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Cognitive functioning in patients with familial bipolar I
disorder and their unaffected relatives
Antila, M., Tuulio-Henriksson, A., Kieseppä, T., Eerola, M., Partonen, T. and Lönnqvist, J. Psychol Med. 2006: 1-9. IF 3.476 Background. Impairments in verbal learning and memory, executive functions and attention are manifest in some euthymic patients with bipolar disorder (BPD). However, evidence is sparse on their putative role as aetiologically important genetic vulnerability markers for the disorder. This population-based study examined the cognitive functions of affected and unaffected individuals in families with BPD. The aim was to discover whether any cognitive function would indicate genetic liability to the disorder and could thus be regarded as endophenotypes of BPD. Method. A diagnostic interview and a neuropsychological test battery were administered to 32 familial bipolar I disorder patients, 40 of their unaffected first-degree relatives and 55 controls, all representing population-based samples. Results. Unaffected first-degree relatives showed impairment in psychomotor performance speed and slight impairment in executive function. Bipolar patients were impaired in verbal learning and memory compared with unaffected relatives and controls. They also differed from controls in tasks of executive functions. There were no difference between the groups in simple attention and working memory tasks. Conclusions. Impaired psychomotor performance speed and executive function may represent endophenotypes of BPD, reflecting possible underlying vulnerability to the disorder. Verbal memory impairments appear to be more related to the fully developed disorder. Brännström, J., Hassler, S., Peltonen, L., Herrmann, B. and Winqvist, O. Clinical Immunology. 2006; 121(3): 265-273. Article. IF 3.217 Patients with Autoimmune polyendocrine syndrome type I (APS I) present with multiple endocrine failures due to organ-specific autoimmune disease, thought to be T-cell-mediated. Paradoxically, APS I patients suffer from chronic mucocutaneous candidiasis. The mutated gene has been identified as the Autoimmune regulator (AIRE). Aire is expressed in medullary epithelial cells of the thymus and in antigen presenting cells in the periphery. T cells from Aire deficient mice and men displayed an enhanced proliferative response against Candida antigen in vitro, suggesting that Aire deficient T cells are competent in recognizing Candida albicans. In contrast, monocytes from APS I patients displayed a decreased and delayed internalization of zymosan. Furthermore, Candida antigen activated monocytes from APS I patients show decreased and altered phoshotyrosine kinase activation. In conclusion, Aire deficient APCs have a defect receptor mediated internalization of Candida which affects kinase activation, likely altering the innate Candida immune response. (c) 2006 Elsevier Inc. All rights reserved. Complement C3 contributes to ethanol-induced liver steatosis in mice Bykov, I., Junnikkala, S., Pekna, M., Lindros, K. O. and Meri, S. Ann Med. 2006; 38(4): 280-6. IF 3.848 BACKGROUND: It is becoming increasingly clear that liver steatosis, a typical early consequence of alcohol exposure, sensitizes the liver to more severe inflammatory and fibrotic changes. On the other hand, activation of the key complement component C3, a central player in causing inflammation and tissue damage, is also known to be involved in the regulation of lipid metabolism. This prompted us to study the development of alcoholic liver steatosis in mice lacking C3 (C3-/-). RESULTS: Both C3-/- and normal C3+/+ mice were fed a steatosis-promoting high-fat diet with or without ethanol for 6 weeks. The diet without ethanol caused moderate liver steatosis in C3-/- but not in C3+/+ mice. As expected, ethanol-containing diet caused marked macrovesicular steatosis and increased the liver triglyceride content in C3+/+ mice. In contrast, ethanol diet tended to reduce steatosis and had no further effect on liver triglycerides in C3-/- mice. Furthermore, while in normal mice ethanol significantly increased the liver/body weight ratio, liver malondialdehyde level and serum alanine aminotransferase (ALT) activity, these effects were absent or small in C3-/- mice. A separate experiment with mice on chow diet confirmed the aberrant steatotic effect of ethanol in C3-/-mice: 4 hours after acute dosing of ethanol the liver triglyceride level had increased by 138% in C3+/+ mice (P<0.001), but only by 64% in C3-/- mice (n.s.). CONCLUSION. In C3-/- mice alcohol-induced liver steatosis is absent or strongly reduced after chronic or acute alcohol exposure. This suggests that the complement system and its component C3 contribute to the development of alcohol-induced fatty liver and its consequences. Early growth and adult health outcomes - lessons learned from the Helsinki Birth Cohort Study Eriksson, J. G. Maternal and Child Nutrition. 