Medical Research Center Oulu

Oulu, Finland

Medical Research Center Oulu

Oulu, Finland
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Jansson M.M.,University of Oulu | Jansson M.M.,Medical Research Center Oulu | Ala-Kokko T.I.,University of Oulu | Ohtonen P.P.,University of Oulu | And 3 more authors.
American Journal of Infection Control | Year: 2014

Background Knowledge among critical care nurses and their adherence to evidence-based guidelines for preventing ventilator-associated pneumonia is reported to be low. The aim of our study was to evaluate the effectiveness of human patient simulation (HPS) education in the nursing management of patients requiring mechanical ventilation. Methods A prospective, parallel, randomized controlled trial with repeated measurements was conducted in a 22-bed adult mixed medical-surgical intensive care unit in Finland from February-October 2012. Thirty critical care nurses were allocated evenly to intervention and control groups (n = 15 each). The effectiveness of HPS education was evaluated through the validated Ventilator Bundle Questionnaire and Ventilator Bundle Observation Schedule at baseline and repeated twice-after the clinical and simulation settings, respectivley. Results After HPS education, the average skill scores (Ventilator Bundle Observation Schedule) in the intervention group increased significantly (46.8%-60.0% of the total score) in the final postintervention observation. In the average skill scores, a linear mixed model identified significant time (Pt <.001) and group (Pg =.03) differences and time-group interactions (Pt*g =.02) between the study groups after the HPS education. In contrast, the model did not identify any significant change over time (Pt =.29) or time-group interactions (Pt =.69) between groups in average knowledge scores (Ventilator Bundle Questionnaire). Conclusions Our study identified significant transfer of learned skills to clinical practice following HPS education but no influence on the level of participants' factual knowledge. Copyright © 2014 Published by Elsevier Inc.


Perjes A.,University of Oulu | Perjes A.,University of Pécs | Skoumal R.,University of Pécs | Tenhunen O.,University of Oulu | And 8 more authors.
PLoS ONE | Year: 2014

Background: Apelin, the endogenous ligand for the G protein-coupled apelin receptor, is an important regulator of the cardiovascular homoeostasis. We previously demonstrated that apelin is one of the most potent endogenous stimulators of cardiac contractility; however, its underlying signaling mechanisms remain largely elusive. In this study we characterized the contribution of protein kinase C (PKC), extracellular signal-regulated kinase 1/2 (ERK1/2) and myosin light chain kinase (MLCK) to the positive inotropic effect of apelin. Methods and Results: In isolated perfused rat hearts, apelin increased contractility in association with activation of prosurvival kinases PKC and ERK1/2. Apelin induced a transient increase in the translocation of PKCε, but not PKCα, from the cytosol to the particulate fraction, and a sustained increase in the phosphorylation of ERK1/2 in the left ventricle. Suppression of ERK1/2 activation diminished the apelin-induced increase in contractility. Although pharmacological inhibition of PKC attenuated the inotropic response to apelin, it had no effect on ERK1/2 phosphorylation. Moreover, the apelin-induced positive inotropic effect was significantly decreased by inhibition of MLCK, a kinase that increases myofilament Ca 2+ sensitivity. Conclusions: Apelin increases cardiac contractility through parallel and independent activation of PKCε and ERK1/2 signaling in the adult rat heart. Additionally MLCK activation represents a downstream mechanism in apelin signaling. Our data suggest that, in addition to their role in cytoprotection, modest activation of PKCe and ERK1/2 signaling improve contractile function, therefore these pathways represent attractive possible targets in the treatment of heart failure. © 2014 Perjés et al.


Buler M.,University of Oulu | Buler M.,Medical Research Center Oulu | Aatsinki S.-M.,University of Oulu | Aatsinki S.-M.,Medical Research Center Oulu | And 5 more authors.
FASEB Journal | Year: 2014

