|
New articles - Uudet artikkelit 26.5.2008 - ISI Web of Knowledge & PubMed Search Alert
|
|
Consistently replicating locus linked to migraine on 10q22-q23
Anttila, V., Nyholt, D. R., Kallela, M., Artto, V., Vepsalainen, S., Jakkula, E., Wennerstrom, A., Tikka-Kleemola, P., Kaunisto, M. A., Hamalainen, E., Widen, E., Terwilliger, J., Merikangas, K., Montgomery, G. W., Martin, N. G., Daly, M., Kaprio, J., Peltonen, L., Farkkila, M., Wessman, M. and Palotie, A. American Journal of Human Genetics. 2008; 82(5): 1051-1063. Article. IF 12.629 Here, we present the results of two genome-wide scans in two diverse populations in which a consistent use of recently introduced migraine-phenotyping methods detects and replicates a locus on 10q22-q23, with an additional independent replication. No genetic variants have been convincingly established in migraine, and although several loci have been reported, none of them has been consistently replicated. We employed the three known migraine-phenotyping methods (clinical end diagnosis, latent-class analysis, and trait-component analysis) with robust multiple testing correction in a large sample set of 1675 individuals from 210 migraine families from Finland and Australia. Genome-wide multipoint linkage analysis that used the Kong and Cox exponential model in Finns detected a locus on 10q22-q23 with highly significant evidence of linkage (LOD 7.68 at 103 cM in female-specific analysis). The Australian sample showed a LOD score of 3.50 at the same locus (100 cM), as did the independent Finnish replication study (LOD score 2.41, at 102 cM). In addition, four previously reported loci on 8q21, 14q21, 18q12, and Xp21 were also replicated. A shared-segment analysis of 10q22-q23 linked Finnish families identified a 1.6-9.5 cM segment, centered on 101 cM, which shows in-family homology in 95% of affected Finns. This region was further studied with 1323 SNPs. Although no significant association was observed, four regions warranting follow-up studies were identified. These results support the use of symptomology-based phenotyping in migraine and suggest that the 10q22-q23 locus probably contains one or more migraine susceptibility variants. USF1 gene variants contribute to metabolic traits in men in a longitudinal 32-year follow-up study Auro, K., Kristiansson, K., Zethelius, B., Berne, C., Lannfelt, L., Taskinen, M. R., Jauhiainen, M., Perola, M., Peltonen, L. and Syvanen, A. C. Diabetologia. 2008; 51(3): 464-72. IF 5.247 AIMS/HYPOTHESIS: Genetic variants of upstream transcription factor 1 (USF1) have previously been associated with dyslipidaemias in family studies. Our aim was to further address the role of USF1 in metabolic syndrome and cardiovascular traits at the population level in a large Swedish male cohort (n=2,322) with multiple measurements for risk factors during 32 years of follow-up. METHODS: Participants, born in 1920-1924, were examined at 50, 60, 70 and 77 years of age. The follow-up period for cardiovascular events was 1970-2002. We genotyped three haplotype tagging polymorphisms capturing the major allelic variants of USF1. RESULTS: SNP rs2774279 was associated with the metabolic syndrome. The minor allele of rs2774279 was less common among individuals with metabolic syndrome than among healthy controls [p=0.0029 when metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III; p=0.0073 when defined according to the International Diabetes Federation (IDF)]. The minor allele of rs2774279 was also associated with lower BMI, lower fasting glucose values and higher HDL-cholesterol concentrations in longitudinal analyses. With SNP rs2073658, a borderline association with metabolic syndrome was observed (p=0.036, IDF), the minor allele being the risk-increasing allele. The minor allele of rs2073658 also associated with higher total and LDL-cholesterol, apolipoprotein B-100 and lipoprotein(a) concentrations in longitudinal analyses. Importantly, these trends with respect to the allelic variants prevailed throughout the follow-up time of three decades. CONCLUSIONS/INTERPRETATION: Our results suggest that USF1 variants associate with the metabolic syndrome at population level and influence the cardiovascular risk factors throughout adulthood in a consistent, longitudinal manner. Bakari, M., Arbeit, R. D., Mtei, L., Lyimo, J., Waddell, R., Matee, M., Cole, B. F., Tvaroha, S., Horsburgh, C. R., Soini, H., Pallangyo, K. and von Reyn, C. F. BMC Infectious Diseases. 2008; 8. Article. IF 1.898 Background: Active tuberculosis (TB) is common among HIV-infected persons living in tuberculosis endemic countries, and screening for tuberculosis (TB) is recommended routinely. We sought to determine the role of chest x-ray and sputum culture in the decision to treat for presumptive TB using active case finding in a large cohort of HIV-infected patients. Methods: Ambulatory HIV-positive subjects with CD4 counts >= 200/mm(3) entering a Phase III TB vaccine study in Tanzania were screened for TB with a physical examination, standard interview, CD4 count, chest x-ray (CXR), blood culture for TB, and three sputum samples for acid fast bacillus (AFB) smear and culture. Results: Among 1176 subjects 136 (12%) were treated for presumptive TB. These patients were more frequently male than those without treatment (34% vs. 25%, respectively; p = 0.049) and had lower median CD4 counts (319/mu L vs. 425/mu L, respectively; p < .0001). Among the 136 patients treated for TB, 38 (28%) had microbiologic confirmation, including 13 (10%) who had a normal CXR and no symptoms. There were 58 (43%) treated patients in whom the only positive finding was an abnormal CXR. Blood cultures were negative in all patients. Conclusion: Many ambulatory HIV- infected patients with CD4 counts >= 200/mm(3) are treated for presumptive TB. Our data suggest that optimal detection requires comprehensive evaluation, including CXR and sputum culture on both symptomatic and asymptomatic subjects. Coffee consumption, serum gamma-glutamyltransferase and risk of type II diabetes Bidel, S., Silventoinen, K., Hu, G., Lee, D. H., Kaprio, J. and Tuomilehto, J. Eur J Clin Nutr. 2008; 62(2): 178-85. IF 2.116 OBJECTIVES: To study the joint association of coffee consumption and serum gamma-glutamyltransferase (GGT) levels on the risk of developing type II diabetes. DESIGN, SETTING AND SUBJECTS: A total of 21,826 Finnish men and women who were 35-74 years of age and without any history of diabetes at baseline (years 1982, 1987, 1992 and 1997) were included in the present analyses. They were prospectively followed up for onset of type II diabetes (n=862 cases), death or until the end of the year 2002. Coffee consumption, serum GGT and other study parameters were determined at baseline using standardized measurements. Analyses were stratified by the serum GGT level classified into two classes using the 75th sex-specific percentiles as the cut point. RESULTS: Coffee consumption was significantly and inversely associated with incident diabetes among both men and women. Serum GGT modified the association between coffee consumption and incident diabetes. Subjects in the high category of coffee consumption with the GGT level > or = 75th percentile showed a significant inverse association for women, and for both sexes combined. The association was not significant in subjects with the GGT level < or = 75th percentile. There was a significant interaction effect of GGT and coffee consumption on risk of type II diabetes in data of women (P=0.05) and in both sexes combined (P=0.02). CONCLUSIONS: Habitual coffee consumption is associated with lower incidence of type II diabetes particularly in those with higher baseline serum GGT levels. A review on cognitive impairments in depressive and anxiety disorders with a focus on young adults Castaneda, A. E., Tuulio-Henriksson, A., Marttunen, M., Suvisaari, J. and Lönnqvist, J. J Affect Disord. 