1.9.2008

Al-Hello, H., Paananen, A., Eskelinen, M., Ylipaasto, P., Hovi, T., Salmela, K., Lukashev, A. N., Bobegamage, S. and Roivainen, M.

Journal of General Virology. 2008; 89: 1949-1959. Article. IF 3.120

An enterovirus strain (designated D207) isolated from a Slovakian diabetic child and originally serotyped as coxsackievirus A9 (CAV-9) was found to cause rapid cytolysis coinciding with severe functional damage of the surviving cells in primary cultures of human pancreatic islets.

This finding prompted us to clone the isolate for full-length genome sequencing and molecular characterization as the prototype strain of CAV-9 is known to cause only minimal damage to insulin-producing fl-cells. Based on capsid-coding sequence comparisons, the isolate turned out to be echovirus 11 (E-1 1). Phylogenetic analyses demonstrated that E-1 1 /D207 was closely related to a specific subgroup B of E-1 1 strains known to cause uveitis. To study further antigenic properties of isolate E-1 1 /D207 and uveitis-causing E-1 1 strains, neutralization experiments were carried out with CAV-9- and E-1 1 -specific antisera. Unlike the prototype strains, the isolate E-1 1 /D207 and uveitis-causing E-1 1 strains were well neutralized with both CAV-9- and E-1 1 specific antisera. Attempts to identify recombination of the capsid coding sequences as a reason for double-reactivity using the Simplot analysis failed to reveal major transferred motifs. However, pepticle scanning technique was able to identify antigenic regions of capsid proteins of E-11 1 /D207 as well as regions cross-reacting with an antiserurn raised to CAV-9. Thus, double specificity of E- 11 /D207 seems to be a real characteristic shared by the phylogenetically closely related virus strains in the genetic subgroup B of E-1 1.

Prenatal exposure to a farm environment modifies atopic sensitization at birth

Ege, M. J., Herzum, I., Buchele, G., Krauss-Etschmann, S., Lauener, R. P., Roponen, M., Hyvarinen, A., Vuitton, D. A., Riedler, J., Brunekreef, B., Dalphin, J. C., Braun-Fahrlander, C., Pekkanen, J., Renz, H. and von Mutius, E.

Journal of Allergy and Clinical Immunology. 2008; 122(2): 407-412. Article. IF 8.115

Background: Previous cross-sectional surveys have suggested that maternal exposure to animal sheds during pregnancy exerted a protective effect on atopic sensitization in children lasting until school age.

Objective: We sought to evaluate the effects of maternal exposure to animal sheds and other farm-related exposures during pregnancy on cord blood IgE levels in a prospective birth cohort.

Methods: Pregnant women living in rural areas in Austria, Finland, France, Germany, and Switzerland were recruited in the third trimester of pregnancy. Information on maternal farm-related exposures, nutrition, and health during pregnancy was obtained by means of interviews. Specific IgE levels for food and common inhalant allergens were assessed in cord blood of 922 children and peripheral blood samples of their mothers.

Results: Different sensitization patterns in cord blood of farm and nonfarm children were observed. In multivariable analysis consumption of boiled, but not unboiled, farm milk during pregnancy was positively associated with specific IgE to cow's milk independently from maternal IgE. In contrast, there was an inverse relationship between maternal exposure to animal sheds and cord blood IgE levels against seasonal allergens (adjusted odds ratio, 0.38; 95% CI, 0.21-0.70). This association was not confounded by maternal IgE levels. Maternal contact with hay enhanced the protective effect of exposure to animal sheds on IgE levels to grass pollen in cord blood.

Sucrose in the diet of 3-year-old Finnish children: sources, determinants and impact on food and nutrient intake

Erkkola, M., Kronberg-Kippila, C., Kyttala, P., Lehtisalo, J., Reinivuo, H., Tapanainen, H., Veijola, R., Knip, M., Ovaskainen, M. L. and Virtanen, S. M.

Br J Nutr. 2008: 1-9. IF 2.339

The aim was to identify the important sources of added sucrose and determinants of high intake, and to evaluate what impact a high proportion of energy from added sucrose has on the intake of foods and nutrients.

The subjects consisted of children invited to the nutrition study within the Type 1 Diabetes Prediction and Prevention birth cohort and born in 2001 (n 846). Of these, 471 returned 333%, naturally occurring sucrose for 15% of the total sucrose. Juice drinks, yoghurt/cultured milks, and chocolate and confectionery were the main contributors to added sucrose intake. Consumption of rye bread, porridge, fresh vegetables, cooked potatoes, skimmed milk, hard cheeses, margarine and fat spread as well as intake of most nutrients decreased across the quartiles of added sucrose (P0.05). Being cared for at home, having a father with a vocational school degree, having at least two siblings and a milk-restricted diet increased the risk for a high-sucrose diet.

