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New articles - Uudet artikkelit 6.7.2009 - ISI Web of Knowledge & PubMed Search Alert
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AUDIT and its abbreviated versions in detecting heavy and binge drinking in a general population survey
Aalto, M., Alho, H., Halme, J. T. and Seppä, K. Drug and Alcohol Dependence. 2009; 103(1-2): 25-29. Article. IF 3.371 Background: The aim of this study was to define optimal cut points for the Alcohol Use Disorders Identification Test (AUDIT) and its abbreviated versions (AUDIT-C, AUDIT-QF, and AUDIT-3), and to evaluate how effectively these questionnaires detect heavy drinking in the general population. Methods: The study population consisted of a sub-sample of the National FINRISK Study. A stratified random sample of 3216 Finns, aged 25-64, was invited to a health check. Of these, 1851 (57.6%) completed the AUDIT and participated in person in the Timeline Followback (TLFB) interview regarding their alcohol consumption. The TLFB-based definition of heavy drinking was used as a primary gold standard (for males >= 16 standard drinks average in a week or >= 7 drinks at least once a month; for females, respectively, >= 10 and >= 5 drinks). Areas under receiving operating characteristics curves (AUROCs), sensitivities and specificities were used to compare the performance of the tests. Results and conclusions: The AUDIT and its abbreviated versions are valid for detecting heavy drinking also in a general population sample. However, performance seems to vary between the different versions and accuracy of each test is achieved only by using tailored cut points according to gender. The AUDIT and AUDIT-C are effective for both males and females. The optimal cut points for males were found to be >= 7 or 8 for AUDIT and >= 6 for AUDIT-C. Among females the optimal cut points were found to be >= 5 for AUDIT and >= 4 for AUDIT-C. The Study also indicates that AUDIT-QF among females and AUDIT-3 among males are relatively effective. The cut points for detecting all heavy drinkers (including binge drinkers without exceeding weekly thresholds) were lower than for detecting heavy drinkers excluding those who are only binge drinkers. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Global safety of vaccines: strengthening systems for monitoring, management and the role of GACVS Autran, B., Asturias, E. J., Evans, S., Harrigan-Go, K., Hussey, G., John, T. J., Lambert, P. H., Law, B., Midthun, K., Nohynek, H., Salmaso, S., Smith, P. G., Zuber, P. L. F., Bentsi-Enchill, A., Caric, A., Pfeifer, D., Duclos, P. and Wood, D. Expert Review of Vaccines. 2009; 8(6): 705-716. Article. IF 2.979 Vaccines have contributed enormously in reducing the impact of many infectious diseases, and the expanded use of new and existing vaccines provides unprecedented potential for further reducing the global burden of infectious diseases. Yet, as with the deployment of other technologies, their use may also sometimes be associated with undesirable effects that need to be identified rapidly, understood and minimized. In this article, we review the models and systems that have been developed to monitor and respond to concerns regarding vaccine safety and we give illustrative examples of real or perceived vaccine safety issues. The Global Advisory Committee on Vaccine Safety (GACVS) was set up 10 years ago and charged to provide the WHO with independent advice on vaccine safety issues. The role of the GACVS is both to analyze and to interpret reports of the adverse effects of vaccines that impact on global vaccination programs and strategies, and to foster the development of improved surveillance systems to detect any adverse effects of vaccines, particularly in low- and middle-income countries. It also monitors the development of new vaccines during clinical testing and advises on the safe use of vaccines in immunization programs. As success is achieved with reducing the burden of vaccine-preventable diseases, there will be increasing attention focused on potential adverse effects, on the development of effective surveillance systems to detect adverse effects, and on improved methods to manage and control any harmful consequences of vaccination. Bauer, A. M., Hoti, F., von Korff, M., Pillen, K., Leon, J. and Sillanpää, M. Theoretical and Applied Genetics. 2009; 119(1): 105-123. Article. IF 3.490 A common difficulty in mapping quantitative trait loci (QTLs) is that QTL effects may show environment specificity and thus differ across environments. Furthermore, quantitative traits are likely to be influenced by multiple QTLs or genes having different effect sizes. There is currently a need for efficient mapping strategies to account for both multiple QTLs and marker-by-environment interactions. Thus, the objective of our study was to develop a Bayesian multi-locus multi-environmental method of QTL analysis. This strategy is compared to (1) Bayesian multi-locus mapping, where each environment is analysed separately, (2) Restricted Maximum Likelihood (REML) single-locus method using a mixed hierarchical model, and (3) REML forward selection applying a mixed hierarchical model. For this study, we used data on multi-environmental field trials of 301 BC2DH lines derived from a cross between the spring barley elite cultivar Scarlett and the wild donor ISR42-8 from Israel. The lines were genotyped by 98 SSR markers and measured for the agronomic traits "ears per mA(2)," "days until heading," "plant height," "thousand grain weight," and "grain yield". Additionally, a simulation study was performed to verify the QTL results obtained in the spring barley population. In general, the results of Bayesian QTL mapping are in accordance with REML methods. In this study, Bayesian multi-locus multi-environmental analysis is a valuable method that is particularly suitable if lines are cultivated in multi-environmental field trials. Blomqvist, S., Savolainen-Kopra, C., Paananen, A., Hovi, T. and Roivainen, M. J Gen Virol. 2009; 90(Pt 6): 1371-81. IF 3.092 Human rhinoviruses (HRVs), which are the most frequent causative agents of acute upper respiratory tract infections, are abundant worldwide. We have identified HRV strains in environmental specimens collected in Finland, Latvia and Slovakia during the surveillance of polio- and other enteroviruses. These acid-sensitive HRV strains were isolated under conditions optimized for growth of most of the enteroviruses, i.e. in stationary human rhabdomyosarcoma cells incubated at 36 degrees C. Phylogenetic analysis of the sequences derived from the partial 5' non-coding region and the capsid region coding for proteins VP4/VP2 and VP1 showed that the HRV field strains clustered together with prototype strains of the HRV minor receptor group. Partial sequences of the 3D polymerase coding region generally followed this pattern, with the exception of a set of three HRV field strains that formed a subcluster not close to any of the established HRV-A types, suggesting that recombination may have occurred during evolution of these HRV strains. Phylogenetic analysis of the VP4/VP2 capsid protein coding region showed that the 'environmental' HRV field strains were practically identical to HRV strains recently sequenced by others in Australia, the United States and Japan. Analysis of amino acids corresponding to the intercellular adhesion molecule-1 receptor footprint in major receptor group HRVs and also in the low-density lipoprotein receptor footprint of minor receptor group HRVs showed conservation of the 'minor receptor group-like' amino acids, indicating that the field strains may have maintained their minor receptor group specificity. Canoy, D., Pouta, A., Ruokonen, A., Hartikainen, A. L., Saikku, P. and Järvelin, M. R. Journal of Clinical Endocrinology & Metabolism. 2009; 94(6): 1916-1922. Article. IF 6.325 Context: Impaired fetal growth is associated with increased risk for coronary heart disease and diabetes in adulthood, but the underlying mechanism is unclear. Objective: The objective of the study was to examine the relation between early growth (weight at birth and first year) and adult total leukocyte count, the primary cell effectors of inflammation. Design: This was a birth cohort study (Northern Finland Birth Cohort 1966) with participants prospectively and longitudinally followed up from birth to age 31 yr. Setting: This was a general population-based cohort in Finland. Participants: A total of 5619 offspring of expectant mothers who attended a clinical examination and blood draw at 31-yr follow-up (4486 with complete data on weight at 1 yr) participated in the study. Main Exposure Variables: Weight at birth and at 1 year. Main Outcome Measure: Absolute leukocyte count was measured. Results: Total leukocyte count was lower at higher birth weight categories with or without adjustments for adult systolic blood pressure, total cholesterol, fasting insulin, body mass index, cigarette smoking, sex, gestational age, and other life course factors. The covariate-adjusted regression coefficient for log-transformed total leukocyte count (x 10(9) cells/liter) per 1 SD (525 g) increase in birth weight was -0.012(95% confidence interval -0.021 to -0.004). The association persisted, even when limiting our analyses among healthy and nonsmoking individuals, and the inversely linear relation was steepest among those with lower weight attained at 1 yr (P for interaction = 0.027). Conclusion: Poorer growth in early life was associated with systemic low-grade inflammation in adulthood. This relation suggests a plausible inflammatory mechanism linking early growth impairment with risk of coronary heart disease and diabetes later in life. (J Clin Endocrinol Metab 94: 1916-1922, 2009) Local and systemic oxidant/antioxidant status before and during lung cancer radiotherapy Crohns, M., Saarelainen, S., Kankaanranta, H., Moilanen, E., Alho, H. and Kellokumpu-Lehtinen, P. Free Radical Research. 2009; 43(7): 646-657. Article. IF 2.826 To examine local and systemic oxidative status of lung cancer (LC) and oxidant effects of radiotherapy (RT), this study evaluated antioxidants and markers of oxidative and nitrosative stress in bronchoalveolar lavage (BAL) fluid and in the blood of 36 LC patients and 36 non-cancer controls at baseline and during and after RT for LC. LC patients had higher baseline serum urate, plasma nitrite and lower serum oxidized proteins than controls (p=0.016, p0.001 and p=0.027, respectively), but BAL fluid oxidative stress markers were similar. RT tended to raise some antioxidants, however, significant increases were seen in serum urate, conjugated dienes and TBARS (p=0.044, p=0.034 and p=0.004, respectively) 3 months after RT. High urate at baseline may compensate against the oxidative stress caused by LC. RT shifts the oxidant/antioxidant balance towards lipid peroxidation, although the antioxidant defense mechanisms of the body appear to counteract the increased oxidative stress rather effectively. Grisoni, M. L., Proust, C., Alanne, M., DeSuremain, M., Salomaa, V., Kuulasmaa, K., Cambien, F., Nicaud, V., Wiklund, P. G., Virtamo, J., Kee, F., Tiret, L., Evans, A. and Tregouet, D. A. Bmc Medical Genetics. 