PKXb8^refs.MYD n _||74Waldmann, P. Hallander, J. Hoti, F. Sillanpaa, M. J.2008Efficient markov chain monte carlo implementation of bayesian analysis of additive and dominance genetic variances in noninbred pedigrees1101-12Genetics1792 2008/06/19Jun-Accurate and fast computation of quantitative genetic variance parameters is of great importance in both natural and breeding populations. For experimental designs with complex relationship structures it can be important to include both additive and dominance variance components in the statistical model. In this study, we introduce a Bayesian Gibbs sampling approach for estimation of additive and dominance genetic variances in the traditional infinitesimal model. The method can handle general pedigrees without inbreeding. To optimize between computational time and good mixing of the Markov chain Monte Carlo (MCMC) chains, we used a hybrid Gibbs sampler that combines a single site and a blocked Gibbs sampler. The speed of the hybrid sampler and the mixing of the single-site sampler were further improved by the use of pretransformed variables. Two traits (height and trunk diameter) from a previously published diallel progeny test of Scots pine (Pinus sylvestris L.) and two large simulated data sets with different levels of dominance variance were analyzed. We also performed Bayesian model comparison on the basis of the posterior predictive loss approach. Results showed that models with both additive and dominance components had the best fit for both height and diameter and for the simulated data with high dominance. For the simulated data with low dominance, we needed an informative prior to avoid the dominance variance component becoming overestimated. The narrow-sense heritability estimates in the Scots pine data were lower compared to the earlier results, which is not surprising because the level of dominance variance was rather high, especially for diameter. In general, the hybrid sampler was considerably faster than the blocked sampler and displayed better mixing properties than the single-site sampler.yWaldmann, Patrik Hallander, Jon Hoti, Fabian Sillanpaa, Mikko J United States Genetics Genetics. 2008 Jun;179(2):1101-12.0016-6731 (Print)185586554.001VDepartment of Vaccines, National Public Health Institute, FIN-00300 Helsinki, Finland.2179/2/1101 [pii] 10.1534/genetics.107.084||7\Kaijalainen, T. Kharit, S. M. Kvetnaya, A. S. Sirkia, K. Herva, E. Parkov, O. V. Nohynek, H.2008Invasive infections caused by Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae among children in St Petersburg, Russia507-10Clin Microbiol Infect145 2008/03/06JAdolescent Child Child, Preschool Haemophilus influenzae/isolation & purification Humans Infant Meningitis, Haemophilus/ epidemiology Meningitis, Meningococcal/ epidemiology Meningitis, Pneumococcal/ epidemiology Neisseria meningitidis/isolation & purification Russia/epidemiology Streptococcus pneumoniae/isolation & purificationMayThis study investigated the causes of invasive bacterial infections in children aged <15 years in St Petersburg, Russia, during 2001-2003, using culture and antigen detection methods (rapid antigen latex agglutination (RAL)) for normally sterile body fluids. A pathogen was detected in 90 cases (culture 50, RAL 40). Neisseria meningitidis was the most common pathogen (66%), followed by Haemophilus influenzae (19%) and Streptococcus pneumoniae (16%). Meningitis was the main clinical diagnosis (68/90, 76%), with N. meningitidis serogroup B, H. influenzae type b (Hib), and S. pneumoniae serogroup 1 being the most common isolates. Hib was less prevalent in St Petersburg than it was in industrialised countries before the introduction of Hib vaccinations.AKaijalainen, T Kharit, S M Kvetnaya, A S Sirkia, K Herva, E Parkov, O V Nohynek, H Research Support, Non-U.S. Gov't France Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases Clin Microbiol Infect. 2008 May;14(5):507-10. Epub 2008 Mar 1.1198-743X (Print)183187432.980tNational Public Health Institute, Department of Child and Adolescent Health, Oulu, Finland. tarja.kaijalainen@ktl.fi4CLM1967 [pii] 10.1111/j.1469-0691.2008.019 0||7@Kajantie, E. Barker, D. J. Osmond, C. Forsen, T. Eriksson, J. G.2008]Growth before 2 years of age and serum lipids 60 years later: the Helsinki Birth Cohort study280-9Int J Epidemiol372 2008/02/133Aged Apolipoproteins B/blood Atherosclerosis/etiology Body Height Body Mass Index Body Weight Cholesterol, HDL/blood Female Finland/epidemiology Follow-Up Studies Growth/ physiology Humans Infant Infant, Low Birth Weight Infant, Newborn Lipids/ blood Male Middle Aged Pregnancy Prenatal Nutrition PhysiologyApr;BACKGROUND: Small body size at birth and slow growth during the first 2 years after birth, leading to low body mass index (BMI) at 2 years, are associated with coronary heart disease and stroke in adult life. We tested the hypothesis that this path of growth is associated with an atherogenic lipid profile in later life. METHODS: We measured serum lipid concentrations at age 57-70 years in 1999 members of the Helsinki Birth Cohort. They were randomly selected from an original cohort of 8760 people and had on average 11 measurements of height and weight between birth and 2 years of age. RESULTS: The 18% of subjects who used lipid-lowering medication had a lower BMI at birth and at 2 years. These subjects were excluded from the analyses of lipid profiles. A 1 kg/m(2) lower BMI at birth was associated with 0.051 mmol/l (95% CI -0.001 to 0.103; P = 0.05) higher non-HDL cholesterol and 0.018 g/l higher (0.005-0.031; P = 0.006) apolipoprotein B concentrations. A slower increase in BMI during the first 6 months after birth was associated with lower HDL and higher non-HDL cholesterol concentrations. A 1 kg/m(2) lower BMI at 2 years was associated with 0.020 mmol/l lower (0.004-0.036; P = 0.02) HDL cholesterol and 0.059 mmol/l (0.020-0.099; P = 0.003) higher non-HDL cholesterol and 0.018 mmol/l higher (0.008-0.028; P < 0.001) apolipoprotein B concentrations. The age at weaning off breast milk was not associated with lipid profile in later life. CONCLUSION: Small body size at birth and slow weight gain during infancy are associated with an atherogenic lipid profile in adult life.Kajantie, Eero Barker, David J P Osmond, Clive Forsen, Tom Eriksson, Johan G United Kingdom British Heart Foundation Research Support, Non-U.S. Gov't England International journal of epidemiology Int J Epidemiol. 2008 Apr;37(2):280-9. Epub 2008 Feb 11.1464-3685 (Electronic)182679645.151RThe National Public Health Institute, Helsinki, Finland. eero.kajantie@helsinki.fi%dyn012 [pii] 10.1093/ije/ Μ||7Yan, D. Mayranpaa, M. I. Wong, J. Perttila, J. Lehto, M. Jauhiainen, M. Kovanen, P. T. Ehnholm, C. Brown, A. J. Olkkonen, V. M.2008aOSBP-related protein 8 (ORP8) suppresses ABCA1 expression and cholesterol efflux from macrophages332-40 J Biol Chem2831 2007/11/10ATP-Binding Cassette Transporters/genetics/ metabolism Antigens, CD/metabolism Antigens, Differentiation, Myelomonocytic/metabolism Blotting, Western Carrier Proteins/genetics/ metabolism Cell Line Cholesterol/ metabolism Coronary Vessels/chemistry/metabolism DNA-Binding Proteins/antagonists & inhibitors Humans Immunohistochemistry Luciferases/genetics/metabolism Macrophages/cytology/drug effects/ metabolism Microscopy, Fluorescence Models, Genetic Promoter Regions (Genetics)/genetics RNA Interference RNA, Messenger/genetics/metabolism Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors Receptors, Steroid/genetics/ metabolism Recombinant Fusion Proteins/genetics/metabolism Sulfonamides/pharmacology Transcription, Genetic/drug effects TransfectionJan 4ORP8 is a previously unexplored member of the family of oxysterol-binding protein-related proteins (ORP). We now report the expression pattern, the subcellular distribution, and data on the ligand binding properties and the physiological function of ORP8. ORP8 is localized in the endoplasmic reticulum (ER) via its C-terminal transmembrane span and binds 25-hydroxycholesterol, identifying it as a new ER oxysterol-binding protein. ORP8 is expressed at highest levels in macrophages, liver, spleen, kidney, and brain. Immunohistochemical analysis revealed ORP8 in the shoulder regions of human coronary atherosclerotic lesions, where it is present in CD68(+) macrophages. In advanced lesions the ORP8 mRNA was up-regulated 2.7-fold as compared with healthy coronary artery wall. Silencing of ORP8 by RNA interference in THP-1 macrophages increased the expression of ATP binding cassette transporter A1 (ABCA1) and concomitantly cholesterol efflux to lipid-free apolipoprotein A-I but had no significant effect on ABCG1 expression or cholesterol efflux to spherical high density lipoprotein HDL(2). Experiments employing an ABCA1 promoter-luciferase reporter confirmed that ORP8 silencing enhances ABCA1 transcription. The silencing effect was partially attenuated by mutation of the DR4 element in the ABCA1 promoter and synergized with that of the liver X receptor agonist T0901317. Furthermore, inactivation of the E-box in the promoter synergized with ORP8 silencing, suggesting that the suppressive effect of ORP8 involves both the liver X receptor and the E-box functions. Our data identify ORP8 as a negative regulator of ABCA1 expression and macrophage cholesterol efflux. ORP8 may, thus, modulate the development of atherosclerosis.,Yan, Daoguang Mayranpaa, Mikko I Wong, Jenny Perttila, Julia Lehto, Markku Jauhiainen, Matti Kovanen, Petri T Ehnholm, Christian Brown, Andrew J Olkkonen, Vesa M Research Support, Non-U.S. Gov't United States The Journal of biological chemistry J Biol Chem. 2008 Jan 4;283(1):332-40. Epub 2007 Nov 8.0021-9258 (Print)179917395.581kDepartment of Molecular Medicine, National Public Health Institute, Biomedicum, FI-00251 Helsinki, Finland.-M705313200 [pii] 10.1074/jbc.M70531||7Haukka, K. Siitonen, A.2008iEmerging resistance to newer antimicrobial agents among Shigella isolated from Finnish foreign travellers476-82Epidemiol Infect1364 2007/06/21aAnti-Bacterial Agents/pharmacology Communicable Diseases, Emerging/drug therapy/epidemiology/etiology/prevention & control Drug Resistance, Microbial Dysentery, Bacillary/drug therapy/ epidemiology/etiology/prevention & control Finland/epidemiology Humans Microbial Sensitivity Tests Shigella/ classification/drug effects/isolation & purification TravelAprIn Finland, most cases of shigellosis are related to travel abroad. Antimicrobial drug resistance of 1814 Shigella strains isolated from Finnish patients during 1990-2005 was studied using discs of 12 antimicrobial agents. Since 2000, the E-test has been performed to determine ciprofloxacin minimum inhibitory concentrations of nalidixic acid-resistant isolates. The proportion of multi-resistant strains (resistant to >or =4 antimicrobials) was highest among isolates from China and India, but is increasing significantly in other parts of Asia. Resistance to nalidixic acid has become common among the strains from the Far East, and the first isolates also resistant to ciprofloxacin were detected during 2004-2005. All the ciprofloxacin-resistant isolates belonged to the S. flexneri 2a serotype. All the nalidixic acid-resistant S. flexneri strains had reduced susceptibility to ciprofloxacin, whereas 23% of the nalidixic acid-resistant S. sonnei strains were still completely susceptible to ciprofloxacin.tHaukka, K Siitonen, A England Epidemiology and infection Epidemiol Infect. 2008 Apr;136(4):476-82. Epub 2007 Jun 20.0950-2688 (Print)175786021.900Enteric Bacteria Laboratory, Department of Bacterial and Inflammatory Diseases, National Public Health Institute KTL, Helsinki, Finland.7S0950268807008862 [pii] 10.1017/S0950268807  $||7Hintsanen, M. Elovainio, M. Puttonen, S. Kivimaki, M. Lehtimaki, T. Kahonen, M. Juonala, M. Rontu, R. Viikari, J. S. Raitakari, O. T. Keltikangas-Jarvinen, L.2008yVal/Met Polymorphism of the COMT Gene Moderates the Association Between Job Strain and Early Atherosclerosis in Young Men649-657J Occup Environ Med506 2008/06/12JunOBJECTIVE:: Several studies support job strain as a risk factor for coronary heart disease (CHD) but null findings also exist. Individual differences in innate stress vulnerability might in part explain the mixed findings. COMT gene influences dopamine transmission and dopaminergic activity might moderate effects of stress on CHD risk. We examine whether COMT Val158Met polymorphism moderates the association between job strain and atherosclerosis. METHODS:: Participants (mean age 32.5) were 347 women and 353 men from the population-based Young Finns study. Preclinical atherosclerosis was measured using carotid intima-media thickness (IMT) ultrasound. RESULTS:: COMT polymorphism moderated the job strain-IMT association in men. Job strain was associated with higher IMT in Val/Val carriers but not among others. CONCLUSIONS:: Our findings support a general model in which the interaction between genotype and job strain is assumed to predispose to increased atherosclerotic processes.Journal of occupational and environmental medicine / American College of Occupational and Environmental Medicine J Occup Environ Med. 2008 Jun;50(6):649-657.1076-2752 (Print)185450922.097From the Department of Psychology (Drs Hintsanen, Elovainio, Puttonen, and Keltikangas-Jarvinen), University of Helsinki, Helsinki, Finland; National Research and Development Centre for Welfare and Health (Dr Elovainio), Helsinki, Finland; Finnish Institute of Occupational Health (Drs Puttonen and Kivimaki), Helsinki, Finland; Department of Epidemiology and Public Health (Dr Kivimaki), University College London, London, United Kingdom; Laboratory of Atherosclerosis Genetics (Dr Lehtimaki), Department of Clinical Chemistry, the Medical School at the University of Tampere, Tampere, Finland; Centre for Laboratory Medicine (Drs Lehtimaki and Rontu), Tampere University Hospital, Tampere, Finland; Department of Clinical Physiology (Dr Kahonen), Tampere University Hospital, Tampere, Finland; Research Centre of Applied and Preventive Cardiovascular Medicine (Dr Juonala), University of Turku, Turku, Finland; Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry (Dr Rontu), The Medical School at the University of Tampere, Tampere, Finland; Department of Medicine (Dr Viikari), University of Turku, Turku, Finland; and Department of Clinical Physiology (Dr Raitakari), University of Turku, Turku, Finland."10.1097/JOM.0b013e318165-(||7OYliharsila, H. Kajantie, E. Osmond, C. Forsen, T. Barker, D. J. Eriksson, J. G.2008YBody mass index during childhood and adult body composition in men and women aged 56-70 y1769-75Am J Clin Nutr876 2008/06/11JunhBACKGROUND: The relation between the change in body mass index (BMI) through childhood and body composition in adult life is important because body composition is known to affect adult health. OBJECTIVE: The objective was to examine how the change in BMI throughout childhood is related to adult lean and fat mass. DESIGN: We examined how the change in BMI in childhood was related to adult body composition in 885 men and 1032 women born during 1934-1944, whose weights and heights during childhood were recorded serially. Adult lean and fat mass were measured by bioelectrical impedance with an 8-polar tactile electrode system. RESULTS: In these 56-70-y-old men and women, adult lean body mass index (lean mass/height(2); in kg/m(2)) was positively