|
New articles - Uudet artikkelit 22.6.2009 - ISI Web of Knowledge & PubMed Search Alert
|
|
Relative Risks for Stroke by Age, Sex, and Population Based on Follow-Up of 18 European Populations in the MORGAM Project
Asplund, K., Karvanen, J., Giampaoli, S., Jousilahti, P., Niemela, M., Broda, G., Cesana, G., Dallongeville, J., Ducimetriere, P., Evans, A., Ferrieres, J., Haas, B., Jorgensen, T., Tamosiunas, A., Vanuzzo, D., Wiklund, P. G., Yarnell, J., Kuulasmaa, K. and Kulathinal, S. Stroke. 2009. IF 6.499 BACKGROUND AND PURPOSE: Within the framework of the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project, the variations in impact of classical risk factors of stroke by population, sex, and age were analyzed. METHODS: Follow-up data were collected in 43 cohorts in 18 populations in 8 European countries surveyed for cardiovascular risk factors. In 93 695 persons aged 19 to 77 years and free of major cardiovascular disease at baseline, total observation years were 1 234 252 and the number of stroke events analyzed was 3142. Hazard ratios were calculated by Cox regression analyses. RESULTS: Each year of age increased the risk of stroke (fatal and nonfatal together) by 9% (95% CI, 9% to 10%) in men and by 10% (9% to 10%) in women. A 10-mm Hg increase in systolic blood pressure involved a similar increase in risk in men (28%; 24% to 32%) and women (25%; 20% to 29%). Smoking conferred a similar excess risk in women (104%; 78% to 133%) and in men (82%; 66% to 100%). The effect of increasing body mass index was very modest. Higher high-density lipoprotein cholesterol levels decreased the risk of stroke more in women (hazard ratio per mmol/L 0.58; 0.49 to 0.68) than in men (0.80; 0.69 to 0.92). The impact of the individual risk factors differed somewhat between countries/regions with high blood pressure being particularly important in central Europe (Poland and Lithuania). CONCLUSIONS: Age, sex, and region-specific estimates of relative risks for stroke conferred by classical risk factors in various regions of Europe are provided. From a public health perspective, an important lesson is that smoking confers a high risk for stroke across Europe. Blomqvist, S., Savolainen-Kopra, C., Paananen, A., Hovi, T. and Roivainen, M. Journal of General Virology. 2009; 90: 1371-1381. Article. IF 3.092 Human rhinoviruses (HRVs), which are the most frequent causative agents of acute upper respiratory tract infections, are abundant worldwide. We have identified HRV strains in environmental specimens collected in Finland, Latvia and Slovakia during the surveillance of polio-and other enteroviruses. These acid-sensitive HRV strains were isolated under conditions optimized for growth of most of the enteroviruses, i.e. in stationary human rhabdomyosarcoma cells incubated at 36 degrees C. Phylogenetic analysis of the sequences derived from the partial 5' non-coding region and the capsid region coding for proteins VP4/VP2 and VP1 showed that the HRV field strains clustered together with prototype strains of the HRV minor receptor group. Partial sequences of the 3D polymerase coding region generally followed this pattern, with the exception of a set of three HRV field strains that formed a subcluster not close to any of the established HRV-A types, suggesting that recombination may have occurred during evolution of these HRV strains. Phylogenetic analysis of the VP4/VP2 capsid protein coding region showed that the 'environmental' HRV field strains were practically identical to HRV strains recently sequenced by others in Australia, the United States and Japan. Analysis of amino acids corresponding to the intercellular adhesion molecule-1 receptor footprint in major receptor group HRVs and also in the low-density lipoprotein receptor footprint of minor receptor group HRVs showed conservation of the 'minor receptor group-like' amino acids, indicating that the field strains may have maintained their minor receptor group specificity. Type 2 Diabetes Risk Alleles Are Associated With Reduced Size at Birth Freathy, R. M., Bennett, A. J., Ring, S. M., Shields, B., Groves, C. J., Timpson, N. J., Weedon, M. N., Zeggini, E., Lindgren, C. M., Lango, H., Perry, J. R. B., Ponta, A., Ruokonen, A., Hyppönen, E., Power, C., Elliott, P., Strachan, D. P., Järvelin, M. R., Smith, G. D., McCarthy, M. I., Frayling, T. M. and Hattersley, A. T. Diabetes. 2009; 58(6): 1428-1433. Proceedings Paper. IF 8.398 OBJECTIVE-Low birth weight is associated with an increased risk of type 2 diabetes. The mechanisms underlying this association are unknown and may represent intrauterine programming or two phenotypes of one genotype. The fetal insulin hypothesis proposes that common genetic variants that reduce insulin secretion or action may predispose to type 2 diabetes and also reduce birth weight, since insulin is a key fetal growth factor. We tested whether common genetic variants that predispose to type 2 diabetes also reduce birth weight. RESEARCH DESIGN AND METHODS-We genotyped single-nucleotide polymorph isms (SNPs) at five recently identified type 2 diabetes loci (CDKAL1, CDKN2A/B, HHEX-IDE, IGF2BP2, and SLC30A8) in 7,986 mothers and 19,200 offspring from four studies of white Europeans. We tested the association between maternal or fetal genotype at each locus and birth weight of the offspring. RESULTS-We found that type 2 diabetes risk alleles at the CDKAL1 and HHEX-IDE loci were associated with reduced birth weight when inherited by the fetus (21 g [95% CI 11-31], P 2 x 10(-5), and 14 g [4-23], P = 0.004, lower birth weight per risk allele, respectively). The 4% of offspring carrying four risk alleles at these two loci were 80 g (95% CI 39-120) lighter at birth than the 8% carrying none = 5 x 10(-7)). There were no associations between birth weight and fetal genotypes at the three other loci or maternal genotypes at any locus. CONCLUSIONS-Our results are in keeping with the fetal insulin hypothesis and provide robust evidence that common disease-associated variants can alter size at birth directly through the fetal genotype. Diabetes 58:1428-1433, 2009 Giltay, E. J., Dortland, A., Nissinen, A., Giampaoli, S., van Veen, T., Zitman, F. G., Bots, S. and Kromhout, D. Journal of Affective Disorders. 2009; 115(3): 471-477. Article. IF 3.271 Background: Cohort and case-control studies found that lower serum total cholesterol is associated with depression. It is, however, unclear whether low cholesterol or its lipoprotein fractions are causally related to depression. Using a Mendelian randomization design, the potential association between apolipoprotein E (APOE) genotype (affecting lifetime cholesterol levels) and depressive symptoms was studied. Methods: In the longitudinal Finland, Italy, the Netherlands Elderly (FINE) Study 1089 men were included in 1985. The 435 men from Finland, 418 men from The Netherlands, and 236 men from Italy (aged 65-84 years) were free of myocardial infarction, stroke, diabetes mellitus and cancer at all time points. They were prospectively studied around 1985 (n=658), 1990 (n=668), 1995 (n=327), and 2000 (n=82). Associations between serum cholesterol, lipoprotein fractions and APOE genotype, with depressive symptoms (by Zung self-rating depression scale [SDS]) were analyzed using multilevel regression models. Results: Serum total cholesterol was inversely associated with the Zung SDS (-0.61 points per 1 mmol/L increase in cholesterol; 95% confidence interval: -1.05 to -0.17; P=0.007), after adjustment for country, age, body mass index, smoking, and alcohol intake. However, none of the cholesterol lipoprotein fractions were associated with the Zung SDS. The APOE genotypes epsilon 4/4, epsilon 4/3; epsilon 3/3; epsilon 4/2, and epsilon 3/2 or epsilon 2/2 were associated with decreasing levels of serum total and LDL cholesterol (Ps < 0.001), but not with increasing depressive symptoms (P=0.67). Limitations: APOE genotype was assessed through protein isoforms and not actual DNA-based typing. Conclusions: There was a modest inverse relationship between depression scores and serum total cholesterol in elderly men, but no associations with lipoprotein fractions or with the APOE genotype. (C) 2008 Elsevier B.V. All rights reserved. Epidemiological Evidence for Serotype-Independent Acquired Immunity to Pneumococcal Carriage Granat, S. M., Ollgren, J., Herva, E., Mia, Z., Auranen, K. and Mäkelä, P. H. Journal of Infectious Diseases. 