2009; 10. Article. IF 2.762 Background: Interleukin-18 is a pro-inflammatory cytokine suspected to be associated with atherosclerosis and its complications. We had previously shown that one single nucleotide polymorphism (SNP) of the IL18 gene was associated with cardiovascular disease (CVD) through an interaction with smoking. As a further step for elucidating the contribution of the IL-18 pathway to the etiology of CVD, we here investigated the association between the genetic variability of two IL-18 receptor genes, IL18R1 and IL18RAP, with the risk of developing CVD. Methods: Eleven tagging SNPs, 5 in IL18R1 and 6 in IL18RAP, characterizing the haplotypic variability of the corresponding genes; were genotyped in 5 European prospective CVD cohorts including 1416 cases and 1772 non-cases, as part of the MORGAM project. Both single-locus and haplotypes analyses were carried out to investigate the association of these SNPs with CVD. Results: We did not find any significant differences in allele, genotype and haplotype frequencies between cases and non-cases for either of the two genes. Moreover, the search for interactions between SNPs located in different genes, including 5 IL18 SNPs previously studied in the MORGAM project, and between SNPs and environmental factors remained unfruitful. Conclusion: Our analysis suggests that the variability of IL18R1 and IL18RAP genes are unlikely to contribute to modulate the risk of CVD. Does the frequency of Prevotella intermedia increase during pregnancy? Gursoy, M., Haraldsson, G., Hyvönen, M., Sorsa, T., Pajukanta, R. and Könönen, E. Oral Microbiology and Immunology. 2009; 24(4): 299-303. Article. IF 2.015 Introduction: The former Bacteroides intermedius, currently including Prevotella intermedia and Prevotella nigrescens, has been associated with hormone-induced pregnancy gingivitis. The aim of the present longitudinal study was to determine whether only P. intermedia or P. nigrescens, or both species, are involved in the demonstrated microbial shift during pregnancy. Methods: Subgingival plaque and saliva samples, collected from 30 healthy pregnant women and 24 healthy non-pregnant women as their controls, were examined for the presence of pigmented gram-negative anaerobes. Altogether 2628 isolates were preliminarily identified as P. intermedia sensu lato, based on phenotypic testing. Their further identification was performed by using a 16S ribosomal DNA-based polymerase chain reaction (PCR). Results: A mean of 8.3 P. intermedia sensu lato isolates from each subject/sampling was examined. During the second trimester, the mean number of P. intermedia sensu lato in plaque increased along with increasing signs of pregnancy gingivitis, and then both decreased. After delivery, gingival inflammation still decreased while the number of P. intermedia sensu lato transiently increased both in plaque and saliva. In the present study, the vast majority of isolates (95.3%) proved to be P. nigrescens and 2.5% were P. intermedia. The remaining 2.2% of the isolates could not be identified with PCR as P. intermedia or P. nigrescens. The corresponding percentages in the control population were 94.2%, 5.5%, and 0.3%. Conclusion: In the oral cavity of relatively young women without periodontitis, P. nigrescens, unlike P. intermedia, is a frequent finding. Conceivably, pregnant women harbor increasing numbers of P. nigrescens associated with pregnancy gingivitis. Gursoy, U. K., Könönen, E. and Uitto, V. J. Oral Microbiology and Immunology. 2009; 24(4): 304-309. Article. IF 2.015 Introduction: The Prevotella intermedia group bacteria, namely P. intermedia, Prevotella nigrescens, and Prevotella pallens, are phylogenetically closely related and potentially connected with oral and gastrointestinal tract disease pathogenesis. The aim of the present study was to examine whether these species differ in their capabilities of adhesion to and invasion of epithelial cells. Methods: Adhesion and invasion were assayed by standard antibiotic/culture assays and fluorescent microscopy techniques. The effect of Prevotella strains on epithelial cell viability was measured using a commercial cell proliferation assay. Results: The strains P. intermedia ATCC 25611 and P. nigrescens ATCC 33263 adhered to epithelial cells, the adhesion numbers of P. intermedia being twice as high as those of P. nigrescens. These strains invaded epithelial cells but invasion was weak. The adhesion of P. intermedia was specifically targeted to epithelial cell lamellipodia. The number of adhered P. intermedia cells increased or decreased when the formation of lamellipodia was stimulated or inhibited, respectively. None of the tested strains showed toxic effects on epithelial cells; a clinical P. intermedia strain even increased the number of viable cells by about 20%. Conclusion: The results suggest that among the P. intermedia group bacteria, P. intermedia and P. nigrescens type strains can adhere to and invade epithelial cells, the capability of P. intermedia ATCC 25611(T)f being highest in this context. This strain proved to have a special affinity in binding to epithelial cell lamellipodia. Häkkinen, M., Nakari, U. M. and Siitonen, A. Appl Environ Microbiol. 2009. IF 3.801 A substantial sampling among domestic human campylobacter cases, chicken process lots, and cattle at slaughter was performed during the seasonal peak of human infections. Campylobacter jejuni isolates (n = 419) were subtyped using pulsed-field gel electrophoresis with SmaI, and isolates representing overlapping types (n = 212) were further subtyped using KpnI for restriction. SmaI/KpnI profiles of 55.4% (97/175) of the human isolates were indistinguishable from those of the chicken or cattle isolates. The overlapping SmaI/KpnI subtypes accounted for 69.8% (30/43) and 15.9% (32/201) of the chicken and cattle isolates, respectively. The occurrence of identical SmaI/KpnI subtypes with human C. jejuni isolates was significantly associated with animal host species (P < 0.001). A temporal association of isolates from chickens and patients was possible in 31.4% (55/175) of the human infections. Beside chickens as a source of C. jejuni in the sporadic infections, the role of cattle appears notable. New approaches to restrict the occurrence of campylobacters in other farm animals may be needed in addition to hygienic measures in chicken production. However, only about half the human infections were attributable to these sources. Hänninen, O. O., Salonen, R. O., Koistinen, K., Lanki, T., Barregard, L. and Jantunen, M. J Expo Sci Environ Epidemiol. 2009; 19(4): 414-22. IF 2.196 Long-range transported particulate matter (PM) air pollution episodes associated with wildfires in the Eastern Europe are relatively common in Southern and Southeastern Finland. In severe cases such as in August-September 2002, the reduced visibility and smell of the smoke, and symptoms such as irritation of eyes and airways experienced by the population raise the issue into the headlines. Because PM air pollution, in general, has been identified as a major health risk, and the exposures are of repeating nature, the issue warrants a risk assessment to estimate the magnitude of the problem. The current work uses the available air quality data in Finland to estimate population exposures caused by one of the worst episodes experienced in this decade. This episode originated from wildfires in Russia, Belarus, Ukraine, and the Baltic countries. The populations of 11 Southern Finnish provinces were exposed between 26 August and 8 September 2002, for 2 weeks to an additional population-weighted average PM(2.5) level of 15.7 microg/m(3). Assuming similar effect on mortality for these particles as observed in epidemiological time series studies on urban particles (0.5%-2% increase in mortality per 10 microg/m(3), central estimate 1%), this exposure level would be associated with 9-34 cases (17 cases central estimate) of additional mortality. Epidemiological evidence specific to particles from biomass combustion is scarce, affecting also the reliability of the current risk assessment. Do the wildfire aerosols exhibit the same level of toxicity as the urban particles? To shed light on this question, it is interesting to look at the exposure data in relationship to the observed daily mortality in Finland, even though the limited duration of the episode allows only for a weak statistical power. The percentage increases observed (0.8%-2.1% per 10 microg/m(3) of fine PM) are in line with the more general estimates for urban PM and those used in the current risk assessment. Ankle blood pressure as a predictor of total and cardiovascular mortality Hietanen, H., Paakkonen, R. and Salomaa, V. Bmc Cardiovascular Disorders. 2008; 8. Article. Background: The ankle blood pressure is commonly used as a ratio to the brachial blood pressure, called ankle-brachial index (ABI). Very few studies have considered the independent value of the ankle blood pressure without indexing it to the brachial blood pressure. We examined the value of ankle blood pressure, together with the exercise blood pressure, as a predictor of cardiovascular (CVD) and total mortality. Methods: A prospective follow-up study of 3,858 consecutive ambulatory patients ( mean age 51 years, 65,9% male) referred to a symptom-limited exercise test between August 1989 and December 1995. The cohort was followed up for all-cause and CVD mortality until December 31, 2004, by record linkage with the National Causes-of-Death Register. The independent value of ankle blood pressure as a predictor of cardiovascular and total mortality was assessed using Cox proportional hazards modelling. Results: The average follow-up time was 14 years, during which 346 persons died, 108 of them due to CVD. Persons with normal (<140 mmHg) resting brachial blood pressure, ankle blood pressure <175 mmHg and exercise blood pressure at moderate exercise level <= 215 mmHg at baseline investigation, had the best prognosis and were taken as the reference category. Among persons with elevated ankle blood pressure (>= 175 mmHg) but normal or borderline resting brachial pressure and normal exercise blood pressure (<= 215 mmHg) at moderate exercise level the multivariate-adjusted hazard ratios (HR, 95% confidence interval) for CVD and total mortality were 2.70 (1.52-4.80) and 2.13 (1.58-2.85), respectively. Similar and equally significant HRs were observed in persons with both elevated ankle blood pressure and elevated exercise blood pressure, as well as in those persons with elevated exercise blood pressure but ankle blood pressure < 175 mmHg. Conclusion: These results suggest that the ankle blood pressure has an independent value as a marker of arterial stiffness or subclinical atherosclerosis and a risk of future mortality in middle-aged, asymptomatic persons. Hu, G., Jousilahti, P., Tuomilehto, J., Antikainen, R., Sundvall, J. and Salomaa, V. Journal of Clinical Endocrinology & Metabolism. 2009; 94(6): 2099-2105. Article. IF 6.325 Objective: Our objective was to assess whether the association of serum C-reactive protein (CRP) with type 2 diabetes risk is modified by sex. Design and Subjects: We prospectively followed 12,861 Finnish men and women who were 35-74 yr of age, and free of diabetes, coronary heart disease, stroke, and cancer at baseline. Hazard ratios of type 2 diabetes were estimated for different levels of serum CRP. Results: During the follow-up, 208 men and 113 women developed diabetes. The multivariable-adjusted (age, physical activity, education, smoking, alcohol and coffee drinking, family history of diabetes, use of antihypertensive drugs, cholesterol-lowering agents, and hormone replacement therapy in women, systolic blood pressure, serum high-density lipoprotein cholesterol, serum triglycerides, and body mass index) hazard ratios of diabetes at three different levels of CRP (0.05-0.99, 1.0-2.99, and >= 3.0 mg/liter) based on the recommendation by Centers for Disease Control and the American Heart Association were 1.00, 1.46, and 1.85 (P for trend = 0.006) in men, and 1.00, 3.83, and 8.37 (P for trend <0.001) in women, respectively. CRP had a stronger association with diabetes risk in women than men (P for interaction: chi(2) = 6.42; 1 df; P < 0.025). This positive association between CRP and diabetes risk did not change when participants were stratified by age group, smoking status, level of obesity, alcohol drinking habit, or family history of diabetes. Conclusions: High baseline level of serum CRP was associated with an increased risk of diabetes among both men and women, but this association was stronger in women than men. (J Clin Endocrinol Metab 94: 2099-2105, 2009) Hu, G., Jousilahti, P., Tuomilehto, J., Antikainen, R., Sundvall, J. and Salomaa, V. J Clin Endocrinol Metab. 