Mechanism of Daunomycin Intercalation into DNA from Enhanced Sampling Simulations.

Daunomycin is a widely used anticancer drug, yet the mechanism underlying how it binds to DNA remains contested. 469 all-atom trajectories of daunomycin binding to the DNA oligonucleotide (GCG CAC GTG CGC) were collected using weighted ensemble (WE)-enhanced sampling. Mechanistic insights were revealed through analysis of the ensemble of trajectories.

Molecular Mechanism of Ligand Binding to the Minor Groove of DNA.

Although DNA-ligand binding is pervasive in biology, little is known about molecular-level binding mechanisms. Using all-atom, explicit-solvent molecular dynamics simulations in conjunction with weighted ensemble (WE)-enhanced sampling, an ensemble of 2562 binding trajectories of Hoechst 33258 (H33258) to d(CGC AAA TTT GCG) was generated from which the binding mechanism was extracted. In particular, the electrostatic interaction between the positively charged H33258 and the negatively charged DNA backbone drives the formation of initial H33258-DNA contacts.

[Advantages of pH-impedance monitoring in gastroesophageal reflux and dysphagia investigations].

ENT symptoms of gastro-esophageal reflux are frequent. pH-impedance can detect acid and non-acid reflux and measure their proximal extension. The technique identifies the refluxate by changes in impedance.

[Gastroesophageal reflux: a possible cause of paroxysmal laryngeal dyspnea].

An important number of patients are referred to the ENT specialist because of extraoesophageal manifestations of gastroesophageal reflux. The most alarming symptom is a paroxysmal dyspnea secondary to a laryngospasm. The patients report a laryngeal choking sensation associated to an aphonia.

Horizontal partial laryngectomy for supraglottic squamous cell carcinoma.

Between 1981-1999, 75 patients treated for supraglottic SCC with horizontal supraglottic laryngectomy (HSL) at the Otolaryngology Head and Neck Surgery Department of Lausanne University Hospital were retrospectively studied. There were 16 patients with T1, 46 with T2 and 13 with T3 tumors. Among these, 16 patients (21%) had clinical neck disease corresponding to stage I, II, III and IV in 12, 39, 18 and 6 patients, respectively.