2008; 106(1-2): 1-27. IF 3.138 BACKGROUND: There is growing evidence for cognitive dysfunction in depressive and anxiety disorders. Nevertheless, the neuropsychological profile of young adult patients has not received much systematic investigation. The following paper reviews the existing literature on cognitive impairments in depressive and anxiety disorders particularly among young adults. Additionally, the focus of young adult age group and the effect of confounding variables on study results are discussed. METHODS: Electronic database searches were conducted to identify research articles focusing on cognitive impairments in depressive or anxiety disorders among young adults published in English during years 1990-2006. RESULTS: Cognitive impairments are common in young adults with major depression and anxiety disorders, although their nature remains partly unclear. Accordingly, executive dysfunction is evident in major depression, but other more specific deficits appear to depend essentially on disorder characteristics. The profile of cognitive dysfunction seems to depend on anxiety disorder subtype, but at least obsessive-compulsive disorder is associated with deficits in executive functioning and visual memory. The conflicting results may be explained by heterogeneity within study participants, such as illness status, comorbid mental disorders, and medication, and other methodological issues, including inadequate matching of study groups and varying testing procedures. LIMITATIONS: The study is a comprehensive review, but not a formal meta-analysis, due to methodological heterogeneity. CONCLUSIONS: Cognitive impairments are common in major depression and anxiety disorders. However, more research is needed to confirm and widen these findings, and to expand the knowledge into clinical practice. Controlling of confounding variables in future studies is highly recommended. Safety profile of pneumococcal conjugate vaccines: systematic review of pre- and post-licensure data DeStefano, F., Pfeifer, D. and Nohynek, H. Bulletin of the World Health Organization. 2008; 86(5): 373-380. Article. IF 5.029 A 7-valent pneumococcal polysaccharide-protein conjugate vaccine (PCV7) was licensed in the United States of America in 2000, but no comprehensive postmarketing review of safety has been carried out. We conducted a systematic review of the safety of PCV7 and other pneumococcal conjugate vaccines. A total of 42 studies were included in the review. Reactogenicity data from some randomized trials suggest that PCV7 may result in more local reactions and fever than certain comparison vaccines. However, the reactions were mild and self-limited, and PCV7 did not carry an increased risk of severe injection-site reactions or high fever Some, although not all, of the randomized trials in children found that mild local and systemic reactions associated with PCV7 may increase with the number of doses, at least over the three-dose primary series. In addition, PCV7 and other pneumococcal conjugate vaccines were found to have tolerable reactogenicity in Native American and African populations and in medically high-risk groups for which pneumococcal vaccination is recommended. Two of the largest studies of PCVs, one involving PCV7 and the other, PCV9, found a statistically significant increased risk of hospitalization for reactive airway disease, including asthma. Another large trial of PCV9, however, did not find an increased risk of asthma. In conclusion, this review of the evidence did not identify any major safety problems with PCV7 or any other pneumococcal conjugate vaccine, with the possible exception of reactive airway disease, which may bear further scrutiny as additional data become available. Freathy, R. M., Timpson, N. J., Lawlor, D. A., Pouta, A., Ben-Shlomo, Y., Ruokonen, A., Ebrahim, S., Shields, B., Zeggini, E., Weedon, M. N., Lindgren, C. M., Lango, H., Melzer, D., Ferrucci, L., Paolisso, G., Neville, M. J., Karpe, F., Palmer, C. N. A., Morris, A. D., Elliott, P., Jarvelin, M. R., Smith, G. D., McCarthy, M. I., Hattersley, A. T. and Frayling, T. M. Diabetes. 2008; 57(5): 1419-1426. Article. IF 7.955 OBJECTIVE-Common variation in the FTO gene is associated with BMI and type 2 diabetes. Increased BMI is associated with diabetes risk factors, including raised insulin, glucose, and triglycerides. We aimed to test whether FTO genotype is associated with variation in these metabolic traits. RESEARCH DESIGN AND METHODS-We tested the association between FTO genotype and 10 metabolic traits using data from 17,037 white European individuals. We compared the observed effect of FTO genotype on each trait to that expected given the FTO-BMI and BMI-trait associations. RESULTS-Each copy of the FTO rs9939609 A allele was associated with higher fasting insulin (0.039 SD [95% Cl 0.013-0.064]; P = 0.003), glucose (0.024 [0.001-0.0481]; P = 0.044), and triglycerides (0.028 [0.003-0.052]; P = 0.025) and lower HDL cholesterol (0.032 [0.008-0.057]; P = 0.009). There was no evidence of these associations when adjusting for BMI. Associations with fasting alanine aminotransferase, gamma-glutamyl-transferase, LDL cholesterol, A1C, and systolic and diastolic blood pressure were in the expected direction but did not reach P < 0.05. For all metabolic traits, effect sizes were consistent with those expected for the per allele change in BMI. FTO genotype was associated with a higher odds of metabolic syndrome (odds ratio 1.17 [95% CI 1.10-1.25]; P = 3 x 10(-6)). CONCLUSIONS-FTO genotype is associated with metabolic traits to an extent entirely consistent with its effect on BMI. Sample sizes of > 12,000 individuals were needed to detect associations at P < 0. 05. Our findings highlight the importance of using appropriately powered studies to assess the effects of a known diabetes or obesity variant on secondary traits correlated with these conditions. Gao, W. G., Qiao, Q., Tuomilehto, J., Balkau, B., Ruotolo, G., Calor, G., Garancini, M. P., Alberti, K. and Stehouwer, C. International Journal of Obesity. 2008; 32(5): 757-762. Article. IF 4.055 Aims: To evaluate whether the metabolic syndrome (MetS) defined by the International Diabetes Federation (IDF) criteria, which has abdominal adiposity as a mandatory element, predicts cardiovascular disease (CVD) mortality better than the cluster of other IDF-defined abnormalities not including abdominal adiposity. Methods: Data from nine European population-based studies, including 7782 men and 7739 women (aged 30-89 years), with a median follow-up of 8.55 years, were jointly analyzed. Hazard ratios for CVD mortality were calculated with Cox regression models. Results: In total, 41% of the men and 38% of the women had the IDF MetS. Individuals with the IDF MetS were by definition more obese and had a higher prevalence of diabetes than non-obese subjects with >= 2 IDF abnormalities; whereas non-obese men with >= 3 factors had more atherogenic lipid profiles. Multivariate adjusted hazard ratio for CVD death in men and women with the IDF MetS was 2.44 (1.69-2.98) and 2.32 (1.27-4.23); in non-obese men with 2 and >= 3 factors the hazard ratio was 1.60 (1.12-2.30) and 2.44 (1.62-3.66), respectively, and in non-obese women with 2 factors the hazard ratio was 2.41 (1.09-5.33). Conclusions: The cluster of the CVD risk factors predicted CVD mortality regardless of the presence or absence of the abdominal adiposity. Inclusion of abdominal adiposity as a prerequisite will miss those non-obese individuals who have increased CVD mortality. Harald, K., Koskinen, S., Jousilahti, P., Torppa, J., Vartiainen, E. and Salomaa, V. J Epidemiol Community Health. 2008; 62(3): 251-7. IF 2.805 AIM: To investigate to what extent the changes in traditional risk factors (total cholesterol, smoking, hypertension) explain the changes in socioeconomic (defined by occupational class and household income) differences in cardiovascular mortality in Finland during the past 20 years. DESIGN: Study population comprised 14,642 men and women aged 35-64 years who were selected from population-based FINRISK surveys in 1987, 1992, 1997 or 2002 in three areas of Finland. The 1982 and 1987 FINRISK cohorts were used to determine a model for the probability of cardiovascular death based on risk factor values at the baseline for each socioeconomic group. These predicted changes in cardiovascular mortality were then contrasted with observed mortality rates in different socioeconomic groups to determine the contribution of the changes in risk factors to changes in actual mortality. RESULTS: We found that among men during 1987-97, when risk factor levels were improving in all socioeconomic groups, the model explained 29-44% of the observed mortality decline. The risk factors explained a larger part of the decline among lower socioeconomic groups. During the period 1997-2002 the risk factor levels stopped improving in all socioeconomic groups but observed mortality rates kept declining. The predicted mortality rates were 16-34% of the observed rates during the period 1987-2002. CONCLUSIONS: Changes in traditional risk factors no longer provide a good explanation of the changes in cardiovascular mortality and its socioeconomic differences. However, risk factors did explain the cardiovascular mortality decline among lower socioeconomic groups. Aire deficiency causes increased susceptibility to streptozotocin-induced murine type 1 diabetes Hassler, S., Peltonen, L., Sandler, S. and Winqvist, O. Scandinavian Journal of Immunology. 