2009; 200(1): 99-106. Proceedings Paper. IF 5.682 Background. Asymptomatic nasopharyngeal carriage is the main reservoir for transmission of Streptococcus pneumoniae. The rate of both carriage and pneumococcal disease decreases with age. To what extent these changes are the result of developing natural immunity is currently a subject of debate. Objective. To study the hypothesis that previous carriage induces serotype-independent protective immunity to new colonization. Methods. We compared the rates of pneumococcal acquisition for children with different previous carriage histories. We identified 435 episodes of carriage during the first year of life in follow-up data for 99 Bangladeshi children. Cox regression analysis was adjusted for serotype-specific exposure within the family and other confounding factors. Results. Previous pneumococcal carriage was associated with serotype-independent protection from subsequent acquisition (hazard ratio, 0.60 [95% confidence interval, 0.39-0.90]), whereas recent serotype-specific exposure within the family was associated with an 8-fold increase in the rate of acquisition for that serotype. Conclusion. Our findings are consistent with the hypothesis that serotype-independent protective immunity is stimulated in young children by previous pneumococcal carriage and reduces the rate of new colonization. This immunity has the potential to modulate the development of carriage, irrespective of the colonizing serotype, and to do so starting early in infancy. Antidepressant use and mortality in Finland: a register-linkage study from a nationwide cohort Haukka, J., Arffman, M., Partonen, T., Sihvo, S., Elovainio, M., Tiihonen, J., Lönnqvist, J. and Keskimäki, I. European Journal of Clinical Pharmacology. 2009; 65(7): 715-720. Article. IF 2.497 It is generally acknowledged that depressed patients need specific attention during the first weeks after initiation of antidepressant (AD) treatment because of the increased risk of suicide. The study population consisted of all individuals residing in Finland from 1999 to 2003 who had purchased a prescribed antidepressant at least once but had no preceding antidepressant prescription. Data sources were the National Prescription Register, the Causes of Death Register, Census Data of Statistics Finland, and the National Care Register. Follow-up started at the first purchase and ended at the end of 2003 or death. Data on prescriptions were used to construct contiguous treatment periods of follow-up time. Life-table analysis with Poisson regression was used to estimate risk ratios (RR) of antidepressant use with respect to all-cause mortality and to deaths from suicide. Current AD use was associated with a lowered all-cause mortality (RR = 0.18, 95% CI = 0.18-0.19) compared with those who filled one previous prescription only. There was no difference in suicide mortality when any current antidepressant usage was compared to the one-prescription group. Current SSRI usage was associated with lower risk of suicide compared to the one-prescription or other antidepressant groups (RR 0.47, 0.38-0.59). Current AD treatment is associated with decreased all-cause mortality rates in patients who have ever had AD treatment. Pre-Eclampsia Is a Risk Factor of Carotid Artery Atherosclerosis Haukkamaa, L., Moilanen, L., Kattainen, A., Luoto, R., Kähönen, M., Leinonen, M., Jula, A., Kesäniemi, Y. A. and Kaaja, R. Cerebrovascular Diseases. 2009; 27(6): 599-607. Article. IF 3.041 Background: A history of pre-eclampsia has been shown to be associated with an increased risk of subsequent coronary artery disease. The intima-media thickness of carotid arteries and the detection of plaques are useful measures as regards preclinical atherosclerosis. The aim of this study was to examine whether women with a history of pre-eclampsia more often show signs of atherosclerosis compared with 2 control groups. Methods: We used data from a large Finnish cross-sectional health examination survey. We had women with previous pre-eclampsia (n = 35) or pregnancy-induced hypertension (n = 61) and 2 control groups. Laboratory tests and physical examination were performed. Information on reproductive and medical history was obtained at the home interview. Carotid atherosclerosis was assessed by ultrasonography. Results: The women with previous pre-eclampsia had significantly (p = 0.008) more atherosclerotic plaques than the healthy parous controls. The intima-media thickness in the women with previous pre-eclampsia also tended to be higher than in the other groups, although the differences did not reach statistical significance. In logistic regression analysis, advanced age (OR: 1.08; 95% CI: 1.04-1.13; p < 0.001) and pre-eclampsia (OR: 3.63; 95% CI: 1.50-8.79; p = 0.004) were independent risk factors as regards plaque, and in linear regression analysis advanced age (estimate: 0.012; 95% CI: 0.010-0.014; p < 0.001), HDL cholesterol (estimate: -0.049; 95% CI: -0.088 to -0.010; p = 0.013), systolic blood pressure, BMI (estimate: 0.005; 95% CI: 0.000-0.009; p = 0.043) and high-sensitivity C-reactive protein (estimate: -0.003; 95% CI: -0.007 to -0.000; p = 0.048) were independent risk factors with respect to intima-media thickness. Conclusions: Our data suggest that pre- eclampsia is an independent risk factor as regards developing plaque later in life. Copyright (C) 2009 S. Karger AG, Basel Holmlund, E., Quiambao, B., Ollgren, J., Jaakkola, T., Neyt, C., Poolman, J., Nohynek, H. and Käyhty, H. Clinical and Vaccine Immunology. 2009; 16(6): 916-923. Article. IF 2.237 This study focuses on the immunogenicity of the following three pneumococcal vaccine candidate proteins in Filipino infants, all inducing protection in animal models: pneumococcal histidine triad protein D (PhtD), choline binding protein A (CbpA), and the lysozyme LytC. The immunoglobulin G antibody concentrations to PhtD, its putative, protective, and exposed C-terminal fragment (PhtD C), CbpA, and LytC were measured by enzyme immunoassay in 52 serum samples from pregnant women, 39 cord blood samples, and consecutive serum samples (n = 263) from 52 newborns between 6 weeks and 10 months of age scheduled to be taken at six time points. A nasopharyngeal swab to detect pneumococcal carriage was taken parallel to the serum samples. The antibody concentrations in the cord blood samples were similar to those in the samples from the mothers. In infant sera, the geometric mean antibody concentrations (GMCs) for all three proteins decreased until the age of 18 weeks and started to increase after that age, suggesting that the infants' own antibody production started close to the age of 4 to 5 months. The increase in GMCs by age, most clear-cut for CbpA, was associated with pneumococcal carriage. Anti-PhtD concentrations were higher than anti-PhtD C concentrations but correlated well (r of 0.89 at 10.5 months), suggesting that antibodies are directed to the supposedly exposed and protective C-terminal part of PhtD. Our results show that young children are able to develop an antibody response to PhtD, CbpA, and LytC and encourage the development of pneumococcal protein vaccines for this age group. Kaste, K., Kivinummi, T., Piepponen, T. P., Kiianmaa, K. and Ahtee, L. Pharmacology Biochemistry and Behavior. 2009; 92(4): 655-662. Article. IF 2.751 Besides alcohol, alcohol-preferring AA and alcohol-avoiding ANA rats differ also with respect to other abused drugs. To study the molecular basis of these differences, we examined the expression of two transcription factors implicated in addiction, Delta FosB and pCREB, in brain dopaminergic regions of AA and ANA rats. The effects of morphine and nicotine were studied to relate the behavioral and molecular changes induced by these drugs. Baseline FosB/Delta FosB immunoreactivity (IR) in the nucleus accumbens core and pCREB IR in the prefrontal cortex (PFC) were elevated in AA rats. Morphine increased Delta FosB-like IR more readily in the caudate-putamen of AA rats than in ANA rats. In the PFC morphine decreased pCREB IR in AA rats, but increased it in ANA rats. In addition to enhanced locomotor response, the development of place preference to morphine was enhanced in AA rats. The enhanced nicotine-induced locomotor sensitization found in AA compared with ANA rats seems to depend in addition to dopamine and Delta FosB on other mechanisms. These findings Suggest that enhanced sensitivity of AA rats to morphine is related to augmented morphine-induced expression of FosB/Delta FosB and morphine-induced reduction of pCREB levels. Moreover, altered innate expression of FosB/Delta FosB and pCREB in AA rats is likely to affect the sensitivity of these rats to abused drugs. (c) 2009 Elsevier Inc. All rights reserved. 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. European Journal of Human Genetics. 