associated with BMI at birth (0.24 and 0.20 higher for each 1-SD increase in BMI at birth, respectively) and with more rapid gain in BMI from birth to 1 y (0.17 and 0.22), 1-2 y (0.21 and 0.20), 2-7 y (0.44 and 0.46), and 7-11 y (0.32 and 0.26) of age. Fat mass index (fat mass/height(2)) was positively associated with more rapid increases in BMI between 2 and 11 y of age. CONCLUSIONS: Rapid gain in BMI before the age of 2 y increased adult lean body mass without excess fat accumulation, whereas rapid gain in BMI in later childhood, despite the concurrent rise in lean mass, resulted in relatively larger increases in fat mass.Yliharsila, Hilkka Kajantie, Eero Osmond, Clive Forsen, Tom Barker, David Jp Eriksson, Johan G United Kingdom British Heart Foundation Research Support, Non-U.S. Gov't United States The American journal of clinical nutrition Am J Clin Nutr. 2008 Jun;87(6):1769-75.0002-9165 (Print)185415676.603~National Public Health Institute, Department of Epidemiology and Health Promotion, Helsinki, Finland. hilkka.yliharsila@ktl.fi87/  h||7AHu, G. Antikainen, R. Jousilahti, P. Kivipelto, M. Tuomilehto, J.20083Total cholesterol and the risk of Parkinson disease1972-9 Neurology7021 2008/04/11Adult Cholesterol/ blood Female Follow-Up Studies Humans Incidence Male Middle Aged Parkinson Disease/ blood/ epidemiology Proportional Hazards Models Prospective Studies Risk Factors Smoking/epidemiologyMay 20OBJECTIVE: To examine the association between serum total cholesterol at baseline and the risk of Parkinson disease (PD). METHODS: Study cohorts included 24,773 Finnish men and 26,153 women aged 25 to 74 years without a history of PD and stroke at baseline. Hazard ratios (HRs) of incident PD were estimated for different levels of total cholesterol. RESULTS: During a mean follow-up period of 18.1 years, 321 men and 304 women developed incident PD. After adjustment for confounding factors (age, study years, body mass index, systolic blood pressure, education, leisure-time physical activity, smoking, alcohol consumption, coffee and tea consumption, and history of diabetes), the HRs of PD at different levels of total cholesterol (<5, 5-5.9, 6-6.9, and >or=7 mmol/L) were 1.00, 1.33, 1.53, and 1.84 (p for trend = 0.035) in men; 1.00, 1.55, 1.57, and 1.86 (p for trend = 0.113) in women; and 1.00, 1.42, 1.56, and 1.86 (p for trend = 0.002) in men and women combined (adjusted also for sex). In both sexes combined, the increased risk of PD associated with increasing levels of serum total cholesterol was present both in subjects aged 25-44 years and in subjects aged 45-54 years at baseline, and in never smokers and smokers; however, no association was found among subjects aged 55 years or older at baseline. CONCLUSION: This large prospective study suggests that high total cholesterol at baseline is associated with an increased risk of Parkinson disease.Hu, G Antikainen, R Jousilahti, P Kivipelto, M Tuomilehto, J Research Support, Non-U.S. Gov't United States Neurology Neurology. 2008 May 20;70(21):1972-9. Epub 2008 Apr 9.1526-632X (Electronic)184010186.014Department of Health Promotion and Chronic Diseases Prevention, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland. hu.gang@ktl.fiI01.wnl.0000312511.62699.a8 [pii] 10.1212/01.wnl.0000312511.6269F|7 TLanki, T. Hoek, G. Timonen, K. L. Peters, A. Tiittanen, P. Vanninen, E. Pekkanen, J.2008qHourly variation in fine particle exposure is associated with transiently increased risk of ST segment depressionOccup Environ Med 2008/06/06Jun 4Objectives To evaluate whether hourly changes in fine particle (PM2.5, diameter<2.5 microm) exposure or outdoor particle concentrations are associated with rapid ischemic responses. Methods Forty-one non-smoking elderly persons with coronary heart disease were followed up with biweekly clinic visits and air pollution measurements in Helsinki, Finland. The occurrence of ST segment depressions >0.1 mV was recorded during submaximal exercise test. Hourly variations in personal PM2.5 exposure and outdoor levels of PM2.5 and ultrafine particles (<0.1 microm) were recorded during 24-hrs before the clinic visit. Associations between particulate air pollution and ST segment depressions were evaluated using logistic regression. Results Both personal and outdoor PM2.5 concentrations, but not outdoor ultrafine particle counts, were associated with ST segment depressions. Odds ratio [per 10 microg/m3] for personal PM2.5 concentration during the hour preceding clinic visit was 3.26, 95% CI: 1.07-9.99, and for 4-h average outdoor PM2.5 2.47, 95% CI 1.05-5.85. Conclusions Even very short-term elevations in fine particle exposure might increase the risk of myocardial ischemia. The mechanism is still open, but could involve changes in autonomic nervous control of heart.GOccupational and environmental medicine Occup Environ Med. 2008 Jun 4;.1470-7926 (Electronic)185248402.8170National Public Health Institute (KTL), Finland.3oem.2007.037531 [pii] 10.1136/oem.2007.03  LF|7 QHanninen, O. O. Salonen, R. O. Koistinen, K. Lanki, T. Barregard, L. Jantunen, M.2008vPopulation exposure to fine particles and estimated excess mortality in Finland from an East European wildfire episodeJ Expo Sci Environ Epidemiol 2008/06/05Jun 4;Long-range transported particulate matter (PM) air pollution episodes associated with wildfires in the Eastern Europe are relatively common in Southern and Southeastern Finland. In severe cases such as in August-September 2002, the reduced visibility and smell of the smoke, and symptoms such as irritation of eyes and airways experienced by the population raise the issue into the headlines. Because PM air pollution, in general, has been identified as a major health risk, and the exposures are of repeating nature, the issue warrants a risk assessment to estimate the magnitude of the problem. The current work uses the available air quality data in Finland to estimate population exposures caused by one of the worst episodes experienced in this decade. This episode originated from wildfires in Russia, Belarus, Ukraine, and the Baltic countries. The populations of 11 Southern Finnish provinces were exposed between 26 August and 8 September 2002, for 2 weeks to an additional population-weighted average PM(2.5) level of 15.7 mug/m(3). Assuming similar effect on mortality for these particles as observed in epidemiological time series studies on urban particles (0.5%-2% increase in mortality per 10 mug/m(3), central estimate 1%), this exposure level would be associated with 9-34 cases (17 cases central estimate) of additional mortality. Epidemiological evidence specific to particles from biomass combustion is scarce, affecting also the reliability of the current risk assessment. Do the wildfire aerosols exhibit the same level of toxicity as the urban particles? To shed light on this question, it is interesting to look at the exposure data in relationship to the observed daily mortality in Finland, even though the limited duration of the episode allows only for a weak statistical power. The percentage increases observed (0.8%-2.1% per 10 mug/m(3) of fine PM) are in line with the more general estimates for urban PM and those used in the current risk assessment.Journal of Exposure Science and Environmental Epidemiology advance online publication, 4 June 2008; doi:10.1038/jes.2008.31.cJournal of exposure science & environmental epidemiology J Expo Sci Environ Epidemiol. 2008 Jun 4;.1559-064X (Electronic)185234592.880[1] aDepartment of Environmental Health, National Public Health Institute (KTL), Kuopio, Finland [2] bWorld Health Organization European Centre for Environment and Health, Bonn, Germany [3] cInstitute of Epidemiology, Helmholz Zentrum Munchen, Munchen, Germany.)jes200831 [pii] 10.1038/jes.2xF|7 Chen, W. M. Erdos, M. R. Jackson, A. U. Saxena, R. Sanna, S. Silver, K. D. Timpson, N. J. Hansen, T. Orru, M. Grazia Piras, M. Bonnycastle, L. L. Willer, C. J. Lyssenko, V. Shen, H. Kuusisto, J. Ebrahim, S. Sestu, N. Duren, W. L. Spada, M. C. Stringham, H. M. Scott, L. J. Olla, N. Swift, A. J. Najjar, S. Mitchell, B. D. Lawlor, D. A. Smith, G. D. Ben-Shlomo, Y. Andersen, G. Borch-Johnsen, K. Jorgensen, T. Saramies, J. Valle, T. T. Buchanan, T. A. Shuldiner, A. R. Lakatta, E. Bergman, R. N. Uda, M. Tuomilehto, J. Pedersen, O. Cao, A. Groop, L. Mohlke, K. L. Laakso, M. Schlessinger, D. Collins, F. S. Altshuler, D. Abecasis, G. R. Boehnke, M. Scuteri, A. Watanabe, R. M.2008XVariations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels J Clin Invest 2008/06/04Jun 2Identifying the genetic variants that regulate fasting glucose concentrations may further our understanding of the pathogenesis of diabetes. We therefore investigated the association of fasting glucose levels with SNPs in 2 genome-wide scans including a total of 5,088 nondiabetic individuals from Finland and Sardinia. We found a significant association between the SNP rs563694 and fasting glucose concentrations (P = 3.5 x 10(-7)). This association was further investigated in an additional 18,436 nondiabetic individuals of mixed European descent from 7 different studies. The combined P value for association in these follow-up samples was 6.9 x 10(-26), and combining results from all studies resulted in an overall P value for association of 6.4 x 10(-33). Across these studies, fasting glucose concentrations increased 0.01-0.16 mM with each copy of the major allele, accounting for approximately 1% of the total variation in fasting glucose. The rs563694 SNP is located between the genes glucose-6-phosphatase catalytic subunit 2 (G6PC2) and ATP-binding cassette, subfamily B (MDR/TAP), member 11 (ABCB11). Our results in combination with data reported in the literature suggest that G6PC2, a glucose-6-phosphatase almost exclusively expressed in pancreatic islet cells, may underlie variation in fasting glucose, though it is possible that ABCB11, which is expressed primarily in liver, may also contribute to such variation.AThe Journal of clinical investigation J Clin Invest. 2008 Jun 2;.0021-9738 (Print)1852118516.915 Department of Public Health Sciences and Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA. Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland, USA. Center for Statistical Genetics and Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. Istituto di Neurogenetica e Neurofarmacologia, Consiglio Nazionale delle Ricerche, Cagliari, Italy. Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA. MRC Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine, University of Bristol, Bristol, United Kingdom. Steno Diabetes Center, Gentofte, Denmark. Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, University Hospital Malmo, Malmo, Sweden. Department of Medicine, University of Kuopio and Kuopio University Hospital, Kuopio, Finland. Department of Epidemiology and Population Health, Non-communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, University of London, London, United Kingdom. Gerontology Research Center, National Institute on Aging, Baltimore, Maryland, USA. Social Medicine Department, University of Bristol, Bristol, United Kingdom. Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark. Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark. Savitaipale Health Center, Savitaipale, Finland. Diabetes Unit, Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute, and Department of Public Health, University of Helsinki, Helsinki, Finland. Department of Medicine, Division of Endocrinology, and Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. South Ostrobothnia Central Hospital, Senajoki, Finland. Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA. Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore, Maryland, USA. Unita Operativa Geriatria, Istituto Nazionale Ricovero E Cura Anziari, Rome, Italy. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.10.1172/JCIop||7 <Tallila, J. Jakkula, E. Peltonen, L. Salonen, R. Kestila, M.2008cIdentification of CC2D2A as a Meckel syndrome gene adds an important piece to the ciliopathy puzzle1361-7Am J Hum Genet826 2008/06/03JunMeckel syndrome (MKS) is a lethal malformation disorder characterized classically by encephalocele, polycystic kidneys, and polydactyly. MKS is also one of the major contributors to syndromic neural tube defects (NTDs). Recent findings have shown primary cilia dysfunction in the molecular background of MKS, indicating that cilia are critical for early human development. However, even though four genes behind MKS have been identified to date, they elucidate only a minor proportion of the MKS cases. In this study, instead of traditional linkage analysis, we selected 10 nonrelated affected fetuses and looked for the homozygous regions shared by them. Based on this strategy, we identified the sixth locus and the fifth gene, CC2D2A (MKS6), behind MKS. The biological function of CC2D2A is uncharacterized, but the corresponding polypeptide is predicted to be involved in ciliary functions and it has a calcium binding domain (C2). Immunofluorescence staining of patient's fibroblast cells demonstrates that the cells lack cilia, providing evidence for the critical role of CC2D2A in cilia formation. Our finding is very significant not only to understand the molecular background of MKS, but also to obtain additional information about the function of the cilia, which can help to understand their significance in normal development and also in other ciliopathies, which are an increasing group of disorders with overlapping phenotypes.Tallila, Jonna Jakkula, Eveliina Peltonen, Leena Salonen, Riitta Kestila, Marjo P01 ES11253-03/ES/United States NIEHS Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States American journal of human genetics Am J Hum Genet. 2008 Jun;82(6):1361-7.1537-6605 (Electronic)1851368011.092dNational Public Health Institute, Institute for Molecular Medicine Finland, Helsinki 00290, Finland.<S0002-9297(08)00312-1 [pii] 10.1016/j.ajhg.2008.0 p||7 )Harjutsalo, V. Sjoberg, L. Tuomilehto, J.2008STime trends in the incidence of type 1 diabetes in Finnish children: a cohort study1777-82Lancet3719626 2008/05/27Adolescent Age Distribution Child Child, Preschool Cohort Studies Diabetes Mellitus, Type 1/ epidemiology Female Finland/epidemiology Humans Incidence Infant Infant, Newborn Male Population Surveillance/ methods Registries Sex Distribution Time FactorsMay 242BACKGROUND: Finland has the highest incidence of type 1 diabetes worldwide, reaching 40 per 100,000 people per year in the 1990s. Our aim was to assess the temporal trend in type 1 diabetes incidence since 2000 in Finnish children aged younger than 15 years and to predict the number of cases of type 1 diabetes in the future. METHODS: Children with newly diagnosed type 1 diabetes in Finland who were listed on the National Public Health Institute diabetes register, Central Drug Register, and Hospital Discharge Register in 1980-2005 were included in a cohort study. We excluded patients with type 2 diabetes and diabetes occurring secondary to other conditions, such as steroid use, Down's syndrome, and congenital malformations of pancreas. FINDINGS: 10,737 children-5816 boys and 4921 girls-were diagnosed with type 1 diabetes before 15 years of age during 1980-2005. The average age-standardised incidence was 42.9 per 100,000 per year (95% CI 42.6-44.3) during this period, increasing from 31.4 per 100,000 per year in 1980 to 64.2 per 100,000 per year in 2005. The age-specific rates per 100,000 per year were 31.0, 50.5, and 50.6 at ages 0-4 years, 5-9 years, and 10-14-years, respectively. We noted a significant non-linear component to the time trend (p<0.0003). In children aged 0-4 years, the increase was largest, at 4.7% more affected every year. The overall boy-to-girl ratio of incidence was 1.1; at the age of 13 years, it was 1.7 (1.4-2.0). The predicted cumulative number of new cases with type 1 diabetes before 15 years of age between 2006 and 2020 was about 10 800. INTERPRETATION: The incidence of type 1 diabetes in Finnish children is increasing even faster than before. The number of new cases diagnosed at or before 14 years of age will double in the next 15 years and the age of onset will be younger (0-4 years).Harjutsalo, Valma Sjoberg, Lena Tuomilehto, Jaakko Research Support, Non-U.S. Gov't England Lancet Lancet. 