2008; 67(6): 569-580. Article. IF 2.090 Aire-deficient mice are a model of the human monogenic disorder autoimmune polyendocrine syndrome type I (APS I) characterized by a progressive autoimmune destruction of multiple endocrine glands such as the adrenal cortex, the parathyroids and the beta-cells of the pancreas. The disease is caused by mutations in the autoimmune regulator (AIRE) gene, a putative transcription factor expressed in thymic medullary epithelial cells and in antigen-presenting cells of the myeloid lineage in peripheral lymphoid organs. As Aire(-/-) mice do not spontaneously develop endocrinopathies, we wanted to evaluate the autoimmune multiple low-dose streptozotocin (MLDSTZ) diabetes model in Aire(-/-) mice. Surprisingly, Aire heterozygote mice were most susceptible to MLDSTZ-induced diabetes, whereas Aire(-/-) mice displayed an intermediate sensitivity to diabetes. Furthermore, Aire(-/-) macrophages produced higher levels of TNF-alpha and lower levels of IL-10 following streptozotocin stimulation, and Aire(-/-) mice developed a higher frequency of islet cells autoantibodies as a sign of increased activation. However, the number of islet infiltrating F4/80(+) Aire(-/-) macrophages was significantly decreased which was attributed to an increased susceptibility to streptozotocin cytotoxicity of Aire(-/-) macrophages. In conclusion, Aire(-/-) macrophages display an increased activation after STZ stimuli, but suffer from increased susceptibility to STZ cytotoxicity. These results support an important function of Aire in the control of peripheral tolerance through myeloid antigen-presenting cells. Determinants and outcomes of serious attempted suicide: a nationwide study in Finland, 1996-2003 Haukka, J., Suominen, K., Partonen, T. and Lönnqvist, J. Am J Epidemiol. 2008; 167(10): 1155-63. IF 5.241 Suicide is among the 10 leading causes of death. Attempted suicide is 10-40 times more frequent than completed suicide and is the strongest single predictor of subsequent suicide. The current study population included all persons in Finland who were hospitalized with a diagnosis of attempted suicide between 1996 and 2003 (N = 18,199). Information on background variables and mortality was obtained by register linkage. The risk of repeated attempted suicide was 30% and the risk of suicide was 10%. The risks of repeated attempted suicide, completed suicide, and death from any cause were high immediately after discharge from the hospital. Analysis of competing causes of death revealed that while alcohol-related disorder was not associated with suicide, it markedly increased the risk of other violent death: The subdistribution hazards rate (SHR) was 2.61 (95% confidence interval (CI): 2.12, 3.21). Schizophrenia-related disorders (SHR = 1.87, 95% CI: 1.57, 2.21) and mood disorders (SHR = 1.72, 95% CI: 1.47, 2.01) were associated with the risk of suicide. The risks of suicide and all-cause mortality were extremely high immediately after hospitalization for attempted suicide. Heinonen, K., Raikkonen, K., Pesonen, A. K., Kajantie, E., Andersson, S., Eriksson, J. G., Niemela, A., Vartia, T., Peltola, J. and Lano, A. Pediatrics. 2008; 121(5): E1325-E1333. Article. IF 5.012 OBJECTIVE. The aim of the study was to investigate whether weight, length, BMI (kilograms per meter squared), and head circumference at birth and their postnatal growth are associated with cognitive abilities at 56 months of age among infants born at term. PATIENTS AND METHODS. Our sample was composed of 1056 Finnish children born at term, (37(0/7) to 41(6/7) weeks) free of any major impairments. Weight, length, and head circumference were measured at birth and at 5, 20, and 56 months of age, and BMI was calculated. We assessed cognitive abilities by conducting tests of general reasoning, visual-motor integration, verbal competence, and language comprehension at 56 months of age. RESULTS. Firstly, for every 1 SD lower in weight or BMI at birth, general reasoning and/or visual-motor integration was > 1.20 points lower, and for every 1 SD lower in length or head circumference at birth, abilities across all of the cognitive domains were > 1.31 points lower. Second, for every 1 SD slower gain in weight or BMI from birth to 5 months, general reasoning and visual-motor integration decreased by > 0.97 points; for every 1 SD slower gain in length from 5 to 20 months and from 20 to 56 months, respectively, visual-motor integration, and verbal competence and language comprehension decreased by > 1.03 points; and for every 1 SD slower increase in head circumference from birth to 5 months and from 5 to 20 months, respectively, visual-motor integration and language comprehension decreased by > 1.17 points. Third, tests for nonlinear relationships revealed that, in some cases, large body size and faster growth were also associated with lower scores in cognitive tests. CONCLUSIONS. Our findings suggest that, even within the range of children born at term, prenatal and postnatal growth in body size are associated with individual differences in cognitive abilities. Helakorpi, S., Martelin, T., Torppa, J., Vartiainen, E., Uutela, A. and Patja, K. Preventive Medicine. 2008; 46(4): 340-345. Article. IF 2.390 Objective. To assess the impact of the 1976 Tobacco Control Act (TCA) on smoking initiation across socioeconomic groups. Methods. Nationwide data from independent annual cross-sectional postal surveys in 1978-2002 in Finland. Subjects were 25-64-year-old men and women born 1926-1975 (n = 68 071). Socioeconomic status was derived individually from population census data. Logistic regression was applied to assess the impact of the 1976 TCA on the prevalence of ever daily smoking in birth cohorts and socioeconomic groups. Results. Clear socioeconomic differences in ever daily smoking among men and women were found. In all socioeconomic groups a declining cohort trend was observed among men whereas women showed an increasing trend in early cohorts and a declining one thereafter. A statistically significant decline in the proportion of ever daily smokers compatible with the impact of the TCA was found in all socioeconomic groups except farmers. Among women the decline was roughly similar in each socioeconomic group, while among men it varied and was most pronounced among white collar employees. Conclusions. The impact of the 1976 TCA was less pronounced among male lower socioeconomic groups. In spite of the even impact of the TCA on female smoking across socioeconomic groups, large socioeconomic disparities remain. Tobacco control policy measures specifically directed at lower socioeconomic groups are needed. (C) 2007 Elsevier Inc. All rights reserved. Training improves physical fitness and decreases CRP also in asthmatic conscripts Juvonen, R., Bloigu, A., Peitso, A., Silvennoinen-Kassinen, S., Saikku, P., Leinonen, M., Hassi, J. and Harju, T. Journal of Asthma. 