inflammation Score (MIS) appears to be a useful tool for risk stratification of chronic HD patients. We assessed the correlation between MIS and phagocyte function in HD patients. Methods Forty-four chronic HD patients were enrolled from the dialysis unit. The patients were divided into two groups according to the MIS 1 to 12 (normal-mild) and 13 to 30 (severely malnourished). Hydrogen peroxide release by polymorphonuclear leukocytes was evaluated using the dihydrorhodamine 123 method. Phagocytic activity of neutrophils was evaluated after stimulation with Escherichia coli bacteria and phorbol 12-myristate 13-acetate (PMA) (positive control). Results Neutrophil oxidative activity in all HD patients versus healthy controls was significantly lower in median fluorescence intensity (MdFI)-E. coli and MdFI-PMA. We found significant correlations among MdFI-PMA and calculated MIS and other nutritional parameters in chronic HD patients. Conclusions Impaired phagocytic function was identified in chronic HD patients. The severity of the impairment was associated with nutrition and inflammation parameters, as well as Malnutrition-Inflammation Score.
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