Synthesis and characterisation of peroxypinic acids as proxies for highly oxygenated molecules (HOMs) in secondary organic aerosol

Peroxy acids were recently found to be involved in new particle formation in the atmosphere and could also substantially contribute towards particle toxicity. However, a lack of suitable analytical methods for the detection and characterisation of peroxy acids in the particle phase is currently hindering the quantitative investigation of their contribution to these important atmospheric processes. Further development of appropriate techniques and relevant standards is therefore urgently needed. In this study, we synthesised three peroxypinic acids, developed a liquid chromatography separation method and characterised them with tandem mass spectrometry. The observed fragmentation patterns clearly distinguish the different peroxypinic acids from both the acid and each other, showing several neutral losses previously already observed for other peroxy acids. Both monoperoxypinic acids were found to be present in secondary organic aerosol generated from ozonolysis of α-pinene in laboratory experiments. The yield of monoperoxypinic acid formation was not influenced by humidity. Monoperoxypinic acid quickly degrades on the filter, with about 60% lost within the first 5h. This fast degradation shows that time delays in traditional off-line analysis will likely lead to severe underestimates of peroxy compound concentrations in ambient particles.Sarah S. Steimer acknowledges funding support from the Swiss National Science Foundation (project no. 162258). Funding by the European Research Council (ERC starting grant 279405) and the European Union’s Horizon 2020 research and innovation programme through the EUROCHAMP-2020 Infrastructure Activity under grant agreement no. 730997 is acknowledged

The effect of viscosity and diffusion on the HO₂ uptake by sucrose and secondary organic aerosol particles

We report the first measurements of HO2 uptake coefficients, γ, for secondary organic aerosol (SOA) particles and for the well-studied model compound sucrose which we doped with copper(II). Above 65% relative humidity (RH), γ for copper(II)-doped sucrose aerosol particles equalled the surface mass accommodation coefficient α=0.22±0.06, but it decreased to γ=0.012±0.007 upon decreasing the RH to 17 %. The trend of γ with RH can be explained by an increase in aerosol viscosity and the contribution of a surface reaction, as demonstrated using the kinetic multilayer model of aerosol surface and bulk chemistry (KM-SUB). At high RH the total uptake was driven by reaction in the near-surface bulk and limited by mass accommodation, whilst at low RH it was limited by surface reaction. SOA from two different pre-cursors, α-pinene and 1,3,5-trimethylbenzene (TMB), was investigated, yielding low uptake coefficients of γ<0.001 and γ=0.004±0.002, respectively. It is postulated that the larger values measured for TMB-derived SOA compared to α-pinene-derived SOA are either due to differing viscosity, a different liquid water content of the aerosol particles, or an HO2 + RO2 reaction occurring within the aerosol particles

Association between the number of coadministered P-glycoprotein inhibitors and serum digoxin levels in patients on therapeutic drug monitoring

BACKGROUND: The ABC transporter P-glycoprotein (P-gp) is recognized as a site for drug-drug interactions and provides a mechanistic explanation for clinically relevant pharmacokinetic interactions with digoxin. The question of whether several P-gp inhibitors may have additive effects has not yet been addressed. METHODS: We evaluated the effects on serum concentrations of digoxin (S-digoxin) in 618 patients undergoing therapeutic drug monitoring. P-gp inhibitors were classified as Class I, with a known effect on digoxin kinetics, or Class II, showing inhibition in vitro but no documented effect on digoxin kinetics in humans. Mean S-digoxin values were compared between groups of patients with different numbers of coadministered P-gp inhibitors by a univariate and a multivariate model, including the potential covariates age, sex, digoxin dose and total number of prescribed drugs. RESULTS: A large proportion (47%) of the digoxin patients undergoing therapeutic drug monitoring had one or more P-gp inhibitor prescribed. In both univariate and multivariate analysis, S-digoxin increased in a stepwise fashion according to the number of coadministered P-gp inhibitors (all P values < 0.01 compared with no P-gp inhibitor). In multivariate analysis, S-digoxin levels were 1.26 ± 0.04, 1.51 ± 0.05, 1.59 ± 0.08 and 2.00 ± 0.25 nmol/L for zero, one, two and three P-gp inhibitors, respectively. The results were even more pronounced when we analyzed only Class I P-gp inhibitors (1.65 ± 0.07 for one and 1.83 ± 0.07 nmol/L for two). CONCLUSIONS: Polypharmacy may lead to multiple drug-drug interactions at the same site, in this case P-gp. The S-digoxin levels increased in a stepwise fashion with an increasing number of coadministered P-gp inhibitors in patients taking P-gp inhibitors and digoxin concomitantly. As coadministration of digoxin and P-gp inhibitors is common, it is important to increase awareness about P-gp interactions among prescribing clinicians

