PKf>:6[hhrefs.MYD |?bBattie, M. C. Videman, T. Kaprio, J. Gibbons, L. E. Gill, K. Manninen, H. Saarela, J. Peltonen, L.2009KThe Twin Spine Study: Contributions to a changing view of disc degeneration47-59 Spine Journal91ArticleJan BACKGROUND CONTEXT: Disc degeneration was commonly viewed over much of the last century as a result of aging and "wear and tear" from mechanical insults and injuries. Thus, prevention strategies and research in lumbar degenerative changes and associated clinical conditions focused largely on mechanical factors as primary causes using an "injury model." The Twin Spine Study. a research program on the etiology and pathogenesis of disc degeneration, has contributed to a substantial revision of this view of determinants of lumbar disc degeneration. PURPOSE: To provide a review of the methods and findings of the Twin Spine Study project. STUDY DESIGN/SETTING: Narrative review of the Twin Spine Study. METHODS: The Twin Spine Study, which started in 1991, is a multidisciplinary, multinational research project with collaborators primarily in Canada, Finland, and the United States. The most significant investigations related to determinants of disc degeneration included occupational exposures, driving and whole-body vibration exposure, smoking exposure, anthropomorphic factors. heritability, and the identification of genotypes associated with disc degeneration. RESULTS: Among the most significant findings were a substantial influence of heredity on lumbar disc degeneration and the identification of the first gene forms associated with disc degeneration. Conversely, despite extraordinary discordance between twin siblings in occupational and leisure-time physical loading conditions throughout adulthood, surprisingly little effect on disc degeneration was observed. Studies on the effects of smoking on twins with large discordance in smoking exposure demonstrated an increase in disc degeneration associated with smoking, but this effect was small. No evidence was found to suggest that exposure to whole-body vibration through motorized vehicles leads to accelerated disc degeneration in these well-controlled studies. More recent results indicate that the effect of anthropometric factors, such as body weight and muscle strength on disc degeneration, although modest, appear in this work to be greater than those of occupational physical demands. In fact, some indications were found that routine loading may actually have some benefits to the disc. CONCLUSIONS: The once commonly held view that disc degeneration is primarily a result of aging and "wear and tear" from mechanical insults and injuries was not supported by this series of studies. Instead, disc degeneration appears to be determined in great part by genetic influences. Although environmental factors also play a role, it is not primarily through routine physical loading exposures (eg, heavy vs. light physical demands) as once suspected. (C) 2009 Elsevier Inc. All rights reserved.://000262378500007}Battie, Michele C. Videman, Tapio Kaprio, Jaakko Gibbons, Laura E. Gill, Kevin Manninen, Hannu Saarela, Janna Peltonen, Leena 1529-9430ISI:00026237850000710.1016/j.spinee.2008.11.011|?VHaapasalo, K. Jarva, H. Siljander, T. Tewodros, W. Vuopio-Varkila, J. Jokiranta, T. S.2008zComplement factor H allotype 402H is associated with increased C3b opsonization and phagocytosis of Streptococcus pyogenes583-594Molecular Microbiology703ArticleNovThe main virulence factor of group A streptococcus (GAS), M protein, binds plasma complement regulators factor H (FH) and FH-like protein 1 (FHL-1) leading to decreased opsonization. The M protein binding site on FH is within domain 7 in which also the age-related macular degeneration (AMD)-associated polymorphism Y402H is located. We studied if FH allotypes 402H and 402Y have different binding affinities to GAS. Plasma-derived FH allotype 402H and its recombinant fragment FH5-7(402H) showed decreased binding to several GAS strains. Growth of GAS in human blood taken from FH(402H) homozygous individuals was decreased when compared with blood taken from FH(402Y) homozygous individuals. The effect of the allotype 402H can be explained by combining the previous M protein mutagenesis data and the recently published crystal structure of FH6-8. In conclusion the data indicate that the AMD-associated allotype 402H leads to diminished binding of FH to GAS and increased opsonophagocytosis of the bacteria in blood. These results suggest that the homozygous presence of the allele 402H could be associated with decreased risk for severe GAS infections offering an explanation for the high frequency of the allele despite its association with visual impairment.://000262305000005lHaapasalo, Karita Jarva, Hanna Siljander, Tuula Tewodros, Wezenet Vuopio-Varkila, Jaana Jokiranta, T. Sakari 0950-382XISI:0002623050000055.462 10.1111/j.1365-  |?Nakanishi, S. Vikstedt, R. Soderlund, S. Lee-Rueckert, M. Hiukka, A. Ehnholm, C. Muilu, M. Metso, J. Naukkarinen, J. Palotie, L. Kovanen, P. T. Jauhiainen, M. Taskinen, M. R.2009{Serum, but not monocyte macrophage foam cells derived from low HDL-C subjects, displays reduced cholesterol efflux capacity183-192Journal of Lipid Research502ArticleFebKThe main antiatherogenic function of HDL is to promote the efflux of cholesterol from peripheral cells and transport it to the liver for excretion in a process termed reverse cholesterol transport. The aim of this study was to evaluate the cholesterol efflux capacity in low- and high-HDL subjects by utilizing monocytes and serum from 18 low-HDL and 15 high-HDL subjects. Low and high HDL levels were defined, respectively, as HDL <= 10(th) and HDL <= 90(th) Finnish age/sex-specific percentile. Cholesterol efflux from [H-3]cholesterol-oleate-acetyl-LDL-loaded monocyte-derived macrophages to standard apolipoprotein A-I ( apoA-I), HDL2, and serum was measured. In addition, cholesterol efflux from acetyl-LDL-loaded human THP-1 macrophages to individual sera ( 0.5%) derived from the study subjects was evaluated. Cholesterol efflux to apoA-I, HDL2, and serum from macrophage foam cells derived from low- and high-HDL subjects was similar. The relative ABCA1 and ABCG1 mRNA expression levels in unloaded macrophages, as well as their protein levels in loaded macrophage foam cells, were similar in the two study groups. Cholesterol efflux from THP-1 foam cells to serum recovered from high-HDL subjects was slightly higher than that to serum from low- HDL subjects ( P = 0.046). Cholesterol efflux from THP-1 macrophages to serum from study subjects correlated with serum apoB ( P = 0.033), apoA-I ( P=0.004), apoA-II ( P<0.0001), and the percentage of apoA-I present in the form of pre beta-HDL ( P = 0.0001). Our data reveal that macrophages isolated from either low- or high-HDL subjects display similar cholesterol efflux capacity to exogenous acceptors. However, sera from low-HDL subjects have poorer cholesterol acceptor ability as compared with sera from high-HDL subjects. - Nakanishi, S., R. Vikstedt, S. Soderlund, M. Lee-Rueckert, A. Hiukka, C. Ehnholm, M. Muilu, J. Metso, J. Naukkarinen, L. Palotie, P. T. Kovanen, M. Jauhiainen, and M-R. Taskinen. Serum, but not monocyte macrophage foam cells derived from low HDL-C subjects, displays reduced cholesterol efflux capacity. J. Lipid Res. 2009. 50: 183-192.://000262500800001Nakanishi, Shuhei Vikstedt, Riikka Soderlund, Sanni Lee-Rueckert, Miriam Hiukka, Anne Ehnholm, Christian Muilu, Mikko Metso, Jari Naukkarinen, Jussi Palotie, Leena Kovanen, Petri T. Jauhiainen, Matti Taskinen, Marja-Riitta 0022-2275ISI:0002625008000014.33610.1194/jlr 8|?Kivipelto, M. Rovio, S. Ngandu, T. Kareholt, I. Eskelinen, M. Winblad, B. Hachinski, V. Cedazo-Minguez, A. Soininen, H. Tuomilehto, J. Nissinen, A.2008[Apolipoprotein E epsilon 4 magnifies lifestyle risks for dementia: a population-based study 2762-2771*Journal of Cellular and Molecular Medicine126BArticleDecThe risk of dementia and Alzheimer's disease (AD) probably results from an interaction between genetic and environmental factors. The aim of this study was to investigate the effects and putative interactions between the apoE epsilon 4 allele and lifestyle related risk factors for dementia and AD. Participants of the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study were derived from random, population-based samples previously studied in 1972, 1977, 1982 or 1987. After an average follow-up of 21 years, 1449 individuals (72.5%) aged 65-79 years were re-examined in 1998. The apoE epsilon 4 allele was an independent risk factor for dementia/AD even after adjustments for sociodemographic, lifestyle and vascular factors (odds ratio [OR] = 2.83, 95% confidence interval [CI] epsilon 1.61-4.97). Physical inactivity, alcohol drinking and smoking increased the risk of dementia/AD particularly among the apoE epsilon 4 carriers. Furthermore, low-moderate intake of polyunsaturated, and moderate-high intake of saturated fats were associated with an increased risk of dementia/AD more pronouncedly among apoE epsilon 4 carriers. Composite effect of the lifestyle factors was particularly seen among the epsilon 4 carriers (OR = 11.42, 95% CI = 1.94-67.07 in the 4(th) quartile). Physical inactivity, dietary fat intake, alcohol drinking and smoking at midlife are associated with the risk of dementia and AD, especially among the apoE epsilon 4 carriers. The apoE epsilon 4 carriers may be more vulnerable to environmental factors, and thus, lifestyle interventions may greatly modify dementia risk particularly among the genetically susceptible individuals.://000262311700019Kivipelto, Miia Rovio, Suvi Ngandu, Tiia Kareholt, Ingemar Eskelinen, Marjo Winblad, Bengt Hachinski, Vladimir Cedazo-Minguez, Angel Soininen, Hilkka Tuomilehto, Jaakko Nissinen, Aulikki 1582-1838ISI:0002623117000196.807 10.1111/j.1582-49|?EMustelin, L. Silventoinen, K. Pietilainen, K. Rissanen, A. Kaprio, J.2009wPhysical activity reduces the influence of genetic effects on BMI and waist circumference: a study in young adult twins29-36 International Journal of Obesity331ArticleJanObjective: Both obesity and exercise behavior are influenced by genetic and environmental factors. However, whether obesity and physical inactivity share the same genetic vs environmental etiology has rarely been studied. We therefore analyzed these complex relationships, and also examined whether physical activity modifies the degree of genetic influence on body mass index (BMI) and waist circumference (WC). Methods: The FinnTwin16 Study is a population-based, longitudinal study of five consecutive birth cohorts (1975-1979) of Finnish twins. Data on height, weight, WC and physical activity of 4343 subjects at the average age of 25 (range, 22-27 years) years were obtained by a questionnaire and self-measurement of WC. Quantitative genetic analyses based on linear structural equations were carried out by the Mx statistical package. The modifying effect of physical activity on genetic and environmental influences was analyzed using gene-environment interaction models. Results: The overall heritability estimates were 79% in males and 78% in females for BMI, 56 and 71% for WC and 55 and 54% for physical activity, respectively. There was an inverse relationship between physical activity and WC in males (r = -0.12) and females (r = -0.18), and between physical activity and BMI in females (r = -0.12). Physical activity significantly modified the heritability of BMI and WC, with a high level of physical activity decreasing the additive genetic component in BMI and WC. Conclusions: Physically active subjects were leaner than sedentary ones, and physical activity reduced the influence of genetic factors to develop high BMI and WC. This suggests that the individuals at greatest genetic risk for obesity would benefit the most from physical activity.://000262377300006EMustelin, L. Silventoinen, K. Pietilainen, K. Rissanen, A. Kaprio, J. 0307-0565ISI:0002623773000063.56010.1 , |?Kallio, P. Tolppanen, A. M. Kolehmainen, M. Poutanen, K. Lindstrom, J. Tuomilehto, J. Kuulasmaa, T. Kuusisto, J. Pulkkinen, L. Uusitupa, M.2009uAssociation of sequence variations in the gene encoding insulin-like growth factor binding protein 5 with adiponectin80-88 International Journal of Obesity331ArticleJanBackground: Insulin-like growth factor binding protein 5 (IGFBP5) binds to IGF and thus modulates IGF signaling pathway. We have shown earlier that the IGFBP5 gene was downregulated in the adipose tissue after 12-week carbohydrate diet with low insulinemic response. Objective: The aim was to examine the putative contribution of genetic variation of the IGFBP5 gene to the characteristics of metabolic syndrome and incidence of type 2 diabetes (T2DM) in the Finnish Diabetes Prevention Study (DPS). Methods: DPS is a longitudinal study where 522 subjects with impaired glucose tolerance were randomized to either lifestyle intervention group or control group. DNA was available from 507 subjects ( mean body mass index (BMI) 31.2 +/- 4.5 kg/m(2), age 55 +/- 7 years). The eight single-nucleotide polymorphisms ( SNPs) were selected from HapMap database and genotyped by Taqman allelic discrimination protocol. The main results were confirmed in a larger cross-sectional study population (METSIM). In addition, the gene expression of IGFBP5 was studied in two previously published study populations (FUNGENUT and GENOBIN) of 124 subjects with insulin resistance (BMI 32.2 +/- 3.5 