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Aalto, M., Hyvönen, S. and Seppä, K. Drug Alcohol Depend. 2005. BACKGROUND: To define whether the Alcohol Use Disorders Identification Test (AUDIT) scores of primary care physicians themselves predict their willingness to use brief alcohol intervention. METHODS: Cross-sectional self-administered questionnaire survey to all 3193 physicians providing primary health care in Finland. The response rate was 1909 (59.8%). Odds ratios from multinomial regression analysis were calculated for self-reported frequency (never, occasionally or regularly) of conducting brief interventions by physicians with AUDIT scores of 0-1, 2, 3, 4, 5-7 or >/=8. RESULTS: The prevalence of heavy drinkers based on AUDIT score (>/=8) was 14.5% among all physicians, 7.0% among females and 27.0% among males. Of the respondents 9.4% reported doing brief intervention regularly and 50.0% occasionally. AUDIT scores did not significantly predict either regular or occasional use of brief intervention. Instead, some other independent predictors for more frequent use of brief intervention were found. These included having a specialist licence in general practice or occupational health care and the location of the practice, but not gender or age. CONCLUSIONS: The present results indicate that in general heavy drinking among primary care physicians do not explain the low frequency with which brief intervention is used in primary health care. Bosnyak, Z., Nishimura, R., Hagan Hughes, M., Tajima, N., Becker, D., Tuomilehto, J. and Orchard, T. J. Diabetic Medicine. 2005; 22(12): 1636-1641. Aims Excess mortality in Type 1 diabetes has previously been found among Black individuals. The aim of the present study was therefore to determine underlying causes. Methods A longitudinal study of 1261 [1184 White (93.9%) and 76 Black (6.0%)] individuals diagnosed with Type 1 diabetes between 1965 and 1979, at age < 17 years from the Allegheny County, Pennsylvania and Children's Hospital of Pittsburgh registries. Subjects were contacted in 1999 to determine living status and, where appropriate, cause of death. Living status was determined in 1183 participants (93.8%). Results Of the 200 deaths overall, cause of death was determined in 157 subjects (79%); 31 dying from acute and 101 from chronic complications, and 25 from non-diabetes related causes. Seven deaths were investigated but no cause determined. Black participants had a significantly higher mortality rate compared with White participants for acute complications (hazard ratio = 4.9, 95% confidence interval: 2.0, 11.6), but not for any other cause. There was a temporal decline in the 20-year mortality rates in both racial groups across the three cohorts diagnosed in 1965-69, 1970-74 and 1975-79. Conclusions These results show that the excess mortality in Black people was attributed to acute complications which therefore should be a focus for prevention. Aetiology of community-acquired pneumonia: Serological results of a paediatric survey Don, M., Fasoli, L., Paldanius, M., Vainionpaa, R., Kleemola, M., Raty, R., Leinonen, M., Korppi, M., Tenore, A. and Canciani, M. Scandinavian Journal of Infectious Diseases. 2005; 37(11-12): 806-812. Serological methods are routinely used in the diagnosis of viral and atypical bacterial respiratory infections. Recently, they have also been applied to typical bacteria, such as Streptococcus pneumoniae. The aim of this study was to determine the aetiology of paediatric community-acquired pneumonia (CAP) in both ambulatory and hospitalized patients, by using antibody assays. During a 15-month prospective surveillance, paired sera were studied for antibodies to 14 microbes in 101 children with symptoms of acute infection and infiltrates compatible with pneumonia on chest radiographs. A potential causative agent was detected in 66 (65%) patients. Evidence of bacterial, viral and mixed viral-bacterial infection was demonstrated in 44%, 42% and 20% of the CAP cases, respectively. The most commonly found agents included Mycoplasma pneumoniae (27%), Pneumococcus (18%) and respiratory syncytial virus (17%). Human metapneumovirus (hMPV) was detected in 5 (5%) children. Pneumococcal infections were evenly distributed among the age groups studied. Our results confirm the role of S. pneumoniae in paediatric CAP at all ages, those of M. pneumoniae at >2 y of age and emphasize the emerging role of hMPV. The high proportion of mixed viral-bacterial infections highlights the need to treat all children with CAP with antibiotics. Eklund, M., Nuorti, J. P., Ruutu, P. and Siitonen, A. Epidemiol Infect. 2005; 133(5): 845-52. During 1998-2002, 124 microbiologically confirmed infections caused by shigatoxigenic Escherichia coli (STEC) were reported in Finland. Of these, 25 (20%) were associated with recent foreign travel. Temporal, geographical and type distribution of the domestically acquired infections (n=99) caused by strains of serogroup O157 (n=52) and non-O157 (n=47) were analysed further. The median age of the patients was 6.8 years (range 0.2-73.1 years). Of the index cases within 26 families, 71% were <5 years old. Family-related infections accounted for 49%, sporadic infections 39%, and 11% were associated with three clusters. Only strains of serogroup O157 carrying eae and stx 2 or its variants caused separate clusters. The incidence of STEC infections was at its highest (0.64/100000) in 1998. Since 1999 it has declined considerably (0.17/100000 in 2002). STEC infections occurred in 14 hospital districts, mostly (28%) in the Helsinki region. However, the incidence was highest (10.3) in northwest Finland. Erkkila, L., Jauhiainen, M., Laitinen, K., Haasio, K., Tiirola, T., Saikku, P. and Leinonen, M. Antimicrob Agents Chemother. 2005; 49(9): 3959-62. The effects of simvastatin treatment on Chlamydia pneumoniae lung infection, inflammation, and serum lipids in mouse model were studied. Simvastatin decreased viable chlamydial counts and increased inflammatory cell infiltrates in the lung tissue, suggesting that simvastatin treatment had both antichlamydial and immunomodulatory effects during an acute C. pneumoniae infection. Haarasilta, L., Marttunen, M., Kaprio, J. and Aro, H. Eur J Public Health. 