Bennetsenstern3917

Despite the great promise for therapies using antisense oligonucleotides (ASOs), their adverse effects, which include pro-inflammatory effects and thrombocytopenia, have limited their use. Previously, these effects have been linked to the phosphorothioate (PS) backbone necessary to prevent rapid ASO degradation in plasma. The main aim of this study was to assess the impact of the nucleic acid portion of an ASO-type drug on platelets and determine if it may contribute to thrombosis or thrombocytopenia.

Platelets were isolated from healthy donors and men with advanced prostate cancer. Effects of antisense oligonucleotides (ASO), oligonucleotides, gDNA, and microRNA on platelet activation and aggregation were evaluated. A mouse model of lung thrombosis was used to confirm the effects of PS-modified oligonucleotides in vivo.

Platelet exposure to gDNA, miRNA, and oligonucleotides longer than 16-mer at a concentration above 8mM resulted in the formation of hypersensitive platelets, characterized by an increas before initiation of patient treatment.

Oral anticoagulants (OAC) have shown to affect bone mineral density and cause osteoporosis. Limited studies have investigated the relationship between its use and risk of osteoporosis. We aim to compare the risk of osteoporosis in patients on warfarin versus direct oral anticoagulants (DOACs).

A retrospective single-center cohort study was conducted in veterans age>18years of age in whom warfarin or DOACs were newly initiated between January 1st, 2012 to April 1st, 2020 at Salem VA Medical Center. Patients on OAC for at least 90days qualified for inclusion and excluded if they were pregnant or had history of mechanical valve and mitral stenosis, on edoxaban or had previous history of osteoporosis or use of antiosteoporosis medication. Primary outcome was comparing incidence of new-onset osteoporosis between warfarin and DOACs. Secondary outcomes included comparing incidence of all clinical fractures, hip fractures, major bleeding and intracranial bleed between the treatments. Cox proportional hazard raents.

Overall, as compared to warfarin, prolonged use of DOACs is associated with lower risk of new-onset osteoporosis. We hope that our study findings will enlighten current clinical practices assuring safe use of OAC in veteran patients.

Venous thromboembolism (VTE) is a well-recognized complication in pediatric cancer patients. It has been demonstrated that the incidence of VTE in pediatric patients with central nervous system (CNS) tumors is lower than that of patients with other cancers. Risk factors for developing cancer-related thrombosis are numerous and can include patient, disease, or treatment-related influences. The present study was designed to assess the VTE incidence in a pediatric oncology population, and to investigate whether intensity of treatment has similar associated with risk of VTE development in patients with and without CNS tumors.

A retrospective population-based cohort study of pediatric oncology patients in Atlantic Canada was conducted. Data collected from medical records included demographics, cancer type, treatment, presence of central venous catheters (CVC), and presence of thrombosis. Treatment intensity was assessed using the intensity of treatment rating scale (ITR-3). Study period was from January 2000 tg VTE.Frequent cyanobacterial blooms in reservoirs used for human supply increase the risk of noxious secondary metabolites, endangering human health and ecological balance, and requiring constant monitoring by water companies. Although hydrogen peroxide (H2O2) has been widely reported as an effective agent for the control of cyanobacteria, being Microcystis aeruginosa one of the most studied species, very limited data is available on its effects over Dolichospermum circinale. Therefore, this study aimed to evaluate the impact of H2O2 on D. circinale and comparing it to the effects over the M. aeruginosa. The treatment was performed in cyanobacterial cultures with the application of 2 and 5 mg L-1 of H2O2 under visible light. To measure the impact of the treatment, intact cells were counted and cell re-growth monitored. Geosmin and microcystin, cell pigments, color, and organic matter in water were also analyzed during the treatment. The results showed that even the smallest H2O2 concentration (2 mg L-1) was able to completely remove D. circinale cells. Although M. aeruginosa could only be completely removed using 5 mg L-1, the few cells remaining after the application of 2 mg L-1 were not viable and did not re-grew after 15 days. Total microcystin concentration increased after M. aeruginosa was exposed to H2O2, suggesting that oxidative stress may increase the detection of this metabolite when the cells are lysed. While 2 mg L-1 was able to significantly decrease total geosmin, the addition of 5 mg L-1 did not improve removal. JAK assay Chlorophyll-a was readily degraded after cell rupture but the same did not happen to phycocyanin, demonstrating its high resilience to this oxidant. Color and organic matter increased for the M. aeruginosa but decreased for the D. circinale suspension, probably because the higher concentration of the M. aeruginosa yielded more extracellular content to the water which was not able to be degraded by the amount of H2O2 applied.Colloidal nanoparticles (NPs) have attracted significant attention due to their unique physicochemical properties suitable for diagnosing and treating different human diseases. Nevertheless, the successful implementation of NPs in medicine demands a proper understanding of their interactions with the different proteins found in biological fluids. Once introduced into the body, NPs are covered by a protein corona (PC) that determines the biological behavior of the NPs. The formation of the PC can eventually favor the rapid clearance of the NPs from the body before fulfilling the desired objective or lead to increased cytotoxicity. The PC nature varies as a function of the different repulsive and attractive forces that govern the NP-protein interaction and their colloidal stability. This review focuses on the phenomenon of PC formation on NPs from a physicochemical perspective, aiming to provide a general overview of this critical process. Main issues related to NP toxicity and clearance from the body as a result of protein adsorption are covered, including the most promising strategies to control PC formation and, thereby, ensure the successful application of NPs in nanomedicine.