2009; 17(6): 840-843. Article. IF 3.925 Single-nucleotide polymorphisms (SNPs) in the 30 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 (2009) 17, 840-843; doi: 10.1038/ejhg.2008.251; published online 14 January 2009 Do childhood social circumstances affect overweight and obesity in early adulthood? Kestilä, L., Rahkonen, O., Martelin, T., Lahti-Koski, M. and Koskinen, S. Scand J Public Health. 2009; 37(2): 206-19. IF 1.537 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 < or = BMI<30), but the effects were largely attenuated by other childhood factors and early adult circumstances. In men, no significant childhood predictors of overweight were found. Single-parent family (RRR=2.32), parental alcohol problem (RRR= 2.71), parental mental health problems (RRR=2.28) and being bullied at school (RRR=3.13) predicted obesity (BMI > or = 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. Kiiskinen, U., Suominen-Taipale, A. L. and Cairns, J. Health Econ. 2009. IF 1.994 This study concerns the choice of primary dental service provider by consumers. If the health service delivery system allows individuals to choose between public-care providers or if complementary private services are available, it is typically assumed that utilisation is a three-stage decision process. The patient first makes a decision to seek care, and then chooses the service provider. The final stage, involving decisions over the amount and form of treatment, is not considered here. The paper reports a discrete choice experiment (DCE) designed to evaluate attributes affecting individuals' choice of dental-care provider. The feasibility of the DCE approach in modelling consumers' choice in the context of non-acute need for dental care is assessed. The aim is to test whether a separate two-stage logit, a multinomial logit, or a nested logit best fits the choice process of consumers. A nested logit model of indirect utility functions is estimated and inclusive value (IV) constraints are tested for modelling implications. The results show that non-trading behaviour has an impact on the choice of appropriate modelling technique, but is to some extent dependent on the choice of scenarios offered. It is concluded that for traders multinomial logit is appropriate, whereas for non-traders and on average the nested logit is the method supported by the analyses. The consistent finding in all subgroup analyses is that the traditional two-stage decision process is found to be implausible in the context of consumer's choice of dental-care provider. Copyright (c) 2009 John Wiley & Sons, Ltd. Korhonen, T., Kujala, U. M., Rose, R. J. and Kaprio, J. Twin Research and Human Genetics. 2009; 12(3): 261-268. Article. IF 2.097 We investigated prospectively whether physical activity level in adolescence predicts use of alcohol and illicit drugs in early adulthood. We studied 4,240 individual twins (1,870 twin pairs). We classified those who consistently reported frequent leisure physical activity at ages 16, 17 and 181/2 as persistent exercisers, those exercising less than three times monthly as persistently inactive, and all others as occasional exercisers. To control for familial confounds, within-family analyses compared activity-substance use associations in co-twins discordant for baseline physical activity. Individual-based analyses showed no clear association between baseline physical activity and subsequent weekly alcohol consumption. However, weekly alcohol intoxication (OR = 1.9, p = .002) and problems due to alcohol use (OR = 2.0, p < .001) were more common among persistently inactive participants. After excluding those reporting weekly intoxication at baseline, the risk for alcohol intoxication remained elevated among women occasionally (OR = 2.4, p = .017) or persistently (OR = 5.8, p < .001) inactive at baseline, but this association was not replicated within discordant twin pairs. Individual-based analyses showed that drug use in adulthood was more common among those persistently physically inactive in adolescence (OR = 3.7, p < .001) in comparison to those persistently active. This finding was replicated within discordant twin pairs. Among those with no drug experience during adolescence, persistent inactivity (OR = 1.9, p = .007) increased risk for drug use. We conclude that persistent physical inactivity in adolescence may increase the risk of later problems due to excess alcohol use. Sedentary lifestyle predicts illicit drug use even when controlling for familial factors. Dioxins interfere with differentiation of osteoblasts and osteoclasts Korkalainen, M., Kallio, E., Olkku, A., Nelo, K., Ilvesaro, J., Tuukkanen, J., Mähönen, A. and Viluksela, M. Bone. 2009; 44(6): 1134-1142. Article. IF 4.145 We have previously shown that the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects bone growth, modelling and mechanical strength in vivo. In this study, we utilized differentiation of bone marrow stem cells to osteoblasts and osteoclasts as a model system to study the effects of TCDD on bones. Stem cells Were isolated from bone marrow of femurs and tibias of rats and mice. Progress of osteoblastic differentiation was monitored by measuring mRNA expression levels of differentiation markers from control and TCDD-treated cells using quantitative RT-PCR. TCDD significantly and dose-dependently decreased the mRNA levels of RUNX2, alkaline phosphatase and osteocalcin. Also the activity of alkaline phosphatase was significantly inhibited in both rat and mice cells. In the case of osteoclasts, TCDD decreased the number of TRACP+ multinucleated cells, with corresponding decreases in the number of F-actin rings and the area of resorption. Studies in AHR-knockout mice indicated that TCDD has no effect on the expression of osteoblastic differentiation markers suggesting that TCDD mediates its effects by AHR. Both osteoblastic and osteoclastic effects took place at very low doses of TCDD, as in most cases 100 fM TCDD was enough to significantly affect the differentiation markers. Therefore, differentiation of osteoblasts and osteoclasts from bone marrow stem cells seems to be a very sensitive target for TCDD. Disrupting effects in osteoblastic cells, in addition to disturbed osteoclastogenesis, may thus play a role in adverse effects on bone quality in TCDD exposed animals. (C) 2009 Elsevier Inc. All rights reserved. Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors Kotronen, A., Peltonen, M., Hakkarainen, A., Sevastianova, K., Bergholm, R., Johansson, L. M., Lundbom, N., Rissanen, A., Ridderstrale, M., Groop, L., Orho-Melander, M. and Yki-Järvinen, H. Gastroenterology. 2009. IF 12.591 AIMS:: To develop a method to accurately predict non-alcoholic fatty liver disease (NAFLD) and liver fat content based on routinely available clinical and laboratory data, and to test whether knowledge of the recently discovered genetic variant in the PNPLA3 gene (rs738409) increases accuracy of the prediction. METHODS:: Liver fat content was measured using proton magnetic resonance spectroscopy in 470 subjects, who were randomly divided into estimation (2/3 of the subjects, n=313) and validation (n=157) groups. Multivariate logistic and linear regression analyses were used to create a NAFLD liver fat Score to diagnose NAFLD, and Liver fat equation to estimate liver fat % in each individual. RESULTS:: The presence of the metabolic syndrome and type 2 diabetes, fasting serum (fS) insulin, fS-AST, and the AST/ALT-ratio were independent predictors of NAFLD. The NAFLD liver fat Score was as follows: -2.89+1.18*Metabolic syndrome(yes=1/no=0)+0.45*Type 2 diabetes(yes=2/no=0)+0.15*fS-insulin (mU/l)+0.04*fS-AST(U/l) -0.94*AST/ALT. The score had an area under the receiver operating characteristic curve of 0.87 in the estimation and 0.86 in the validation group. The optimal cut-off point of -0.640 predicted increased liver fat content with sensitivity of 86% and specificity of 71%. Addition of the genetic information to the Score improved the accuracy of the prediction only by <1%. Using the same variables, we developed an Liver fat equation from which liver fat % of each individual could be estimated. CONCLUSIONS:: The NAFLD liver fat Score and Liver fat equation provide simple and non-invasive tools to predict NAFLD and liver fat content. Laatikainen, T., Janus, E., Kilkkinen, A., Heistaro, S., Tideman, P., Baird, A., Tirimacco, R., Whiting, M., Franklin, L., Chapman, A., Kao-Philpot, A. and Dunbar, J. Asia-Pacific Journal of Public Health. 