2009; 94(6): 2099-105. IF 6.325 OBJECTIVE: Our objective was to assess whether the association of serum C-reactive protein (CRP) with type 2 diabetes risk is modified by sex. DESIGN AND SUBJECTS: We prospectively followed 12,861 Finnish men and women who were 35-74 yr of age, and free of diabetes, coronary heart disease, stroke, and cancer at baseline. Hazard ratios of type 2 diabetes were estimated for different levels of serum CRP. RESULTS: During the follow-up, 208 men and 113 women developed diabetes. The multivariable-adjusted (age, physical activity, education, smoking, alcohol and coffee drinking, family history of diabetes, use of antihypertensive drugs, cholesterol-lowering agents, and hormone replacement therapy in women, systolic blood pressure, serum high-density lipoprotein cholesterol, serum triglycerides, and body mass index) hazard ratios of diabetes at three different levels of CRP (0.05-0.99, 1.0-2.99, and > or =3.0 mg/liter) based on the recommendation by Centers for Disease Control and the American Heart Association were 1.00, 1.46, and 1.85 (P for trend = 0.006) in men, and 1.00, 3.83, and 8.37 (P for trend <0.001) in women, respectively. CRP had a stronger association with diabetes risk in women than men (P for interaction: chi2 = 6.42; 1 df; P < 0.025). This positive association between CRP and diabetes risk did not change when participants were stratified by age group, smoking status, level of obesity, alcohol drinking habit, or family history of diabetes. CONCLUSIONS: High baseline level of serum CRP was associated with an increased risk of diabetes among both men and women, but this association was stronger in women than men. Hynynen, R., Suchanek, M., Spandl, J., Back, N., Thiele, C. and Olkkonen, V. M. Journal of Lipid Research. 2009; 50(7): 1305-1315. Article. IF 4.409 Oxysterol binding protein-related protein 2 (ORP2) is a member of the oxysterol binding protein family, previously shown to bind 25-hydroxycholesterol and implicated in cellular cholesterol metabolism. We show here that ORP2 also binds 22(R)-hydroxycholesterol [22(R)OHC], 7-ketocholesterol, and cholesterol, with 22(R) OHC being the highest affinity ligand of ORP2 (K-d 1.4 x 10(-8) M). We report the localization of ORP2 on cytoplasmic lipid droplets (LDs) and its function in neutral lipid metabolism using the human A431 cell line as a model. The ORP2 LD association depends on sterol binding: Treatment with 5 mu M 22(R) OHC inhibits the LD association, while a mutant defective in sterol binding is constitutively LD bound. Silencing of ORP2 using RNA interference slows down cellular triglyceride hydrolysis. Furthermore, ORP2 silencing increases the amount of [C-14] cholesteryl esters but only under conditions in which lipogenesis and LD formation are enhanced by treatment with oleic acid.glr The results identify ORP2 as a sterol receptor present on LD and provide evidence for its role in the regulation of neutral lipid metabolism, possibly as a factor that integrates the cellular metabolism of triglycerides with that of cholesterol.-Hynynen, R., M. Suchanek, J. Spandl, N. Back, C. Thiele, and V. M. Olkkonen. OSBP-related protein 2 is a sterol receptor on lipid droplets that regulates the metabolism of neutral lipids. J. Lipid Res. 2009. 50: 1305-1315. Järvelin, J., Rosenqvist, G., Häkkinen, U. and Sintonen, H. J Health Serv Res Policy. 2009; 14(3): 150-5. OBJECTIVES: To analyse the association between individual patients' risk factors and rates of claims and compensations for patient injuries in an insurance scheme in which proof of negligence is not required. And to explore whether either hospital productivity or volume of procedures is related to claims and compensation rates. METHODS: A two-step sequential logistic regression was applied on data collected from administrative registers. It included 17,834 patients who had undergone coronary artery bypass grafting at public hospitals in Finland between 1998 and 2002. The main outcome measure was the odds of claiming and receiving compensation. RESULTS: Men were less likely to claim compensation (odds ratio [OR] 0.66; 95% confidence interval 0.54-0.81), but among those having claimed were more likely to receive compensation (OR 2.08; 1.15-3.75) than women. Patients with a co-morbidity were more likely to claim (OR 1.29; 1.06-1.57), but among those having claimed were less likely to receive compensation (OR 0.52; 0.31-0.86) than those without a co-morbidity. Advanced age reduced the probability of claiming (OR 0.71; 0.52-0.96). CONCLUSIONS: Although high-risk patients file a claim more frequently than low-risk patients, the latter have a higher probability of getting their claims accepted and receiving compensation. This risk pattern is probably a reflection of compensation practices related to patient injuries involving an infection. Kaikkonen, R., Rahkonen, O., Lallukka, T. and Lahelma, E. Eur J Public Health. 2009. IF 2.176 BACKGROUND: Socio-economic health inequalities are well documented, but efforts to explain health inequalities are less. However, previous studies suggest that working conditions provide potential explanations for inequalities in health. METHODS: Cross-sectional questionnaire survey data, collected from municipal employees of the City of Helsinki, aged 40-60 years (n = 8960, response rate 67%) in 2000-02, were examined using binomial regression analysis. Socio-economic position was measured by six occupational social classes ranging from top managers to manual workers, and the outcome was self-rated health (SRH). Key physical and psychosocial working conditions and work arrangements were included as explanatory factors for inequalities in health. RESULTS: Occupational class inequalities in SRH were clear among women [prevalence ratio (PR) 1.89, 95% confidence interval (CI) 1.54-2.32] and men (PR 1.78, 95% CI 1.40-2.25). Heavy physical workload explained a half of the health inequalities among women and almost one-third among men. Physical and chemical exposures at work explained one-fifth of the health inequalities among women and a half among men. Job control explained 24% of the men's and 40% of women's inequalities, whereas job demands widened the inequalities by 13-14%. The effects of shift work and working hours were negligible. In the fully adjusted model, 60% of the women's and 32% of the men's inequalities in SRH were explained. CONCLUSION: Physical working conditions explained a large part and job control, a somewhat smaller part of socio-economic inequalities in SRH. Improving physical working conditions and increasing job control provide potential routes to reduced inequalities in health among employees. Bordetella pertussis strain variation and evolution postvaccination Kallonen, T. and He, Q. Expert Rev Vaccines. 2009; 8(7): 863-75. IF 2.979 Bordetella pertussis is a Gram-negative bacterium that causes pertussis or whooping cough in humans. The incidence of pertussis has increased in young infants, adolescents and adults in many countries where the vaccination against pertussis has been used extensively. Marked changes have been found in the B. pertussis population and differences have been observed between vaccine strains and circulating isolates. Moreover, clonal expansion of certain B. pertussis strains has been associated with the recent epidemics of pertussis in several European countries. In this review, we present data on strain variation and evolution of B. pertussis in different vaccinated populations and summarize the common methods for typing of B. pertussis and their relative discriminatory power. Visualizing covariates in proportional hazards model Karvanen, J. and Harrell, F. E. Statistics in Medicine. 2009; 28(14): 1957-1966. Article. IF 2.111 We present a graphical method called the rank-hazard plot that visualizes the relative importance of covariates in a proportional hazards model. The key idea is to rank the covariate values and plot the relative hazard as a function of ranks scaled to interval [0, 1]. The relative hazard is plotted with respect to the reference hazard, which can be, for example, the hazard related to the median of the covariate. Transformation to scaled ranks allows plotting of covariates measured in different units in the same graph, which helps in the interpretation of the epidemiological relevance of the covariates. Rank-hazard plots show the difference of hazards between the extremes of the covariate values present in the data and can be used as a tool to check if the proportional hazards assumption leads to reasonable estimates for individuals with extreme covariate values. Alternative covariate definitions or different transformations applied to covariates can be also compared using rank-hazard plots. We apply rank-hazard plots to the data from the FINRISK Study where population-based cohorts have been followed LIP for events of cardiovascular diseases and compare the relative importance of the covariates cholesterol, smoking, blood pressure and body mass index. The data from the Study to Understand Prognoses Preferences Outcomes and Risks of Treatment (SUPPORT) are used to visualize nonlinear covariate effects. The proposed graphics work in other regression models with different interpretations of the y-axis. Copyright (C) 2009 John Wiley & Sons, Ltd. Kauppi, M., Impivaara, O., Maki, J., Heliovaara, M., Marniemi, J., Montonen, J. and Jula, A. Bone. 2009; 45(1): 119-124. Article. IF 4.145 Calcaneal quantitative ultrasound (QUS) can predict bone strength and fracture risk. Bone fragility has no single cause but results from a complex interplay of several etiologic or contributing factors. Vitamin D is essential for bone health even though it is still unclear flow Much Of this vitamin is required to maintain bone strength and prevent fractures. Measurements of serum 25-hydroxyvitamin D[S-25(OH)D] have indicated a high prevalence of inadequate vitamin D status in a number Of Studies mostly based oil selected Study Populations. The objective of this study was to examine the associations between S-25(OH)D, common risk factors for bone fragility, and QUS variables in a large unselected Population Sample. The Study population consisted of 2736 men and 3299 women from a nationally representative Population sample, aged 30 years or over. Information oil lifestyle was elicited by means of interviews and questionnaires. Body fat mass was estimated using all impedance-meter. S-25(OH)D was measured by radioimmunoassay, Calcaneal QUS was performed oil the Hologic Sahara apparatus recording broadband ultrasound attenuation (BUA) and speed of sound (SOS). The potential determinants of BUA and SOS were analysed using separate multiple linear regression models for men and women. S-25(OH)D proved to be all independent determinant of BUA (P<0.0001 for men, P<0.001 for women) and SOS (P<0.0001 for men, P<0.05 for women). BUA was also independently associated with age, height, weight, alcohol Consumption, and postmenopausal status in women, and with weight, alcohol consumption, smoking and physical activity in men. All of the above variables, except for weight in women, were also found to be independent determinants of SOS in both men and women. A reverse association Was found between S-25(OH)D and adiposity in spite of higher intakes of vitamin D in those with higher fat mass. In this unselected sample of men and women, vitamin D status, several lifestyle factors and physical characteristics proved to be significant determinants of BUA and SOS. Inadequate vitamin D Status Was common, and measures ensuring adequate intakes of vitamin D in the Population thus deserve continued attention. Obesity should be taken into account ill future assessments of vitamin D status in Finland as in other countries. (C) 2009 Elsevier Inc. All rights reserved. Cardiac repolarization and striatal dopamine transporter function are interrelated Kauppila, E., Vanninen, E., Kuusela, T., Kaurijoki, S., Karhunen, L., Pietiläinen, K. H., Rissanen, A., Kaprio, J., Tiihonen, J. and Kuikka, J. Nucl Med Commun. 