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New articles - Uudet artikkelit 11.5.2009 - ISI Web of Knowledge & PubMed Search Alert
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Type 2 diabetes prevention in the "real world": Three-year results of the GOAL implementation trial
Absetz, P., Oldenburg, B., Hankonen, N., Valve, R., Heinonen, H., Nissinen, A., Fogelholm, M., Talja, M. and Uutela, A. Diabetes Care. 2009. IF 7.851 Objective: We study the effectiveness of the GOAL Lifestyle Implementation Trial at 36-month follow-up. Research Design and Methods: Participants (N = 352, FINDRISC = 16.2 +/- 3.3, BMI 32.6 +/- 5.0) received six lifestyle counseling sessions over eight months. Measurements were at baseline, 12 months (88.6%) and at 36 months (77.0%). Results: Statistically significant risk reduction at 12 months was maintained at 36 months in weight (-1.0 +/- 5.6 kg), BMI (-0.5 +/- 2.1), and serum total cholesterol (-0.4 +/- 1.1 mmol/l). Conclusions: Maintenance of risk reduction in this "real world" trial proves the intervention's potential for significant public health impact. Occupational burnout as a predictor of disability pension: a population-based cohort study Ahola, K., Gould, R., Virtanen, M., Honkonen, T., Aromaa, A. and Lönnqvist, J. Occupational and Environmental Medicine. 2009; 66(5): 284-290. Article. IF 2.817 Objectives: The aim of this study was to investigate whether burnout predicts new disability pension at population level during a follow-up of approximately 4 years. The diagnosis for which the disability pension was granted was also examined in relation to the level of burnout. Methods: We used a population-based cohort sample (n=3125) of 30-60-year-old employees from an epidemiological health study, the Health 2000 Study, gathered during 2000-2001 in Finland. The data collection comprised an interview, a clinical health examination including a standardised mental health interview, and a questionnaire including the Maslach Burnout Inventory-General Survey. Disability pensions and their causes until December 2004 were extracted from national pension records. The association between burnout and new disability pension was analysed with logistic regression models adjusted for sociodemographic factors and health at baseline. Results: Altogether 113 persons were granted a new disability pension during the follow-up: 22% of those with severe burnout, 6% of those with mild burnout, and 2% of those with no burnout at baseline. After sociodemographic factors and health were adjusted for, each one-point increase in the overall burnout sum score was related to 49% increase in the odds for a future disability pension. A disability pension was most often granted on the basis of mental and behavioural disorders and diseases of the musculoskeletal system among those with burnout. After adjustments, exhaustion dimension among men and cynicism dimension among a combined group of men and women predicted new disability pensions. Conclusion: Burnout predicts permanent work disability and could therefore be used as a risk marker of chronic health-related work stress. To prevent early exit from work life, working conditions and employee burnout should be regularly assessed with the help of occupational health services. Large Scale Association Analysis of Novel Genetic Loci for Coronary Artery Disease Amouyel, P., Arveiler, D., Boekholdt, S. M., Braund, P., Bruse, P., Bumpstead, S. J., Bugert, P., Cambien, F., Danesh, J., Deloukas, P., Doering, A., Ducimetiere, P., Dunn, R. M., El Mokhtari, N. E., Erdmann, J., Evans, A., Ewels, P., Ferrieres, J., Fischer, M., Frossard, P., Garner, S., Gieger, C., Gohri, M. J. R., Goodall, A. H., Grosshennig, A., Hall, A., Hardwick, R., Haukijarvi, A., Hengstenberg, C., Illig, T., Karvanen, J., Kastelein, J., Kee, F., Khaw, K. T., Kluter, H., Konig, I. R., Kuulasmaa, K., Laiho, P., Luc, G., Marz, W., McGinnis, R., McLaren, W., Meisinger, C., Morrison, C., Ou, X., Ouwehand, W. H., Preuss, M., Proust, C., Ravindrarajah, R., Renner, W., Rice, K., Ruidavets, J. B., Saleheen, D., Salomaa, V., Samani, N. J., Sandhu, M. S., Schafer, A. S., Scholz, M., Schreiber, S., Schunkert, H., Silander, K., Singh, R., Soranzo, N., Stark, K., Stegmayr, B., Stephens, J., Thompson, J., Tiret, L., Trip, M. D., van der Schoot, E., Virtamo, J., Wareham, N. J., Wichmann, H. E., Wiklund, P. G., Wright, B., Ziegler, A. and Zwaginga, J. J. Arteriosclerosis Thrombosis and Vascular Biology. 2009; 29(5): 774-U356. Article. IF 7.221 Background-Combined analysis of 2 genome-wide association studies in cases enriched for family history recently identified 7 loci (on 1p13.3, 1q41, 2q36.3, 6q25.1, 9p21, 10q11.21, and 15q22.33) that may affect risk of coronary artery disease (CAD). Apart from the 9p21 locus, the other loci await substantive replication. Furthermore, the effect of these loci on CAD risk in a broader range of individuals remains to be determined. Methods and Results-We undertook association analysis of single nucleotide polymorphisms at each locus with CAD risk in 11 550 cases and 11 205 controls from 9 European studies. The 9p21.3 locus showed unequivocal association (rs1333049, combined odds ratio [OR]=1.20, 95% CI [1.16 to 1.25], probability value=2.81x10(-21)). We also confirmed association signals at 1p13.3 (rs599839, OR=1.13 [1.08 to 1.19], P=1.44x10(-7)), 1q41 (rs3008621, OR=1.10 [1.04 to 1.17], P=1.02x10(-3)), and 10q11.21 (rs501120, OR=1.11 [1.05 to 1.18], P=4.34x10(-4)). The associations with 6q25.1 (rs6922269, P=0.020) and 2q36.3 (rs2943634, P=0.032) were borderline and not statistically significant after correction for multiple testing. The 15q22.33 locus did not replicate. The 10q11.21 locus showed a possible sex interaction (P = 0.015), with a significant effect in women (OR=1.29 [1.15 to 1.45], P=1.86x10(-5)) but not men (OR=1.03 [0.96 to 1.11], P=0.387). There were no other strong interactions of any of the loci with other traditional risk factors. The loci at 9p21, 1p13.3, 2q36.3, and 10q11.21 acted independently and cumulatively increased CAD risk by 15% (12% to 18%), per additional risk allele. ConclusionsThe findings provide strong evidence for association between at least 4 genetic loci and CAD risk. Cumulatively, these novel loci have a significant impact on risk of CAD at least in European populations. (Arterioscler Thromb Vasc Biol. 2009; 29: 774-780.) Badeau, R. M., Metso, J., Wahala, K., Tikkanen, M. J. and Jauhiainen, M. J Steroid Biochem Mol Biol. 2009. IF 2.799 High-density lipoprotein (HDL) and 17-beta estradiol independently provide protection against atherosclerosis. Estradiol fatty acyl esters incorporate into HDL and whether this association enhances the atheroprotective properties of HDL is unclear. The study objective was to clarify the role that HDL-associated estradiol fatty acyl esters play in mediating the initial steps of reverse cholesterol transport. Cholesterol efflux potential from cholesterol loaded macrophage cells to HDL-associated estradiol ester or between HDL from premenopausal women and age-matched males and the cellular receptors involved were examined. Human THP-1 macrophages, loaded with [(3)H]cholesterol oleate, acetylated low-density lipoprotein, were pretreated with or without SR-BI inhibitors or an estrogen receptor antagonist and incubated with either HDL-associated estradiol oleate, HDL lacking estradiol oleate, or isolated HDL from females and males, and cholesterol efflux was measured. Cellular internalization and hydrolysis of HDL-associated [(3)H]estradiol ester were determined. HDL-associated estradiol oleate and premenopausal female HDL demonstrated significantly higher cholesterol efflux capacity to media than male HDL. SR-BI and estrogen receptor inhibition significantly reduced this effect. Cells internalized and subsequently hydrolyzed HDL-associated [(3)H]estadiol ester to [(3)H]estradiol and again SR-BI inhibition reduced this internalization. These results demonstrate that HDL mediated macrophage cholesterol efflux potential is enhanced by HDL-associated estradiol esters. A follow-up study of chromosome 19q13 in multiple sclerosis susceptibility Bonetti, A., Koivisto, K., Pirttila, T., Elovaara, I., Reunanen, M., Laaksonen, M., Ruutiainen, J., Peltonen, L., Rantamaki, T. and Tienari, P. J. Journal of Neuroimmunology. 2009; 208(1-2): 119-124. Article. IF 2.920 A possible role of allelic variation on chromosome 19q13 in multiple sclerosis (MS) susceptibility has been suggested. We tested association of sixteen 19q13 markers with MS in 459 families. Nominally significant associations were tested in an independent set of 323 families as well as in the pooled set of 782 families. We were not able to confirm previously suggested associations with APOE, GIPR, ZNF45, ILT6 and D19S535. In the screening dataset nominally significant associations were found with D19S867 and with APOE haplotype (p = 0.007 in both), but these were not replicated in the independent dataset nor in the pooled analysis of 757 families. Thus, we were not able to detect any statistically significant allelic associations. Re-sequencing based approaches may be required for elucidating the role chromosome 19q13 with MS. (C) 2009 Elsevier B.V. All rights reserved. Dioxin-Sensitive Proteins in Differentiating Osteoblasts: Effects on Bone Formation In Vitro Carpi, D., Korkalainen, M., Airoldi, L., Fanelli, R., Hakansson, H., Muhonen, V., Tuukkanen, J., Viluksela, M. and Pastorelli, R. Toxicological Sciences. 2009; 108(2): 330-343. Article. IF 3.814 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an endocrinedisrupting environmental pollutant which affects bone tissue, although the mechanistic basis of this action is far from clear. We adopted a proteome approach to investigate the disturbance of osteogenesis evoked by TCDD in an in vitro osteoblast differentiation model of rat mesenchymal stem cells. Eighteen individual proteins showed a significant change in abundance as results of ten days of TCDD exposure, at which time mRNA changes in osteoblast differentiation markers were also observed. These proteins were mostly involved in cytoskeleton organization and biogenesis, actin filament-based processes, protein transport, and folding. The alteration in cell architecture and increase in cell adhesion were confirmed by confocal microscopy. The TCDD-induced decrease in the expression of calcium-binding proteins may interfere with osteoblast calcium deposition, which was in fact reduced by TCDD. This is the first report investigating, at the protein expression level, the effect of TCDD during osteoblastic differentiation. Interestingly, MetaCore pathway analysis grouped the majority of these proteins around two principal nodes (c-fos and c-myc) suggesting that they may participate in the transcriptional activation of key pathways in TCDD-driven