2005; 15(5): 489-93. BACKGROUND: This paper aimed to investigate associations between major depressive episode (MDE) and chronic illness, disability, self-perceived health and number of sick-days among adolescents and young adults in the general population. METHODS: The Finnish Health Care Survey 1996 was a cross-sectional nationwide epidemiological study. A random sample of 509 adolescents and 433 young adults was interviewed in 1996. DSM-III-R MDE during the past 12 months was defined using The University of Michigan Composite International Diagnostic Interview Short-Form algorithm. Data on physical health were gathered in the interview. RESULTS: In multivariable logistic regression, chronic illness [odds ratio (OR) 1.78; 95% confidence interval (CI) 1.03, 3.05], poor self-rated health (OR 2.26; 95% CI 1.01, 5.07), more than three sick-days in the past 6 months (OR 1.72; 95% CI 1.02, 2.92) and respiratory allergies (OR 2.40; 95% CI 1.00, 5.75) were associated with MDE. Among 15- to 19-year-olds, disabling chronic illness was related to MDE (OR 2.59; 95% CI 1.06, 6.36), and thoughts of death were more prevalent in the presence of chronic illness among those with MDE [35.2% versus 65.7%; F(1,67) P = 0.024]. Migraine was associated with MDE among young adults (OR 6.18; 95% CI 1.14, 30.8). CONCLUSIONS: Symptoms of depression should be investigated among adolescents with chronic illness or frequent sick-days. The degree of reported disability should be noted. Young people with both chronic illness and depressive symptoms should be assessed for thoughts of death and possible suicidality. Leisure participation predicts survival: a population-based study in Finland Hyyppä, M. T., Mäki, J., Impivaara, O. and Aromaa, A. Health Promot Int. 2005. SUMMARY The authors study whether leisure participation is an independent predictor of survival over 20 years. Of the nationally representative sample of 8000 adult Finns (Mini-Finland Health Survey), aged >/=30 years, the cohort of 30-59 years (n 5087) was chosen for the Cox proportional survival analyses. The sum score of leisure participation was divided in quartiles (the lowest quartile = scarce = 0-6), two intermediate quartiles = 7-11 and the highest quartile = abundant = 12-21). Adjusted for statistically significant covariates (age, tobacco smoking, alcohol consumption, obesity, self-rated health and diagnosed chronic diseases), and with scarce participation as the reference, the hazard ratios and 95% confidence intervals (CIs) for the risk of death were 0.80, 0.67-0.95 (intermediate) and 0.66, 0.52-0.84 (abundant) for men. The association was insignificant in women with good health. The results show that leisure participation predicts survival in middle-aged Finnish men and its effect is independent of demographic features, of health status and of several other health-related factors. The beneficial effect emphasizes the significance of leisure activities for the promotion of men's health. Johansson, M., Lehto, M., Tanhuanpää, K., Cover, T. L. and Olkkonen, V. M. Molecular Biology of the Cell. 2005; 16(12): 5480-5492. ORP1L is a member of the human oxysterol-binding protein (OSBP) family. ORP1L localizes to late endosomes (LEs)/lysosomes, colocalizing with the GTPases Rab7 and Rab9 and lysosome-associated membrane protein-1. We demonstrate that ORP1L interacts physically with Rab7, preferentially with its GTP-bound form, and provide evidence that ORP1L stabilizes GTP-bound Rab7 on LEs/lysosomes. The Rab7-binding determinant is mapped to the ankyrin repeat (ANK) region of ORP1L. The pleckstrin homology domain (PHD) of ORP1L binds phosphoinositides with low affinity and specificity. ORP1L, ANK- and ANK+PHD fragments induce perinuclear clustering of LE/lysosomes. This is dependent on an intact microtubule network and a functional dynein/dynactin motor complex. The dominant inhibitory Rab7 mutant T22N reverses the LE clustering, suggesting that the effect is dependent on active Rab7. Transport of fluorescent dextran to LEs is inhibited by overexpression of ORP1L. Overexpression of ORP1L, and in particular the N-terminal fragments of ORP1L, inhibits vacuolation of LE caused by Helicobacter pylori toxin VacA, a process also involving Rab7. The present study demonstrates that ORP1L binds to Rab7, modifies its functional cycle, and can interfere with LE/lysosome organization and endocytic membrane trafficking. This is the first report of a direct connection between the OSBP-related protein family and the Rab GTPases. Jousilahti, P., Hu, G., Borodulin, K. and Tuomilehto, J. Circulation. 2005; 112(17): U838-U838. Meeting abstract. Kakela, R., Tanhuanpaa, K., Laitinen, S., Somerharju, P. and Olkkonen, V. M. Biochemistry and Cell Biology-Biochimie Et Biologie Cellulaire. 2005; 83(5): 677-683. We have previously shown that overexpression Of human OSBP-related protein 2 (ORP2) in Chinese hamster ovary (CHO) cells results in increased efflux and reduced esterification of cholesterol. The ORP2-expressing cells also have a reduced level of triacylglycerols. We investigated the effects of ORP2 expression on the phospholipid (PL) molecular species and the neutral lipid (NL) fatty acid composition of CHO cells cultured in the presence or absence of serum lipoproteins. In the presence of lipoproteins, ORP2/CHO cells display an increase in polyunsaturated PL species, and Polyunsaturated fatty acids (PUFA) in the diminished NL pool are reduced. The increase Of polyunsaturated PL may represent a compensatory response to alterations in cholesterol metabolism. Upon lipoprotein deprivation, the ORP2/CHO cells display a drop in polyunsaturated and an increase in mono and diunsaturated PL species. Our results suggest that this is due to defective recycling of PUFA from the diminished NL pool to PL. Furthermore, the PL PUFA, which are elevated in ORP2/CHO cells, are most likely subject to more rapid turnover than the NL-associated pool. The results provide evidence for a delicate integration of cholesterol, PL, and NL metabolism and a role of ORP2 as a regulator of the cellular lipidome. Gender differences in the treatment and secondary prevention of CHD at population level Kattainen, A., Salomaa, V., Jula, A., Antero Kesäniemi, Y., Kukkonen-Harjula, K., Kahonen, M., Majahalme, S., Moilanen, L., Nieminen, M. S., Aromaa, A. and Reunanen, A. Scand Cardiovasc J. 2005; 39(6): 327-33. Objectives. Treatment and secondary prevention measures, received by persons with coronary heart disease (CHD), are insufficiently known at the moment. The aim of this study was to investigate the state of treatment and secondary prevention of CHD in a population-based sample and to analyze possible gender differences in different age groups. Design. 