The study implied that a high proportion of added sucrose in the diet had mainly an unfavourable impact on the intake of recommended foods and key nutrients in Finnish children. The rationale for the recommendation to reduce the intake of refined sugars to ensure adequate intakes of nutrients seems reasonable.

Depression and school performance in middle adolescent boys and girls

Frojd, S. A., Nissinen, E. S., Pelkonen, M. U. I., Marttunen, M. J., Koivisto, A. M. and Kaltiala-Heino, R.

Journal of Adolescence. 2008; 31(4): 485-498. Article. IF 1.207

The study aimed to investigate the associations between different levels of depression with different aspects of school performance.

The target population included 2516 7th-9th grade pupils (13-17 years) of whom 90% completed the questionnaire anonymously in the classroom. Of the girls 18.4% and of the boys 11. 1% were classified as being depressed (R-Beck Depression Inventory (BDI), the Finnish version of the 13-item BDI). The lower the self-reported grade point average (GPA) or the more the GPA had declined from the previous term, the more commonly the adolescents were depressed. Depression was associated with difficulties in concentration, social relationships, self-reliant school performance and reading and writing as well as perceiving schoolwork as highly loading. The school performance variables had similar associations with depression among both sexes when a wide range of depression was studied but gender differences appeared when studying the severe end of the depression scale.

Our study indicates that pupils reporting difficulties in academic performance should be screened for depression. (c) 2007 The Association for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Stimulation of epithelial cell matrix metalloproteinase (MMP-2,-9,-13) and interleukin-8 secretion by fusobacteria

Gursoy, U. K., Könönen, E. and Uitto, V. J.

Oral Microbiology and Immunology. 2008; 23(5): 432-434. Article. IF 1.854

Background/aim: Bacterial pathogens involved in periodontal diseases exert their destructive effects primarily by stimulating the host cells to increase their secretion of proinflammatory cytokines and matrix metalloproteinases (MMPs). This study aimed to determine the epithelial cell matrix metalloproteinase and interleukin-8 (IL-8) secretion upon exposure to fusobacteria.

Methods: Eight different oral and non-oral Fusobacterium strains were incubated with HaCaT epithelial cells. Gelatin zymography and Western blot analysis were performed to detect collagenase 3 (MMP-13), gelatinase A (MMP-2), gelatinase B (MMP-9), and IL-8 secretion by epithelial cells.

Results: All Fusobacterium strains, especially Fusobacterium necrophorum ATCC 25286, Fusobacterium nucleatum ATCC 25586, and Fusobacterium varium ATCC 51644, increased MMP-9 and MMP-13 secretion. Fusobacterium simiae ATCC 33568, and to a lesser extent F. nucleatum and F. necrophorum, increased epithelial MMP-2 secretion. F. nucleatum and F. necrophorum also increased IL-8 secretion. F. varium ATCC 27725, a strain that only weakly stimulated MMP production, strongly increased the IL-8 production, suggesting that their expression is differently regulated.

Conclusion: We conclude that the pathogenic potential of fusobacteria may partly result from their ability to stimulate secretion of MMP-9, MMP-13, and IL-8 from epithelial cells.

Maintenance pharmacotherapy for recurrent major depressive disorder: 5-year follow-up study

Holma, I. A. K., Holma, K. M., Melartin, T. K. and Isometsä, E. T.

British Journal of Psychiatry. 2008; 193(2): 163-164. Article. IF 5.446

Practice guidelines endorse maintenance antidepressant treatment for recurrent major depressive disorder. In the Vantaa Depression Study, we followed 218 psychiatric patients with major depressive disorder for up to 5 years with a life-chart. Of these patients, 86 (39.4%) had more than three lifetime episodes and an indication for maintenance pharmacotherapy. However, of these, only 57% received treatment and only for 16% of the time indicated. Good adherence to pharmacotherapy in the acute phase independently predicted maintenance treatment.

The tertiary preventive impact of maintenance treatment may remain limited, as many patients with major depressive disorder either do not receive it, or receive it for too short a period.

Role of individual, peer and family factors in the use of cannabis and other illicit drugs: A longitudinal analysis among Finnish adolescent twins

Korhonen, T., Huizink, A. C., Dick, D. M., Pulkkinen, L., Rose, R. J. and Kaprio, J.