inhibition of osteoblast differentiation. Our findings provide evidence of new molecular players in the effects of TCDD on bone development. Castaneda, A. E., Marttunen, M., Suvisaari, J., Perala, J., Saarni, S. I., Aalto-Setala, T., Aro, H., Lönnqvist, J. and Tuulio-Henriksson, A. Psychol Med. 2009: 1-11. IF 4.212 BACKGROUND: Psychiatric co-morbidity is often inadequately controlled for in studies on cognitive functioning in depression. Our recent study established no major deficits in cognition among young adults with a history of pure unipolar depression. The present study extends our previous work by examining the effects of psychiatric co-morbidity and other disorder characteristics on depression-related cognitive functioning.MethodPerformance in verbal and visual short-term memory, verbal long-term memory and learning, attention, processing speed, and executive functioning was compared between a population-based sample aged 21-35 years with a lifetime history of unipolar depressive disorders (n=126) and a random sample of healthy controls derived from the same population (n=71). Cognitive functioning was also compared between the subgroups of pure (n=69) and co-morbid (n=57) depression. RESULTS: The subgroups of pure and co-morbid depression did not differ in any of the cognitive measures assessed. Only mildly compromised verbal learning was found among depressed young adults in total, but no other cognitive deficits occurred. Received treatment was associated with more impaired verbal memory and executive functioning, and younger age at first disorder onset with more impaired executive functioning. CONCLUSIONS: Psychiatric co-morbidity may not aggravate cognitive functioning among depressed young adults. Regardless of co-morbidity, treatment seeking is associated with cognitive deficits, suggesting that these deficits relate to more distress. Large genomic rearrangements and germline epimutations in Lynch syndrome Gylling, A., Ridanpää, M., Vierimaa, O., Aittomäki, K., Avela, K., Kääriäinen, H., Laivuori, H., Pöyhönen, M., Sallinen, S. L., Wallgren-Pettersson, C., Jarvinen, H. J., Mecklin, J. P. and Peltomäki, P. International Journal of Cancer. 2009; 124(10): 2333-2340. Article. IF 4.555 In one-third of families fulfilling the Amsterdam criteria for hereditary nonpolyposis colorectal cancer/Lynch syndrome, and a majority or those not fulfilling these criteria point mutations in DNA mismatch repair (MMR) genes are not found. The role of large genomic rearrangements and germline epimutations in MLH1, MSH2 and MSH6 was evaluated in 2 such cohorts. All 45 index patients were mutation-negative by genomic sequencing and testing for a prevalent population-specific founder mutation, and selectively lacked MMR protein expression in tumor tissue. Eleven patients ("research cohort") represented 11 mutation-negative families among 81 verified or putative Lynch syndrome families from the nation-wide Hereditary Colorectal Cancer Registry of Finland. Thirty-four patients from 33 families ("clinic-based cohort") represented suspected Lynch syndrome patients tested for MMR gene mutations in a diagnostic laboratory during 2004-2007. Multiplex ligation-dependent probe amplification (MLPA) and methylation-specific (MS)-MLPA were used to detect rearrangements and epimutations, respectively. Large genomic deletions occurred in 12/45 patients (27%), being present in 3/25 (12%), 9/16 (56%) and 0/4 (0%) among index patients lacking MLH1, MSH2 or MSH6 expression, respectively. Germline epimutations of MLH1, one of which coexisted with a genomic deletion, occurred in 2 patients (4%) and were accompanied by monoallelic expression in mRNA. Large genomic deletions (mainly MSH2) and germline epimutations (MLH1) together explain a significant fraction of point inutation-negative families suspected of Lynch syndrome and are associated with characteristic clinical and family features. Our findings have important implications in the diagnosis and management of such families. (C) 2008 Wiley-Liss, Inc. Hänninen, O. O., Salonen, R. O., Koistinen, K., Lanki, T., Barregard, L. and Jantunen, M. Journal of Exposure Science and Environmental Epidemiology. 2009; 19(4): 414-422. Article. IF 2.880 Long-range transported particulate matter (PM) air pollution episodes associated with wild. res 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 wild. res 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 PM2.5 level of 15.7 mu g/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 mu g/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 wild. re 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 mu g/m(3) of fine PM) are in line with the more general estimates for urban PM and those used in the current risk assessment. Hirvonen, J., Tuominen, U., Seitsalo, S., Lehto, M., Paavolainen, P., Hietaniemi, K., Rissanen, P., Sintonen, H. and Blom, M. Value Health. 2009. IF 3.387 Objective: This prospective randomized study assessed the effect of waiting time (WT) on health outcomes in Finnish patients admitted to hospital for primary total hip replacement (THR). Methods: A total of 395 consecutive patients with a need for a primary THR because of osteoarthritis and who were placed on the waiting list between August 2002 and November 2003. After placement on the waiting list, the patients were randomly assigned to a short WT (</=3 group p (HHS).