2008; 45(3): 237-242. Article. IF 1.476 To study the respiratory and physical health of young men, 224 asthmatic and 668 non-asthmatic military conscripts were recruited from the intake groups of July 2004 and January 2005 in Kajaani, Finland. Factors affecting respiratory health were elicited by a questionnaire at the beginning of the service, and results of high sensitive C-reactive protein (hsCRP) determination, peak expiratory flow (PEF), and 12-minute running test were collected at the beginning and the end of the service. Respiratory infections were diagnosed by a study physician. Upon entering military service, asthmatics had frequent exercise- and cold-related asthma symptoms (69.6% and 76.3%), and 48% of them had no medication for asthma. At the beginning, 25.8% of asthmatics and 19.1% of non-asthmatics had a poor result of less than 2,200 m (p = 0.05) in the 12-minute running test, and after 180 to 362 days of service, the corresponding percentages were 11.7% and 9.7% (p = 0.434). The levels of hsCRP, a marker of low-grade systemic inflammation, decreased significantly among both asthmatics, 1.5 (p =0.001), and non-asthmatics, 1.6 mg/L (p < 0.001). Asthmatic men had 0.2 and non-asthmatics 0.1 respiratory infections per month (p < 0.00 1). In summary, asthmatic conscripts can enhance their physical fitness by training similarly to non-asthmatic ones. Their levels of hsCRP also decrease. Early-life events. Effects on aging Kajantie, E. Hormones (Athens). 2008; 7(2): 101-13. 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. Serum Vitamin D and Subsequent Occurrence of Type 2 Diabetes Knekt, P., Laaksonen, M., Mattila, C., Harkanen, T., Marniemi, J., Heliovaara, M., Rissanen, H., Montonen, J. and Reunanen, A. Epidemiology. 2008. IF 4.339 BACKGROUND:: Low vitamin D status has been suggested as a risk factor for type 2 diabetes. Although the epidemiologic evidence is scarce, 2 recent studies have suggested an association. The present study investigated the relation of serum vitamin D with type 2 diabetes incidence using pooled data from these 2 cohorts. METHODS:: Two nested case-control studies, collected by the Finnish Mobile Clinic in 1973-1980, were pooled for analysis. The study populations consisted of men and women aged 40-74 years and free of diabetes at baseline. During a follow-up period of 22 years, 412 incident type 2 diabetes cases occurred, and 986 controls were selected by individual matching. Serum vitamin D (serum 25(OH)D) was determined from frozen samples, stored at baseline. Pooled estimates of the relationship between serum vitamin D concentration and type 2 diabetes incidence were calculated. RESULTS:: Men had higher serum vitamin D concentrations than women and showed a reduced risk of type 2 diabetes in their highest vitamin D quartile. The relative odds between the highest and lowest quartiles was 0.28 (95% confidence interval = 0.10-0.81) in men and 1.14 (0.60-2.17) in women after adjustment for smoking, body mass index, physical activity, and education. CONCLUSIONS:: The results support the hypothesis that high vitamin D status provides protection against type 2 diabetes. Residual confounding may contribute to this association. Knekt, P., Lindfors, O. and Laaksonen, M. A. European Psychiatry. 2008; 23: S255-S256. Meeting Abstract. IF 1.463 Characterization and fate of black currant and bilberry flavonols in enzyme-aided processing Koponen, J. M., Happonen, A. M., Auriola, S., Kontkanen, H., Buchert, J., Poutanen, K. S. and Torronen, A. R. Journal of Agricultural and Food Chemistry. 2008; 56(9): 3136-3144. Article. IF 2.322 The fate of black currant (Ribes nigrum L.) and bilberry (Vaccinium myrtillus L.) flavonols in enzyme-aided processing was studied. The flavonols were quantified and characterized by high-performance liquid chromatography equipped with a diode array detector and an electrospray ionization mass spectrometer. A tentative identification for 14 black currant and 19 bilberry flavonols is presented representing 11 previously unpublished conjugates. For the first time in any berry, the presence of laricitrin conjugates is reported. The enzyme-aided processing affected the flavonol extractability, elevating the yield in juices and decreasing that in press residues. Importantly, no significant loss of the berry flavonols was observed during the experiments, although some hydrolysis of flavonol conjugates was recorded. To maximize the effect on flavonol extractability, higher enzyme dosages were needed for black currants than for bilberries. The data show that the flavonol extractability and hydrolysis are dependent on the texture of raw material, the glycosylation pattern of the conjugates, and the activity profile of the enzyme preparation. Serotonin transporter binding and acquired obesity - An imaging study of monozygotic twin pairs Koskela, A. K., Kaurijoki, S., Pietilainen, K. H., Karhunen, L., Pesonen, U., Kuikka, J. T., Kaprio, J. and Rissanen, A. Physiology & Behavior. 2008; 93(4-5): 724-732. Article. IF 2.445 Serotonin (5-HT) has been implicated as one factor controlling body weight and feeding behaviour. We studied the association between obesity and 5-HT by investigating the brain serotonin transporter (SERT) binding in 16 monozygotic twin pairs with varying body mass index (BMI) differences. The radioligand [I-123]nor-beta-CIT was used for single photon emission computed tomography (SPECT) imaging of SERT binding. SERT genotype was also identified for each subject. We hypothesized reduced SERT binding in twins with higher BMI as compared to their leaner co-twins, and increased SERT binding in subjects with LL homozygotes compared to LS heterozygotes and SS homozygotes. In pairwise analyses, twins with higher BMI had higher SERT binding than their leaner co-twins in the hypothalamus/thalamus (specific binding ratios 1.21 +/- 0.23 vs. 1.12 +/- 0.16, p=0.04). The difference was striking in women (1.17 +/- 0.24 vs. 1.04 +/- 0.16, p=0.01), but not in men (1.26 +/- 0.22 vs. 1.22 +/- 0.08, p=0.61). In individuals, no correlation between SERT binding and BMI was evident, and no differences were found in SERT binding between the three SERT genotypes. Our finding suggests an association between acquired obesity and the 5-HT system, particularly in women. However, this association was seen only in twin data, where genetic effects and many shared environmental factors are eliminated. (c) 2007 Elsevier Inc. All rights reserved. Kousa, A., Havulinna, A. S., Moltchanova, E., Taskinen, O., Nikkarinen, M., Salomaa, V. and Karvonen, M. Applied Geochemistry. 2008; 23(4): 632-640. Article. IF 1.866 The protective role of water hardness and Mg in cardiovascular illness has been suggested in several epidemiological studies. In the present ecological study, the association of Ca, Mg, Al, Cu, F, Fe, Zn and NO3 in local ground water and spatial variation of acute myocardial infarction (AMI) incidence among men and women 35-74 years of age in rural Finland in 1991-2003 were examined. Data on AMI cases, 67,755 men and 25,450 women, were obtained from the Finnish Cardiovascular Disease Register. The statistical analysis was carried out using Bayesian modeling. 10 x 10 km grid cells were used instead of administrative boundaries to partition the study area. On average, 1 mg/L increment in Mg level in local ground water was associated with 2% (95% HDR -0.0391, -0.0028) decrease in incidence of AMI in the rural population. In conclusion, high AMI incidence in eastern Finland is associated with soft ground water, low in Mg. (C) 2007 Elsevier Ltd. All rights reserved. Prediction of a suitability score on psychiatric symptoms in short- and long-term therapy Laaksonen, M. A., Knekt, P. and Lindfors, O. European Psychiatry. 2008; 23: S257-S257. Meeting Abstract. IF 1.463 Lahti, S., Suominen-Taipale, L. and Hausen, H. European Journal of Oral Sciences. 2008; 116(3): 260-266. Article. IF 1.747 The aims of the present study were to evaluate the prevalence and severity of oral health impacts among adults and to analyse the effects of age, gender, level of education, number of teeth, and removable denture wearing on these impacts. Nationally representative data (n = 5,987) on Finnish adults aged 30+ yr were gathered in an interview, in a clinical examination, and by a questionnaire including the 14-item Oral Health Impact Profile. Subject age and the number of teeth were significantly associated with oral impacts (occurring fairly or very often) when the effects of gender, educational level, and removable dentures were considered. When subjects >= 75 yr of age were used as the reference group, the odds ratios (95% confidence interval) were 0.5 (0.3-0.8) and 0.7 (0.5-0.9) for 30-34-yr-old and 34-74-yr-old subjects, respectively. The odds ratios for those with 1-9 teeth and for those who were edentate were 3.4 (2.4-4.9) and 4.0 (2.6-6.3), respectively (20+ teeth as reference). Number of teeth modified the effect of denture wearing, and age modified the effect of educational level on oral impacts. Impaired subjective oral health related to many missing teeth might be improved by wearing removable dentures. Population groups needing special attention are young people with low education and those for whom only a few missing teeth are replaced with removable dentures. Use of eye care services and need for assistance in the visually impaired Laitinen, A., Koskinen, S., Rudanko, S. L., Martelin, T., Laatikainen, L. and Aromaa, A. Optometry and Vision Science. 