Drug and Alcohol Dependence. 2008; 97(1-2): 33-43. Article. IF 3.222

Background: Although use of illicit drugs shows varying degree of heritability, the influence of shared and unique environmental factors predominate among adolescents. We explored factors predicting use of cannabis and other illicit drugs among Finnish adolescent twins.

Methods: We used longitudinal data from the FinnTwin 12-17 study with baseline at age 11-12 and follow-up at ages 14 and 171/2, including 4138 individuals. The outcome was self-reported ever use of cannabis or other illicit drugs at age 171/2. The potential predictors were measures reported by the twins, their parents or teachers. As individual factors we tested smoking, alcohol use, behavioral and emotional problems; as peer factors: number of smoking friends and acquaintances with drug experience; as family factors: parental substance use, socio-economic status and pre-natal exposure to nicotine. We used logistic regression models, controlling for twinship, age and sex, to compute odds ratios (OR) for each potential predictor. To adjust for within-family confounds, we conducted conditional logistic regressions among 246 twin pairs discordant for drug use.

Results: 13.5% of subjects had initiated use of cannabis or other illicit drugs by age of 171/2. When adjusted for within-family confounds, smoking, drinking, and aggressiveness, as well as smoking and drug use among peers predicted use of illicit drugs. In the final regression model, the significant predictors were female sex, early smoking onset, drinking to intoxication, having smoking peers and acquaintances with drug experience, father's weekly drinking to intoxication, and aggressive behavior among boys. Smoking initiation by age of 12 was the most powerful predictor among individuals (OR = 26, p < 0.001) and within discordant pairs (OR = 22, p < 0.001).

Conclusions: Early onset smoking is a powerful predictor for subsequent use of illicit drugs among Finnish adolescents, but the causal nature of this relationship needs to be clarified. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Gastric malignancies in adult patients after cure of H. pylori infection

Kosunen, T. U., Pukkala, E., Sarna, S., Seppälä, K., Aromaa, A., Knekt, P. and Rautelin, H.

Helicobacter. 2008; 13(5): 404-405. Meeting Abstract. IF 2.423

Body size at birth and socio-economic status in childhood: Implications for Cloninger's psychobiological model of temperament at age 60

Lahti, J., Räikkönen, K., Heinonen, K., Pesonen, A. K., Kajantie, E., Forsen, T., Osmond, C., Barker, D. J. P. and Eriksson, J. G.

Psychiatry Research. 2008; 160(2): 167-174. Article. IF 2.298

Small birth size predicts various psychiatric outcomes, including depression.

While biologically based temperamental traits may constitute a vulnerability factor for depression, the extent to which birth size predicts these traits in adulthood is not known. We studied, in 1369 women and men identified from a cohort born in 1934-44 in Helsinki, Finland, whether birth size predicts the temperamental traits measured with Cloninger's Tridimensional Personality Questionnaire at an average age of 63 years. Moreover, we examined whether socio-economic status (SES) in childhood modified the associations. Data on birth size were obtained from birth records, and SES in childhood was obtained from school records. Weight and length at birth showed curvilinear, reverse J-shaped effects on harm avoidance (HA), such that the highest HA scores were most characteristic of those born small. Furthermore, high HA was confined to those belonging to a low SES group in childhood regardless of birth size, and to those belonging to the high SES group in childhood if their birth size was small. The associations were independent of several confounders.

Since small birth size as well as high HA in adulthood may associate with subsequent depression, our findings might shed light on understanding the early neurodevelopmental processes that predispose to depression through vulnerability characteristics. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

The SH2D2A gene and susceptibility to multiple sclerosis

Lorentzen, A. R., Smestad, C., Lie, B. A., Oturai, A. B., Akesson, E., Saarela, J., Myhr, K. M., Vartdal, F., Celius, E. G., Sorensen, P. S., Hillert, J., Spurkland, A. and Harbo, H. F.

Journal of Neuroimmunology. 2008; 197(2): 152-158. Article. IF 2.920

We previously reported an association between the SH2D2A gene encoding TSAd and multiple sclerosis (MS). Here a total of 2128 Nordic MS patients and 2004 controls were genotyped for the SH2D2A promoter GA repeat polymorphism and rs926103 encoding a serine to asparagine substitution at amino acid position 52 in TSAd. The GA(16)-rs926103*A haplotype was associated with MS in Norwegians (OR 1.4, P=0.04). A similar trend was observed among Danes. In the independent Norwegian, Danish and Swedish sample sets the GA(16) allele showed a combined OR of 1.13, P = 0.05. Thus, the present study shows that the SH2D2A gene may contribute to susceptibility to MS. (C) 2008 Elsevier B.V. All rights reserved.

