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  • Becker, Anna; Backman, Janne T.; Itkonen, Outi (2020)
    Introduction: Life-long monitoring of immunosuppressive drugs (ISDs) in blood is essential after organ transplantation. However, the ISD concentrations vary depending on the assay employed. ISDs are strongly bound to cytoplasmic proteins in erythrocytes in circulation. Therefore, the relatively rapid sedimentation of blood cells in whole blood samples may affect the results when using liquid handling robots. Methods: We used 1115 blood samples from outpatients and ward patients with kidney (n = 373), liver (n = 101), heart (n = 29) and bone marrow (n = 155) transplant. Whole blood samples were pretreated by protein precipitation. Alternatively, the samples were hemolyzed by freezing prior to precipitation. ISDs were analyzed by a 2-plexing liquid chromatography tandem mass spectrometry (LC-MS/MS) assay and commercial chemiluminescent microparticle immunoassays (CMIA). Results: The difference between the two sample preparation practices was negligible (<2%). Overall, the measured ISD concentrations in patient samples were lower by LC-MS/MS than by CMIA. The difference was the largest (20.2%) and the smallest (9.1%) in samples from liver and from heart transplant patients, respectively. Conclusions: CMIA overestimates blood ISD concentrations as compared to LC-MS/MS. The extent of the difference was found to be organ transplant dependent. The ISDs can be quantitated either from intact or hemolyzed blood samples.
  • Kirjavainen, Pirkka V.; Karvonen, Anne M.; Adams, Rachel I.; Täubel, Martin; Roponen, Marjut; Tuoresmäki, Pauli; Loss, Georg; Jayaprakash, Balamuralikrishna; Depner, Martin; Ege, Markus Johannes; Renz, Harald; Pfefferle, Petra Ina; Schaub, Bianca; Lauener, Roger; Hyvärinen, Anne; Knight, Rob; Heederik, Dick J. J.; von Mutius, Erika; Pekkanen, Juha (2019)
    Asthma prevalence has increased in epidemic proportions with urbanization, but growing up on traditional farms offers protection even today(1). The asthma-protective effect of farms appears to be associated with rich home dust microbiota(2,3), which could be used to model a health-promoting indoor microbiome. Here we show by modeling differences in house dust microbiota composition between farm and non-farm homes of Finnish birth cohorts(4) that in children who grow up in non-farm homes, asthma risk decreases as the similarity of their home bacterial microbiota composition to that of farm homes increases. The protective microbiota had a low abundance of Streptococcaceae relative to outdoor-associated bacterial taxa. The protective effect was independent of richness and total bacterial load and was associated with reduced proinflammatory cytokine responses against bacterial cell wall components ex vivo. We were able to reproduce these findings in a study among rural German children(2) and showed that children living in German non-farm homes with an indoor microbiota more similar to Finnish farm homes have decreased asthma risk. The indoor dust microbiota composition appears to be a definable, reproducible predictor of asthma risk and a potential modifiable target for asthma prevention.
  • Lattouf, Elie; Anttalainen, Osmo Antero; Kotiaho, Tapio; Hakulinen, Hanna Idamaria; Vanninen, Paula; Eiceman, Gary Alan (2021)
    Gas phase reactions between hydrated protons H+(H2O)(n) and a substance M, as seen in atmospheric pressure chemical ionization (APCI) with mass spectrometry (MS) and ion mobility spectrometry (IMS), were modeled computationally using initial amounts of [M] and [H+(H2O)(n)], rate constants k(1) to form protonated monomer (MH+(H2O)(x)) and k(2) to form proton bound dimer (M2H+(H2O)(z)), and diffusion constants. At 1 x 10(10) cm(-3) (0.4 ppb) for [H+(H2O)(n)] and vapor concentrations for M from 10 ppb to 10 ppm, a maximum signal was reached at 4.5 mu s to 4.6 ms for MH+(H2O)(x) and 7.8 mu s to 46 ms for M2H+(H2O)(z). Maximum yield for protonated monomer for a reaction time of 1 ms was similar to 40% for k(1) from 10(-11) to 10(-8) cm(3).s(-1), for k(2)/k(1) = 0.8, and specific values of [M]. This model demonstrates that ion distributions could be shifted from [M2H+(H2O)(z)] to [MH+(H2O)(x)] using excessive levels of [H+(H2O)(n)], even for [M] > 10 ppb, as commonly found in APCI MS and IMS measurements. Ion losses by collisions on surfaces were insignificant with losses of