28.4.

Aittoniemi, J., Turpeinen, H., Tfittanen, M., Knip, M., Simell, O., Ilonen, J. and Vaarala, O.

Human Immunology. 2008; 69(2): 108-111. Article. IF 2.605

Mannose-binding lectin (MBL) is a key mediator of innate immunity, the insufficiency of which is caused by point mutations in the MBL2 gene. MBL insufficiency is associated with increased susceptibility to infections and certain autoimmune diseases, but its impact in the pathogenesis and risk of type 1 diabetes (T1D) is controversial.

We investigated the significance of the MBL2 genotype on the risk of T1D in a Finnish study population comprising 470 diabetic children and 501 controls. Furthermore, the effect of MBL2 gene polymorphism on the emergence of beta-cell. autoantibodies in 289 unaffected children with human leukocyte antigen-conferred susceptibility to T1D was assessed. MBL genotype had no significant effect on the risk or onset age of T1D. However, children with the bialletic variant genotype reflecting total MBL deficiency tested positive more frequently for >= 3 autoantibodies compared with children with another genotype (odds ratio = 6.0, 95% confidence interval 1.3-28; p = 0.013). In conclusion, the MBL2 genotype did not affect susceptibility to T1D in children, and this finding does not support previous reports implicating a role of the MBL2 genotype as a factor predisposing to T1D.

The association of the bialletic variant genotype with positivity for multipte autoantibodies suggests that intermolecular epitope spreading may be linked with impaired clearance of autoantigens as a result of MBL deficiency. (C) 2008 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Antibiotic susceptibility of faecal bacteria in Antarctic penguins

Bonnedahl, J., Olsen, B., Waldenstrom, J., Broman, T., Jalava, J., Huovinen, P. and Osterblad, M.

Polar Biology. 2008; 31(6): 759-763. Article. IF 1.502

Faecal bacteria from 49 Gentoo penguins on the Antarctic Peninsula were identified by biochemical methods and sequencing, and tested for antibiotic susceptibility using agar dilution. Of the 42 Enterobacteriaceae isolates found, 39 belonged to the genus Edwardsiella. All isolates were susceptible to the 17 antibiotics tested. This implies that antibiotic selection pressure is a prerequisite to a high prevalence of antibiotic resistance, and in the absence of contact with human activities, antibiotic resistance in Enterobacteriaceae remains undetectable.

Measurement of blood glucose: comparison between different types of specimens

Carstensen, B., Lindstrom, J., Sundvall, J., Borch-Johnsen, K. and Tuomilehto, J.

Annals of Clinical Biochemistry. 2008; 45: 140-148. Article. IF 1.741

Aim: To provide conversion formulae between measurements based on different specimens in use in epidemiological studies and clinical practice, and to evaluate the relative precision for the different methods.

Background: The current guidelines emphasize the use of venous plasma for determining glucose concentration. Nevertheless, the World Health Organization (WHO) guidelines provide cut-off points for different specimens for the determination of the glucose concentration in circulating blood (venous plasma, whole blood, serum and capillary blood). There is a lack of data about the comparability between the values obtained by using different specimens.

Methods: Eleven different combinations of specimens and methods of measurement of blood glucose were used in 294 blood samples from 74 subjects. The methods were grouped by the specimen used for analysis (venous plasma, whole blood, serum and capillary blood).

Results: The result of the analysis is a set of linear equations allowing conversion of the result from one specimen or method to another. Furthermore, it was estimated how much of the variation for each method can be attributed to laboratory variance. Conclusions: Measurements based on capillary blood had a very large variability compared with other methods. Measurements based on venous whole blood tended to give results 0.5 mmol/L lower than other methods.

Our data indicate that the current diagnostic cut-off points, as recommended by WHO for non-plasma specimens, are not fully compatible and may differ as much as 0.5 mmol/L between specimens.

Enhancing global capacity in the surveillance, prevention, and control of chronic diseases: seven themes to consider and build upon

Choi, B. C. K., McQueen, D. V., Puska, P., Douglas, K. A., Ackland, M., Campostrini, S., Barcelo, A., Stachenko, S., Mokdad, A. H., Granero, R., Corber, S. J., Valleron, A. J., Skinner, H. A., Potemkina, R., Lindner, M. C., Zakus, D., De Salazar, L. M., Pak, A. W. P., Ansari, Z., Zevallos, J. C., Gonzalez, M., Flahault, A. and Torres, R. E.

Journal of Epidemiology and Community Health. 2008; 62(5): 391-397. Review. IF 2.805

Background: Chronic diseases are now a major health problem in developing countries as well as in the developed world. Although chronic diseases cannot be communicated from person to person, their risk factors ( for example, smoking, inactivity, dietary habits) are readily transferred around the world. With increasing human progress and technological advance, the pandemic of chronic diseases will become an even bigger threat to global health.

Methods: Based on our experiences and publications as well as review of the literature, we contribute ideas and working examples that might help enhance global capacity in the surveillance of chronic diseases and their prevention and control. Innovative ideas and solutions were actively sought.

Results: Ideas and working examples to help enhance global capacity were grouped under seven themes, concisely summarised by the acronym "SCIENCE'': Strategy, Collaboration, Information, Education, Novelty, Communication and Evaluation.

Conclusion: Building a basis for action using the seven themes articulated, especially by incorporating innovative ideas, we presented here, can help enhance global capacity in chronic disease surveillance, prevention and control. Informed initiatives can help achieve the new World Health Organization global goal of reducing chronic disease death rates by 2% annually, generate new ideas for effective interventions and ultimately bring global chronic diseases under greater control.

Genetic and environmental influences on non-specific low back pain in children: a twin study

El-Metwally, A., Mikkelsson, M., Stahl, M., Macfarlane, G. J., Jones, G. T., Pulkkinen, L., Rose, R. J. and Kaprio, J.

European Spine Journal. 2008; 17(4): 502-508. Article. IF 1.824

Aggregation of low back symptoms in families of children with low back pain (LBP) has been described. However, this may be due to genetic factors or common exposure to environmental factors.

The aim of this study was to evaluate the relative contribution of genetic and environmental factors to childhood LBP by comparing the pairwise similarity of LBP in pairs of monozygotic (MZ) and dizygotic (DZ) twin children.

