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  • 1.
    Balla, Hajnal Zsuzsanna
    et al.
    Orebro Univ, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Ström, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Orebro Univ, Sweden.
    Evaluation of commercial, wireless dermal thermometers for surrogate measurements of core temperature2019In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 79, no 1-2Article in journal (Refereed)
    Abstract [en]

    Extensive research has been devoted to developing methods for assessing core body temperature, and to determine which method is most accurate. A number of wireless dermal thermometers for home use are presently available, but their relation to core body temperature and suitability for use in clinical research has hitherto not been assessed. The current study aimed to evaluate such thermometers by comparing them to the results of a rectal thermometer. Four wireless dermal thermometers for home use (FeverSmart, iThermonitor, Quest Temp Sitter, and Thermochron iButton) were applied to 15 patients during 24 h, and rectal temperature was measured at four occasions. Pearson correlation revealed moderate correlation for the Feversmart (r = 0.75), iThermonitor (r = 0.79), and Thermochron iButton (r = 0.71) systems. The Quest Temp Sitter system malfunctioned repeatedly, and the correlation (r = 0.29) for this method should therefore be assessed with caution. All dermal thermometers rendered lower average temperatures than Terumo c405 (Feversmart -0.70 +/- 0.65 degrees C; iThermonitor -0.77 +/- 0.53 degrees C, Quest Temp Sitter -1.18 +/- 0.66 degrees C, and Thermochron iButton -0.87 +/- 0.65 degrees C). Sensitivity of the dermal thermometers for detecting core temperatures amp;gt;= 38.0 degrees C was low, ranging from 0.33 to 0.6, but improved to 0.60 to 0.80 after adjusting temperatures by the methods average deviation from rectal temperature. The results from the dermal thermometers tested here showed an insufficient correlation to core temperature to be used for core temperature monitoring in clinical research and practice. Unfortunately, other options for non-invasive temperature measurements are few. The two thermometers with the least unsatisfactory performance profile in our evaluations were the Feversmart and iThermonitor systems.

  • 2.
    Kallner, Anders
    et al.
    Karolinska Univ Hosp, Sweden.
    Petersmann, Astrid
    Univ Med, Germany; Univ Med, Germany.
    Nauck, Matthias
    Univ Med, Germany.
    Theodorsson, Elvar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Measurement repeatability profiles of eight frequently requested measurands in clinical chemistry determined by duplicate measurements of patient samples2020In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686Article in journal (Refereed)
    Abstract [en]

    Measurement uncertainties in clinical chemistry are commonly regarded as heteroscedastic - having a constant relative standard deviation irrespective of the concentration of the measurand. The uncertainty is usually determined at two concentrations using stabilized control materials and assumed to represent the analytical goal. The purpose of the present study was to use duplicates of unselected patient samples to calculate the absolute and relative repeatability component of the intra-laboratory measurement uncertainty from duplicates, using the Dahlberg formula and analysis of variance components. Estimates were made at five different concentration intervals of ALT, AST, Calcium, Cholesterol, Creatinine, CRP, Triglycerides and TSH covering the entire concentration interval of the patient cohort. This partioning allows detailing their repeatability profiles. The calculations of the profiles were based on randomly selected results from sets of duplicates ranging from 12,000 to 65,000 pairs. The repeatability of the measurands showed substantial variability within the measuring interval. Therefore, characterizing imprecision profiles as purely homo- or heteroscedastic or by a single number may not be optimal for the intended use. The present data make a case for nuancing the evaluation of analytical goals and minimal differences of measurement results by establishing uncertainty profiles under repeatability conditions, using natural patient samples.

  • 3.
    Kallner, Anders
    et al.
    Karolinska Univ Hosp, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Repeatability imprecision from analysis of duplicates of patient samples and control materials2020In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686Article in journal (Refereed)
    Abstract [en]

    Measurement imprecision is usually calculated from measurement results of the same stabilized control material(s) obtained over time, and is therefore, principally, only valid at the concentration(s) of the selected control material(s). The resulting uncertainty has been obtained under reproducibility conditions and corresponds to the conventional analytical goals. Furthermore, the commutability of the control materials used determines whether the imprecision calculated from the control materials reflects the imprecision of measuring patient samples. Imprecision estimated by measurements of patient samples uses fully commutable samples, freely available in the laboratories. It is commonly performed by calculating the results of routine patient samples measured twice each. Since the duplicates are usually analysed throughout the entire concentration interval of the patient samples processed in the laboratory, the result will be a weighted average of the repeatability imprecision measured in the chosen measurement intervals or throughout the entire interval of concentrations encountered in patient care. In contrast, the uncertainty derived from many measurements of control materials over periods of weeks is usually made under reproducibility conditions. Consequently, the repeatability and reproducibility imprecision play different roles in the inference of results in clinical medicine. The purpose of the present review is to detail the properties of the imprecision calculated by duplicates of natural samples, to explain how it differs from imprecision calculated from single concentrations of control materials, and to elucidate what precautions need to be taken in case of bias, e.g. due to carry-over effects.