2009; 21(1): 51-62. Article. The aim of this article was to assess the level and prevalence of major chronic disease risk factors among rural adults. Two cross-sectional surveys were carried out in 2004 and 2005 in the southeast of South Australia and the southwest of Victoria. Altogether 891 randomly selected persons aged 25 to 74 years participated in the studies. Surveys included a self-administered questionnaire, physical measurements, and a venous blood specimen for lipid analyses. Two thirds of participants had cholesterol levels >= 5.0 mmol/L. The prevalence of high diastolic blood pressure (>= 90 mm Hg) was 22% for men and 10% for women in southeast of South Australia, and less than 10% for both sexes in southwest of Victoria. Two thirds of participants were overweight or obese (body mass index >= 25 kg/m(2)). About 15% of men and slightly less women were daily smokers. The abnormal risk factor levels underline the need for targeted prevention activities in the Greater Green Triangle region. Continuing surveillance of levels and patterns of risk factors is fundamentally important for planning and evaluating preventive activities. Impact of human papillomavirus vaccination depends on effective vaccination strategy Lehtinen, M. and Paavonen, J. Int J Cancer. 2009. IF 4.734 Lucero, M. G., Nohynek, H., Williams, G., Tallo, V., Simoes, E. A. F., Lupisan, S., Sanvictores, D., Forsyth, S., Puumalainen, T., Ugpo, J., Lechago, M., de Campo, M., Abucejo-Ladesma, E., Sombrero, L., Nissinen, A., Soininen, A., Ruutu, P., Riley, I. and Mäkelä, H. P. Pediatric Infectious Disease Journal. 2009; 28(6): 455-462. Article. IF 3.176 Background: Pneumococcus is a leading cause of childhood pneumonia worldwide. Pneumococcal Conjugate vaccines (PCV) have demonstrated efficacy against childhood invasive pneumococcal disease (IPD) and pneumonia in the United States and Africa. No information is available from Asia on the impact of PCV oil childhood pneumonia. Methods: We conducted a randomized, placebo-controlled, double-blind trial in Bohol, the Philippines (ISRCTN 62323832). Children 6 weeks to <6 months of-age were randomly allocated to receive 3 doses of either an 11-valent PCV (11PCV, sanofi Pasteur. Lyon, France) or a saline placebo, with a minimum interval of 4 weeks between doses to determine vaccine efficacy (VE) against the primary outcome of a child experiencing first episode Of community-acquired radiologically defined Pneumonia in the first 2 years of life. Secondary end points were clinical pneumonia. IPD, safety, and immunogenicity. Results: Twelve thousand One hundred ninety-one children were enrolled. By per protocol (PP) analysis, 93 of 6013 fully vaccinated 11PCV recipient children had a first episode of radiologic pneumonia compared with 120 of 6018 placebo recipients. VE against radiologically defined pneumonia for the PP cohort of children 3 to 23 months old was 22.9%, (95% CI: - 1.1, 41.2 P = 0.06), for the prespecified subgroups of children 3 to 11 months of age, 34.0% (95% CI: 4.8, 54.3: P = 0.02), kind of those 12 to 23 months old, 2.7% (95% CI: -43.5, 34.0; P = 0.88). By intent-to-treat (ITT) analysis, 119 of 6097 11PCV recipient children had all episode of radiologic pneumonia compared with 141 of 6094 placebo recipients. VE against radiologic pneumonia for the ITT cohort of children <2 years old was 16.01% (95% CI -7.3, 34.2; P = 0.16), for a subgroup of children <12 months of age. 19.8% (95% CI: -8.8, 40.8: P = 0.15) VE against clinical pneumonia by PP was not significant (VE 0.1%, 95% CI -9.4, 8.7; P = 0.99). IPD was rare: only 3 cases of IPD due to vaccine serotypes were observed during the study. 11PCV was immunogenic and well tolerated. Among 11PCV recipients, a small excess of serious adverse respiratory events was observed in the first 28 days after the first and second dose of vaccine, and of nonrespiratory events after the first dose. All excess of pneumonia episodes in 11PCV recipients in the month following the second dose of vaccination was the principal reason for lower VE by ITT analysis than by PP analysis. Conclusions: In PP analysis, a 22.9% reduction of community-acquired radiologically confirmed pneumonia in children younger than 2 years of age in the 11-valent tetanus-diphtheria toxoid-conjugated PCV vaccinated group was observed; a reduction similar as observed in other PCV trials. We Could not demonstrate any VE against clinical pneumonia. Our finding confirms for the first little that in a low-income, low-mortality developing Country in Asia, in least one-fifth of radiologically confirmed pneumonia is caused by pneumococcus, and thus preventable by PCV. Whether PCV should be included in national program in Such settings, however, depends oil careful country specific disease burden measurement and cost-effectiveness calculation. Makkonen, J., Pietiläinen, K. H., Rissanen, A., Kaprio, J. and Yki-Järvinen, H. Journal of Hepatology. 2009; 50(5): 1035-1042. Article. IF 7.056 Background/Aims: This study aimed to determine the heritability of serum alanine aminotransferase (S-ALT) and fasting serum insulin (fS-insulin) concentration as well as determine the association of these measures with liver fat content in young adult monozygotic (MZ) and dizygotic (DZ) twins. Methods: Three hundred and thirteen individual twins were recruited from a population-based cohort (n = 4929). The study subjects represented a wide range of body mass indexes (BMI), were free of any diseases or regular medications and had an intake of less than two drinks of alcohol/day. To verify that S-ALT is a marker of liver fat, it was measured by proton magnetic resonance spectroscopy (H-1 MRS) in 66 subjects. Heritability estimations were performed using BMI-and gender-adjusted values. Results: Intro-pair correlations were significantly higher in the MZ twins than the DZ twins for both S-ALT (0.65 for MZ and 0.04 for DZ) and tS-insulin (0.58 and 0.34, respectively). Heritability of S-ALT was 55%, and that of IS-insulin 61%. In the 66 subjects S-ALT (r = 0.70 for women and r = 0.50 for men, p <= 0.01 for both) and fS-insulin (r = 0.58 and r = 0.59, respectively, p <= 0.01 for both) concentrations correlated significantly with liver fat content. Conclusions: These twin data suggest that approximately 60%, of the variation in S-ALT, a marker of liver fat content, is genetically determined. (c) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Predictors of fasting serum insulin and glucose and the risk of pancreatic cancer in smokers Meinhold, C. L., de Gonzalez, A. B., Albanes, D., Weinstein, S. J., Taylor, P. R., Virtamo, J. and Stolzenberg-Solomon, R. Z. Cancer Causes & Control. 2009; 20(5): 681-690. Article. IF 3.690 A history of type 2 diabetes is one of few consistent risk factors for pancreatic cancer. Potentially modifiable factors related to fasting insulin and glucose concentrations may influence pancreatic cancer risk. Multiple linear regression models were used to identify anthropometric, clinical, behavioral, and dietary factors associated with fasting insulin and glucose in a subcohort of non-diabetics in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (n = 366). Hazards ratios (HRs) and 95% confidence intervals (CIs) were calculated among the larger cohort (n = 27,035). During follow-up (median 16.1 years), 305 participants developed pancreatic cancer. Fasting insulin and/or glucose were positively associated with body mass index (BMI), height, and dietary total and saturated fat and inversely associated with serum high-density lipoprotein cholesterol (HDL) and dietary available carbohydrates, sucrose, and alcohol. Comparing highest to lowest quintiles, total fat (HR = 1.54, 95% CI 1.05-2.25, p-trend = 0.01) and saturated fat (HR = 1.38, 95% CI 0.97-1.98, p-trend = 0.06) were positively associated and available carbohydrates (HR = 0.63, 95% CI 0.44-0.90, p-trend = 0.01), particularly sucrose (HR = 0.62, 95% CI 0.43-0.89, p-trend = 0.09), were inversely associated with risk of pancreatic cancer. BMI, HDL, height, and alcohol were not associated with pancreatic cancer risk. Dietary fat is associated with higher fasting insulin concentrations and may increase pancreatic cancer risk in smokers. Determinants of cow's milk allergy in childhood - a population-based medical birth register study Metsälä, J., Kilkkinen, A., Kaila, M., Gissler, M., Klaukka, T. and Virtanen, S. Allergy. 