kg/m(2), age 57.7 +/- 7.4 years). Results: Three out of eight IGFBP5 markers (rs9341234, rs3276 and rs11575134) were significantly associated with circulating adiponectin concentrations in men. Furthermore, mRNA expression studies of subcutaneous adipose tissue showed that mRNA concentrations of IGFBP5 correlated with adiponectin concentrations in all subjects and in women. None of the IGFBP5 SNPs were associated with T2DM. Conclusions: Our findings show that IGFBP5 has a gender-specific association with adiponectin, which may modulate the development of metabolic syndrome.://000262377300013Kallio, P. Tolppanen, A-M Kolehmainen, M. Poutanen, K. Lindstrom, J. Tuomilehto, J. Kuulasmaa, T. Kuusisto, J. Pulkkinen, L. Uusitupa, M. 0307-0565ISI:0002623773000133.56010.!F|?1Roos, A. Kumpulainen, S. Jarvelin, K. Hedlund, T.2008@The information environment of researchers in molecular medicine8Information Research-an International Electronic Journal133ArticleSepIntroduction. Describes and analyses the information environment of research work in molecular medicine. We presume an interdependence between the information environment, the research process and the related work tasks. Method. This is a qualitative case study using mixed methods. Empirical data were gathered using two surveys and six semi-structured thematic interviews. Analysis. Analysis was carried out on the merged data of the two surveys. Respondents were divided into groups and information resources were categorized. Results. The information environment consists of broad categories of data, tools, published material and interpersonal communication. The usage of portals and other integrated resources was substantial. The role of PubMed was central in searching scientific facts. Google was used to locate general Web pages, research groups, methods and tools. Interpersonal communication seemed to be effective in providing information about methods and tools among groups which do laboratory work. The problems reported concerned lack of knowledge about useful resources and how to use them properly, some query formulation problems were also reported, e. g. problems with acronyms, personal names and gene name synonymy. Conclusions. The information related tasks occupied much of the researchers' time. If information problems were solved, more time to the research would be released. The database and tool interfaces should be easier to use.://000262254300007ARoos, Annikki Kumpulainen, Sanna Jarvelin, Kalervo Hedlund, Turid 1368-1613ISI:000262254300007353'|? Kajantie, E.2008#Early-life events. Effects on aging101-113>Hormones-International Journal of Endocrinology and Metabolism72ReviewApr-Jun$During the last two decades, a considerable body of evidence has emerged showing that circumstances during the fetal period and childhood may have lifelong programming effects on different body functions with a considerable impact on disease susceptibility. From a medical point of view, these long-term effects are today referred to as the Developmental Origins of Health and Disease (DOHaD) concept. The DOHaD concept may have a fundamental impact on our ideas about when and how to intervene in order to prevent aging-related loss of function and disease. The aim of this review is to provide a synopsis of epidemiological findings relating early-life conditions with key aging-related disorders, including cardiovascular disease, type 2 diabetes, depression, cognitive impairments and osteoporosis. There are several mechanisms that have been suggested as linking early-life events with late-life disease. This review will discuss programming of the hypothalamic-pituitary-adrenal axis function as one of the best characterised examples of such mechanisms.://000262363600001Kajantie, Eero 1109-3099ISI:000262363600001F7|? FPetkeviciene, J. Simila, M. Becker, W. Kriaucioniene, V. Valsta, L. M.2009KValidity and reproducibility of the NORBAGREEN food frequency questionnaire141-149&European Journal of Clinical Nutrition631ArticleJanObjective: To measure the validity and reproducibility of the NORBAGREEN food frequency questionnaire (FFQ). Subjects/methods: In Finland, 125 subjects aged 25-64 years sampled from the five main regions of the FINDIET 2002 Study and in Lithuania, 99 citizens of Kaunas aged 19-75 years participated in the study. Reference methods for the FFQ were two 3-day FFQs in Finland and four 24-h recalls in Lithuania. The FFQ was repeated after 6-8 months in both countries. The outcome of the FFQ1 was correlated with the outcome of the reference methods and with the outcome of repeated FFQ2. Cross-classification of food intakes by FFQ1 and the reference methods was examined in tertiles. Results: Validity correlations (FFQ vs the reference method, Spearman's correlation) were for vegetables, fruit and bread 0.50 (P<0.01), 0.53 (P<0.01) and 0.54 (P<0.01) in Finland; and 0.55 (P<0.01), 0.31 (P<0.01) and 0.51 (P<0.01) in Lithuania, respectively. Correlations were smaller for potatoes and fish. The overall proportion categorized in the same or adjacent intake tertiles with the two instruments was over 83% in both countries. Reproducibility correlations varied between 0.51 and 0.75 in the Finnish study, and between 0.51 and 0.83 in the Lithuanian study. Conclusions: The NORBAGREEN FFQ can be used to rank subjects according to vegetable, fruit and bread consumption. Questions on fish and potato consumption need to be developed further.://000262293700019FPetkeviciene, J. Simila, M. Becker, W. Kriaucioniene, V. Valsta, L. M. 0954-3007ISI:0002622937000192.32610.1038/2#|? Verta, M. Kiviranta, H. Salo, S. Malve, O. Korhonen, M. Verkasalo, P. K. Ruokojarvi, P. Rossi, E. Hanski, A. Paatalo, K. Vartiainen, T.2009fA decision framework for possible remediation of contaminated sediments in the River Kymijoki, Finland95-105,Environmental Science and Pollution Research161ArticleJanThe paper describes the spatial contamination of the River Kymijoki, South-Eastern Finland, and the coastal region of the Gulf of Finland with PCDD/Fs and mercury. The findings of ecotoxicologial and human health studies are also reported, including environmental and human risk assessments. Sediments from the River Kymijoki, draining into the Gulf of Finland, have been heavily polluted by the pulp and paper industry and by chemical industries. A wood preservative, known as Ky-5, was manufactured in the upper reaches of the river between 1940 and 1984 causing severe pollution of river sediments with polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF). Moreover, the sediments have been polluted with mercury (Hg) from chlor-alkali production and the use of Hg as a slimicide in pulp and paper manufacturing. An extensive sediment survey was conducted as well as sediment transport modeling, toxicity screening of sediment invertebrates, and a survey of contaminant bioaccumulation in invertebrates and fish. Studies on human exposure to PCDD/Fs and the possible effects on hypermineralization of teeth as well as an epidemiological study to reveal increased cancer risk were also conducted. An assessment of the ecological and human health risks with a null hypothesis (no remediation) was undertaken. The sediment survey revealed severe contamination of river and coastal sediments with PCDD/Fs and Hg. The total volume of contaminated sediments was estimated to reach 5 x 10(6) m(3) and hot spots with extremely high concentrations (max 292,000 ng g(-1) or 1,060 ng I-TEQ g(-1) d.w.) were located immediately downstream from the pollution source (approximately 90,000 m(3)). Sediment contamination was accompanied by changes in benthic assemblages, but direct effects were masked by many factors. The fish showed only slightly elevated PCDD/F levels in muscle, but orders of magnitude higher in the liver compared with reference freshwater sites and the Baltic Sea. The concentrations in human fat did not reveal high human exposure in the Kymijoki area in general and was lower than in sea fishermen. The relative risk for total cancer among farmers was marginally higher (RR = 1.13) among those living close to the river, compared with farmers living further away, and the possibility of increased cancer risk cannot be ruled out. A conservative risk assessment revealed that the present probability of exceeding the WHO upper exposure limit of 4 pg WHO-TEQ kg(-1) d(-1) for PCDD/Fs and DL-PCBs was 6%. The probability of exceeding the WHO limit value of 0.23 mu g kg(-1) d(-1) for methyl mercury was estimated to be notably higher at 62%. Based on these studies and the estimated risks connected with different remediation techniques a general remediation plan with cost benefit analysis was generated for several sub-regions in the river. Dredging, on-site treatment, and a close disposal of the most contaminated sediments (90,000 m(3)) was suggested as the first phase of the remediation. The decision regarding the start of remediation will be made during autumn 2008. The sediments in the River Kymijoki are heavily polluted with PCDD/Fs and mercury from earlier chlorophenol, chlor-alkali, and pulp and paper manufacturing. A continuous transport of contaminants is taking place to the Gulf of Finland in the Baltic Sea. The highly increased PCDD/F and Hg levels in river sediments pose an ecotoxicological risk to benthic fauna, to fish-eating predators and probably to human health. The risks posed by mercury exceed those from PCDD/Fs and need to be evaluated for (former) chlor-alkali sites and other mercury releasing industries as one basis for remediation decision making. The studies form the basis of a risk management strategy and a plan for possible remediation of contaminated sediments currently under consideration in the Southeast Finland Regional Environment Centre. It is recommended that a detailed restoration plan for the most seriously contaminated areas should be undertaken. Based on current knowledge, the restoration of the whole river is not feasible, considering the current risk caused by the contaminated sediment in the river and the costs of an extensive restoration project. The experiences gained in the present case should be utilized in the evaluation of PCDD/F- and mercury-contaminated sites in other countries. The case demonstrates that the historic reservoirs are of contemporary relevance and should be addressed, e.g., in the national implementation plans of the Stockholm Convention.://000262312900011Verta, Matti Kiviranta, Hannu Salo, Simo Malve, Olli Korhonen, Markku Verkasalo, Pia K. Ruokojarvi, Paivi Rossi, Esko Hanski, Ari Paatalo, Kare Vartiainen, Terttu 0944-1344ISI:0002623129000113.89410.1007/s1J;|? [Tyynela, P. Goebeler, S. Ilveskoski, E. Mikkelsson, J. Perola, M. Loytonen, M. Karhunen, P.2009Birthplace predicts risk for prehospital sudden cardiac death in middle-aged men who migrated to metropolitan area: The Helsinki Sudden Death Study57-65Annals of Medicine411Article2Background. Eastern-born male Finns, irrespective of their place of residence, have high mortality from coronary heart disease (CHD), and half of such deaths are sudden. Aim. To study whether eastern birthplace alone or combined with life-style factors predicts risk for prehospital sudden cardiac death (SCD) in the new (west) low-mortality area of residence. Method. Prospective case-control autopsy study of all (700) out-of-hospital deaths of men aged 35-69 years in metropolitan Helsinki during 1981-82 and 1991-92. Data on CHD risk factors were obtained for 405, of whom 149 died of SCD (cases) and 256 of other causes (controls). Results. A birthplace-by-age interaction with SCD (P=0.024) and with myocardial infarction (P=0.005) appeared. Men 54 years born in the east were more often victims of SCD (odds ratio 2.99, 95% confidence interval 1.38-6.49, P=0.006) than were men born in the west, independently of CHD risk factors. SCD was predicted also by alcohol consumption, age, smoking, and hypertension. Amongst older (54 years) men no association with birthplace was any longer evident, but alcohol and socio-economic status predicted SCD. Conclusions. Birthplace-based risk for SCD suggests the contribution of early life environment or genetic east-west differences, reflecting Finns' two-phase settlement history.://000262475500008vTyynela, Petri Goebeler, Sirkka Ilveskoski, Erkki Mikkelsson, Jussi Perola, Markus Loytonen, Markku Karhunen, Pekka J. 0785-3890ISI:0002624755000085.77910.1080/07&p|? }Alastalo, H. Raikkonen, K. Pesonen, A. K. Osmond, C. Barker, D. J. P. Kajantie, E. Heinonen, K. Forsen, T. J. Eriksson, J. G.2009<Cardiovascular health of Finnish war evacuees 60 years later66-72Annals of Medicine411Article!Background. Early life experiences might have long-term effects on health. Aim. To assess prevalence of cardiovascular disease and diabetes in later life among individuals exposed to traumatic separation in early childhood due to World War II. Methods. Of the participants of the Helsinki Birth Cohort 1934-44 Study (n=2003), 320 had been evacuated abroad to temporary foster care in childhood. The remaining participants served as controls. The mean age at evacuation was 4.8 (SD=2.4) years and the mean duration of the evacuation was 1.7 (SD=1.0) years. Results. Cardiovascular morbidity was higher among the former war evacuees (14.7% versus 7.9%; odds ratio (OR)=2.0, 95% confidence interval (95% CI) 1.4-2.9; P0.001). A similar difference in prevalence of type 2 diabetes was observed (19.7% versus 14.8%; OR=1.4, 95% CI 