Data was collected from 1995 to 1998 from a national sample of Finnish 11-year-old twins born between 1984 and 1987. This study sample constituted of 1,790 twin pairs: 610 MZ pairs, 598 same-sex DZ pairs, 582 opposite-sex DZ pairs. LBP pain was determined by using a validated pain questionnaire designed to assess musculoskeletal pains during the preceding 3 months. The outcome measure, LBP, was considered in three categories: none, once a month and at least once a week. Twin similarity in the report of LBP was quantified by correlations. Variance components for genetic and environmental factors were estimated by using biometric structural equation modelling techniques. The prevalence of LBP at least once a month was 15.7%, and at least once a week was 6.6%. The prevalence of frequent LBP in boys was significantly higher than that in girls (P = 0.04). In both genders, there were no differences in LBP reporting by zygosity (P > 0.2). There were no statistically significant differences between polychoric correlations in male MZ and DZ pairs and between polychoric correlations in female MZ and DZ pairs, suggesting little genetic influence. Results obtained from the best-fitting genetic model suggests that, of the total variance in LBP, 41% (95% CI 34-48) could be attributed to shared environmental factors within families; and 59% (52-66) to unique (unshared) environmental factors.

Our results suggest that genetic factors play, at most, a minor role in LBP in children; instead, symptoms seem to be related to a mixture of shared and unshared environmental factors. This study underscore the need for further high-quality research, preferably prospective studies, to identify important modifiable risk factors in order to guide interventions that may prevent LBP in childhood.

The role of genes in growth and later health

Eriksson, J. G.

Nestle Nutr Workshop Ser Pediatr Program. 2008; 61: 69-77.

Genetic factors are of importance for the development of the metabolic syndrome and type 2 diabetes, but despite extensive research the identification of the underlying genes has not been fruitful. This report focuses on the interactions between intrauterine growth and genes in relation to adult health outcomes based upon findings from the Helsinki Birth Cohort Study. Candidate genes for type 2 diabetes and the metabolic syndrome have been focused upon and we report on interactions between polymorphisms of the peroxisome proliferator-activated receptor (PPAR)gamma-2, plasma cell glycoprotein (PC-1) and the glucocorticoid receptor (GR) genes and - prenatal growth in relation to adult health outcomes. In elderly individuals the effects of the Pro12Pro/Pro12Ala polymorphisms of the PPARgamma-2 gene depend on their body size at birth. Individuals, who had a small body size at birth and were carriers of the Ala allele, seem to be protected against insulin resistance and type 2 diabetes in later life. Similar gene environment interactions will be described in relation to the PC-1 and the GR genes.

We propose that these findings reflect gene-early environment interactions and can be attributed to the phenomenon of developmental plasticity.

Intragastric primary infection sensitizes to lung reinfection in a Chlamydia pneumoniae mouse model

Erkkila, L., Saario, E., Laitinen, K., Saikku, P. and Leinonen, M.

Vaccine. 2008; 26(20): 2503-9. IF 3.159

The most frequently used infection route in Chlamydia pneumoniae animal models is intranasal (i.n.), while the intragastric (i.g.) infection route has not been studied previously. The aim of the present study was to examine the course of Chlamydia pneumoniae infection in mice infected via the i.g. route and to compare the outcome of i.n. reinfection in these mice to i.n. reinfection of primarily i.n. infected mice. C57BL/6JBom mice were used, and the infection was monitored using chlamydial culture, C. pneumoniae PCR and histological examination of several tissues, and antibody measurements. C. pneumoniae was able to disseminate from the gastrointestinal tract to other organs, and i.g. inoculation led to an immunological response. In addition, the primary i.g. challenge made mice more susceptible to i.n. reinfection. In conclusion, the results suggest that the nature of the immune response to a previous C. pneumoniae infection affects the outcome of reinfection.

Clinical changes in periodontium during pregnancy and post-partum

Gursoy, M., Pajukanta, R., Sorsa, T. and Kononen, E.

J Clin Periodontol. 2008. IF 2.380

Background and Aim: Pregnancy has been presented to increase susceptibility to gingival inflammation. It is unclear whether pregnancy gingivitis exposes or proceeds to periodontitis. We examined longitudinally the severity of periodontal changes during pregnancy and post-partum, and compared the findings with an age-matched group of non-pregnant women.

Material and Methods: Thirty generally healthy, non-smoking women at an early phase of their pregnancy and 24 non-pregnant women as controls were recruited. The pregnant group was examined three times during pregnancy and twice during post-partum, and the non-pregnant group three times, once per subsequent month. At each visit, visible plaque index (VPI), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL) were measured from six sites per tooth.

Results: In the pregnant group, BOP and PPD increased simultaneously without relation to plaque between the first and second trimesters, and thereafter decreased during subsequent visits. No changes were detected in CAL during the study period. In the non-pregnant group, BOP stayed invariable during the follow-up and correlated with the amount of plaque. Neither periodontal pocket formation nor significant changes in attachment levels were observed.

Conclusion: Based on this study, changes in clinical parameters during pregnancy are reversible, indicating that pregnancy gingivitis does not predispose or proceed to periodontitis.

Functional interaction of AIRE with PIAS1 in transcriptional regulation

Ilmarinen, T., Kangas, H., Kytomaa, T., Eskelin, P., Saharinen, J., Seeler, J. S., Tanhuanpaa, K., Chan, F. Y., Slattery, R. M., Alakurtti, K., Palvimo, J. J. and Ulmanen, I.

Mol Immunol. 2008; 45(7): 1847-62. IF 4.768

AIRE (autoimmune regulator) promotes the establishment of self-tolerance by regulating gene expression in the thymus. Mutations in AIRE lead to an autoimmune disease, APECED. Here we have identified PIAS proteins as novel AIRE interaction partners. Although PIAS proteins function as E3 SUMO ligases, AIRE is not sumoylated.

We expressed AIRE, wt PIAS1, and PIAS1 mutants with deleted SP-RING domain or SUMO interaction motif (SIM) in different cell lines and demonstrate that AIRE and PIAS1 localize to adjacent nuclear bodies (NBs). The expression of AIRE enhances the formation of PIAS1 NBs. The ability of PIAS1 to localize into NBs and interconnect with AIRE is neither dependent on the SP-RING domain nor the SIM. Further, we show that PIAS1 is able to attract AIRE into SUMO1-containing complexes and that the process is dependent on the SIM of PIAS1. PIAS1 and AIRE concurrently activate the human insulin promoter, a known target gene of AIRE, and the SP-RING is required for this activation. Moreover, AIRE represses and PIAS1 activates the CSTB promoter, used as a model for a housekeeping promoter, and both the SP-RING and SIM are needed for its activation by PIAS1.

Collectively, our data suggest that AIRE and PIAS1 interact functionally to regulate the activities of the target genes of AIRE.