300 men and 300 women with CHD were identified from a nationally representative health examination survey with 88% participation rate, carried out in Finland in 2000-2001. Results. Revascularization had been performed on 34% (95% confidence interval 29, 40%) of men and 13% (8, 18%) of women. Moreover, 76% (71, 81%) of the men and 63% (57, 69%) of the women used antithrombotic medications. Two thirds of both men and women used beta-blockers and one third lipid-lowering medication. Smoking was more common among men, whereas obesity and high total cholesterol concentration were more common among women. Conclusions. Secondary prevention of CHD is far from optimal and there are gender differences in the care of CHD. Use of antimicrobials and risk of type 1 diabetes in a population-based mother-child cohort Kilkkinen, A., Virtanen, S. M., Klaukka, T., Kenward, M. G., Salkinoja-Salonen, M., Gissler, M., Kaila, M. and Reunanen, A. Diabetologia. 2005: 1-5. AIMS/HYPOTHESIS: The aim of this study was to investigate whether the use of antimicrobials is associated with the risk of childhood type 1 diabetes. MATERIALS AND METHODS: The study population included all children born in Finland between 1996 and 2000 who were diagnosed with type 1 diabetes by the end of 2002. For each case (n=437), four matched controls were selected. Data on diabetes and the maternal use of antimicrobials was derived from nationwide registries. RESULTS: Maternal use of phenoxymethyl penicillins (odds ratio [OR]=1.70, 95% CI 1.08-2.68, p=0.022) or quinolone antimicrobials (OR=2.43, 95% CI 1.16-5.10, p=0.019) before pregnancy was associated with an increased risk of type 1 diabetes in the child, whereas the use of other specific antimicrobials was not related to the risk. The risk was also higher among mother-child pairs where macrolides were used both by the mother before pregnancy and by the child, compared with pairs where neither used macrolides (OR=1.76, 95% CI 1.05-2.94, p=0.032). Maternal use of antimicrobials during pregnancy was not associated with an increased risk. The high use of antimicrobials by the child (more than seven vs seven or less purchases) was related to greater risk (OR=1.66, 95% CI 1.24-2.24, p=0.001). CONCLUSIONS/INTERPRETATION: Overall, the use of antimicrobials before pregnancy, during pregnancy or during childhood was not related to the risk of childhood type 1 diabetes. However, the use of some specific antimicrobials by the mother before pregnancy and by the child may be associated with an increased risk. Further studies are needed to confirm these associations and to elucidate the underlying mechanisms of action. Environmental triggers and determinants of type 1 diabetes Knip, M., Veijola, W., Virtanen, S. M., Hyoty, H., Vaarala, O. and Akerblom, H. K. Diabetes. 2005; 54: S125-S136. Type 1 diabetes is perceived as a chronic immune-mediated disease with a subclinical prodromal period characterized by selective loss of insulin-producing beta-cells in the pancreatic islets in genetically susceptible subjects. A series of evidence supports a critical role of exogenous factors in the development of type 1 diabetes, such as 1) the fact that < 10% of individuals with HLA-conferred diabetes susceptibility do progress to clinical disease, 2) a pairwise concordance of type 1 diabetes of < 40% among monozygotic twins, 3) a more than 10-fold difference in the disease incidence among Caucasians living in Europe, 4) a several-fold increase in the incidence over the last 50 years, and 5) migration studies indicating that the disease incidence has increased in population groups who have moved from a low-incidence to a high-incidence region. This article discusses the trigger-booster hypothesis claiming that the diabetic disease process is triggered by an exogenous factor with definite seasonal variation and driven by one or several other environmental determinants. In addition, there are a series of modifying factors affecting the fate and pace of the process. Accordingly, progression to clinical type 1 diabetes typically requires the unfortunate combination of genetic disease susceptibility, a diabetogenic trigger, and a high exposure to a driving antigen. Explaining the decline in coronary heart disease mortality in Finland between 1982 and 1997 Laatikainen, T., Critchley, J., Vartiainen, E., Salomaa, V., Ketonen, M. and Capewell, S. Am J Epidemiol. 2005; 162(8): 764-73. In Finland since the 1980s, coronary heart disease mortality has declined more than might be predicted by risk factor reductions alone. The aim of this study was to assess how much of the decline could be attributed to improved treatments and risk factor reductions. The authors used the cell-based IMPACT mortality model to synthesize effectiveness of treatments and risk factor reductions with data on treatments administered to patients and trends in cardiovascular risk factors in the population. Cardiovascular risk factors were measured in random samples of patients in 1982 (n=8,501) and 1997 (n=4,500). Mortality and treatment data were obtained from the National Causes of Death Register, Hospital Discharge Register, social insurance data, and medical records. Estimated and observed changes in coronary heart disease mortality were used as main outcome measures. Between 1982 and 1997, coronary heart disease mortality rates declined by 63%, with 373 fewer deaths in 1997 than expected from baseline mortality rates in 1982. Improved treatments explained approximately 23% of the mortality reduction, and risk factors explained some 53-72% of the reduction. These findings highlight the value of a comprehensive strategy that promotes primary prevention programs and actively supports secondary prevention. It also emphasizes the importance of maximizing population coverage of effective treatments. Laitinen, A., Koskinen, S., Harkanen, T., Reunanen, A., Laatikainen, L. and Aromaa, A. Ophthalmology. 