A U.K. Multicenter Retrospective Study of the Learning Curve and Relative Impact on Success Rates and Procedural Metrics of the RHYTHMIA HDx™ Mapping System.

The learning curve for the novel RHYTHMIA HDx™ 3-dimensional electroanatomic system is unknown. Retrospective data collection was carried out at 3 U.K. centers from the introduction of RHYTHMIA HDx™ (Boston Scientific, Marlborough, MA, USA) and associated mapping and ablation catheters. Patients were matched with controls using the CARTO® 3 mapping system (Biosense Webster Inc., Diamond Bar, CA, USA). Fluoroscopy, radiofrequency ablation, and procedure times; acute and long-term success; and complications were assessed. A total of 253 study patients along with 253 controls were included. Significant correlations existed between procedural efficiency metrics and center experience for de novo atrial fibrillation (AF) ablation (procedure time, Spearman's ρ = -0.624; ablation time, ρ = -0.795; both P < .0005) and de novo atrial flutter (AFL) ablation (ablation time, ρ = -0.566; fluoroscopy time, ρ = -0.520; both P = .001). No correlations existed for other assessed atrial arrhythmias. For de novo AF and AFL, metrics significantly improved after 10 procedures in each center (procedure time [AF only, P = .001], ablation time [AF, P < .0005; AFL, P < .0005], and fluoroscopy time [AFL only, P = .0022]) and became comparable to those of controls. Acute success and long-term success did not experience significant improvements with experience, but they were comparable to the control group throughout. Complications with RHYTHMIA HDx™ were comparable to those associated with CARTO® 3. In conclusion, a short learning curve exists with the use of RHYTHMIA HDx™ for standardized procedures (de novo AF/AFL). Procedural performance improved and became comparable to that seen with CARTO® 3 following 10 cases at each center. Clinical outcomes at 6 and 12 months and complications were no different from those observed in controls.

The Anticancer Properties of Artemisia aucheri Boiss Extract on HT29 Colon Cancer Cells.

BACKGROUND: Colon cancer is one of the most common cancers in the world, and efforts toward its treatment have not been completely successful. In recent years, more attention has been focused on herbal medicine (HM) due to their anticancer and cytotoxic properties. This study investigated the anticancer and antioxidant effects of Artemisia aucheri (A. aucheri) Boiss extract against HT29 colon cancer cells compared with HEK239 natural cells. METHODS: This study was performed on human HT29 colon cancer cells. Various doses of 0, 10, 100, 500, and 1000 µg/ml of A. aucheri extract were subjected to cells at specified time intervals. After treatment, the trypan blue test was employed to determine the viability of the cells. MTT and annexin tests were used to determine cell viability and the apoptosis induced by the extract. Malondialdehyde (MDA) testing was applied to investigate the antioxidant properties of the extract on fatty acids. Data analysis was performed using SPSS version 22. One-way ANOVA and paired comparison tests were employed for data analysis. RESULTS: The highest cytotoxicity effect of A. aucheri extract was observed at 1000 µg/ml (80.63 ± 3.66) being dose-dependent compared with the control in both cell lines (p < 0.001). Additionally, the survival rate of HT29 (IC50 = 57.88 µg/ml) and HEK (IC50 = 295 µg/ml) cancer cells decreased with increasing concentration of A. aucheri (the lowest cell viability was at 1000 µg/ml). Furthermore, the induction of membrane lipid peroxidation was significantly higher in HT29 compared with the control (p < 0.001). Another cytotoxic mechanism for the extract was the induction of apoptosis being significantly higher in HT29 colon cancer cells compared with the control group (p < 0.001). CONCLUSION: Cytotoxic effects of A. aucheri extract were dose-dependent. This HM exerted cytotoxic effects against HT29 cells through the induction of membrane lipid peroxidation and apoptosis.

Risk factors for unsuccessful tuberculosis treatment outcomes in children.