2005; 1(3): 149-154. Article. Slow growth during fetal life and infancy is often followed by accelerated weight gain in childhood. These patterns of growth seem to precede the development of coronary heart disease (CHD) and type 2 diabetes in adult life. Patterns of growth associated with CHD and type 2 diabetes in adult life are described based upon findings from the Helsinki Birth Cohort Study. We are beginning to understand that adult degenerative diseases are associated with different patterns of early growth. Yet it is not clear what optimal growth is and how it can be achieved. Most data suggest that the development of many non-communicable diseases involve a number of interactions including genetic ones. Therefore these diseases can best be focused upon from a life cycle perspective. Grönroos, P., Raitakari, O. T., Kähönen, M., Hutri-Kähönen, N., Marniemi, J., Viikari, J. and Lehtimäki, T. Atherosclerosis Supplements. 2006; 7(3): 68-68. Meeting Abstract. IF 8.963 Hedman, M., Pahlman, R., Sundvall, J., Ehnholm, C., Syvänne, M., Jokinen, E., Jauhiainen, M., Holmberg, C. and Antikainen, M. Atherosclerosis Supplements. 2006; 7(3): 576-577. Meeting Abstract. IF 8.963 Hennah, W., Tomppo, L., Hiekkalinna, T., Palo, O. M., Kilpinen, H., Ekelund, J., Tuulio-Henriksson, A., Silander, K., Partonen, T., Paunio, T., Terwilliger, J. D., Lonnqvist, J. and Peltonen, L. Hum Mol Genet. 2006. IF 7.764 We have previously reported a robust association between an allelic haplotype of DISC1 and schizophrenia in a nationwide collection of Finnish schizophrenia families. This specific DISC1 allele was later identified to associate with visual working memory, selectively in males. DISC1 association to schizophrenia has since been replicated in multiple independent study samples from different populations. In this study we conditioned our sample of Finnish families for the presence of the Finnish tentative risk allele for DISC1, and re-analyzed our genome-wide scan data of 443 markers based on this stratification. Two additional loci displayed evidence of linkage (lod > 3), and included a locus on 16p13, proximal to the gene encoding NDE1 that has been shown to biologically interact with DISC1. Although none of the observed linkages remained significant after multiple test correction through simulation, further analysis of NDE1 revealed an association between a tag-haplotype and schizophrenia (p = 0.00046) specific to females, that proved to be significant (p = 0.011) after multiple test correction. Our finding would support the concept that initial gene findings in multifactorial diseases will assist in the identification of other components of complex genetic etiology. Notably, this and other converging lines of evidence underline the importance of DISC1-related functional pathways in the etiology of schizophrenia. Isosaari, P., Hallikainen, A., Kiviranta, H., Vuorinen, P. J., Parmanne, R., Koistinen, J. and Vartiainen, T. Environ Pollut. 2006; 141(2): 213-25. IF 2.451 A total of 156 fish composite samples were collected from five areas of the Baltic Sea and from three lakes and analysed for polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), polychlorinated naphthalenes (PCNs) and polybrominated diphenyl ethers (PBDEs). The European Union's maximum permissible level for PCDD/Fs, 4 pg WHO-TEQ/g fresh weight (fw), was exceeded in salmon, river lamprey and Baltic herring. In other species from the Baltic Sea, the 90th percentile was 3.42 pg WHO(PCDD/F)-TEQ/g fw. In the lake fish, the concentrations of PCDD/Fs, PCBs and PCNs were only 29-46% of those in the same species caught from the Baltic Sea, whereas the concentrations of PBDEs in the lake fish were as high as in the Baltic Sea fish. Dioxin-like PCBs contributed to the total dioxin-like toxicity of PCBs and PCDD/Fs by 49+/-12% in all the analysed samples. Kajantie, E., Phillips, D. I. W., Osmond, C., Barker, D. J. P., Forsen, T. and Eriksson, J. G. Journal of Clinical Endocrinology and Metabolism. 2006; 91(12): 4953-4956. Article. IF 6.020 Background: The relationships of early growth with coronary heart disease and type 2 diabetes have received considerable attention. It is not known whether fetal or childhood growth is linked with autoimmune disorders. Objective: Our objective was to assess whether the risk of adult-onset spontaneous hypothyroidism is predicted by body size at birth and during childhood. Design and Setting: We conducted a birth cohort study in Helsinki, Finland. Participants: A total of 293 women who were born between 1934 and 1944 and had their heights and weights recorded at birth and during childhood participated in the study. Measurements: We measured spontaneous hypothyroidism, defined as: 1) a disease history confirmed from medical records, or 2) previously undiagnosed hypothyroidism (TSH > 10 mU/liter). Results: Twenty women (6.8%) had spontaneous hypothyroidism; 18 had been diagnosed previously, between 43 and 65 yr of age, and two had undiagnosed subclinical hypothyroidism. In addition, 59 women were thyroid peroxidase antibody positive. Compared with the 214 thyroid peroxidase antibody-negative women with no thyroid disorder, those with spontaneous hypothyroidism had on average 252 g [95% confidence interval (CI), 61 to 443 g; P = 0.01] lower birth weight and 1.2 cm (95% CI, 0.5 to 2.0 cm; P = 0.002) shorter length at birth. The odds of developing hypothyroidism increased 4.4-fold per kilogram decrease in birth weight (95% CI, 1.4 to 14.1). Hypothyroid subjects had been shorter in early childhood and had lower body mass index during later childhood. Conclusions: Small body size at birth and during childhood increases the risk of spontaneous hypothyroidism in adult women. Estimation of quantile mixtures via L-moments and trimmed L-moments Karvanen, J. Computational Statistics & Data Analysis. 