1.1-1.9, P=0.025). The former war evacuees were also more likely to be hypertensive (P0.05). The effects on morbidity were not explained by age at testing or socio-economic circumstances in childhood or adulthood. Conclusion. Early life traumatic events may extend lifelong effects on health. This study is among the first to show that early life trauma predicts higher prevalence of cardiovascular disease and type 2 diabetes in late adulthood, in a longitudinal clinical study setting.://000262475500009Alastalo, Hanna Raikkonen, Katri Pesonen, Anu-Katriina Osmond, Clive Barker, David J. P. Kajantie, Eero Heinonen, Kati Forsen, Tom J. Eriksson, Johan G. 0785-3890ISI:0002624755000095.77910.1080/07|? OSchreier, N. K. Moltchanova, E. V. Lammi, N. M. Karvonen, M. L. Eriksson, J. G.2009MTemporal variation in case fatality of acute myocardial infarction in Finland73-80Annals of Medicine411ArticleBackground. Previous studies have suggested that seasonal variation and weather conditions have an influence on the incidence and mortality of acute myocardial infarction (AMI). The influence of these factors on AMI case fatality is less studied. Aims. The aim of this study was to examine the temporal variation of AMI case fatality and the effect of daily weather conditions on it. Methods. We analysed death registry and hospital discharge data from all men and women (n=7328) with their first AMI occurrence in the seven largest cities in Finland in the years 1983, 1988, and 1993, aged 25 to 74 years. Results. The mean annual 28-day case fatality was 44%. We found significant weekly and monthly variation of case fatality (P0.001). The December holiday season had the highest case fatality throughout the year in women and men aged 65-74 years (P0.05). The highest weekly case fatality was on Sundays; it differed significantly from the rest of the weekdays only for the oldest age-group (64-74) (P0.01). Conclusions. There is significant weekly and monthly variation in case fatality of AMI. The highest case fatality risk for AMI is during the Christmas season and on Sundays. Weather conditions were not found to have an effect on the case fatality.://000262475500010aSchreier, Nadja K. Moltchanova, Elena V. Lammi, Niina M. Karvonen, Marjatta L. Eriksson, Johan G. 0785-3890ISI:0002624755000105.77910.1080/O?L|?Kurkela, S. Helve, T. Raatti, O. Manni, T. Huhtamo, E. Uzcategui, N. Y. Myllynen, J. Laakkonen, J. Nuorti, J. P. Vaheri, A. Vapalahti, O.2008KSINDBIS ALPHAVIRUS INFECTION: CLINICAL FEATURES, DIAGNOSIS AND EPIDEMIOLOGY3171American Journal of Tropical Medicine and Hygiene796Meeting AbstractDec://000261644600317Kurkela, Satu Helve, Tapani Raetti, Osmo Manni, Tytti Huhtamo, Eili Uzcategui, Nathalie Yumari Myllynen, Johanna Laakkonen, Juha Nuorti, Juha Pekka Vaheri, Antti Vapalahti, Olli Suppl. S 0002-9637ISI:0002616|?jAliev, F. Dick, D. M. Viken, R. J. Winter, T. Vuoksimaa, E. Happola, A. Siltala, M. Kaprio, J. Rose, R. J.2008Selection on Rutgers Alcohol Problem Index (RAPI) Scores in Adolescence Predicts High Rates of Alcohol Dependence in Young Adulthood613-613Behavior Genetics386Meeting AbstractNov://000260539000009Aliev, Fazil Dick, Danielle M. Viken, Richard J. Winter, Torsten Vuoksimaa, Eero Happola, Anja Siltala, Mari Kaprio, Jaakko Rose, Richard J. 0001-8244ISI:0002605l[|?ZPergadia, M. L. Glowinski, A. L. Agrawal, A. Montgomery, G. W. Loukola, A. Broms, U. Saccone, S. F. Korhonen, T. Wang, J. C. Grant, J. D. Lessov-Schalggar, C. N. Todorov, A. A. Wray, N. R. Heikkila, K. Statham, D. J. Henders, A. Campbell, M. Rice, J. P. Todd, R. D. Goate, A. M. Peltonen, L. Heath, A. C. Kaprio, J. Martin, N. G. Madden, P. A. F.2008Genetic Linkage and Association Findings for DSM-IV Major Depressive Disorder: Is the Metabotropic Glutamate Receptor 7 Gene (GRM7) an Important Risk Factor for Depression in Smokers?643-643Behavior Genetics386Meeting AbstractNov://000260539000121Pergadia, Michele L. Glowinski, Anne L. Agrawal, Arpana Montgomery, Grant W. Loukola, Anu Broms, Ulla Saccone, Scott F. Korhonen, Tellervo Wang, Jen C. Grant, Julia D. Lessov-Schalggar, Christina N. Todorov, Alexandre A. Wray, Naomi R. Heikkila, Kauko Statham, Dixie J. Henders, Anjali Campbell, Megan Rice, John P. Todd, Richard D. Goate, Alison M. Peltonen, Leena Heath, Andrew C. Kaprio, Jaakko Martin, Nicholas G. Madden, Pamela A. F. 0001-8244ISI:000260{@|?GVuoksimaa, E. Tuulio-Henriksson, A. Hokkanen, L. Kaprio, J. Rose, R. J.2008CExtreme Male/Female Brain Defined with Two Neuropsychological Tests652-652Behavior Genetics386Meeting AbstractNov://000260539000154[Vuoksimaa, Eero Tuulio-Henriksson, Annamari Hokkanen, Laura Kaprio, Jaakko Rose, Richard J. 0001-8244ISI:00026053k[@F|7Kemppinen, A. Suvela, M. Tienari, P. J. Elovaara, I. Koivisto, K. Pirttila, T. Reunanen, M. Rautakorpi, I. Hillert, J. Lundmark, F. Oturai, A. Ryder, L. Harbo, H. F. Celius, E. G. Palotie, A. Daly, M. Peltonen, L. Saarela, J.2009)MYO9B polymorphisms in multiple sclerosisEur J Hum Genet 2009/01/15Jan 14Single-nucleotide polymorphisms (SNPs) in the 3' region of myosin IXB (MYO9B) gene have recently been reported to associate with different inflammatory or autoimmune diseases. We monitored for the association of MYO9B variants to multiple sclerosis (MS) in four Northern European populations. First, 18 SNPs including 6 SNPs with previous evidence for association to immune disorders, were tested in 730 Finnish MS families, but no linkage or family-based association was observed. To ensure the power to detect variants with a modest effect size, we further analyzed 10 variants in 899 Finnish cases and 1325 controls, and in a total of 1521 cases and 1476 controls from Denmark, Norway and Sweden, but found no association. Our results thereby do not support a major function of the tested MYO9B variants in MS.European Journal of Human Genetics advance online publication, 14 January 2009; doi:10.1038/ejhg.2008.251.GEuropean journal of human genetics : EJHG Eur J Hum Genet. 2009 Jan 14.1018-4813 (Print)191422074.003[1] 1Department of Molecular Medicine, National Public Health Institute and Institute for Molecular Medicine Finland, FIMM, Helsinki, Finland [2] 2Department of Medical Genetics, University of Helsinki, Helsinki, Finland.-ejhg2008251 [pii] 10.1038/ejhg.2008 6 'F|7BKestila, L. Rahkonen, O. Martelin, T. Lahti-Koski, M. Koskinen, S.2009SDo childhood social circumstances affect overweight and obesity in early adulthood?Scand J Public Health 2009/01/15Jan 13<AIMS: The aim of the study was to examine the association of childhood circumstances with overweight and obesity in early adulthood, to analyse whether the respondent's education and current circumstances mediate these associations, and to explore whether the respondent's health behaviour affects these associations. DESIGN: This was a cross-sectional study with retrospective inquiries. METHODS: The study was based on a representative two-stage cluster sample (N = 1894, participation rate 79%) of young adults aged 18-29 years in Finland in 2000. The outcome measure was three-class body mass index (BMI) (normal weight, overweight, and obesity). Multinomial logistic regression was used as the main statistical tool. RESULTS: In women, childhood circumstances (low parental education (relative risk ratio (RRR) = 2.43), parental unemployment (RRR = 2.09) and single-parent family (RRR = 1.99)) increased the risk of overweight (25 /= 30) in women in the age-adjusted models, and being bullied at school remained a significant predictor after adjusting for all childhood and current determinants. In both genders, the strong association between parental education and obesity remained significant after adjusting for all other determinants (for the lowest educational category, RRR = 3.56 in women, and RRR = 6.55 in men). CONCLUSIONS: Childhood factors predict overweight and obesity in early adulthood. This effect is stronger on obesity than on overweight and in women than in men, and it seems to be partly mediated by adult circumstances. The results emphasize the lasting effect of childhood socioeconomic position on adult obesity. When preventive policies are being planned, social circumstances in childhood should be addressed.IScandinavian journal of public health Scand J Public Health. 2009 Jan 13.1403-4948 (Print)191415441.222hDepartment of Health and Functional Capacity, National Public Health Institute (KTL), Helsinki, Finland.51403494808100827 [pii] 10.1177/1403494808100F|70Nummela, O. Sulander, T. Rahkonen, O. Uutela, A.2009eThe effect of trust and change in trust on self-rated health: A longitudinal study among aging peopleArch Gerontol Geriatr 2009/01/13Jan 9BThis study examined whether trust predicted subsequent self-rated health over time at 3 years follow-up among aging people, and whether changes in trust were associated with self-rated health. Longitudinal, questionnaire-based data were collected from three age cohorts (born in 1926-1930, 1936-1940, and 1946-1950) living in the Province of Paijat-Hame, southern Finland. The response rate at the baseline in 2002 was 66% (n=2815). The follow-up was carried out in 2005, with 79% of eligible individuals participating (n=2216). Logistic regression analyses were used to derive the results. High trust was a strong predictor for good self-rated health at the follow-up. Adjusting for background variables, however, attenuated the association. In addition, good self-rated health was most common among men with sustained high trust, among women the association was somewhat weaker. Among men improvement in trust was associated with good self-rated health, but this correlation weakened after multiple adjustments. Thus, longitudinally trust is an important contributor to self-rated health among aging people. Moreover, improvement of trust but also the stability of high trust especially among men indicate better self-rated health. Trust has a positive effect on health and should therefore be seen as a significant element in health promotion.IArchives of gerontology and geriatrics Arch Gerontol Geriatr. 2009 Jan 9.1872-6976 (Electronic)191361601.289Health Promotion Unit, Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute (KTL), Mannerheimintie 166, FIN-00300 Helsinki, Finland.?S0167-4943(08)00235-5 [pii] 10.1016/j.archger.2008.  ||7rHappo, M. S. Hirvonen, M. R. Halinen, A. I. Jalava, P. I. Pennanen, A. S. Sillanpaa, M. Hillamo, R. Salonen, R. O.2008Chemical compositions responsible for inflammation and tissue damage in the mouse lung by coarse and fine particulate samples from contrasting air pollution in Europe1215-31 Inhal Toxicol2014 2008/10/16Air Pollutants/ adverse effects/ chemistry Air Pollution Animals Europe Fuel Oils/adverse effects Male Metals/adverse effects/chemistry Mice Mice, Inbred C57BL Organic Chemicals/adverse effects/chemistry Particle Size Particulate Matter/ adverse effects/ chemistry Vehicle EmissionsNovInflammation is regarded as an important mechanism in mortality and morbidity associated with exposures of cardiorespiratory patients to urban air particulate matter. We investigated the association of the chemical composition and sources of urban air fine (PM(2.5-0.2)) and coarse (PM(10-2.5)) particulate samples with the inflammatory activity in the mouse lung. The particulate samples were collected during selected seasons in six European cities using a high-volume cascade impactor. Healthy C57BL/6J mice were intratracheally instilled with a single dose (10 mg/kg) of the particulate samples. At 4, 12, and 24 h after the exposure, the lungs were lavaged and the bronchoalveolar lavage fluid (BALF) was assayed for indicators of inflammation and tissue damage: cell number, total protein, and cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6, and KC). Dicarboxylic acids and transition metals, especially Ni and V, in PM(2.5-0.2) correlated positively and some secondary inorganic ions (NO3(-), NH4(+)) negatively with the inflammatory activity. Total organic matter and SO4(2-) had no consistent correlations. In addition, the soil-derived constituents (Ca2+, Al, Fe, Si) showed positive correlations with the PM(2.5-0.2)-induced inflammatory activity, but their role in PM(10-2.5) remained obscure, possibly due to largely undefined biogenic material. Markers of poor biomass and coal combustion, i.e., monosaccharide anhydrides and As, were associated with elevated PAH contents in PM(2.5-0.2) and a consistent immunosuppressive effect. Overall, our results support epidemiological findings that the local sources of incomplete combustion and resuspended road dust are important in urban air particulate pollution-related health effects.Happo, Mikko S Hirvonen, Maija-Riitta Halinen, Arja I Jalava, Pasi I Pennanen, Arto S Sillanpaa, Markus Hillamo, Risto Salonen, Raimo O United States Inhalation toxicology Inhal Toxicol. 