Effect of discontinuation of ticagrelor and switching-over to other P2Y12 agents in patients with acute coronary syndrome: a single-center real-world experience from India.

BACKGROUND: Dual antiplatelet therapy is the current standard of care after acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI). We intended to study the pattern of use of ticagrelor in patients with acute coronary syndrome undergoing PCI and the effect of switching over to other P2Y12 receptor inhibition on clinical outcomes. RESULTS: All patients aged > 18 years who had been admitted with acute coronary syndrome and had been provided ticagrelor as the second antiplatelet agent were included as study participants. The primary outcome of the study was the composite outcome of death, recurrent myocardial infarctions, re-intervention, and major bleeding. We studied 321 patients (54 female patients, 16.82%). The mean age of the patients was 56.65 ± 11.01 years. Ticagrelor was stopped in 76.7% on follow-up. It was stopped in 6.3%, 13.5%, 13.1%, 21.9%, and 45.1% of patients during the first month but after discharge, between first and third months, between 3 and 6 months, between 6 and 12 months, and after 12 months, respectively. In the majority of patients, ticagrelor was replaced by clopidogrel (97.9%). It was stopped according to the physician's discretion in 79.3% of patients, whereas it was the cost of the drug that made the patient to get swapped to another agent in 18.6%. No difference in the primary composite outcome was observed between the groups where ticagrelor was continued post 12 months and ticagrelor was continued and ticagrelor was switched-over to another agent. Similarly, no difference in death, recurrent myocardial infarctions, re-interventions, or major bleeding manifestations was observed between the two groups. CONCLUSION: In patients with acute coronary syndrome who undergo PCI, we observed that early discontinuation of ticagrelor and switching over to other P2Y12 inhibitors after discharge did not affect clinical outcomes.

Geochemical fractionation of trace elements in the coral reef sediments of the Lakshadweep Archipelago, Indian Ocean.

Geochemical fractionation of seven trace elements (Cr, Mn, Fe, Cu, Zn, Cd, and Pb) was investigated in the surficial coral reef sediments of three inhabited islands (Kavaratti, Kadmat, and Agatti) belonging to the Lakshadweep Archipelago. The observations indicated that the metals showed their highest contents in the residual fraction of geological origin. The extent of risk, bioavailability, and contamination of trace elements was assessed by risk assessment codes and contamination factors. Based on the results, medium potential adverse effects were observed in the sediments of Kavaratti and Agatti. The concentration of Cd in the exchangeable and carbonate-bound fractions was above its global average shale value in the sediments of Kavaratti and Agatti, suggesting its high mobility and bioavailability and thus an environmental threat to the coral reef ecosystem.

Functional Autophagic Flux Regulates AgNP Uptake And The Internalized Nanoparticles Determine Tumor Cell Fate By Temporally Regulating Flux.

BACKGROUND: Silver nanoparticles (AgNPs) are known to induce the conserved, cellular, homeostatic process- autophagy in tumor cells. Previous studies primarily focus on the pro-survival role of autophagy post AgNP exposure in tumor cells, but seldom on its role in AgNP uptake, or on the functional significance of autophagy temporal dynamics. Our study sheds more light on the extensive crosstalk that exists between AgNP and autophagy, which can be critical to the improvement of AgNP-induced therapeutic effects. METHODS: ß-cyclodextrin (ß-CD) coated AgNPs of two different sizes were synthesized by nucleation method and characterized by transmission electron microscopy. Fluorescence microscopy and flow cytometry were used to probe intracellular uptake of AgNPs. Endocytic mechanism of AgNPs was classically analyzed through use of various endocytosis inhibitors. Autophagy was evaluated by immunoblot and fluorescence microscopy. Additionally, immunoblot was performed to monitor Janus Kinase (JNK) signalling, ubiquitination of proteins, expression of endo-lysosomal and apoptotic markers in correlation to AgNP-induced autophagy. RESULTS: The intra-cellular route of entry for the small NPs (~9 nm; ss-AgNPs) was different than the large NPs (~19 nm; ls-AgNPs) studied. However, irrespective of their unique route of entry an inhibition of autophagic flux by chloroquine (CQ) reduced uptake of both the AgNPs. In contrary, rapamycin (Rapa), an autophagy inducer enhanced it. Importantly, JNK activation was required for autophagy induction and AgNP uptake. Furthermore, effect of AgNPs on autophagy showed temporal dependency. An enhanced autophagic flux was noted at early time points; however, prolonged exposure resulted in inhibition of flux marked by increase in Rab7, LC3B-II and p62 proteins. Inhibition of flux was associated with lysosomal dysfunction, decreased LAMP1 expression and an increased accumulation of ubiquitinated (Ub) proteins. This resulted in heightened reactive oxygen species (ROS) and consequent cytotoxicity. CONCLUSION: In this study, we observed that a functional autophagic flux aids AgNP uptake, but AgNPs in turn, overtime, inhibits flux and endo-lysosomal function. We provide critical, novel insights into crosstalk between AgNP and autophagy which can be vital to future AgNP-based therapy development.

Spatial variation of trace element concentration and contamination assessment in the coral reef sediments of Lakshadweep Archipelago, Indian Ocean.

Surface sediments were collected from the shore and lagoons of Kavaratti, Kadmat and Agatti islands of Lakshadweep Archipelago and analysed for trace element concentration. The sediment contamination was assessed on the basis of geochemical, biological hazard and ecological risk indices. Except Cd and Pb, all the other trace elements selected for the study were below the contamination level. Compared to Kadmat, Kavaratti and Agatti were more polluted and the pollution was pronounced in lagoons than shore. Population pressure, untreated sewage, diesel based power generation, shipping and tourism activities contribute to sediment contamination. Statistical analysis revealed the association of trace elements with sedimentary characteristics due to anthropogenic sources.