2006; 51(2): 947-959. Article. IF 0.733 Moments or cumulants have been traditionally used to characterize a probability distribution or an observed data set. Recently, L-moments and trimmed L-moments have been noticed as appealing alternatives to the conventional moments. This paper promotes the use of L-mornents proposing new parametric families of distributions that can be estimated by the method of L-moments. The theoretical L-mornents are defined by the quantile function i.e. the inverse of cumulative distribution function. An approach for constructing parametric families from quantile functions is presented. Because of the analogy to mixtures of densities, this class of parametric families is called quantile mixtures. The method of L-mornents is a natural way to estimate the parameters of quantile mixtures. As an example, two parametric families are introduced: the normal-polynomial quantile mixture and the Cauchy-polynomial quantile mixture. The proposed quantile mixtures are applied to model monthly, weekly and daily returns of some major stock indexes. (c) 2005 Elsevier B.V. All rights reserved. Nasopharyngeal colonization: a target for pneumococcal vaccination Käyhty, H., Auranen, K., Nohynek, H., Dagan, R. and Mäkelä, H. Expert Rev Vaccines. 2006; 5(5): 651-67. The pneumococcal conjugate vaccine (PCV), licensed in 2000, is highly efficient in preventing serious disease caused by serotypes in the vaccine and also prevents symptomless colonization of the nasopharynx. Prevention of this first step in the infection cycle has important consequences: it reduces chances of spread of the infection and indirectly protects from disease. Through these indirect effects, the protection afforded by the vaccine extends to the whole population, including those not vaccinated (herd immunity). Already now, after 5 years of wide use of PCV for infant immunization in the USA, more cases are prevented through the indirect effects than by vaccine-induced immunity in those vaccinated. The extended protection increases the cost-effectiveness of PCV and should clearly encourage its use in poorly resourced countries. However, the accumulated experience also shows that the herd immunity, due to PCV, is partly offset by replacement of the vaccine serotypes by other, nonvaccine serotypes. Owing to the general reduced virulence of the latter, this has only had a modest effect on disease, but the possibility of more virulent nonvaccine serotypes arising cannot be ignored and should be the focus of continued surveillance. Kemppainen, U., Tossavainen, K., Vartiainen, E., Jokela, V., Puska, P., Pantelejev, V. and Uhanov, M. Research in Nursing & Health. 2006; 29(6): 543-555. Article. IF 1.077 The purpose of this study was to assess whether similar environmental factors predict adolescents' smoking in two different cultures: in the Pitkäranta district in Russian Karelia and in eastern Finland. The data were gathered by self-administered questionnaires from ninth-grade students in 10 comprehensive schools in Pitkäranta (n=385) and from age-matched students in 24 schools in eastern Finland (n=2,098). Structural equation modeling (SEM) was used to test whether similar path structures fit for boys and for girls in Pitkäranta and in eastern Finland, and to test whether regression coefficients were similar between the cultures by sex. Smoking by family members and best friends was positively related to adolescents' smoking both directly and indirectly. Environmental factors were similar Predictors of smoking between the cultures for boys. For girls, different regression coefficients in Pitkäranta and in eastern Finland were found. Best friend's smoking was the most important predictor of adolescents' own smoking in every sub-sample. When indirect relationships were identified, the significance of parents' and siblings' smoking, in addition to smoking by best friends, was strongly supported. (c) 2006 Wiley Periodicals, Inc. Kestilä, L., Koskinen, S., Martelin, T., Rahkonen, O., Pensola, T., Pirkola, S., Patja, K. and Aromaa, A. European Journal of Public Health. 2006; 16(6): 617-626. Article. IF 1.118 Aims: To assess the association of parental education, childhood living conditions and adversities with daily smoking in early adulthood and to analyse the effect of the respondent's own education, main economic activity, and current family structure on these associations. Methods: The study is based on a representative two-stage cluster sample (N = 1894, participation rate 79%) of young adults aged 18-29, in 2000, in Finland. The outcome measure is daily smoking. Results: Parental smoking and the respondent's own education had the strongest effects on daily smoking. If both parents of the respondent were smokers, then the respondent was most likely to be a smoker too (for men OR (odds ratio) = 3.01, for women OR = 2.41 after all adjustments). Young