2008 Nov;20(14):1215-31.1091-7691 (Electronic)188551531.831^National Public Health Institute and University of Kuopio, Kuopio, Finland. Mikko.Happo@ktl.fi/904079588 [pii] 10.1080/08958370802 ||7Pekkanen, J. Sunyer, J.2008HProblems in using incidence to analyze risk factors in follow-up studies581-4Eur J Epidemiol239 2008/08/16{Asthma/classification/ epidemiology Causality Chronic Disease Follow-Up Studies Health Status Humans Incidence Risk FactorswThe most common practice to analyze epidemiological follow-up studies is to analyze risk factors of new, i.e. incident, cases of disease. However, analysis of incidence assumes that diseases exist in true dichotomies, which is unlikely to be true. It has also recently been shown that in many typical situations it is very difficult to separate the association between risk factors of disease at baseline and during follow-up using analyses of incidence. Situation is especially problematic for diseases that have large misclassification and low incidence, like asthma. We suggest that reliance on analysis of incidence may be a major obstacle into discovering causes of such disease. Only with greater attention into how to define and how to analyze prospective studies are we likely to learn sufficiently of risk factors of such disease to finally arrive at means for their prevention.wPekkanen, J Sunyer, J Netherlands European journal of epidemiology Eur J Epidemiol. 2008;23(9):581-4. Epub 2008 Aug 14.0393-2990 (Print)187047011.727{Environmental Epidemiology Unit, National Public Health Institute, P.O. Box 95, 70701 Kuopio, Finland. Juha.Pekkanen@ktl.fi10.1007/s10654-008-928 ||7RPatja, K. Vainiotalo, S. Laatikainen, T. Kuusimaki, L. Peltonen, K. Vartiainen, E.2008vExposure to environmental tobacco smoke at work, at home, and during leisure time: a cross-sectional population sample1327-33Nicotine Tob Res108 2008/08/08aAdult Aged Cross-Sectional Studies Environmental Monitoring/ statistics & numerical data Female Finland/epidemiology Health Status Housing Humans Inhalation Exposure/ statistics & numerical data Leisure Activities Male Middle Aged Occupational Exposure/ analysis Questionnaires Risk Factors Tobacco Smoke Pollution/ statistics & numerical data WorkplaceAug?Environmental tobacco smoke (ETS) is among the most common environmental health risks, with a striking and immediate biological response and increased disease risk. Exposure studies have looked mostly at worksite or home exposures, whereas total exposure levels at the population level are rarely reported. This study examined ETS exposure at work, at home, and during leisure time in a cross-sectional population sample of working-age adults. Our aim was to monitor changes in ETS exposure from 1992 to 2002. More detailed information on duration of exposure, distribution of exposure sites, and patterns of exposure was obtained in 2002. Data were based on Finland's national population chronic disease risk-factor surveys (conducted every 5 years). Total sample size varied from 8,000 to 13,500. The survey includes a self-administered questionnaire about ETS exposure at different sites. The proportion of nonsmoking persons exposed to ETS declined throughout the study period among both men and women. In 2002, 5.9% of male and 3.6% of female nonsmokers were exposed to ETS 1 hour or more per day, whereas 5.8% of men and 1.7% women were exposed less than 1 hour daily. Worksite exposure was more common among younger age groups of both sexes, but nonsmoking women in older age groups received more exposure at home than at worksites. Policy developments on ETS should aim to protect the whole population from ETS in all environments given that health risks from ETS often persist at home and in leisure environments. Total exposure levels should be studied to assess the health impacts of ETS.Patja, Kristiina Vainiotalo, Sinikka Laatikainen, Tiina Kuusimaki, Leea Peltonen, Kimmo Vartiainen, Erkki Research Support, Non-U.S. Gov't England Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco Nicotine Tob Res. 2008 Aug;10(8):1327-33.1462-2203 (Print)186861802.129National Public Health Institute, KTL, Department of Epidemiology and Health Promotion, Mannerheimintie 166, Helsinki, Finland. kristiina.patja@duodecim.fi/901415790 [pii] 10.1080/14622200802238977 [doi]eng F.0b013e318182c90a  827 [doi]Eng'donen, L.2009KThe Twin Spine Study: Contributions to a changing view of disc degeneration47-59 Spine Journal91ArticleJan BACKGROUND CONTEXT: Disc degeneration was commonly viewed over much of the last century as a result of aging and "wear and tear" from mechanical insults and injuries. Thus, prevention strategies and research in lumbar degenerative changes and associated clinical conditions focused largely on mechanical factors as primary causes using an "injury model." The Twin Spine Study. a research program on the etiology and pathogenesis of disc degeneration, has contributed to a substantial revision of this view of determinants of lumbar disc degeneration. PURPOSE: To provide a review of the methods and findings of the Twin Spine Study project. STUDY DESIGN/SETTING: Narrative review of the Twin Spine Study. METHODS: The Twin Spine Study, which started in 1991, is a multidisciplinary, multinational research project with collaborators primarily in Canada, Finland, and the United States. The most significant investigations related to determinants of disc degeneration included occupational exposures, driving and whole-body vibration exposure, smoking exposure, anthropomorphic factors. heritability, and the identification of genotypes associated with disc degeneration. RESULTS: Among the most significant findings were a substantial influence of heredity on lumbar disc degeneration and the identification of the first gene forms associated with disc degeneration. Conversely, despite extraordinary discordance between twin siblings in occupational and leisure-time physical loading conditions throughout adulthood, surprisingly little effect on disc degeneration was observed. Studies on the effects of smoking on twins with large discordance in smoking exposure demonstrated an increase in disc degeneration associated with smoking, but this effect was small. No evidence was found to suggest that exposure to whole-body vibration through motorized vehicles leads to accelerated disc degeneration in these well-controlled studies. More recent results indicate that the effect of anthropometric factors, such as body weight and muscle strength on disc degeneration, although modest, appear in this work to be greater than those of occupational physical demands. In fact, some indications were found that routine loading may actually have some benefits to the disc. CONCLUSIONS: The once commonly held view that disc degeneration is primarily a result of aging and "wear and tear" from mechanical insults and injuries was not supported by this series of studies. Instead, disc degeneration appears to be determined in great part by genetic influences. Although environmental factors also play a role, it is not primarily through routine physical loading exposures (eg, heavy vs. light physical demands) as once suspected. (C) 2009 Elsevier Inc. All rights reserved.://000262378500007}Battie, Michele C. Videman, Tapio Kaprio, Jaakko Gibbons, Laura E. Gill, Kevin Manninen, Hannu Saarela, Janna Peltonen, Leena 1529-9430ISI:00026237850000710.1016/j.spinee.2008.11.0110apasalo, K. Jarva, H. Siljander, T. Tewodros, W. Vuopio-Varkila, J. Jokiranta, T. S.2008zComplement factor H allotype 402H is associated with increased C3b opsonization and phagocytosis of Streptococcus pyogenes583-594Molecular Microbiology703ArticleNovThe main virulence factor of group A streptococcus (GAS), M protein, binds plasma complement regulators factor H (FH) and FH-like protein 1 (FHL-1) leading to decreased opsonization. The M protein binding site on FH is within domain 7 in which also the age-related macular degeneration (AMD)-associated polymorphism Y402H is located. We studied if FH allotypes 402H and 402Y have different binding affinities to GAS. Plasma-derived FH allotype 402H and its recombinant fragment FH5-7(402H) showed decreased binding to several GAS strains. Growth of GAS in human blood taken from FH(402H) homozygous individuals was decreased when compared with blood taken from FH(402Y) homozygous individuals. The effect of the allotype 402H can be explained by combining the previous M protein mutagenesis data and the recently published crystal structure of FH6-8. In conclusion the data indicate that the AMD-associated allotype 402H leads to diminished binding of FH to GAS and increased opsonophagocytosis of the bacteria in blood. These results suggest that the homozygous presence of the allele 402H could be associated with decreased risk for severe GAS infections offering an explanation for the high frequency of the allele despite its association with visual impairment.://000262305000005lHaapasalo, Karita Jarva, Hanna Siljander, Tuula Tewodros, Wezenet Vuopio-Varkila, Jaana Jokiranta, T. Sakari 0950-382XISI:000262305000005 10.1111/j.1365-2958.2008.06347.x Dkanishi, S. Vikstedt, R. Soderlund, S. Lee-Rueckert, M. Hiukka, A. Ehnholm, C. Muilu, M. Metso, J. Naukkarinen, J. Palotie, L. Kovanen, P. T. Jauhiainen, M. Taskinen, M. R.2009{Serum, but not monocyte macrophage foam cells derived from low HDL-C subjects, displays reduced cholesterol efflux capacity183-192Journal of Lipid Research502ArticleFebKThe main antiatherogenic function of HDL is to promote the efflux of cholesterol from peripheral cells and transport it to the liver for excretion in a process termed reverse cholesterol transport. The aim of this study was to evaluate the cholesterol efflux capacity in low- and high-HDL subjects by utilizing monocytes and serum from 18 low-HDL and 15 high-HDL subjects. Low and high HDL levels were defined, respectively, as HDL <= 10(th) and HDL <= 90(th) Finnish age/sex-specific percentile. Cholesterol efflux from [H-3]cholesterol-oleate-acetyl-LDL-loaded monocyte-derived macrophages to standard apolipoprotein A-I ( apoA-I), HDL2, and serum was measured. In addition, cholesterol efflux from acetyl-LDL-loaded human THP-1 macrophages to individual sera ( 0.5%) derived from the study subjects was evaluated. Cholesterol efflux to apoA-I, HDL2, and serum from macrophage foam cells derived from low- and high-HDL subjects was similar. The relative ABCA1 and ABCG1 mRNA expression levels in unloaded macrophages, as well as their protein levels in loaded macrophage foam cells, were similar in the two study groups. Cholesterol efflux from THP-1 foam cells to serum recovered from high-HDL subjects was slightly higher than that to serum from low- HDL subjects ( P = 0.046). Cholesterol efflux from THP-1 macrophages to serum from study subjects correlated with serum apoB ( P = 0.033), apoA-I ( P=0.004), apoA-II ( P<0.0001), and the percentage of apoA-I present in the form of pre beta-HDL ( P = 0.0001). Our data reveal that macrophages isolated from either low- or high-HDL subjects display similar cholesterol efflux capacity to exogenous acceptors. However, sera from low-HDL subjects have poorer cholesterol acceptor ability as compared with sera from high-HDL subjects. - Nakanishi, S., R. Vikstedt, S. Soderlund, M. Lee-Rueckert, A. Hiukka, C. Ehnholm, M. Muilu, J. Metso, J. Naukkarinen, L. Palotie, P. T. Kovanen, M. Jauhiainen, and M-R. Taskinen. Serum, but not monocyte macrophage foam cells derived from low HDL-C subjects, displays reduced cholesterol efflux capacity. J. Lipid Res. 2009. 50: 183-192.://000262500800001Nakanishi, Shuhei Vikstedt, Riikka Soderlund, Sanni Lee-Rueckert, Miriam Hiukka, Anne Ehnholm, Christian Muilu, Mikko Metso, Jari Naukkarinen, Jussi Palotie, Leena Kovanen, Petri T. Jauhiainen, Matti Taskinen, Marja-Riitta 0022-2275ISI:00026250080000110.1194/jlr.M800196-JLR200 Pvipelto, M. Rovio, S. Ngandu, T. Kareholt, I. Eskelinen, M. Winblad, B. Hachinski, V. Cedazo-Minguez, A. Soininen, H. Tuomilehto, J. Nissinen, A.2008[Apolipoprotein E epsilon 4 magnifies lifestyle risks for dementia: a population-based study 2762-2771*Journal of Cellular and Molecular Medicine126BArticleDecThe risk of dementia and Alzheimer's disease (AD) probably results from an interaction between genetic and environmental factors. The aim of this study was to investigate the effects and putative interactions between the apoE epsilon 4 allele and lifestyle related risk factors for dementia and AD. Participants of the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study were derived from random, population-based samples previously studied in 1972, 1977, 1982 or 1987. After an average follow-up of 21 years, 1449 individuals (72.5%) aged 65-79 years were re-examined in 1998. The apoE epsilon 4 allele was an independent risk factor for dementia/AD even after adjustments for sociodemographic, lifestyle and vascular factors (odds ratio [OR] = 2.83, 95% confidence interval [CI] epsilon 1.61-4.97). Physical inactivity, alcohol drinking and smoking increased the risk of dementia/AD particularly among the apoE epsilon 4 carriers. Furthermore, low-moderate intake of polyunsaturated, and moderate-high intake of saturated fats were associated with an increased risk of dementia/AD more pronouncedly among apoE epsilon 4 carriers. Composite effect of the lifestyle factors was particularly seen among the epsilon 4 carriers (OR = 11.42, 95% CI = 1.94-67.07 in the 4(th) quartile). Physical inactivity, dietary fat intake, alcohol drinking and smoking at midlife are associated with the risk of dementia and AD, especially among the apoE epsilon 4 carriers. The apoE epsilon 4 carriers may be more vulnerable to environmental factors, and thus, lifestyle interventions may greatly modify dementia risk particularly among the genetically susceptible individuals.://000262311700019Kivipelto, Miia Rovio, Suvi Ngandu, Tiia Kareholt, Ingemar Eskelinen, Marjo Winblad, Bengt Hachinski, Vladimir Cedazo-Minguez, Angel Soininen, Hilkka Tuomilehto, Jaakko Nissinen, Aulikki 1582-1838ISI:000262311700019 10.1111/j.1582-4934.2008.00296.xstelin, L. Silventoinen, K. Pietilainen, K. Rissanen, A. Kaprio, J.2009wPhysical