< score hip Harris self-report patient the by measured were function and pain Hip instrument. 15D generic was life of quality Health-related admission. hospital at list waiting on placing time questionnaires self-administered completed patients The (n="174)" WT nonfixed a or months)> Results: Of the 395 patients, 312 (79%) completed the follow-up (140 patients with short and 172 with nonfixed WT). At admission, the mean 15D scores for patients with short and nonfixed WT were 0.784 and 0.783, respectively. In the intention-to-treatment analysis, the difference between the groups (Delta0.001, 95% confidence interval [CI]: -0.019 to 0.021) was not statistically significant or clinically important. The mean self-report HHS in patients with short WT was 43.5, and among those with nonfixed WT was 41.9. The difference (Delta1.6, 95% CI: -1.77 to 4.87) was not statistically significant. Conclusions: Both generic and disease-specific measures revealed that longer WTs did not result in poorer health status at admission. Holmlund, E., Quiambao, B., Ollgren, J., Jaakkola, T., Neyt, C., Poolman, J., Nohynek, H. and Käyhty, H. Clin Vaccine Immunol. 2009. IF 1.995 This study focuses on the immunogenicity in Filipino infants of three pneumococcal vaccine candidate proteins; pneumococcal histidin triad protein D (PhtD), choline binding protein A (CbpA) and the lysozyme LytC, all inducing protection in animal models. The IgG antibody concentrations to PhtD and its putative protective and exposed C-terminal fragment, PhtD C, CbpA and LytC were measured by EIA in 52 serum samples of pregnant women, 39 cord bloods and consecutive serum samples (N=263) from 52 newborns scheduled to be taken at 6 time points between 6 weeks and 10 months of age. A nasopharyngeal swab to detect pneumococcal carriage was taken parallel to the serum samples. The antibody concentrations in the cord bloods were similar to those of the mothers. In infant sera, the geometric mean antibody concentrations (GMCs) for all three proteins decreased until the age of 18 weeks and started to increase after that age, suggesting that the infants own antibody production started close to the age of 4-5 months. The increase in GMCs by age, most clear cut for CbpA, was associated with pneumococcal carriage. Anti-PhtD concentrations were higher than anti-PhtD C concentrations, but correlated well (r= 0.89 at 10.5 months), suggesting that antibodies are directed to the supposedly exposed and protective C- terminal part of PhtD. Our results show that young children are able to develop an antibody response to PhtD, CbpA and LytC, and encourage the development of pneumococcal protein vaccines for this age group. Jakobsen, M. U., O'Reilly, E. J., Heitmann, B. L., Pereira, M. A., Balter, K., Fraser, G. E., Goldbourt, U., Hallmans, G., Knekt, P., Liu, S. M., Pietinen, P., Spiegelman, D., Stevens, J., Virtamo, J., Willett, W. C. and Ascherio, A. American Journal of Clinical Nutrition. 2009; 89(5): 1425-1432. Article. IF 6.603 Background: Saturated fatty acid (SFA) intake increases plasma LDL-cholesterol concentrations; therefore, intake should be reduced to prevent coronary heart disease (CHD). Lower habitual intakes of SFAs, however, require substitution of other macronutrients to maintain energy balance. Objective: We investigated associations between energy intake from monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), and carbohydrates and risk of CHD while assessing the potential effect-modifying role of sex and age. Using substitution models, our aim was to clarify whether energy from unsaturated fatty acids or carbohydrates should replace energy from SFAs to prevent CHD. Design: This was a follow-up study in which data from 11 American and European cohort studies were pooled. The outcome measure was incident CHD. Results: During 4-10 y of follow-up, 5249 coronary events and 2155 coronary deaths occurred among 344,696 persons. For a 5% lower energy intake from SFAs and a concomitant higher energy intake from PUFAs, there was a significant inverse association between PUFAs and risk of coronary events (hazard ratio: 0.87; 95% CI: 0.77, 0.97); the hazard ratio for coronary deaths was 0.74 (95% CI: 0.61, 0.89). For a 5% lower energy intake from SFAs and a concomitant higher energy intake from carbohydrates, there was a modest significant direct association between carbohydrates and coronary events (hazard ratio: 1.07; 95% CI: 1.01, 1.14); the hazard ratio for coronary deaths was 0.96 (95% CI: 0.82, 1.13). MUFA intake was not associated with CHD. No effect modification by sex or age was found. Conclusion: The associations suggest that replacing SFAs with PUFAs rather than MUFAs or carbohydrates prevents CHD over a wide range of intakes. Am J Clin Nutr 2009;89:1425-32. Neuronal ceroid lipofuscinoses Jalanko, A. and Braulke, T. Biochimica Et Biophysica Acta-Molecular Cell Research. 