Associations of dyslipidemias from childhood to adulthood with carotid intima-media thickness, elasticity, and brachial flow-mediated dilatation in adulthood - The Cardiovascular Risk in Young Finns Study

Juonala, M., Viikari, J. S. A., Ronnemaa, T., Marniemi, J., Jula, A., Loo, B. M. and Raitakari, O. T.

Arteriosclerosis Thrombosis and Vascular Biology. 2008; 28(5): 1012-1017. Article. IF 6.883

Background-Dyslipidemias are the major cause for atherosclerosis. They may act synergistically with nonlipid risk factors to increase atherogenesis. In the present study, we examined the effects of dyslipidemias from childhood to adulthood and their interaction with nonlipid risk factors on markers of subclinical atherosclerosis.

Methods and Results-Study subjects were participants of the longitudinal Cardiovascular Risk in Young Finns Study started in 1980 (n = 2265, age 3 to 18 years). To phenotype type IIa, IIb, and IV dyslipidemias and hypoHDL-cholesterolemia, we calculated age and sex-specific z scores for lipid values for each subject in 1980, 1983, 1986, and 2001. Subjects with mean z score over 90th percentile for LDL-cholesterol or triglycerides were considered having type IIa or IV dyslipidemia. Subjects with mean z score over 90th percentile for LDL-cholesterol and triglycerides had type IIb dyslipidemia, and those with mean z score below 10th percentile for HDL-cholesterol had hypoHDL-cholesterolemia. Compared to controls, subjects with type IIb dyslipidemia had increased carotid IMT (P < 0.01). This difference remained significant when adjusted with other risk factors (P < 0.05). Carotid IMT also increased significantly more with increasing number of nonlipid risk factors (P < 0.001) or presence of the metabolic syndrome (P < 0.05) in subjects with type IIb than in controls. Subjects with type IIb or type IV dyslipidemia had decreased carotid elasticity (P < 0.05), but these differences became nonsignificant (P > 0.3) when adjusted with blood pressure.

Conclusions-Our findings suggest that type IIb dyslipidemia has deleterious effects on vasculature already since childhood. Subjects with type IIb dyslipidemia are more vulnerable to the effects of cardiovascular risk factors and metabolic syndrome.

Invasive infections caused by Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae among children in St Petersburg, Russia

Kaijalainen, T., Kharit, S. M., Kvetnaya, A. S., Sirkia, K., Herva, E., Parkov, O. V. and Nohynek, H.

Clinical Microbiology and Infection. 2008; 14(5): 507-510. Article. IF 3.254

This study investigated the causes of invasive bacterial infections in children aged < 15 years in St Petersburg, Russia, during 2001-2003, using culture and antigen detection methods (rapid antigen latex agglutination (RAL)) for normally sterile body fluids. A pathogen was detected in 90 cases (culture 50, RAL 40). Neisseria meningitidis was the most common pathogen (66%), followed by Haemophilus influenzae (19%) and Streptococcus pneumoniae (16%). Meningitis was the main clinical diagnosis (68/90, 76%), with N. meningitidis serogroup B, H. influenzae type b (Hib), and S. pneumoniae serogroup 1 being the most common isolates. Hib was less prevalent in St Petersburg than it was in industrialised countries before the introduction of Hib vaccinations.

The Connection between Trimethoprim-sulfamethoxazole Use and Resistance in Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis

Karpanoja, P., Nyberg, S. T., Bergman, M., Voipio, T., Paakkari, P., Huovinen, P. and Sarkkinen, H.

Antimicrob Agents Chemother. 2008. IF 4.153

The association between trimethoprim-sulfamethoxazole use and resistance among the major respiratory tract pathogens was investigated by comparing regional consumption of the drug to regional resistance in the following year in 21 central hospital districts in Finland. A total of 23,530 Streptococcus pneumoniae isolates, 28,320 Haemophilus influenzae isolates and 14,138 Moraxella catarrhalis isolates were tested for trimethoprim-sulfamethoxazole susceptibility during the study period (1998 - 2004). Among the S. pneumoniae isolates, a statistically significant connection was found between regional consumption and resistance. No statistically significant connection was found between regional trimethoprim-sulfamethoxazole use and resistance among H. influenzae and M. catarrhalis isolates. According to our results it seems that only in pneumococci can the development of trimethoprim-sulfamethoxazole resistance be influenced by restricting its use. However, trimethoprim-sulfamethoxazole remains an important antimicrobial agent because of its reasonable price. Hence the resistance to trimethoprim-sulfamethoxazole among these pathogens needs continuous monitoring.

Probiotic intervention has strain-specific anti-inflammatory effects in healthy adults

Kekkonen, R. A., Lummela, N., Karjalainen, H., Latvala, S., Tynkkynen, S., Jarvenpaa, S., Kautiainen, H., Julkunen, I., Vapaatalo, H. and Korpela, R.

World Journal of Gastroenterology. 2007; 14(13): 2029-2036. Article.

AIM: To evaluate the effects of three potentially anti-inflammatory probiotic bacteria from three different genera on immune variables in healthy adults in a clinical setting based on previous in vitro characterization of cytokine responses.

METHODS: A total of 62 volunteers participated in this randomized, double-blind and placebo-controlled parallel group intervention study. The volunteers were randomized to receive a milk-based drink containing either Lactobacillus rhamnosus GG (LGG), Bifidobacterium animalis ssp. lactis Bb12 (Bb12), or Propionibacterium freudenreichii ssp. shermanii JS (PJS) or a placebo drink for 3 wk. Venous blood and saliva samples were taken at baseline and on d 1, 7 and 21. Fecal samples were collected at baseline and at the end of intervention.

RESULTS: The serum hsCRP expressed as the median AUC(0-21) (minus baseline) was 0.018 mg/L in the placebo group, -0.240 mg/L in the LGG group, 0.090 mg/L in the Bb12 group and -0.085 mg/L in the PIS group (P = 0.014). In vitro production of TNF-alpha from in vitro cultured peripheral blood mononuclear cells (PBMC) was significantly lower in subjects receiving LGG vs placebo. IL-2 production from PBMC in the Bb12 group was significantly lower compared with the other groups.

CONCLUSION: In conclusion, probiotic bacteria have strain-specific anti-inflammatory effects in healthy adults. (c) 2008 WJG. All rights reserved.

Association analysis of allelic variants of USF1 in coronary atherosclerosis

Kristiansson, K., Ilveskoski, E., Lehtimaki, T., Peltonen, L., Perola, M. and Karhunen, P. J.

Arteriosclerosis Thrombosis and Vascular Biology. 2008; 28(5): 983-989. Article. IF 6.883

Objective-USF1 regulates the transcription of more than 40 cardiovascular related genes and is well established as a gene associated with familial combined hyperlipidemia, a condition increasing the risk for coronary heart disease. No detailed data, however, exists on the impact of this gene to the critical outcome at the tissue level: different types of atherosclerotic lesions.