2008 May 24;371(9626):1777-82.1474-547X (Electronic)1850230228.638Diabetes Unit, Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute, Helsinki, Finland. valma.harjutsalo@ktl.fi?S0140-6736(08)60765-5 [pii] 10.1016/S0140-6736(08)60 2356002065.014  80000115.822 62742000271.910 293000062.197 34566 [doi]Eng 60742000073.377 192000084.901 60806000073.974  52000032.314 4924000032.678 008.31 [doi]Eng 765-5 [doi]eng 008862 [doi]eng 10.008 [doi]eng 3937000153.207 .3.329 [doi]eng c7ec [doi]Eng  475 [doi]Eng 9.a8 [doi]eng  89000201.285 61166000113.175 (356001835.014G7||7Vartiainen, E.2008/Controlling the cardiovascular disease epidemic623-5 J Intern Med2636 2008/05/16Cardiovascular Diseases/epidemiology/etiology/ prevention & control Cholesterol/blood Humans Risk Factors Smoking/adverse effects/prevention & controlJunfVartiainen, E Comment Review England Journal of internal medicine J Intern Med. 2008 Jun;263(6):623-5.1365-2796 (Electronic)184792634.901PKTL National Public Health Institute, Helsinki, Finland. erkki.vartiainen@ktl.fi4JIM1954 [pii] 10.1111/j.1365-2796.2008.019 m [~|7fvon Schantz, C. Saharinen, J. Kopra, O. Cooper, J. D. Gentile, M. Hovatta, I. Peltonen, L. Jalanko, A.2008Brain gene expression profiles of Cln1 and Cln5 deficient mice unravels common molecular pathways underlying neuronal degeneration in NCL diseases146 BMC Genomics9 2008/03/29eAdenylate Cyclase/genetics/metabolism Animals Blotting, Western Brain/ metabolism Cells, Cultured GAP-43 Protein/metabolism Gene Expression Profiling Gene Expression Regulation/ genetics Genotype Growth Cones/metabolism/ pathology Immediate-Early Proteins/genetics/metabolism Immunohistochemistry Membrane Glycoproteins/ genetics Mice Mice, Knockout Neuronal Ceroid-Lipofuscinoses/ genetics/pathology Protein Tyrosine Phosphatases/genetics/metabolism Receptor-Like Protein Tyrosine Phosphatases, Class 2/genetics/metabolism Synapsins/metabolism Thiolester Hydrolases/ genetics rab3 GTP-Binding Proteins/metabolismBACKGROUND: The neuronal ceroid lipofuscinoses (NCL) are a group of children's inherited neurodegenerative disorders, characterized by blindness, early dementia and pronounced cortical atrophy. The similar pathological and clinical profiles of the different forms of NCL suggest that common disease mechanisms may be involved. To explore the NCL-associated disease pathology and molecular pathways, we have previously produced targeted knock-out mice for Cln1 and Cln5. Both mouse-models replicate the NCL phenotype and neuropathology; the Cln1-/- model presents with early onset, severe neurodegenerative disease, whereas the Cln5-/- model produces a milder disease with a later onset. RESULTS: Here we have performed quantitative gene expression profiling of the cortex from 1 and 4 month old Cln1-/- and Cln5-/- mice. Combined microarray datasets from both mouse models exposed a common affected pathway: genes regulating neuronal growth cone stabilization display similar aberrations in both models. We analyzed locus specific gene expression and showed regional clustering of Cln1 and three major genes of this pathway, further supporting a close functional relationship between the corresponding gene products; adenylate cyclase-associated protein 1 (Cap1), protein tyrosine phosphatase receptor type F (Ptprf) and protein tyrosine phosphatase 4a2 (Ptp4a2). The evidence from the gene expression data, indicating changes in the growth cone assembly, was substantiated by the immunofluorescence staining patterns of Cln1-/- and Cln5-/- cortical neurons. These primary neurons displayed abnormalities in cytoskeleton-associated proteins actin and beta-tubulin as well as abnormal intracellular distribution of growth cone associated proteins GAP-43, synapsin and Rab3. CONCLUSION: Our data provide the first evidence for a common molecular pathogenesis behind neuronal degeneration in INCL and vLINCL. Since CLN1 and CLN5 code for proteins with distinct functional roles these data may have implications for other forms of NCLs as well.von Schantz, Carina Saharinen, Juha Kopra, Outi Cooper, Jonathan D Gentile, Massimiliano Hovatta, Iiris Peltonen, Leena Jalanko, Anu Comparative Study Research Support, Non-U.S. Gov't England BMC genomics BMC Genomics. 2008 Mar 28;9:146.1471-2164 (Electronic)183712314.180yNational Public Health Institute and FIMM, Institute for Molecular Medicine, Helsinki, Finland. carina.von.schantz@ktl.fi31471-2164-9-146 [pii] 10.1186/1471-2164~|7Silander, K. Saarela, J.2008vWhole genome amplification with Phi29 DNA polymerase to enable genetic or genomic analysis of samples of low DNA yield1-18Methods Mol Biol439 2008/03/29Bacteriophages/enzymology/ genetics Base Sequence DNA Primers DNA-Directed DNA Polymerase/ metabolism Gene Amplification Genome, Viral$In many large genetic studies, the amount of available DNA can be one of the criteria for selecting samples for study. In the case of large population cohorts, selecting samples based on their DNA yield can lead to biased sample selection. In addition, many valuable clinical and research sample collections exist in which the amount of DNA is very small. Unbiased whole genome amplification (WGA) of such unique samples enables genomewide scale genetic studies that would have been impossible otherwise. Multiply primed rolling circle amplification (MPRCA) and multiple displacement amplification (MDA) methods are based on the same principle. The DNA amplification is non-PCR based and uses Phi29 DNA polymerase and random hexamer primers for unbiased whole genome amplification. MDA is used for linear DNA molecules, such as genomic DNA. This chapter reviews the various applications in which whole genome amplified DNA can be used, the types of commercial kits available, and the quality control steps necessary before using the DNA in the genetic studies.Silander, Kaisa Saarela, Janna Review United States Methods in molecular biology (Clifton, N.J.) Methods Mol Biol. 2008;439:1-18.1064-3745 (Print)183700924National Public Health Institute, Helsinki, Finland.!10.1007/978-1-59745-188-8_1 [doi]eng||77Havulinna, A. S. Paakkonen, R. Karvonen, M. Salomaa, V.2008oGeographic patterns of incidence of ischemic stroke and acute myocardial infarction in Finland during 1991-2003206-13 Ann Epidemiol183 2008/02/19Adult Aged Aged, 80 and over Bayes Theorem Brain Ischemia/ epidemiology Female Finland/epidemiology Humans Incidence Male Middle Aged Myocardial Infarction/ epidemiology Stroke/ epidemiologyMar PURPOSE: To examine geographic variation in the incidence of ischemic stroke (IS) and acute myocardial infarction (AMI) in Finland during 1991-2003. METHODS: Data included all cases of first IS (n = 115,383) and AMI (n = 205,213) in persons aged 35-84 years. We used full Bayesian spatial shared component disease models for mapping the geographic risk patterns. RESULTS: The risk component shared by IS and AMI explained 73% (95% credible interval [CI]; 59%, 87%) of the geographic variation in IS risk and 68% (41%, 91%) in AMI risk. The spatial variation was similar in men and women. In the northeastern part of Finland, annual age-adjusted IS incidence was 356.4/100,000 (95% CI; 350.3, 362.6) in men and 231.2 (226.9, 235.4) in women. Annual AMI incidence was 855.6 (846.1, 865.2) in men and 351.4 (346.2, 356.5) in women. In the southwestern part of the country, annual IS incidence was 334.7 (331.6, 337.8) in men and 210.6 (208.5, 212.6) in women. Annual AMI incidence was 707.3 (702.8, 711.8) in men and 278.3 (276.0, 280.7) in women. CONCLUSION: A marked part of the spatial variation in IS and AMI incidence was disease specific, even though these diseases share a similar atherosclerotic background. Further studies are warranted for understanding the reasons for the different geographic variation.Havulinna, Aki S Paakkonen, Rauni Karvonen, Marjatta Salomaa, Veikko Research Support, Non-U.S. Gov't United States Annals of epidemiology Ann Epidemiol. 2008 Mar;18(3):206-13.1047-2797 (Print)182809202.353Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute, Helsinki, Finland. aki.havulinna@ktl.fi AS1047-2797(07)00445-0 [pii] 10.1016/j.annepidem.2007..HF|7Holtta, V. Klemetti, P. Sipponen, T. Westerholm-Ormio, M. Kociubinski, G. Salo, H. Rasanen, L. Kolho, K. L. Farkkila, M. Savilahti, E. Vaarala, O.20085IL-23/IL-17 immunity as a hallmark of Crohn's diseaseInflamm Bowel Dis 2008/05/31May 29Background: We studied the balance between ileal T-effector cells versus T-regulatory cells in active and inactive Crohn's disease (CD).Methods: We compared effector and regulatory T-cell-related markers such as interleukin (IL)-17, interferon (IFN)-gamma, IL-4, and Foxp3 transforming growth factor (TGF)-beta CTLA-4 and markers for innate immune activation such as IL-6, IL-10, IL-18, IL-23, tumor necrosis factor (TNF)-alpha, and IL-12p70, studied with immunohistochemistry and RT-PCR in ileal biopsies from patients with active or inactive CD and from control subjects. IL-17 in fecal samples was detected by ELISA. The effect of IL-17 on IL-8 and TNF-alpha mRNA expression in epithelial cell line Caco-2 was studied.Results: The numbers of IL-4-, IL-17-, and IL-23(p19)-positive cells in the lamina propria were higher in patients with CD, both active and inactive, than in the controls. mRNA expression of IL-17A, IL-6, and Foxp3 was increased in the biopsies both from patients with active disease and those in remission, whereas mRNA expression of IL-23 was increased only in active disease. Fecal IL-17 concentration was increased in patients with active disease. IL-17 enhanced the IL-8 and TNF-alpha response of the epithelial cell line to lipopolysaccharide (LPS) in vitro.Conclusions: Our findings suggest that activation of the IL-23/IL-17 axis is fundamentally connected to the etiology of CD and may represent the basis for the relapsing nature of the disease by increasing the sensitivity of epithelium to microbial LPS.(Inflamm Bowel Dis 2008).<Inflammatory bowel diseases Inflamm Bowel Dis. 2008 May 29;.1078-0998 (Print)185122484.705Laboratory for Immunobiology, Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland.10.1002/ibd.20eSLF|7ZMetsala, J. Kilkkinen, A. Kaila, M. Tapanainen, H. Klaukka, T. Gissler, M. Virtanen, S. M.2008cPerinatal Factors and the Risk of Asthma in Childhood--A Population-based Register Study in FinlandAm J Epidemiol 2008/05/31May 28UThe aim of the study was to assess whether perinatal factors are associated with the risk of asthma in childhood in a register-based, nested case-control study in Finland. All children born between January 1, 1996, and April 30, 2004, who were entitled to a special reimbursement for antiasthmatic drugs (i.e., had diagnosed asthma by 2006 and had purchased inhaled corticosteroids or montelukast at least once), were identified (n = 21,038). For each case, one matched control child was selected. The associations between perinatal factors, derived from the Finnish Medical Birth Register, and the risk of asthma were analyzed by conditional logistic regression. In the final multivariate model, maternal asthma, young age, smoking, previous miscarriages, and a high number of previous deliveries, as well as cesarean section, low gestational age, and low ponderal index, were associated with an increased risk of asthma in children diagnosed before the age of 3 years. Among children diagnosed at the age of 3 years or later, maternal asthma, low gestational age, and low ponderal index were associated with an increased risk, and a high number of previous deliveries was associated with a decreased risk of asthma. In conclusion, perinatal factors play a role in the development of asthma in childhood, but the etiology may differ in early and late-onset asthma.>American journal of epidemiology Am J Epidemiol. 2008 May 28;.1476-6256 (Electronic)185114275.285sDepartment of Health Promotion and Chronic Disease Prevention, National Public Health Institute, Helsinki, Finland.%kwn105 [pii] 10.1093/aje/m[~|7He, Q. Mertsola, J.2008,Factors contributing to pertussis resurgence329-39Future Microbiol3 2008/05/29JunDespite extensive immunization, the disease pertussis remains one of the world's leading causes of vaccine-preventable deaths. An estimated 50 million cases and 300,000 deaths occur every year. A resurgence of pertussis is observed in highly immunized populations. Increasing numbers of pertussis are reported in adolescents and adults who transmit bacteria to newborns and infants to whom pertussis may be a life-threatening disease. Many studies have shown that the causes for the resurgence are multiple, such as increased awareness of disease, use of better diagnostic tools, improved surveillance methods and waning vaccine-induced immunity. Recently, antigenic divergence has been found between vaccine strains and clinical isolates in many countries with high vaccination coverage. Here, we summarize these findings and discuss the factors contributing to pertussis resurgence in immunized populations.}He, Qiushui Mertsola, Jussi Research Support, Non-U.S. Gov't England Future microbiology Future Microbiol. 