Pneumococcal Surface Protein A Families 1 and 2 in Acute Otitis Media and Nasopharyngeal Carriage Isolates of Finnish Children

Melin, M. M., Hollingshead, S. K., Briles, D. E., Hanage, W. P., Lahdenkari, M., Kaijalainen, T., Kilpi, T. M. and Käyhty, H. M.

Clin Vaccine Immunol. 2008. IF 1.995

PspA is a structurally variable surface protein important to the virulence of pneumococci. PspAs are serologically cross-reactive and exist as two major families. In this study, we determined the distribution of PspA families 1 and 2 among pneumococcal strains isolated from the middle ear fluid (MEF) of children with acute otitis media and from nasopharyngeal specimens of children with pneumococcal carriage.

We characterised the association between the two PspA families, capsular serotypes and multi locus sequence types (STs) of the pneumococcal isolates. MEF isolates (n=201) of 109 patients and nasopharyngeal isolates (n=173) of 49 children were PspA family typed by whole cell enzyme immunoassay (EIA). Genetic typing (PCR) of PspA family was done for 60 isolates to confirm EIA typing results. The prevalence of PspA families 1 and 2 was similar among pneumococci isolated from MEF (51% and 45%, respectively) and nasopharyngeal specimens (48% each). Isolates of certain capsule types as well as isolates of certain STs showed statistical associations with either family 1 or family 2 PspA. Pneumococci from seven children with multiple pneumococcal isolates appeared to express serologically different PspA families in different isolates of the same serotype; in three of the children the STs of the isolates were the same suggesting that antigenic changes in the PspA expressed may have taken place.

The majority of the isolates (97%) belonged to either PspA family 1 or 2 suggesting that a combination including the two main PspA families would make a good vaccine candidate.

D evelopment of Antibodies to PspA Families 1 and 2 in Children after Exposure to Streptococcus pneumoniae

Melin, M. M., Hollingshead, S. K., Briles, D. E., Lahdenkari, M. I., Kilpi, T. M. and Käyhty, H. M.

Clin Vaccine Immunol. 2008. IF 1.995

Pneumococcal surface protein A (PspA) is an important virulence factor of Streptococcus pneumoniae. PspA exists as two major families, which include variable but serologically cross-reactive proteins. Previous studies with a family 1 PspA antigen suggested that children develop low concentrations of anti-PspA after pneumococcal carriage or infection. In this study antibody to PspA families 1 and 2 were measured with enzyme immunoassay in serum and saliva of children, with history of culture-proven pneumococcal colonisation and/or acute otitis media, and in serum and saliva of adults. The PspA families of the pneumococcal strains isolated from children were determined. The majority of the children had high serum and salivary anti-PspA concentrations to the PspA family they had encountered and low to the other, whereas adults had high antibody concentrations to both PspA families, both in serum and in saliva.

The results suggest that children have a relatively family-specific antibody response to the PspA family they have been exposed to and that any PspA vaccine for children should contain members of both major PspA families.

Exposure to environmental tobacco smoke at work, at home, and during leisure time: A cross-sectional population sample

Patja, K., Vainiotalo, S., Laatikainen, T., Kuusimäki, L., Peltonen, K. and Vartiainen, E.

Nicotine & Tobacco Research. 2008; 10(8): 1327-1333. Article. IF 2.129

Environmental tobacco smoke (ETS) is among the most common environmental health risks, with a striking and immediate biological response and increased disease risk. Exposure studies have looked mostly at worksite or home exposures, whereas total exposure levels at the population level are rarely reported.

This study examined ETS exposure at work, at home, and during leisure time in a cross-sectional population sample of working-age adults. Our aim was to monitor changes in ETS exposure from 1992 to 2002. More detailed information on duration of exposure, distribution of exposure sites, and patterns of exposure was obtained in 2002.

Data were based on Finland's national population chronic disease risk-factor surveys (conducted every 5 years). Total sample size varied from 8,000 to 13,500. The survey includes a self-administered questionnaire about ETS exposure at different sites. The proportion of nonsmoking persons exposed to ETS declined throughout the study period among both men and women. In 2002, 5.9% of male and 3.6% of female nonsmokers were exposed to ETS 1 hour or more per day, whereas 5.8% of men and 1.7% women were exposed less than 1 hour daily. Worksite exposure was more common among younger age groups of both sexes, but nonsmoking women in older age groups received more exposure at home than at worksites.

Policy developments on ETS should aim to protect the whole population from ETS in all environments given that health risks from ETS often persist at home and in leisure environments. Total exposure levels should be studied to assess the health impacts of ETS.