Methods and Results-We analyzed the USF1 in 2 autopsy series of altogether 700 middle-aged men (the Helsinki Sudden Death Study) with quantitative morphometric measurements of coronary atherosclerosis. SNP rs2516839, tagging common USF1 haplotypes, associated with the presence of several types of atherosclerotic lesions, particularly with the proportion of advanced atherosclerotic plaques (P = 0.02) and area of calcified lesions (P < 0.001) of the coronary arteries. Importantly, carriers of risk alleles of rs2516839 also showed a 2-fold risk for sudden cardiac death (genotype TT versus CC; OR 2.10, 95% CI 1.17 to 3.75, P = 0.04). The risk effect of rs2516839 was present also in aorta samples of the men.

Conclusions-Our findings in this unique study sample suggest that USF1 contributes to atherosclerosis, the pathological arterial wall phenotype resulting in coronary heart disease and in its most dramatic consequence-sudden cardiac death.

Spectral power and fractal dimension: Methodological comparison in a sample of normal sleepers and chronic insomniacs

Kronholm, E., Virkkala, J., Karki, T., Karjalainen, P., Lang, H. and Hamalainen, H.

Sleep and Biological Rhythms. 2007; 5(4): 239-250. Article.

This methodological study compared the feasibility of the time domain fractal dimensions (FD) and a quantitative electroencephalogram (QEEG) when characterizing the daytime cortical activation in insomniacs and normal sleepers.

We hypothesized that FD would yield additional non-redundant information when compared to conventional QEEG, suggesting that FD could be useful in future insomnia studies. The original source sample consisted of 157 adults (104 women and 53 men) aged 33-71 years. From this sample, 44 normal sleepers and 35 chronic habitual insomniacs were selected for this study. Conventional QEEG and time domain FD, calculated by the Higuchi algorithm, were obtained and analyzed on the day following a laboratory night. The reactivity of the cortical arousal caused by eye-closing and task performance-induced fatigue was operationalized in daytime electroencephalogram activity by FD and QEEG variables. FD, delta power, and beta power measures were independently able to predict chronic subjective-type insomnia in multivariable binary logistic regression models. The cortical arousal reactivity was not related to the previous night's subjective sleep quality. The hypothesis that FD may yield additional non-redundant information about cortical arousal in insomniacs when compared to information carried by conventional QEEG was supported.

The findings provide cumulative support for the hyperarousal theory of insomnia. No support, however, was gained for the hypothesis that the cortical hyperarousal, as defined by FD, would be modulated by the previous night's perceived quality of sleep. In combination with conventional QEEG measures, FD might be used to refine the descriptions of insomnia subtypes.

Sub-chronic nandrolone treatment modifies neurochemical and behavioral effects of amphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in rats

Kurling, S., Kankaanpaa, A. and Seppala, T.

Behavioural Brain Research. 2008; 189(1): 191-201. Article. IF 2.591

Misuse of anabolic-androgenic steroids (AASs) is increasing, and appears to have much in common with the use of substances known to induce drug dependence. Moreover, persons who abuse AASs also tend to abuse other psychotropic drugs such as amphetamine or 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy").

The aim of this study was to investigate whether nandrolone (5 x 5 or 5 x 20 mg/kg) pre-exposure modulates the acute neurochemical and behavioral effects of amphetamine (I mg/kg) and MDMA (5 mg/kg) in rats. Dopamine (DA), 5-hydroxytryptamine (5-HT) and their metabolites were measured from samples collected from the nucleus accumbens (NAc) by in vivo microdialysis.

The behavior of the animals was recorded on videotapes, from which it was later rated. Our results demonstrate that sub-chronic treatments with supraphysiological doses of nandrolone attenuate dose-dependently the increase in extracellular DA concentration evoked by amphetamine or MDMA. The lower dose of nandrolone attenuated MDMA-induced increase in 5-HT-levels, while the higher dose potentiated it. Analysis of the behavioral data suggests that effects of the amphetamine and MDMA are dose-dependently attenuated by AAS-treatment, paralleling DA results.

In conclusion, the results of this study show that AAS-pre-treatment is able to modulate the reward-related neurochemical and behavioral effects of amphetamine and MDMA. (c) 2008 Elsevier B.V. All rights reserved.

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.

Optom Vis Sci. 2008; 85(5): 341-349. 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.

Marked temporal increase in the incidence of type 1 and type 2 diabetes among young adults in Finland

Lammi, N., Blomstedt, P. A., Moltchanova, E., Eriksson, J. G., Tuomilehto, J. and Karvonen, M.

Diabetologia. 2008; 51(5): 897-899. Letter. IF 5.247

Folate, vitamin B-6, vitamin B-12, and methionine intakes and risk of stroke subtypes in male smokers

Larsson, S. C., Mannisto, S., Virtanen, M. J., Kontto, J., Albanes, D. and Virtamo, J.

American Journal of Epidemiology. 2008; 167(8): 954-961. Article. IF 5.241

The associations of dietary folate, vitamin B-6, vitamin B-12, and methionine intakes with risk of stroke subtypes were examined among 26,556 male Finnish smokers, aged 50-69 years, enrolled in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Dietary intake was assessed at baseline by using a validated food frequency questionnaire.

During a mean follow-up of 13.6 years, from 1985 through 2004, 2,702 cerebral infarctions, 383 intracerebral hemorrhages, and 196 subarachnoid hemorrhages were identified from national registers. In analyses adjusting for age and cardiovascular risk factors, a high folate intake was associated with a statistically significant lower risk of cerebral infarction but not intracerebral or subarachnoid hemorrhages. The multivariate relative risk of cerebral infarction was 0.80 (95% confidence interval: 0.70, 0.91; p(trend) = 0.001) for men in the highest versus lowest quintile of folate intake. Vitamin B-6, vitamin B-12, and methionine intakes were not significantly associated with any subtype of stroke.

These findings in men suggest that a high dietary folate intake may reduce the risk of cerebral infarction.

Analytical techniques for drug detection in oral fluid

Lillsunde, P.