2009. IF 1.706 OBJECTIVE: In Parkinson's disease, striatal dopamine transporter (DAT) binding and cardiac sympathetic function are disturbed. In addition, heart rate (HR)-corrected cardiac repolarisation time (QTc interval), which is partly under autonomic control, is prolonged. Whether there is physiological coupling between striatal DAT binding and QTc time (QTc-DAT relation) is not known. The purpose of this study is to evaluate QTc-DAT relation in healthy young adults. METHODS: Thirty-five participants (18 women, age 26.4+/-1.8 years; mean+/-SD) were studied with iodine-123 labelled 2beta-carbomethoxy-3beta-(4-iodophenyl) nortropane single photon emission tomography. Signal-averaged ECG was recorded at rest from each participant. QTc interval was computed with Bazett's correction and with the approach by Karjalainen, getting QTc and QTk intervals, respectively. RESULTS: Mean striatal DAT binding, as (striatum-cerebellum)/cerebellum, was 2.63+/-0.31. Mean HR, QT, QTc and QTk intervals were 66+/-9 bpm, 340+/-25 ms, 354+/-18 ms and 351+/-16 ms, respectively. HR-QT correlation was -0.63, P value of less than 0.001. HR was not related to striatal DAT binding. QTc-DAT and QTk-DAT relations were significant, r = -0.50, P = 0.004 and r = -0.59, P = 0.0002, respectively. In linear regression model, striatal DAT binding explained 35% of the variance of QTk interval (95% confidence interval: -46.9 to -13.0, P = 0.0002). CONCLUSION: This study suggests significant physiological QTc-DAT relation in young healthy adults. QTc interval measurements might carry diagnostically important information in clinical conditions, which have an effect on both striatal DAT binding and cardiac sympathetic function. Keski-Nisula, L., Katila, M. L., Remes, S., Heinonen, S. and Pekkanen, J. J Allergy Clin Immunol. 2009; 123(6): 1305-11. IF 9.773 BACKGROUND: Microbial colonization of the airways and intestine during birth might have an effect on the risk of asthma and allergic diseases later in life. OBJECTIVE: We sought to evaluate the association between intrauterine microbial growth at the time of delivery and the development of asthma and allergic sensitization among offspring. METHODS: Intrauterine bacterial culture results were recorded at the time of cesarean delivery of 460 children who were born at Kuopio University Hospital during 1990-1992. When the children reached the age of 15 to 17 years, self-administered questionnaires were sent to the mothers, and 382 of the children were also examined by using skin prick tests. RESULTS: Intrauterine growth of potential pathogenic anaerobic bacteria and Streptococcus species at birth was associated with an increased risk of doctor-diagnosed asthma ever (odds ratio [OR], 4.51 [95% CI, 1.56-13.0]; OR, 2.53 [95% CI, 1.19-5.38]) and doctor-diagnosed current asthma (OR, 7.34 [95% CI, 2.44-22.03]; OR, 3.37 [95% CI, 1.46-7.76]) at the age of 15 to 17 years compared with the risk seen in subjects with negative microbial cultures. These findings remained significant also after applying the Bonferroni correction. No significant association after the Bonferroni correction was detected between intrauterine microbial growth and allergic sensitization among offspring. CONCLUSION: The results of this study indicated that specific intrauterine microbial growth at the time of birth might increase the risk of asthma among offspring through inflammatory mechanisms. These results indicate new potential targets for future studies on the effects of maternal vaginal microflora and intrauterine infection in the development of asthma among children. Knekt, P., Laaksonen, M. A., Raitasalo, R., Haaramo, P. and Lindfors, O. Eur Psychiatry. 2009. IF 2.433 OBJECTIVES: Lifestyle is less favourable among individuals suffering from psychiatric disorders. We studied whether psychotherapy brings along changes in lifestyle and whether these changes differ between short-term and long-term psychodynamic psychotherapy (SPP and LPP) and solution-focused therapy (SFT). METHODS: A total of 326 outpatients, 20-46 years of age, with mood or anxiety disorder were randomly assigned to LPP, SPP and SFT. The lifestyle variables considered were alcohol consumption, smoking, body mass index (BMI), leisure time exercise and serum cholesterol. The patients were monitored for three years from the start of treatment. RESULTS: During the three-year follow-up, BMI and serum cholesterol rose statistically significantly although no statistically significant trends were shown for alcohol consumption, smoking or exercise. SPP showed a disadvantage of increased alcohol consumption and serum cholesterol level when compared with LPP. SFT showed an advantage of reduced smoking in comparison with SPP. DISCUSSION: Small therapy-specific changes in lifestyle may be a result from psychotherapy treatment. These lifestyle changes are apparently more common in short-term therapy. More studies are needed to verify these findings. Mortality in diabetic patients undergoing non-cardiac surgery: a 7-year follow-up study Krolikowska, M., Kataja, M., Pöyhia, R., Drzewoski, J. and Hynynen, M. Acta Anaesthesiologica Scandinavica. 2009; 53(6): 749-758. Article. IF 1.953 The prognosis of diabetic patients after non-cardiac surgery remains controversial. This study was designed to compare the long-term mortality between diabetic and non-diabetic control patients undergoing non-cardiac surgery and to evaluate the possible risk factors. We investigated 274 consecutive diabetic patients and 282 non-diabetic control patients who underwent non-cardiac surgery within 1 year in a tertiary care hospital in Finland. The control group was matched for the same type of operations. Patients were followed for up to 7 years on average. The main outcome measure was mortality within 7 years. Mortality both in the short-term postoperatively (<= 21 days) and in the long-term (up to 87 1/2 months) was significantly higher in the diabetic patients compared with the non-diabetic group: 3.5 vs. 0% (P < 0.05) and 37.2 vs. 15% (P < 0.00001), respectively. The major causes of death among diabetic subjects were diseases of the cardiovascular system (56.8%) compared with non-diabetic patients (18.6%), P < 0.0001. We found that diabetes mellitus per se is not a risk factor for post-operative mortality but a combination of variables had a significant effect on both short- and long-term mortality. Diabetic patients undergoing non-cardiac surgery had a significantly higher incidence of short-term post-operative and long-term mortality compared with non-diabetic subjects. We propose a model of predictors of death among diabetic individuals undergoing non-cardiac surgery within a 7-year follow-up. The majority of deaths were associated with cardiovascular diseases. Lee, J. E., Mannisto, S., Spiegelman, D., Hunter, D. J., Bernstein, L., van den Brandt, P. A., Buring, J. E., Cho, E., English, D. R., Flood, A., Freudenheim, J. L., Giles, G. G., Giovannucci, E., Hakansson, N., Horn-Ross, P. L., Jacobs, E. J., Leitzmann, M. F., Marshall, J. R., McCullough, M. L., Miller, A. B., Rohan, T. E., Ross, J. A., Schatzkin, A., Schouten, L. J., Virtamo, J., Wolk, A., Zhang, S. M. and Smith-Warner, S. A. Cancer Epidemiology Biomarkers & Prevention. 2009; 18(6): 1730-1739. Article. IF 4.770 Fruit and vegetable consumption has been hypothesized to reduce the risk of renal cell cancer. We conducted a pooled analysis of 13 prospective studies, including 1,478 incident cases of renal cell cancer (709 women and 769 men) among 530,469 women and 244,483 men followed for up to 7 to 20 years. Participants completed a validated food-frequency questionnaire at baseline. Using the primary data from each study, the study-specific relative risks (RR) were calculated using the Cox proportional hazards model and then pooled using a random effects model. We found that fruit and vegetable consumption was associated with a reduced risk of renal cell cancer. Compared with <200 g/d of fruit and vegetable intake, the pooled multivariate RR for >= 600 g/d was 0.68 [95% confidence interval (95% CI) = 0.54-0.87; P for between-studies heterogeneity = 0.86; P for trend = 0.001]. Compared with <100 g/d, the pooled multivariate RRs (95% CI) for 400 g/d were 0.79 (0.63-0.99; P for trend = 0.03) for total fruit and 0.72 (0.48-1.08; P for trend = 0.07) for total vegetables. For specific carotenoids, the pooled multivariate RRs (95% CIs) comparing the highest and lowest quintiles were 0.87 (0.73-1.03) for alpha-carotene, 0.82 (0.69-0.98) for beta-carotene, 0.86 (0.73-1.01) for beta-cryptoxanthin, 0.82 (0.64-1.06) for lutein/zeaxanthin, and 1.13 (0.95-1.34) for lycopene. In conclusion, increasing fruit and vegetable consumption is associated with decreasing risk of renal cell cancer; carotenoids present in fruit and vegetables may partly contribute to this protection. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1730-9) Undertreatment of osteoporosis following hip fracture in the elderly Luthje, P., Nurmi-Luthje, I., Kaukonen, J. P., Kuurne, S., Naboulsi, H. and Kataja, M. Archives of Gerontology and Geriatrics. 2009; 49(1): 153-157. Article. IF 1.270 The national Finnish guidelines for medical treatment of hip fracture patients are: osteoporosis medication and the daily concomitant use of vitamin D and calcium supplements. We investigated the post-fracture medical therapy for osteoporosis and the calcium and vitamin D therapy among hip fracture patients in two Finnish hospitals. The pre-fracture osteoporosis medication and use of calcium and vitamin D supplements of the patients were inquired on admission. The patient-specific use of osteoporosis medication and of prescribed calcium and vitamin D therapy during the follow-up time were checked from The Finnish Social Insurance Institution. At the end of the follow-up, those who were alive were inquired about the use of medication at the time. Eight percent of the 223 patients used osteoporosis medication and 8% used prescribed calcium and vitamin D supplements before the fracture. During the follow-up, the figures were 39% (52/133) and 53% (70/133), respectively, and at the end of the follow-up, correspondingly, 25% (29/114) and 44% (50/114). The follow-up time was 19.5-35 months. The post-fracture medical therapy for osteoporosis was insufficient. More effort should be focused on the secondary prevention following hip fracture in order to ensure the recommended treatment of osteoporosis. (C) 2008 Elsevier Ireland Ltd. All rights reserved. Mäkelä, P. and Österberg, E. Addiction. 