2008; 85(5): 341-349. Article. IF 1.371 Purpose. To assess the use of eye care services and unmet need for assistance in visually impaired people. Methods. Cross-sectional population-based survey on a sample representing the Finnish population aged 30 years and older. Of the 7979 eligible people, 6645 (83.3%) were both interviewed and had their distance visual acuity (VA) assessed. One hundred forty-seven people were classified as visually impaired (VA <= 0.25). A home interview included an assessment of the use of eye care services, need for assistance, sociodemographic variables, cognitive functioning, and mobility. Binocular VA for distance was measured with the participants' current spectacles, if any, as a part of a comprehensive health examination. Results. One-half (58%) of visually impaired people had had a recent vision examination and 79% had received some vision rehabilitation services, mainly in form of spectacles (70%). Only one third (31%) had received formal low vision rehabilitation. People with moderate visual impairment (VA 0.1 to 0.25) were less likely to have received low vision rehabilitation, magnifying glasses, or other low vision aids compared with people with severe low vision (VA < 0.1). Furthermore, low cognitive capacity and living in an institution were associated with limited use of vision rehabilitation services. Of the visually impaired people living in the community, 71% reported need for assistance and 24% of them had unmet need for assistance in everyday activities. Although need for assistance was more common in people with severe low vision (83% vs. 67%, p = 0.09), unmet need for assistance seemed to be more common in people with moderate low vision (20% vs. 9%, p = 0.23). Conclusions. Many visually impaired people, older persons in particular, have not had a recent vision examination and lack adequate low vision rehabilitation. This highlights the need for regular evaluation of vision function in elderly people and for actively supplying information about rehabilitation services. Lyly, A., Marjavaara, S. K., Kyttala, A., Uusi-Rauva, K., Luiro, K., Kopra, O., Martinez, L. O., Tanhuanpaa, K., Kalkkinen, N., Suomalainen, A., Jauhiainen, M. and Jalanko, A. Human Molecular Genetics. 2008; 17(10): 1406-1417. Article. IF 8.099 Infantile neuronal ceroid lipofuscinosis (INCL) is a severe neurodegenerative disease caused by deficiency of palmitoyl protein thioesterase 1 (PPT1). INCL results in dramatic loss of thalamocortical neurons, but the disease mechanism has remained elusive. In the present work we describe the first interaction partner of PPT1, the F-1-complex of the mitochondrial ATP synthase, by co-purification and in vitro-binding assays. In addition to mitochondria, subunits of F-1-complex have been reported to localize in the plasma membrane, and to be capable of acting as receptors for various ligands such as apolipoprotein A-1. We verified here the plasma membrane localization of F-1-subunits on mouse primary neurons and fibroblasts by cell surface biotinylation and TIRF-microscopy. To gain further insight into the Ppt1-mediated properties of the F-1-complex, we utilized the Ppt1-deficient Ppt1(Delta ex4) mice. While no changes in the mitochondrial function could be detected in the brain of the Ppt1(Delta ex4) mice, the levels of F-1-subunits a and beta on the plasma membrane were specifically increased in the Ppt1(Delta ex4) neurons. Significant changes were also detected in the apolipoprotein A-I uptake by the Ppt1(Delta ex4) neurons and the serum lipid composition in the Ppt1(Delta ex4) mice. These data indicate neuron-specific changes for F-1-complex in the Ppt1-deficient cells and give clues for a possible link between lipid metabolism and neurodegeneration in INCL. One-year course and predictors of outcome of adolescent depression Marttunen, M. J., Karlsson, L., Kiviruusu, O., Miettunen, J., Heila, H., Holi, M., Ruuttu, T., Tuisku, V. and Pelkonen, M. European Psychiatry. 2008; 23: S74-S74. Meeting Abstract. IF 1.463 Alexithymia among Finnish male prisoners Mattila, A. K., Hypen, K., Andersson, N., Samppala, M. and Joukamaa, M. European Psychiatry. 2008; 23: S38-S38. Meeting Abstract. IF 1.463 Miettunen, J., Veijola, J., Isohanni, M. K., Paunio, T., Freimer, N., Jaaskelainen, E., Ekelund, J., Peltonen, L., Joukamaa, M. and Lichtermann, D. European Psychiatry. 2008; 23: S132-S132. Meeting Abstract. IF 1.463 Muhonen, L. H., Lönnqvist, J., Juva, K. and Alho, H. J Clin Psychiatry. 2008; 69(3): 392-9. IF 5.533 OBJECTIVE: The aim of the study was to evaluate possible new treatments for major depressive disorder in patients with comorbid alcohol dependence in a municipal alcohol treatment unit. The efficacy of memantine, a noncompetitive glutamate N-methyl-D-aspartate (NMDA)-receptor blocker used for the treatment of moderate to severe Alzheimer's disease, was compared with that of escitalopram, a selective serotonin reuptake inhibitor antidepressant. METHOD: Eighty alcohol-dependent outpatients with major depressive disorder (DSM-IV criteria) seeking treatment from municipal alcohol treatment clinics in Helsinki, Finland, were randomly assigned 1:1 to receive memantine 20 mg/day or escitalopram 20 mg/day. During the study period, patients continued their routine treatment at the clinics. Abstinence was not required. Concomitant interventions or imposed treatment goals were not offered by the study physician. The patients returned to the treatment clinics at weeks 1, 2, 4, 12, and 26 for data collection and for medication checking and dispensing. Outcome measures were the Montgomery-Asberg Depression Rating Scale (MADRS) and Beck Depression Inventory-II for depression, Hamilton Rating Scale for Anxiety (HAM-A) and Beck Anxiety Inventory for anxiety, Consortium to Establish a Registry for Alzheimer's Disease test battery for cognitive functions, and Social and Occupational Functioning Assessment Scale for social and occupational functions and quality-of-life measures. Twenty-nine patients in each group completed the study. All primary and secondary outcome statistical analyses were performed by an independent source for intent-to-treat populations, which included all patients randomly assigned to treatment. The study was conducted from December 2004 to May 2006. RESULTS: Both treatments significantly reduced the baseline level of depression and anxiety according to MADRS and HAM-A, which were the primary measures (p < .0001). There was no significant difference between the memantine and escitalopram groups. Assessed cognitive functioning scores were primarily within the normative range and were unchanged in both groups. Quality-of-life outcomes equally improved in both treatment groups. CONCLUSIONS: These data provide new evidence for the safety and potential efficacy of memantine and escitalopram for major depressive disorder in patients with comorbid alcohol dependence. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00368862. Serum uric acid and incident diabetes in Mauritian Indian and Creole populations Nan, H. R., Qiao, Q., Soderberg, S., Pitkaniemi, J., Paul, Z., Shaw, J., Alberti, G., Ulla, U., Pauvaday, V., Chitson, P. and Tuomilehto, J. Diabetes Research and Clinical Practice. 