activity reduces the influence of genetic effects on BMI and waist circumference: a study in young adult twins29-36 International Journal of Obesity331ArticleJanObjective: Both obesity and exercise behavior are influenced by genetic and environmental factors. However, whether obesity and physical inactivity share the same genetic vs environmental etiology has rarely been studied. We therefore analyzed these complex relationships, and also examined whether physical activity modifies the degree of genetic influence on body mass index (BMI) and waist circumference (WC). Methods: The FinnTwin16 Study is a population-based, longitudinal study of five consecutive birth cohorts (1975-1979) of Finnish twins. Data on height, weight, WC and physical activity of 4343 subjects at the average age of 25 (range, 22-27 years) years were obtained by a questionnaire and self-measurement of WC. Quantitative genetic analyses based on linear structural equations were carried out by the Mx statistical package. The modifying effect of physical activity on genetic and environmental influences was analyzed using gene-environment interaction models. Results: The overall heritability estimates were 79% in males and 78% in females for BMI, 56 and 71% for WC and 55 and 54% for physical activity, respectively. There was an inverse relationship between physical activity and WC in males (r = -0.12) and females (r = -0.18), and between physical activity and BMI in females (r = -0.12). Physical activity significantly modified the heritability of BMI and WC, with a high level of physical activity decreasing the additive genetic component in BMI and WC. Conclusions: Physically active subjects were leaner than sedentary ones, and physical activity reduced the influence of genetic factors to develop high BMI and WC. This suggests that the individuals at greatest genetic risk for obesity would benefit the most from physical activity.://000262377300006EMustelin, L. Silventoinen, K. Pietilainen, K. Rissanen, A. Kaprio, J. 0307-0565ISI:00026237730000610.1038/ijo.2008.258 (P llio, P. Tolppanen, A. M. Kolehmainen, M. Poutanen, K. Lindstrom, J. Tuomilehto, J. Kuulasmaa, T. Kuusisto, J. Pulkkinen, L. Uusitupa, M.2009uAssociation of sequence variations in the gene encoding insulin-like growth factor binding protein 5 with adiponectin80-88 International Journal of Obesity331ArticleJanBackground: Insulin-like growth factor binding protein 5 (IGFBP5) binds to IGF and thus modulates IGF signaling pathway. We have shown earlier that the IGFBP5 gene was downregulated in the adipose tissue after 12-week carbohydrate diet with low insulinemic response. Objective: The aim was to examine the putative contribution of genetic variation of the IGFBP5 gene to the characteristics of metabolic syndrome and incidence of type 2 diabetes (T2DM) in the Finnish Diabetes Prevention Study (DPS). Methods: DPS is a longitudinal study where 522 subjects with impaired glucose tolerance were randomized to either lifestyle intervention group or control group. DNA was available from 507 subjects ( mean body mass index (BMI) 31.2 +/- 4.5 kg/m(2), age 55 +/- 7 years). The eight single-nucleotide polymorphisms ( SNPs) were selected from HapMap database and genotyped by Taqman allelic discrimination protocol. The main results were confirmed in a larger cross-sectional study population (METSIM). In addition, the gene expression of IGFBP5 was studied in two previously published study populations (FUNGENUT and GENOBIN) of 124 subjects with insulin resistance (BMI 32.2 +/- 3.5 kg/m(2), age 57.7 +/- 7.4 years). Results: Three out of eight IGFBP5 markers (rs9341234, rs3276 and rs11575134) were significantly associated with circulating adiponectin concentrations in men. Furthermore, mRNA expression studies of subcutaneous adipose tissue showed that mRNA concentrations of IGFBP5 correlated with adiponectin concentrations in all subjects and in women. None of the IGFBP5 SNPs were associated with T2DM. Conclusions: Our findings show that IGFBP5 has a gender-specific association with adiponectin, which may modulate the development of metabolic syndrome.://000262377300013Kallio, P. Tolppanen, A-M Kolehmainen, M. Poutanen, K. Lindstrom, J. Tuomilehto, J. Kuulasmaa, T. Kuusisto, J. Pulkkinen, L. Uusitupa, M. 0307-0565ISI:00026237730001310.1038/ijo.2008.196$Ds, A. Kumpulainen, S. Jarvelin, K. Hedlund, T.2008@The information environment of researchers in molecular medicine8Information Research-an International Electronic Journal133ArticleSepIntroduction. Describes and analyses the information environment of research work in molecular medicine. We presume an interdependence between the information environment, the research process and the related work tasks. Method. This is a qualitative case study using mixed methods. Empirical data were gathered using two surveys and six semi-structured thematic interviews. Analysis. Analysis was carried out on the merged data of the two surveys. Respondents were divided into groups and information resources were categorized. Results. The information environment consists of broad categories of data, tools, published material and interpersonal communication. The usage of portals and other integrated resources was substantial. The role of PubMed was central in searching scientific facts. Google was used to locate general Web pages, research groups, methods and tools. Interpersonal communication seemed to be effective in providing information about methods and tools among groups which do laboratory work. The problems reported concerned lack of knowledge about useful resources and how to use them properly, some query formulation problems were also reported, e. g. problems with acronyms, personal names and gene name synonymy. Conclusions. The information related tasks occupied much of the researchers' time. If information problems were solved, more time to the research would be released. The database and tool interfaces should be easier to use.://000262254300007ARoos, Annikki Kumpulainen, Sanna Jarvelin, Kalervo Hedlund, Turid 1368-1613ISI:000262254300007353, pjantie, E.2008#Early-life events. Effects on aging101-113>Hormones-International Journal of Endocrinology and Metabolism72ReviewApr-Jun$During the last two decades, a considerable body of evidence has emerged showing that circumstances during the fetal period and childhood may have lifelong programming effects on different body functions with a considerable impact on disease susceptibility. From a medical point of view, these long-term effects are today referred to as the Developmental Origins of Health and Disease (DOHaD) concept. The DOHaD concept may have a fundamental impact on our ideas about when and how to intervene in order to prevent aging-related loss of function and disease. The aim of this review is to provide a synopsis of epidemiological findings relating early-life conditions with key aging-related disorders, including cardiovascular disease, type 2 diabetes, depression, cognitive impairments and osteoporosis. There are several mechanisms that have been suggested as linking early-life events with late-life disease. This review will discuss programming of the hypothalamic-pituitary-adrenal axis function as one of the best characterised examples of such mechanisms.://000262363600001Kajantie, Eero 1109-3099ISI:000262363600001DDtkeviciene, J. Simila, M. Becker, W. Kriaucioniene, V. Valsta, L. M.2009KValidity and reproducibility of the NORBAGREEN food frequency questionnaire141-149&European Journal of Clinical Nutrition631ArticleJanObjective: To measure the validity and reproducibility of the NORBAGREEN food frequency questionnaire (FFQ). Subjects/methods: In Finland, 125 subjects aged 25-64 years sampled from the five main regions of the FINDIET 2002 Study and in Lithuania, 99 citizens of Kaunas aged 19-75 years participated in the study. Reference methods for the FFQ were two 3-day FFQs in Finland and four 24-h recalls in Lithuania. The FFQ was repeated after 6-8 months in both countries. The outcome of the FFQ1 was correlated with the outcome of the reference methods and with the outcome of repeated FFQ2. Cross-classification of food intakes by FFQ1 and the reference methods was examined in tertiles. Results: Validity correlations (FFQ vs the reference method, Spearman's correlation) were for vegetables, fruit and bread 0.50 (P<0.01), 0.53 (P<0.01) and 0.54 (P<0.01) in Finland; and 0.55 (P<0.01), 0.31 (P<0.01) and 0.51 (P<0.01) in Lithuania, respectively. Correlations were smaller for potatoes and fish. The overall proportion categorized in the same or adjacent intake tertiles with the two instruments was over 83% in both countries. Reproducibility correlations varied between 0.51 and 0.75 in the Finnish study, and between 0.51 and 0.83 in the Lithuanian study. Conclusions: The NORBAGREEN FFQ can be used to rank subjects according to vegetable, fruit and bread consumption. Questions on fish and potato consumption need to be developed further.://000262293700019FPetkeviciene, J. Simila, M. Becker, W. Kriaucioniene, V. Valsta, L. M. 0954-3007ISI:00026229370001910.1038/sj.ejcn.16028930prta, M. Kiviranta, H. Salo, S. Malve, O. Korhonen, M. Verkasalo, P. K. Ruokojarvi, P. Rossi, E. Hanski, A. Paatalo, K. Vartiainen, T.2009fA decision framework for possible remediation of contaminated sediments in the River Kymijoki, Finland95-105,Environmental Science and Pollution Research161ArticleJanThe paper describes the spatial contamination of the River Kymijoki, South-Eastern Finland, and the coastal region of the Gulf of Finland with PCDD/Fs and mercury. The findings of ecotoxicologial and human health studies are also reported, including environmental and human risk assessments. Sediments from the River Kymijoki, draining into the Gulf of Finland, have been heavily polluted by the pulp and paper industry and by chemical industries. A wood preservative, known as Ky-5, was manufactured in the upper reaches of the river between 1940 and 1984 causing severe pollution of river sediments with polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF). Moreover, the sediments have been polluted with mercury (Hg) from chlor-alkali production and the use of Hg as a slimicide in pulp and paper manufacturing. An extensive sediment survey was conducted as well as sediment transport modeling, toxicity screening of sediment invertebrates, and a survey of contaminant bioaccumulation in invertebrates and fish. Studies on human exposure to PCDD/Fs and the possible effects on hypermineralization of teeth as well as an epidemiological study to reveal increased cancer risk were also conducted. An assessment of the ecological and human health risks with a null hypothesis (no remediation) was undertaken. The sediment survey revealed severe contamination of river and coastal sediments with PCDD/Fs and Hg. The total volume of contaminated sediments was estimated to reach 5 x 10(6) m(3) and hot spots with extremely high concentrations (max 292,000 ng g(-1) or 1,060 ng I-TEQ g(-1) d.w.) were located immediately downstream from the pollution source (approximately 90,000 m(3)). Sediment contamination was accompanied by changes in benthic assemblages, but direct effects were masked by many factors. The fish showed only slightly elevated PCDD/F levels in muscle, but orders of magnitude higher in the liver compared with reference freshwater sites and the Baltic Sea. The concentrations in human fat did not reveal high human exposure in the Kymijoki area in general and was lower than in sea fishermen. The relative risk for total cancer among farmers was marginally higher (RR = 1.13) among those living close to the river, compared with farmers living further away, and the possibility of increased cancer risk cannot be ruled out. A conservative risk assessment revealed that the present probability of exceeding the WHO upper exposure limit of 4 pg WHO-TEQ kg(-1) d(-1) for PCDD/Fs and DL-PCBs was 6%. The probability of exceeding the WHO limit value of 0.23 mu g kg(-1) d(-1) for methyl mercury was estimated to be notably higher at 62%. Based on these studies and the estimated risks connected with different remediation techniques a general remediation plan with cost benefit analysis was generated for several sub-regions in the river. Dredging, on-site treatment, and a close disposal of the most contaminated sediments (90,000 m(3)) was suggested as the first phase of the remediation. The decision regarding the start of remediation will be made during autumn 2008. The sediments in the River Kymijoki are heavily polluted with PCDD/Fs and mercury from earlier chlorophenol, chlor-alkali, and pulp and paper manufacturing. A continuous transport of contaminants is taking place to the Gulf of Finland in the Baltic Sea. The highly increased PCDD/F and Hg levels in river sediments pose an ecotoxicological risk to benthic fauna, to fish-eating predators and probably to human health. The risks posed by mercury exceed those from PCDD/Fs and need to be evaluated for (former) chlor-alkali sites and other mercury releasing industries as one basis for remediation decision making. The studies form the basis of a risk management strategy and a plan for possible remediation of contaminated sediments currently under consideration in the Southeast Finland Regional Environment Centre. It is recommended that a detailed restoration plan for the most seriously contaminated areas should be undertaken. Based