Antisense oligonucleotides (ASOs) are chemically modified nucleic acids with therapeutic potential, some of which have been approved for marketing. We performed a study in rats to investigate mechanisms of toxicity after administration of 3 tool locked nucleic acid (LNA)-containing ASOs with differing established safety profiles. Four male rats per group were dosed once, 3, or 6 times subcutaneously, with 7 days between dosing, and sacrificed 3 days after the last dose. These ASOs were either unconjugated (naked) or conjugated with N-acetylgalactosamine for hepatocyte-targeted delivery. The main readouts were in-life monitoring, clinical and anatomic pathology, exposure assessment and metabolite identification in liver and kidney by liquid chromatography coupled to tandem mass spectrometry, ASO detection in liver and kidney by immunohistochemistry, in situ hybridization, immune electron microscopy, and matrix-assisted laser desorption/ionization mass spectrometry imaging. The highly toxic compounds showed the greatest amount of metabolites and a low degree of tissue accumulation. This study reveals different patterns of cell death associated with toxicity in liver (apoptosis and necrosis) and kidney (necrosis only) and provides new ultrastructural insights on the tissue accumulation of ASOs. We observed that the immunostimulatory properties of ASOs can be either primary from sequence-dependent properties or secondary to cell necrosis.Aim Phenytoin is metabolized through CYP2C9 and CYP2C19. selleck compound Polymorphisms of CYP2C9 and CYP2C19 may increase plasma concentration and side effects. Materials & methods Systematic review and meta-analysis were performed to evaluate the effects of CYP2C9 and CYP2C19 polymorphism on pharmacokinetic parameters. PubMed, Science Direct, Cochrane library, and Thai databases were systematically searched. Results Eight observational studies, comprising a total of 633 patients were included. Michaelis-Menten constant was significantly higher in the polymorphism of CYP2C9IM/CYP2C19EM and CYP2C9IM/CYP2C19IM groups as compared with the control groups (CYP2C9EM/CYP2C19EM) at 2.16 and 1.55 mg/l (p less then 0.00001, p less then 0.0001). The maximum rate of action was significantly lower in the control groups as compared with the polymorphism of CYP2C9IM/CYP2C19EM and CYP2C9IM/CYP2C19IM groups at 3.10 and 3.53 mg/kg/day (p = 0.00001, less then 0.0001). Conclusion The dosage regimen for patients in the CYP2C9IM group to achieve phenytoin therapeutic levels was 2.1-3.4 mg/kg/day.Aim To examine the economic impact of lives lost due to the COVID-19 pandemic across New York State. Materials & methods Death counts by age range and period life expectancy were extracted from the NYS Department of Health, NYC Department of Health and Mental Hygiene, and Social Security Administration website. Years of potential life lost and value of statistical life (VSL) were calculated. Results The average years of potential life lost per person was 12.72 and 15.13, and the VSL was US$119.62 and 90.45 billion, in NYS and NYC, respectively. VSL was greatest in Queens and Brooklyn, followed by the Bronx, Manhattan and Staten Island. Conclusion New York City, specifically Queens and Brooklyn, bore the greatest economic burden of lives lost across the state. Examine the association of Graves' disease with the development of postoperative neck hematoma. A cohort of patients participating in the Thyroid Procedure-Targeted Database of the National Surgical Quality Improvement Program from January 1, 2016 to December 31, 2018. A North American surgical cohort study. 17 906 patients who underwent thyroidectomy were included. Propensity score matching was performed to adjust for differences in baseline covariates. Multivariate logistic regression was used to ascertain the association between thyroidectomy for Graves' disease and risk of postoperative adverse events within 30 days of surgery. The primary outcome was postoperative hematoma. Secondary outcomes were postoperative hypocalcemia and recurrent laryngeal nerve injury. One-to-three propensity score matching yielded 1207 patients with mean age (SD) of 42.6 (14.9) years and 1017 (84.3%) female in the group with Graves' disease and 3621 patients with mean age (SD) of 46.7 (15.0%) years and 2998 (82.8%) female in the group with indications other than Graves' disease for thyroidectomy. The cumulative 30-day incidence of postoperative hematoma was 3.1% (38/1207) in the Graves' disease group and 1.9% (70/3621) in other patients. The matched cohort showed that Graves' disease was associated with higher odds of postoperative hematoma (OR 1.65, 95% CI 1.10-2.46) and hypocalcemia (OR 2.04, 95% CI 1.66-2.50) compared with other indications for thyroid surgery. There was no difference in recurrent laryngeal nerve injury among the 2 groups. Patients with Graves' disease undergoing thyroidectomy are more likely to suffer from postoperative hematoma and hypocalcemia compared to patients undergoing surgery for other indications.Patients with Graves' disease undergoing thyroidectomy are more likely to suffer from postoperative hematoma and hypocalcemia compared to patients undergoing surgery for other indications.Aim Personalized medicine (PM) is revolutionizing biomedical and clinical research while improving the ways healthcare is delivered. The EU is at the forefront of science and innovation in this field, increasing collaborations worldwide. This paper aims to assess the status of recent collaborations between Europe and China in PM-related science, technology and funded research. Methods We analyze scientific literature, patents and funding programs, respectively. Results PM is a scientific and industrial priority in both geographical areas, but current levels of collaboration are suboptimal. To increase these levels, policy makers should promote cooperation between researchers, innovators, industries, regulators, funding agencies and healthcare systems, while providing a forum to exchange best practices, define common guidelines for PM implementation and promote public-private partnerships.