2008 Jun;3:329-39.1746-0921 (Electronic)185053980.645}Pertussis Reference Laboratory, National Public Health Institute, Kiinamyllynkatu 13, 20520 Turku, Finland. qiushui.he@ktl.fi10.2217/17460913.3 T||7=Marttila, H. J. Makinen, J. Marjamaki, M. Ruutu, P. Soini, H.2008^Molecular genetics of drug-resistant Mycobacterium tuberculosis isolates in Finland, 1995-2004338-43Int J Tuberc Lung Dis123 2008/02/21jAntitubercular Agents/pharmacology Bacterial Proteins/genetics Catalase/genetics DNA Mutational Analysis Drug Resistance, Bacterial/ genetics Finland/epidemiology Genotype Humans Isoniazid/pharmacology Mycobacterium tuberculosis/drug effects/ genetics Point Mutation Rifampin/pharmacology Seroepidemiologic Studies Tuberculosis, Multidrug-Resistant/ epidemiologyMarSETTING: Modern molecular methods help us to understand the transmission and epidemiology of Mycobacterium tuberculosis. OBJECTIVE: To analyse the molecular epidemiology of drug-resistant tuberculosis (TB), and to characterise isoniazid (INH) and rifampicin (RMP) resistance conferring mutations in Finland during 1995-2004. DESIGN: A total of 3959 new M. tuberculosis isolates underwent drug susceptibility testing; all phenotypically resistant isolates were genotyped by IS6110 restriction fragment length polymorphism and spoligotyping if necessary. INH- and/or RMP-resistant isolates were sequenced for their resistance associated genes, katG locus 315 and rpoB, respectively. RESULT: Of the 3959 isolates tested (92.4% of culture-positive cases), 183 (4.6%) were resistant to at least one first-line anti-tuberculosis drug; 14 (0.4%) isolates were multidrug-resistant. Thirty-seven (20.4%) resistant isolates belonged to 17 clusters, and the largest cluster included four isolates. The Beijing family genotype accounted for 8.8% (16 isolates) of all drug-resistant isolates. A Ser315Thr mutation in katG was found in 46.7% (56 isolates) of the INH-resistant isolates and rpoB was mutated in 85.7% (18 isolates) of the isolates resistant to RMP. CONCLUSION: Transmission of drug-resistant TB is rare in Finland, especially between indigenous and immigrant populations. Screening of mutations that confer INH and RMP resistance seems to be feasible if risk factors for multidrug resistance exist.Marttila, H J Makinen, J Marjamaki, M Ruutu, P Soini, H France The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease Int J Tuberc Lung Dis. 2008 Mar;12(3):338-43.1027-3719 (Print)182848422.240cMycobacterial Reference Laboratory, National Public Health Institute, Turku, Finland. ha i WH||7+Raulio, S. Roos, E. Mukala, K. Prattala, R.2008SCan working conditions explain differences in eating patterns during working hours?258-70Public Health Nutr113 2007/07/06Adult Cross-Sectional Studies Diet/psychology/standards/ trends Employment/methods/ psychology Female Finland Food Habits Humans Male Middle Aged Restaurants Stress, Psychological Workload/psychology WorkplaceMarOBJECTIVE: The aim of this study was to examine whether there are associations between working conditions and the use of staff canteen or packed meals among Finnish employees. SETTING: Data were obtained from cross-sectional surveys on working conditions, conducted triennially (1997, 2000, 2003) since 1997. SUBJECTS: In each survey, the subjects were 25-64-year-old employed Finnish employees: 3096 men and 3273 women. RESULTS: Employees at large workplaces used canteens far more often than those at smaller workplaces. Working conditions played a different role in canteen use at small and large workplaces, as well as among the different sexes. At small workplaces, physically demanding jobs held by female employees and low job control encouraged employees to use the canteen. On the other hand, at large workplaces, low social support at work encouraged the use of canteens among men whereas high mental strain at work meant they used the canteen less. Among women, eating packed meals was not related to working conditions, but among men, low social support and high mental strain at work were associated with more frequent use of packed meals. CONCLUSIONS: The use of a staff canteen is largely determined by the size of the workplace and by employee education. The underlying factor could be the availability of canteens, a question which must be confirmed in further studies, since well-planned mass catering at workplaces has major effects on public health, well-being and the nutrition education of employees.Raulio, Susanna Roos, Eva Mukala, Kristiina Prattala, Ritva Research Support, Non-U.S. Gov't England Public health nutrition Public Health Nutr. 2008 Mar;11(3):258-70. Epub 2007 Jul 5.1368-9800 (Print)176107501.858Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute (KTL), Mannerheimintie 166, 00300, Helsinki, Finland. susanna.raulio@ktl.fi7S1368980007000286 [pii] 10.1017/S1368980007`|?RMustonen, S. M. Tissari, S. Huikko, L. Kolehmainen, M. Lehtola, M. J. Hirvonen, A.2008Evaluating online data of water quality changes in a pilot drinking water distribution system with multivariate data exploration methods 2421-2430Water Research4210-11ArticleMayThe distribution of drinking water generates soft deposits and biofilms in the pipelines of distribution systems. Disturbances in water distribution can detach these deposits and biofilms and thus deteriorate the water quality. We studied the effects of simulated pressure shocks on the water quality with online analysers. The study was conducted with copper and composite plastic pipelines in a pilot distribution system. The online data gathered during the study was evaluated with Self-Organising Map (SOM) and Sammon's mapping, which are useful methods in exploring large amounts of multivariate data. The objective was to test the usefulness of these methods in pinpointing the abnormal water quality changes in the online data. The pressure shocks increased temporarily the number of particles, turbidity and electrical conductivity. SOM and Sammon's mapping were able to separate these situations from the normal data and thus make those visible. Therefore these methods make it possible to detect abrupt changes in water quality and thus to react rapidly to any disturbances in the system. These methods are useful in developing alert systems and predictive applications connected to online monitoring. (c) 2008 Elsevier Ltd. All rights reserved.://000256335400009cMustonen, Satu M. Tissari, Soile Huikko, Laura Kolehmainen, Mikko Lehtola, Markku J. Hirvonen, Arja 0043-1354ISI:00025633|?oVirtanen, S. M. Roivainen, M. Andersson, M. A. Ylipaasto, P. Hoornstra, D. Mikkola, R. Salkinoja-Salonen, M. S.2008FIn vitro toxicity of cereulide on porcine pancreatic Langerhans islets 1029-1037Toxicon516ArticleMayCereulide is a K+ ionophore cytotoxic and mitochondriotoxic to primary cells and cell lines of human and other mammalian origins. It is a heat-stable, highly lipophilic (log K-ow 5.96)peptide (1152gmol(-1)) produced by certain strains of Bacillus cereus, a bacterium connected to emetic food poisonings. In this study the pancreatic toxicity of purified cereulide, and cereulide-containing bacterial extracts, was studied using fetal porcine Langerhans islets in culture. Exposure to 1 ng ml(-1) of purified cereulide caused necrotic cell death of the islet cells impairing their insulin content within 2 days. Cell extracts of cereulide-positive B. cereus strains connected to food poisoning or isolated from foodstuffs were toxic, corresponding to their measured cereulide content. Extracts of B. cereus strains producing or not producing the B. cereus diarrheal toxin, but no cereulide, were tolerated by the porcine islet cultures up to concentrations 1000-fold higher compared to extracts from strains containing cereulide, and up to exposure times of 7 d. Cereulide thus was identified as the B. cereus-produced substance toxic towards porcine fetal Langerhans islets and beta cells. (c) 2008 Elsevier Ltd. All rights reserved.://000256500300009Virtanen, Suvi M. Roivainen, Merja Andersson, Maria A. Ylipaasto, Petri Hoornstra, Douwe Mikkola, Raimo Salkinoja-Salonen, Mirja S. 0041-0101ISI:000256o|?|Havulinna, A. S. Tienari, P. J. Marttila, R. J. Martikainen, K. K. Eriksson, J. G. Taskinen, O. Moltchanova, E. Karvonen, M.2008OGeographical variation of medicated parkinsonism in Finland during 1995 to 2000 1024-1031Movement Disorders237ArticleMay}We performed a nation-wide study on geographical variation in the incidence and prevalence of medicated parkinsomism among the Finns aged 30 years using Bayesian spatial conditional autoregressive models. Registry of reimbursed medication for parkinsonism and a prescription database of purchase of these drugs were used to identify the study subjects. They were located by the map coordinates of the place of residence and aggregated into regular 100 km 2 grid cells. A total of 7,190 incident and 10,616 prevalent cases were found. The age-adjusted annual incidence was 32.6/100,000 (95% HDR 31.8-33.4) during the years 1995 to 2000 and prevalence was 268/100,000 (95% HDR 263-274) in 2000. The male to female ratio was 1.45 (95% HDR 1.39-1.51) in incidence and 1.54 (95% HDR 1.47-1.61) in prevalence. There was strong evidence for geographic variation in incidence and prevalence. A zone with high incidence and prevalence was identified in the eastern and central part of Finland. There was no evidence for difference in incidence and prevalence between urban and rural areas. The marked (more than twofold) geographic variation can hardly be caused solely by practices of the registration and collection of data on diagnosis or by methodological issues, but rather suggests to geographic variation in protective and predisposing factors of Parkinsonism in Finland. (c) 2008 Movement Disorder Society.://000256393700015Havulinna, Aki S. Tienari, Pentti J. Marttila, Reijo J. Martikainen, Kirsti K. Eriksson, Johan G. Taskinen, Olli Moltchanova, Elena Karvonen, Marjatta 0885-3185ISI:000256 P|?eKristjansdottir, G. Sandling, J. K. Bonetti, A. Roos, I. M. Milani, L. Wang, C. Gustafsdottir, S. M. Sigurdsson, S. Lundmark, A. Tienari, P. J. Koivisto, K. Elovaara, I. Pirttila, T. Reunanen, M. Peltonen, L. Saarela, J. Hillert, J. Olsson, T. Landegren, U. Alcina, A. Fernandez, O. Leyva, L. Guerrero, M. Lucas, M. Izquierdo, G. Matesanz, F. Syvanen, A. C.2008xInterferon regulatory factor 5 (IRF5) gene variants are associated with multiple sclerosis in three distinct populations362-369Journal of Medical Genetics456ArticleJunBackground: IRF5 is a transcription factor involved both in the type I interferon and the toll-like receptor signalling pathways. Previously, IRF5 has been found to be associated with systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel diseases. Here we investigated whether polymorphisms in the IRF5 gene would be associated with yet another disease with features of autoimmunity, multiple sclerosis (MS). Methods: We genotyped nine single nucleotide polymorphisms and one insertion-deletion polymorphism in the IRF5 gene in a collection of 2337 patients with MS and 2813 controls from three populations: two case control cohorts from Spain and Sweden, and a set of MS trio families from Finland. Results: Two single nucleotide polymorphism (SNPs) (rs4728142, rs3807306), and a 5 bp insertion-deletion polymorphism located in the promoter and first intron of the IRF5 gene, showed association signals with values of p<0.001 when the data from all cohorts were combined. The predisposing alleles were present on the same common haplotype in all populations. Using electrophoretic mobility shift assays we observed allele specific differences in protein binding for the SNP rs4728142 and the 5 bp indel, and by a proximity ligation assay we demonstrated increased binding of the transcription factor SP1 to the risk allele of the 5 bp indel. Conclusion: These findings add IRF5 to the short list of genes shown to be associated with MS in more than one population. Our study adds to the evidence that there might be genes or pathways that are common in multiple autoimmune diseases, and that the type I interferon system is likely to be involved in the development of these diseases.://000256369500006eKristjansdottir, G. Sandling, J. K. Bonetti, A. Roos, I. M. Milani, L. Wang, C. Gustafsdottir, S. M. Sigurdsson, S. Lundmark, A. Tienari, P. J. Koivisto, K. Elovaara, I. Pirttila, T. Reunanen, M. Peltonen, L. Saarela, J. Hillert, J. Olsson, T. Landegren, U. Alcina, A. Fernandez, O. Leyva, L. Guerrero, M. Lucas, M. Izquierdo, G. Matesanz, F. Syvanen, A.-C. 0022-2593ISI:0002563WG|?qFeldt, K. Raikkonen, K. Eriksson, J. G. Andersson, S. Osmond, C. Barker, D. J. P. Phillips, D. I. W. Kajantie, E.2008[Childhood growth and cardiovascular reactivity to psychological stressors in late adulthood72-82Journal of Internal Medicine2641ArticleJulqObjective. Specific childhood growth patterns relate to risk of cardiovascular (CV) disease later in life, but the underlying mechanisms are unclear. We studied whether CV reactivity, a predictor of CV disease risk, is associated with childhood growth trajectories. Methods. A total of 144 (77 women and 67 men) participants of the Helsinki Birth Cohort Study born 1934-1944, whose height and weight were recorded repeatedly during the first 11 years, underwent the Trier Social Stress Test at the average age of 63 years. Beat-to-beat blood pressure was monitored via noninvasive finger photoplethysmograph (Finometer((R))), and CV reactivity scores were determined as the mean increment from baseline. Results. In both women and men, systolic blood pressure (SBP) reactivity increased by 3.8 mmHg (95% CI 0.8-6.9) and diastolic BP (DBP) reactivity by 1.4 mmHg (95% CI 0.0-2.8) for every standard deviation increase in gain in body mass index (kg m(-2)) between 7 and 11 years. By contrast, effects of height gain were dissimilar between sexes. In women, higher DBP reactivity was associated with a slow gain in height between 0 and 2 years, whilst in men higher SBP reactivity was associated with a slow gain in height between 2 and 7 years, which was preceded by a more rapid gain in height between 0 and 2 years. Adjusting for adult body size, body size at birth or childhood socio-economic status did not change the results. Conclusions. We found that growth during childhood is associated with CV reactivity to stress later in adulthood. Early life programming of CV reactivity may partly underlie the link between early growth and CV disease.://000256619200008qFeldt, K. Raikkonen, K. Eriksson, J. G. Andersson, S. Osmond, C. Barker, D. J. P. Phillips, D. I. W. Kajantie, E. 0954-6820ISI:0002566 (|?.Gursoy, M. Pajukanta, R. Sorsa, T. Kononen, E.2008AClinical changes in periodontium during pregnancy and post-partum576-583"Journal of Clinical Periodontology357ArticleJulBackground and Aim: Pregnancy has been presented to increase susceptibility to gingival inflammation. It is unclear whether pregnancy gingivitis exposes or proceeds to periodontitis. We examined longitudinally the severity of periodontal changes during pregnancy and post-partum, and compared the findings with an age-matched group of non-pregnant women. Material and Methods: Thirty generally healthy, non-smoking women at an early phase of their pregnancy and 24 non-pregnant women as controls were recruited. The pregnant group was examined three times during pregnancy and twice during post-partum, and the non-pregnant group three times, once per subsequent month. At each visit, visible plaque index (VPI), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL) were measured from six sites per tooth. Results: In the pregnant group, BOP and PPD increased simultaneously without relation to plaque between the first and second trimesters, and thereafter decreased during subsequent visits. No changes were detected in CAL during the study period. In the non-pregnant group, BOP stayed invariable during the follow-up and correlated with the amount of plaque. Neither periodontal pocket formation nor significant changes in attachment levels were observed. Conclusion: Based on this study, changes in clinical parameters during pregnancy are reversible, indicating that pregnancy gingivitis does not predispose or proceed to periodontitis.://0002564924000039Gursoy, Mervi Pajukanta, Riitta Sorsa, Timo Kononen, Eija 0303-6979ISI:000256|?