Lactoperoxidase (LPO) is an enzyme found in several exocrine secretions including the airway surface liquid producing antimicrobial substances from mainly halide and pseudohalide substrates. Although the innate immune function of LPO has been documented against several microbes, a detailed characterization of its mechanism of action against influenza viruses is still missing. Our aim was to study the antiviral effect and substrate specificity of LPO to inactivate influenza viruses using a cell-free experimental system. Inactivation of different influenza virus strains was measured in vitro system containing LPO, its substrates, thiocyanate (SCN-) or iodide (I-), and the hydrogen peroxide (H2O2)-producing system, glucose and glucose oxidase (GO). Physiologically relevant concentrations of the components of the LPO/H2O2/(SCN-/I-) antimicrobial system were exposed to twelve different strains of influenza A and B viruses in vitro and viral inactivation was assessed by determining plaque-forming units of non-inactivated viruses using Madin-Darby canine kidney cells (MDCK) cells. Our data show that LPO is capable of inactivating all influenza virus strains tested: H1N1, H1N2 and H3N2 influenza A viruses (IAV) and influenza B viruses (IBV) of both, Yamagata and Victoria lineages. The extent of viral inactivation, however, varied among the strains and was in part dependent on the LPO substrate. Inactivation of H1N1 and H1N2 viruses by LPO showed no substrate preference, whereas H3N2 influenza strains were inactivated significantly more efficiently when iodide, not thiocyanate, was the LPO substrate. Although LPO-mediated inactivation of the influenza B strains tested was strain-dependent, it showed slight preference towards thiocyanate as the substrate. The results presented here show that the LPO/H2O2/(SCN-/I-) cell-free, in vitro experimental system is a functional tool to study the specificity, efficiency and the molecular mechanism of action of influenza inactivation by LPO. These studies tested the hypothesis that influenza strains are all susceptible to the LPO-based antiviral system but exhibit differences in their substrate specificities. We propose that a LPO-based antiviral system is an important contributor to anti-influenza virus defense of the airways.

A BS TRACT: Background: In patients with medically refractory essential tremor, unilateral magnetic resonanceguided focused ultrasound thalamotomy can improve contralateral tremor. However, this procedure does not address ipsilateral symptoms. Objective: The objective of the current study was to determine whether bilateral thalamotomies can be performed with an acceptable safety profile where benefits outweigh adverse effects. Methods: We conducted a prospective, single-arm, single-blinded phase 2 trial of second-side magnetic resonance-guided focused ultrasound thalamotomy in patients with essential tremor. Patients were followed for 3 months. The primary outcome was the change in quality of life relative to baseline, as well as the answer to the question "Given what you know now, would you treat the second side again?". Secondary outcomes included tremor, gait, speech, and adverse effects. Results: Ten patients were analyzed. The study met both primary outcomes, with the intervention resulting in clinically significant improvement in quality of life at 3 months (mean Quality of Life in Essential Tremor score difference, 19.7; 95%CI,; P = 0.004) and all patients reporting that they would elect to receive the secondside treatment again. Tremor significantly improved in all patients. Seven experienced mild adverse effects, including 2 with transient gait impairment and a fall, 1 with dysarthria and dysphagia, and 1 with mild dysphagia persisting at 3 months.

Complexes of metal monocations and phosphoserine (pSer) were generated by electrospray ionization (ESI), and were subjected to collision-induced dissociation (CID). The primary fragmentation pathways of [LiÁpSer] + , [NaÁpSer] + , and [AgÁpSer] + are dephosphorylation, dehydration, and Ser residue loss whereas metal ion loss is dominant for [RbÁpSer] + and [CsÁpSer] + . Density functional theory (DFT) calculations suggest a correlation between structures, ion-ligand binding energies, and fragmentation behavior: [LiÁp-Ser] + , [NaÁpSer] + , and [AgÁpSer] + , which exhibit a preference for charge-solvated structures, have high binding energies and dissociate through intramolecular fragmentation of the ligand, whereas [RbÁpSer] + and [CsÁpSer] + likely have salt-bridge structures with low binding energies, making the metal ion loss the dominant dissociation channel. Calculations also suggest that the salt-bridge structure of [NaÁpSer] + may be present in the current work.

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