Mortality in the presence of a vertebral fracture, scoliosis, or Scheuermann's disease in the thoracic spine

Puisto, V., Rissanen, H., Heliövaara, M., Knekt, P. and Helenius, I.

Ann Epidemiol. 2008; 18(8): 595-601. IF 2.353

PURPOSE: Vertebral fractures and scoliosis, unlike Scheuermann's disease, have been associated with increased mortality. Total and cause-specific mortalities of these spinal deformities were studied to produce epidemiologic knowledge.

METHODS: A population of 16,010 Finnish men and women 20 to 92 years of age participated in a health examination from 1973-1976. Their spinal deformities were assessed from chest radiographs by two radiologists. Logistic regression and Cox's model were used to estimate risk ratios and to control confounding. The follow-up period was 30 years.

RESULTS: Vertebral fracture significantly predicted total mortality, and this increase in mortality was due to an excess of cancer and respiratory deaths. The increased risk of cancer death persisted even when those subjects with a history of cancer and the first 5 years of follow-up were excluded to avoid the effect of metastatic fractures, and when confounding was controlled. In this analysis the relative risk of cancer death in subjects with a baseline vertebral fracture was 2.02 (95% confidence interval: 1.23-3.31).

CONCLUSION: Vertebral fracture significantly predicted increased mortality from cancer. To clarify the mechanism, the fractures should be studied further for their associations with defined and site-specific cancer types.

Mannose-Binding Lectin Concentrations, MBL2 Polymorphisms, and Susceptibility to Respiratory Tract Infections in Young Men

Rantala, A., Lajunen, T., Juvonen, R., Bloigu, A., Silvennoinen-Kassinen, S., Peitso, A., Saikku, P., Vainio, O. and Leinonen, M.

J Infect Dis. 2008. IF 6.035

Background. Mannose-binding lectin (MBL) is an important component of innate immunity, and its deficiency is associated with susceptibility to recurrent infections.

Methods. This exploratory study investigated the association of serum MBL concentrations and MBL2 gene polymorphisms with respiratory tract infections in young men. We genotyped 6 single-nucleotide polymorphisms (SNPs) in the promoter region (alleles H/L, X/Y, and P/Q) and exon 1 (variant alleles B, C, and D and wild-type allele A) of the MBL2 gene by real-time polymerase chain reaction and measured serum MBL concentrations in 111 Finnish military recruits with asthma and 362 without.

Results. An MBL level below the median concentration was a significant risk factor for infections (asthma status-adjusted odds ratio [OR], 2.5 [95% confidence interval {CI}, 1.4-4.5]). Among the 6 SNPs, there was a significant association between the promoter Y/Y genotype and infections (OR, 2.3 [95% CI, 1.2-4.4]) and a borderline significant association between exon 1 variant alleles and infections (OR, 1.7 [95% CI, 0.9-3.1]), after adjustment for asthma status.

Conclusion. These preliminary results suggest, for the first time, an association between MBL level and respiratory tract infections in young men and a possible association between infections and MBL2 polymorphisms.

Revised Finnish dietary supplement database

Reinivuo, H., Marjamäki, L., Heikkilä, M., Virtanen, S. M. and Valsta, L.

Journal of Food Composition and Analysis. 2008; 21(6): 464-468. Article. IF 2.106

The aim of the project was to revise the Finnish dietary supplement database used for the purpose of estimating total dietary intakes in food consumption surveys, and as a valuable tool for dietary risk assessment.

Data for the revised database were compiled from the relevant governmental agencies and from the dietary supplement database of the Type I Diabetes Prediction and Prevention Nutrition study. In addition, information on dietary supplements was obtained from product labels and manufacturers' websites. The dietary supplement database thus compiled contained a total of 491 dietary supplements, including 154 vitamin and mineral products, 138 vitamin supplements, 106 mineral supplements, and 93 other dietary supplement products. The total number of nutrients per dietary supplement ranges from 1 to 36 (median 2). The dietary supplement database is now integrated into the national food composition database. In conclusion, for the purposes of estimating total dietary intakes, there is an increasing need to revise and update the dietary supplement database.

The rapidly developing dietary supplement market makes the updating of the dietary supplement database a challenging and time-consuming task. Thus, a recommendation for the construction and compilation of dietary supplement databases, together with a standard for data transfer, is needed. (C) 2008 Elsevier Inc. All rights reserved.

A "Screen-and-Treat" approach for H-pylori infection

Salomaa-Rasanen, A., Kosunen, T. U., Aromaa, A., Knekt, P., Sarna, S. and Rautelin, H.

Helicobacter. 2008; 13(5): 414-414. Meeting Abstract. IF 2.423