adults in the lowest educational category had a much higher risk of daily smoking than those in the highest category (OR = 5.88 for women, 4.48 for men). For women parental divorce (OR = 2.31) and current family structure also determined daily smoking. Parental education had a strong gradient in daily smoking and the effect appeared to be mediated largely by the respondent's own educational level. Conclusions: Childhood living conditions are strong determinants of daily smoking. Much of their influence seems to be mediated through current living conditions, which are also determined by childhood conditions. Determinants of smoking behaviour are developed throughout the life course. The findings stress the importance of the respondent's education and parental smoking as determinants of smoking behaviour. Our results support the notion that intervention on smoking initiation and cessation should be considered throughout the life course. Parental involvement in fostering non-smoking would be important. Kuokkanen, M., Myllyniemi, M., Vauhkonen, M., Helske, T., Kaariainen, I., Karesvuori, S., Linnala, A., Härkönen, M., Järvelä, I. and Sipponen, P. Endoscopy. 2006; 38(7): 708-12. IF 4.072 BACKGROUND AND STUDY AIMS: The usefulness of a new quick test for endoscopic diagnosis of adult-type hypolactasia was tested in duodenal biopsies. In this test, an endoscopic biopsy from the postbulbar duodenum is incubated with lactose on a test plate, and a color reaction develops within 20 min as a result of hydrolyzed lactose (a positive result) in patients with normolactasia, whereas no reaction (a negative result) develops in patients with severe hypolactasia. PATIENTS AND METHODS: Two postbulbar duodenal biopsies were taken from 80 prospectively enrolled adult outpatients with dyspepsia. The biopsies were used for the Quick Lactase Test (Biohit PLC, Helsinki, Finland) and in biochemical disaccharidase (lactase, sucrase, and maltase) assays. In addition, the C/T (-13,910) genotype was determined from DNA extracted from gastric antral biopsies using polymerase chain reaction sequencing in genomic analysis of adult-type hypolactasia. RESULTS: Twenty-one of 22 patients (95 %; 95 % CI, 87 - 100 %) with biochemical lactase activity < 10 U/g protein, but none of the 58 patients with lactase activity of 10 U/g protein or more had a negative result in the Quick Lactase Test. Seven of the 80 patients (9 %; 95 % CI, 3 - 15 %) had a Quick Lactase Test result that indicated mild hypolactasia (a mild color reaction). All patients with celiac disease (n = 6) had a negative Quick Lactase Test result. Nine of 74 patients (six patients with celiac disease were excluded) had a CC (-13,910) genotype in genomic testing, indicating adult-type hypolactasia. All of them had negative test results with the Quick Lactase Test. Twenty-six patients had a TT genotype, indicating normolactasia, and none of these patients had a negative test result in the Quick Lactase Test. Six of 39 patients (15 %; 95 % CI, 4 - 27 %) with a CT genotype had a negative result in the Quick Lactase Test. CONCLUSIONS: The Quick Lactase Test effectively identifies patients with severe duodenal hypolactasia. In comparison with CC (adult-type hypolactasia) and TT individuals (normolactasia), the sensitivity and specificity of the Quick Lactase Test result was 100 %. In comparison with biochemical lactase assays, the sensitivity and specificity of a negative Quick Lactase Test for indicating hypolactasia (lactase activity < 10 U/g protein) were 95 % (95 % CI, 87 - 100 %) and 100 %, respectively. Lanki, T., Pekkanen, J., Aalto, P., Elosua, R., Berglind, N., D'Ippoliti, D., Kulmala, M., Nyberg, F., Peters, A., Picciotto, S., Salomaa, V., Sunyer, J., Tiittanen, P., von Klot, S. and Forastiere, F. Occupational and Environmental Medicine. 2006; 63(12): 844-851. Article. IF 1.934 Background: Acute myocardial infarction (AMI) is the leading cause of death attributed to cardiovascular diseases. An association between traffic related air pollution and AMI has been suggested, but the evidence is still limited. Objectives: To evaluate in a multicentre study association between hospitalisation for first AMI and daily levels of traffic related air pollution. Methods: The authors collected data on first AMI hospitalisations in five European cities. AMI registers were available in Augsburg and Barcelona; hospital discharge registers (HDRs) were used in Helsinki, Rome and Stockholm. NO2, CO, PM10 (particles < 10 mu m), and O-3 were measured at central monitoring sites. Particle number concentration (PNC), a proxy for ultrafine particles (< 0.1 mu m), was measured for a year in each centre, and then modelled retrospectively for the whole study period. Generalised additive models were used for statistical analyses. Age and 28 day fatality and season were considered as potential effect modifiers in the three HDR centres. Results: Nearly 27 000 cases of first AMI were recorded. There was a suggestion of an association of the same day CO and PNC levels with AMI: RR = 1.005 (95% CI 1.000 to 1.010) per 0.2 mg/m(3) and RR = 1.005 (95% CI 0.996 to 1.015) per 10000 particles/cm(3), respectively. However, associations were only observed in the three cities with