The sirtuins (SIRTs; SIRT1-7) are a family of NAD+-dependent enzymes that dynamically regulate cellular physiology. Apart from SIRT1, the functions and regulatory mechanisms of the SIRTs are poorly defined. We explored regulation of the SIRT family by 2 energy metabolism-controlling factors: peroxisome proliferator-activated receptor y coactiva-tor 1-a (PGC-1α) and AMP-activated protein kinase (AMPK). Overexpression of PGC-1α in mouse primary hepatocytes increased SIRT5 mRNA expression 4-fold and also the protein in a peroxisome proliferator-activated receptor a (PPARa)- and estrogen-related receptor a (ERRa)-dependent manner. Furthermore, food withdrawal increased SIRT5 mRNA 1.3-fold in rat liver. Overexpression of AMPK in mouse hepatocytes increased expression of SIRT1, SIRT2, SIRT3, and SIRT6 < 2-fold. In contrast, SIRT5 mRNA was down-regulated by 58%. The antidiabetes drug metformin (1 mM), an established AMPK activator, reduced the mouse SIRT5 protein level by 44% in cultured hepatocytes and by 31% in liver in vivo (300 mg/kg, 7 d). Metformin also induced hypersuccinylation of mitochondrial proteins. Moreover, SIRT5 overexpression increased ATP synthesis and oxygen consumption in HepG2 cells, but did not affect mitochondrial biogenesis. In summary, our results identified SIRT5 as a novel factor that controls mitochondrial function. Moreover, SIRT5 levels are regulated by PGC-1α and AMPK which have opposite effects on its expression. © FASEB.


Tarkiainen M.,University of Helsinki | Tynjala P.,University of Helsinki | Vahasalo P.,Medical Research Center Oulu | Vahasalo P.,University of Oulu | Lahdenne P.,University of Helsinki
Rheumatology (United Kingdom) | Year: 2015

Objective. The aim of this study was to carry out a safety evaluation of biologic agents in patients with JIA and associated uveitis. Methods. In three tertiary centres in Finland, all adverse events (AEs) in 348 consecutive patients were collected. AEs were classified according to the Common Terminology Criteria for AEs. Results. A total of 1516 patient-years (py) were included: 710 on etanercept, 591 on infliximab, 188 on adalimumab, 8 on rituximab, 5 on anakinra, 6 on tocilizumab, 6 on abatacept and 1 on golimumab. The median follow-up of an individual patient was 51 months (range 1-155). The most common of the 2902 AEs (191/100 py) observed were mild infections, infusion or injection site reactions and alanine aminotransferase elevations. At least one AE occurred in 319 (92%) patients and 121 (35%) had at least one serious AE (SAE). The rate of SAEs was 11.4/100 py on etanercept, 11.8 on infliximab, 10.1 on adalimumab, 15.7 on abatacept, 31.2 on tocilizumab and 87.5 on rituximab, higher than with most anti-TNF agents (P = 0.005). No cases of malignant neoplasms or tuberculosis were detected. New-onset uveitis occurred in 9 patients, psoriasis or psoriasiform lesions in 13 and IBD in 6. Conclusion. Mild and moderate AEs in patients with JIA treated with biologics were more frequent than previously reported. SAEs were observed in one-third of the patients, but SAEs seldom led to drug discontinuation. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.


Tseveenjav B.,Dental Health Care | Tseveenjav B.,University of Oulu | Pesonen P.,University of Oulu | Virtanen J.I.,University of Oulu | Virtanen J.I.,Medical Research Center Oulu
Tobacco Induced Diseases | Year: 2015

Background: The relationship between the use of snus and lifestyle-related habits - especially in adolescence, when these behaviours begin and become established - is not widely studied. Our aim was to analyse associations between snus use and habits of and attitudes towards smoking and alcohol consumption among Finnish adolescents. Methods: The study is a part of the National School Health Promotion Study in Finland. The study population consisted of a representative sample of Finnish adolescents (n∈=∈183 226). A questionnaire enquired about pupils' use of snus, habits of and attitudes towards smoking and alcohol consumption, as well as their (age, gender, school type) and their parents' (education and smoking) background factors. Chi-square tests and logistic regression models served in the statistical analyses. Results: Of the adolescents, 18 % had used snus (2 % daily, 16 % experimented) while 82 % never had. Snus use was more common among boys than girls (p∈<∈0.05). Concerning smoking, 19 % were daily and 15 % occasional smokers. Regarding alcohol, 11 % consumed it weekly and 57 % monthly or less frequently. More than two thirds of the adolescents held positive attitudes towards smoking (71 %), and alcohol (67 %). Male gender (OR∈=∈9.9; 95 % CI 9.4-10.4), current (OR∈=∈32.8; 95 % CI 26.1-41.1) or former (OR∈=∈10.1; 95 % CI 8.0-12.9) smoking, weekly consumption of alcohol (OR∈=∈27.4; 95 % CI 21.0-35.8), positive attitude towards smoking (OR∈=∈1.4; 95 % CI 1.3-1.6), and higher parental education (OR∈=∈1.4; 95 % CI 1.3-1.4) associated significantly with adolescents' current snus use, whereas parental smoking did not. Conclusion: Current snus use among adolescents may signal an accumulation of other lifestyle-related risky behaviours such as current or past smoking and alcohol consumption as well as a positive attitude towards smoking. In addition to these possible co-existing health-related risk factors, health promotion activities should take into account gender and school differences in order to target preventive messages to youth more effectively. © 2015 Tseveenjav et al.