_Ritakallio, M. Koivisto, A. M. von der Pahlen, B. Pelkonen, M. Marttunen, M. Kaltiala-Heino, R.2008Continuity, comorbidity and longitudinal associations between depression and antisocial behaviour in middle adolescence: A 2-year prospective follow-up study355-370Journal of Adolescence313ArticleJunThe study investigated continuity, comorbidity and longitudinal associations between depression Beck depression inventory (RBDI) and antisocial behaviour Youth self-report (YSR) in middle adolescence. Data were used from a community sample of 2070 adolescents who participated in a 2-year prospective follow-up study. The results indicate that both depression and antisocial behaviour had considerable continuity, and concurrent comorbidity between these disorders was strong. In contrast to several previous studies, antisocial behaviour did not predict subsequent depression, but conversely, depression predicted subsequent antisocial behaviour among girls. Among boys history of depression seemed to protect from subsequent antisocial behaviour. Gender differences in longitudinal associations are discussed. (C) 2007 The Association for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.://000256526500005~Ritakallio, Minna Koivisto, Anna-Maija von der Pahlen, Bettina Pelkonen, Mirjami Marttunen, Mauri Kaltiala-Heino, Riittakerttu 0140-1971ISI:00025ͨ|?pLajunen, T. Vikatmaa, P. Ikonen, T. Lepantalo, M. Lounatmaa, K. Sormunen, R. Rantala, A. Leinonen, M. Saikku, P.2008Comparison of polymerase chain reaction methods, in situ hybridization, and enzyme immunoassay for detection of Chlamydia pneumoniae in atherosclerotic carotid plaques156-164.Diagnostic Microbiology and Infectious Disease612ArticleJuntChlamydia pneumoniae has been associated with cardiovascular diseases and has been shown by different methods to be present in atherosclerotic lesions. However, not all studies have found C. pneumoniae in atherosclerotic tissues. We compared polymerase chain reaction (PCR) methods, in situ hybridization (ISH), and measurement of chlamydial lipopolysaccharide (cLPS) by enzyme immunoassay (EIA) from homogenized atherosclerotic tissue in the detection of C. pneumoniae. In a study population of 110 patients with carotid artery disease, cLPS was found in 22.2%, and DNA by PCR was found in 34.3% and by ISH in 39.4% of the samples. Poor repeatability was shown to complicate PCR, and the technical problems inherent in ISH were not insignificant. In contrast, the cLPS EIA test was fast and easy to perform. If the sensitivity could be increased, for example, by testing multiple tissue pieces, cLPS EIA might provide a standardized commercial method for the detection of chlamydia in tissue samples, and it, thus, merits further characterization and validation in different patient populations. (C) 2008 Elsevier Inc. All rights reserved.://000256489400005Lajunen, Taina Vikatmaa, Pirkka Ikonen, Tuija Lepantalo, Mauri Lounatmaa, Kari Sormunen, Raija Rantala, Aino Leinonen, Maija Saikku, Pekka 0732-8893ISI:00025  |? Barber, T. M. Bennett, A. J. Groves, C. J. Sovio, U. Ruokonen, A. Martikainen, H. Pouta, A. Hartikainen, A. L. Elliott, P. Lindgren, C. M. Freathy, R. M. Koch, K. Ouwehand, W. H. Karpe, F. Conway, G. S. Wass, J. A. H. Jarvelin, M. R. Franks, S. McCarthy, M. I.2008hAssociation of variants in the fat mass and obesity associated (FTO) gene with polycystic ovary syndrome 1153-1158 Diabetologia517ArticleJulAims/hypothesis Variants in the fat-mass and obesity-associated gene (FTO) influence susceptibility to type 2 diabetes via an effect on adiposity/obesity. Given the important role of obesity in the aetiology of both polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus, our aim was to establish whether FTO variants are also implicated in PCOS susceptibility. Methods We performed a genetic association study of FTO variant rs9939609 using case-control analyses, conducted in 463 PCOS patients (geometric mean BMI 27.5 kg/m(2)) and 1,336 female controls (geometric mean BMI 25.3 kg/m(2)) of UK British/Irish origin. We also sought evidence for associations between FTO variation and circulating testosterone levels in 324 UK PCOS patients and 1,000 women from the Northern Finland Birth Cohort of 1966. Outcome measures included FTO rs9939609 genotype frequencies by participant group and androgen measures (testosterone, free androgen index) by genotype. Results There was a significant association between FTO genotype and PCOS status in the UK case-control analysis, which was attenuated by adjustment for BMI (Cochran-Armitage test, odds ratio [per minor allele copy] 1.30 [95% CI 1.12, 1.51], p=7.2x10(-4) [unadjusted], p=2.9x10(-3) [adjusted]). This association was most evident in obese PCOS patients (PCOS patients below median BMI vs UK controls, p=0.11; above median BMI vs controls, p=2.9x10(-4)). No relationship between FTO genotype and androgen levels was seen. Conclusions/interpretation We provide the first evidence that variants that predispose to common obesity also result in altered susceptibility to PCOS, confirming the mechanistic link between these conditions. The predominant effect of FTO variants on PCOS susceptibility is probably mediated through adiposity.://000256428000011Barber, T. M. Bennett, A. J. Groves, C. J. Sovio, U. Ruokonen, A. Martikainen, H. Pouta, A. Hartikainen, A. -L. Elliott, P. Lindgren, C. M. Freathy, R. M. Koch, K. Ouwehand, W. H. Karpe, F. Conway, G. S. Wass, J. A. H. Jarvelin, M. -R. Franks, S. McCarthy, M. I. 0012-186XISI:00025642M; |?!JSurakka, J. Ruutiainen, J. Romberg, A. Puukka, P. Kronholm, E. Karanko, H.2008.Pupillary function in early multiple sclerosis150-154Clinical Autonomic Research183ArticleJunAutonomic pupillary function was assessed with pupillometry in 95 mildly or moderately disabled patients with multiple sclerosis (MS) and 81 healthy subjects. The parasympathetic pupillary function was measured as initial diameter (mm), time to minimum diameter (seconds), reflex amplitude (mm), relative reflex amplitude (%), and maximal constriction velocity (mm/seconds). To reflect the sympathetic pupillary function maximal redilatation velocity (mm/seconds), and time of 75% of redilatation (seconds) were measured. Of MS patients 85-99% were within the reference values of healthy subjects. In MS patients the effect of age was observed in the initial diameter, reflex amplitude, and time of 75% redilatation. There were no such age related effects in healthy subjects. In age adjusted analysis the initial diameter and time of 75% redilatation differed significantly from healthy controls. Autonomic pupillary functions were not associated with fatigue, visual defect, or bladder disturbance, as measured by Fatigue Severity Scale, Kurtzke's Functional System Scales, Expanded Disability Status Scale, or the Multiple Sclerosis Functional Composite. Our results suggest that both parasympathetic and sympathetic pupillary functions are disturbed already early in the course of MS. However, the disturbance is not severe at this stage of the disease. The dysfunction is age-dependent and thus possibly related to the dimished remyelination capacity of the central nervous system.://000256427200006^Surakka, Jukka Ruutiainen, Juhani Romberg, Anders Puukka, Pauli Kronholm, Erkki Karanko, Hannu 0959-9851ISI:00025>|?"bKekkonen, R. A. Sysi-Aho, M. Seppanen-Laakso, T. Julkunen, I. Vapaatalo, H. Oresic, M. Korpela, R.2008qEffect of probiotic Lactobacillus rhamnosus GG intervention on global serum lipidomics profiles in healthy adults 3188-3194!World Journal of Gastroenterology1420ArticleMayEAIM: To investigate the effect of three weeks' intervention with a probiotic Lactobacillus rhamnosus GG (LGG) bacteria on global serum lipidomic profiles and evaluate whether the changes in inflammatory variables (CRP, TNF-alpha and IL-6) are reflected in the global lipidomic profiles of healthy adults. METHODS: We performed UPLC/MS-based global lipidomic platform analysis of serum samples (n = 26) in a substudy of a randomised, double-blind, placebo-controlled 3-wk clinical intervention trial investigating the immunomodulatory effects of probiotics in healthy adults. RESULTS: A total of 407 lipids were identified, corresponding to 13 different lipid classes. Serum samples showed decreases in the levels of lysophosphatidylcholines (LysoGPCho), sphingomyelins (SM) and several glycerophosphatidylcholines (GPCho), while triacylglycerols (TAG) were mainly increased in the probiotic LGG group during the intervention. Among the inflammatory variables, IL-6 was moderately associated by changes in global lipidomic profiles, with the top-ranked lipid associated with IL-6 being the proinflammatory LysoGPCho (20:4). There was a weak association between the lipidomic profiles and the two other inflammatory markers, TNF-alpha and CRP. CONCLUSION: This was the first study to investigate the effects of probiotic intervention on global lipidomic profiles in humans. There are indications that probiotic LGG intervention may lead to changes in serum global lipid profiles, as reflected in decreased GPCho, LysoGPCho and SM as well as mainly increased TAG. (C) 2008 The WJG Press. All rights reserved.://000256364900011|Kekkonen, Riina A. Sysi-Aho, Marko Seppanen-Laakso, Tuulikki Julkunen, Ilkka Vapaatalo, Heikki Oresic, Matej Korpela, Riitta 1007-9327ISI:000256364900011|?#AGullstrand, C. Wahlberg, J. Ilonen, J. Vaarala, O. Ludvigsson, J.2008Progression to type 1 diabetes and autoantibody positivity in relation to HLA-risk genotypes in children participating in the ABIS study182-190Pediatric Diabetes93ArticleJun&Background: Autoantibodies against beta-cell antigens together with human leukocyte antigen (HLA)-risk genotypes are used as predictive markers for type 1 diabetes (T1D). In this study, we have investigated the role of HLA-risk and -protective genotypes for development of beta-cell autoantibodies and progression to T1D in healthy children. Methods: T1D-related HLA genotypes and autoantibodies against glutamic acid decarboxylase [glutamic acid decarboxylase antibodies (GADA)] and islet antigen-2 (IA-2A) were studied at 1, 2.5 and 5 yr of age in unselected healthy children and children with T1D participating in the All Babies In Southeast Sweden (ABIS) study. Results: GADA or IA-2A positivity at 5 yr of age was associated with DR4-DQ8 haplotype and DR3-DQ2/DR4-DQ8 genotype. By the age of 6-7 yr, we identified 32 children with T1D among the 17 055 participants in the ABIS study. Eight of 2329 (0.3%) non-diabetic children had permanent autoantibodies, and 143 of 2329 (6%) children had transient autoantibodies. HLA-risk genotypes associated with T1D, whereas protective genotypes were seldom found in children with T1D. Children with permanent autoantibodies had more often risk-associated DR4-DQ8 haplotype than autoantibody-negative children. No associations with HLA-risk or -protective genotypes were found for transient autoantibodies. Conclusions: The strong relation between HLA-risk alleles and T1D once again confirmed that HLA-risk genotypes play an important role for development of T1D. However, HLA genotypes seem not to explain induction of autoantibodies, especially transient autoantibodies, in the general population, emphasizing the role of environmental factors in the initiation of autoimmunity. It seems that HLA-risk genotypes are responsible for maturation of the permanent autoantibody response.://000256355200003\Gullstrand, Camilla Wahlberg, Jeanette Ilonen, Jorma Vaarala, Outi Ludvigsson, Johnny Part 1 1399-543XISI:00025635s|?$NKnip, M. Reunanen, A. Virtanen, S. M. Nuutinen, M. Viikari, J. Akerblom, H. K.2008mDoes the secular increase in body mass in children contribute to the increasing incidence of type 1 diabetes?46-49Pediatric Diabetes93ArticleJunBackground: The incidence of type 1 diabetes in children has increased in most developed countries after World War II, and simultaneously, normal children have experienced accelerated weight gain and growth. Objective: We set out to explore whether any relationship can be seen between the incidence of childhood type 1 diabetes and changes in linear growth and body mass in Finnish children over a 12-yr period. Methods: Incidence rates for type 1 diabetes in Finnish children under the age of 15 yr were obtained from the National Central Drug Registry. The rates were averaged for 3-yr intervals over the 15-yr period 1979-1993 and related to data on mean height, weight, and body mass index (BMI) in 15-yr-old children generated for the years 1980, 1983, 1986, 1989, and 1992 by the 'Cardiovascular Risk in Young Finns' study. Results: There was a positive correlation between the incidence of childhood type 1 diabetes and mean heights (r = 0.84; p = 0.039), mean weights (r = 0.85; p = 0.036), and mean BMIs (r = 0.87; p = 0.028) in 15-yr-old children over the 12-yr study period. Conclusions: This observation suggests that accelerated linear growth and increasing body mass may contribute to the rising incidence of childhood type 1 diabetes seen in most developed countries since World War II. This effect might be mediated through increased beta-cell stress induced by hyperinsulinemia and decreased insulin sensitivity, associated with rapid linear growth and obesity.://000256355500006fKnip, Mikael Reunanen, Antti Virtanen, Suvi M. Nuutinen, Matti Viikari, Jorma AKerblom, Hans K. Part 2 1399-543XISI:00025ϼ|?%6Loos, R. J. F. Lindgren, C. M. Li, S. X. Wheeler, E. Zhao, J. H. Prokopenko, I. Inouye, M. Freathy, R. M. Attwood, A. P. Beckmann, J. S. Berndt, S. I. Bergmann, S. Bennett, A. J. Bingham, S. A. Bochud, M. Brown, M. Cauchi, S. Connell, J. M. Cooper, C. Smith, G. D. Day, I. Dina, C. De, S. Dermitzakis, E. T. Doney, A. S. F. Elliott, K. S. Elliott, P. Evans, D. M. Farooqi, I. S. Froguel, P. Ghori, J. Groves, C. J. Gwilliam, R. Hadley, D. Hall, A. S. Hattersley, A. T. Hebebrand, J. Heid, I. M. Herrera, B. Hinney, A. Hunt, S. E. Jarvelin, M. R. Johnson, T. Jolley, J. D. M. Karpe, F. Keniry, A. Khaw, K. T. Luben, R. N. Mangino, M. Marchini, J. McArdle, W. L. McGinnis, R. Meyre, D. Munroe, P. B. Morris, A. D. Ness, A. R. Neville, M. J. Nica, A. C. Ong, K. K. O'Rahilly, S. Owen, K. R. Palmer, C. N. A. Papadakis, K. Potter, S. Pouta, A. Qi, L. Randall, J. C. Rayner, N. W. Ring, S. M. Sandhu, M. S. Scherag, A. Sims, M. A. Song, K. Soranzo, N. Speliotes, E. K. Syddall, H. E. Teichmann, S. A. Timpson, N. J. Tobias, J. H. Uda, M. Vogel, C. I. G. Wallace, C. Waterworth, D. M. Weedon, M. N. Willer, C. J. Wraight, V. L. Yuan, X. Zeggini, E. Hirschhorn, J. N. Strachan, D. P. Ouwehand, W. H. Caulfield, M. J. Samani, N. J. Frayling, T. M. Vollenweider, P. Waeber, G. Mooser, V. Deloukas, P. McCarthy, M. I. Wareham, N. J. Barroso, I.2008RCommon variants near MC4R are associated with fat mass, weight and risk of obesity768-775Nature Genetics406ArticleJunTo identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.://000256212000019Loos, Ruth J. F. Lindgren, Cecilia M. Li, Shengxu Wheeler, Eleanor Zhao, Jing Hua Prokopenko, Inga Inouye, Michael Freathy, Rachel M. Attwood, Antony P. Beckmann, Jacques S. Berndt, Sonja I. Bergmann, Sven Bennett, Amanda J. Bingham, Sheila A. Bochud, Murielle Brown, Morris Cauchi, Stephane Connell, John M. Cooper, Cyrus Smith, George Davey Day, Ian Dina, Christian De, Subhajyoti Dermitzakis, Emmanouil T. Doney, Alex S. F. Elliott, Katherine S. Elliott, Paul Evans, David M. Farooqi, I. Sadaf Froguel, Philippe Ghori, Jilur Groves, Christopher J. Gwilliam, Rhian Hadley, David Hall, Alistair S. Hattersley, Andrew T. Hebebrand, Johannes Heid, Iris M. Herrera, Blanca Hinney, Anke Hunt, Sarah E. Jarvelin, Marjo-Riitta Johnson, Toby Jolley, Jennifer D. M. Karpe, Fredrik Keniry, Andrew Khaw, Kay-Tee Luben, Robert N. Mangino, Massimo Marchini, Jonathan McArdle, Wendy L. McGinnis, Ralph Meyre, David Munroe, Patricia B. Morris, Andrew D. Ness, Andrew R. Neville, Matthew J. Nica, Alexandra C. Ong, Ken K. O'Rahilly, Stephen Owen, Katharine R. Palmer, Colin N. A. Papadakis, Konstantinos Potter, Simon Pouta, Anneli Qi, Lu Randall, Joshua C. Rayner, Nigel W. Ring, Susan M. Sandhu, Manjinder S. Scherag, Andre Sims, Matthew A. Song, Kijoung Soranzo, Nicole Speliotes, Elizabeth K. Syddall, Holly E. Teichmann, Sarah A. Timpson, Nicholas J. Tobias, Jonathan H. Uda, Manuela Vogel, Carla I. Ganz Wallace, Chris Waterworth, Dawn M. Weedon, Michael N. Willer, Cristen J. Wraight, Vicki L. Yuan, Xin Zeggini, Eleftheria Hirschhorn, Joel N. Strachan, David P. Ouwehand, Willem H. Caulfield, Mark J. Samani, Nilesh J. Frayling, Timothy M. Vollenweider, Peter Waeber, Gerard Mooser, Vincent Deloukas, Panos McCarthy, Mark I. Wareham, Nicholas J. Barroso, Ines 1061-4036ISI:00025,|?