2009; 104(4): 554-63. IF 4.244 AIMS: To review the consequences of the changes in Finnish alcohol policy in 2004, when quotas for travellers' tax-free imports of alcoholic beverages from other European Union (EU) countries were abolished, Estonia joined the EU and excise duties on alcoholic beverages were reduced in Finland by one-third, on average. DESIGN: A review of published research and routinely available data. SETTING: Finland. MEASUREMENTS: Prices of alcoholic beverages, recorded and unrecorded alcohol consumption, data on criminality and other police statistics, alcohol-related deaths and hospitalizations, service use. FINDINGS: Alcohol consumption increased 10% in 2004, clearly more than in the early 2000s. With few exceptions, alcohol-related harms increased. Alcohol-induced liver disease deaths increased the most, by 46% in 2004-06 compared to 2001-03, which indicates a strong effect on pre-2004 heavy drinkers. Consumption and harms increased most among middle-aged and older segments of the population, and harms in the worst-off parts of the population in particular. CONCLUSIONS: Alcohol taxation and alcohol prices affect consumption and related harms, and heavy drinkers are responsive to price. In Finland in 2004, the worst-off parts of the population paid the highest price in terms of health for cuts in alcohol prices. The removal of travellers' import quotas, which was an inherent part of creating the single European market, had serious public health consequences in Finland. Malinen, H., Lehtonen, M. and Hyytiä, P. Alcohol Clin Exp Res. 2009. IF 3.166 Background: The central nervous system cannabinoid CB1 receptors have been implicated in regulation of alcohol consumption. Less data are available on the role of the endogenous ligands for these receptors, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), in alcohol-related behaviors. The purpose of this study was to assess the effects of voluntary alcohol consumption on the levels of these endocannabinoids in key brain areas mediating alcohol reinforcement. Methods: Female and male alcohol-preferring AA (Alko, Alcohol) rats were trained to drink 10% (v/v) alcohol during 90-min limited access sessions every second day. Following establishment of stable alcohol drinking, half of the subjects were killed immediately before the daily alcohol access ("pre-session" group), while the other half was killed after the drinking session ("post-session" group). A separate control group consisted of water-drinking rats. AEA and 2-AG levels were measured from prefrontal cortex (PFC), nucleus accumbens (NAc), caudate putamen (CPu), amygdala, and hippocampus using liquid chromatography-tandem mass spectrometry (LC/MS/MS). Results: Voluntary alcohol drinking caused widespread alterations in the levels of both AEA and 2-AG. Compared to the water group, increased AEA levels were seen in the pre-session group, but they were decreased immediately following limited access drinking in the female AA rats. Also 2-AG levels were significantly elevated after long alcohol exposure, and an additional increase was found after limited access drinking in PFC. In males, however, the only alterations caused by alcohol drinking were significantly elevated AEA levels in NAc and CPu in the post-session group. No changes were seen in the levels of 2-AG. Conclusions: These results demonstrate that voluntary alcohol drinking modulates the levels of endocannabinoids in several brain areas implicated in alcohol reinforcement. AEA and 2-AG were differentially affected, suggesting that they could have partially separate modulatory roles. Alterations were more widespread in females than males, possibly reflecting their higher alcohol intake. Taken together, alcohol-induced release of endocannabinoids may have an important role in alcohol reinforcement and development of alcohol addiction. Melartin, T., Häkkinen, M., Koivisto, M., Suominen, K. and Isometsä, E. Nord J Psychiatry. 2009: 1-5. IF 0.779 Background: Detecting patients with borderline personality disorder (BPD) is important, and feasible screening instruments are needed. Aims: To investigate our Finnish translation of the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD) as a screen for BPD among psychiatric outpatients, its psychometric and screening properties, and feasibility in improving the recognition of BPD. Methods: We screened 302 consecutive psychiatric outpatients at the Department of Psychiatry at the Helsinki University Central Hospital in Finland for BPD using the Finnish MSI-BPD. Of the patients, 69 (23%) were assigned to a random sample that was stratified according to the number of screens returned to the outpatient clinics, and further stratified into the three strata, high scores deliberately enriched, according to the MSI-BPD scores. Finally, a stratified random sample of 45 patients was interviewed with the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II) by the interviewers blind to the patients' MSI-BPD scores. Results: One third (29%) of 302 screened patients had a positive MSI-BPD. The internal consistency of the MSI-BPD was good (Cronbach's alpha = 0.77). Of the 45 patients interviewed with the SCID-II, 11 (24%) were found to have BPD, five (46%) of whom a previously clinical diagnosis. In a ROC analysis, the optimal cut-off score was 7. Conclusions: The translated MSI-BPD was found to be a feasible screen for BPD in Finnish psychiatric outpatient care. Further studies investigating the clinical utility of MSI-BPD in larger clinical samples are warranted. Milne, R. L., Benitez, J., Nevanlinna, H., Heikkinen, T., Aittomaki, K., Blomqvist, C., Arias, J. I., Zamora, M. P., Burwinkel, B., Bartram, C. R., Meindl, A., Schmutzler, R. K., Cox, A., Brock, I., Elliott, G., Reed, M. W., Southey, M. C., Smith, L., Spurdle, A. B., Hopper, J. L., Couch, F. J., Olson, J. E., Wang, X., Fredericksen, Z., Schurmann, P., Bremer, M., Hillemanns, P., Dork, T., Devilee, P., van Asperen, C. J., Tollenaar, R. A., Seynaeve, C., Hall, P., Czene, K., Liu, J., Li, Y., Ahmed, S., Dunning, A. M., Maranian, M., Pharoah, P. D., Chenevix-Trench, G., Beesley, J., Bogdanova, N. V., Antonenkova, N. N., Zalutsky, I. V., Anton-Culver, H., Ziogas, A., Brauch, H., Justenhoven, C., Ko, Y. D., Haas, S., Fasching, P. A., Strick, R., Ekici, A. B., Beckmann, M. W., Giles, G. G., Severi, G., Baglietto, L., English, D. R., Fletcher, O., Johnson, N., Dos Santos Silva, I., Peto, J., Turnbull, C., Hines, S., Renwick, A., Rahman, N., Nordestgaard, B. G., Bojesen, S. E., Flyger, H., Kang, D., Yoo, K. Y., Noh, D. Y., Mannermaa, A., Kataja, V., Kosma, V. M., Garcia-Closas, M., Chanock, S., Lissowska, J., Brinton, L. A., Chang-Claude, J., Wang-Gohrke, S., Shen, C. Y., Wang, H. C., Yu, J. C., Chen, S. T., Bermisheva, M., Nikolaeva, T., Khusnutdinova, E., Humphreys, M. K., Morrison, J., Platte, R. and Easton, D. F. J Natl Cancer Inst. 2009. IF 14.933 Background A recent genome-wide association study identified single-nucleotide polymorphism (SNP) 2q35-rs13387042 as a marker of susceptibility to estrogen receptor (ER)-positive breast cancer. We attempted to confirm this association using the Breast Cancer Association Consortium. Methods 2q35-rs13387042 SNP was genotyped for 31 510 women with invasive breast cancer, 1101 women with ductal carcinoma in situ, and 35 969 female control subjects from 25 studies. Odds ratios (ORs) were estimated by logistic regression, adjusted for study. Heterogeneity in odds ratios by each of age, ethnicity, and study was assessed by fitting interaction terms. Heterogeneity by each of invasiveness, family history, bilaterality, and hormone receptor status was assessed by subclassifying case patients and applying polytomous logistic regression. All statistical tests were two-sided. Results We found strong evidence of association between rs13387042 and breast cancer in white women of European origin (per-allele OR = 1.12, 95% confidence interval [CI] = 1.09 to 1.15; P(trend) = 1.0 x 10(-19)). The odds ratio was lower than that previously reported (P = .02) and did not vary by age or ethnicity (all P >/= .2). However, it was higher when the analysis was restricted to case patients who were selected for a strong family history (P = .02). An association was observed for both ER-positive (OR = 1.14, 95% CI = 1.10 to 1.17; P = 10(-15)) and ER-negative disease (OR = 1.10, 95% CI = 1.04 to 1.15; P = .0003) and both progesterone receptor (PR)-positive (OR = 1.15, 95% CI = 1.11 to 1.19; P = 5 x 10(-14)) and PR-negative disease (OR = 1.10, 95% CI = 1.06 to 1.15; P = .00002). Conclusion The rs13387042 is associated with both ER-positive and ER-negative breast cancer in European women. Seasonal variation of diagnosis of Type 1 diabetes mellitus in children worldwide Moltchanova, E. V., Schreier, N., Lammi, N. and Karvonen, M. Diabet Med. 2009; 26(7): 673-678. IF 3.172 Aims To determine if there is a worldwide seasonal pattern in the clinical onset of Type 1 diabetes. Methods Analysis of the seasonality in diagnosis of Type 1 diabetes was based on the incidence data in 0- to 14-year-old children collected by the World Health Organization Diabetes Mondiale (WHO DiaMond) Project over the period 1990-1999. One hundred and five centres from 53 countries worldwide provided enough data for the seasonality analysis. The incidence seasonality patterns were also determined for age- and sex-specific groups. Results Forty-two out of 105 centres exhibited significant seasonality in the incidence of Type 1 diabetes (P < 0.05). The existence of significant seasonal patterns correlated with higher level of incidence and of the average yearly counts. The correlation disappeared after adjustment for latitude. Twenty-eight of those centres had peaks in October to January and 33 had troughs in June to August. Two out of the four centres with significant seasonality in the southern hemisphere demonstrated a different pattern with a peak in July to September and a trough in January to March. Conclusions The seasonality of the incidence of Type 1 diabetes mellitus in children under 15 years of age is a real phenomenon, as was reported previously and as is now demonstrated by this large standardized study. The seasonality pattern appears to be dependent on the geographical position, at least as far as the northern/southern hemisphere dichotomy is concerned. However, more data are needed on the populations living below the 30th parallel north in order to complete the picture. Interactions of oxysterols with membranes and proteins Olkkonen, V. M. and Hynynen, R. Molecular Aspects of Medicine. 2009; 30(3): 123-133. Review. IF 7.320 Oxysterols are oxidized derivatives of cholesterol or by-products of cholesterol biosynthesis with multiple functions. Even though they are heterogeneous in their biological activities, they have the common property of transferring between membranes orders of magnitude faster than cholesterol, due to higher polarity and poorer membrane packing. Depending on the nature and location of the oxygen substitution, oxysterols have distinct impacts on the biophysical properties of membranes, including the formation of liquid ordered domains. This is Suggested to explain differences in the cytotoxic potential of various oxysterols. Besides the effects of oxysterols on membrane biophysical properties, the endogenous cellular oxysterols are suggested to execute important functions via interactions with receptor proteins. Increasing evidence suggests that oxysterols act as ligands of liver X receptors, transcription factors with key roles in lipid metabolism. Oxysterols were also shown to interact with the Insig (insulin-induced gene) proteins, revealing a mechanism by which they regulate the transport and maturation of sterol-regulatory element binding proteins as well as the stability of a rate-limiting sterol biosynthetic enzyme. Furthermore, a number of other cellular receptors for oxysterols involved in cell signaling, lipid metabolism, and vesicle transport have been discovered, enhancing the interest in these compounds in several branches of biomedical research. (C) 2009 Published by Elsevier Ltd. Regulation of exocytotic protein expression and Ca2+-dependent peptide secretion in astrocytes Paco, S., Margeli, M. A., Olkkonen, V. M., Imai, A., Blasi, J., Fischer-Colbrie, R. and Aguado, F. Journal of Neurochemistry. 