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New articles - Uudet artikkelit 23.1.2009 - ISI Web of Knowledge & PubMed Search Alert
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Cardiovascular health of Finnish war evacuees 60 years later
Alastalo, H., Raikkonen, K., Pesonen, A. K., Osmond, C., Barker, D. J. P., Kajantie, E., Heinonen, K., Forsen, T. J. and Eriksson, J. G. Annals of Medicine. 2009; 41(1): 66-72. Article. IF 5.779 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. Aliev, F., Dick, D. M., Viken, R. J., Winter, T., Vuoksimaa, E., Happola, A., Siltala, M., Kaprio, J. and Rose, R. J. Behavior Genetics. 2008; 38(6): 613-613. Meeting Abstract. IF 2.953 Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts Aulchenko, Y. S., Ripatti, S., Lindqvist, I., Boomsma, D., Heid, I. M., Pramstaller, P. P., Penninx, B., Janssens, A., 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. and Peltonen, L. Nature Genetics. 2009; 41(1): 47-55. Article. IF 25.556 Recent 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. The Twin Spine Study: Contributions to a changing view of disc degeneration Battie, M. C., Videman, T., Kaprio, J., Gibbons, L. E., Gill, K., Manninen, H., Saarela, J. and Peltonen, L. Spine Journal. 2009; 9(1): 47-59. Article. 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. Intracellular replication of fusobacteria requires new actin filament formation of epithelial cells Gursoy, U. K., Kononen, E. and Uitto, V. J. Apmis. 2008; 116(12): 1063-1070. Article. IF 1.421 We 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. Haapasalo, K., Jarva, H., Siljander, T., Tewodros, W., Vuopio-Varkila, J. and Jokiranta, T. S. Molecular Microbiology. 2008; 70(3): 583-594. Article. IF 5.462 The 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. Happo, M. S., Hirvonen, M. R., Halinen, A. I., Jalava, P. I., Pennanen, A. S., Sillanpaa, M., Hillamo, R. and Salonen, R. O. Inhal Toxicol. 2008; 20(14): 1215-31. IF 1.831 Inflammation 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. Carriage of Methicillin-Resistant Staphylococci and Their SCCmec Types in a Long-Term-Care Facility Ibrahem, S., Salmenlinna, S., Virolainen, A., Kerttula, A. M., Lyytikainen, O., Jagerroos, H., Broas, M. and Vuopio-Varkila, J. Journal of Clinical Microbiology. 2009; 47(1): 32-37. Article. IF 3.708 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. Early-life events. Effects on aging Kajantie, E. Hormones-International Journal of Endocrinology and Metabolism. 2008; 7(2): 101-113. Review. 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. Kallio, P., Tolppanen, A. M., Kolehmainen, M., Poutanen, K., Lindstrom, J., Tuomilehto, J., Kuulasmaa, T., Kuusisto, J., Pulkkinen, L. and Uusitupa, M. International Journal of Obesity. 2009; 33(1): 80-88. Article. IF 3.560 Background: 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. Common variants at 30 loci contribute to polygenic dyslipidemia 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. and Cupples, L. A. Nature Genetics. 2009; 41(1): 56-65. Article. IF 25.556 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. MYO9B polymorphisms in multiple sclerosis Kemppinen, 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. and Saarela, J. Eur J Hum Genet. 2009. IF 4.003 Single-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. Do childhood social circumstances affect overweight and obesity in early adulthood? Kestila, L., Rahkonen, O., Martelin, T., Lahti-Koski, M. and Koskinen, S. Scand J Public Health. 2009. IF 1.222 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. Apolipoprotein E epsilon 4 magnifies lifestyle risks for dementia: a population-based study Kivipelto, M., Rovio, S., Ngandu, T., Kareholt, I., Eskelinen, M., Winblad, B., Hachinski, V., Cedazo-Minguez, A., Soininen, H., Tuomilehto, J. and Nissinen, A. Journal of Cellular and Molecular Medicine. 2008; 12(6B): 2762-2771. Article. IF 6.807 The 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. SINDBIS ALPHAVIRUS INFECTION: CLINICAL FEATURES, DIAGNOSIS AND EPIDEMIOLOGY Kurkela, S., Helve, T., Raatti, O., Manni, T., Huhtamo, E., Uzcategui, N. Y., Myllynen, J., Laakkonen, J., Nuorti, J. P., Vaheri, A. and Vapalahti, O. American Journal of Tropical Medicine and Hygiene. 2008; 79(6): 317. Meeting Abstract. IF 2.183 Lajunen, T., Vikatmaa, P., Bloigu, A., Ikonen, T., Lepantalo, M., Pussinen, P. J., Saikku, P. and Leinonen, M. Innate Immunity. 2008; 14(6): 375-382. Article. Objective: 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. Lyssenko, 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. and Groop, L. Nature Genetics. 2009; 41(1): 82-88. Article. IF 25.556 Genome-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. Menotti, A., Lanti, M., Kromhout, D., Blackburn, H., Jacobs, D., Nissinen, A., Dontas, A., Kafatos, A., Nedeljkovic, S. and Adachi, H. European Journal of Cardiovascular Prevention & Rehabilitation. 