&lKarlsson, L. Kiviruusu, O. Miettunen, J. Heila, H. Holi, M. Ruuttu, T. Tuisku, V. Pelkonen, M. Marttunen, M.2008cOne-year course and predictors of outcome of adolescent depression: A case-control study in Finland844-853Journal of Clinical Psychiatry695ArticleMayBackground: Clinical studies on the outcome of adolescent depression beyond treatment trials are scarce. Objective: To investigate the impact of characteristics of the depressive episode and current comorbidity on the 1-year outcome of depression. Method: A sample of 174 consecutive adolescent psychiatric outpatients (aged 13 through 19 years) and 17 school-derived matched controls, all with unipolar depressive disorders at baseline, were reinterviewed for DSM-IV Axis I and Axis II disorders at 12 months. The study was conducted between January 1998 and May 2002. Results: The outpatients had equal recovery rate and episode duration but shorter time to recurrence than the controls. Among the outpatients, Axis II comorbidity predicted shorter time to recurrence (p = .02). Longer time to recovery was predicted by earlier lifetime age at onset for depression (p = .02), poor psychosocial functioning (p = .003), depressive disorder diagnosis (p <= .05), and longer episode duration by study entry (p = .001), with an interaction between episode duration and depressive disorder diagnosis (p = .04). Conclusions: Characteristics of depression generally predicted the outcome better than comorbidity. Axis II comorbidity has prognostic value in adolescent depression.://000256279600019Karlsson, Linnea Kiviruusu, Olli Miettunen, Jouko Heila, Hannele Holi, Matti Ruuttu, Titta Tuisku, Virpi Pelkonen, Mirjami Marttunen, Mauri 0160-6689ISI:0002562x|?'ATiirikainen, K. Lounamaa, A. Paavola, M. Kumpula, H. Parkkari, J.20086Trend in sports injuries among young people in Finland529-536(International Journal of Sports Medicine296ArticleJun[The main purpose of this study was to explore how the number of home, sports, and other leisure time injuries among young people aged 15 - 25 years has developed in Finland in 1988 2003. In 1988, 2559 people aged 15-25 years were interviewed by Statistics Finland. In 1993, 1997 and 2003 those amounts were 751, 1638 and 1382. The subjects were asked in a telephone interview to report the injuries in which they had been involved during the previous 12 months. The crude injury incidence in 2003 was 364 per 1000 person years in men and 246 in women. The total number of injuries increased 49% between the years 1988 and 2003. The number of sports injuries increased the most. The increase was greater among men than women, and the injury rate was higher among both men and women aged 15-19 years than those aged 20-25 years. More research is needed on whether and how exercise and time at home have changed and become riskier among young people. It is also essential to find out which prevention methods are the most effective among young people and implement these measures in a well-planned and targeted manner.://000256313100015ATiirikainen, K. Lounamaa, A. Paavola, M. Kumpula, H. Parkkari, J. 0172-4622ISI:000250|?(8Borodulin, K. Laatikainen, T. Juolevi, A. Jousilahti, P.2008lThirty-year trends of physical activity in relation to age, calendar time and birth cohort in Finnish adults339-344!European Journal of Public Health183ArticleJun Background: The aim of this article was to investigate time trends 1972-2002 in leisure time, occupational and commuting physical activity across birth cohorts in Finnish adults. Methods: The study population comprised 59 028 men and women aged 25-64 years who participated in the FINRISK Study. The first birth cohort was born in 1913 and the last in 1977. Prevalence of physical activity was reported across birth cohorts and study years and change in the prevalence was tested using log-linear regression analysis. Results: The prevalence of leisure-time physical activity increased between 1972 and 2002 from 66 to 77 in men and from 49 to 76 in women. In each study year, the younger people were more active than the older ones. However, within the birth cohorts, physical activity tended to increase with age. The prevalence of physically demanding work decreased from 60 to 38 in men and from 47 to 25 in women and the prevalence of daily commuting activity decreased from 30 to 10 in men and from 34 to 22 in women, in the same time period. In the 1970s and the 80s, the older people had more physically demanding work than the younger ones, but within the birth cohorts, occupational activity decreased with age. Conclusion: During the past 30 years, the prevalence of leisure-time physical activity has increased, while the prevalence of occupational and commuting physical activity has decreased. The cross-sectional association of age with different types of physical activity was different from that assessed within the birth cohorts.://000256274200027CBorodulin, Katja Laatikainen, Tiina Juolevi, Anne Jousilahti, Pekka 1101-1262ISI:00025B3d|?)Riley, T. V. Huovinen, P.2008VInfection control measures to limit the spread of Clostridium difficile - Introduction1-1#Clinical Microbiology and Infection14Editorial MaterialMay://000256258700001"Riley, T. V. Huovinen, P. Suppl. 5 1198-743XISI:00025625=+̔|?*0Kallio, M. K. Koskinen, S. V. P. Prattala, R. S.2008WFunctional disabilities do not prevent the elderly in Finland from eating regular meals97-103Appetite511ArticleJulThe aim of this study was to depict the prevalence of different meal patterns of the elderly in Finland and to analyse the role of socio-demographic factors, functional capacity and help received as the determinants of following a conventional meal pattern. A nationally representative sample of elderly people aged 65 years and over and living at home (n = 1697) in 2000-2001 was obtained. A structured (personal) interview was used for data collection. Regular hot meals are common among the elderly. Functional disability affecting the carrying out of food-related activities does not have an independent effect on the regularity of meals. The conventional meal pattern, which consists of breakfast, a hot lunch and a hot dinner, is more seldom followed by the elderly who have a low socio-economic status than by those whose educational level and monthly income are higher. The help received in carrying out food-related activities contributes to the ability to maintain a conventional meal pattern. In order to allow elderly people to live independently at home for as long as possible, special attention should be paid to the problems regarding meals in the lower socio-economic groups. (C) 2008 Elsevier Ltd. All rights reserved.://000256227700017MKallio, Maija Katariina Koskinen, Seppo Vaino Pellervo Prattala, Ritva Sylvia 0195-6663ISI:00025/|?+2Karppinen, A. Brummer-Korvenkontio, H. Reunala, T.20082Treatment of mosquito-bite allergy with rupatadine82-83Allergy63Meeting Abstract://000256235600183<Karppinen, A. Brummer-Korvenkontio, H. Reunala, T. Suppl. 88 0105-4538ISI:0002562xg|?,5Abrahamsson, T. Bjorksten, B. Vaarala, O. Jenmalm, M.2008uIgE-associated allergic disease during infancy is associated with low levels of C-reactive protein at one year of age92-92Allergy63Meeting Abstract://000256235600206?Abrahamsson, T. Bjorksten, B. Vaarala, O. Jenmalm, M. Suppl. 88 0105-4538ISI:000256sc|?--Pennanen, S. Sahlman, M. Reiman, M. Putus, T.2008~Exposure of health-care staff to biological dust in indoor air: the case of microbes and mites associated with moisture damage131-131Allergy63Meeting Abstract://0002562356003097Pennanen, S. Sahlman, M. Reiman, M. Putus, T. Suppl. 88 0105-4538ISI:00025625#|?.%Piirainen, L. Seppala, U. Vaarala, O.2008PChallenge induced allergen specific IgA in saliva in allergic and healthy adults338-338Allergy63Meeting Abstract://000256235600899/Piirainen, L. Seppala, U. Vaarala, O. Suppl. 88 0105-4538ISI:00025˼|?/WMetsala, J. Kilkkinen, A. Kaila, M. Tapanainen, H. Klaukka, T. Gissler, M. Virtanen, S.2008dPerinatal factors and the risk of asthma in childhood - a population based register study in Finland464-464Allergy63Meeting Abstract://000256235601259aMetsala, J. Kilkkinen, A. Kaila, M. Tapanainen, H. Klaukka, T. Gissler, M. Virtanen, S. Suppl. 88 0105-4538ISI:000256'|?0TKoort, J. K. Makinen, T. J. Suokas, E. Veirant, M. Jalava, J. Tormala, P. Aro, H. T.2008SSustained release of ciprofloxacin from an osteoconductive poly(DL)-lactide implant295-301Acta Orthopaedica792ArticleBackground and purpose Antibiotic-releasing bioresorbable implants are used for local treatment of bone infections, but most drug delivery systems release antibiotic for too short a time. Methods We used pellets (0.9 x 1.0 mm) made of bioabsorbable poly(DL) lactic acid matrix, ciprofloxacin (7.3 +/- 0.4 wt%), and bioactive glass microspheres of 90-125 mu m (29.3 +/- 0.2 wt%). The ciprofloxacin release and antibacterial activity was measured in elution tests in vitro and local tissue concentrations were measured in rabbits. Results In elution tests in vitro, the therapeutic level (> 2 mu g/mL) of ciprofloxacin was achieved within 6 h of the start of the test, and it was maintained for up to 300 days. The antibacterial activity of the antibiotic released from sterilized composites was similar to that of the unprocessed ciprofloxacin. In vivo measurements showed high local tissue concentrations (16-86 mu g/g of bone tissue) for 3 months. Compared to previous experiments on two-component polymeric matrices (PLGA or PDLLA) with ciprofloxacin alone, adding bioactive glass microspheres into the composite resulted in morphological changes that facilitated fluid intrusion into the microstructure and quickened ciprofloxacin release. Interpretation This type of composition of implant may fulfill the requirements of bone infection therapy, for sustained local release of the selected antibiotic over several months.://000256188900020eKoort, Jyri K. Makinen, Tatu J. Suokas, Esa Veirant, Minna Jalava, Jari Tormala, Pertti Aro, Hannu T. 1745-3674ISI:00025618|?1NLarsson, S. C. Mannisto, S. Virtanen, M. J. Kontto, J. Albanes, D. Virtamo, J.2008FCoffee and tea consumption and risk of stroke subtypes in male smokers 1681-1687Stroke396ArticleJunoBackground and Purpose-Coffee and tea consumption could potentially reduce the risk of stroke because these beverages have antioxidant properties, and coffee may improve insulin sensitivity. We examined the associations of coffee and tea consumption with risk of stroke subtypes. Methods-We used prospective data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a cohort study of 26 556 male Finnish smokers aged 50 to 69 years without a history of stroke at baseline. Coffee and tea consumption was assessed at baseline using a validated food-frequency questionnaire. During a mean follow-up of 13.6 years, from 1985 through December 2004, 2702 cerebral infarctions, 383 intracerebral hemorrhages, and 196 subarachnoid hemorrhages were ascertained from national registries. Results-After adjustment for age and cardiovascular risk factors, both consumption of coffee and tea was statistically significantly inversely associated with the risk of cerebral infarction but not intracerebral or subarachnoid hemorrhage. The multivariate relative risk of cerebral infarction for men in the highest category of coffee consumption (>= 8 cups/d) was 0.77 (95% CI, 0.66 to 0.90; P for trend < 0.001) compared with those in the lowest category (< 2 cups/d). The corresponding relative risk comparing men in the highest category of tea consumption (>= 2 cups/d) with those in the lowest category (nondrinkers) was 0.79 (95% CI, 0.68 to 0.92; P for trend = 0.002). Conclusions-These results suggest that high consumption of coffee and tea may reduce the risk of cerebral infarction among men, independent of known cardiovascular risk factors.://000256162600011eLarsson, Susanna C. Mannisto, Satu Virtanen, Mikko J. Kontto, Jukka Albanes, Demetrius Virtamo, Jarmo 0039-2499ISI:00025616д|?2vUuskula, A. Fischer, K. Raudne, R. Kilgi, H. Krylov, R. Salminen, M. Brummer-Korvenkontio, H. St Lawrence, J. Aral, S.2008LA study on HIV and hepatitis C virus among commercial sex workers in Tallinn189-191Sexually Transmitted Infections843ArticleJun,Introduction: Estonia is confronted by a dramatic expansion of the initially injection drug use-driven HIV epidemic. Little is known about HIV occurrence in population groups at high risk other than injection drug users. Objective: To obtain data on the prevalence of HIV and hepatitis C virus (HCV) among female sex workers (FSW) in Tallinn. Design: An unlinked, anonymous, cross-sectional survey of FSW recruited in Tallinn from October 2005 to May 2006. Methods: 227 FSW were recruited for the survey and biological sample collection (HIV, HCV antibodies detection) using a combination of time-location, community and respondent-driven sampling. Results: Among 227 women the HIV and HCV prevalences were 7.6% (95% CI 4.6% to 12.5%) and 7.9% (95% CI 4.5% to 12.6%), respectively. HIV prevalence was higher among FSW working in the street (odds ratio (OR) 6.4; 95% CI 1.1 to 35.6) and at the brothels and apartments supervised by the organised sex industry (OR 5.0; 95% CI 1.3 to 18.4). The duration of sex work was negatively associated with HIV prevalence (OR 0.78; 95% CI 0.63 to 0.97). Conclusions: Prevention needs of FSW in this area include increasing rates of HIV testing and putting in place effective programmes that can help extend HIV prevention behaviours across a range of sexual and drug use risk behaviours.://000256206600010vUuskula, A. Fischer, K. Raudne, R. Kilgi, H. Krylov, R. Salminen, M. Brummer-Korvenkontio, H. St Lawrence, J. Aral, S. 1368-4973ISI:00025TCl|?3]Juvonen, R. Bloigu, A. Peitso, A. Silvennoinen-Kassinen, S. Saikku, P. Leinonen, M. Harju, T.2008GRisk factors for acute respiratory tract illness in military conscripts575-580 Respirology134ArticleJunBackground and objective: Acute respiratory tract infections are the leading cause of missed service days among military conscripts. The aim of this study was to identify factors that possibly predicted and contributed to frequent respiratory tract infections among military conscripts. Methods: Data on episodes of respiratory illness were collected during the 180-day period of military service in Kajaani, Finland, between July 2004 and July 2005. Results: There were 518 military conscripts recruited, 124 of whom had a diagnosis of asthma. Conscripts with frequent (three or more) infections were more often atopic or suffered from allergic rhinitis or asthma. Overweight (BMI >= 25 kg/m(2)) and previous respiratory tract infections were the two independent risk factors for frequent respiratory infections. Overall, 4.8% of those who had no risk factors, 10. 