2009; 1793(4): 697-709. Review. IF 4.374 The neuronal ceroid lipofuscinoses (NCL) are severe neurodegenerative lysosomal storage disorders of childhood, characterized by accumulation of autofluorescent ceroid lipopigments in most cells. NCLs are caused by mutations in at least ten recessively inherited human genes, eight of which have been characterized. The NCL genes encode soluble and transmembrame proteins, localized to the endoplasmic reticulum (ER) or the endosomal/lysosomal organelles. The precise function of most of the NCL proteins has remained elusive, although they are anticipated to carry pivotal roles in the central nervous system. Common clinical features in NCL, including retinopathy, motor abnormalities, epilepsia and dementia, also suggest that the proteins may be functionally linked. All subtypes of NCLs present with selective neurodegeneration in the cerebral and cerebellar cortices. Animal models have provided valuable data about the pathological characteristics of NCL and revealed that early glial activation precedes neuron loss in the thalamocortical system. The mouse models have also been efficiently utilized for the evaluation of therapeutic strategies. The tools generated by the accomplishments in genomics have further substantiated global analyses and these have initially provided new insights into the NCL field. This review summarizes the current knowledge of the NCL proteins, basic characteristics of each disease and studies of pathogenetic mechanisms in animal models of these diseases. (C) 2008 Elsevier B.V. All rights reserved. The role of Chlamydia trachomatis infection in male infertility Joki-Korpela, P., Sahrakorpi, N., Halttunen, M., Surcel, H. M., Paavonen, J. and Tiitinen, A. Fertility and Sterility. 2009; 91(4): 1448-1450. Article. IF 3.168 To study the association between plasma antibodies to Chlamydia trachomatis and male infertility, 90 men from infertile couples attending a University Hospital IVF clinic for IVF/intracytoplasmic sperm injection, and 190 healthy blood donors as control subjects were studied for IgG and IgA antibodies to C. trachomatis, and for the men from infertile couples seminal fluid analysis was performed according to the World Health Organization criteria. The prevalence of plasma IgG antibodies to C. trachomatis was higher among men from infertile couples than control men, and men with chlamydial antibodies had lower sperm counts than those without. (Fertil Steril (R) 2009;91:1448-50. (C) 2009 by American Society for Reproductive Medicine.) Use of a genetic isolate to identify rare disease variants: C7 on 5p associated with MS Kallio, S. P., Jakkula, E., Purcell, S., Suvela, M., Koivisto, K., Tienari, P. J., Elovaara, I., Pirttila, T., Reunanen, M., Bronnikov, D., Viander, M., Meri, S., Hillert, J., Lundmark, F., Harbo, H. F., Lorentzen, A. R., De Jager, P. L., Daly, M. J., Hafler, D. A., Palotie, A., Peltonen, L. and Saarela, J. Human Molecular Genetics. 2009; 18(9): 1670-1683. Article. IF 7.806 Large case-control genome-wide association studies primarily expose common variants contributing to disease pathogenesis with modest effects. Thus, alternative strategies are needed to tackle rare, possibly more penetrant alleles. One strategy is to use special populations with a founder effect and isolation, resulting in allelic enrichment. For multiple sclerosis such a unique setting is reported in Southern Ostrobothnia in Finland, where the prevalence and familial occurrence of multiple sclerosis (MS) are exceptionally high. Here, we have studied one of the best replicated MS loci, 5p, and monitored for haplotypes shared among 72 regional MS cases, the majority of which are genealogically distantly related. The haplotype analysis over the 45 Mb region, covering the linkage peak identified in Finnish MS families, revealed only modest association at IL7R (P = 0.04), recently implicated in MS, whereas most significant association was found with one haplotype covering the C7-FLJ40243 locus (P = 0.0001), 5.1 Mb centromeric of IL7R. The finding was validated in an independent sample from the isolate and resulted in an odds ratio of 2.73 (P = 0.000003) in the combined data set. The identified relatively rare risk haplotype contains C7 (complement component 7), an important player of the innate immune system. Suggestive association with alleles of the region was seen also in more heterogeneous populations. Interestingly, also the complement activity correlated with the identified risk haplotype. These results suggest that the MS predisposing locus on 5p is more complex than assumed and exemplify power of population isolates in the identification of rare disease alleles. Kanerva, M., Ollgren, J., Virtanen, M. J. and Lyytikäinen, O. American Journal of Infection Control. 2009; 37(3): 227-230. Article. IF 1.907 Background: We estimated the burden of health care-associated infections (HAIs) occurring in Finnish adult acute care hospitals using national hospitalization data and estimates of HAI based on a recent national prevalence survey. Methods: A total of 7531 non-HAI patients and 703 HAI patients (8.5%) identified in the prevalence survey were included in the study. Using the patients' national identity numbers and the prevalence survey date, we obtained data on hospitalizations, including discharge diagnoses from the National Hospital Discharge Registry (NHDR), and the dates and causes of death from the National Population Information System. We converted the prevalence of HAI into incidence using the Rhame-Sudderth formula, assessed the 28-day case fatality of the HAI patients, and then extrapolated the annual estimates of HAI burden from the total number of hospitalizations in adult acute care hospitals in 2005 (n = 804,456). We also assessed the sensitivity or the NHDR diagnoses in identifying HAIs. Results: The estimated incidence of HAIs was 5.7% (95% confidence interval = 5.0% to 6.5%), and the 28-day case fatality was 9.8%. Thus > 8500 hospitalizations per million population annually would result in at least 1 HAI and similar to 270 HAI-associated deaths within 28 days. The sensitivity of the NHDR diagnoses was 34% (range by infection type, 0% to 67%). Conclusion Our disease burden estimates can be used in health care planning and resource allocation. The NHDR was not a reliable source for case finding of HAIs. Copyright (c) 2009 by the Association for Professionals in Infection Control and Epidemiology. Inc. Prevalence, awareness and treatment of hypertension in Finland during 1982-2007 Kastarinen, M., Antikainen, R., Peltonen, M., Laatikainen, T., Barengo, N. C., Jula, A., Salomaa, V., Jousilahti, P., Nissinen, A., Vartiainen, E. and Tuomilehto, J. J Hypertens. 