  • 4.
    Magnusson, Per
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Nilsen, Per
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Schedvin, Göran
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Appropriate Use of Vitamin D Assessments in Primary Health Care: Impact of New Strategies for the Introduction and Follow-Up of Analyses in Östergötland2019In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 116, no 14, article id FFPXArticle in journal (Refereed)
  • 5.
    Makitie, Riikka E.
    et al.
    Univ Helsinki, Finland; Imperial Coll London, England.
    Kampe, Anders
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Costantini, Alice
    Karolinska Inst, Sweden.
    Alm, Jessica J.
    Karolinska Inst, Sweden.
    Magnusson, Per
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Makitie, Outi
    Univ Helsinki, Finland; Karolinska Inst, Sweden; Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Univ Helsinki, Finland; Univ Helsinki, Finland; Helsinki Univ Hosp, Finland.
    Biomarkers in WNT1 and PLS3 Osteoporosis: Altered Concentrations of DKK1 and FGF232020In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681Article in journal (Refereed)
    Abstract [en]

    Recent advancements in genetic research have uncovered new forms of monogenic osteoporosis, expanding our understanding of the molecular pathways regulating bone health. Despite active research, knowledge on the pathomechanisms, disease-specific biomarkers, and optimal treatment in these disorders is still limited. Mutations in WNT1, encoding a WNT/beta-catenin pathway ligand WNT1, and PLS3, encoding X chromosomally inherited plastin 3 (PLS3), both result in early-onset osteoporosis with prevalent fractures and disrupted bone metabolism. However, despite marked skeletal pathology, conventional bone markers are usually normal in both diseases. Our study aimed to identify novel bone markers in PLS3 and WNT1 osteoporosis that could offer diagnostic potential and shed light on the mechanisms behind these skeletal pathologies. We measured several parameters of bone metabolism, including serum dickkopf-1 (DKK1), sclerostin, and intact and C-terminal fibroblast growth factor 23 (FGF23) concentrations in 17 WNT1 and 14 PLS3 mutation-positive subjects. Findings were compared with 34 healthy mutation-negative subjects from the same families. Results confirmed normal concentrations of conventional metabolic bone markers in both groups. DKK1 concentrations were significantly elevated in PLS3 mutation-positive subjects compared with WNT1 mutation-positive subjects (p amp;lt; .001) or the mutation-negative subjects (p = .002). Similar differences were not seen in WNT1 subjects. Sclerostin concentrations did not differ between any groups. Both intact and C-terminal FGF23 were significantly elevated in WNT1 mutation-positive subjects (p = .039 and p = .027, respectively) and normal in PLS3 subjects. Our results indicate a link between PLS3 and DKK1 and WNT1 and FGF23 in bone metabolism. The normal sclerostin and DKK1 levels in patients with impaired WNT signaling suggest another parallel regulatory mechanism. These findings provide novel information on the molecular networks in bone. Extended studies are needed to investigate whether these biomarkers offer diagnostic value or potential as treatment targets in osteoporosis. (c) 2020 American Society for Bone and Mineral Research.

  • 6.
    Sauveroche, Mathilde
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Henriksson, Josefine
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Theodorsson, Elvar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Svensson Holm, Ann-Charlotte B.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Roth, Lina
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Hair cortisol in horses (Equus caballus) in relation to management regimes, personality and breed2020In: Journal of Veterinary Behavior, ISSN 1558-7878Article in journal (Refereed)
    Abstract [en]

    Hair cortisol is a promising biomarker to measure long-term stress since cortisol is incorporated into the hair shaft as it grows. However, few studies have previously assessed hair cortisol concentrations (HCC) in horses. In this study, HCC was evaluated in both mane hair from the neck and body hair from the withers in 153 horses of different breeds, from seven different stables with three different management regimes (Free-roaming horses, Riding school horses, Trotter horses). In addition, 4 hours of behavioral observations were performed at each stable, and for 43 of the horses, a personality survey was completed. Mane and withers HCC correlated moderately, but significantly (rs=0.48, p<0.001). Differences between the stables were found for both mane and withers hair (both p<0.01) and the stable with lowest HCC also showed highest occurrences of positive social and resting behaviors (both p<0.01). There were no significant differences in HCC between the management regimes even though Free-roaming horses showed less negative social behavior compared to Riding school horses (p=0.041) and Trotter horses (p=0.055). The personality traits Dominance, Anxiousness, and Excitability revealed weak to moderate correlations with mane HCC (rs=-0.34, p=0.027; rs=-0.46, p=0.002; rs=-0.31, p=0.043 respectively) which might suggest that personality could also be related to long-term stress levels in horses.