Therapeutic Drug Monitoring. 2008; 30(2): 181-187. Article. IF 3.032

Analytical techniques for detection of drugs in oral fluid (OF) are reviewed with emphasis on applications used in European Union (EU) roadside testing projects. Oral fluid is readily accessible and collectible. It has become an interesting material because no medical personnel are needed for sampling; This matrix is especially applicable for preliminary drug testing in driving under the influence controls and for monitoring illicit drug use in drug treatment. Oral fluid is also an increasingly used specimen in epidemiologic studies and in workplace drug testing. Drugs are present at lower levels in OF than in urine. The window of detection of drugs in OF reflects the corresponding window in blood, suggesting OF as a specimen of choice for roadside testing. Saliva/blood ratios vary from drug to drug, from person to person, and even intraindividually making therapeutic drug monitoring in OF challenging. Several sensitive methods for drug testing in OF have been developed during the last years.

Cigarette smoking and cancer: Intensity patterns in the alpha-tocopherol, beta-carotene cancer prevention study in Finnish men

Lubin, J. H., Virtamo, J., Weinstein, S. J. and Albanes, D.

American Journal of Epidemiology. 2008; 167(8): 970-975. Article. IF 5.241

Relative risks for lung and bladder cancers by smoking intensity level off at more than 15-20 cigarettes per day. A three-parameter excess relative risk model in pack-years and intensity quantified this leveling (Lubin et al., Am J Epidemiol 2007;166:479-89).

Above 15-20 cigarettes per day was an "inverse exposure rate" effect whereby, for equal pack-years, the excess relative risk/pack-year decreased with increasing intensity; that is, smoking at a lower intensity for a longer duration was more deleterious than smoking at a higher intensity for a shorter duration. After adjustment for pack-years, intensity effects were quantitatively homogeneous across multiple case-control studies of lung, bladder, oral cavity, pancreas, and esophagus cancers.

The authors extended those analyses to examine intensity patterns for incident bladder, esophagus, kidney, larynx, liver, lung, oropharynx, and pancreas cancers by using data from a single prospective cohort in Finland, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, with follow-up from enrollment, which occurred between 1985 and 1988, through April 2004. At more than 10 cigarettes per day, they found an inverse exposure rate pattern for each cancer site. After adjustment for pack-years, intensity effects were quantitatively homogeneous across the diverse cancer sites and homogeneous with intensity effects from the prior analysis of multiple studies.

Consistency of intensity patterns suggested a general phenomenon and may provide clues to the molecular basis of smoking-related cancer risk.

Healthcare-associated infections in Finnish acute care hospitals: a national prevalence survey, 2005

Lyytikainen, O., Kanerva, M., Agthe, N., Mottonen, T., Ruutu, P. and The Finnish Prevalence Survey Study, G.

J Hosp Infect. 2008. IF 2.442

The objectives of the first national prevalence survey on healthcare-associated infections (HAIs) in Finland were to assess the extent of HAI, distribution of HAI types, causative organisms, prevalence of predisposing factors and use of antimicrobial agents.

The voluntary survey was performed during February-March 2005 in 30 hospitals, including tertiary and secondary care hospitals and 10 (25%) other acute care hospitals in the country. The overall prevalence of HAI was 8.5% (703/8234). Surgical site infection was the most common HAI (29%), followed by urinary tract infection (19%) and primary bloodstream infection or clinical sepsis (17%). HAI prevalence was higher in males, among intensive care and surgical patients, and increased with age and severity of underlying illness. The most common causative organisms, identified in 56% (398/703) of patients with HAIs, were Escherichia coli (13%), Staphylococcus aureus (10%) and Enterococcus faecalis (9%). HAIs caused by multi-resistant microbes were rare (N=6). A total of 122 patients were treated in contact isolation due to the carriage of multi-resistant microbes. At the time of the survey, 19% of patients had a urinary catheter, 6% central venous line and 1% were ventilated. Antimicrobial treatment was given to 39% of patients.

These results can be used for prioritising infection control measures and planning more detailed incidence surveillance of HAI. The survey was a useful tool to increase the awareness of HAI in participating hospitals and to train infection control staff in diagnosing HAIs.

Only half of bipolar I and II patients report prodromal symptoms

Mantere, O., Suominen, K., Valtonen, H. M., Arvilommi, P. and Isometsa, E.

J Affect Disord. 2008. IF 3.138

BACKGROUND: Learning to detect prodromal symptoms is a key element of psychosocial treatment of bipolar disorder (BD). However, previous studies have described only prodromes of manic and depressive phases of BD I patients, while information on prodromes in BD II, or other phases is lacking.

METHODS: The Jorvi Bipolar Study included 191 in- and outpatients with DSM-IV BD (90 BD I, 101 BD II) in any acute phase of illness at baseline. The prevalence, type and duration of preceding prodromes were investigated using open-ended questions. The effects of type I or II disorder, index phase, socio-demographic factors, comorbidity, illness history and other correlates on report and duration of prodromes were investigated.

RESULTS: Prodromes were reported by 45.0% of BD I and 50.0% of BD II patients. The first prodromal symptom was usually mood congruent, but sometimes non-specific for mood or a symptom of anxiety; the median duration was 30.5 days. No differences between BD I and II, or between patients who did and those who did not report prodromes were found. Only Axis I comorbidity associated with longer prodromes, but not independently after adjusting for age, gender and type of phase.

LIMITATIONS: The study was cross-sectional. Reporting prodromes depends on patients' insight which was likely affected by a sub-acute phase at time of interview.

CONCLUSIONS: Only half of ordinary, secondary care bipolar patients are able to report prodromes. The chronic and fluctuating course of illness, and sometimes short time interval to full episode may limit the potentials of prodrome-based interventions.

Differences in outcome of DSM-IV bipolar I and II disorders

Mantere, O., Suominen, K., Valtonen, H. M., Arvilommi, P., Leppamaki, S., Melartin, T. and Isometsa, E.

Bipolar Disorders. 2008; 10(3): 413-425. Article. IF 3.494

Objectives: To investigate whether the course of bipolar disorder (BD) type II is more depressive than that of BD I, and, if so, to explore the underlying factors that cause this difference.

Methods: In a prospective, naturalistic study of 191 secondary care psychiatric in- and outpatients diagnosed in an acute phase of BD I or II, 160 patients (85.1%) were followed for 18 months. Using a life chart, the exact timing of symptom states in follow-up was examined. Differences between BD I (n = 75) and II (n = 85) in duration of index phase and episode, time to full remission and recurrence, and time in any mood episode were investigated.

Results: Patients with BD II spent a higher proportion of time ill (47.5% versus 37.7%; p = 0.02) and in depressive symptom states (58.0% versus 41.7%; p = 0.003) than BD I patients. This was a result of the higher proportion (61.7% versus 48.6%; p = 0.03) and mean number (1.69 versus 1.11; p = 0.006) of depressive illness phases in BD II, rather than of differences in the duration of depressive phases. Type of index phase strongly predicted the outcome. In linear regression models, both BD II and type of index phase predicted more time spent in depressive symptom states.