2009; 64: 472. Meeting Abstract. IF 6.204 Muhonen, L. H., Lönnqvist, J., Lahti, J. and Alho, H. Psychiatry Res. 2009; 167(1-2): 115-22. IF 2.666 The aim of this study was to determine predictors of the response to escitalopram, a selective serotonin re-uptake inhibitor antidepressant and memantine, a non-competitive glutamate NMDA receptor blocker, for the treatment of major depression comorbid with alcohol dependence. Eighty alcohol dependent treatment-seeking adult patients with comorbid major depressive disorder were randomized to receive either memantine 20 mg or escitalopram 20 mg for 26 weeks. In both treatment groups, depression was reduced significantly. Comparisons were made between patients in remission (final Montgomery-Asberg Depression Rating Scale (MADRS)<50%). The age at onset of the first major depressive episode significantly correlated with the treatment response in the escitalopram group; the mean age at onset of depression among patients on the non-responders group was 13.7+/-4.0 years and 31.9+/-11.9 years in remission. These results are significantly different from those with memantine. Our study provides evidence that the onset of the first major depressive episode might be a clinically relevant predictor of a response to escitalopram treatment in patients with major depression and comorbid alcohol dependence. Different Clinical Phenotypes in Monozygotic CADASIL Twins With a Novel NOTCH3 Mutation Mykkänen, K., Junna, M., Amberla, K., Bronge, L., Kaariainen, H., Pöyhönen, M., Kalimo, H. and Viitanen, M. Stroke. 2009; 40(6): 2215-2218. Article. IF 6.499 Background and Purpose-CADASIL is a hereditary arteriopathy causing recurrent strokes and cognitive decline. Because monozygotic twins have identical genetic background, differences in their environment and lifestyle could reveal factors that may influence CADASIL patients' clinical course, which is highly variable even within the same family. Methods-We describe differences in clinical and imaging findings in a pair of monozygotic CADASIL twins. Results-Twin B experienced his first-ever stroke 14 years earlier than twin A, and his symptoms, signs, and imaging findings were more severe. Distinguishing factors were twin B's smoking as well as twin A's physical activity and earlier statin treatment. Causative NOTCH3 mutation was a novel c.752G>A -substitution (p.Cys251Tyr). Conclusions-The phenotypic differences in these monozygotic twins suggest influence of environmental and lifestyle factors on the clinical course of CADASIL. (Stroke. 2009; 40: 2215-2218.) Genome-wide association study identifies eight loci associated with blood pressure Newton-Cheh, C., Johnson, T., Gateva, V., Tobin, M. D., Bochud, M., Coin, L., Najjar, S. S., Zhao, J. H., Heath, S. C., Eyheramendy, S., Papadakis, K., Voight, B. F., Scott, L. J., Zhang, F., Farrall, M., Tanaka, T., Wallace, C., Chambers, J. C., Khaw, K. T., Nilsson, P., van der Harst, P., Polidoro, S., Grobbee, D. E., Onland-Moret, N. C., Bots, M. L., Wain, L. V., Elliott, K. S., Teumer, A., Luan, J., Lucas, G., Kuusisto, J., Burton, P. R., Hadley, D., McArdle, W. L., Brown, M., Dominiczak, A., Newhouse, S. J., Samani, N. J., Webster, J., Zeggini, E., Beckmann, J. S., Bergmann, S., Lim, N., Song, K., Vollenweider, P., Waeber, G., Waterworth, D. M., Yuan, X., Groop, L., Orho-Melander, M., Allione, A., Di Gregorio, A., Guarrera, S., Panico, S., Ricceri, F., Romanazzi, V., Sacerdote, C., Vineis, P., Barroso, I., Sandhu, M. S., Luben, R. N., Crawford, G. J., Jousilahti, P., Perola, M., Boehnke, M., Bonnycastle, L. L., Collins, F. S., Jackson, A. U., Mohlke, K. L., Stringham, H. M., Valle, T. T., Willer, C. J., Bergman, R. N., Morken, M. A., Doring, A., Gieger, C., Illig, T., Meitinger, T., Org, E., Pfeufer, A., Wichmann, H. E., Kathiresan, S., Marrugat, J., O'Donnell, C. J., Schwartz, S. M., Siscovick, D. S., Subirana, I., Freimer, N. B., Hartikainen, A. L., McCarthy, M. I., O'Reilly, P. F., Peltonen, L., Pouta, A., de Jong, P. E., Snieder, H., van Gilst, W. H., Clarke, R., Goel, A., Hamsten, A., Peden, J. F., Seedorf, U., Syvanen, A. C., Tognoni, G., Lakatta, E. G., Sanna, S., Scheet, P., Schlessinger, D., Scuteri, A., Dorr, M., Ernst, F., Felix, S. B., Homuth, G., Lorbeer, R., Reffelmann, T., Rettig, R., Volker, U., Galan, P., Gut, I. G., Hercberg, S., Lathrop, G. M., Zelenika, D., Deloukas, P., Soranzo, N., Williams, F. M., Zhai, G., Salomaa, V., Laakso, M., Elosua, R., Forouhi, N. G., Volzke, H., Uiterwaal, C. S., van der Schouw, Y. T., Numans, M. E., Matullo, G., Navis, G., Berglund, G., Bingham, S. A., Kooner, J. S., Connell, J. M., Bandinelli, S., Ferrucci, L., Watkins, H., Spector, T. D., Tuomilehto, J., Altshuler, D., Strachan, D. P., Laan, M., Meneton, P., Wareham, N. J., Uda, M., Jarvelin, M. R., Mooser, V., Melander, O., Loos, R. J. F., Elliott, P., Abecasis, G. R., Caulfield, M. and Munroe, P. B. Nature Genetics. 2009; 41(6): 666-676. Article. IF 30.259 Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N <= 71,225 European ancestry, N <= 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease. Niinikoski, H., Jula, A., Viikari, J., Ronnemaa, T., Heino, P., Lagström, H., Jokinen, E. and Simell, O. Hypertension. 2009; 53(6): 918-924. Article. IF 7.368 Blood pressure was measured in the prospective randomized Special Turku Coronary Risk Factor Intervention Project Study with an oscillometric method every year from 7 months to 15 years of age in 540 children receiving a low-saturated-fat, low-cholesterol diet and in 522 control children. Dietary intakes, family history of parental hypertension, and grandparental vascular disease were recorded. Systolic and diastolic blood pressures were 1.0 mm Hg lower (95% CI for systolic: -1.7 to -0.2 mm Hg; 95% CI for diastolic: -1.5 to -0.4 mm Hg) in children receiving low-saturated-fat counseling through childhood than in control children. Intakes of saturated fat were lower (P < 0.001), those of polyunsaturated fat higher (P < 0.001), and intakes of potassium slightly higher (P < 0.002) in the intervention group, but sodium intakes were not influenced by the intervention (P < 0.76). Children whose parents were hypertensive had 4-to 6-mm Hg higher systolic and 3-to 4-mm Hg higher diastolic blood pressures than children of normotensive parents (P < 0.001). Diastolic blood pressure of children with grandparental vascular disease, ie, early cardiovascular or cerebrovascular disease, tended to be higher than that of children with no grandparental disease (P = 0.051). We conclude that restriction of saturated fat from infancy until 15 years of age decreases childhood and adolescent blood pressure with a meaningful population-attributable amount. The importance of childhood lifestyle counseling and primary prevention of hypertension should be emphasized, especially in those children with a family history of hypertension or atherosclerotic vascular disease. (Hypertension. 2009; 53: 918-924.) Patja, K., Hakala, S., Prattala, R., Ojala, K., Boldo, E. and Öberg, M. Prev Med. 2009. IF 2.757 OBJECTIVE: International comparability of environmental tobacco smoke (ETS) exposure levels is difficult. This study assesses whether estimating children's exposure from information on adult smoking and exposure to ETS makes international comparisons more reliable. METHODS: The exposure among children was estimated using three different combinations (models) based on different sets of information on adult smoking, household composition or adult exposure to ETS at home in three cross-sectional nationally representative samples drawn from data sets from Estonia (n=2650), Finland (n=2829) and Latvia (n=5440) in the years 2002 and 2004. The first two models were based on adult smoking and the third also included ETS exposure. RESULTS: The parental smoking rate was similar to the general smoking prevalence. ETS exposure in non-smoking parents ranged from 22% in Finland to 60% in Latvia. All models gave rather comparative ranges except in Latvia, where the proportion of children with exposure varied from 67% with the simplest model to 81% with the most complex one. CONCLUSIONS: Adult exposure at home or adult smoking prevalence, preferably among people with children, could be used as a proxy for children's exposure to ETS. It is recommended that population questionnaires include detailed information on exposure and household composition. Trends of tobacco use in Sweden and Finland: do differences in tobacco policy relate to tobacco use? Patja, K., Hakala, S. M., Boström, G., Nordgren, P. and Haglund, M. Scand J Public Health. 