2009. IF 4.364 OBJECTIVES: To assess the trends in prevalence and in control of hypertension in various parts of Finland during 1982-2007. METHODS: Three independent cross-sectional population surveys were conducted in 1982, 2002 and 2007 with age-stratified samples of men and women aged 25-64 years from the national population register. The total number of participants with complete blood pressure (BP) measurements was 16 775. RESULTS: Overall, during 1982-2007, the prevalence of hypertension (systolic BP >/= 140 mmHg and/or diastolic BP >/= 90 mmHg and/or current use of antihypertensive drug treatment) fell significantly in both sexes. In men, it fell from 63.3 to 52.1%; in women, from 48.1 to 33.6% (P < 0.001 for both sexes). However, during the past 5-year period, a decline was observed only in women in south-western Finland (P = 0.003). Furthermore, previously observed significant increases in the proportions of treated and controlled hypertensive individuals did not continue among men during 2002-2007. Despite the evident progress in all aspects of hypertension care since 1982, still in 2007, only 68% of all hypertensive individuals were aware of their condition, 52% of those who were aware were treated with antihypertensive drugs and 37% of the drug-treated patients had normal BP. CONCLUSION: Steady progress has been made in the prevention and treatment of hypertension in Finland. However, further improvements are clearly needed. Keski-Nisula, L., Katila, M. L., Remes, S., Heinonen, S. and Pekkanen, J. J Allergy Clin Immunol. 2009. IF 8.115 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. The prototype endothelial marker PAL-E is a leukocyte trafficking molecule Keuschnigg, J., Henttinen, T., Auvinen, K., Karikoski, M., Salmi, M. and Jalkanen, S. Blood. 2009. IF 10.896 "Pathologische anatomie leiden endothelium" (PAL-E) antibody has been used for over 20 years as a marker for vascular endothelium. Despite its widespread use the target of this antibody was only recently identified as "plasmalemma vesicle associated protein-1" (PV-1). However, thus far no function has been identified for this molecule. Here we report that activation of human umbilical vein endothelial cells (HUVECs) with TNF-alpha resulted in a remarkable redistribution of PV-1 towards the peripheral areas of the cells. Furthermore, in vitro end point transmigration experiments showed that transcellularly migrating lymphocytes are surrounded by rings containing PV-1 and caveolin-1. Moreover, PV-1 physically associates with vimentin. In addition, administration of anti PV-1 antibody during capillary flow assays resulted in a significant inhibition of lymphocyte transmigration through the endothelial cell layer, while rolling and adhesion were unaffected. In vivo blockage of PV-1 by an antibody in acute peritonitis and air pouch model resulted in a significant decrease in the number of migrating leukocytes. Here we thus define leukocyte transendothelial migration as the first known function for PV-1. Associations of genetic lactase non-persistence and sex with bone loss in young adulthood Laaksonen, M. M. L., Impivaara, O., Sievanen, H., Viikari, J. S. A., Lehtimaki, T. J., Lamberg-Allardt, C. J. E., Karkkainen, M. U. M., Valimaki, M., Heikkinen, J., Kroger, L. M., Kroger, H. P. J., Jurvelin, J. S., Kahonen, M. A. P. and Raitakari, O. T. Bone. 2009; 44(5): 1003-1009. Article. IF 3.966 Some studies have reported that after attainment of peak bone mass (PBM), slow bone loss may occur in both men and women; however, findings are inconsistent. Genetic factors play a significant role in bone loss, but the available evidence is conflicting. Genetic lactase non-persistence (lactase C/C-13910 genotype) is suggested to increase risk for inadequate calcium intake predisposing to poorer bone health. We investigated whether this genotype is associated with PBM and bone loss in young Finnish adults. Subjects belong to the Cardiovascular Risk in Young Finns Study that is an ongoing multi-centre follow-up of atherosclerosis risk factors. From the original cohort, randomly selected subjects aged 20-29 participated in baseline bone mineral density (BMD) measurements (n = 358), and in follow-up measurements 12 years later (n = 157). Bone mineral content (BMC) and BMD at lumbar spine (LS) and femoral neck (FN) were measured at baseline and follow-Lip with dual energy X-ray absorptiometry (DXA). Lactase C/T-13910 polymorphism was determined by PCR and allele-specific fluorogenic probes. Information on lifestyle was elicited with questionnaires. During the follow-tip, bone loss at both bone sites was greater in males (LS BMD: - 1.1%. FN BMD: - 5.2%) than in females (LS BMD: + 2.1%, FN BMD: - 0.7%) (both