2005; 112(12): 2227-37. PURPOSE: To estimate the prevalence rates of habitual visual acuity (VA) levels and visual impairment in Finland and to assess their correlation with self-reported visual function. DESIGN: Cross-sectional population-based study. PARTICIPANTS: Subjects were selected randomly from the Finnish population aged 30 years or older. Of 7979 eligible people, 7393 (93%) were interviewed, 6771 (85%) were examined, and 6663 (84%) had distance VA assessed. METHODS: Participants underwent a home interview and a comprehensive examination including measuring binocular VA for distance and for near with the participants' current spectacles, if any. MAIN OUTCOME MEASURES: The level of VA for distance and for near with current spectacle correction. The self-reported capability to read newsprint and television text and the ability to move about without being restricted by reduced vision. RESULTS: The prevalence of good to moderate VA for distance (VA> or =0.5 [> or =20/40]) measured with current spectacles was 95.9%, and 87.4% had a VA level of 0.8 (20/25) or better. The prevalence of habitual visual impairment (VA< or =0.25 [< or =20/80]) was 1.6%, and 0.5% were blind (VA<0.1 [<20/200]). The prevalence of visual impairment increased significantly with age (P<0.001), especially in the age group of 65 to 74 years and upward. There was no gender difference in VA for distance, but decreased near vision (VA< or =0.25 [< or =20/80]) was significantly more common in men than in women (P<0.01). By applying the imputated numbers of visually impaired and blind participants to the Finnish population (approximately 3 million aged 30 years or older), there were approximately 65000 (2.1%) visually impaired and 17000 (0.6%) blind adult persons in the country in 2000. The correlation between self-reported visual ability and measured visual function was moderate but statistically significant (r = 0.27-0.40; P<0.0001). The proportion of people with reading difficulties or who were unable to read newsprint has decreased 7% during the last 2 decades. CONCLUSIONS: Functional visual impairment increased with age especially in the age group of 65 to 74 years and upward and was as prevalent in women as in men. The prevalence of people with reading difficulties has decreased considerably since 1980. Lehto, M., Hynynen, R., Karjalainen, K., Kuismanen, E., Hyvärinen, K. and Olkkonen, V. M. Exp Cell Res. 2005; 310(2): 445-62. The intracellular targeting determinants of oxysterol binding protein (OSBP)-related protein 3 (ORP3) were studied using a series of truncated and point mutated constructs. The pleckstrin homology (PH) domain of ORP3 binds the phosphoinositide-3-kinase (PI3K) products, PI(3,4)P2 and PI(3,4,5)P3. A functional PH domain and flanking sequences are crucial for the plasma membrane (PM) targeting of ORP3. The endoplasmic reticulum (ER) targeting of ORP3 is regulated the by a FFAT motif (EFFDAxE), which mediates interaction with VAMP-associated protein (VAP)-A. The targeting function of the FFAT motif dominates over that of the PH domain. In addition, the exon 10/11 region modulates interaction of ORP3 with the ER and the nuclear membrane. Analysis of a chimeric ORP3:OSBP protein suggests that ligand binding by the C-terminal domain of OSBP induces allosteric changes that activate the N-terminal targeting modules of ORP3. Notably, over-expression of ORP3 together with VAP-A induces stacked ER membrane structures also known as organized smooth ER (OSER). Moreover, lipid starvation promotes formation of dilated peripheral ER (DPER) structures dependent on the ORP3 protein. Based on the present data, we introduce a model for the inter-relationships of the functional domains of ORP3 in the membrane targeting of the protein. Lukka, M., Tasa, G., Ellonen, P., Moilanen, K., Vassiljev, V. and Ulmanen, I. Forensic Sci Int. 2005. We report triallelic patterns in several short tandem repeat (STR) loci revealed by routine paternity testing using the commercial AMPFlSTR((R))Profilertrade mark and AMPFlSTR((R))SGMplustrade mark 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 (>1.59Mb) 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. Rewarding properties of the stereoisomers of 4-methylaminorex: involvement of the dopamine system Meririnne, E., Kajos, M., Kankaanpää, A., Koistinen, M., Kiianmaa, K. and Seppälä, T. Pharmacol Biochem Behav. 2005; 81(4): 715-24. 4-Methylaminorex is a potential psychostimulant drug of abuse that exists as four stereoisomers: cis-4R,5S, cis-4S,5R, trans-4S,5S, and trans-4R,5R. The racemic mixture of the cis-isomers has been encountered in illicit samples, but previous animal studies suggest that also the trans-isomers could have similar stimulant-like properties. We tested whether the stereoisomers possess rewarding properties and compared their potency using the conditioned place preference method in rats. Furthermore, the involvement of the brain dopaminergic system in the 4-methylaminorex reward was tested with the dopamine D1- and D2-receptor antagonists SCH 23390 and raclopride administered systemically, or with the neurotoxin 6-hydroxydopamine injected into the nucleus accumbens. All the four isomers induced place preference, with no apparent differences in their potency. SCH 23990 and raclopride attenuated 4-methylaminorex-induced increase in place preference, and 6-hydroxydopamine also tended to be efficacious. These findings indicate that all the four stereoisomers of 4-methylaminorex possess rewarding properties and thus abuse potential; the trans-isomers are at least as potent as the cis-isomers. Furthermore, the brain dopaminergic system appears to be involved in the 4-methylaminorex-reward. Childhood growth and future development of psychotic disorder among Helsinki high-risk children Niemi, L. T., Suvisaari, J. M., Haukka, J. K. and Lönnqvist, J. K. Schizophr Res. 2005; 76(1): 105-12. BACKGROUND: The Helsinki High-Risk (HR) Study is a follow-up study of offspring (born between 1960 and 1964) of all females treated for schizophrenia spectrum disorders in mental hospitals in Helsinki before 1975, and controls. AIM: To compare childhood growth among HR and control children, and to determine if any patterns in childhood growth predict later development of psychotic disorders within the HR group. METHODS: We accessed growth information from childhood health cards, which we obtained for 114 HR and 53 control offspring. The growth of HR children was compared with that of control children. Within the HR group, we investigated whether any association existed between childhood growth patterns and morbidity from psychotic disorders using logistic regression models. RESULTS: The HR girls were shorter than controls at birth (p=0.030), but this disparity vanished by age 7. In contrast, HR boys were only slightly shorter at birth than controls, but the height difference increased with age, being statistically significant at 10 years (p=0.020). Among HR children, the combination of being in the