OBJECTIVE: Pakistan has a high pediatric burden of tuberculosis, but few studies describe the treatment experience of children with tuberculosis in Pakistan. We sought to identify risk factors for unsuccessful treatment outcomes in children with drug-susceptible tuberculosis identified in eight hospitals in Karachi, Pakistan. DESIGN: We conducted a retrospective cohort study among children (<15 years old) treated with first-line anti-tuberculosis drugs for presumed or confirmed drug-susceptible tuberculosis between 2016 and 2017. We assessed risk factors for experiencing an unsuccessful treatment outcome through multivariable logistic regression analysis. RESULTS: In total, 1,665 children initiated tuberculosis treatment, including 916 (55.0%) identified through intensified case finding. Unsuccessful treatment outcomes were experienced by 197 (11.8%) children, comprising 27 (1.6%) deaths, 16 (1.0%) treatment failures, and 154 (9.3%) lost to follow-up. An additional 47 (2.8%) children had outcomes not evaluable. In multivariable analysis, children 0-4 years old (OR: 1.80, 95% CI: 1.07-3.04), males (OR: 1.48, 95% CI: 1.04, 2.11), and those with bacteriologic confirmation of disease (OR: 3.39, 95% CI: 1.98, 5.80) had increased odds of experiencing an unsuccessful treatment outcome. CONCLUSION: Our findings suggest a need to deploy strategies to identify children earlier in the disease process and point to the need for interventions tailored for young children once treatment is initiated.

Cytokines secreted by human Wharton's jelly stem cells inhibit the proliferation of ovarian cancer (OVCAR3) cells in vitro.

Cytokines enhance tumour cell recognition via cytotoxic effector cells and are therefore effectively used in cancer immunotherapy. Mesenchymal stem cells have efficient homing potential and have been used to target and inhibit various types of cancer mediated by the release of soluble/bioactive factors. Initial evaluation of the human Wharton's jelly stem cell conditioned medium (hWJSC-CM) and cell lysate (hWJSC-CL) against an ovarian cancer cell line (OVCAR3) demonstrated their inhibitory effect in vitro. The secreted cytokine profile was then studied to understand whether the OVCAR3 inhibitory effect was mediated by the cytokines. Expression of cytokines in OVCAR3 following 48 h treatment with hWJSC extracts, namely the hWJSC-CM (50%) and hWJSC-CL (10 µg/ml), was evaluated using multiplex cytokine assay. Paclitaxel (5 nM) was used as a positive control. Cytokines tumour necrosis factor α, interleukin (IL)-4, IL-6, IL-8, IL-10, IL-13, IL-17, IL-1ß and granulocyte colony-stimulating factor, reported to be involved in tumour growth, invasion and migration, were significantly decreased. Cytokines with antitumour effects, namely IL-1 receptor antagonist (IL-1RA), IL-2, IL-2 receptor, IL-5, IL-7, IL-12, IL-15, interferon (IFN)-α and IFN-γ, were mildly increased or decreased. Only the increases in IL-1RA (with paclitaxel, hWJSC-CM and hWJSC-CL) and granulocyte-macrophage colony-stimulating factor (with hWJSC-CL) were statistically significant. The chemokines monocyte chemoattractant protein 1, macrophage inflammatory protein (MIP)-1α, MIP-1ß and Regulated Upon Activation, Normally T-Expressed, and Secreted were significantly decreased while monokine induced by IFN-γ, IFN-γ induced protein 10 and Eotaxin demonstrated mild decreases. The growth factors basic fibroblast growth factor, vascular endothelial growth factor and hepatocyte growth factor were significantly decreased. Heatmaps demonstrated differential fold changes in cytokines and hierarchical cluster analysis revealed 3 major and 7 minor sub-clusters of associated cytokines, chemokines and growth factors. In conclusion, the hWJSC extracts decreased the expression of oncogenic cytokines, chemokines and growth factors, which mediated the inhibition of OVCAR3 cells in vitro.

Synthesis and anticonvulsant activity of some novel fused heterocyclic 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole derivatives.

In the present investigation, a series of 3,6-disubstituted-1,2,4-triazolo-1,3,4-thiadiazole derivatives (6a-t) were synthesized and evaluated for their anticonvulsant activity and neurotoxicity. The structures of synthesized compounds were confirmed on the basis of their elemental analysis and spectral data results. In anti-MES activity compounds 6b, 6c, 6g, 6j, 6k, 6q and 6r showed potent activity comparable to that of standard drugs: phenytoin and carbamazepine. Compounds 6c, 6k, 6n, 6p and 6s successfully passed the rotorod test without any sign of neurological deficit.