HDR, where power for city-specific analyses was higher. The authors observed in these cities the most consistent associations among fatal cases aged < 75 years: RR at 1 day lag for CO = 1.021 (95% CI 1.000 to 1.048) per 0.2 mg/m(3), for PNC = 1.058 (95% CI 1.012 to 1.107) per 10000 particles/cm(3), and for NO2 = 1.032 (95% CI 0.998 to 1.066) per 8 mu g/m(3). Effects of air pollution were more pronounced during the warm than the cold season. Conclusions: The authors found support for the hypothesis that exposure to traffic related air pollution increases the risk of AMI. Most consistent associations were observed among fatal cases aged < 75 years and in the warm season. Lee-Rueckert, M., Vikstedt, R., Metso, J., Ehnholm, C., Kovanen, P. and Jauhiainen, M. Atherosclerosis Supplements. 2006; 7(3): 540-541. Meeting Abstract. IF 8.963 Lehto, S., Koukkunen, H., Ketonen, M., Immonen-Räihä, P., Kesäniemi, Y. A., Havulinna, A. S., Salomaa, V. and Pyörälä, K. European Heart Journal. 2006; 27: 776-776. Meeting Abstract. IF 7.341 Lehtola, M. J., Pitkänen, T., Miebach, L. and Miettinen, I. T. Water Sci Technol. 2006; 54(3): 57-61. IF 0.875 Campylobacteria are important foodborne pathogens. C. jejuni bacteria have caused several drinking water-related epidemics in Finland. Normally, C. jejuni is not able to multiply in drinking water or in biofilms although it may survive in biofilms. The survival of C. jejuni in biofilms was studied using the Propella biofilm reactor. The number of bacteria was analysed with traditional culture methods and with fluorescence in situ hybridisation (FISH). By culture methods C. jejuni was detectable for only 1 d after spiking whereas bacteria were found from biofilms for at least 1 week after spiking and from outlet water of the reactor for 3 weeks when using FISH. These results suggested that C. jejuni may survive in biofilms and culture methods probably seriously underestimate the real number in water and in biofilms. Lukka, M., Tasa, G., Ellonen, P., Moilanen, K., Vassiljev, V. and Ulmanen, I. Forensic Science International. 2006; 164(1): 3-9. Article. IF 1.577 We report triallelic patterns in several short tandem repeat (STR) loci revealed by routine paternity testing using the commercial AMPFlSTR((R))Profiler(TM) and AMPFlSTR((R))SGMplus(TM) kits. One case where the TPOX-locus (2p25.3) produced three peaks from the blood sample of a child was analysed further. Quantitative polymerase chain reaction (QPCR) and STR typing of the DNAs of the family trio revealed a large (> 1.59 Mb) duplication flanking the TPOX-locus in chromosome 2 in both the mother and child. The implications of such genetic anomalies for paternity testing are discussed. (c) 2005 Elsevier Ireland Ltd. All rights reserved. Macfarlane, G. J., Jones, G. T., Knekt, P., Aromaa, A., McBeth, J., Mikkelsson, M. and Heliövaara, M. Rheumatology (Oxford). 2006. IF 4.226 Objective. To determine whether an observation in a UK study, that persons with chronic widespread pain are at long-term increased risk of cancer mortality, can be replicated in a different setting. Methods. Subjects were participants aged >/=30 yrs in the Mini-Finland Health Survey conducted between 1979 and 1980. Information collected included prevalent pains at different joints throughout the body, demographic, anthropometric, lifestyle and occupational factors. During follow-up, until 1994, information on vital status and cause of death was obtained. Results. 7182 persons participated (89.8%). The prevalence of widespread body pain (pain at four or more sites) was 20% in females and 12% in males, and during follow-up there were a total of 1647 deaths. The risk of death was not elevated amongst those with widespread pain [relative risk (RR): 0.86; 95% confidence interval (CI): 0.74-1.00], and in particular, those with widespread pain were at a slightly lower risk of several disease-specific causes of death and cancer death (RR: 0.64; 95% CI: 0.46-0.91). Conclusions. This study of multiple pains has not confirmed a previous observation of an association between the reporting of widespread pain and subsequent increased risk of cancer death. Differences in the definitions used or, more probably, the population studied, in particular, a larger rural population with more multiple pains related to physical activity may account for the differences. Matee, M., Lahey, T., Vuola, J. M., Mtei, L., Cole, B. F., Bakari, M., Arbeit, R. D., Horsburgh, C. R., Pallangyo, K. and von Reyn, C. F. Journal of Infectious Diseases. 