bone sites p = 0.001). Younger age predicted greater loss of FN BMC and BMD in females (p = 0.013 and p = 0.001, respectively). Increased calcium intake predicted FN BMD gain in both sexes (in females B = 0.007 g/cm(2)/mg, p = 0.002; in males B = 0.006, p = 0.045), and increased physical activity LS BMD gain in females (B=0.091 g/cm(2)/physical activity point, p=0.023). PBM did not differ between the lactase genotypes, but males with the CC-13910 genotype seemed to be prone to greater bone loss during the follow-up (LS BMD: C/C vs. T/T p = 0.081). In conclusion, bone loss in Young adulthood was more common in males than in females and seemed to occur mainly at the femoral neck. Young males with the lactase CC-13910 genotype may be more susceptible to bone loss; however, calcium intake predicts changes in bone mass more than the lactase genotype. (C) 2009 Elsevier Inc. All rights reserved. Maturation of cytokine-producing capacity from birth to 1 yr of age Lappalainen, M., Roponen, M., Pekkanen, J., Huttunen, K. and Hirvonen, M. R. Pediatr Allergy Immunol. 2009. IF 2.454 Little is known about the immunologic maturation in the early stages of life. The aim of this study was to investigate maturation of immune system from birth to 1 yr of age and to compare immune functions between mothers and their children. Also the effect of atopy to the immune responses of children was examined. Cord blood samples (n = 228) and peripheral blood samples of children (n = 200) and their mothers (n = 208) 1 yr after birth were collected. Whole blood samples were stimulated for 24 and 48 h with Staphylococcal enterotoxin B (SEB), lipopolysaccharide (LPS) and the combination of phorbol ester and ionomycin (P/I). Production of TNF-alpha, IFN-gamma, IL-5, IL-8 and IL-10 was determined using ELISA. Significant mother-to-child correlation was detected in cytokine-producing capacity at the age of 1 yr. TNF-alpha (P/I, SEB and LPS stimulation), IFN-gamma (P/I and SEB), IL-5 (P/I and SEB) and IL-10 (P/I, SEB and LPS) producing capacity increased from birth to 1 yr of age. In general, stimulated cytokine responses were higher in mothers' than in children's blood samples, except in the case of P/I and LPS-stimulated IL-8, which were highest at birth. Maternal inhalation atopy was associated with increased cord blood IL-5 (24 and 48 h) and IL-10 (48 h) production following P/I stimulation. Also children of food atopic mothers expressed elevated cord blood IL-10 (48 h, P/I) responses and decreased IFN-gamma/IL-5 ratio (24 h, P/I). In addition, the production of IFN-gamma (24 and 48 h, P/I) and the IFN-gamma/IL-5 ratio (24 h and 48 h, P/I) at the age of 1 yr was lower among children with food atopic mothers. In conclusion, our results suggest that both adaptive and innate immune responses increase from birth to 1 yr of age, but are still weak in comparison to adult responses. Cytokine responses of children begin to correlate with those of their mothers during the first year of life. Although only few associations were observed between atopy and cytokine-producing capacity, our results suggest that children of atopic mothers express T(h)2-polarized cytokine pattern. Dairy Foods and Risk of Stroke Larsson, S. C., Mannisto, S., Virtanen, M. J., Kontto, J., Albanes, D. and Virtamo, J. Epidemiology. 2009; 20(3): 355-360. Article. IF 5.283 Background: Consumption of milk and other dairy foods has been associated with reduced risk of stroke, although not all studies have shown this consistently. Methods: We examined the association between dairy food intake and risk of stroke subtypes within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Between 1985 and 1988, 26,556 Finnish male smokers aged 50-69 years who had no history of stroke completed a food frequency questionnaire. We used Cox proportional hazards models to estimate relative risks (RRs) and 95% confidence intervals (CIs), adjusted for potential confounders. Results: During a mean follow-up of 13.6 years, 2702 cerebral infarctions, 383 intracerebral hemorrhages, and 196 subarachnoid hemorrhages were ascertained. We observed positive associations between whole milk intake and risk of intracerebral hemorrhage (RR = 1.41 for the highest vs. lowest quintile of intake; 95% CI = 1.02-1.96) and between yogurt intake and subarachnoid hemorrhage (RR = 1.83 for the highest vs. lowest quintile of intake; 95% CI = 1.20-2.80). Men in the highest quintile of cream intake had a moderate decreased risk of cerebral infarction (0.81; 0.72-0.92) and intracerebral hemorrhage (0.72; 0.52-1.00). There were no strong associations between intakes of total dairy, low-fat milk, sour milk, cheese, ice cream, or butter and risk of any stroke subtype. Conclusions: Theses findings suggest that intake of certain dairy foods may be associated with risk of stroke. A novel, colorimetric neutralization assay for measuring antibodies to influenza viruses Lehtoranta, L., Villberg, A., Santanen, R. and Ziegler, T. J Virol Methods. 