Molluscicidal and biochemical effects of green-synthesized F-doped ZnO nanoparticles against land snail Monacha cartusiana under laboratory and field conditions.

The glass clover snail, Monacha cartusiana (M. cartusiana) is one of the most seriously impacting economic animal pests spreading across Egypt which inflicts severe damages to the agriculture. A green route is developed by deploying an abundant Rosemary plant leaves aqueous extract to synthesize ZnO and F-doped ZnO (F-ZnO) nanoparticles (NPs) that display high molluscicidal activities against the M. cartusiana land snails via leaf dipping and contact techniques. The effect of lethal concentrations, that kills 50% of exposed snails (LC50) value of the treatments, is examined on the activity of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), enzymes, total protein (TP), total lipids (TL) and cholesterol level of snails, including the histopathological evaluation of the digestive gland and foot of M. Cartusiana. Their molluscicidal activity as poisonous baits under field conditions is also evaluated and compared to the recommended molluscicide, Neomyl. The results show that F- doping dramatically improves the snail control capability of ZnO NPs, and promotes a considerable increase in both ALT and AST enzymes with an enhancement of TL and Cholesterol levels, but a significant decrease in TP content and ALP activity in treated snails compared to the control group. The LC50 values are found to be 1381.55 and 2197.59 ppm using the leaf dipping for F-ZnO and ZnO, while 237.51 and 245.90 ppm can be achieved using the contact technique, respectively. The greenly synthesized F-ZnO and ZnO NPs induce severe histological alterations in the digestive gland and foot of M. cartusiana, including a complete destruction of the digestive tubules. The histological evaluation of the foot of M. cartusiana exposed to ZnO, shows a rupture of the epithelial layer of the foot sole, while F- ZnO NPs causes the folds of the foot becoming deeper and the rupture of epithelial layer. Our field experiments further demonstrate that F-ZnO achieves 60.08% reduction, while ZnO attains 56.39% diminution in snail population compared to the commercial, Neomyl (69.55%), exhibiting great potentials in controlling the harmful land snail populations.

Adverse Events Associated With the Addition of Aspirin to Direct Oral Anticoagulant Therapy Without a Clear Indication.

Importance: It is unclear how many patients treated with a direct oral anticoagulant (DOAC) are using concomitant acetylsalicylic acid (ASA, or aspirin) and how this affects clinical outcomes. Objective: To evaluate the frequency and outcomes of prescription of concomitant ASA and DOAC therapy for patients with atrial fibrillation (AF) or venous thromboembolic disease (VTE). Design, Setting, and Participants: This registry-based cohort study took place at 4 anticoagulation clinics in Michigan from January 2015 to December 2019. Eligible participants were adults undergoing treatment with a DOAC for AF or VTE, without a recent myocardial infarction (MI) or history of heart valve replacement, with at least 3 months of follow-up. Exposures: Use of ASA concomitant with DOAC therapy. Main Outcomes and Measures: Rates of bleeding (any, nonmajor, major), rates of thrombosis (stroke, VTE, MI), emergency department visits, hospitalizations, and death. Results: Of the study cohort of 3280 patients (1673 [51.0%] men; mean [SD] age 68.2 [13.3] years), 1107 (33.8%) patients without a clear indication for ASA were being treated with DOACs and ASA. Two propensity score-matched cohorts, each with 1047 patients, were analyzed (DOAC plus ASA and DOAC only). Patients were followed up for a mean (SD) of 20.9 (19.0) months. Patients taking DOAC and ASA experienced more bleeding events compared with DOAC monotherapy (26.0 bleeds vs 31.6 bleeds per 100 patient years, P = .01). Specifically, patients undergoing combination therapy had significantly higher rates of nonmajor bleeding (26.1 bleeds vs 21.7 bleeds per 100 patient years, P = .02) compared with DOAC monotherapy. Major bleeding rates were similar between the 2 cohorts. Thrombotic event rates were also similar between the cohorts (2.5 events vs 2.3 events per 100 patient years for patients treated with DOAC and ASA compared with DOAC monotherapy, P = .80). Patients were more often hospitalized while undergoing combination therapy (9.1 vs 6.5 admissions per 100 patient years, P = .02). Conclusion and Relevance: Nearly one-third of patients with AF and/or VTE who were treated with a DOAC received ASA without a clear indication. Compared with DOAC monotherapy, concurrent DOAC and ASA use was associated with increased bleeding and hospitalizations but similar observed thrombosis rate. Future research should identify and deprescribe ASA for patients when the risk exceeds the anticipated benefit.