2008; 80(2): 321-327. Article. IF 1.837 Objective: To investigate the predictive value of serum uric acid (UA) for the development of diabetes in Asian Indians and Creoles living in Mauritius. Methods: A total of 1941 men (1409 Indians, 532 Creoles) and 2318 non-pregnant women (1645 Indians, 673 Creoles), aged 25-74years and free of diabetes, cardiovascular disease and gout at baseline examinations in 1987 or 1992, were re-examined in 1992 and/or 1998. Diabetes was determined according to WHO/IDF 2006 criteria. The relationship between baseline UA and the development of diabetes during the follow-up was estimated using interval censored survival analysis. Results: In this cohort 337 (17.4%) men and 379 (16.4%) women developed diabetes during the follow-up. Individuals who developed diabetes during the follow-up had a lower serum UA levels at follow-up compared with their baseline UA levels, but this is not observed for postmenopausal women. Multivariate adjusted hazard ratios (HRs) (95% CIs) for the development of diabetes corresponding to one S.D. increase in UA concentration at baseline were 1.14 (1.01, 1.30) in Indian men and 1.37 (1.11, 1.68) in Creole men. They were 1.07 (0.95, 1.22) and 1.01 (0.84, 1.22), respectively, in Indians and Creole women. Conclusion: Elevated serum UA is an independent risk marker for future diabetes in Mauritian men, whereas the prediction is weak in women. (C) 2008 Elsevier Ireland Ltd. All rights reserved. Air pollution and PEF measurements of children in the vicinity of a steel works Oravisjarvi, K., Rautio, A., Ruuskanen, J., Tiittanen, P. and Timonen, K. L. Boreal Environment Research. 2008; 13(2): 93-102. Article. IF 1.188 The effects of short-term changes in particulate air pollution on the respiratory health of symptomatic children living near a steel works at Raahe, Finland, were assessed to determine whether particulate air pollution is associated with adverse respiratory effects, and whether specific sources of air pollution are responsible for these effects. A screening questionnaire on respiratory symptoms was distributed to 1355 primary school children during the winter, asking about lower respiratory symptoms (wheezing, attacks of wheezing, dry cough, asthma). 56 symptomatic children (34 with asthma and 16 with dry cough) were followed up for four months with measurements of daily peak expiratory flow (PEF). The acute effects of inhalable particles (PM10), fine particles (PM2.5), elements (Al, K, Cu, Zn, SO42-) and sulphur dioxide (SO2) were estimated by linear first-order autoregressive model. Mean daily PM2.5 concentrations were 10 mu g m(-3). Most regression coefficients between air pollution and morning and evening PEF were negative but not statistically significant. There was no statistically significant association between particulate air pollution and respiratory health among these symptomatic children. The only significant association was between Cu lag 3 (three days before) and morning PEF, it is difficult to assess, the meaning of this association, because the other variables related to Cu had no significant associations with morning or evening PER The significance of this observation therefore requires confirmation and further investigation. Accuracy in the estimation of food servings against the portions in food photographs Ovaskainen, M. L., Paturi, M., Reinivuo, H., Hannila, M. L., Sinkko, H., Lehtisalo, J., Pynnonen-Polari, O. and Mannisto, S. European Journal of Clinical Nutrition. 2008; 62(5): 674-681. Article. IF 2.116 Objective: In diet surveys, quantitative underestimation of food consumption may be due to intentional misreporting or false portion-size reporting. Perception of food photographs used as aids for assessing the actual amounts may have an effect. This study was carried out to assess the validity of food photographs. Design: A real-time test protocol where 52 presented food servings were compared against photographed portions with similar food items. Subjects: Volunteers from the Rehabilitation Company Petrea (in Turku) were recruited, 161 adults participated, and for 146 subjects, complete data were collected. Methods: The proportions of correct estimations and reporting errors, in weights and percentages, are presented by gender and food group. Food descriptors, portion- size options and subject characteristics were studied as potential determinants of accuracy in portion- size estimation. Results: The total proportion of exactly correct estimations was 51% in men and 49% in women. The overall reporting error was -10 g in men and +1 g in women for the 52 food servings. Underreporting was typical for bread, spread and cold cuts and dishes in both genders. Over-reporting was typical for cereals in both genders and for snacks, vegetables and fruit in women. The estimation error was associated with the portion- size options but not associated with the energy density of food items, education or body mass index. Conclusions: Food portions in photographs seem to be a useful aid for the quantification of most food items. However, validation studies are needed to test the applicability of photographs for estimating current portions and for searching better tools in dietary surveys. Pajala, S., Era, P., Koskenvuo, M., Kaprio, J., Tormakangas, T. and Rantanen, T. Journals of Gerontology Series a-Biological Sciences and Medical Sciences. 2008; 63(2): 171-178. Article. IF 2.861 Background. Inability to maintain balance while standing increases risk of falls in older people. The present study assessed whether center of pressure (COP) movement measured with force platform technology predicts risk for falls among older people with no manifest deficiency in standing balance. Methods. Participants were 434 community-dwelling women, aged 63-76 years. COP was measured in six stances on a force platform. Following balance tests, participants reported their falls with 12 monthly calendars. Incidence rate ratios (IRR) with 95% confidence intervals (CI) were computed from negative binomial regression models. For the analysis, those with >= 1 fall indoors were coded "indoor fallers," those with >= 1 fall outdoors, but no indoor falls, were coded "outdoor fallers." Outcome in the models was number of falls. Analyses were repeated including only participants without fall history prior to follow-up. Results. Among 198 fallers, there were 57 indoor and 132 outdoor fallers. The participants in the highest COP movement tertile, irrespective of the balance test, had a two- to fourfold risk for indoor falls compared to participants in the lowest COP tertile of the test. Inability to complete the tandem stance was also a significant predictor of the fall risk. The trend for increased risk for indoor falls was found also for participants in the highest COP movement tertile and without fall history. The COP movement in balance tests was not associated with outdoor falls. Conclusion. Force platform balance tests provide valid information of postural control that can be used to predict fall risk even among older people without apparent balance problems or fall history. When the force platform is not available, tandem stance provides a screening tool to show increased fall risk in community-dwelling older people. Pelkonen, M., Marttunen, M., Kaprio, J., Huurre, T. and Aro, H. J Affect Disord. 2008; 106(1-2): 123-31. IF 3.138 BACKGROUND: We examined mid-adolescent psychosocial problems as risk factors for subsequent depression up to adulthood proper, and differences in these for episodic and persistent depression. METHODS: In a 16-year follow-up of an urban Finnish community cohort (547 males and 714 females) from age 16 years risk factors for subsequent depression (S-BDI) were studied. Data were collected with a classroom questionnaire at 16 years and a postal questionnaire at 22 and 32 years. Differences in predictors for episodic depression (only at age of 22 or 32 y) and persistent depression (both at 22 and 32 y) were studied using logistic and multinomial regression analyses. RESULTS: Mid-adolescent depressive symptoms predicted persistent and female sex episodic depression. Low self-esteem, dissatisfaction with academic achievement, problems with the law, having no dating experiences, and parental divorce all predicted both episodic and persistent depression. LIMITATIONS: We had two assessment points in adulthood, but no information about depression between these. CONCLUSIONS: The associations between mid-adolescent psychosocial problems and subsequent depression extended up to adulthood proper, somewhat differently for episodic and persistent depression. Preventive efforts should be focused towards young people at risk. Piirainen, L., Haahtela, S., Helin, T., Korpela, R., Haahtela, T. and Vaarala, O. Ann Allergy Asthma Immunol. 