Conclusions: In medium-term follow-up, BD II patients spend about 40% more time in depressive symptom states than BD I patients because a higher proportion of BD II patients have depressive phases and the frequency of these is higher. Differences in type of index phase may markedly confound differences in outcome between BD I and II.

Macrophage mannose receptor on lymphatics controls cell trafficking

Marttila-Ichihara, F., Turja, R., Miiluniemi, M., Karikoski, M., Maksimow, M., Niemela, J., Martinez-Pomares, L., Salmi, M. and Jalkanen, S.

Blood. 2008. IF 10.370

Macrophage mannose receptor (MR) participates in pathogen recognition, clearance of endogenous serum glycoproteins and antigen presentation. MR is also present on lymphatic vessels, where its function is unknown. Here we show that migration of lymphocytes from the skin into the draining lymph nodes through the afferent lymphatics is reduced in MR-deficient mice, whilst the structure of lymphatic vasculature remains normal in these animals. Moreover, in a tumor model the primary tumors grow significantly bigger in MR-/- mice than in the wild-type (WT) controls, whereas the regional lymph node metastases are markedly smaller. Adhesion of both normal lymphocytes and tumor cells to lymphatic vessels is significantly decreased in MR deficient mice. Ability of macrophages to present tumor antigens is indistinguishable between the two genotypes. Thus, MR on lymphatic endothelial cells is involved in leukocyte trafficking and contributes to the metastatic behavior of cancer cells. Blocking of MR may provide a new approach to controlling inflammation and cancer metastasis by targeting the lymphatic vasculature.

Introducing human papillomavirus vaccines - questions remain

Paavonen, J. and Lehtinen, M.

Annals of Medicine. 2008; 40(3): 162-166. Review. IF 4.594

Genital human papillornavirus (HPV) infection and HPV-associated cervical and other anogenital cancers are significant public health problems. HPV 16 and HPV 18 are responsible for approximately 70% of all invasive cervical cancers worldwide. The first prophylactic HPV virus-like particle (VLP) vaccine against HPV types 6/11/16/18 was licensed in 2006 for girls and women aged 9-26 years. The second prophylactic HPV vaccine against HPV types 16 and 18 has been licensed this year. These vaccines are almost 100% effective in preventing infection and high-grade precancer associated with the HPV types included in the vaccine. The vaccines are well tolerated, safe, and highly immunogenic when given in three doses within 6 months. Efficacy of the vaccine against external vulvar and HPV-related vaginal lesions is also high. Even though the vaccine is highly effective against high-grade cervical, vaginal, or vulvar precancers, this only applies to women unexposed to these HPV types and only to high-grade intraepithelial lesions caused by these HPV types. Therefore, it is important to understand that the population impact of the vaccines will be much lower than vaccinating naive populations. Implementing HPV vaccine is a great opportunity but also a great challenge. However, mandatory HPV vaccination may raise many questions, and more answers are needed.

Quantitative PCR analysis of fungi and bacteria in building materials and comparison to culture-based analysis

Pietarinen, V. M., Rintala, H., Hyvarinen, A., Lignell, U., Karkkainen, P. and Nevalainen, A.

J Environ Monit. 2008; 10(5): 655-63. IF 1.523

Prolonged moisture on building materials can lead to microbial growth on them. Microbes can emit spores, metabolites and structural parts into the indoor air and thus, cause adverse health effects of people living and working in these buildings. So far, culture methods have been used for assessment of microbial contamination of building materials.

In this work, we used quantitative PCR (qPCR) for the detection of selected fungal and bacterial groups in 184 building materials of different types and compared the results with culture-based analysis. Nine either commonly found species, genera or groups of fungi, or those considered as moisture damage indicators, and one bacterial genus, Streptomyces, were determined using qPCR. Fungi and mesophilic actinomycetes were also cultivated using standard media and conditions of the routine analysis.The bacterial genus Streptomyces and the fungal group Penicillium/Aspergillus/Paecilomyces were the most prevalent microbial groups in all building material types, followed by Stachybotrys chartarum and Trichoderma viride/atroviride/koningii. The highest prevalences, concentrations and species diversity was observed on wooden materials.

In general, the results of the two methods did not correlate well, since concentrations of fungi and streptomycetes were higher and their occurrence more prevalent when determined by qPCR compared to culture-based results. However, with increasing concentrations, the correlation generally increased. The qPCR assay did not detect Aspergillus versicolor and Acremonium strictum as often as culture.

Labelling the salt content in foods: a useful tool in reducing sodium intake in Finland

Pietinen, P., Valsta, L. M., Hirvonen, T. and Sinkko, H.

Public Health Nutrition. 2008; 11(4): 335-340. Article. IF 2.123

Objective: To estimate the impact of choosing food products labelled either as low or high in salt on salt intake in the Finnish adult population.

Setting and subject: The National FINDIET 2002 survey with 48-hour recalls from 2007 Subjects aged 25-64 years. Sodium intake was calculated based on the Fineli((R)) food composition database including the sodium content of natural and processed foods as well as the salt content of recipes. The distribution of salt intake was calculated in different ways: the present situation; assuming that all breads, cheeses, processed meat and fish, breakfast cereals and fat spreads consumed Would be either 'lightly salted' or 'heavily salted' based on the current labelling practice; and, in addition, assuming that all foods Would be prepared with 50% less or more salt.

Results: Excluding underreporters, the mean salt intake Would be reduced by 1.8 g in men and by 1.0g in women if the entire population were to choose lightly salted products and further by 2.5 and 1.8g, respectively, if also salt used in cooking were halved. Choosing heavily salted products would increase salt intake by 2.1 g in men and by 1.4 g in women. In the worst scenarios, salt intake would be further increased by 2.3 g in men and by 1.6 g in women.

Conclusions: These calculations show that the potential impact of labelling and giving consumers the possibility to choose products with less salt is of public health importance. In addition, strategies to reduce the salt content of all food groups are needed.

Effect of Lactobacillus rhamnosus GG on rBet v1 and rMal d1 specific IgA in the saliva of patients with birch pollen allergy

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.

Want growth and hostility in adult life

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

Psychosomatic Medicine. 2008; 70(3): 306-313. Article. IF 3.857

Objective: Hostility may confer a risk of cardiovascular disease and all-cause mortality, but why is uncertain. A common origin in suboptimal fetal and early postnatal life may lie beneath. This study tested whether prenatal and postnatal growth predicts hostility in adult life.

Methods: Women (n = 939) and men (n = 740) born in Helsinki, Finland, from 1934 through 1944 filled out the Cook-Medley Hostility Scale at an average age of 63.4 years. Growth was estimated from birth, child welfare clinic, and school records. Adult body size was measured in a clinic.