  • 7.
    Sorbo, Ann
    et al.
    Sodra Alvsborg Hosp, Sweden; Uddevalla Cent Hosp, Sweden; Univ Gothenburg, Sweden.
    Eiving, Ingrid
    Sahlgrens Univ Hosp, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Rydenhag, Bertil
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Jonsdottir, Ingibjorg H.
    Inst Stress Med, Sweden.
    Pre-traumatic conditions can influence cortisol levels before and after a brain injury2020In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404Article in journal (Refereed)
    Abstract [en]

    Objective Satisfactory anabolic reactions, including the activation of the hypothalamic-pituitary-adrenal (HPA) axis, are essential following severe traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH). Many factors may influence this activation. This study aimed to investigate whether individuals who reported chronic diseases, psychosocial afflictions, or stressful events before a severe brain injury display a different pattern regarding cortisol levels retrospectively and up to three months compared with those who did not report stressful experiences. Materials and Methods Fifty-five patients aged 16-68 years who were admitted to the neurointensive care unit (NICU) were included. Hair cortisol measurements offer a unique opportunity to monitor cortisol levels retrospectively and after the trauma. Hair strands were collected as soon as possible after admission to the NICU and every month until three months after the injury/insult. The participants/relatives were asked about stressful events, psychosocial afflictions and recent and chronic diseases. Results The group who reported chronic diseases and/or stressful events before the brain injury had more than twice as high median hair cortisol levels before the brain injury compared with those who did not report stress, but the difference was not statistically significant (P = .12). Those who reported stress before the brain injury had statistically significantly lower hair cortisol values after the brain injury and they remained until three months after the injury. Conclusions Stressful events and/or chronic disease before brain injury might affect mobilization of adequate stress reactions following the trauma. However, the large variability in cortisol levels in these patients does not allow firm conclusions and more studies are needed.

  • 8.
    Törnudd, Mattias
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Ramström, Sofia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Orebro Univ, Sweden.
    Kvitting, John-Peder Escobar
    Oslo Univ Hosp, Norway.
    Alfredsson, Joakim
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Pihl, Richard
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Sci, Linkoping, Sweden; Linkoping Univ, Dept Clin Chem, Linkoping, Sweden; Linkoping Univ, Dept Clin and Expt Med, Linkoping, Sweden.
    Berg, Sören
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Protamine stimulates platelet aggregation in vitro with activation of the fibrinogen receptor and alpha-granule release, but impairs secondary activation via ADP and thrombin receptors2020In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635Article in journal (Refereed)
    Abstract [en]

    Heparin and protamine are fundamental in the management of anticoagulation during cardiac surgery. Excess protamine has been associated with increased bleeding. Interaction between protamine and platelet function has been demonstrated but the mechanism remains unclear. We examined the effect of protamine on platelet function in vitro using impedance aggregometry, flow cytometry, and thrombin generation. Platelets were exposed to protamine at final concentrations of 0, 20, 40, and 80 mu g/mL, alone or together with adenosine diphosphate (ADP) or thrombin PAR1 receptor-activating peptide (TRAP). We found that in the absence of other activators, protamine (80 mu g/mL) increased the proportion of platelets with active fibrinogen receptor (binding of PAC-1) from 3.6% to 97.0% (p amp;lt; .001) measured with flow cytometry. Impedance aggregometry also increased slightly after exposure to protamine alone. When activated with ADP or TRAP protamine at 80 mu g/mL reduced aggregation, from 73.8 +/- 29.4 U to 46.9 +/- 21.1 U (p amp;lt; .001) with ADP and from 126.4 +/- 16.1 U to 94.9 +/- 23.7 U (p amp;lt; .01) with TRAP. P-selectin exposure (a marker of alpha-granule release) measured by median fluorescence intensity (MFI) increased dose dependently with protamine alone, from 0.76 +/- 0.20 (0 mu g/mL) to 10.2 +/- 3.1 (80 mu g/mL), p amp;lt; .001. Protamine 80 mu g/mL by itself resulted in higher MFI (10.16 +/- 3.09) than activation with ADP (2.2 +/- 0.7, p amp;lt; .001) or TRAP (5.7 +/- 2.6, p amp;lt; .01) without protamine. When protamine was combined with ADP or TRAP, there was a concentration-dependent increase in the alpha-granule release. In conclusion, protamine interacts with platelets in vitro having both a direct activating effect and impairment of secondary activation of aggregation by other agonists.

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