2008; 100(4): 338-42. IF 2.254 BACKGROUND: Lactobacillus rhamnosus GG (LGG) has demonstrated promising results in the treatment and prevention of atopic eczema. OBJECTIVE: To study the effects of LGG on the oral immune response in adolescents and adults with birch pollen allergy combined with oral allergy syndrome. METHODS: Patients received either LGG (n = 19) or a placebo (n = 19) for 5.5 months (from February 8 to August 6, 1999), starting 2.5 months before the birch pollen season. An oral apple challenge test was performed before, during, and after the pollen season. Saliva samples were collected before and after the challenges, and serum samples were collected before the challenges. Total IgA, IgG, and IgM and rBet v1 and rMal dl specific IgA, IgG, IgG1, and IgG4 levels were measured from saliva with an enzyme-linked immunosorbent assay (ELISA). Serum rBet v1 specific IgE ELISA and birch radioallergosorbent testing were performed. RESULTS: After 5.5 months, rBet v1 and rMal dl specific IgA levels had increased from baseline in the LGG compared with the placebo group (delta rBet v1 IgA, 0.319 vs. -0.136 relative units; P = .02; delta rMal d1 IgA, 0.097 vs -0.117, P = .02). rBet v1 specific IgE serum levels did not differ between the groups. In the LGG group, rBet v1 specific IgE levels correlated positively with stimulated total IgA (P = .04) and IgG (P = .003) in saliva. In the placebo group, rBet vl specific IgE levels correlated negatively with stimulated rBet v1 and rMal d1 IgA levels (P = .009 for both) and IgG (P = .02 and P = .03, respectively). CONCLUSION: LGG showed immunostimulating effects on oral mucosa seen as increased allergen specific IgA levels in saliva. Diversity and seasonal dynamics of bacterial community in indoor environment Rintala, H., Pitkaranta, M., Toivola, M., Paulin, L. and Nevalainen, A. BMC Microbiol. 2008; 8: 56. IF 2.896 BACKGROUND: We spend most of our lives in indoor environments and are exposed to microbes present in these environments. Hence, knowledge about this exposure is important for understanding how it impacts on human health. However, the bacterial flora in indoor environments has been only fragmentarily explored and mostly using culture methods. The application of molecular methods previously utilised in other environments has resulted in a substantial increase in our awareness of microbial diversity. RESULTS: The composition and dynamics of indoor dust bacterial flora were investigated in two buildings over a period of one year. Four samples were taken in each building, corresponding to the four seasons, and 16S rDNA libraries were constructed. A total of 893 clones were analysed and 283 distinct operational taxonomic units (OTUs) detected among them using 97% sequence similarity as the criterion. All libraries were dominated by Gram-positive sequences, with the most abundant phylum being Firmicutes. Four OTUs having high similarity to Corynebacterium-, Propionibacterium-, Streptococcus- and Staphylococcus- sequences were present in all samples. The most abundant of the Gram-negative OTUs were members of the family Sphingomonadaceae, followed by Oxalobacteraceae, Comamonadaceae, Neisseriaceae and Rhizobiaceae. The relative abundance of alpha- and betaproteobacteria increased slightly towards summer at the expense of firmicutes. The proportion of firmicutes and gammaproteobacteria of the total diversity was highest in winter and that of actinobacteria, alpha- and betaproteobacteria in spring or summer, whereas the diversity of bacteroidetes peaked in fall. A statistical comparison of the libraries revealed that the bacterial flora of the two buildings differed during all seasons except spring, but differences between seasons within one building were not that clear, indicating that differences between the buildings were greater than the differences between seasons. CONCLUSION: This work demonstrated that the bacterial flora of indoor dust is complex and dominated by Gram-positive species. The dominant phylotypes most probably originated from users of the building. Seasonal variation was observed as proportional changes of the phyla and at the species level. The microflora of the two buildings investigated differed statistically and differences between the buildings were more pronounced than differences between seasons. Seasonal changes in mood and behaviour are a proxy to metabolic syndrome Rintamaki, R., Grimaldi, S., Englund, A., Haukka, J., Partonen, T., Reunanen, A., Aromaa, A. and Lonnqvist, J. European Psychiatry. 2008; 23: S274-S274. Meeting Abstract. IF 1.463 Saarni, S. I., Joutsenniemi, K., Koskinen, S., Suvisaari, J., Pirkola, S., Sintonen, H., Poikolainen, K. and Loennqvist, J. Alcohol and Alcoholism. 2008; 43(3): 376-386. Article. IF 2.061 Aims: To examine the associations between alcohol consumption and utility-based health-related quality of life (HRQoL), subjective quality of life (QoL), self-rated health (SRH), and mental distress. Methods: Representative general population survey in Finland, with 5871 persons aged 30-64 years. HRQoL was measured with two health utility instruments (15D and EQ-5D), QoL and SRH were measured with RATING scales, and mental distress with a General Health Questionnaire (GHQ-12). Past alcohol problems were diagnosed with a structured psychiatric interview known as the composite international diagnostic interview (CIDI). Alcohol consumption was examined with a self-report questionnaire. Results: Negative associations between alcohol and well-being were observed on several measures for women consuming more than 173 g and men more than 229 g per week. Former drinkers scored worst on most measures, even in comparison to the highest drinking decile. For men, all statistically significant associations between moderate drinking and well-being disappeared when sociodemographic factors and former drinkers were controlled for. For women, moderate alcohol use associated with better SRH and EQ-5D as compared to abstainers. However, the possible health utility benefits associated with moderate alcohol consumption were of clinically insignificant magnitude. Conclusions: Failure to separate former drinkers and other abstainers produces a significant bias favoring moderate drinkers. As the possible health utility benefits of moderate alcohol use were clinically insignificant, it suffices to investigate mortality, when estimating the public health impact of moderate alcohol consumption using quality-adjusted life years. Suvisaari, J., Perala, J., Saarni, S. L., Harkanen, T., Pirkola, S., Joukamaa, M., Koskinen, S., Lonnqvist, J. and Reunanen, A. European Archives of Psychiatry and Clinical Neuroscience. 2008; 258(3): 129-136. Article. IF 3.042 Schizophrenia and other psychotic disorders are associated with increased risk of developing type 2 diabetes. However, previous studies are mainly based on clinical samples where the comorbidity may be stronger. We investigated in a general population survey the prevalence of type 2 diabetes in persons with psychotic disorders and in users of antipsychotic medication. The study was based on a nationally representative two-stage cluster sample of 8,028 persons aged 30 or over from Finland. Diagnostic assessment of psychotic disorders combined SCID-I interview and case note data. Prevalences of type 2 diabetes, adjusting for age and sex, were estimated by calculating predicted marginals. The prevalence estimate of type 2 diabetes was 22.0% among subjects with schizophrenia, 13.4% among subjects with other nonaffective psychosis and 6.1% in subjects without psychotic disorders. Only two subjects (3.4%) with affective psychosis had type 2 diabetes. Users of all types of antipsychotic medication had increased prevalence of type 2 diabetes. Our results suggest that type 2 diabetes is a major health concern among persons with schizophrenia and other nonaffective psychotic disorders and also in users of antipsychotic medication, but persons with affective psychosis in the general population may not have increased prevalence of type 2 diabetes. Tiittanen, M., Westerholm-Ormio, M., Verkasalo, M., Savilahti, E. and Vaarala, O. Clinical and Experimental Immunology. 