COVID-19 Vaccinations: Perceptions and Behaviours in People with Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) is a rare genetic disease that causes recurrent respiratory infections. People with PCD may be at higher risk of severe coronavirus disease 2019 (COVID-19), and therefore vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important. We studied vaccination willingness, speed of vaccination uptake, side effects, and changes in social contact behaviour after vaccination in people with PCD. We used data from COVID-PCD, an international participatory cohort study. A COVID-19 vaccination questionnaire was emailed to participants in May 2021 and 423 participants from 31 countries replied (median age: 30 years, range 1-85 years; 261 (62%) female). Vaccination uptake and willingness were high, with 273 of 287 adults (96%) being vaccinated or willing to be in June 2021; only 4% were hesitant. The most common reason for hesitancy was fear of side effects, reported by 88%. Mild side effects were common, but no participant reported severe side effects. Half of the participants changed their social behaviour after vaccination by seeing friends and family more often. The high vaccination willingness in the study population might reflect the extraordinary effort taken by PCD support groups to inform people about COVID-19 vaccination. Clear and specific information and involvement of representatives is important for high vaccine uptake.

Biological consequences of trinuclear platinum complexes: comparison of [[trans-PtCl(NH3)2]2mu-(trans-Pt(NH3)2(H2N(CH2)6-NH2)2)]4+ (BBR 3464) with its noncovalent congeners.

[[trans-PtCl(NH(3))(2)](2)mu-(trans-Pt(NH(3))(2)(H(2)N(CH(2))(6)NH(2))(2))](4+) (BBR 3464) is a 4+ cationic trinuclear platinum drug that has undergone phase II clinical trials in the treatment of ovarian and lung cancers. The chemical structure of BBR 3464 is distinct from that of clinically used agents such as cisplatin and oxaliplatin. As a consequence, the modes of DNA binding and the structures of BBR 3464 DNA adducts are also structurally distinct from those formed by cisplatin and oxaliplatin. Previous chemical and spectroscopic measurements on BBR 3464 had elucidated a significant noncovalent contribution to DNA binding. To examine this effect further, the biological activity of two BBR 3464 analogs that bind DNA only through noncovalent interactions was investigated in this study, and their cellular effects were compared with those caused by the "parent" drug. The compounds were [[trans-PtL(NH(3))(2)](2)mu-(trans-Pt(NH(3))(2)(H(2)N(CH(2))(6)NH(2))(2))](n+), with L = NH(3), n = 6 for compound I, and L = H(2)N(CH(2))(6)NH(3), n = 8 for compound II. All compounds induce caspase-dependent apoptosis in both primary mast cells and transformed mastocytomas, although with a smaller IC(50) value in the transformed cells. In cells deficient in either the tumor suppressor proteins p53 or Bax, apoptosis was least affected in the case of II, but in all cases the effect of p53 deficiency was greater than that of Bax. Surprisingly, cellular uptake was actually enhanced for the more highly charged compounds, resulting in significant (micromolar) cyotoxicity for II. Cellular accumulation was enhanced in mastocytomas over primary mast cells, suggesting a mechanism for enhancement of tumor cell selectivity.

Synthesis, characterization, and cytotoxicity of a novel highly charged trinuclear platinum compound. Enhancement of cellular uptake with charge.

Charge delocalization (6+ to 8+) in "noncovalent" linear trinuclear platinum complexes produces compounds with cytotoxicity in some cases equivalent to cisplatin. The cellular uptake of a novel 8+ compound is greater than that of neutral cisplatin as well as other multinuclear Pt compounds.