2009; 37(2): 153-60. IF 1.537 BACKGROUND: Sweden and Finland, neighbouring countries in Scandinavia, share features in health and social policies but retain a few differences in tobacco policy, including oral tobacco product regulation. This paper analyses the differences between tobacco policy and tobacco use between these two countries. Material: Representative data sets from both countries, for age groups 18 to 64, were used to compare the status of tobacco use. The study covered the years 1988/89, 1996/97 and 2004/05. RESULTS: Among men, daily use of tobacco products is more common in Sweden than in Finland. The daily smoking rate for men in Sweden is 16% compared to 28% in Finland. In Sweden, 27% of men use snuff daily and 17% of never smoking men reported daily use of snuff. In Finland, 3% of all males report daily use of snuff. Concurrent snuff use was linked to occasional smoking in Sweden, where 23% of male daily snuff users smoke occasionally. Among women smoking prevalence has decreased significantly in Sweden during the study period, but no real change in daily smoking can be detected in Finland. CONCLUSIONS: Tobacco control measures did gain good results among women in Sweden whereas in Finland development was modest. In Sweden, tobacco use has increased mainly due to an increase in snuff use, and snuff seems to appeal not only to switchers, but to young males without a history of smoking. Geographic variation and sociodemographic characteristics of psychotic disorders in Finland Perälä, J., Saarni, S. I., Ostamo, A., Pirkola, S., Haukka, J., Härkänen, T., Koskinen, S., Lönnqvist, J. and Suvisaari, J. Schizophr Res. 2008; 106(2-3): 337-47. IF 4.174 BACKGROUND: Geographical variation and sociodemographic characteristics may differ in affective and nonaffective psychotic disorders. We examined the geographical variation in the lifetime prevalence of psychotic disorders in a comprehensive general population study. METHOD: A nationally representative sample of 8028 Finns aged 30 or over was screened for psychotic and bipolar I disorders and interviewed with the Structured Clinical Interview for DSM-IV. Best-estimate DSM-IV diagnoses were formed by combining interview and case note data. Nationwide health care register data were used for the nonrespondents. Associations with sociodemographic features, place of birth and residence in urban or rural areas and in five regions, and migration between the regions were examined. RESULTS: Schizophrenia and other nonaffective psychoses, but not affective psychoses, showed prominent regional variation, with highest odds found for schizophrenia among those born in the North (OR 7.72 95%CI 2.48-24.04) and the East (OR 3.99 95%CI 1.22-13.11). The risk of any psychotic disorder was lower for those born in urban areas (OR 0.73 95%CI 0.54-0.98), but no associations were found for separate diagnostic groups. Region of birth was the strongest determinant of geographical variation when both place of birth and residence were accounted for. Selective migration was not found. Education and income were higher and being employed more common in subjects with affective psychosis than in subjects with other psychotic disorders. CONCLUSIONS: Large area variation is more important than urban-rural disparity in psychotic disorders in Finland. Affective psychoses were different from nonaffective psychoses in terms of both regional variation and sociodemographic features. Serum chlamydial lipopolysaccharide as a prognostic factor for a new cardiovascular event Pesonen, E., Tiirola, T., Andsberg, E., Jauhiainen, M., Paldanius, M., Persson, K., Saikku, P., Sarna, S., Ohlin, H. and Leinonen, M. Heart & Lung. 2009; 38(3): 176-181. Article. IF 1.094 BACKGROUND: Infections caused by Chlamydia pneumoniae are considered to participate in inflammatory processes leading to coronary artery disease. After a primary infection, the bacteria remain dormant intracellularly causing a chronic inflammatory stimulus. MATERIALS AND METHODS: Blood samples were obtained from 235 patients with acute myocardial infarction (AMI) and 108 patients with unstable angina pectoris (UA). We evaluated the prognostic significance of bacterial and viral antibody titers, serum troponin T, C-reactive protein, and chlamydial lipopolysaccharide (cLPS) concentrations during acute coronary syndrome of patients with AMI and UA for cardiovascular death and new UA and AMI that required hospital care during a 6-year follow-up. RESULTS: Serum cLPS levels correlated with C-reactive protein and serum troponin T concentrations during acute coronary events. Patients with AMI had significantly higher serum concentration of. cLPS compared with patients with UA. Enterovirus antibody titers and cholesterol-lowering therapy at admission of the index event were negatively correlated with cLPS concentration (r = -.198, P = .0003 and r = -.26, P = .019, respectively). The presence of circulating cLPS was associated with a hazard ratio of 2.04 for a new cardiovascular event during the follow-up period (P = .006). The area under the curve in the receiver operating graph was .572. CONCLUSION: cLPS is evidently liberated from the infected atherosclerotic tissue during an acute coronary event. Our study supports the view that inflammation caused by C. pneumoniae infection is an important but as yet poorly understood factor in the development of atherosclerosis and may play a role in acute vascular events. (Heart Lung (R) 2009;38:176-181.) HDL Subspecies in Young Adult Twins: Heritability and Impact of Overweight Pietiläinen, K. H., Soderlund, S., Rissanen, A., Nakanishi, S., Jauhiainen, M., Taskinen, M. R. and Kaprio, J. Obesity. 2009; 17(6): 1208-1214. Article. IF 2.762 The association between abdominal obesity and atherogenic lipid profile emerges from complex interactions of genes and environment. We aimed to explore the heritability and effects of overweight on serum lipid profile (high-density lipoprotein-cholesterol (HDL-C), HDL mean particle size, percentages of HDL2b, 2a, 3a, 3b, and 3c, low-density lipoprotein-cholesterol (LDL-C), LDL peak particle size and triglycerides (TGs)) in healthy, young adults. HDL-C, LDL-C, and TG were measured in 52 monozygotic (MZ) and 89 dizygotic (DZ) twin pairs, aged 23-32 years, chosen to represent a wide range of BMIs (17.6-42.9 kg/m(2)). Of them, 24 MZ and 26 DZ pairs were chosen at random for measurements of HDL mean and LDL peak particle sizes and percentages of HDL subspecies. The heritabilities of the lipid parameters adjusted for BMI were HDL-C 73%, HDL mean particle size 56%, HDL subspecies 46-63%, LDL-C 79%, LDL peak particle size 49%, and TG 64%. Genetic and environmental correlations between BMI and HDL-C, LDL-C, and TG were modest (0.3-0.4). Abdominal overweight (waist circumference >= 94 cm for males and >= 80 cm for females) associated with decreased HDL-C, increased LDL-C, and TG concentrations, smaller HDL mean particle size, lower HDL2b, and higher HDL3c percentages in both genders. Within MZ twins, controlling for genetic influences, within-pair differences in HDL3c percentage were associated with those in waist (r = 0.46, P = 0.032) and BMI (r = 0.51, P = 0.013). In conclusion, serum lipid parameters, including LDL peak and HDL mean particle sizes and HDL subspecies distribution are under strong genetic control. Overweight associated with significant lipid profile changes, particularly, small HDL3c increased in overweight independent of genetic influences. Body composition in psychotic disorders: a general population survey Saarni, S. E., Saarni, S. I., Fogelholm, M., Heliövaara, M., Perälä, J., Suvisaari, J. and Lönnqvist, J. Psychol Med. 2009; 39(5): 801-10. IF 4.718 BACKGROUND: The literature suggests an association between obesity and schizophrenia but fat mass and fat-free mass, which have been shown to be more predictive of all-cause mortality than only waist circumference and obesity [body mass index (BMI) 30 kg/m2], have not been reported in psychotic disorders. We examined the detailed body composition of people with different psychotic disorders in a large population-based sample. METHOD: We used a nationally representative sample of 8082 adult Finns aged 30 years with measured anthropometrics (height, weight, waist circumference, fat percentage, fat-free mass and segmental muscle mass). Psychiatric diagnoses were based on a consensus procedure utilizing the Structured Clinical Interview for DSM-IV (SCID)-interview, case-notes and comprehensive register data. RESULTS: Schizophrenia (including schizo-affective disorder) was associated with obesity [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.5-3.6], abdominal obesity (waist circumference 88 cm for women, 102 cm for men) (OR 2.2, 95% CI 1.3-3.6) and with higher fat percentage (mean difference 3.8%, 95% CI 2.0-5.7%), adjusted for age and gender, than in the remaining sample. The associations between schizophrenia and low fat-free mass and decreased muscle mass on trunk and upper limbs became statistically significant after adjusting for BMI. After further adjusting for current antipsychotic medication, education, diet and smoking, schizophrenia remained associated with obesity (OR 1.9, 95% CI 1.1-3.6) and abdominal obesity (OR 3.8, 95% CI 1.5-9.4). Participants with affective psychoses did not differ from the general population. CONCLUSIONS: Individuals with schizophrenia have metabolically unfavorable body composition, comprising abdominal obesity, high fat percentage and low muscle mass. This leads to increased risk of metabolic and cardiovascular diseases. Sihvonen, L. M., Haukka, K., Kuusi, M., Virtanen, M. J. and Siitonen, A. European Journal of Clinical Microbiology & Infectious Diseases. 