2009; 110(1): 143-156. Article. IF 4.500 Vesicular transmitter release from astrocytes influences neuronal development, function and plasticity. However, secretory pathways and the involved molecular mechanisms in astroglial cells are poorly known. In this study, we show that a variety of SNARE and Munc18 isoforms are expressed by cultured astrocytes, with syntaxin-4, Munc18c, SNAP-23 and VAMP-3 being the most abundant variants. Exocytotic protein expression was differentially regulated by activating and differentiating agents. Specifically, proteins controlling Ca2+-dependent secretion in neuroendocrine cells were up-regulated after long-term 8Br-cAMP administration in astrocytes, but not by proinflammatory cytokines. Moreover, 8Br-cAMP treatment greatly increased the cellular content of the peptidie vesicle marker secretogranin-2. Release assays performed on cAMP-treated astrocytes showed that basal and stimulated secretogranin-2 secretion are dependent on [Ca2+](i). As shown release of the chimeric hormone ANP.emd from transfected cells, cAMP-induced differentiation in astrocytes enhances Ca2+-regulated peptide secretion. We conclude that astroglial cells display distinctive molecular components for exocytosis. Moreover, the regulation of both exocytotic protein expression and Ca2+-dependent peptide secretion in astrocytes by differentiating and activating agents suggest that glial secretory pathways are adjusted in different physiological states. Perttilä, J., Merikanto, K., Naukkarinen, J., Surakka, I., Martin, N. W., Tanhuanpaa, K., Grimard, V., Taskinen, M. R., Thiele, C., Salomaa, V., Jula, A., Perola, M., Virtanen, I., Peltonen, L. and Olkkonen, V. M. J Mol Med. 2009. IF 4.370 Analysis of variants in three genes encoding oxysterol-binding protein (OSBP) homologues (OSBPL2, OSBPL9, OSBPL10) in Finnish families with familial low high-density lipoprotein (HDL) levels (N = 426) or familial combined hyperlipidemia (N = 684) revealed suggestive linkage of OSBPL10 single-nucleotide polymorphisms (SNPs) with extreme end high triglyceride (TG; >90th percentile) trait. Prompted by this initial finding, we carried out association analysis in a metabolic syndrome subcohort (Genmets) of Health2000 examination survey (N = 2,138), revealing association of multiple OSBPL10 SNPs with high serum TG levels (>95th percentile). To investigate whether OSBPL10 could be the gene underlying the observed linkage and association, we carried out functional experiments in the human hepatoma cell line Huh7. Silencing of OSBPL10 increased the incorporation of [(3)H]acetate into cholesterol and both [(3)H]acetate and [(3)H]oleate into triglycerides and enhanced the accumulation of secreted apolipoprotein B100 in growth medium, suggesting that the encoded protein ORP10 suppresses hepatic lipogenesis and very-low-density lipoprotein production. ORP10 was shown to associate dynamically with microtubules, consistent with its involvement in intracellular transport or organelle positioning. The data introduces OSBPL10 as a gene whose variation may contribute to high triglyceride levels in dyslipidemic Finnish subjects and provides evidence for ORP10 as a regulator of cellular lipid metabolism. Breastfeeding stimulates total and cow's milk-specific salivary IgA in infants Piirainen, L., Pesola, J., Pesola, I., Komulainen, J. and Vaarala, O. Pediatr Allergy Immunol. 2009; 20(3): 295-8. IF 2.723 Breastfeeding may increase the rate of mucosal maturation and IgA production. We sought to determine the effect of breastfeeding vs. formula-feeding on the maturation of oral mucosa by measuring the salivary total antibodies and cow's milk protein-specific IgA. Fifty-eight saliva samples were collected from 39 healthy, full term infants. At the age of 3 months (n = 25) eight infants received only breast milk and seventeen formula (cow's milk based n = 10, hydrolysed n = 7) and breast milk; and at the age of 6 months (n = 33) eleven received breast milk, seventeen formula and breast milk and five were not breastfed any more (cow's milk based n = 14, hydrolysed n = 8). Total IgA, IgG, IgM and protein, and beta-lactoglobulin specific IgA were measured from saliva with enzyme-linked immunoassay (ELISA). The antibody results were proportioned to total protein. No differences in antibody levels between the feeding groups were found at 3 months of age. At 6 months, total IgA, total IgM and beta-lactoglobulin-specific IgA were higher among the breastfed infants compared to those receiving formula as supplement to breast milk or not breastfed any more (breast milk vs. any formula p = 0.029, p = 0.015, p = 0.058; breast milk vs. cow's milk formula p = 0.025, p = 0.044, p = 0.038). To conclude, breastfeeding stimulated the mucosal immune system to produce IgA to saliva, which is a marker for immunological maturation and likely provides protection against environmental antigens. Poikonen, K., Lajunen, T., Silvennoinen-Kassinen, S., Leinonen, M. and Saikku, P. Scandinavian Journal of Immunology. 2009; 70(1): 34-39. Article. IF 2.186 Chlamydia pneumoniae is an obligate intracellular gram-negative bacterium, which causes respiratory infections in humans. It can infect various cell types, e. g. vascular endothelial cells, smooth muscle cells and monocyte-derived macrophages in vitro. The susceptibility of macrophages from healthy individuals to C. pneumoniae infection is highly variable. In this study, we evaluated the effects of innate immunity genes CD14 -260 C>T, TLR2 Arg753Gln, TLR4 Asp299Gly, LBP Phe436Leu and IL6 -174 G>C polymorphisms on C. pneumoniae growth in human macrophages in vitro. The growth of C. pneumoniae was highest in CD14 -260 C>T TT genotype cells and the difference to CC and CT genotypes was statistically significant (P = 0.032 and 0.022 respectively). The G-allele of the IL6 -174 G>C polymorphism had a positive influence on chlamydial growth; the difference was statistically significant only between CC and GC genotypes (P = 0.018). TLR2 Arg 753Gln, TLR4 Asp299Gly, LBP Phe436Leu polymorphisms showed no effect on chlamydial growth. Ranta, K., Kaltiala-Heino, R., Rantanen, P. and Marttunen, M. Depression and Anxiety. 2009; 26(6): 528-536. Proceedings Paper. IF 2.526 Background: Few studies have investigated the epidemiology of social phobia (SP) among early to middle adolescents, at the time of suggested mean onset of the disorder. The objective of this study was to investigate the prevalence, comorbidity, individual and familial correlates, and service use associated with SP among Finnish 12-17-year-old adolescents in greneral population. Methods: A sample of 784 adolescents was screened with the Social Phobia Inventory, and a sub-sample (n = 350) was interviewed with a semi-structured clinical interview to identify SP, sub-clinical SP (SSP), and a range of other axis I DSM-IV disorders. Individual and familial correlates, and service use associated with SP were also inquired. Results: We found a 12-month prevalence of 3.2% for SP, and 4.6% for SSR The prevalence rose and the gender ratio shifted to female preponderance as age increased. SP was frequently comorbid with other anxiety disorders (41%) and depressive disorders (41%). Adolescents with SP/SSP were impaired in their academic and global functioning, and reported more parental psychiatric treatment contacts. Two thirds (68%) of adolescents with SP reported having been bullied by peers. Only one fifth of adolescents with non-comorbid SP had been in contact with a mental health professional. Conclusions: We conclude that adolescent SP is a relatively frequent, undertreated and highly comorbid condition, associated with educational impairment, depression and anxiety in parents, and peer victimization. Depression and Anxiety 26:528-536, 2009. (c) 2009 Wiley-Liss, Inc. Health-Related Quality of Life in 5-Year-Old Very Low Birth Weight Infants Rautava, L., Häkkinen, U., Korvenranta, E., Andersson, S., Gissler, M., Hallman, M., Korvenranta, H., Leipälä, J., Linna, M., Peltola, M., Tammela, O. and Lehtonen, L. J Pediatr. 2009. IF 4.122 OBJECTIVE: To investigate the effect of preterm birth, the time of birth, and birth hospital level and district on health-related quality of life (HRQoL) and quality-adjusted life years (QALYs). STUDY DESIGN: This national study included all very low birth weight infants (VLBWIs; birth weight RESULTS: HRQoL at age 5 years was lower and 1.3 QALYs were lost in VLBWIs compared with controls. Regional differences in the QALYs of VLBWIs were found among the 5 university hospital districts. Birth hospital level or birth outside office hours had no effect on the QALYs of live-born VLBWIs. The adjusted HRQoL total score was not affected by birth outside office hours or by the birth hospital level or district. CONCLUSIONS: Differences in QALYs related to hospital district suggest variation in the care of VLBWIs that needs to be addressed. Sanders, A. E., Slade, G. D., John, M. T., Steele, J. G., Suominen-Taipale, A. L., Lahti, S., Nuttall, N. M. and Allen, P. F. Journal of Epidemiology and Community Health. 2009; 63(7): 569-574. Article. IF 3.186 Background: The extent to which welfare states may influence health outcomes has not been explored. It was hypothesised that policies which target the poor are associated with greater income inequality in oral health quality of life than those that provide earnings-related benefits to all citizens. Methods: Data were from nationally representative surveys in the UK (n=4064), Finland (n=5078), Germany (n=1454) and Australia (n=2292) conducted from 1998 to 2002. The typology of Korpi and Palme classifies these countries into four different welfare states. In each survey, subjects completed the Oral Health Impact Profile (OHIP-14) questionnaire, which evaluates the adverse consequence of dental conditions on quality of life. For each country, survey estimation commands were used to create linear regression models that estimated the slope of the gradient between four quartiles of income and OHIP-14 severity scores. Parameter estimates for income gradients were contrasted across countries using Wald chi(2) tests specifying a critical p value of 0.008, equivalent to a Bonferroni correction of p<0.05 for the six pairwise tests. Results: Statistically significant income gradients in OHIP-14 severity scores were found in all countries except Germany. A global test confirmed significant cross-national differences in the magnitude of income gradients. In Australia, where a flat rate of benefits targeted the poor, the mean OHIP-14 severity score reduced by 1.7 units (95% CI 22.15 to 21.34) with each increasing quartile of household income, a significantly steeper gradient than in other countries. Conclusion: The coverage and generosity of welfare state benefits appear to influence levels of inequality in population oral health quality of life. Siira, L., Rantala, M., Jalava, J., Hakanen, A. J., Huovinen, P., Kaijalainen, T., Lyytikainen, O. and Virolainen, A. Antimicrob Agents Chemother. 2009; 53(5): 2066-73. IF 4.716 The antimicrobial resistance of Streptococcus pneumoniae, or pneumococcus, is a growing global problem. In our study, 3,571 invasive pneumococcal isolates, recovered from blood and cerebrospinal fluid samples from patients in Finland between the years 2002 and 2006, showed an increase in erythromycin nonsusceptibility from 16% to 28% (P < 0.0001) over the 5-year study period, as well as a doubling of penicillin nonsusceptibility from 8% to 16% (P < 0.0001). Erythromycin nonsusceptibility increased especially in isolates derived from 0- to 2-year-old children and was 46% for this age group in 2006. Although multiresistance, defined as nonsusceptibility to penicillin, erythromycin, and tetracycline, was fairly rare (5.1% in 2006), 38% of the erythromycin-nonsusceptible isolates were also penicillin nonsusceptible, while 74% of the penicillin-nonsusceptible isolates were nonsusceptible to erythromycin. In contrast to the situation in continental Europe, but mirroring that in North America, the most frequent macrolide resistance determinant carried by 56% of the tested macrolide-resistant pneumococci was the mef gene. Serotypes 14, 9V, 19A, 6B, and 19F were most frequently nonsusceptible to erythromycin or penicillin. The penicillin-resistant invasive isolates (n = 88) were genotyped by multilocus sequence typing, which revealed the presence of 25 sequence types, 9 of which were novel. The majority of the isolates were related to one of several globally disseminated penicillin- or multiresistant clones, most importantly the rlrA adhesion pilus carrying clones Spain(9V) ST156 and Taiwan(19F) ST236. The penicillin-resistant pneumococcal population in Finland is therefore a combination of internationally recognized genotypes as well as novel ones. Similä, M. E., Valsta, L. M., Virtanen, M. J., Hätönen, K. A. and Virtamo, J. British Journal of Nutrition. 