3% of those with one risk factor and 35.7% of those with two risk factors suffered from frequent respiratory infections (P for trend < 0.001). Conclusions: Overweight (BMI >= 25 kg/m(2)) and previous respiratory tract infections are risk factors for frequent respiratory tract infections in young men during military service.://000256140200014pJuvonen, Raija Bloigu, Aini Peitso, Ari Silvennoinen-Kassinen, Sylvi Saikku, Pekka Leinonen, Maija Harju, Terttu 1323-7799ISI:000256-t|?42Zhao, L. K. Fong, Y. Granfors, K. Gu, J. R. Yu, D.2008OIdentification of cytokines that might enhance the promoter activity of HLA-B27862-868Journal of Rheumatology355ArticleMayObjective. Although the mechanism by which HLA-B27 induces ankylosing spondylitis is unclear, a minimum threshold of transcription is essential, a process controlled at the promoter. Our aim was to scan the effect of a panel of cytokines on the promoter of the HLA-1327 gene over serial timepoints. Methods. The promoter region of B*2705 gene was cloned into a luciferase reporter, stably transfected into HeLa cells, and used to monitor the serial effect of 25 cytokines. Results of HLA-B27 promoter-reporter assays were compared to those of real-time polymerase chain reactions. Results. After an initial delay, significant activation of the HLA-1327 promoter was observed with tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and IFN-beta. While early response of the HLA-B27 pro- moter was highest with TNF-alpha and IFN-gamma, ultimately the highest activity was observed with IFN-beta. Conclusion. The only promoter of HLA-B alleles studied in the past was that of HLA-B7, and always at only a single fixed timepoint of culture. This is the first study to show that activation of HLA-1327 promoter is a sequential event, and that TNF-alpha, and IFN-beta are major participants at different timepoints.://000256094800023:Zhao, Like Fong, Yoly Granfors, Kaisa Gu, Jieruo Yu, David 0315-162XISI:00025T|?5<Bots, S. Tijhuis, M. Giampaoli, S. Kromhout, D. Nissinen, A.2008xLifestyle- and diet-related factors in late-life depression - a 5-year follow-up of elderly European men: the FINE study478-484-International Journal of Geriatric Psychiatry235ArticleMayObjective Late-life depression is one of the main health problems among elderly populations and a key element of healthy ageing. Causal relationships of lifestyle- and diet-related factors in late-life depression are unclear. This study investigates prospective associations of lifestyle- and diet-related factors with development of categorically defined late-life depression in a well-documented population of elderly European men. Subjects and methods Altogether 526 not-demented and not-depressed European men aged 70-89 at baseline were included in the analyses. The association of lifestyle-related and dietary factors with development of categorically defined depression (> =48/80 on the Zung Self-rating Depression Scale) was assessed in a follow-up of 5 years. Results Eleven percent (n=59) of the men developed depression during follow-up. An independent association with development of depression was found for baseline depressive status [Odds Ratio (OR) 1.19, 95% Confidence Interval (Cl): 1.10-1.28, p < 0.0011, a decline in serum total cholesterol level between study years (OR 1.76, 95%Cl: 1.01-3.04, p=0.045), physical activity (OR 0.97, 95%Cl: 0.94-1.00, p=0.022) and moderate alcohol intake (OR 0.35, 95%Cl: 0.14-0.87, p = 0.023) but not for dietary factors. Conclusions This study of a well-documented population of elderly European men confirms that physical activity and moderate alcohol consumption may protect against depression in the old-old. Our results are the first to suggest that a decline in serum cholesterol level may predict development of late-life depression. As the effects of age, medication and incipient cognitive decline could not be entirely ruled out; this finding must be interpreted with care. Copyright (c) 2007 John Wiley & Sons, Ltd.://000256129300006OBots, Sinikka Tijhuis, Marja Giampaoli, Simona Kromhout, Daan Nissinen, Aulikki 0885-6230ISI:0002561|?6Kolz, M. Koenig, W. Mueller, M. Andreani, M. Greven, S. Illig, T. Khuseyinova, N. Panagiotakos, D. Pershagen, G. Salomaa, V. Sunyer, J. Peters, A.2008DNA variants, plasma levels and variability of C-reactive protein in myocardial infarction survivors: results from the AIRGENE study 1250-1258European Heart Journal2910ArticleMayAims C-reactive protein represents the classical acute-phase protein produced in the liver in response to inflammatory stimuli. This study evaluated the association of gene polymorphisms with differences in C-reactive protein concentrations and assessed its intra-individual variability as a marker of individual response. Methods and results One thousand and three myocardial infarction (MI) survivors were recruited in six European cities, and C-reactive protein concentrations were measured repeatedly during a 6-month period. We investigated 114 polymorphisms in 13 genes, all involved in the innate inflammatory pathway. We found two polymorphisms within the C-reactive protein (CRP) gene rs1800947 and rs1205, of which the minor alleles were strongly associated with lower levels of C-reactive protein (P < 10(-6)). A haplotype, identified by those two polymorphisms, was associated with the lowest C-reactive protein concentrations (P < 10(-6)). Additionally, the minor alleles of several variants were significantly associated with greater individual variability of C-reactive protein concentrations (P < 10(-3)). Conclusion The present study investigated the association of polymorphisms with inter- and intra-individual variability of C-reactive protein levels. Two minor alleles of C-reactive protein variants were associated with lower C-reactive protein concentrations. Regarding intra-individual variability, we observed associations with the minor alleles of several variants in selected candidate genes, including the CRP gene itself.://000256170200009Kolz, Melanie Koenig, Wolfgang Mueller, Martina Andreani, Mariarita Greven, Sonja Illig, Thomas Khuseyinova, Natalie Panagiotakos, Demosthenes Pershagen, Goeran Salomaa, Veikko Sunyer, Jordi Peters, Annette 0195-668XISI:00025D|?7Salminen, I. Alfthan, G.2008`Plasma ascorbic acid preparation and storage for epidemiological studies using TCA precipitation723-727Clinical Biochemistry419ArticleJunnObjectives: To introduce a procedure to validate an ascorbic acid method using trichloroacetic acid (TCA) for plasma stabilization at different storage temperatures. Methods: EDTA and heparin plasma were precipitated with TCA (1:5) containing 0.54 mol/L EDTA, or without. Samples were stored at 20 degrees C and -70 degrees C and their stability was tested at room temperature for 24 h. Results: A significant 40% loss (p < 0.001) of plasma ascorbic acid was found when EDTA samples with added EDTA were stored at -20 degrees C for 2-4 weeks compared with storage at -70 degrees C. Ascorbic acid in heparin plasma without added EDTA was most unstable and samples left at room temperature for 24 h lead to almost a total loss of ascorbic acid. Addition of EDTA to the TCA solution improved stability of samples of both plasma types at room temperature. Conclusion: The recommended procedure for ascorbic acid determination in plasma stabilized with TCA is immediate storage at -70 degrees C and inclusion of EDTA into the TCA solution. (c) 2008 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.://000256240100013Salminen, Irma Alfthan, Georg 0009-9120ISI:00025624̸|?8bPedersen, T. X. Bro, S. Andersen, M. H. Etzerodt, M. Jauhiainen, M. Moestrup, S. K. Nielsen, L. B.2008nEffect of treatment with human apolipoprotein-A-I on atherosclerosis in uremic apolipoprotein-E-deficient mice E131-E1310Arteriosclerosis Thrombosis and Vascular Biology286Meeting AbstractJun://000256053400533|Pedersen, Tanja X. Bro, Susanne Andersen, Michael H. Etzerodt, Michael Jauhiainen, Matti Moestrup, Soren K. Nielsen, Lars B. 1079-5642ISI:00025605|?9gMakela, S. M. Jauhiainen, M. Ala-Korpela, M. Metso, J. Lehto, T. M. Savolainen, M. J. Hannuksela, M. L.2008uHDL2 of heavy alcohol drinkers enhances cholesterol efflux from raw macrophages via phospholipid-rich HDL2b particles991-1000-Alcoholism-Clinical and Experimental Research326ArticleJunBackground: Alcohol consumption is associated with increased serum high density lipoprotein (HDL) cholesterol levels and a decreased risk for the development of atherosclerosis. However, the effects of heavy alcohol intake on reverse cholesterol transport, one of the key anti-atherogenic processes related to HDL, are poorly known. Methods: The ability of total HDL as well as HDL2 and HDL3 subclasses to promote cholesterol efflux from H-3-cholesterol-labeled RAW 264.7 macrophages was studied among 6 heavy alcohol drinkers and 6 controls. Distribution of HDL subclasses was analyzed by 4 to 30% native gradient gels. Serum phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) activities were analyzed among several other biochemical measures. Results: Cholesterol efflux to HDL2 of heavy drinkers was 22% (p = 0.025) higher relative to controls. The increase in HDL2 phospholipids, with a concomitant 2-fold (p = 0.055) increase in large HDL2b particles, was associated with enhanced cholesterol efflux to HDL2. Interestingly, the cholesterol efflux to HDL3 did not differ between the 2 study groups. These findings may be partially explained by a decreased CETP activity (-26%, p = 0.037) and an increased PLTP activity (39%, p = 0.045) in heavy drinkers. Conclusions: The increased cholesterol efflux potential of HDL2 is most likely an anti-atherogenic feature linked to heavy alcohol consumption. The cholesterol efflux and HDL phospholipids also associated strongly within the whole study group (r(s) = 0.910, p <= 0.01) suggesting a common pathway of enhanced cholesterol efflux via enlarged phospholipid-rich HDL particles.://000256116600011}Maekelae, Sanna M. Jauhiainen, Matti Ala-Korpela, Mika Metso, Jari Lehto, Tiina M. Savolainen, Markku J. Hannuksela, Minna L. 0145-6008ISI:00025<|?:_Saarikoski, S. K. Sillanpaa, M. K. Saarnio, K. M. Hillamo, R. E. Pennanen, A. S. Salonen, R. O.2008\Impact of biomass combustion on urban fine particulate matter in Central and Northern Europe265-277Water Air and Soil Pollution1911-4ArticleJunThe impact of biomass combustion on atmospheric particulate matter was investigated at Central and Northern European urban background sites (Duisburg, Prague, Amsterdam, Helsinki) in 2002-2003. In Helsinki, additional 4-week sampling campaigns were carried out during the four seasons in 2003-2004. During campaigns fine particles (PM2.5) and size-segregated samples were collected with a virtual impactor and a ten-stage Berner low-pressure impactor, respectively. From the aerosol samples monosaccharide anhydrides (MA) were determined as source specific tracers for biomass combustion. MA comprised 0.29-6.3% of the PM2.5 mass and 0.45-7.3% of its organic carbon content. According to size-segregated samples, the mean diameter of a prominent MA mode coincided with the accumulation mode of particulate mass, except for Prague where the MA mode appeared in a slightly smaller particle size range than the mass. The estimated contribution of biomass combustion to the OC and PM2.5 mass concentration was the highest in wintertime Prague, 79% and 37%, respectively. It seems that, in addition to traffic in densely populated areas, incomplete biomass combustion with current heating appliances can be a major source of particulate pollution both at local and regional scales.://000256011700020sSaarikoski, Sanna K. Sillanpaeae, Markus K. Saarnio, Karri M. Hillamo, Risto E. Pennanen, Arto S. Salonen, Raimo O. 0049-6979ISI:0002560|?;Palmu, A. Jokinen, J. Kilpi, T.2008wImpact of different case definitions for acute odds media on the efficacy estimates of a pneumococcal conjugate vaccine 2466-2470Vaccine2620ArticleMayfConsiderably higher vaccine efficacy estimate for clinical acute otitis media (AOM) has been obtained for the 11-valent pneumococcal conjugate vaccine with protein D of Haemophilus influenzae as a carrier (PncPD11) in the POET study than for the 7-valent pneumococcal conjugate vaccine (PncCRM7) in the Finnish Otitis Media (FinOM) Vaccine Trial. We recalculated PncCRM7 efficacy from the FinOM data using a case definition for AOM very close to the POET definition and a definition giving an incidence for AOM in the control group comparable to that obtained in the POET study. The different case definitions had only a slight impact on the vaccine efficacy estimates compared to the original case definitions. We were not able to show that the differences between the study results would be due to the case definitions used. (c) 2008 Elsevier Ltd. All rights reserved.://000256074200003&Palmu, Art Jokinen, Jukka Kilpi, Terhi 0264-410XISI:00025607}k|?<;Erkkila, L. Saario, E. Laitinen, K. Saikku, P. Leinonen, M.2008cIntragastric primary infection sensitizes to lung reinfection in a Chlamydia pneumoniae mouse model 2503-2509Vaccine2620ArticleMayThe most frequently used infection route in Chlamydia pneumoniae animal models is intranasal (i.n.), while the intragastric (i.g.) infection route has not been studied previously. The aim of the present study was to examine the course of Chlamydia pneumoniae infection in mice infected via the i.g. route and to compare the outcome of i.n. reinfection in these mice to i.n. reinfection of primarily i.n. infected mice. C57BL/6JBom mice were used, and the infection was monitored using chlamydial culture, C. pneumoniae PCR and histological examination of several tissues, and antibody measurements. C. pneumoniae was able to disseminate from the gastrointestinal tract to other organs, and i.g. inoculation led to an immunological response. In addition, the primary i.g. challenge made mice more susceptible to i.n. reinfection. In conclusion, the results suggest that the nature of the immune response to a previous C. pneumoniae infection affects the outcome of reinfection. (c) 2008 Elsevier Ltd. All rights reserved.://000256074200007KErkkilae, Leena Saario, Elise Laitinen, Kirsi Saikku, Pekka Leinonen, Maija 0264-410XISI:00025А|?=:Nyberg, S. D. Meurman, O. Jalava, J. Rantakokko-Jalava, K.2008Evaluation of detection of extended-spectrum beta-lactamases among Escherichia coli and Klebsiella spp. isolates by VITEK 2 AST-N029 compared to the agar dilution and disk diffusion methods355-362+Scandinavian Journal of Infectious Diseases405ArticleA total of 123 clinical Escherichia coli and Klebsiella spp. isolates were included in the study in order to evaluate VITEK 2 AST-N029 (Nordic) card for detection of extended-spectrum beta-lactamases (ESBL) and to compare the results with genotypic ESBL verification. The results were also compared to alternative phenotypic methods, i.e. agar dilution and disk diffusion. The strains that were ESBL-positive according to AST-N029 were further analysed with the ESBL test card, VITEK 2 AST-N041. Using genotype as reference, Vitek 2 AES had the highest accuracy of the tested methods in classifying the strains as ESBL-positive or -negative (91.1%). When VITEK 2 gave ESBL as the only option for E. coli or K. pneumoniae, 44 of 45 (97.8%) strains had an ESBL gene. VITEK 2 achieved an accuracy of 94.9% and disk diffusion 95.9% compared to the agar dilution method as the phenotypic reference method for the E. coli and K. pneumoniae strains. For the K. oxytoca strains VITEK 2 achieved the highest accuracy (84.0%) of the methods used in this work.://000255955900001DNyberg, Sofia D. Meurman, Olli Jalava, Jari Rantakokko-Jalava, Kaisu 0036-5548ISI:0002559w(|?