on current knowledge, the restoration of the whole river is not feasible, considering the current risk caused by the contaminated sediment in the river and the costs of an extensive restoration project. The experiences gained in the present case should be utilized in the evaluation of PCDD/F- and mercury-contaminated sites in other countries. The case demonstrates that the historic reservoirs are of contemporary relevance and should be addressed, e.g., in the national implementation plans of the Stockholm Convention.://000262312900011Verta, Matti Kiviranta, Hannu Salo, Simo Malve, Olli Korhonen, Markku Verkasalo, Pia K. Ruokojarvi, Paivi Rossi, Esko Hanski, Ari Paatalo, Kare Vartiainen, Terttu 0944-1344ISI:00026231290001110.1007/s11356-008-0061-9H,ynela, P. Goebeler, S. Ilveskoski, E. Mikkelsson, J. Perola, M. Loytonen, M. Karhunen, P.2009Birthplace predicts risk for prehospital sudden cardiac death in middle-aged men who migrated to metropolitan area: The Helsinki Sudden Death Study57-65Annals of Medicine411Article2Background. Eastern-born male Finns, irrespective of their place of residence, have high mortality from coronary heart disease (CHD), and half of such deaths are sudden. Aim. To study whether eastern birthplace alone or combined with life-style factors predicts risk for prehospital sudden cardiac death (SCD) in the new (west) low-mortality area of residence. Method. Prospective case-control autopsy study of all (700) out-of-hospital deaths of men aged 35-69 years in metropolitan Helsinki during 1981-82 and 1991-92. Data on CHD risk factors were obtained for 405, of whom 149 died of SCD (cases) and 256 of other causes (controls). Results. A birthplace-by-age interaction with SCD (P=0.024) and with myocardial infarction (P=0.005) appeared. Men 54 years born in the east were more often victims of SCD (odds ratio 2.99, 95% confidence interval 1.38-6.49, P=0.006) than were men born in the west, independently of CHD risk factors. SCD was predicted also by alcohol consumption, age, smoking, and hypertension. Amongst older (54 years) men no association with birthplace was any longer evident, but alcohol and socio-economic status predicted SCD. Conclusions. Birthplace-based risk for SCD suggests the contribution of early life environment or genetic east-west differences, reflecting Finns' two-phase settlement history.://000262475500008vTyynela, Petri Goebeler, Sirkka Ilveskoski, Erkki Mikkelsson, Jussi Perola, Markus Loytonen, Markku Karhunen, Pekka J. 0785-3890ISI:00026247550000810.1080/07853890802258753$$Pastalo, H. Raikkonen, K. Pesonen, A. K. Osmond, C. Barker, D. J. P. Kajantie, E. Heinonen, K. Forsen, T. J. Eriksson, J. G.2009<Cardiovascular health of Finnish war evacuees 60 years later66-72Annals of Medicine411Article!Background. Early life experiences might have long-term effects on health. Aim. To assess prevalence of cardiovascular disease and diabetes in later life among individuals exposed to traumatic separation in early childhood due to World War II. Methods. Of the participants of the Helsinki Birth Cohort 1934-44 Study (n=2003), 320 had been evacuated abroad to temporary foster care in childhood. The remaining participants served as controls. The mean age at evacuation was 4.8 (SD=2.4) years and the mean duration of the evacuation was 1.7 (SD=1.0) years. Results. Cardiovascular morbidity was higher among the former war evacuees (14.7% versus 7.9%; odds ratio (OR)=2.0, 95% confidence interval (95% CI) 1.4-2.9; P0.001). A similar difference in prevalence of type 2 diabetes was observed (19.7% versus 14.8%; OR=1.4, 95% CI 1.1-1.9, P=0.025). The former war evacuees were also more likely to be hypertensive (P0.05). The effects on morbidity were not explained by age at testing or socio-economic circumstances in childhood or adulthood. Conclusion. Early life traumatic events may extend lifelong effects on health. This study is among the first to show that early life trauma predicts higher prevalence of cardiovascular disease and type 2 diabetes in late adulthood, in a longitudinal clinical study setting.://000262475500009Alastalo, Hanna Raikkonen, Katri Pesonen, Anu-Katriina Osmond, Clive Barker, David J. P. Kajantie, Eero Heinonen, Kati Forsen, Tom J. Eriksson, Johan G. 0785-3890ISI:00026247550000910.1080/07853890802301983,*hreier, N. K. Moltchanova, E. V. Lammi, N. M. Karvonen, M. L. Eriksson, J. G.2009MTemporal variation in case fatality of acute myocardial infarction in Finland73-80Annals of Medicine411ArticleBackground. Previous studies have suggested that seasonal variation and weather conditions have an influence on the incidence and mortality of acute myocardial infarction (AMI). The influence of these factors on AMI case fatality is less studied. Aims. The aim of this study was to examine the temporal variation of AMI case fatality and the effect of daily weather conditions on it. Methods. We analysed death registry and hospital discharge data from all men and women (n=7328) with their first AMI occurrence in the seven largest cities in Finland in the years 1983, 1988, and 1993, aged 25 to 74 years. Results. The mean annual 28-day case fatality was 44%. We found significant weekly and monthly variation of case fatality (P0.001). The December holiday season had the highest case fatality throughout the year in women and men aged 65-74 years (P0.05). The highest weekly case fatality was on Sundays; it differed significantly from the rest of the weekdays only for the oldest age-group (64-74) (P0.01). Conclusions. There is significant weekly and monthly variation in case fatality of AMI. The highest case fatality risk for AMI is during the Christmas season and on Sundays. Weather conditions were not found to have an effect on the case fatality.://000262475500010aSchreier, Nadja K. Moltchanova, Elena V. Lammi, Niina M. Karvonen, Marjatta L. Eriksson, Johan G. 0785-3890ISI:00026247550001010.1080/07853890802392511L$P`rkela, S. Helve, T. Raatti, O. Manni, T. Huhtamo, E. Uzcategui, N. Y. Myllynen, J. Laakkonen, J. Nuorti, J. P. Vaheri, A. Vapalahti, O.2008KSINDBIS ALPHAVIRUS INFECTION: CLINICAL FEATURES, DIAGNOSIS AND EPIDEMIOLOGY3171American Journal of Tropical Medicine and Hygiene796Meeting AbstractDec://000261644600317Kurkela, Satu Helve, Tapani Raetti, Osmo Manni, Tytti Huhtamo, Eili Uzcategui, Nathalie Yumari Myllynen, Johanna Laakkonen, Juha Nuorti, Juha Pekka Vaheri, Antti Vapalahti, Olli Suppl. S 0002-9637ISI:000261644600317I7|?&CSavolainen-Kopra, C. Blomqvist, S. Kilpi, T. Roivainen, M. Hovi, T.20099NOVEL SPECIES OF HUMAN RHINOVIRUSES IN ACUTE OTITIS MEDIA59-61$Pediatric Infectious Disease Journal281ArticleJanWe have studied human rhinovirus (HRV) recovered from nasopharyngeal aspirates and middle car fluids collected during acute otitis media with RT-PCR sequencing followed by phylogenetic analysis. In addition to a great diversity of traditional HRV types we found genetic relative., of the novel HRV Species, Suggested HRV-C, in both sample types. Our results indicate the presence of HRV-C in the middle car for the first time.://000262247200016TSavolainen-Kopra, Carita Blomqvist, Soile Kilpi, Terhi Roivainen, Merja Hovi, Tapani 0891-3668ISI:0002622472000163.08610.1097/INsc|?'Willer, C. J. Speliotes, E. K. Loos, R. J. F. Li, S. X. Lindgren, C. M. Heid, I. M. Berndt, S. I. Elliott, A. L. Jackson, A. U. Lamina, C. Lettre, G. Lim, N. Lyon, H. N. McCarroll, S. A. Papadakis, K. Qi, L. Randall, J. C. Roccasecca, R. M. Sanna, S. Scheet, P. Weedon, M. N. Wheeler, E. Zhao, J. H. Jacobs, L. C. Prokopenko, I. Soranzo, N. Tanaka, T. Timpson, N. J. Almgren, P. Bennett, A. Bergman, R. N. Bingham, S. A. Bonnycastle, L. L. Brown, M. Burtt, N. L. P. Chines, P. Coin, L. Collins, F. S. Connell, J. M. Cooper, C. Smith, G. D. Dennison, E. M. Deodhar, P. Elliott, P. Erdos, M. R. Estrada, K. Evans, D. M. Gianniny, L. Gieger, C. Gillson, C. J. Guiducci, C. Hackett, R. Hadley, D. Hall, A. S. Havulinna, A. S. Hebebrand, J. Hofman, A. Isomaa, B. Jacobs, K. B. Johnson, T. Jousilahti, P. Jovanovic, Z. Khaw, K. T. Kraft, P. Kuokkanen, M. Kuusisto, J. Laitinen, J. Lakatta, E. G. Luan, J. Luben, R. N. Mangino, M. McArdle, W. L. Meitinger, T. Mulas, A. Munroe, P. B. Narisu, N. Ness, A. R. Northstone, K. O'Rahilly, S. Purmann, C. Rees, M. G. Ridderstraale, M. Ring, S. M. Rivadeneira, F. Ruokonen, A. Sandhu, M. S. Saramies, J. Scott, L. J. Scuteri, A. Silander, K. Sims, M. A. Song, K. Stephens, J. Stevens, S. Stringham, H. M. Tung, Y. C. L. Valle, T. T. Van Duijn, C. M. Vimaleswaran, K. S. Vollenweider, P. Waeber, G. Wallace, C. Watanabe, R. M. Waterworth, D. M. Watkins, N. Witteman, J. C. M. Zeggini, E. Zhai, G. J. Zillikens, M. C. Altshuler, D. Caulfield, M. J. Chanock, S. J. Farooqi, I. S. Ferrucci, L. Guralnik, J. M. Hattersley, A. T. Hu, F. B. Jarvelin, M. R. Laakso, M. Mooser, V. Ong, K. K. Ouwehand, W. H. Salomaa, V. Samani, N. J. Spector, T. D. Tuomi, T. Tuomilehto, J. Uda, M. Uitterlinden, A. G. Wareham, N. J. Deloukas, P. Frayling, T. M. Groop, L. C. Hayes, R. B. Hunter, D. J. Mohlke, K. L. Peltonen, L. Schlessinger, D. Strachan, D. P. Wichmann, H. E. McCarthy, M. I. Boehnke, M. Barroso, I. Abecasis, G. R. Hirschhorn, J. N.2009eSix new loci associated with body mass index highlight a neuronal influence on body weight regulation25-34Nature Genetics411ArticleJanCommon variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.://000262085300013 Willer, Cristen J. Speliotes, Elizabeth K. Loos, Ruth J. F. Li, Shengxu Lindgren, Cecilia M. Heid, Iris M. Berndt, Sonja I. Elliott, Amanda L. Jackson, Anne U. Lamina, Claudia Lettre, Guillaume Lim, Noha Lyon, Helen N. McCarroll, Steven A. Papadakis, Konstantinos Qi, Lu Randall, Joshua C. Roccasecca, Rosa Maria Sanna, Serena Scheet, Paul Weedon, Michael N. Wheeler, Eleanor Zhao, Jing Hua Jacobs, Leonie C. Prokopenko, Inga Soranzo, Nicole Tanaka, Toshiko Timpson, Nicholas J. Almgren, Peter Bennett, Amanda Bergman, Richard N. Bingham, Sheila A. Bonnycastle, Lori L. Brown, Morris Burtt, Noel L. P. Chines, Peter Coin, Lachlan Collins, Francis S. Connell, John M. Cooper, Cyrus Smith, George Davey Dennison, Elaine M. Deodhar, Parimal Elliott, Paul Erdos, Michael R. Estrada, Karol Evans, David M. Gianniny, Lauren Gieger, Christian Gillson, Christopher J. Guiducci, Candace Hackett, Rachel Hadley, David Hall, Alistair S. Havulinna, Aki S. Hebebrand, Johannes Hofman, Albert Isomaa, Bo Jacobs, Kevin B. Johnson, Toby Jousilahti, Pekka Jovanovic, Zorica Khaw, Kay-Tee Kraft, Peter Kuokkanen, Mikko Kuusisto, Johanna Laitinen, Jaana Lakatta, Edward G. Luan, Jian'an Luben, Robert N. Mangino, Massimo McArdle, Wendy L. Meitinger, Thomas Mulas, Antonella Munroe, Patricia B. Narisu, Narisu Ness, Andrew R. Northstone, Kate O'Rahilly, Stephen Purmann, Carolin Rees, Matthew G. Ridderstrale, Martin Ring, Susan M. Rivadeneira, Fernando Ruokonen, Aimo Sandhu, Manjinder S. Saramies, Jouko Scott, Laura J. Scuteri, Angelo Silander, Kaisa Sims, Matthew A. Song, Kijoung Stephens, Jonathan Stevens, Suzanne Stringham, Heather M. Tung, Y. C. Loraine Valle, Timo T. Van Duijn, Cornelia M. Vimaleswaran, Karani S. Vollenweider, Peter Waeber, Gerard Wallace, Chris Watanabe, Richard M. Waterworth, Dawn M. Watkins, Nicholas Witteman, Jacqueline C. M. Zeggini, Eleftheria Zhai, Guangju Zillikens, M. Carola Altshuler, David Caulfield, Mark J. Chanock, Stephen J. Farooqi, I. Sadaf Ferrucci, Luigi Guralnik, Jack M. Hattersley, Andrew T. Hu, Frank B. Jarvelin, Marjo-Riitta Laakso, Markku Mooser, Vincent Ong, Ken K. Ouwehand, Willem H. Salomaa, Veikko Samani, Nilesh J. Spector, Timothy D. Tuomi, Tiinamaija Tuomilehto, Jaakko Uda, Manuela Uitterlinden, Andre G. Wareham, Nicholas J. Deloukas, Panagiotis Frayling, Timothy M. Groop, Leif C. Hayes, Richard B. Hunter, David J. Mohlke, Karen L. Peltonen, Leena Schlessinger, David Strachan, David P. Wichmann, H-Erich McCarthy, Mark I. Boehnke, Michael Barroso, Ines Abecasis, Goncalo R. Hirschhorn, Joel N. 1061-4036ISI:00026208530001325.556 : 't|?