lowest tertile for ponderal index at birth but in the highest tertile for BMI at 7 years predicted later development of schizophrenia (OR 22.8, 95% CI 2.0, >100, p=0.040). CONCLUSIONS: Catch-up growth increases the risk of schizophrenia among offspring of mothers with psychotic disorder. Whether this is an independent risk factor or merely a reflection of some other risk factors needs further research. Pajari, P. M., Jallinoja, P. and Absetz, P. Soc Sci Med. 2005. This study analyses arguments for and against the notion of healthy lifestyles, and the construction of responsibility for health, in group discussions in Finland. With data from four focus groups, we identified five interpretative repertoires: a strong activity repertoire reflects the dominant cultural value of health and emphasizes self-control. Three other repertoires-illness, external barriers, and weak character-share the underlying values of the activity repertoire, but exemplify situations where the individual lacks control, seeking to justify deviations from the norm of activity. One counter-repertoire, the pleasure repertoire, questions the hegemonic value of health, and discusses other competing values. The discussion of health is an ongoing dialectical process drawing from the different repertoires. In order to avoid stigmatization and to save face in the social situation of a focus group, the subjects strive to balance their accounts of behaviours considered unhealthy by also claiming healthy behaviours. They also strike a balance between extreme rigidity and carelessness, emphasizing the ideal of moderation and harmony. The findings point to a need to consider variations in and underpinnings of a "good life" at the individual level. Encouraging people to specify the meaning and content of moderation in their personal lives could provide a new perspective for health education and health promotion. Pajunen, P., Koukkunen, H., Ketonen, M., Jerkkola, T., Immonen-Räihä, P., Karja-Koskenkari, P., Kuulasmaa, K., Palomäki, P., Mustonen, J., Lehtonen, A., Arstila, M., Vuorenmaa, T., Lehto, S., Miettinen, H., Torppa, J., Tuomilehto, J., Kesäniemi, Y. A., Pyörälä, K. and Salomaa, V. Diabetologia. 2005; 48(12): 2519-2524. Aims/hypothesis: We compared the risk of acute coronary events in diabetic and non-diabetic persons with and without prior myocardial infarction (MI), stratified by age and sex. Methods: A Finnish MI-register study known as FINAMI recorded incident MIs and coronary deaths (n=6988) among people aged 45 to 74 years in four areas of Finland between 1993 and 2002. The population-based FINRISK surveys were used to estimate the numbers of persons with prior diabetes and prior MI in the population. Results: Persons with diabetes but no prior MI and persons with prior MI but no diabetes had a markedly greater risk of a coronary event than persons without diabetes and without prior MI. The rate of recurrent MI among non-diabetic men with prior MI was higher than the incidence of first MI among diabetic men aged 45 to 54 years. The rate ratio was 2.14 (95% CI 1.40-3.27) among men aged 50. Among elderly men, diabetes conferred a higher risk than prior MI. Diabetic women had a similar risk of suffering a first MI as non-diabetic women with a prior MI had for suffering a recurrent MI. Conclusions/interpretation: Both persons with diabetes but no prior MI, and persons with a prior MI but no diabetes are high-risk individuals. Among men, a prior MI conferred a higher risk of a coronary event than diabetes in the 45-54 year age group, but the situation was reversed in the elderly. Among diabetic women, the risk of suffering a first MI was similar to the risk that non-diabetic women with prior MI had of suffering a recurrent MI. Dietary fiber intake and risk of colorectal cancer - A pooled analysis of prospective cohort studies Park, Y., Hunter, D. J., Spiegelman, D., Bergkvist, L., Berrino, F., van den Brandt, P. A., Buring, J. E., Colditz, G. A., Freudenheim, J. L., Fuchs, C. S., Giovannucci, E., Goldbohm, R. A., Graham, S., Harnack, L., Hartman, A. M., Jacobs, D. R., Kato, I., Krogh, V., Leitzmann, M. F., McCullough, M. L., Miller, A. B., Pietinen, P., Rohan, T. E., Schatzkin, A., Willett, W. C., Wolk, A., Zeleniuch-Jacquotte, A., Zhang, S. M. M. and Smith-Warner, S. A. Jama-Journal of the American Medical Association. 2005; 294(22): 2849-2857. Context Inconsistent findings from observational studies have continued the controversy over the effects of dietary fiber on colorectal cancer. Objective To evaluate the association between dietary fiber intake and risk of colorectal cancer. Design, Setting, and Participants From 13 prospective cohort studies included in the Pooling Project of Prospective Studies of Diet and Cancer, 725 628 men and women were followed up for 6 to 20 years across studies. Study- and sex-specific relative risks (RRs) were estimated with the Cox proportional hazards model and were subsequently pooled using a random-effects model. Main Outcome Measure Incident colorectal cancer. Results During 6 to 20 years of follow-up across studies, 8081 colorectal cancer cases were identified. For comparison of the highest vs lowest study- and sex-specific quintile of dietary fiber intake, a significant inverse association was found in the age-adjusted model (pooled RR=0.84; 95% confidence interval [CI], 0.77-0.92). However, the association was attenuated and no longer statistically significant after adjusting for other risk factors (pooled multivariate RR=0.94; 95% Cl, 0.86-1.03). In categorical analyses compared with dietary fiber intake of 10 to <15 g/d, the pooled multivariate RR was 1.18 (95% Cl, 1.05-1.31) for less than 10 g/d (11% of the overall study population); and RR, 1.00 (95% Cl, 0.85-1.17) for 30 or more g/d. Fiber intake from cereals, fruits, and vegetables was not associated with risk of colorectal cancer. The pooled multivariate RRs comparing the highest vs lowest study- and sex-specific quintile of dietary fiber intake were 1.00 (95% Cl, 0.90-1.11) for colon cancer and 0.85 (95% Cl, 0.72-1.01) for rectal cancer (P for common effects by tumor site=.07). Conclusions In this large pooled analysis, dietary fiber intake was inversely associated with risk of colorectal cancer in age-adjusted analyses. However, after accounting for other dietary risk factors, high dietary fiber intake was not associated with a reduced risk of colorectal cancer. Turnip rape and oilseed rape are new potential food allergens in children with atopic dermatitis Poikonen, S., Puumalainen, T. J., Kautiainen, H., Burri, P., Palosuo, T., Reunala, T. and Turjanmaa, K. Allergy. 