2007; 195(1): 118-123. Article. IF 4.953 Background. Most new tuberculosis vaccines will be administered as a booster to subjects primed with bacille Calmette-Guerin (BCG) during childhood. Methods. We investigated in vivo and in vitro immune responses to mycobacteria in human immunodeficiency virus (HIV)-positive subjects in Tanzania primed with BCG during childhood and entering a tuberculosis booster vaccine trial. Tests included intradermal skin testing for Mycobacterium tuberculosis purified protein derivative (PPD) and Mycobacterium avium sensitin (MAS); lymphocyte proliferation assays and interferon (IFN)-gamma levels after stimulation with Mycobacterium vaccae sonicate (MVS), M. tuberculosis early secreted antigen (ESAT)-6, M. tuberculosis antigen 85 (Ag85), or M. tuberculosis whole-cell lysate (WCL); and determination of serum antibody to lipoarabinomannin (LAM). Results. A total of 888 subjects with CD4 cell counts >= 200 cells/mm(3) were enrolled. PPD and MAS test results were positive in 34% and 30% of the subjects, respectively. Proliferative responses were detected as follows: MVS, 6%; Ag85, 24%; ESAT-6, 21%; and WCL, 59%. IFN-gamma responses were 2%, 6%, 12%, and 38%, respectively. LAM antibody was detected in 28% of the subjects. Subjects were more likely to have detectable proliferative and IFN-gamma responses if they had positive PPD test results or CD4 cell counts >= 500 cells/mm(3). Overall, 94% of the subjects had evidence of primed mycobacterial immune responses. Conclusion. Of HIV-positive BCG-immunized adults with CD4 cell counts >= 200 cells/mm(3) in Tanzania, 94% are primed for booster mycobacterial immunization. Adolescent adjustment disorder: Precipitant stressors and distress symptoms of 89 outpatients Pelkonen, M., Marttunen, M., Henriksson, M. and Lönnqvist, J. Eur Psychiatry. 2006. IF 1.273 OBJECTIVE: Research on adolescent adjustment disorder (AD) is scarce. We characterized adolescent outpatients with AD in psychosocial background and treatment received compared with patients with other non-psychotic disorders (OND). Furthermore, we explored precipitant stressors, distress symptoms and behavioral problems among males and females with AD. METHOD: Data were collected prospectively on 290 consecutive psychiatric outpatients, aged 12-22 yrs, at a secondary care clinic in Finland. DSM-III-R diagnoses were assigned, based on all available information, at the end of treatment. RESULTS: AD was the second most common diagnosis among non-psychotic patients (31% of 290). Compared to OND-patients, those with AD were predominantly female and had less severe psychosocial impairment. In multivariate comparisons school-related stressors, problems with law and restlessness characterized males, and parental illness and internalizing symptoms females with AD. Intensity and duration of treatment of AD-patients varied widely. CONCLUSIONS: Adjustment disorder comprised a common clinical entity among adolescent outpatients. Psychiatric assessment and treatment should be individually targeted by taking into account gender-specific stressors and distress symptoms among young people with AD. Fetal programming of temperamental negative affectivity among children born healthy at term Pesonen, A. K., Räikkonen, K., Kajantie, E., Heinonen, K., Strandberg, T. E. and Järvenpää, A. L. Developmental Psychobiology. 2006; 48(8): 633-643. Article. IF 1.583 The fetal programming hypothesis suggests that an adverse in utero environment, reflected in small body size at birth, has life-long effects on different physiological systems that may affect both health and behavior We explored whether fetal growth was associated with biologically based temperamental outcomes (negative affectivity scales, the CBQ) among 51/2-year-old children (n=416) born healthy at term (gestational weeks 37-42). In line with the hypotheses, small body size at birth (thinness measured by ponderal index, kg/m(3)) was related to increased negative affectivity and its subscales: anger-, discomfort-, and sadness-proneness in childhood. Longer length at birth was predictive of higher levels of child anger- and sadness-proneness. Length of gestation moderated the associations of weight and length at birth with negative affectivity. The results suggest that the biological basis of temperament may be subjected to antenatal environmental influences, and that the mechanisms, proposed to be related to fetal glucocorticoid environment, may operate even within the normal range of term birth. (c) 2006 Wiley Periodicals, Inc. Pietilä, T. E., Veckman, V., Lehtonen, A., Lin, R., Hiscott, J. and Julkunen, I. J Immunol. 2007; 178(1): 253-61. IF 6.387 CCL19 chemokine has a central role in dendritic cell (DC) biology regulating DC traffic and recruitment of naive T cells to the vicinity of activated DCs. In this study, we have analyzed the regulation of CCL19 gene expression in human monocyte-derived DCs. DCs infected with Salmonella enterica or Sendai virus produced CCL19 at late times of infection. The CCL19 promoter was identified as having two putative NF-kappaB binding sites and one IFN-stimulated response element (ISRE). Transcription factor binding experiments demonstrated that Salmonella or Sendai virus infection increased the binding of classical p50+p65 and alternative p52+RelB NF-kappaB proteins to both of the CCL19 promoter NF-kappaB elements. Interestingly, Salmonella or Sendai virus infection also increased the binding of multiple IFN regulatory factors (IRFs), STAT1, and STAT2, to the ISRE element. Enhanced binding of IRF1, IRF3, IRF7, and IRF9 to the CCL19 promoter ISRE site was detected in Salmonella or Sendai virus-infected cell extracts. The CCL19 promoter in a luciferase reporter construct was activated by the expression of NF-kappaB p50+p65 or p52+RelB dimers. IRF1, IRF3, and IRF7 proteins also activated CCL19 promoter in the presence of Sendai virus infection. CCL19 promoter constructs mutated at NF-kappaB and/or ISRE sites were only weakly activated. Ectopic expression of RIG-I (DeltaRIG-I, CARDIF) or TLR3/4 (TRIF, MyD88, IKKepsilon, or TBK1) signaling pathway components induced CCL19 promoter activity, suggesting that these pathways are important in CCL19 gene expression. Our experiments reveal that expression of the CCL19 gene is regulated by a combined action of several members of the NF-kappaB, IRF, and STAT family transcription factors. Prättälä, R., Paalanen, L., Grinberga, D., Helasoja, V., Kasmel, A. and Petkeviciene, J. Eur J Public Health. 