Hukkanen J.,University of Oulu | Hakkola J.,University of Oulu | Hakkola J.,Medical Research Center Oulu | Rysa J.,University of Oulu | Rysa J.,Medical Research Center Oulu
Drug Metabolism and Drug Interactions | Year: 2014

Pregnane X receptor (PXR), a ligand-activated nuclear receptor, was originally identified as a regulator of drug and bile acid metabolism. Studies in experimental animals and humans within the last decade have revealed PXR as a regulator of energy metabolism repressing gluconeogenesis and hepatic lipid oxidation. The most recent in vivo studies demonstrate that PXR activation has a detrimental role in the regulation of glucose metabolism. The prevalence of many PXR agonists in low concentrations in our environments as well as the PXR-activating properties of numerous commonly used medications and herbal remedies may have unanticipated health effects. It could be speculated that, due to its dual role as a xenosensor and a regulator of energy metabolism, PXR, in concert with a mixture of PXR agonists in the environment, contributes to the present-day type 2 diabetes epidemic. With this hypothesis in mind, we review the current literature on PXR as a regulator of glucose and hepatic lipid metabolism and the association of exposure to PXR agonists with diabetes susceptibility. © 2014 by Walter de Gruyter Berlin Boston 2014.


Hyrkas H.,University of Oulu | Hyrkas H.,Medical Research Center Oulu | Jaakkola M.S.,University of Oulu | Jaakkola M.S.,Medical Research Center Oulu | And 6 more authors.
Respiratory Medicine | Year: 2014

Background: The occurrence of cold temperature-related symptoms has not been investigated previously in young adults, although cold weather may provoke severe symptoms leading to activity limitations, and those with pre-existing respiratory conditions may form a susceptible group. We tested the hypothesis that young adults with asthma and allergic rhinitis experience cold-related respiratory symptoms more commonly than young adults in general. Methods: A population-based study of 1623 subjects 20-27 years old was conducted with a questionnaire inquiring about cold weather-related respiratory symptoms, doctor-diagnosed asthma and rhinitis, and lifestyle and environmental exposures. Results: Current asthma increased the risk of all cold weather-related symptoms (shortness of breath adjusted PR 4.53, 95% confidence interval 2.93-6.99, wheezing 10.70, 5.38-21.29, phlegm production 2.51, 1.37-4.62, cough 3.41, 1.97-5.87 and chest pain 2.53, 0.82-7.79). Allergic rhinitis had additional effect especially on shortness of breath (7.16, 5.30-9.67) and wheezing (13.05, 7.75-22.00), some on phlegm production (3.69, 2.49-5.47), but marginal effect on cough and chest pain. Interpretation: Our study shows that already in young adulthood those with asthma, and especially those with coexisting allergic rhinitis, experience substantially more cold temperature-related respiratory symptoms than healthy young adults. Hence, young adults with a respiratory disease form a susceptible group that needs special care and guidance for coping with cold weather. © 2013 Elsevier Ltd. All rights reserved.