>Loukola, A. Broms, U. Maunu, H. Widen, E. Heikkila, K. Siivola, M. Salo, A. Pergadia, M. L. Nyman, E. Sammalisto, S. Perola, M. Agrawal, A. Heath, A. C. Martin, N. G. Madden, P. A. F. Peltonen, L. Kaprio, J.2008sLinkage of nicotine dependence and smoking behavior on 10q, 7q and 11p in twins with homogeneous genetic background209-219Pharmacogenomics Journal83ArticleJunThe significant worldwide health burden introduced by tobacco smoking highlights the importance of studying the genetic determinants of smoking behavior and the key factor sustaining compulsive smoking, that is, nicotine dependence (ND). We have here addressed the genetic background of smoking in a special study sample of twins, harmonized for early life events and specifically ascertained for smoking from the nationwide twin cohort of the genetically unique population of Finland. The twins and their families were carefully examined for extensive phenotype profiles and a genome-wide scan was performed to identify loci behind the smoking status, ND and the comorbid phenotype of ND and alcohol use in 505 individuals from 153 families. We replicated previous linkage findings on 10q (max logarithm of the odds (LOD) 3.12) for a smoker phenotype, and on 7q and 11p (max LOD 2.50, and 2.25, respectively) for the ND phenotype. The loci linked for ND also showed evidence for linkage for the comorbid phenotype. Our study provides confirmatory evidence for the involvement of these genome regions in the genetic etiology of smoking behavior and ND and for the first time associates drinking and smoking to a shared locus on 10q.://000256068100005Loukola, A. Broms, U. Maunu, H. Widen, E. Heikkila, K. Siivola, M. Salo, A. Pergadia, M. L. Nyman, E. Sammalisto, S. Perola, M. Agrawal, A. Heath, A. C. Martin, N. G. Madden, P. A. F. Peltonen, L. Kaprio, J. 1470-269XISI:00025606Ϙ|??Lindstrom, J. Uusitupa, M.2008<Lifestyle intervention, diabetes, and cardiovascular disease 1731-1733Lancet3719626Editorial MaterialMay://000256103400008 Lindstrom, Jaana Uusitupa, Matti 0140-6736ISI:000256 62356012595.014 356003095.014 62356008995.014 6/1769 [pii]eng kwn105 [doi]Eng 5.004 [doi]eng 62277000171.929  34005337.221 -9-146 [doi]eng 67.x [doi]eng 64272000061.557  01000132.072  87000012.980 60163000047.851 64894000052.448 61702000097.924  160 [doi]eng  01000051.185 dyn012 [doi]eng rmar@utu.fieng 63131000151.524 3200 [doi]eng 54.x [doi]eng 65265000051.207 60571000034.432 796000195.060 695000065.535 60948000233.151 10340000828.638  621200001925.556 7531 [doi]Eng 63555000062.314  81000054.968 000286 [doi]eng 1402000141.847 559000011.209 62066000102.616  26000116.296 5003000092.246  42000033.377 117000201.224  54000093.4274 years, the increase was largest, at 4.7% more affected every year. The overall boy-to-girl ratio of incidence was 1 . 1; at the age of 13 years, it was 1 . 7 (1-4-2-0). The predicted cumulative number of new cases with type 1 diabetes before 15 years of age between 2006 and 2020 was about 10 800. Interpretation The incidence of type 1 diabetes in Finnish children is increasing even faster than before. The number of new cases diagnosed at or before 14 years of age will double in the next 15 years and the age of onset will be younger (0-4 years). Funding Academy of Finland, Sigrid Juselius Foundation, Juvenile Diabetes Research Foundation.://0002561034000322Harjutsalo, Valma Sjoberg, Lena Tuomilehto, Jaakko 0140-6736ISI:000256103400032|?AnPesonen, A. K. Raikkonen, K. Heinonen, K. Andersson, S. Hovi, P. Jarvenpaa, A. L. Eriksson, J. G. Kajantie, E.2008`Personality of young adults born prematurely: the Helsinki study of very low birth weight adults609-617*Journal of Child Psychology and Psychiatry496ArticleJunBackground: Today, the first generations of very low birth weight (VLBW <= 1500 g) infants are entering adulthood but very little is known of their personality traits, associated with both psychopathological vulnerability and resilience. Methods: In this cohort study we compared personality traits among young adults (age range 18 to 27 years, mean 21.4, SD 2.19) with VLBW (n = 158) with those of term-born controls (n = 168) of same gender, age, and maternity hospital. The participants completed the Neo-Personality Inventory. Results: Of the five main traits, the VLBW participants scored significantly higher in conscientiousness (MD .1, 95% CI .0 to .3; p < .03), agreeableness (MD .2, 95% CI .0 to .3; p < .001), and lower in openness to experience (MD -.1, 95% CI -.2 to .0; p < .02). In addition, the VLBW group differed from the controls with regard to facets of neuroticism (lower hostility and impulsivity, ps < .05) and extraversion (less assertiveness p < .01). Furthermore, there were fewer undercontrolled personality profiles among the VLBW subjects (p < .01). All differences were independent of gender, age at assessment, parental education, individual school grade average, and maternal pre-eclampsia and smoking during pregnancy. Conclusions: Young adults born with VLBW showed markedly different personality traits compared with their controls. The VLBW group displayed less negative emotions, were more dutiful and cautious, and displayed more warmth in their social relationships than their term-born peers. We present two potential mechanisms underlying these findings. The first relates to parental influences and the other to evidence linking biological mechanisms associated with prematurity with personality characteristics in adulthood.://000256057100003Pesonen, Anu-Katriina Raikkonen, Katri Heinonen, Kati Andersson, Sture Hovi, Petteri Jarvenpaa, Anna-Liisa Eriksson, Johan G. Kajantie, Eero 0021-9630ISI:000257|?B(Patja, K. Sund, R. Kaski, M. Pukkala, E.2008DCancer incidence among persons with Prader-Willi syndrome in Finland69-729International Journal on Disability and Human Development71ArticleJan-MarPrader-Willi syndrome (PWS) is an inherited, genetic condition with an incidence of 1 in 26-28,000 and most common hereditary reason for life threatening obesity. There is a base to consider increased risk of cancer in PWS. Methods: Persons with PWS (n = 56) were identified from the Finnish registry on persons with ID. Follow-up for cancer incidence was performed in the Finnish Cancer Registry with personal identifier as linkage keys. Results: There were three cancers (acute lymphatic leukemia, testicular cancer and breast cancer) during the follow up; the expected number based on average Finnish population was 1.51 (SIR 2,0, CI95% 0.4-5.8). There is a possibility of increased risk of cancer among persons with PWS.://0002559710000117Paja, Kristiina Sund, Reijo Kaski, Markus Pukkala, Eero 1565-012XISI:000255971000011s|?CuKarinen, L. Leinonen, M. Bloigu, A. Paldanius, M. Koskela, P. Saikku, P. Hartikainen, A. L. Jarvelin, M. R. Pouta, A.2008uMaternal serum Chlamydia pneumoniae antibodies and CRP levels in women with preeclampsia and gestational hypertension143-158Hypertension in Pregnancy272ArticleaObjective. To determine whether Chlamydia pneumoniae antibodies and highly sensitive C-reactive protein (hsCRP) levels in maternal sera are associated with preeclampsia or gestational hypertension. Methods. C. pneumoniae antibodies and hsCRP levels were measured in maternal serum during first trimester (mean, 10.4 weeks of gestation) using the microimmunofluorescence (MIF) test and a highly sensitive immunoenzymometric assay, respectively. Results. No differences in the IgG antibody levels against C. pneumoniae or hsCRP levels were seen between the women with preeclampsia or gestational hypertension and those in the reference group. However, the women with preeclampsia and preterm delivery had serum IgG antibodies to C. pneumoniae (IgG titre 32) significantly more often in their first trimester sera compared with women having preeclampsia and full-term deliveries (p = 0.03). In addition, the proportion of subjects with C. pneumoniae IgG antibodies (IgG titre 32) and/or elevated CRP levels (3.8 mg/L, upper quartile) was double among the women with preeclampsia and elective preterm delivery compared with the women with preeclampsia who delivered at term (p = 0.01). Conclusion. Our results suggest that chronic C. pneumoniae infection and systemic low-grade inflammation may be associated with preeclampsia requiring elective delivery before 37 weeks gestation.://000256000100005Karinen, Liisa Leinonen, Maija Bloigu, Aini Paldanius, Mika Koskela, Pentti Saikku, Pekka Hartikainen, Anna-Liisa Jarvelin, Marjo-Riitta Pouta, Anneli 1064-1955ISI:00025600|?DgFinnon, P. Robertson, N. Dziwura, S. Raffy, C. Zhang, W. Ainsbury, L. Kaprio, J. Badie, C. Bouffler, S.2008aEvidence for significant heritability of apoptotic and cell cycle responses to ionising radiation485-493Human Genetics1235ArticleJunGenetic factors are likely to affect individual cancer risk, but few quantitative estimates of heritability are available. Public health radiation protection policies do not in general take this potentially important source of variation in risk into account. Two surrogate cellular assays that relate to cancer susceptibility have been developed to gain an insight into the role of genetics in determining individual variation in radiosensitivity. These flow cytometric assays for apoptosis induction and cell cycle delay following radiation are sufficiently sensitive to distinguish lymphocytes from a healthy donor population from those of a sample of obligate carriers of ATM mutations (P = 0.01 and P = 0.02, respectively). Analysis of 54 unselected twin pairs (38 dizygotic, 16 monozygotic) indicated much greater intrapair correlation in response in monozygotic than in dizygotic pairs. Structural equation modelling indicated that models including unique environmental factors only fitted the data less well than those incorporating two or more of additive genetic factors, common environmental factors and unique environmental factors. A model incorporating additive genetic factors and unique environmental factors yielded estimates of heritability for the two traits of 68% (95% CI 40-82%, cell cycle) and 59% (95% CI 22-79%, apoptosis). Thus, these data suggest that genetic factors contribute significantly to human variation in these two measures of radiosensitivity that relate to cancer susceptibility.://000256080600007Finnon, Paul Robertson, Naomi Dziwura, Sylwia Raffy, Claudine Zhang, Wei Ainsbury, Liz Kaprio, Jaakko Badie, Christophe Bouffler, Simon 0340-6717ISI:00025 ̈́|?ELindstrom, J. Peltonen, M. Eriksson, J. G. Aunola, S. Hamalainen, H. Ilanne-Parikka, P. Keinanen-Kiukaanniemi, S. Uusitupa, M. Tuomilehto, J.2008eDeterminants for the effectiveness of lifestyle intervention in the Finnish diabetes prevention study857-862 Diabetes Care315ArticleMayOBJECTIVE - intensive lifestyle intervention significantly reduced diabetes incidence among the participants in the Finnish Diabetes Prevention Study. We investigated whether and to what extent risk factors for type 2 diabetes and other baseline characteristics of the study participants modified the effectiveness of the lifestyle intervention. RESEARCH DESIGN AND METHODS - Overweight, middle-aged volunteers with impaired glucose tolerance were randomly assigned to intensive lifestyle intervention (n = 265) or to a control group (n = 257) for a median of 4 years. Diabetes status was ascertained annually with repeated oral glucose tolerance testing. Incidence rates of diabetes and hazard ratios (HRs) comparing the intervention group with the control group were calculated by sex and baseline tertiles of age, BMI, waist circumference, plasma glucose concentration at fastiing and 2 h after a glucose load, fasting serum insulin and insulin resistance index, and categories of composite baseline Finnish Diabetes Risk Score (FINDRISC). Interactions between the intervention assignment and baseline risk factors on diabetes risk were analyzed. RESULTS - The intervention was most effective among the oldest individuals (HRs 0.77, 0.49, and 0.36 by increasing age tertiles, respectively; P-interaction = 0-0130) and those with a high baseline FINDRISC (HRs 1.09, 0.84, 0.34, and 0.22 by increasing risk score category, respectively; P-interaction = 0.0400). The effect of the intervention on diabetes risk was not modified by other baseline characteristics or risk factors. CONCLUSIONS - The FINDRISC maybe useful in identifying high-risk groups most likely to benefit from intensive lifestyle intervention to prevent type 2 diabetes.://000256016300004Lindstrom, Jaana Peltonen, Markku Eriksson, Johan G. Aunola, Sirkka Hamalainen, Helena Ilanne-Parikka, Pirjo Keinanen-Kiukaanniemi, Sirkka Uusitupa, Matti Tuomilehto, Jaakko 0149-5992ISI:00025|?F&Savilahti, E. Kuitunen, M. Vaarala, O.2008BPre and probiotics in the prevention and treatment of food allergy243-2482Current Opinion in Allergy and Clinical Immunology83ReviewJunPurpose of the review Recent studies on the pathogenesis of allergy in both man and experimental animals continue to show the importance of commensal bacteria in the gastrointestinal tract in stimulating and directing the immune system. The interest in modulating commensal bacterial flora with prebiotics and probiotics to prevent and treat food allergy has multiplied in recent years. Recent findings Studies on prevention suggest that probiotic supplementation reduces IgE-associated eczema. It seems that prenatal administration is of importance. Colonization seems to be readily achieved, so there is proof of concept. However, after cessation of the administration, a rapid decline in colonization is evident. IgE sensitization in atopic eczema is a risk factor for allergic airways disease, and the reduced IgE-associated atopic eczema demonstrated may be an indication of less respiratory allergic disease later. Administration of probiotics to children with allergy or at risk of allergy seems to stimulate a low-grade inflammation by activating the innate immune system and further production of IL-10. Summary Modulation of commensal bacteria of the gut with probiotics has been shown to modulate the immune system and to have an effect on both the prevention and treatment of food allergy. The effects have been highly variable depending on the mode of treatment and the optimal treatment remains unsettled at present.://000255931800006/Savilahti, Erkki Kuitunen, Mikael Vaarala, Outi 1528-4050ISI:0002559318000063.378PKQa8I/**refs.FRM 0B< !// !HPRIMARYyearIndex 6ByP/) idreference_type text_stylesauthoryear title pages secondary_title volume numbernumber_of_volumessecondary_authorplace_published publishersubsidiary_authoredition keywords type_of_workdate2)  abstractlabelurltertiary_titletertiary_author notes isbn custom_1 custom_2 custom_3 custom_4alternate_titleaccession_number call_number short_title custom_5 custom_6sectionoriginal_publicationH) reprint_editionreviewed_itemauthor_addressimagecaption custom_7 electronic_resource_number link_to_pdf translated_author translated_titlename_of_databasedatabase_providerresearch_notes language access_datelast_modified_date !! H!H!H! (H! 3H! >H! IH! TH!_H!jH!uH! H!H!H! H! H!H! H!H!H!H!H! H! H! H! H! %H! 0H!;H!FH! 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