2006; 61(1): 124-127. Background: When skin prick testing (SPT) young children with atopic dermatitis (AD) for suspected food allergy, we frequently found positive reactions with turnip rape (Brassica rapa) and oilseed rape (Brassica napus). We performed food challenge to examine whether these children react clinically to turnip rape. Methods: A total of 1887 children were screened with SPTs for sensitization to turnip rape and oilseed rape. Twenty-eight children with clearly positive SPT (>= 5 mm) were first subjected to labial challenge with turnip rape seeds followed, if negative, by open oral challenge for up to 7 days. Twenty-five children with AD but negative SPT to turnip rape and oilseed rape served as controls. Results: Two-hundred and six (10.9%) children had positive SPT to turnip rape and/or oilseed rape. Twenty-five (89%) of 28 children showed a positive challenge reaction to turnip rape. Seventeen reacted with labial whealing, and eight in oral challenge with facial urticaria, flare-up of AD or abdominal symptoms. All 25 control children remained negative in the labial challenge. Conclusions: Turnip rape and oilseed rape seem to be new important food allergens in young children with AD. The modes of exposure to these allergens and the possible routes of sensitization remain to be established. Change in IFN-gamma-producing capacity in early life and exposure to environmental microbes Roponen, M., Hyvarinen, A., Hirvonen, M. R., Keski-Nisula, L. and Pekkanen, J. J Allergy Clin Immunol. 2005; 116(5): 1048-52. BACKGROUND: Exposure to environmental microbes in early life might lead to type 1-skewed T cell responses and therefore reduce the risk of allergic diseases. OBJECTIVE: To investigate whether the cytokine responses at birth and at age 3 months are associated with environmental factors, especially exposure to microbes. Living in a farm, level of house dust endotoxin, cleanliness of the home, and presence of cats and dogs in the household were studied as possible determinants of cytokine production. METHODS: Twelve farmers' and 17 nonfarmers' children were studied. Production of IL-4, IL-6, TNF-alpha, and IFN-gamma in cord blood and in peripheral blood at 3 months was measured after 8-hour and 24-hour stimulation with phorbol ester plus concanavalin A. RESULTS: IFN-gamma responses at age 3 months were associated with farming (median, 53 vs 17 pg/mL; P = .019) and cats and dogs (49 vs 14 pg/mL; P = .014) (8 hours). Change in IFN-gamma-producing capacity from birth to 3 months was larger in children with higher than median endotoxin concentration in bed dust (P = .038) and in children with a cat or dog (P = .005) (8 hours). Increased IL-6 responses at birth were associated with cat or dog exposure (P = .004; 8 hours) and endotoxin level in settled dust (P = .039; 24 hours). CONCLUSION: The development of IFN-gamma-producing capacity during the first 3 months of life is associated with farming, endotoxin in house dust, and cat and dog exposure. These environmental characteristics may indicate some microbial exposure capable of driving developing immune system toward T(H)1 responses. Economic evaluation of pneumococcal conjugate vaccination in Finland Salo, H., Sintonen, H., Nuorti, J. P., Linna, M., Nohynek, H., Verho, J. and Kilpi, T. Scandinavian Journal of Infectious Diseases. 2005; 37(11-12): 821-832. The aim of this study was to evaluate cost-effectiveness of pneumococcal conjugate vaccine (PCV7) in children <5 y of age. A Markov simulation model was used to compare the cost-effectiveness of 4 doses (assumed E50.5 per dose) of PCV7 with no intervention. Only direct effects of the vaccine were taken into account. In Finland, vaccination of a birth cohort of 57,500 healthy infants would potentially prevent annually 60 cases of invasive PD, 1,400 cases of pneumococcal pneumonia, 15,000 episodes of acute otitis media, 3,000 otological surgery procedures and 0.9 deaths in children aged <5 y. Investing E12.0 million to vaccinate a birth cohort would save annually E6.3 million in medical, and E2.0 million in productivity and other, costs. Therefore, investing E1 in a vaccination programme would return E0.53 in medical costs and E0.70 in societal costs. In the base case, vaccination would cost society E134,986 per life y gained. To achieve cost savings from a health care provider (societal) perspective, without considering herd effects or replacement phenomenon, the price of PCV7 should be 50% (70%) of the price used in the base case. Salomaa, V., Ketonen, M., Koukkunen, H. and Kesaniemi, Y. A. Circulation. 2005; 112(17): U856-U856. Meeting abstract. A male-specific quantitative trait locus on 1p21 controlling human stature Sammalisto, S., Hiekkalinna, T., Suviolahti, E., Sood, K., Metzidis, A., Pajukanta, P., Lilja, H. E., Soro-Paavonen, A., Taskinen, M. R., Tuomi, T., Almgren, P., Orho-Melander, M., Groop, L., Peltonen, L. and Perola, M. Journal of Medical Genetics. 2005; 42(12): 932-939. Background: Many genome-wide scans aimed at complex traits have been statistically underpowered due to small sample size. Combining data from several genome-wide screens with comparable quantitative phenotype data should improve statistical power for the localisation of genomic regions contributing to these traits. Objective: To perform a genome-wide screen for loci affecting adult stature by combined analysis of four previously performed genome-wide scans. Methods: We developed a web based computer tool, Cartographer, for combining genetic marker maps which positions genetic markers accurately using the July 2003 release of the human genome sequence and the deCODE genetic map. Using Cartographer, we combined the primary genotype data from four genome-wide scans and performed variance components (VC) linkage analyses for human stature on the pooled dataset of 1417 individuals from 277 families and performed VC analyses for males and females separately. Results: We found significant linkage to stature on 1p21 (multipoint LOD score 4.25) and suggestive linkages on 9p24 and 18q21 (multipoint LOD scores 2.57 and 2.39, respectively) in males-only analyses. We also found suggestive linkage to 4q35 and 22q13 (multipoint LOD scores 2.18 and 2.85, respectively) when we analysed both females and males and to 13q12 (multipoint LOD score 2.66) in females-only analyses. Conclusions: We strengthened the evidence for linkage to previously reported quantitative trait loci (QTL) for stature and also found significant evidence of a novel male-specific QTL on 1p21. Further investigation of several interesting candidate genes in this region will help towards characterisation of this first sex-specific locus affecting human stature. Seldin, M. F., Shigeta, R., Laiho, K., Li, H., Saila, H., Savolainen, A., Leirisalo-Repo, M., Aho, K., Tuomilehto-Wolf, E., Kaarela, K., Kauppi, M., Alexander, H. C., Begovich, A. B. and Tuomilehto, J. Genes and Immunity. 