Results: Men and women who had higher levels of hostility in adulthood were born lighter and thinner, showed slower weight gain from birth to 6 months of age, were lighter throughout childhood (standardized regression coefficients (beta) <-0.05; 95% confidence intervals (95% Cl), -0.14 to -0.00; p values <.05), but were heavier in adulthood (beta values > 0.06; 95% CIs, 0.02-0.14; p values < .01). They were also shorter from 6 months until the age of 1 year (beta values <-0.09; 95% CIs, -0.14 to -0.03; p values < .003), and tended to be shorter in adulthood (beta = -0.05; 95% CI, -0.09 to 0.00; p = .06). The latter effects were largely attributable to slower growth in stature from birth to 6 months (P = -0.08; 95% CI, -0.14 to -0.02; p = .005). The associations were not explained by major confounders.

Conclusions: Our study suggests that slow prenatal and infant growth is linked with hostility in adult life.

Activation of pro-matrix metalloproteinase-9 and degradation of gelatin by the surface protease PgtE of Salmonella enterica serovar Typhimurium

Ramu, P., Lobo, L. A., Kukkonen, M., Bjur, E., Suomalainen, M., Raukola, H., Miettinen, M., Julkunen, I., Holst, O., Rhen, M., Korhonen, T. K. and Lahteenmaki, K.

International Journal of Medical Microbiology. 2008; 298(3-4): 263-278. Article. IF 2.760

Mammalian matrix metalloproteinases (MMPs) degrade collagen networks in extracellular matrices by cleaving collagen and its denatured form gelatin, and thus enhance migration of mammalian cells. The gastrointestinal pathogen Salmonella enterica survives and grows within host macrophages and dendritic cells, and can disseminate in the host by travelling within infected host cells.

Here, we report that S. enterica serovar Typhimurium activates proMMP-9 (gelatinase B) secreted by human primary macrophages, and degrades gelatin after growth within J774A.1 murine macrophage-like cells. Both proMMP-9 activation and gelatin degradation were due to expression of the Salmonella surface protease PgtE. Following intraperitoneal infection in BALB/c mice, the amount of a pgtE deletion derivative was nearly ten-fold lower in the livers and spleens of mice than the amount of wild-type S. enterica, suggesting that PgtE contributes to dissemination of Salmonella in the host. PgtE belongs to the omptin family of bacterial beta-barrel transmembrane proteases. The ortholog of PgtE in Yersinia pestis, Pla, which is central for bacterial virulence in plague, was poor in proMMP-9 activation and in gelatin degradation. To model the evolution of these activities in the omptin barrel, we performed a substitution analysis in Pla and genetically modified it into a PgtE-like gelatinase.

Our results indicate that PgtE and Pla have diverged in substrate specificity, and suggest that Salmonella PgtE has evolved to functionally mimic mammalian MMPs. (c) 2007 Elsevier GmbH. All rights reserved.

Blood levels of organotin compounds and their relation to fish consumption in Finland

Rantakokko, P., Turunen, A., Verkasalo, P. K., Kiviranta, H., Mannisto, S. and Vartiainen, T.

Sci Total Environ. 2008. IF 2.359

The objective of this study was to measure the concentrations of organotin compounds in the whole blood of Finnish male fishermen (n=133), their wives (n=94), and other family members (n=73), and to investigate their associations with background variables. The concentrations were generally low, less than the limit of quantification (LOQ) for the vast majority of compounds and samples. Of the organotin compounds (mono-, di-, and tributyltin, mono-, di-, and triphenyltin, and dioctyltin), only triphenyltin was detected in more than just a few samples (in 37 of 300 samples, LOQ=0.04 ng/ml). These were mainly the samples of fishermen (26/37) and their wives (10/37).

For statistical analysis, concentrations of triphenyltin were divided into two categories, <LOQ and >LOQ. Of the different background variables, age and fish consumption contributed the most to the triphenyltin concentrations. When age and fish consumption (g/day) were divided into three categories, odds ratios comparing the highest with the lowest category were 3.88 for age (95% CI 1.36-11.09) and 3.48 for fish consumption (1.36-8.94), respectively. Compared with females, males had an odds ratio of 1.51 of having the concentration of triphenyltin >LOQ (0.72-3.14).

To the best of our knowledge, this study confirmed for the first time with human samples that fish consumption can be associated with triphenyltin concentration in whole blood.

Depressive symptoms, suicidal ideation and acne: a study of male Finnish conscripts

Rehn, L. M. H., Meririnne, E., Hook-Nikanne, J., Isometsa, E. and Henriksson, M.

Journal of the European Academy of Dermatology and Venereology. 2008; 22(5): 561-567. Article. IF 1.532

Objective To investigate the association among acne, depressive symptoms and suicidal ideation in Finnish male military conscripts.

Methods Consecutive 165 acne patients and 150 patients with mild knee symptoms for comparison were enrolled in the study conducted in the Central Military Hospital, Helsinki, Finland. They filled out the following questionnaires: General Health Questionnaire (GHQ-12), Beck Depression Inventory (BDI), Alcohol Use Disorders Identification Test and Rosenberg Self-Esteem Scale. The Leeds acne grading scale was used to estimate the severity of acne.

Results Sixteen (9.7%) acne patients and 20 (13.3%) comparison patients had at least moderate level of depressive symptoms (BDI score 10; P > 0.05, between groups). Suicidal ideation (BDI suicidal item score 1) was reported by 24 (14.5%) acne patients and 16 (10.7%) comparison patients (P > 0.05, between groups). When comparing the mild facial acne patients (Leeds score 0-3) with those with moderate-severe facial acne (Leeds score 4), there were no statistical differences in depressive symptoms (9.5% vs. 10.0%) or suicidal ideation (13.7% vs. 15.7%). No linear relationship was observed between the BDI and facial Leeds scores (P > 0.05). Risk factors for suicidal ideation among the acne patients were depression and alcohol risk use.

Conclusion Young male patients with acne do not suffer more depressive symptoms or suicidal ideation than patients with mild knee symptoms, and the severity of acne is not associated with the presence of depressive symptoms. The risk factors for suicidal ideation among acne patients seem to be similar to those found in the general population.

Xylitol-supplemented nutrition enhances bacterial killing and prolongs survival of rats in experimental pneumococcal sepsis

Renko, M., Valkonen, P., Tapiainen, T., Kontiokari, T., Mattila, P., Knuuttila, M., Svanberg, M., Leinonen, M., Karttunen, R. and Uhari, M.