2006. IF 1.118 BACKGROUND: Women's diets are healthier than men's. Finnish women eat more fruits and vegetables but less meat than men. Gender differences may be larger in the Baltic countries, which represent Eastern European transition societies than in Finland, a society characterized by the Scandinavian welfare ideology and a high degree of gender equality. METHODS: The data are based on questionnaires to random samples of adults in Finland, Estonia, Latvia and Lithuania. The data provide a way of addressing gender differences at the turn of the century in the economically and culturally different countries. The purpose is to explore whether the consumption of foods classified as masculine or feminine-meat, fruits and vegetables-follow a similar gender pattern in Finland and the Baltic countries. RESULTS: Men ate meat more often while women ate fruits and vegetables. A high educational level was associated with frequent consumption of fruits and vegetables. Educational differences in the consumption of meat were few and inconsistent. The consumption of fruits and vegetables was more common in urban areas except in Finland. Gender differences were similar in all countries throughout age and educational groups and in rural and urban areas. CONCLUSION: The consistent association of gender and food and the similarity of gender patterning in population subgroups point to the stability of masculine versus feminine food habits. The similarity suggests that food habits contribute equally to the gender gap in health in the Baltic countries as they do in Finland. Metabolic syndrome in non-diabetic Europeans: Relation to cardiovascular mortality Pyörälä, K., Qiao, Q., Gao, W. G., Balkau, B., Borch-Johnsen, K., Alberti, K. and Tuomilehto, J. Atherosclerosis Supplements. 2006; 7(3): 154-154. Meeting Abstract. IF 8.963 emm typing of invasive T28 group A streptococci, 1995-2004, Finland Siljander, T., Toropainen, M., Muotiala, A., Hoe, N. P., Musser, J. M. and Vuopio-Varkila, J. J Med Microbiol. 2006; 55(Pt 12): 1701-6. IF 2.318 A total of 985 group A streptococcus (GAS) bacteraemia isolates collected in Finland during 1995-2004 were T-serotyped, and of these, 336 isolates of serotype T28 were subjected to further emm typing. The total number of isolates referred per year showed an increase within the study period, from 43 in 1995 to 130 in 2004. The annual incidence of invasive GAS (iGAS) bacteraemia showed a general increase during the study period, from 1.1 to 2.5 per 100 000 population. Serotype T28 remained among the most common serotypes, in addition to serotypes TB3264 and T1. The serotype T28 isolates were found to be distributed across six distinct emm types: emm28, emm77, emm53 (including subtypes 53.2 and 53.4), emm87, emm2 and emm4. The serotype distribution and the emm type distribution of serotype T28 fluctuated over time. Within the study period, the proportion of T28/emm28 isolates became the most prominent. During periods of low emm28 incidence, emm types 77 and 53 seemed to show a resurgence. emm typing revealed T28 isolates to be a genetically heterogeneous group harbouring a variety of distinct M proteins. This study confirms that T serotyping alone is not a sufficient method for epidemiological surveillance of iGAS. Söderberg, S., Zimmet, P., Tuomilehto, J., Alberti, K. and Shaw, J. E. European Heart Journal. 2006; 27: 571-571. Meeting Abstract. IF 7.341 Syrjänen, R. K., Herva, E. E., Mäkelä, P. H., Puhakka, H. J., Auranen, K. J., Takala, A. K. and Kilpi, T. M. Pediatr Infect Dis J. 2006; 25(11): 1032-6. IF 3.047 BACKGROUND: In selecting treatment of acute otitis media (AOM), knowledge of its etiology would be valuable. We revisited the possibility to use the nasopharyngeal culture of Streptococcus pneumoniae (Pnc) and Haemophilus influenzae (Hi) for predicting their presence in the middle ear fluid (MEF) during AOM. METHODS: The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of bacterial culture of the nasopharyngeal aspirate (NPA) in predicting the presence of the same pathogen in the MEF were assessed during AOM events among children followed from 2 to 24 months of age. RESULTS: The data comprised 586 AOM events. For Pnc, the sensitivity and NPV were high, 99% (95% confidence interval = 95-100%) and >99% (97-100%), respectively. The specificity and PPV were relatively low, 63% (57-68%) and 50% (43-56%). For Hi, the sensitivity and the NPV were lower (77%, 69-83% and 93%, 90-95%) than for Pnc, but the specificity and the PPV were higher (88%, 85-91% and 64%, 56-71%). The quantity of Pnc and Hi in the NPA was clearly related to their presence in the MEF. If both Pnc and Hi were found in the nasopharynx, Hi was more likely cultured from MEF. CONCLUSION: Together with clinical and epidemiologic features of AOM, the nasopharyngeal culture can be helpful in selecting specific antimicrobial therapy. Tiirola, T., Sinisalo, J., Nieminen, M. S., Silvennoinen-Kassinen, S., Paldanius, M., Saikku, P., Jauhiainen, M. and Leinonen, M. Atherosclerosis Supplements. 