2005; 6(8): 720-722. Several studies have identified the PTPN22 allelic variant 1858 C/T that encodes the R620W amino-acid change as a putative susceptibility factor in autoimmune diseases. The current study was undertaken to examine a large cohort of Finnish rheumatoid arthritis ( RA) and juvenile idiopathic arthritis (JIA) subjects using both population control and, importantly, family-based association methods. The latter is particularly important when, as is the case for the 1858 C/ T polymorphism, the frequency of the variant allele ( T) differs in both major ancestral populations and in subpopulations. The analysis of rheumatoid factor-positive 1030 RA probands from Finland provides strong support for association of this variant in both population studies ( allele specific odds ratio (OR) = 1.47, 95% confidence interval (CI) = 1.27 - 1.70, P = 3 x 10(-7)) and in family studies (P<10(-6)). In contrast, no allelic association was seen with JIA ( 230 probands) and only weak evidence for a genotypic effect of 1858T homozygotes was observed in this population. Insulin, glucose, insulin resistance, and pancreatic cancer in male smokers Stolzenberg-Solomon, R. Z., Graubard, B. I., Chari, S., Limburg, P., Taylor, P. R., Virtamo, J. and Albanes, D. Jama-Journal of the American Medical Association. 2005; 294(22): 2872-2878. Context Obesity, diabetes mellitus, and glucose intolerance have been associated with increased pancreatic cancer risk; however, prediagnostic serum insulin concentration has not been evaluated as a predictor of this malignancy. Objective To investigate whether prediagnostic fasting glucose and insulin concentrations and insulin resistance are associated with subsequent incidence of exocrine pancreatic cancer in a cohort of male smokers. Design, Setting, and Participants A case-cohort prospective study within,the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (1985-1988) cohort of 29 133 male Finnish smokers ages 50 to 69 years. The study included 400 randomly sampled subcohort control participants and 169 incident pancreatic cancer cases that occurred after the fifth year of follow-up. All participants were followed up through December 2001 (up to 16.7 years of follow-up). Main Outcome Measures Incident exocrine pancreatic cancer identified from the Finnish Cancer Registry. Results After adjusting forage, smoking, and body mass index, higher baseline fasting serum concentrations of glucose, insulin, and insulin resistance were positively associated with pancreatic cancer. The presence of biochemically defined diabetes mellitus (glucose, >= 126 mg/dL [>= 6.99 mmo/L]) and insulin concentration in the highest vs lowest quartile both showed a significant 2-fold increased risk (hazard ratio [HRI], 2.13; 95% confidence interval [CI], 1.04-4.35; and HR, 2.01; 95% Cl, 1.03-3.93; respectively). There were significant interactions for all the biomarker exposures by follow-up time, such that the positive associations were stronger among the cases that occurred more than 10 years after baseline (highest vs lowest quartile: glucose, HR, 2.16; 95% Cl, 1.05-4.42; P for trend=.02; insulin, HR, 2.90; 95% Cl, 1.22-6.92; P for trend=.005; and insulin resistance, HR, 2.71; 95% Cl, 1.19-6.18; P for trend =.006). Conclusions These results support the hypothesis that exposure to higher insulin concentrations and insulin resistance predicts the risk of exocrine pancreatic cancer. Cross-Species Analyses Implicate Lipin 1 Involvement in Human Glucose Metabolism Suviolahti, E., Reue, K., Cantor, R. M., Phan, J., Gentile, M., Naukkarinen, J., Soro-Paavonen, A., Oksanen, L., Kaprio, J., Rissanen, A., Salomaa, V., Kontula, K., Taskinen, M. R., Pajukanta, P. and Peltonen, L. Hum Mol Genet. 2005. Recent studies in the mouse have demonstrated that variations in lipin expression levels in adipose tissue have marked effects on adipose tissue mass and insulin sensitivity. In the mouse, lipin deficiency prevents normal adipose tissue development, resulting in lipodystrophy and insulin resistance, whereas excess lipin levels promote fat accumulation and insulin sensitivity. Here we investigated the effects of genetic variation in lipin levels on glucose homeostasis across species by analyzing lipin transcript levels in human and mouse adipose tissue. A strong negative correlation was observed between lipin mRNA levels and fasting glucose and insulin levels, as well as an indicator of insulin resistance (HOMA-IR), in both mice and humans. We subsequently analyzed the allelic diversity of the LPIN1 gene in dyslipidemic Finnish families, as well as in a case-control sample of obese (n = 477) and lean (n = 821) individuals. Alleles were defined by genotyping seven single nucleotide polymorphisms (SNPs) of the critical DNA region over the LPIN1 gene. Intragenic SNPs and corresponding allelic haplotypes exhibited associations with serum insulin levels and body mass index (BMI) (p = 0.002-0.04). Both the expression levels in adipose tissue across species and genetic data in human study samples highlight the importance of lipin in glucose homeostasis and imply that allelic variants of this gene have significance in human metabolic traits. Törmäkangas, L., Erkkilä, L., Korhonen, T., Tiirola, T., Bloigu, A., Saikku, P. and Leinonen, M. Infect Immun. 