2008; 152(3): 498-507. Article. IF 2.747 Because the role of regulatory T cells in the intestinal inflammation is unknown in coeliac disease (CD) and type 1 diabetes (T1D), the expression of forkhead box P3 (FoxP3), CD25, transforming growth factor-beta, interferon (IFN)-gamma, interleukin (IL)-4, IL-8, IL-10, IL-15 and IL-18 was measured by quantitative reverse transcription-polymerase chain reaction in the small intestinal biopsies from paediatric patients with active or potential CD, T1D and control patients. The numbers of FoxP3- and CD25-expressing cells were studied with immunohistochemistry. Enhanced intestinal expressions of FoxP3, IL-10 and IFN-gamma mRNAs were found in active CD when compared with controls (P-values < 0.001, 0.004, < 0.001). In potential CD, only the expression of IFN-gamma mRNA was increased. The numbers of FoxP3-expressing cells were higher in active and potential CD (P < 0.001, P = 0.05), and the ratio of FoxP3 mRNA to the number of FoxP3-positive cells was decreased in potential CD when compared with controls (P = 0.007). The ratio of IFN-gamma to FoxP3-specific mRNA was increased in active and potential CD (P = 0.001 and P = 0.002). Patients with T1D had no changes in regulatory T cell markers, but showed increased expression of IL-18 mRNA. The impaired up-regulation of FoxP3 transcripts despite the infiltration of FoxP3-positive cells in potential CD may contribute to the persistence of inflammation. The increased ratio of IFN-gamma to FoxP3 mRNA in active and potential CD suggests an imbalance between regulatory and effector mechanisms. The increased intestinal expression of IL-18 mRNA in patients with T1D adds evidence in favour of the hypothesis that T1D is associated with derangements in the gut immune system. Tuomilehto, H., Peltonen, M., Partinen, M., Seppa, J., Saaristo, T., Korpi-Hyovalti, E., Oksa, H., Saltevo, J., Puolijoki, H., Vanhala, M. and Tuomilehto, J. Diabetes Obesity & Metabolism. 2008; 10(6): 468-475. Article. IF 2.434 Aim: To determine the association between sleep-disordered breathing (SDB) and obesity, diabetes and glucose intolerance among middle-aged men and women in Finland. Methods: A multicentre, population-based, cross-sectional survey in Finland. A total of 1396 men and 1500 women aged 45-74 years participated in the survey between 2004 and 2005. The study subjects underwent a health examination including an oral glucose tolerance test and filled a questionnaire describing their sleep habits. Results: Middle-aged men with SDB had an increased prevalence of diabetes and abnormal glucose tolerance. These associations were not found among middle-aged women. After adjustments for age, body mass index, smoking and central nervous system-affecting medication, SDB was independently associated with diabetes and glucose intolerance in men, but not in women. Conclusion: Middle-aged men with SDB have an independent risk of type 2 diabetes. However, both diabetes and SDB exhibit a strong association with obesity and especially with central obesity, reflecting increased visceral fat. In clinical practice especially male patients with diabetes should always be asked about habitual snoring and about possible sleep apnoea. Varjosalo, M., Bjorklund, M., Cheng, F., Syvanen, H., Kivioja, T., Kilpinen, S., Sun, Z., Kallioniemi, O., Stunnenberg, H. G., He, W. W., Ojala, P. and Taipale, J. Cell. 2008; 133(3): 537-48. IF 29.194 To allow genome-scale identification of genes that regulate cellular signaling, we cloned >90% of all human full-length protein kinase cDNAs and constructed the corresponding kinase activity-deficient mutants. To establish the utility of this resource, we tested the effect of expression of the kinases on three different cellular signaling models. In all screens, many kinases had a modest but significant effect, apparently due to crosstalk between signaling pathways. However, the strongest effects were found with known regulators and novel components, such as MAP3K10 and DYRK2, which we identified in a mammalian Hedgehog (Hh) signaling screen. DYRK2 directly phosphorylated and induced the proteasome-dependent degradation of the key Hh pathway-regulated transcription factor, GLI2. MAP3K10, in turn, affected GLI2 indirectly by modulating the activity of DYRK2 and the known Hh pathway component, GSK3beta. Our results establish kinome expression screening as a highly effective way to identify physiological signaling pathway components and genes involved in pathological signaling crosstalk. Controlling the cardiovascular disease epidemic Vartiainen, E. Journal of Internal Medicine. 2008; 263(6): 623-625. Editorial Material. IF 4.730 von Schantz, C., Saharinen, J., Kopra, O., Cooper, J. D., Gentile, M., Hovatta, I., Peltonen, L. and Jalanko, A. BMC Genomics. 2008; 9. Article. IF 4.029 Background: The neuronal ceroid lipofuscinoses (NCL) are a group of children's inherited neurodegenerative disorders, characterized by blindness, early dementia and pronounced cortical atrophy. The similar pathological and clinical profiles of the different forms of NCL suggest that common disease mechanisms may be involved. To explore the NCL-associated disease pathology and molecular pathways, we have previously produced targeted knock-out mice for Cln1 and Cln5. Both mouse-models replicate the NCL phenotype and neuropathology; the Cln1-/- model presents with early onset, severe neurodegenerative disease, whereas the Cln5-/- model produces a milder disease with a later onset. Results: Here we have performed quantitative gene expression profiling of the cortex from 1 and 4 month old Cln1-/- and Cln5-/- mice. Combined microarray datasets from both mouse models exposed a common affected pathway: genes regulating neuronal growth cone stabilization display similar aberrations in both models. We analyzed locus specific gene expression and showed regional clustering of Cln1 and three major genes of this pathway, further supporting a close functional relationship between the corresponding gene products; adenylate cyclase-associated protein 1 (Cap1), protein tyrosine phosphatase receptor type F (Ptprf) and protein tyrosine phosphatase 4a2 (Ptp4a2). The evidence from the gene expression data, indicating changes in the growth cone assembly, was substantiated by the immunofluorescence staining patterns of Cln1-/- and Cln5-/- cortical neurons. These primary neurons displayed abnormalities in cytoskeleton-associated proteins actin and beta-tubulin as well as abnormal intracellular distribution of growth cone associated proteins GAP-43, synapsin and Rab3. Conclusion: Our data provide the first evidence for a common molecular pathogenesis behind neuronal degeneration in INCL and vLINCL. Since CLN1 and CLN5 code for proteins with distinct functional roles these data may have implications for other forms of NCLs as well. Yegutkin, G. G. Biochimica Et Biophysica Acta-Molecular Cell Research. 2008; 1783(5): 673-694. Review. IF 6.900 The involvement of extracellular nucleotides and adenosine in an array of cell-specific responses has long been known and appreciated, but the integrative view of purinergic signalling as a multistep coordinated cascade has emerged recently. Current models of nucleotide turnover include: (i) transient release of nanomolar concentrations of ATP and ADP; (ii) triggering of signalling events via a series of ligand-gated (M) and metabotropic (M) receptors; (iii) nucleotide breakdown by membrane-bound and soluble nucleotidases, including the enzymes of ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) family, ecto-nucleotide pyrophosphatase/phosphodiesterase (E-NPP) family, ecto-5'-nucleotidase/CD73, and alkaline phosphatases-1 (iv) interaction of the resulting adenosine with own nucleoside-selective receptors; and finally, (v) extracellular adenosine inactivation via adenosine deaminase and purine nucleoside phosphorylase reactions and/or nucleoside uptake by the cells. In contrast to traditional paradigms that focus on purine-inactivating mechanisms, it has now become clear that "classical" intracellular ATP-regenerating enzymes, adenylate kinase, nucleoside diphosphate (NDP) kinase and ATP synthase can also be co-expressed on the cell surface. Furthermore, data on the ability of various cells to retain micromolar ATP levels in their pericellular space, as well as to release other related compounds (adenosine, UTP, dinucleotide polyphosphates and nucleotide sugars) gain another important insight into our understanding of mechanisms regulating a signalling cascade. This review summarizes recent advances in this rapidly evolving field, with particular emphasis on the nucleotide-releasing and purine-converting pathways in the vasculature. (C) 2008 Elsevier B.V. All rights reserved. |