(?Sabatti, C. Service, S. K. Hartikainen, A. L. Pouta, A. Ripatti, S. Brodsky, J. Jones, C. G. Zaitlen, N. A. Varilo, T. Kaakinen, M. Sovio, U. Ruokonen, A. Laitinen, J. Jakkula, E. Coin, L. Hoggart, C. Collins, A. Turunen, H. Gabriel, S. Elliot, P. McCarthy, M. I. Daly, M. J. Jarvelin, M. R. Freimer, N. B. Peltonen, L.2009`Genome-wide association analysis of metabolic traits in a birth cohort from a founder population35-46Nature Genetics411ArticleJanZGenome-wide association studies (GWAS) of longitudinal birth cohorts enable joint investigation of environmental and genetic influences on complex traits. We report GWAS results for nine quantitative metabolic traits (triglycerides, high-density lipoprotein, low-density lipoprotein, glucose, insulin, C-reactive protein, body mass index, and systolic and diastolic blood pressure) in the Northern Finland Birth Cohort 1966 (NFBC1966), drawn from the most genetically isolated Finnish regions. We replicate most previously reported associations for these traits and identify nine new associations, several of which highlight genes with metabolic functions: high-density lipoprotein with NR1H3 (LXRA), low-density lipoprotein with AR and FADS1-FADS2, glucose with MTNR1B, and insulin with PANK1. Two of these new associations emerged after adjustment of results for body mass index. Gene-environment interaction analyses suggested additional associations, which will require validation in larger samples. The currently identified loci, together with quantified environmental exposures, explain little of the trait variation in NFBC1966. The association observed between low-density lipoprotein and an infrequent variant in AR suggests the potential of such a cohort for identifying associations with both common, low-impact and rarer, high-impact quantitative trait loci.://000262085300014Sabatti, Chiara Service, Susan K. Hartikainen, Anna-Liisa Pouta, Anneli Ripatti, Samuli Brodsky, Jae Jones, Chris G. Zaitlen, Noah A. Varilo, Teppo Kaakinen, Marika Sovio, Ulla Ruokonen, Aimo Laitinen, Jaana Jakkula, Eveliina Coin, Lachlan Hoggart, Clive Collins, Andrew Turunen, Hannu Gabriel, Stacey Elliot, Paul McCarthy, Mark I. Daly, Mark J. Jarvelin, Marjo-Riitta Freimer, Nelson B. Peltonen, Leena 1061-4036ISI:00026208530001425.5 |?)Aulchenko, Y. S. Ripatti, S. Lindqvist, I. Boomsma, D. Heid, I. M. Pramstaller, P. P. Penninx, Bwjh Janssens, Acjw Wilson, J. F. Spector, T. Martin, N. G. Pedersen, N. L. Kyvik, K. O. Kaprio, J. Hofman, A. Freimer, N. B. Jarvelin, M. R. Gyllensten, U. Campbell, H. Rudan, I. Johansson, A. Marroni, F. Hayward, C. Vitart, V. Jonasson, I. Pattaro, C. Wright, A. Hastie, N. Pichler, I. Hicks, A. A. Falchi, M. Willemsen, G. Hottenga, J. J. de Geus, E. J. C. Montgomery, G. W. Whitfield, J. Magnusson, P. Saharinen, J. Perola, M. Silander, K. Isaacs, A. Sijbrands, E. J. G. Uitterlinden, A. G. Witteman, J. C. M. Oostra, B. A. Elliott, P. Ruokonen, A. Sabatti, C. Gieger, C. Meitinger, T. Kronenberg, F. Doring, A. Wichmann, H. E. Smit, J. H. McCarthy, M. I. van Duijn, C. M. Peltonen, L.2009_Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts47-55Nature Genetics411ArticleJanRecent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.://000262085300015Aulchenko, Yurii S. Ripatti, Samuli Lindqvist, Ida Boomsma, Dorret Heid, Iris M. Pramstaller, Peter P. Penninx, Brenda W. J. H. Janssens, A. Cecile J. W. Wilson, James F. Spector, Tim Martin, Nicholas G. Pedersen, Nancy L. Kyvik, Kirsten Ohm Kaprio, Jaakko Hofman, Albert Freimer, Nelson B. Jarvelin, Marjo-Riitta Gyllensten, Ulf Campbell, Harry Rudan, Igor Johansson, Asa Marroni, Fabio Hayward, Caroline Vitart, Veronique Jonasson, Inger Pattaro, Cristian Wright, Alan Hastie, Nick Pichler, Irene Hicks, Andrew A. Falchi, Mario Willemsen, Gonneke Hottenga, Jouke-Jan de Geus, Eco J. C. Montgomery, Grant W. Whitfield, John Magnusson, Patrik Saharinen, Juha Perola, Markus Silander, Kaisa Isaacs, Aaron Sijbrands, Eric J. G. Uitterlinden, Andre G. Witteman, Jacqueline C. M. Oostra, Ben A. Elliott, Paul Ruokonen, Aimo Sabatti, Chiara Gieger, Christian Meitinger, Thomas Kronenberg, Florian Doering, Angela Wichmann, H-Erich Smit, Johannes H. McCarthy, Mark I. van Duijn, Cornelia M. Peltonen, Leena 1061-4036ISI:00026208530001525.5 V C|?*-Kathiresan, S. Willer, C. J. Peloso, G. M. Demissie, S. Musunuru, K. Schadt, E. E. Kaplan, L. Bennett, D. Li, Y. Tanaka, T. Voight, B. F. Bonnycastle, L. L. Jackson, A. U. Crawford, G. Surti, A. Guiducci, C. Burtt, N. P. Parish, S. Clarke, R. Zelenika, D. Kubalanza, K. A. Morken, M. A. Scott, L. J. Stringham, H. M. Galan, P. Swift, A. J. Kuusisto, J. Bergman, R. N. Sundvall, J. Laakso, M. Ferrucci, L. Scheet, P. Sanna, S. Uda, M. Yang, Q. Lunetta, K. L. Dupuis, J. de Bakker, P. I. W. O'Donnell, C. J. Chambers, J. C. Kooner, J. S. Hercberg, S. Meneton, P. Lakatta, E. G. Scuteri, A. Schlessinger, D. Tuomilehto, J. Collins, F. S. Groop, L. Altshuler, D. Collins, R. Lathrop, G. M. Melander, O. Salomaa, V. Peltonen, L. Orho-Melander, M. Ordovas, J. M. Boehnke, M. Abecasis, G. R. Mohlke, K. L. Cupples, L. A.2009?Common variants at 30 loci contribute to polygenic dyslipidemia56-65Nature Genetics411ArticleJan;Blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels are risk factors for cardiovascular disease. To dissect the polygenic basis of these traits, we conducted genome-wide association screens in 19,840 individuals and replication in up to 20,623 individuals. We identified 30 distinct loci associated with lipoprotein concentrations (each with P < 5 x 10(-8)), including 11 loci that reached genome-wide significance for the first time. The 11 newly defined loci include common variants associated with LDL cholesterol near ABCG8, MAFB, HNF1A and TIMD4; with HDL cholesterol near ANGPTL4, FADS1-FADS2-FADS3, HNF4A, LCAT, PLTP and TTC39B; and with triglycerides near AMAC1L2, FADS1-FADS2-FADS3 and PLTP. The proportion of individuals exceeding clinical cut points for high LDL cholesterol, low HDL cholesterol and high triglycerides varied according to an allelic dosage score (P < 10(-15) for each trend). These results suggest that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia.://000262085300016Kathiresan, Sekar Willer, Cristen J. Peloso, Gina M. Demissie, Serkalem Musunuru, Kiran Schadt, Eric E. Kaplan, Lee Bennett, Derrick Li, Yun Tanaka, Toshiko Voight, Benjamin F. Bonnycastle, Lori L. Jackson, Anne U. Crawford, Gabriel Surti, Aarti Guiducci, Candace Burtt, Noel P. Parish, Sarah Clarke, Robert Zelenika, Diana Kubalanza, Kari A. Morken, Mario A. Scott, Laura J. Stringham, Heather M. Galan, Pilar Swift, Amy J. Kuusisto, Johanna Bergman, Richard N. Sundvall, Jouko Laakso, Markku Ferrucci, Luigi Scheet, Paul Sanna, Serena Uda, Manuela Yang, Qiong Lunetta, Kathryn L. Dupuis, Josee de Bakker, Paul I. W. O'Donnell, Christopher J. Chambers, John C. Kooner, Jaspal S. Hercberg, Serge Meneton, Pierre Lakatta, Edward G. Scuteri, Angelo Schlessinger, David Tuomilehto, Jaakko Collins, Francis S. Groop, Leif Altshuler, David Collins, Rory Lathrop, G. Mark Melander, Olle Salomaa, Veikko Peltonen, Leena Orho-Melander, Marju Ordovas, Jose M. Boehnke, Michael Abecasis, Goncalo R. Mohlke, Karen L. Cupples, L. Adrienne 1061-4036ISI:00026208530001625.5P|?+Prokopenko, I. Langenberg, C. Florez, J. C. Saxena, R. Soranzo, N. Thorleifsson, G. Loos, R. J. F. Manning, A. K. Jackson, A. U. Aulchenko, Y. Potter, S. C. Erdos, M. R. Sanna, S. Hottenga, J. J. Wheeler, E. Kaakinen, M. Lyssenko, V. Chen, W. M. Ahmadi, K. Beckmann, J. S. Bergman, R. N. Bochud, M. Bonnycastle, L. L. Buchanan, T. A. Cao, A. Cervino, A. Coin, L. Collins, F. S. Crisponi, L. De Geus, E. J. C. Dehghan, A. Deloukas, P. Doney, A. S. F. Elliott, P. Freimer, N. Gateva, V. Herder, C. Hofman, A. Hughes, T. E. Hunt, S. Illig, T. Inouye, M. Isomaa, B. Johnson, T. Kong, A. Krestyaninova, M. Kuusisto, J. Laakso, M. Lim, N. Lindblad, U. Lindgren, C. M. McCann, O. T. Mohlke, K. L. Morris, A. D. Naitza, S. Orru, M. Palmer, C. N. A. Pouta, A. Randall, J. Rathmann, W. Saramies, J. Scheet, P. Scott, L. J. Scuteri, A. Sharp, S. Sijbrands, E. Smit, J. H. Song, K. Steinthorsdottir, V. Stringham, H. M. Tuomi, T. Tuomilehto, J. Uitterlinden, A. G. Voight, B. F. Waterworth, D. Wichmann, H. E. Willemsen, G. Witteman, J. C. M. Yuan, X. Zhao, J. H. Zeggini, E. Schlessinger, D. Sandhu, M. Boomsma, D. I. Uda, M. Spector, T. D. Penninx, Bwjh Altshuler, D. Vollenweider, P. Jarvelin, M. R. Lakatta, E. Waeber, G. Fox, C. S. Peltonen, L. Groop, L. C. Mooser, V. Cupples, L. A. Thorsteinsdottir, U. Boehnke, M. Barroso, I. S. Van Duijn, C. Dupuis, J. Watanabe, R. M. Stefansson, K. McCarthy, M. I. Wareham, N. J. Meigs, J. B. Abecasis, G. R.20093Variants in MTNR1B influence fasting glucose levels77-81Nature Genetics411ArticleJan8To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.://000262085300019HProkopenko, Inga Langenberg, Claudia Florez, Jose C. Saxena, Richa Soranzo, Nicole Thorleifsson, Gudmar Loos, Ruth J. F. Manning, Alisa K. Jackson, Anne U. Aulchenko, Yurii Potter, Simon C. Erdos, Michael R. Sanna, Serena Hottenga, Jouke-Jan Wheeler, Eleanor Kaakinen, Marika Lyssenko, Valeriya Chen, Wei-Min Ahmadi, Kourosh Beckmann, Jacques S. Bergman, Richard N. Bochud, Murielle Bonnycastle, Lori L. Buchanan, Thomas A. Cao, Antonio Cervino, Alessandra Coin, Lachlan Collins, Francis S. Crisponi, Laura De Geus, Eco J. C. Dehghan, Abbas Deloukas, Panos Doney, Alex S. F. Elliott, Paul Freimer, Nelson Gateva, Vesela Herder, Christian Hofman, Albert Hughes, Thomas E. Hunt, Sarah Illig, Thomas Inouye, Michael Isomaa, Bo Johnson, Toby Kong, Augustine Krestyaninova, Maria Kuusisto, Johanna Laakso, Markku Lim, Noha Lindblad, Ulf Lindgren, Cecilia M. McCann, Owen T. Mohlke, Karen L. Morris, Andrew D. Naitza, Silvia Orru, Marco Palmer, Colin N. A. Pouta, Anneli Randall, Joshua Rathmann, Wolfgang Saramies, Jouko Scheet, Paul Scott, Laura J. Scuteri, Angelo Sharp, Stephen Sijbrands, Eric Smit, Jan H. Song, Kijoung Steinthorsdottir, Valgerdur Stringham, Heather M. Tuomi, Tiinamaija Tuomilehto, Jaakko Uitterlinden, Andre G. Voight, Benjamin F. Waterworth, Dawn Wichmann, H-Erich Willemsen, Gonneke Witteman, Jacqueline C. M. Yuan, Xin Zhao, Jing Hua Zeggini, Eleftheria Schlessinger, David Sandhu, Manjinder Boomsma, Dorret I. Uda, Manuela Spector, Tim D. Penninx, Brenda W. J. H. Altshuler, David Vollenweider, Peter Jarvelin, Marjo Riitta Lakatta, Edward Waeber, Gerard Fox, Caroline S. Peltonen, Leena Groop, Leif C. Mooser, Vincent Cupples, L. Adrienne Thorsteinsdottir, Unnur Boehnke, Michael Barroso, Ines Van Duijn, Cornelia Dupuis, Josee Watanabe, Richard M. Stefansson, Kari McCarthy, Mark I. Wareham, Nicholas J. Meigs, James B. Abecasis, Goncalo R. 1061-4036ISI:00026208530001925.556,|?,9Lyssenko, V. Nagorny, C. L. F. Erdos, M. R. Wierup, N. Jonsson, A. Spegel, P. Bugliani, M. Saxena, R. Fex, M. Pulizzi, N. Isomaa, B. Tuomi, T. Nilsson, P. Kuusisto, J. Tuomilehto, J. Boehnke, M. Altshuler, D. Sundler, F. Eriksson, J. G. Jackson, A. U. Laakso, M. Marchetti, P. Watanabe, R. M. Mulder, H. Groop, L.2009oCommon variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion82-88Nature Genetics411ArticleJanGenome-wide association studies have shown that variation in MTNR1B (melatonin receptor 1B) is associated with insulin and glucose concentrations. Here we show that the risk genotype of this SNP predicts future type 2 diabetes (T2D) in two large prospective studies. Specifically, the risk genotype was associated with impairment of early insulin response to both oral and intravenous glucose and with faster deterioration of insulin secretion over time. We also show that the MTNR1B mRNA is expressed in human islets, and immunocytochemistry confirms that it is primarily localized in beta cells in islets. Nondiabetic individuals carrying the risk allele and individuals with T2D showed increased expression of the receptor in islets. Insulin release from clonal beta cells in response to glucose was inhibited in the presence of melatonin. These data suggest that the circulating hormone melatonin, which is predominantly released from the pineal gland in the brain, is involved in the pathogenesis of T2D. Given the increased expression of MTNR1B in individuals at risk of T2D, the pathogenic effects are likely exerted via a direct inhibitory effect on beta cells. In view of these results, blocking the melatonin ligand-receptor system could be a therapeutic avenue in T2D.://000262085300020Lyssenko, Valeriya Nagorny, Cecilia L. F. Erdos, Michael R. Wierup, Nils Jonsson, Anna Spegel, Peter Bugliani, Marco Saxena, Richa Fex, Malin Pulizzi, Nicolo Isomaa, Bo Tuomi, Tiinamaija Nilsson, Peter Kuusisto, Johanna Tuomilehto, Jaakko Boehnke, Michael Altshuler, David Sundler, Frank Eriksson, Johan G. Jackson, Anne U. Laakso, Markku Marchetti, Piero Watanabe, Richard M. Mulder, Hindrik Groop, Leif 1061-4036ISI:00026208530002025.556XGX|?-uIbrahem, S. Salmenlinna, S. Virolainen, A. Kerttula, A. M. Lyytikainen, O. Jagerroos, H. Broas, M. Vuopio-Varkila, J.2009cCarriage of Methicillin-Resistant Staphylococci and Their SCCmec Types in a Long-Term-Care Facility32-37 Journal of Clinical Microbiology471ArticleJan.Following an outbreak caused by staphylococcal cassette chromosome mec (SCCmec) type V methicillin (meticillin)-resistant Staphylococcus aureus (MRSA), a point-prevalence survey of the nasal carriage of staphylococci was conducted in a long-term-care facility in northern Finland in 2004. The focus was directed at methicillin-resistant coagulase-negative staphylococci (MR-CNS) and their SCCmec elements. A nasal swab was taken from 76 of the 80 residents 6 months after the onset of the outbreak. Staphylococcal isolates were identified by conventional methods and the GenoType Staphylococcus test, and their SCCmec elements were analyzed. Of the 76 individuals, 24 (32%) carried S. aureus and 67 (88%) CNS in their nostrils. Of the CNS carriers, 41 (61%) had at least one mecA-positive MR-CNS, and two individuals (3%) had both MRSA and methicillin-resistant Staphylococcus epidermidis (MRSE). Among the 61 MR-CNS isolates identified, 49 (80%) were MRSE. The distribution of the SCCmec types was diverse: 20 (33%) were of type IV, 11 (18%) of type V, 4 (6%) of type I or IA, 3 (4%) of type II, and 23 (38%) of new types (with six different combinations of ccr and other mec genes or only mecA). Both of the individuals with MRSA and MRSE shared SCCmec type V among their isolates. Nasal MR-CNS carriage was common among the residents of this long-term-care facility. A variety of SCCmec types, including many new types, were identified among the MR-CNS strains. The horizontal transfer of SCCmec elements is speculated based on the sharing of SCCmec type V between MRSA and MRSE.://000262158000002Ibrahem, Salha Salmenlinna, Saara Virolainen, Anni Kerttula, Anne-Marie Lyytikainen, Outi Jagerroos, Henrik Broas, Markku Vuopio-Varkila, Jaana 0095-1137ISI:0002621580000023.70810.9'||?.SPaju, S. Pussinen, P. J. Suominen-Taipale, L. Hyvonen, M. Knuuttila, M. Kononen, E.2009eDetection of Multiple Pathogenic Species in Saliva Is Associated with Periodontal Infection in Adults235-238 Journal of Clinical Microbiology471ArticleJanVWe investigated whether certain bacterial species and their combinations in saliva can be used as markers for periodontitis. In 1,198 subjects, the detection of multiple species, rather than the presence of a certain pathogen, in saliva was associated with periodontitis as determined by the number of teeth with deepened periodontal pockets.://000262158000037fPaju, Susanna Pussinen, Pirkko J. Suominen-Taipale, Liisa Hyvonen, Mari Knuuttila, Matti Kononen, Eija 0095-1137ISI:0002621580000373.70810 x|?