Bmc Microbiology. 2008; 8. Article. IF 2.896

Background: Xylitol has antiadhesive effects on Streptococcus pneumoniae and inhibits its growth, and has also been found to be effective in preventing acute otitis media and has been used in intensive care as a valuable source of energy.

Results: We evaluated the oxidative burst of neutrophils in rats fed with and without xylitol. The mean increase in the percentage of activated neutrophils from the baseline was higher in the xylitol-exposed group than in the control group (58.1% vs 51.4%, P = 0.03 for the difference) and the mean induced increase in the median strength of the burst per neutrophil was similarly higher in the xylitol group (159.6 vs 140.3, P = 0.04). In two pneumococcal sepsis experiments rats were fed either a basal powder diet (control group) or the same diet supplemented with 10% or 20% xylitol and infected with an intraperitoneal inoculation of S. pneumoniae after two weeks. The mean survival time was 48 hours in the xylitol groups and 34 hours in the control groups (P < 0.001 in log rank test).

Conclusion: Xylitol has beneficial effects on both the oxidative killing of bacteria in neutrophilic leucocytes and on the survival of rats with experimental pneumococcal sepsis.

The European perspective of type 2 diabetes prevention: Diabetes in Europe - Prevention using lifestyle, physical activity and nutritional intervention (DE-PLAN) project

Schwarz, P. E. H., Lindstrom, J., Kissimova-Scarbeck, K., Szybinski, Z., Barengo, N. C., Peltonen, M. and Tuomilehto, J.

Experimental and Clinical Endocrinology & Diabetes. 2008; 116(3): 167-172. Article. IF 1.356

Background: The prevalence of type 2 diabetes (T2D) has dramatically increased in Europe, and the age-at-diagnosis has become younger. Action is needed now to develop targeted prevention management program for T2D). The DE-PLAN ("Diabetes in Europe - Prevention using Lifestyle, Physical Activity and Nutritional intervention") project, led by the University of Helsinki is currently addressing this major public health concern in Europe.

Methods: The DE-PLAN project aims at developing and testing models of efficient identification and intervention of individuals at high risk of type 2 diabetes in the community. It conducts a lifestyle modification intervention in people at high risk for T2D. Furthermore, it tests the feasibility and cost-effectiveness of the translation of the current research evidence about preventive intervention program into clinical settings within existing health care systems in 17 European countries.

Results: This 3-year project spanning has commenced mid-2005. By now, 25 institutions from 17 countries are involved.

Conclusion: The development of efficient screening strategies for type 2 diabetes risk as well as the development of core intervention strategies for the primary prevention of type 2 diabetes should significantly enhance the ability of health care professionals to respond swiftly to the drastic increase of T2D and its burden to the society.

Infiltration of forkhead box P3-expressing cells in small intestinal mucosa in coeliac disease but not in type 1 diabetes

Tiittanen, M., Westerholm-Ormio, M., Verkasalo, M., Savilahti, E. and Vaarala, O.

Clin Exp Immunol. 2008. 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.

Size at birth, weight gain over the life course, and low-grade inflammation in young adulthood: northern Finland 1966 birth cohort study

Tzoulaki, I., Jarvelin, M. R., Hartikainen, A. L., Leinonen, M., Pouta, A., Paldanius, M., Ruokonen, A., Canoy, D., Sovio, U., Saikku, P. and Elliott, P.

European Heart Journal. 2008; 29(8): 1049-1056. Article. IF 7.286

Aims Low-grade inflammation might mediate associations between size at birth, early life growth, excessive weight gain, and subsequent risk of cardiovascular disease in adult life. Our aim was to investigate relationships between fetal growth, weight over the life course, and low-grade inflammation measured by serum high sensitivity C-reactive protein (CRP) levels at 31 years.

Methods and results General population-based northern Finland 1966 Birth Cohort study of 5840 participants attending a clinical examination at 31 years, including measurement of CRP. Weight and height were assessed at birth, 12 months, and 14 and 31 years of age. CRP levels at 31 years were 16% [95% confidence interval (CI) 8, 23] higher per 1 kg lower birth weight, 21% (95% CI 2, 37) higher per 10 cm lower birth length, and 24% (95% CI 10, 36) higher per 1 kg/m(3) lower ponderal index, after adjustment for potential confounders. Participants with highest tertile body mass index (BMI) at 31 years and lowest tertile birth weight had the highest average CRP levels. Per unit increase in BMI from 14 to 31 years was associated with 16% (95% CI 14, 17) higher CRP levels; the association was larger for those in the top BMI tertile at age 14 years.

Conclusion Systemic low-grade inflammation may lie on the causal pathway that relates impaired fetal growth and weight gain from childhood to adulthood to adverse adult cardiovascular health. Lifestyle changes from early life might be an important step in reducing cardiovascular risk in adults.

Serum alpha- and gamma-tocopherol concentrations and risk of advanced beta cell autoimmunity in children with HLA-conferred susceptibility to type 1 diabetes mellitus

Uusitalo, L., Nevalainen, J., Niinisto, S., Alfthan, G., Sundvall, J., Korhonen, T., Kenward, M. G., Oja, H., Veijola, R., Simell, O., Ilonen, J., Knip, M. and Virtanen, S. M.

Diabetologia. 2008; 51(5): 773-780. Article. IF 5.247

Aims/hypothesis The aim of our study was to assess the associations of serum alpha- and gamma-tocopherol concentrations with the risk of advanced beta cell autoimmunity in children with HLA-conferred genetic susceptibility to type 1 diabetes mellitus.

Methods A case-control study with 108 cases with advanced beta cell autoimmunity and 216 matched control participants nested within the birth cohort of the Type 1 Diabetes Prediction and Prevention Project. A serum sample for vitamin E analyses was collected from all the children in the cohort at the age of 1 year and thereafter at 12 month intervals. For each case-control group, all the repeated serum samples up to the age of seroconversion to autoantibody positivity in the case were analysed. A conditional logistic regression model was used to determine potential associations between seroconversion and serum tocopherol concentrations.

Results Serum alpha- or gamma-tocopherol concentrations were not significantly associated with the risk of advanced beta cell autoimmunity. The odds ratio (95% CI) for mu mol/l increase in serum concentration of the first-year sample was 0.97 (0.92-1.03) for alpha-tocopherol and 1.10 (0.70-1.74) for gamma-tocopherol. However, there was an interaction between high values of gamma-tocopherol at the age of 1 year and the time of seroconversion (p=0.024).

Conclusions/Interpretation It seems unlikely that high concentrations of alpha- or gamma-tocopherol protect against advanced beta cell autoimmunity in young children.