2009; 28(7): 757-765. Article. IF 2.866 This study investigated the prevalence of Yersinia enterocolitica (YE) bio/serotypes and YE-like species in clinical stool specimens. The special aim was to find the best methods for accurate identification of YE species and, further, pathogenic strains among YE isolates. Of the 41,848 specimens cultured in ten laboratories during a 12-month period, 473 Yersinia strains were isolated from 462 patients. The strains were identified by 21 biochemical tests, serotyping, colony morphology, as well as by 16S rRNA and gyrB gene sequencing. The most prevalent Yersinia findings were YE biotype 1A (64% of the strains) and pathogenic bio/serotype 4/O:3 (16%). The cold-enrichment increased the number of all isolates, and 25% of the bio/serotype 4/O:3 and 2/O:9 strains were only found by cold-enrichment. In routine diagnostic laboratories, 50% of the YE-like species were identified as YE and in 26% the identification differed from that of the reference laboratory. The microscopic colony identification on CIN agar with positive CR-MOX test, combined with several biochemical tests, identified reliably the pathogenic YE bioserotypes and most YE BT 1A strains, but some strains of the YE-like species were so heterogenic that gene sequencing was the only way to identify them. Simell, B., Ahokas, P., Lahdenkari, M., Poolman, J., Henckaerts, I., Kilpi, T. M. and Käyhty, H. Vaccine. 2009. IF 3.298 We assessed the development and role of serum anti-CbpA and -PhtD in early childhood in relation to pneumococcal exposure. Serum IgG concentrations to CbpA and PhtD were measured with enzyme immunoassay in serum samples collected at the ages of 6, 12, 18, and 24 months from 50 healthy children and from 50 adults. Furthermore, antibodies to CbpA, PhtD and the C-terminal fragment of PhtD (PhtD C) were measured in serum samples collected at 12 (N=286) and 18 months (N=259) to evaluate the risk of subsequent pneumococcal acute otitis media (AOM) in relation to antibody concentrations. The increase in anti-CbpA and -PhtD concentrations was related to prior pneumococcal exposure. At 12 and 18 months, in the risk model of pneumococcal AOM adjusted for prior pneumococcal AOM, higher concentrations of anti-CbpA, but not anti-PhtD, were associated with a lowered risk of subsequent pneumococcal AOM. In conclusion, pneumococcal exposure induces the development of serum anti-CbpA and -PhtD in early childhood. Anti-CbpA antibodies may play a role in the prevention of subsequent pneumococcal AOM during the second year of life. Metabolic syndrome and carotid intima media thickness in the Health 2000 Survey Sipilä, K., Moilanen, L., Nieminen, T., Reunanen, A., Jula, A., Salomaa, V., Kaaja, R., Kukkonen-Harjula, K., Lehtimäki, T., Kesäniemi, Y. A., Koivistoinen, T., Nieminen, M. S., Tuomilehto, J. and Kähönen, M. Atherosclerosis. 2009; 204(1): 276-281. Article. IF 4.601 Background and purpose: Metabolic syndrome has been associated with increased carotid intima-media thickness (CIMT) and cardiovascular disease (CVD). The objective of this study was to examine metabolic syndrome as a determinant of CIMT in men and women and to compare the Framingham risk score (FRS) and metabolic syndrome as risk factors for increased carotid atherosclerosis. Methods: The study population consisted of 1353 Finnish men and women aged 45 years and above who participated in Finnish population-based Health 2000 Survey. CIMT was used as a marker of subclinical atherosclerosis. The National Cholesterol Education Program Adult Treatment Panel III criterion was used to define the presence of metabolic syndrome. Results: In multivariable models, metabolic syndrome was an independent determinant of CIMT in both sexes (p <= 0.001 for both). When metabolic syndrome was included in the regression models along with its components, it was an independent determinant of CIMT in women but not in men. After dividing the population into risk categories according to FIRS and the presence of metabolic syndrome, FRS predominantly determined CIMT regardless of the presence of metabolic syndrome in men. In women, however, CIMT was significantly higher in Subjects with metabolic syndrome than in those without it, independently of the FRS. Conclusions: Metabolic syndrome is an independent determinant of CIMT in both sexes. In women but not in men, metabolic syndrome is associated with CIMT independently of its components. Metabolic syndrome provides additional information on a person's risk for early atherosclerosis beyond FRS in women but not in men. (C) 2008 Elsevier Ireland Ltd. All rights reserved. Association of Sense of Coherence and Clinical Signs of Temporomandibular Disorders Sipilä, K., Ylöstalo, P., Kononen, M., Uutela, A. and Knuuttila, M. Journal of Orofacial Pain. 2009; 23(2): 147-152. Article. IF 2.054 Aims: To investigate the association of sense of coherence (SOC) with clinical findings of temporomandibular disorders (TMD) among 30- to 64-year-old subjects. Methods: A nationally representative health examination survey called the Health 2000 Survey was carried out from 2000 to 2001. The data for this study were obtained from 4,859 subjects aged 30 to 64 years who bad participated in an interview, been clinically examined, and returned a self-administered questionnaire. The questionnaire included a SOC scale which was a 12-item version of the SOC-13 scale. Based on a clinical examination for TMD, the following variables were formed: maximum interincisal distance < 40 mm, clicking, crepitation, pain in the temporomandibular joints (TMJs), and pain in the masticatory muscles. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models. Results: Subjects with low SOC had higher odds to have distinct TMD findings, especially masticatory muscle pain, than those with high SOC. After adjustment for confounders, those with low SOC bad more than twofold odds to have masticatory muscle pain (in at least one painful site) compared to those with high SOC (OR 2.2, 95% CI 1.4-3.6). Low SOC was also associated with TMJ pain on palpation (OR 3.2, 95% Cl 1.5-6.6). Conclusion: Low SOC associates with myogenous TMD findings. SOC as a psychosocial aspect has a role in the background of TMD. J OROFAC PAIN 2009;23:147-152 Smura, T., Blomqvist, S., Hovi, T. and Roivainen, M. Arch Virol. 2009. IF 2.020 Enterovirus 96 (EV-96) is a recently described genotype in the species Human enterovirus C. So far, only partial genome sequences of this enterovirus type have been available. In this study, we report complete genome sequences for two EV-96 strains isolated from healthy children during enterovirus surveillance in Finland. Sequence analysis revealed substantial nucleotide divergence between EV-96 strains and suggested several recombination events between EV-96 and other HEV-C types. Soininen, A., Nohynek, H., Lucero, M., Jousimies, K., Ugpo, J., Williams, G. and Käyhty, H. Vaccine. 2009; 27(20): 2680-8. IF 3.298 BACKGROUND: Pneumococcal pneumonia is a major cause of morbidity and mortality worldwide. Efficacy of pneumococcal conjugate vaccines (PCV) in reducing childhood pneumonia has been estimated in four double-blind, randomized, controlled trials. An investigational 11-valent pneumococcal conjugate vaccine (11PCV) had an efficacy of 22.9% against radiologically defined pneumonia during first 2 years of life in Filipino infants. We report here the immunogenicity of the vaccine in a nested study of 1111 infants randomized 1:1 to receive 11PCV or placebo scheduled to be given according to the National EPI Program at 6, 10, and 14 weeks of age. METHODS: IgG antibody concentrations to pneumococcal capsular polysaccharides were measured by a standardized enzyme immuno-assay in serum samples drawn post-3rd dose for peak antibody response and at the time of measles vaccination at 9 months of age for persistence of the antibodies. RESULTS: The geometric mean concentrations (GMCs) of antibodies were significantly higher in 11PCV than in placebo recipients against vaccine serotypes at both sampling points. One month post-3rd dose, 93-100% of 11PCV recipients had > or =0.35microg/ml for 9 serotypes, 76% for 6B, and 87% for 23F. The same proportions varied between 24% and 97% at 9.5 months of age due to antibody decrease. GMC to vaccine-related serotype 19A, but not to 6A, was higher in 11PCV than in placebo recipients. 