Force spectroscopy in studying infection

Biophysical force spectroscopy tools - for example optical tweezers, magnetic tweezers, atomic force microscopy, - have been used to study elastic, mechanical, conformational and dynamic properties of single biological specimens from single proteins to whole cells to reveal information not accessible by ensemble average methods such as X-ray crystallography, mass spectroscopy, gel electrophoresis and so on. Here we review the application of these tools on a range of infection-related questions from antibody-inhibited protein processivity to virus-cell adhesion. In each case we focus on how the instrumental design tailored to the biological system in question translates into the functionality suitable for that particular study. The unique insights that force spectroscopy has gained to complement knowledge learned through population averaging techniques in interrogating biomolecular details prove to be instrumental in therapeutic innovations such as those in structure-based drug design

Isolated patellofemoral osteoarthritis: A systematic review of treatment options using the GRADE approach

Background and purpose The optimal treatment for isolated patellofemoral osteoarthritis is unclear at present. We systematically reviewed the highest level of available evidence on the nonoperative and operative treatment of isolated patellofemoral osteoarthritis to develop an evidenced-based discussion of treatment options

Seizure prediction : ready for a new era

Acknowledgements: The authors acknowledge colleagues in the international seizure prediction group for valuable discussions. L.K. acknowledges funding support from the National Health and Medical Research Council (APP1130468) and the James S. McDonnell Foundation (220020419) and acknowledges the contribution of Dean R. Freestone at the University of Melbourne, Australia, to the creation of Fig. 3.Peer reviewedPostprin

Mass Spectrometry Characterization of Peroxycarboxylic Acids as Proxies for Reactive Oxygen Species and Highly Oxygenated Molecules in Atmospheric Aerosols

A significant fraction of atmospheric aerosol particles is composed of organic material with a highly complex but poorly characterized composition. For a better understanding of aerosol effects and processes in the atmosphere, a more detailed knowledge of aerosol components at a molecular level is needed. Peroxy acids might play a significant role in particle toxicity, due to their oxidizing properties, and they were recently found to be involved in particle formation. Because of the lack of appropriate standards, the identification and quantification of peroxy acids is often highly uncertain. Mass spectrometry (MS) is a powerful tool to characterize unidentified compounds in complex mixtures. However, so far there is only little information regarding the ionization and fragmentation behavior of peroxy acids in mass spectrometers. To study their fragmentation patterns, we synthesized 12 peroxy acids with C$_{8}$ to C$_{10}$ carbon backbones and mono- or diperoxy acid functionality. The peroxy acids were separated using liquid chromatography, detected via negative mode electrospray ionization high-resolution MS, and their fragmentation patterns (MS/MS spectra) were identified. The MS/MS spectra of the peroxy acids showed fragmentation patterns clearly different from the corresponding acid, with a strong similarity between compounds of different chain length but analogous functional groups. Neutral loss of CH$_{2}$O$_{2}$ was observed for all investigated linear peroxy acids but not for carboxylic acids and could therefore serve as a diagnostic ion for peroxy acids. The obtained results are a large step toward unambiguous characterization of peroxy acids in the atmosphere.This work was supported by ERC grant no. 279405. S.S.S. acknowledges support from the Swiss National Science Foundation (project no. 162258)