2009; 101(9): 1400-1405. Article. IF 2.764 Interest in the dietary glycaemic index (GI) and glycaemic load (GL) as risk factors for chronic diseases has grown in recent years but findings have been controversial. We describe the compilation of the GI database for the cohort studies within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study and the main characteristics associating with diet GI and GL. The ATBC Study enrolled 29 133 male smokers aged 50-69 years who filled in a dietary history questionnaire upon study entry. The dietary data included 1097 foods, of which 195 foods with no or a negligible amount of available carbohydrates were assigned a GI of zero. Based on preset methodological criteria for published GI studies, the GI value of a similar food was available for 130 foods, and the GI of related food was assigned to 360 foods. The GI values of these foods served in the GI calculation of 412 composite foods. The median diet GI among the ATBC Study participants was 673 (interquartile range 64.8-70.0), and the median diet GL was 175 (interquartile range 158-192). The intakes of carbohydrates, protein and fat decreased, and the intake of fibre increased, with increasing GI. The GL showed a positive correlation with intakes of carbohydrates and dietary fibre and a negative correlation with intakes of protein and fat. The GI studies available that fulfilled the minimum methodological requirements cover a sufficient amount of foods to form a meaningful GI database for epidemiological study. This, however, requires the availability of GI values for relevant local carbohydrate-containing foods. Ståhl, T. P. Eur J Public Health. 2009. IF 2.176 BACKGROUND: The European Commission has an Impact Assessment (IA) procedure that aims to inform decision-makers of the all important impacts that decisions may have. This article studies how health is considered in the IA procedure and how it is reflected in the reports: what aspects, whose and simply in what context health is mentioned in the IA reports. METHODS: Half of the Commissions IAs from 2006 were studied. The analysis was text based and informed by content analysis. In total, 48 reports by 17 DGs were analysed. RESULTS: Five DGs (29%) and 10 reports (21%) made no reference to human health, public health or health systems. Five DGs were clearly considering health impacts more often than others; DG EMPL, SANCO, AGRI, ELARG and ENV. Health systems/services were most often and human health next most common referred to (39% and 29% of all, respectively). Health impacts were usually referred to in the sections on the definition of problems and the analysis of impacts. Seldom were they reported on in the sections on policy options, comparing options, or in the monitoring and evaluation sections. CONCLUSION: The results partly support concerns about the potential neglect of health impacts. The results also suggest that health is not considered an important factor when discussing alternative policy choices, and neither does it seem to be an important objective. There is a clear need for further exploration on ways in which health could be more appropriately considered when impacts of other policies are considered by the various DGs. Stenholm, S., Alley, D., Bandinelli, S., Griswold, M. E., Koskinen, S., Rantanen, T., Guralnik, J. M. and Ferrucci, L. International Journal of Obesity. 2009; 33(6): 635-644. Article. IF 3.640 Objective: Both obesity and muscle impairment are increasingly prevalent among older persons and negatively affect health and physical functioning. However, the combined effect of coexisting obesity and muscle impairment on physical function decline has been little studied. We examined whether obese persons with low muscle strength experience significantly greater declines in walking speed and mobility than persons with only obesity or low muscle strength. Design: Community-dwelling adults aged >= 65 years (n = 930) living in the Chianti geographic area (Tuscany, Italy) were followed for 6 years in the population-based InCHIANTI study. Measurements: On the basis of baseline measurements (1998-2000), obesity was defined as body mass index (BMI) >= 30 kg/m(2) and low muscle strength as lowest sex-specific tertile of knee extensor strength. Walking speed and self-reported mobility disability (ability to walk 400m or climb one flight of stairs) were assessed at baseline and at 3-and 6-year follow-up. Results: At baseline, obese persons with low muscle strength had significantly lower walking speed compared with all other groups (P <= 0.05). In longitudinal analyses, obese participants with low muscle strength had steeper decline in walking speed and high risk of developing new mobility disability over the 6-year follow-up compared with those without obesity or low muscle strength. After the age of 80, the differences between groups were substantially attenuated. The differences seen in walking speed across combination of low muscle strength and obesity groups were partly explained by 6-year changes in muscle strength, BMI and waist circumference. Conclusions: Obesity combined with low muscle strength increases the risk of decline in walking speed and developing mobility disability, especially among persons <80 years old. International Journal of Obesity (2009) 33, 635-644; doi: 10.1038/ijo.2009.62; published online 21 April 2009 Association of Examination Rates with Children's National Caries Indices in Finland Suominen-Taipale, A. L., Widström, E. and Sund, R. Open Dent J. 2009; 3: 59-67. The objective was to assess the effect of examination rates on national caries indices of 5, 12 and 17-year-old children/adolescents in Finland. The data were gathered from patient records of the Public Dental Service (PDS) units (n=205, 73%) and from a national register. The data included PDS-specific total numbers of examined children/adolescents and means of decayed (d/D) teeth, dmft/DMFT-values and proportions of caries-free. For analytical purposes, the PDS-specific mean values weighted by the PDS population were calculated to imply the traditionally calculated figures. New PDS-specific examination-rate-adjusted mean values were calculated by using the predicted outcome values at 100% examination rates. The results showed that low examination rates were associated with slightly poorer oral health. The examination-rate-adjusted mean d/D- values indicated better oral health than the traditional indices. The adjustment slightly worsened oral health in proportions of caries-free, and had almost no effect on dmft/DMFT-value. Overall, the influence was modest. The high proportions of healthy children that are examined (against recommendation) and the relatively small number of those having extensive disease (frequently examined as recommended) probably mask the influence of examination rates on the indices in Finland. We conclude that in international comparisons, traditionally calculated indices seem to be sufficiently valid. Tainio, M., Sofiev, M., Hujo, M., Tuomisto, J. T., Loh, M., Jantunen, M. J., Karppinen, A., Kangas, L., Karvosenoja, N., Kupiainen, K., Porvari, P. and Kukkonen, J. Atmospheric Environment. 2009; 43(19): 3052-3059. Article. IF 2.890 The intake fraction (iF) has been defined as the integrated incremental intake of a pollutant released from a source category or region summed over all exposed individuals. In this study we evaluated the ifs in the population of Europe for emissions of anthropogenic primary fine particulate matter (PM2.5) from sources in Europe, with a more detailed analysis of the iF from Finnish sources. Parameters for calculating the ifs include the emission strengths, the predicted atmospheric concentrations, European population data, and the average breathing rate per person. Emissions for the whole of Europe and Finland were based on the inventories of the European Monitoring and Evaluation Programme (EMEP) and the Finnish Regional Emission Scenario (FRES) model, respectively. The atmospheric dispersion of primary PM2.5 Was computed using the regional-scale dispersion model SILAM. The ifs from Finnish sources were also computed separately for six emission source categories. The ifs corresponding to the primary PM2.5 emissions from the European countries for the whole population of Europe were generally highest for the densely populated Western European countries, second highest for the Eastern and Southern European countries, and lowest for the Northern European and Baltic countries. For the entire European population, the iF values varied from the lowest value of 0.31 per million for emissions from Cyprus, to the highest value of 4.42 per million for emissions from Belgium. These results depend on the regional distribution of the population and the prevailing long-term meteorological conditions. Regarding Finnish primary PM2.5 emissions, the iF was highest for traffic emissions (0.68 per million) and lowest for major power plant emissions (0.50 per million). The results provide new information that can be used to find the most cost-efficient emission abatement strategies and policies. (C) 2009 Elsevier Ltd. All rights reserved. Prevalence of diabetes and impaired fasting glucose among 769 792 rural Chinese adults Tian, H. G., Song, G. D., Xie, H. X., Zhang, H., Tuomilehto, J. and Hu, G. Diabetes Research and Clinical Practice. 2009; 84(3): 273-278. Article. IF 1.888 Objective: To investigate the prevalence of diabetes and impaired fasting glucose (IFG) among rural Chinese adults. Methods: A cross-sectional whole-population health survey of 364 781 men and 405 011 women aged 35 years and over was undertaken in 2004 in Tianjin rural area. An overnight fasting capillary whole blood specimen was collected for glucose measurement and information on history of previously diagnosed diabetes was obtained by a standard questionnaire. Results: Using the World Health Organization standard, the age-standardized prevalence of IFG (fasting capillary whole blood glucose 5.6-6.0 mmol/l), screen-detected (previously undiagnosed) diabetes (>= 6.1 mmol/l) and previously diagnosed diabetes were 13.7%, 7.9% and 0.4% in men, 14.5%, 9.7% and 0.9% in women, and 14.1%, 8.8% and 0.7% in men and women combined, respectively. The prevalence of IFG, screen-detected diabetes and previously diagnosed diabetes was higher in women than in men (all p < 0.001). The prevalence of IFG and diabetes was higher in participants of rural Tianjin than in the overall Chinese rural and urban population based on the Fourth National Nutritional Survey carried out in 2002. Conclusion: The prevalence of IFG and diabetes is relatively high in the rural population in Tianjin and it has become an important public health problem in China. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Tomppo, L., Hennah, W., Lahermo, P., Loukola, A., Tuulio-Henriksson, A., Suvisaari, J., Partonen, T., Ekelund, J., Lönnqvist, J. and Peltonen, L. Biological Psychiatry. 