2008; 15(6): 719-725. Article. IF 2.221 Background 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 Mustelin, L., Silventoinen, K., Pietilainen, K., Rissanen, A. and Kaprio, J. International Journal of Obesity. 2009; 33(1): 29-36. Article. IF 3.560 Objective: 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. 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. and Taskinen, M. R. Journal of Lipid Research. 2009; 50(2): 183-192. Article. IF 4.336 The 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. Nummela, O., Sulander, T., Rahkonen, O. and Uutela, A. Arch Gerontol Geriatr. 2009. IF 1.289 This 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. Paju, S., Pussinen, P. J., Suominen-Taipale, L., Hyvönen, M., Knuuttila, M. and Könönen, E. Journal of Clinical Microbiology. 2009; 47(1): 235-238. Article. IF 3.708 We 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. Patja, K., Vainiotalo, S., Laatikainen, T., Kuusimäki, L., Peltonen, K. and Vartiainen, E. Nicotine Tob Res. 2008; 10(8): 1327-33. IF 2.129 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. Problems in using incidence to analyze risk factors in follow-up studies Pekkanen, J. and Sunyer, J. Eur J Epidemiol. 2008; 23(9): 581-4. IF 1.727 The 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. Pergadia, 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. and Madden, P. A. F. Behavior Genetics. 2008; 38(6): 643-643. Meeting Abstract. IF 2.953 Validity and reproducibility of the NORBAGREEN food frequency questionnaire Petkeviciene, J., Simila, M., Becker, W., Kriaucioniene, V. and Valsta, L. M. European Journal of Clinical Nutrition. 2009; 63(1): 141-149. Article. IF 2.326 Objective: 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. Determinants of plasma interleukin-6 levels among survivors of myocardial infarction Picciotto, S., Forastiere, F., Pistelli, R., Koenig, W., Lanki, T., Ljungman, P., Pitsavos, C., Ruckerl, R., Sunyer, J. and Peters, A. European Journal of Cardiovascular Prevention & Rehabilitation. 2008; 15(6): 631-638. Article. IF 2.221 Background 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 Variants in MTNR1B influence fasting glucose levels 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, B., 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. and Abecasis, G. R. Nature Genetics. 2009; 41(1): 77-81. Article. IF 25.556 To 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. Roine, I., Saukkoriipi, A., Leinonen, M. and Peltola, H. Diagnostic Microbiology and Infectious Disease. 2009; 63(1): 16-23. Article. IF 2.448 Cerebrospinal 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. The information environment of researchers in molecular medicine Roos, A., Kumpulainen, S., Järvelin, K. and Hedlund, T. Information Research-an International Electronic Journal. 2008; 13(3). Article. Introduction. 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. Genome-wide association analysis of metabolic traits in a birth cohort from a founder population 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. and Peltonen, L. Nature Genetics. 2009; 41(1): 35-46. Article. IF 25.556 Genome-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. NOVEL SPECIES OF HUMAN RHINOVIRUSES IN ACUTE OTITIS MEDIA Savolainen-Kopra, C., Blomqvist, S., Kilpi, T., Roivainen, M. and Hovi, T. Pediatric Infectious Disease Journal. 2009; 28(1): 59-61. Article. IF 3.086 We 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. Temporal variation in case fatality of acute myocardial infarction in Finland Schreier, N. K., Moltchanova, E. V., Lammi, N. M., Karvonen, M. L. and Eriksson, J. G. Annals of Medicine. 2009; 41(1): 73-80. Article. IF 5.779 Background. 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. Prospective associations of early-onset Axis I disorders with developing eating disorders Sihvola, E., Keski-Rahkonen, A., Dick, D. M., Hoek, H. W., Raevuori, A., Rose, R. J., Pulkkinen, L., Marttunen, M. and Kaprio, J. Comprehensive Psychiatry. 2009; 50(1): 20-25. Article. IF 1.857 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. Tyynela, P., Goebeler, S., Ilveskoski, E., Mikkelsson, J., Perola, M., Loytonen, M. and Karhunen, P. Annals of Medicine. 2009; 41(1): 57-65. Article. IF 5.779 Background. 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. Verta, M., Kiviranta, H., Salo, S., Malve, O., Korhonen, M., Verkasalo, P. K., Ruokojarvi, P., Rossi, E., Hanski, A., Paatalo, K. and Vartiainen, T. Environmental Science and Pollution Research. 2009; 16(1): 95-105. Article. IF 3.894 The 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. 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. and Hirschhorn, J. N. Nature Genetics. 2009; 41(1): 25-34. Article. IF 25.556 Common 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. Extreme Male/Female Brain Defined with Two Neuropsychological Tests Vuoksimaa, E., Tuulio-Henriksson, A., Hokkanen, L., Kaprio, J. and Rose, R. J. Behavior Genetics. 2008; 38(6): 652-652. Meeting Abstract. IF 2.953 |