7-12% of the 11PCV recipients had spontaneous antibody increases to serotypes 6B, 23F, and 14 between the two sampling points. These serotypes were common in nasopharyngeal samples of the infants. CONCLUSION: The 11PCV demonstrated good immunogenicity after three doses and persistence of antibodies at least up to 9.5 months of age, comparable to other PCVs that have been evaluated for efficacy against radiologically defined pneumonia in other populations. Sovio, U., Bennett, A. J., Millwood, I. Y., Molitor, J., O'Reilly, P. F., Timpson, N. J., Kaakinen, M., Laitinen, J., Haukka, J., Pillas, D., Tzoulaki, I., Hoggart, C., Coin, L. J. M., Whittaker, J., Pouta, A., Hartikainen, A. L., Freimer, N. B., Widen, E., Peltonen, L., Elliott, P., McCarthy, M. I. and Jarvelin, M. R. Plos Genetics. 2009; 5(3). Article. IF 8.883 Recent genome-wide association (GWA) studies have identified dozens of common variants associated with adult height. However, it is unknown how these variants influence height growth during childhood. We derived peak height velocity in infancy (PHV1) and puberty (PHV2) and timing of pubertal height growth spurt from parametric growth curves fitted to longitudinal height growth data to test their association with known height variants. The study consisted of N = 3,538 singletons from the prospective Northern Finland Birth Cohort 1966 with genotype data and frequent height measurements (on average 20 measurements per person) from 0-20 years. Twenty-six of the 48 variants tested associated with adult height (p<0.05, adjusted for sex and principal components) in this sample, all in the same direction as in previous GWA scans. Seven SNPs in or near the genes HHIP, DLEU7, UQCC, SF3B4/SV2A, LCORL, and HIST1H1D associated with PHV1 and five SNPs in or near SOCS2, SF3B4/SV2A, C17orf67, CABLES1, and DOT1L with PHV2 (p<0.05). We formally tested variants for interaction with age (infancy versus puberty) and found biologically meaningful evidence for an age-dependent effect for the SNP in SOCS2 (p = 0.0030) and for the SNP in HHIP (p = 0.045). We did not have similar prior evidence for the association between height variants and timing of pubertal height growth spurt as we had for PHVs, and none of the associations were statistically significant after correction for multiple testing. The fact that in this sample, less than half of the variants associated with adult height had a measurable effect on PHV1 or PHV2 is likely to reflect limited power to detect these associations in this dataset. Our study is the first genetic association analysis on longitudinal height growth in a prospective cohort from birth to adulthood and gives grounding for future research on the genetic regulation of human height during different periods of growth. Safety assessment of common foods enriched with natural nonesterified plant sterols Tuomilehto, J., Tikkanen, M. J., Hogstrom, P., Keinanen-Kiukaanniemi, S., Piironen, V., Toivo, J., Salonen, J. T., Nyyssonen, K., Stenman, U. H., Alfthan, H. and Karppanen, H. Eur J Clin Nutr. 2009; 63(5): 684-91. IF 1.899 BACKGROUND/OBJECTIVES: To assess safety during a diet based on low-fat foods enriched with nonesterified wood-derived plant sterols and mineral nutrients related to serum phytosterol, sex hormone and fat-soluble vitamin metabolism. SUBJECTS/METHODS: Seventy-one study participants (52 women, 19 men) with mild-to-moderate hypercholesterolemia completed the double-blind, placebo-controlled feeding trial lasting for 15 weeks. The subjects were randomly allocated to the sterol group receiving food items enriched with mineral nutrients as well as with a total of 1.25, 2.5 and 5.0 g per day of plant sterols during the first, second and third 5-week periods, respectively, or to the placebo group receiving similar food items without plant sterols. This outpatient clinical trial with free-living subjects was carried out at two hospital clinics. RESULTS: Two significant findings were observed. Serum sitosterol concentrations increased from 2.84 to 5.35 mg l(-1) (P<0.004 vs placebo) but those of serum total plant sterols did not because of compensatory changes in other phytosterols. The highest plant sterol levels did not exceed 0.6% of total serum sterols. Serum alpha-tocopherol concentrations decreased in the sterol group by 10% (P<0.0002), but the between-group difference disappeared after adjusting for the change in the carrier (LDL cholesterol). CONCLUSIONS: Fifteen-week consumption of natural nonesterified plant sterol-enriched food does not cause any serious adverse effects during such a period. However, serum alpha-tocopherol levels were somewhat reduced in the sterol group suggesting that long-term effects of plant sterols on serum fat-soluble vitamin concentrations should be further explored, especially in relation to very low-fat diets. Tuomisto, J., Holl, K., Rantakokko, P., Koskela, P., Hallmans, G., Wadell, G., Stattin, P., Dillner, J., Ogmundsdottir, H. M., Vartiainen, T., Lehtinen, M. and Pukkala, E. European Journal of Cancer. 2009; 45(9): 1640-1648. Article. IF 4.475 Some large ecological studies have noted a significant association of testicular cancer (TC) with maternal smoking during pregnancy, while several more controlled studies have been negative. It has been difficult to obtain reliable data on exposure because of the long lag time to cancer diagnosis. We performed a case-control study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of maternal smoking in the risk of TC in the offspring. After reviewing the literature, we also performed a meta-analysis of published studies. For each index mother of the TC patient, three to nine matched control mothers with a cancer-free son born at the same time as the TC case were identified within each cohort. First trimester sera were retrieved from the 70 index mothers and 519 control mothers and were tested for cotinine level by a novel HPLC-MS-MS method developed. No statistically significant association between maternal cotinine level and risk of TC in the offspring was found (OR 0.68; 95% CI 0.35, 1.34). This is the first study based on individual exposure measurements. Its results agree with our meta-analysis of seven previous epidemiological studies (total number of 2149 cases, 2762 controls) using indirect exposure assessment (OR 1.0; 95% CI 0.88, 1.12). (c) 2009 Elsevier Ltd. All rights reserved. Maternal vitamin D status determines volumetric bone mineral density of the newborn Viljakainen, H. T., Saarnio, E., Hytinantti, T., Miettinen, M., Surcel, H., Andersson, S., Laitinen, K. and Lamberg-Allardt, C. Bone. 2009; 44(2): S240-S240. Meeting Abstract. IF 4.145 Growth Charts of Length and Height from Birth to Six Years of Age in Japanese Triplets Yokoyama, Y., Sugimoto, M., Silventoinen, K., Pitkäniemi, J. and Kaprio, J. Twin Research and Human Genetics. 2009; 12(3): 320-327. Article. IF 2.097 We analyzed the characteristics associated with the growth in length and height of Japanese triplets from birth to 6 years of age and present the growth charts for them. The study included 354 mothers and their 1,061 triplet children, who were born between 1978 and 2006. Data were collected through a mailed questionnaire sent to the mothers asking for information recorded in medical records. For these births, data on triplets' length and height growth, gestational age, sex, parity, and maternal age at delivery were obtained from records in the Maternal and Child Health Handbooks, which is provided by the authorities after a report of pregnancy. Birth length showed the strongest contribution to height of triplets from 1 to 6 years of age. In addition, birthweight was also a significant contributing factor to height from 1 to 3 years of age. Compared to the 50th percentile of the growth standard for the general population of Japan, the length and height deficit of the triplets was approximately 15% at birth (male, -7.0 cm; female, -7.0 cm), decreased within the first year of age, and fluctuated between 2 and 5% until 6 years of age (male, -3.7 cm; female, -3.3 cm). In conclusion, triplets have lower birth length and subsequent height than singletons. In spite of the catch-up growth during the first year of life, they are behind singletons even in mid-childhood. This study provides height growth curves for triplets. |