/dLajunen, T. Vikatmaa, P. Bloigu, A. Ikonen, T. Lepantalo, M. Pussinen, P. J. Saikku, P. Leinonen, M.2008Chlamydial LPS and high-sensitivity CRP levels in serum are associated with an elevated body mass index in patients with cardiovascular disease375-382Innate Immunity146ArticleDecXObjective: Seropositivity for Chlamydia pneumoniae has been associated with an elevated body mass index (BMI). Our aim was to study if serum chlamydial lipopolysaccharide (cLPS), C. pneumoniae antibodies and high-sensitivity C-reactive protein (hsCRP) levels are associated with BMI Patients and Methods: The stud), population consisted of 174 patients with symptomatic carotid stenosis. abdominal aortic aneurysm or occlusive aortic disease. Information on BMI. diabetes, smoking, hypercholesterolemia. and statin medication was available. Serum C. pneumoniae IgG and IgA antibodies, cLPS, hsCRP and total endotoxin activity (totLPS) were measured. Results: BMI, correlated with cLPS (r = 0.197 ;P < 0.01) and with hsCRP (rho = 0.195; P < 0.01) in addition, there was a positive correlation between cLPS and hsCRP (rho = 0.499: P < 0.01). A trend of,in increasing proportion of C. pneumoniae IgG positivity (titre >= 64: P = 0.018) and higher serum cLPS (P = 0.01) and hsCRP (P = 0.01) concentrations, was observed across the BMI groups (BMI <= 24.9 kp/m(2), BMI = 25.0-29.9 kg/m(2), and BMI >= 30.0 kg/m(2)). Among the three BMI groups, 24.6%, 38.8%, and 48.3% were C. pneumoniae IgG-positive and the median (IQR) cLPS concentrations (ng/ml) of the groups were: 92.6 (50.8-167.0) 128.9 (76.4-163.9) and 146.4 (105.8-175.8). respectively. The median (IQR) hsCRP (mg/l) concentrations of the groups were: 1.70 (0.70-3.05) 1.70 (0.80-5.20), and 3.40 (1.45-8.55), respectively. These associations remained statistically significant in a multivariate analysis. Conclusions: Elevated serum cLPS levels were associated with an elevated BMI. This is a novel finding and it strengthens the link between chlamydial infection and obesity. A lack of association between totLPS and BMI suggests that the association between infection and an elevated BMI may be specific to certain pathogens.://000262097000005}Lajunen, Taina Vikatmaa, Pirkka Bloigu, Aini Ikonen, Tuija Lepantalo, Mauri Pussinen, Pirkko J. Saikku, Pekka Leinonen, Maija 1753-4259ISI:00026209700000510.1177/1753425908099172q_|?0zPicciotto, S. Forastiere, F. Pistelli, R. Koenig, W. Lanki, T. Ljungman, P. Pitsavos, C. Ruckerl, R. Sunyer, J. Peters, A.2008TDeterminants of plasma interleukin-6 levels among survivors of myocardial infarction631-638>European Journal of Cardiovascular Prevention & Rehabilitation156ArticleDecBackground We identify determinants of plasma interleukin-6 (IL-6) levels in a multicenter panel study of myocardial infarction (MI) survivors, using repeated measurements to evaluate both baseline and time-varying factors. Design and methods Survivors of MI (N=1003) recruited in six European cities had repeated measurements (median: 6/patient) of IL-6. At baseline, participants' behaviour and medical histories were determined by interview, and blood pressure, anthropometry, cholesterol and N-terminal B-type natriuretic peptide (NT-proBNP) were measured. Short-term exposures and medication intake were recorded at each visit. Generalized additive mixed models were used to analyze associations of IL-6 with baseline and time-varying risk factors, taking into account repeated measurements. Results Age, hour of blood withdrawal, body mass index, pack-years of smoking, NT-proBNP, systolic blood pressure, high-density lipoprotein cholesterol, persistent cough/phlegm and statin use were significantly and independently associated with IL-6 after adjustment for city, recurrent MI, baseline alcohol intake, current active smoking, tea consumption and extreme anger or stress. Conclusion Among MI survivors, IL-6 levels are associated with many traditional cardiovascular risk factors. Patients with elevated NT-proBNP, respiratory symptoms or obesity had higher IL-6 concentrations and may potentially be at greater risk for coronary artery disease progression. Eur J Cardiovasc Prev Rehabil 15:631-638 (C) 2008 The European Society of Cardiology://000262067200003Picciotto, Sally Forastiere, Francesco Pistelli, Riccardo Koenig, Wolfgang Lanki, Timo Ljungman, Petter Pitsavos, Christos Ruckerl, Regina Sunyer, Jordi Peters, Annette 1741-8267ISI:0002620672000032.22110.1097/HJd|?1zMenotti, A. Lanti, M. Kromhout, D. Blackburn, H. Jacobs, D. Nissinen, A. Dontas, A. Kafatos, A. Nedeljkovic, S. Adachi, H.2008Homogeneity in the relationship of serum cholesterol to coronary deaths across different cultures: 40-year follow-up of the Seven Countries Study719-725>European Journal of Cardiovascular Prevention & Rehabilitation156ArticleDecBackground The aim was to investigate whether multivariate coefficients of serum cholesterol in the prediction of coronary heart disease (CHD) deaths were similar across different cultures in a long-term follow-up. Design Thirteen cohorts for a total of 10 157 men aged 40-59 years at entry, enrolled in seven countries (USA, Finland, the Netherlands, Italy, Serbia, Greece, Japan) were repeatedly examined and followed up for 40 years. Methods Serum cholesterol measured at baseline, and then on repeated occasions, was studied, using multivariate models, in relation with the occurrence of CHD deaths during a 40-year follow-up. Results Homogeneity of multivariate serum cholesterol coefficients was found considering cholesterol levels at baseline, as average of up to three measurements during the first 10 years, as average of up to six measurements in 35 years, using the time-dependent technique with up to three measurements in 10 years, and with up to six measurement in 35 years. Conclusion The strength of the association between serum cholesterol and CHD death seems homogeneous across different cultures characterized by different levels of serum cholesterol and different absolute risk of CHD death. Eur J Cardiovasc Prev Rehabil 15:719-725 (C) 2008 The European Society of Cardiology://000262067200017Menotti, Alessandro Lanti, Mariapaola Kromhout, Daan Blackburn, Henry Jacobs, David Nissinen, Aulikki Dontas, Anastasios Kafatos, Antony Nedeljkovic, Srecko Adachi, Hisashi 1741-8267ISI:0002620672000172.22110.1097/HJRSC|?22Roine, I. Saukkoriipi, A. Leinonen, M. Peltola, H.2009Microbial genome count in cerebrospinal fluid compared with clinical characteristics in pneumococcal and Haemophilus influenzae type b meningitis in children16-23.Diagnostic Microbiology and Infectious Disease631ArticleJancCerebrospinal fluid genome counts were determined by quantitative real-time polymerase chain reaction from 121 children: 36 with Streptococcus pneumoniae and 85 with Haemophilus influenzae meningitis. To examine the interactions of genome count and to determine its prognostic importance, we projected the results against findings on admission and different outcomes. The genome count varied vastly in both meningitides ranging from 0 to 9250 000/mu L. The genome quantity was weakly associated with only some of the patient findings on admission. High counts predicted neurologic (odds ratio [OR] = 1.36; 95% confidence interval [CI], 1.09-1.69; P = 0.006 for 1 log increase) but not audiologic sequelae. They also predicted death in S pneumoniae (OR 2.05; 95% CI, 1.08-3.87; P = 0.03) but not in H. influenzae meningitis. (C) 2008 Elsevier Inc. All rights reserved.://000262092000003BRoine, Irmelil Saukkoriipi, Annika Leinonen, Maija Peltola, Heikki 0732-8893ISI:0002620920000032.448"10.1016/j.diagmicrN|?3vSihvola, E. Keski-Rahkonen, A. Dick, D. M. Hoek, H. W. Raevuori, A. Rose, R. J. Pulkkinen, L. Marttunen, M. Kaprio, J.2009YProspective associations of early-onset Axis I disorders with developing eating disorders20-25Comprehensive Psychiatry501ArticleJan-Feb$Objective: The purpose of this study is to analyze the developmental relationships of adolescent-onset Axis I mental disorders and eating disorders (EDs). Method: One thousand three hundred eighteen adolescent twins born from 1983 to 1987 completed a professionally administered semistructured psychiatric interview at the age of 14 years and a questionnaire follow-up at the age of 17.5 years. Results: Eating disorders at the age of 17.5 years were significantly predicted by major depressive disorder (odds ratio, 5.9; 95% confidence interval, 2.6-15.3) and generalized anxiety disorder (GAD) (odds ratio, 4.7; 95% confidence interval, 1.8-15.6) at the age of 14 years, when baseline EDs were excluded. Early-onset major depressive disorder in combination with GAD increased the likelihood of developing EDs compared with either mood or anxiety disorders alone. Similar risks and trends were evident in within-family analyses of twin pairs discordant for baseline predictors and ED outcome. Conclusions: Depressive disorder and GAD that manifest at that age of 14 years predict future EDs. Analysis of discordant twins suggested that early-onset depressive disorder and GAD prospectively relate to EDs in adolescence, even after familial factors are taken into account. (C) 2009 Elsevier Inc. All rights reserved.://000262090100004Sihvola, Elina Keski-Rahkonen, Anna Dick, Danielle M. Hoek, Hans W. Raevuori, Anu Rose, Richard J. Pulkkinen, Lea Marttunen, Mauri Kaprio, Jaakko 0010-440XISI:0002620901000041.85710.1016/j.comppsych.2008.05.004 obio.2008.09.005  1356-008-0061-9  0-0 [doi]eng .251 [doi]Eng .0b013e328315789c R.0b013e3283069d9a  sj.ejcn.1602893 147282 [doi]eng 1038/ijo.2008.196 038/ijo.2008.258  34.2008.00296.x 1128/jcm.01085-08 .1128/jcm.01824-08  .M800196-JLR200 2958.2008.06347.x  5610.1038/ng.269  5610.1038/ng.291 10.1038/ng.288 10.1038/ng.290  5610.1038/ng.271 10.1038/ng.287`enders, A. Campbell, M. Rice, J. P. Todd, R. D. Goate, A. M. Peltonen, L. Heath, A. C. Kaprio, J. Martin, N. G. Madden, P. A. F.2008Genetic Linkage and Association Findings for DSM-IV Major Depressive Disorder: Is the Metabotropic Glutamate Receptor 7 Gene (GRM7) an Important Risk Factor for Depression in Smokers?643-643Behavior Genetics386Meeting AbstractNov://000260539000121Pergadia, Michele L. Glowinski, Anne L. Agrawal, Arpana Montgomery, Grant W. Loukola, Anu Broms, Ulla Saccone, Scott F. Korhonen, Tellervo Wang, Jen C. Grant, Julia D. Lessov-Schalggar, Christina N. Todorov, Alexandre A. Wray, Naomi R. Heikkila, Kauko Statham, Dixie J. Henders, Anjali Campbell, Megan Rice, John P. Todd, Richard D. Goate, Alison M. Peltonen, Leena Heath, Andrew C. Kaprio, Jaakko Martin, Nicholas G. Madden, Pamela A. F. 0001-8244ISI:000260539000121 446003172.183  853890802301983 07853890802392511  853890802258753 11.010 [doi]Eng 390000092.953 5390001212.953  90001542.953t*on, Annamari Hokkanen, Laura Kaprio, Jaakko Rose, Richard J. 0001-8244ISI:000260539000154|?7&Gursoy, U. K. Kononen, E. Uitto, V. J.2008cIntracellular replication of fusobacteria requires new actin filament formation of epithelial cells 1063-1070Apmis11612ArticleDecWe examined survival and replication of fusobacteria inside epithelial cells. Subconfluent cultures of HaCaT keratinocytes were infected with five bacterial strains representing three Fusobacterium species: F. nucleatum, F. necrophorum, and F. mortiferum. Adhesion and invasion of the bacteria were assayed before and after antibiotic treatment that killed the adhered and extracellular bacteria. The number of live fusobacteria was examined by bacterial culturing after sonication of the epithelial cells. The role of host cell cytoskeleton functions was examined by treating the epithelial cells with cell function inhibitors. Number of viable epithelial cells was measured with the CellTiter96 kit. The tested Fusobacterium species adhered to and invaded the epithelial cells, and multiplied intracellularly for several hours. Thereafter, the intracellular number of bacteria rapidly declined. Concomitantly, viable fusobacteria were detected in the culture medium. Treatment of the infected epithelial cells with an actin formation inhibitor markedly reduced the number of living intracellular fusobacteria. Newly formed actin filaments were seen by confocal microscopy in the epithelial cells associated with the invaded bacteria. Fusobacteria infection did not reduce the number of viable epithelial cells in culture. Thus, fusobacteria are able to adhere to and invade epithelial cells, and survive under aerobic conditions. This property may enable them to survive in mucosa and participate in various disease processes of oral and pharyngeal tissues.://0002621051000065Gursoy, Ulvi Kahraman Kononen, Eija Uitto, Veli-Jukka 0903-4641ISI:0002621051000061.421 10.1111/j.1600-0463.2008.00868.xPKCx;:I/**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! 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