Kummu O.,University of Oulu | Kummu O.,Medical Research Center Oulu | Turunen S.P.,University of Oulu | Turunen S.P.,Medical Research Center Oulu | And 9 more authors.
Immunology | Year: 2014

Oxidized low-density lipoprotein (OxLDL) plays a crucial role in the development of atherosclerosis. Carbamylated LDL has been suggested to promote atherogenesis in patients with chronic kidney disease. Here we observed that plasma IgG and IgM antibodies to carbamylated epitopes were associated with IgG and IgM antibodies to oxidation-specific epitopes (ρ = 0·65-0·86, P < 0·001) in healthy adults, suggesting a cross-reaction between antibodies recognizing carbamyl-epitopes and malondialdehyde (MDA)/malondialdehyde acetaldehyde (MAA) -adducts. We used a phage display technique to clone a human Fab antibody that bound to carbamylated LDL and other carbamylated proteins. Anti-carbamyl-Fab (Fab106) cross-reacted with oxidation-specific epitopes, especially with MDA-LDL and MAA-LDL. We showed that Fab106 bound to apoptotic Jurkat cells known to contain these oxidation-specific epitopes, and the binding was competed with soluble carbamylated and MDA-/MAA-modified LDL and BSA. In addition, Fab106 was able to block the uptake of carbamyl-LDL and MDA-LDL by macrophages and stained mouse atherosclerotic lesions. The observed cross-reaction between carbamylated and MDA-/MAA-modified LDL and its contribution to enhanced atherogenesis in uraemic patients require further investigation. © 2013 John Wiley & Sons Ltd.


PubMed | Medical Research Center Oulu and University of Oulu
Type: Journal Article | Journal: American journal of infection control | Year: 2016

To evaluate how critical nurses knowledge of and adherence to current care hand hygiene (HH) guidelines differ between randomly allocated intervention and control groups before and after simulation education in both a simulation setting and clinical practice during a 2-year follow-up period. It was hypothesized that intervention group knowledge of and adherence to current HH guidelines might increase compared with a control group after simulation education.A prospective, parallel, randomized controlled trial with repeated measurements was conducted in a 22-bed adult mixed medical-surgical intensive care unit in Oulu, Finland. Thirty out of 40 initially randomized critical care nurses participated in the baseline measurements; of these, 17 completed all the study procedures. Participants HH adherence was observed only in high-risk contact situations prior to and postendotracheal suctioning events using a direct, nonparticipatory method of observation. Participants HH knowledge was evaluated at the end of each observational session.The overall HH adherence increased from a baseline value of 40.8% to 50.8% in the final postintervention measurement at 24 months (P=.002). However, the linear mixed model did not identify any significant group (P=.77) or time-group interactions (P=.17) between the study groups after 2 years of simulation education. In addition, simulation education had no impact on participants HH knowledge.After a single simulation education session, critical care nurses knowledge of and adherence to current HH guidelines remained below targeted behavior rates.


PubMed | Medical Research Center Oulu, University of Oulu, University of Helsinki and University of South Carolina
Type: Journal Article | Journal: British journal of cancer | Year: 2016

Uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer (HLRCC) patients are driven by fumarate hydratase (FH) inactivation or occasionally by mediator complex subunit 12 (MED12) mutations. The aim of this study was to analyse whether MED12 mutations and FH inactivation are mutually exclusive and to determine the contribution of MED12 mutations on HLRCC patients myomagenesis.MED12 exons 1 and 2 mutation screening and 2SC immunohistochemistry indicative for FH deficiency was performed on a comprehensive series of HLRCC patients (122 specimens) and sporadic (66 specimens) tumours. Gene expression analysis was performed using Affymetrix GeneChip Human Exon Arrays (Affymetrix, Santa Clara, CA, USA).Nine tumours from HLRCC patients harboured a somatic MED12 mutation and were negative for 2SC immunohistochemistry. All remaining successfully analysed lesions (107/116) were deficient for FH. Of sporadic tumours, 35/64 were MED12 mutation positive and none displayed a FH defect. In global gene expression analysis FH-deficient tumours clustered together, whereas HLRCC patients MED12 mutation-positive tumours clustered together with sporadic MED12 mutation-positive tumours.Somatic MED12 mutations and biallelic FH inactivation are mutually exclusive in both HLRCC syndrome-associated and sporadic uterine leiomyomas. The great majority of HLRCC patients uterine leiomyomas are caused by FH inactivation, but incidental tumours driven by somatic MED12 mutations also occur. These MED12 mutation-positive tumours display similar expressional profiles with their sporadic counterparts and are clearly separate from FH-deficient tumours.

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