2005; 73(10): 6458-66. Chlamydia pneumoniae is a common respiratory tract pathogen, and persistent infections have been associated with atherosclerosis. We studied the effects of repeated chlamydial inoculations on the inflammatory response and on aortic lipid accumulation in C57BL/6J mice. Mice fed a diet supplemented with 0.2% cholesterol were infected three or six times with C. pneumoniae every fourth week. Sera and lungs were analyzed for inflammatory responses, lung tissues were tested for the presence of C. pneumoniae DNA and RNA, and intimal lipid accumulation in the aortic sinus was quantified. High levels of chlamydial heat shock protein 60 (Hsp60) immunoglobulin G2c subclass antibodies were detected in all of the infected mice, and a positive and statistically significant correlation was found between these antibodies and autoantibodies against mouse Hsp60. Both Hsp60 antibody levels correlated with the severity of lung tissue inflammation. The cholesterol supplement in the diet had no effect on serum cholesterol levels. Significantly larger intimal lipid lesions were seen in the mouse group infected six times (6,542 mum(2)) than in the control group (1,376 mum(2); P = 0.034). In conclusion, repeated inoculations increased aortic sinus lipid accumulation in normocholesterolemic mice. The correlation between the antibodies to mouse and chlamydial Hsp60 proteins and their association with lung inflammation further support the theory of the development of an autoimmune response against heat shock proteins after repeated chlamydial infections. Törmäkangas, L., Vuorela, P., Saario, E., Leinonen, M., Saikku, P. and Vuorela, H. Biochem Pharmacol. 2005; 70(8): 1222-30. Increasing evidence suggests that plant polyphenolic compounds may protect from cardiovascular diseases, which have been addressed to their antioxidative properties. In addition, these compounds have been shown to possess anti-inflammatory and anti-microbial potential. In the present study we tested the effects of two flavonoid compounds, quercetin and luteolin, and one alkyl gallate, octyl gallate, on the course of acute Chlamydia pneumoniae infection in vivo. C57BL/6J mice were treated with quercetin, luteolin or octyl gallate for 3 days prior to and 10 days after C. pneumoniae inoculation. Lung tissue was analysed for the presence of chlamydia by culture and quantitative PCR, and inflammatory responses were assessed. Luteolin was found histologically to suppress inflammation in lung tissue, the development of C. pneumoniae-specific antibodies and the presence of chlamydia in lung tissue. Octyl gallate had no significant effect on the course of infection, but quercetin increased both the inflammatory responses and the chlamydial load in the lungs. The infection and inflammation-enhancing effects of quercetin treatment may be attributable to the dose and the route of administration and should be reassessed in further studies with lower doses or with different metabolites of the compound. Contrariwise, the effects of luteolin treatment suggest this compound to have potential in decreasing the infection load and inflammatory reactions in vivo. Monogenic autoimmune diseases - lessons of self-tolerance Ulmanen, I., Halonen, M., Ilmarinen, T. and Peltonen, L. Curr Opin Immunol. 2005; 17(6): 609-15. The molecular defects recently identified in the rare monogenic autoimmune diseases (AIDs) have pinpointed critical steps in the pathways that contribute to the development of normal immune responses and self-tolerance. Recent studies of autoimmune polyendocrinopathy syndrome type 1, autoimmune lymphoproliferative syndrome, immunodysregulation, polyendocrinopathy and enteropathy, X-linked, IL-2 receptor alpha-chain deficiency, and, in particular, their corresponding mouse models, have revealed the details of the molecular mechanisms of normal immune tolerance, and exposed how defects in these mechanisms result in human autoimmunity. In addition to a deeper understanding of the immune system, detailed molecular characterization of monogenic AIDs will help us to understand the mechanisms behind common polygenic AIDs and, furthermore, to develop novel therapies and intervention strategies to treat them. Suicidal ideation and attempts in bipolar I and II disorders Valtonen, H., Suominen, K., Mantere, O., Leppämäki, S., Arvilommi, P. and Isometsä, E. I. Journal of Clinical Psychiatry. 2005; 66(11): 1456-1462. Objective: Few studies have investigated the prevalence of and risk factors for suicidal ideation and attempts among representative samples of psychiatric patients with bipolar I and II disorders. Method: In the Jorvi Bipolar Study (JoBS), psychiatric inpatients and outpatients were screened for bipolar disorders with the Mood Disorder Questionnaire from January 1, 2002, to February 28, 2003. According to Structured Clinical Interviews for DSM-IV Axis I and II Disorders, 191 patients were diagnosed with bipolar disorders (bipolar I, N = 90; bipolar II, N = 101). Suicidal ideation was measured using the Scale for Suicidal Ideation. Prevalence of and risk factors for ideation and attempts were investigated. Results: During the current episode, 39 (20%) of the patients had attempted suicide and 116 (61%) had suicidal ideation; all attempters also reported ideation. During their lifetime, 80% of patients (N = 152) had had suicidal behavior and 51% (N = 98) had attempted suicide. In nominal regression models, severity of depressive episode and hopelessness were independent risk factors for suicidal ideation, and hopelessness, comorbid personality disorder, and previous suicide attempt were independent risk factors for suicide attempts. There were no differences in prevalence of suicidal behavior between bipolar I and II disorder; the risk factors were overlapping but not identical. Conclusion: Over their lifetime, the vast majority (80%) of psychiatric patients with bipolar disorders have either suicidal ideation or ideation plus suicide attempts. Depression and hopelessness, comorbidity, and preceding suicidal behavior are key indicators of risk. The prevalence of suicidal behavior in bipolar I and II disorders is similar, but the risk factors for it may differ somewhat between the two. Wuorimaa, T. K., Dagan, R., Bailleux, F., Haikala, R., Ekström, N., Eskola, J., Yaich, M. and Käyhty, H. Vaccine. 2005; 23(46-47): 5328-5332. Finnish and Israeli infants received an 11-valent mixed carrier pneumococcal conjugate vaccine (11PCV) with or without aluminum adjuvant at the age of 2, 4, 6, and 12 months. We measured opsonophagocytic activity (OPA) of antibodies to pneumococcal strains of serotypes 4, 613, 14, 19F, and 23F. At 7 months, OPA was clearly detected for all the serotypes. At 13 months, OPAs increased further and the proportion of individuals with a positive OPA ranged between 81 and 100%. The adjuvant improved functional activity of antibodies to serotype 613 pneumococci. In conclusion, immunization of infants with the 11PCV induced functionally active antibodies. (c) 2005 Elsevier Ltd. All rights reserved. |