2006; 7(3): 85-85. Meeting Abstract. IF 8.963 Tiittanen, M., Huupponen, J. T., Knip, M. and Vaarala, O. Diabetes. 2006; 55(12): 3446-3454. Article. IF 8.028 Patients with type 1 diabetes are treated with daily injections of human insulin, an autoantigen expressed in thymus. Natural CD4+CD25(high) regulatory T-cells are derived from thymus, and accordingly human insulin-specific regulatory T-cells should exist. We had a chance to study peripheral blood mononuclear cells (PBMCs) from children with type 1 diabetes both before and after starting insulin treatment, and thus we could analyze the effects of insulin treatment on regulatory T-cells in children with type I diabetes. PBMCs were stimulated for 72 h with bovine/human insulin. The mRNA expression of regulatory T-cell markers (transforming growth factor-beta, Foxp3, cytotoxic T-lymphocyte antigen-4 [CTLA-4], and inducible co-stimulator [ICOS]) or cytokines (gamma-interferon [IFN-gamma], interleukin [IL]-5, IL-4) was measured by quantitative RT-PCR. The secretion of IFN-gamma, IL-2, IL-4, IL-5, and IL-10 was also studied. The expression of Foxp3, CTLA-4, and ICOS mRNAs in PBMCs stimulated with bovine or human insulin was higher in patients on insulin treatment than in patients studied before starting insulin treatment. The insulin-induced Foxp3 protein expression in CD4+CD25(high) cells was detectable in flow cytometry. No differences were seen in cytokine activation between the patient groups. Insulin stimulation in vitro induced increased expression of regulatory T-cell markers, Foxp3, CTLA-4, and ICOS only in patients treated with insulin, suggesting that treatment with human insulin activates insulin-specific regulatory T-cells in children with newly diagnosed type 1 diabetes. This effect of the exogenous autoantigen could explain the difficulties to detect in vitro T-cell proliferation responses to insulin in newly diagnosed patients. Furthermore, autoantigen treatment-induced activation of regulatory T-cells may contribute to the clinical remission of the disease. Atherosclerosis induced by major periodontal pathogen in a mouse model: A pilot study Tuomainen, A. M., Jauhiainen, M., Kovanen, P. T., Paju, S. and Pussinen, P. J. Atherosclerosis Supplements. 2006; 7(3): 463-463. Meeting Abstract. IF 8.963 Vähätalo, L., Bärlund, S., Hannila, M. L., Uusitalo, U., Pigg, H. M., Salonen, M., Nucci, A., Krischer, J. P., Knip, M., Åkerblom, H. K. and Virtanen, S. M. Maternal and Child Nutrition. 2006; 2(3): 181-187. Article. The objective of this study was to assess the relative validity of a dietary interview method for use in an infant population. A dietary interview covering a 1-month period was completed during a study visit at 3 or 6 months of age. It included structured questions and a short food frequency questionnaire (FFQ). The information was compared with data from two 48-h recall interviews conducted during the month previous to the study visit. The agreement between the FFQ and 48-h recalls was analysed as proportion of subjects classified into the same categories of consumption frequency and by the kappa analysis. A total of 100 subjects, at the age of 23 months (n = 50) and 5-6 months (n = 50), were included. The kappa values for breastmilk and study formula ranged from 0.82 to 0.95, indicating very good agreement. The agreement for other foods and vitamin D supplementation ranged from fair to very good. We also found a strong correlation for the reported amount of study formula consumed per feeding at 3 months (r(s) = 0.87, n = 24) and 6 months of age (r(s) = 0.73, n = 35) between the questionnaire and 48-h recall data. However, the average amount of study formula per feeding was significantly higher when estimated for a 1-month period, compared with a mean calculated from the two 48-h recalls. As a conclusion, the interview was found to be a useful tool for assessing diet and compliance in a dietary intervention for infants. Van Eck, M., Ye, D., Hildebrand, R. B., Kruijt, J. K., Jauhianen, M. and Van Berkel, T. J. C. Atherosclerosis Supplements. 2006; 7(3): 152-152. Meeting Abstract. IF 8.963 Varjosalo, M. and Taipale, J. J Cell Sci. 2007; 120(Pt 1): 3-6. IF 6.543 Watanabe, H., Soderlund, S., Soro-Paavonen, A., Hiukka, A., Leinonen, E., Salonen, R., Tuomainen, T. P., Ehnholm, C., Jauhiainen, M. and Taskinen, M. R. Atherosclerosis Supplements. 2006; 7(3): 500-500. Meeting Abstract. IF 8.963 Vikstedt, R., Metso, J., Ye, D., Hildebrand, R. B., Van Berkel, T. J. C., Ehnholm, C., Jauhiainen, M. and Van Eck, M. Atherosclerosis Supplements. 2006; 7(3): 320-320. Meeting Abstract. IF 8.963 Hepatic overexpression of oxysterol binding protein(OSBP) results in hypertriglyceridemia Yan, D., Lehto, M., Käkelä, R., Ylä-Herttuala, S., Ehnholm, C., Jauhiainen, M. and Olkkonen, V. M. Atherosclerosis Supplements. 2006; 7(3): 39-39. Meeting Abstract. IF 8.963 |