2009; 65(12): 1055-1062. Article. IF 8.672 Background: Disrupted in Schizophrenia 1 (DISC1) is currently one of the most interesting candidate genes for major mental illness,having been demonstrated to associate with schizophrenia, bipolar disorder, major depression, autism, and Asperger's syndrome. We have previously reported a DISC1 haplotype, HEP3, and an NDE1 spanning tag haplotype to associate to schizophrenia in Finnish schizophrenia families. Because both DISCI and NDE1 display association in our study sample, we hypothesized that other genes interacting with DISCI might also have a role in the etiology of schizophrenia. Methods: We selected 11 additional genes encoding components of the "DISC1 pathway" and studied these in our study sample of 476 families including 1857 genotyped individuals. We performed single nucleotide polymorphism (SNP) and haplotype association analyses in two independent sets of families. For markers and haplotypes found to be consistently associated in both sets, the overall significance was tested with the combined set of families. Results: We identified three SNPs to be associated with schizophrenia in PDE4D (rs1120303, p = .021), PDE4B (rs7412571, p = .018), and NDEL1 (rs17806986, p = .0038). Greater significance was observed with allelic haplotypes of PDE4D(p = .00084),PDE4B(p = .0022 and p = .029), and NDEL1 (p = .0027) that increased or decreased schizophrenia susceptibility. Conclusions: Our findings with other converging lines of evidence support the underlying importance of DISC1-related molecular pathways in the etiology of schizophrenia and other major mental illnesses. A population-based association study of candidate genes for depression and sleep disturbance Utge, S., Soronen, P., Partonen, T., Loukola, A., Kronholm, E., Pirkola, S., Nyman, E., Porkka-Heiskanen, T. and Paunio, T. Am J Med Genet B Neuropsychiatr Genet. 2009. IF 3.932 The clinical manifestation of depression comprises a variety of symptoms, including early morning awakenings and fatigue, features also indicating disturbed sleep. The presence or absence of these symptoms may reflect differences in neurobiological processes leading to prolonged depression. Several neurobiological mechanisms have been indicated in the induction of depression, including disturbances in serotonergic and glutamatergic neurotransmission and in the action of the hypothalamic-pituitary-adrenal (HPA) axis. The same transmitters have also been linked to sleep regulation. We hypothesized that depression without simultaneous symptoms of disturbed sleep would partly have a different genetic background than depression with symptoms of disturbed sleep. We tested this hypothesis using a systematic population-based association study of 14 candidate genes related to depression and disturbed sleep. Association of genetic variants with either depression alone, depression with early morning awakenings, or depression with fatigue was investigated using permutation-based allelic association analysis of a sample of 1,654 adults recruited from Finland's population-based program. The major findings were associations of TPH2 (rs12229394) with depression accompanied by fatigue in women and CREB1 (rs11904814) with depression alone in men. We also found suggestive associations in women for GAD1, GRIA3, and BDNF with depression accompanied by fatigue, and for CRHR1 with depression accompanied by early morning awakenings. The results indicate sex-dependent and symptom-specific differences in the genetic background of depression. These differences may partially explain the broad spectrum of depressive symptoms, and their systematic monitoring could potentially be used for diagnostic purposes. (c) 2009 Wiley-Liss, Inc. Care-related quality of life in old age Vaarama, M. European Journal of Ageing. 2009; 6(2): 113-125. Article. Promoting quality of life is a central theme in recent ageing policies, but what quality of life means in concrete terms for people in different stages of old age is rather unclear. This study presents a multi-dimensional model of care-related quality of life (crQoL) and, based on analyses of three Finnish cross-sectional datasets from the years 2004-2007, examines the distinctions between dimensions of QoL by age and gender, with a special focus on older home care clients. Correlation analyses (Pearson) and stepwise linear regression were applied to analyse variation in QoL by age group and the association between QoL and perceived quality of home care. The results suggest that individual QoL and the priorities of (physical, psychical, social, and environmental) dimensions in the assessment of QoL by older persons vary considerably and exhibit distinct profiles in different stages of ageing. In addition, four dimensions for good care corresponding to the crQoL model were identified and their empirical relevance demonstrated. From the perspective of older people in need of help, home care is not just about giving them the instrumental help they need to perform their daily activities, but rather about giving responsive care that reflects their personal preferences or their view on a "good life", and treats them with dignity and respect. The criteria for the evaluation of quality of home care should reflect these insights, and policy measures should take these differences into account. Hopelessness across phases of bipolar I or II disorder: a prospective study Valtonen, H. M., Suominen, K., Haukka, J., Mantere, O., Arvilommi, P., Leppamäki, S. and Isometsä, E. T. J Affect Disord. 2009; 115(1-2): 11-7. IF 3.271 BACKGROUND: Hopelessness, a key risk factor for suicidal behaviour overall, has been studied little among bipolar disorder (BD) patients. For purposes of prevention, it is important to know whether it is predominantly a patient's permanent trait or merely reflects the highly variable illness states. We investigated the degree to which hopelessness is trait- or state-related during the course of BD. METHODS: The Jorvi Bipolar Study (JoBS) is a naturalistic prospective study representing psychiatric in- and outpatients with DSM-IV BD I and II. Repeated measurements with the Beck Hopelessness Scale of 188 patients at baseline, 6 months and 18 months were analysed using a linear regression model with general estimation equations. Factors covarying with hopelessness during follow-up were investigated. RESULTS: Levels of hopelessness varied markedly between illness phases, being highest in depressive and mixed phases, and lowest in euthymia, hypomania or mania. Hopelessness was independently associated with concurrent severity of depression (estimate 0.231, p<0.001), anxiety (0.105, p<0.001), fewer manic symptoms (-0.096, p=0.001) and comorbid personality disorder (1.741, p=0.001). However, the strongest predictor of degree of hopelessness during follow-up was previous hopelessness (0.403, p<0.001). LIMITATIONS: After baseline, relatively few patients had manic, hypomanic, mixed or depressive mixed phases. Hopelessness was measured at only three time-points. CONCLUSIONS: Level of hopelessness varies markedly between patients in different phases of BD, but is also, to a degree, a permanent feature. Among BD patients, hopelessness appears to be both a trait- and state-related characteristic. Wille, S. M., Raes, E., Lillsunde, P., Gunnar, T., Laloup, M., Samyn, N., Christophersen, A. S., Moeller, M. R., Hammer, K. P. and Verstraete, A. G. Ther Drug Monit. 2009. IF 2.410 In recent years, the interest in the use of oral fluid as a biological matrix has increased significantly, particularly for detecting driving under the influence of drugs (DUID). In this study, the relationship between the oral fluid and the blood concentrations of drugs of abuse in drivers suspected of DUID is discussed. Blood and oral fluid samples were collected from drivers suspected of DUID or stopped during random controls by the police in Belgium, Germany, Finland, and Norway for the ROSITA-2 project. The blood samples were analyzed by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS), sometimes preceded by immunoassay screening of blood or urine samples. The oral fluid samples were analyzed by GC-MS or LC-MS(/MS). Scatter plots and trend lines of the blood and oral fluid concentrations and the median, mean, range, and SD of the oral fluid to blood (OF:B) ratios were calculated for amphetamines, benzodiazepines, cocaine, opiates, and triangle up-2 tetrahydrocannabinol. The ratios found in this study were comparable with those that were published previously, but the range was wider. The OF:B ratios of basic drugs such as amphetamines, cocaine, and opiates were >1 [amphetamine: median (range) 13 (0.5-182), methylenedioxyamphetamine: 4 (1-15), methylenedioxymethamphetamine: 6 (0.9-88), methamphetamine: 5 (2-23), cocaine: 22 (4-119), benzoylecgonine: 1 (0.2-11), morphine: 2 (0.8-6), and codeine: 10 (0.8-39)]. The ratios for benzodiazepines were very low, as could be expected as they are highly protein bound and weakly acidic, leading to low oral fluid concentrations [diazepam: 0.02 (0.01-0.15), nordiazepam: 0.04 (0.01-0.23), oxazepam: 0.05 (0.03-0.14), and temazepam: 0.1 (0.06-0.54)]. For tetrahydrocannabinol, an OF:B ratio of 15 was found (range 0.01-569). In this study, the time of last administration, the dose, and the route of administration were unknown. Nevertheless, the data reflect the variability of the OF:B ratios in drivers thought to be under the influence of drugs. The wide range of the ratios, however, does not allow reliable calculation of the blood concentrations from oral fluid concentrations. Saffold Virus, a Human Theiler's-Like Cardiovirus, Is Ubiquitous and Causes Infection Early in Life Zoll, J., Hulshof, S. E., Lanke, K., Lunel, F. V., Melchers, W. J. G., Schoondermark-van de Ven, E., Roivainen, M., Galama, J. M. D. and van Kuppeveld, F. J. M. Plos Pathogens. 2009; 5(5). Article. IF 9.125 The family Picornaviridae contains well-known human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and parechovirus). In addition, this family contains a number of viruses that infect animals, including members of the genus Cardiovirus such as Encephalomyocarditis virus (EMCV) and Theiler's murine encephalomyelits virus (TMEV). The latter are important murine pathogens that cause myocarditis, type 1 diabetes and chronic inflammation in the brains, mimicking multiple sclerosis. Recently, a new picornavirus was isolated from humans, named Saffold virus (SAFV). The virus is genetically related to Theiler's virus and classified as a new species in the genus Cardiovirus, which until the discovery of SAFV did not contain human viruses. By analogy with the rodent cardioviruses, SAFV may be a relevant new human pathogen. Thus far, SAFVs have sporadically been detected by molecular techniques in respiratory and fecal specimens, but the epidemiology and clinical significance remained unclear. Here we describe the first cultivated SAFV type 3 (SAFV-3) isolate, its growth characteristics, full-length sequence, and epidemiology. Unlike the previously isolated SAFV-1 and -2 viruses, SAFV-3 showed efficient growth in several cell lines with a clear cytopathic effect. The latter allowed us to conduct a large-scale serological survey by a virus-neutralization assay. This survey showed that infection by SAFV-3 occurs early in life (>75% positive at 24 months) and that the seroprevalence reaches >90% in older children and adults. Neutralizing antibodies were found in serum samples collected in several countries in Europe, Africa, and Asia. In conclusion, this study describes the first cultivated SAFV-3 isolate, its full-length sequence, and epidemiology. SAFV-3 is a highly common and widespread human virus causing infection in early childhood. This finding has important implications for understanding the impact of these ubiquitous viruses and their possible role in acute and/or chronic disease. |