2009. IF 1.933 A colorimetric cell proliferation assay for measuring neutralizing antibodies to influenza viruses in human sera is described. Following a 90-min incubation, the serum-virus mixture was transferred to Madin-Darby canine kidney cells cultured in 96-well plates. After further incubation for three days, a tetrazolium salt was added to the wells. Cellular mitochondrial dehydrogenases cleave the tetrazolium salt to formazan, and the resulting color change is read by a spectrophotometer. The absorbance values correlate directly to the number of viable cells in the assay well and thus also to the neutralizing activity of influenza-specific antibodies present in the serum. With the few hands-on manipulations required, this assay allows simultaneous testing of a considerable number of sera, offers opportunities for automation, and is suitable for use under biosafety level-3 conditions. The test was used to study the antibody response after the administration of seasonal, inactivated, trivalent influenza vaccine. Antibody titers determined by the neutralization test in pre- and post-vaccination serum pairs were compared with those obtained by the hemagglutination inhibition assay. The neutralization test yielded higher pre- and post-vaccination titers and a larger number of significant increases in post-vaccination antibody titer than the hemagglutination inhibition test. This new test format could serve as a valuable laboratory tool for influenza vaccine studies. Prolonged impact of a one-week course of clindamycin on Enterococcus spp. in human normal microbiota Lindgren, M., Lofmark, S., Edlund, C., Huovinen, P. and Jalava, J. Scand J Infect Dis. 2009; 41(3): 215-9. IF 1.209 Human intestinal Enterococcus spp. was monitored during a 2-y period after 7 d clindamycin treatment. Consecutive faecal samples were collected from 8 healthy volunteers, 4 of whom had received clindamycin. After treatment, the number of enterococcal colonies was diminished and species variation extended. Erythromycin and clindamycin resistance increased from 19% to 69% and 0% to 67%, respectively. Elevated resistance levels lasted up to 9 months and erm(B) was detected in samples up to 6 months. Our results show that the clindamycin treatment had a prolonged impact on resistance and species variation. Reduced fluoroquinolone susceptibility in Salmonella enterica isolates from travelers, Finland Lindgren, M. M., Kotilainen, P., Huovinen, P., Hurme, S., Lukinmaa, S., Webber, M. A., Piddock, L. J., Siitonen, A. and Hakanen, A. J. Emerg Infect Dis. 2009; 15(5): 809-12. IF 5.775 We tested the fluoroquinolone susceptibility of 499 Salmonella enterica isolates collected from travelers returning to Finland during 2003-2007. Among isolates from travelers to Thailand and Malaysia, reduced fluoroquinolone susceptibility decreased from 65% to 22% (p = 0.002). All isolates showing nonclassical quinolone resistance were from travelers to these 2 countries. Hospitalizations and deaths associated with Clostridium difficile infection, Finland, 1996-2004 Lyytikäinen, O., Turunen, H., Sund, R., Rasinpera, M., Kononen, E., Ruutu, P. and Keskimäki, I. Emerg Infect Dis. 2009; 15(5): 761-5. IF 5.775 To determine whether the rate of Clostridium difficile-associated disease (CDAD) and CDAD-related deaths were increasing in Finland, we analyzed registry data from 1996 through 2004. We determined the number of hospital discharges that had a diagnosis code specific for CDAD from the International Classification of Diseases, 10th revision: "enterocolitis due to Clostridium difficile" (A04.7) and "pseudomembranous enterocolitis associated with antimicrobial therapy" (K52.8), listed as any diagnosis in the National Hospital Discharge Registry. CDAD-related deaths were identified from death certificates. Those discharged with a CDAD diagnosis doubled from 810 (16/100,000 population) in 1996 to 1,787 (34/100,000) in 2004. The increase was most prominent for patients 7gt;64 years of age but concerned only those discharged with diagnosis code A04.7. The number of those discharged with diagnosis code K52.8 remained stable. The age-standardized mortality rate associated with CDAD increased from 9/million in 1998 to 17/million in 2004; the increase was limited to persons 7gt;64 years of age. Martikainen, P., Moustgaard, H., Murphy, M., Einio, E. K., Koskinen, S., Martelin, T. and Noro, A. Gerontologist. 2009; 49(1): 34-45. Article. IF 1.820 Purpose: Due to population aging, the need for long-term institutional care is increasing. We study the potentially modifiable sociodemographic factors that affect the rate of entry into and exit from long-term care. Design and Methods: A 40% sample from the population registration data of Finns aged 65 and older living in private households at the end of 1997 (n = 280,722) was followed for first entry into (n = 35,926) and subsequent exit-due to death or return to the community-from long-term institutional care until the end of 2003. Results: Being female, old, living alone, and of low socioeconomic status increased the risk for entering long-term care. Exit was affected by the same factors, but the associations were weaker and, with the exception of age, in the opposite direction. Women's higher risk for entry was due to older age and greater likelihood of living alone. The effects of living arrangements and socioeconomic factors on entry were stronger among men and were attenuated after adjustment for each other and for health status. The mean duration of care was 1,064 days among women and 686 among men. implications: Gender, age, living arrangements, and socioeconomic status are major determinants of institutional residence. Women and certain other population groups, e.g., those living alone, are likely to spend a longer time in institutional care because of higher rates of entry and lower rates of exit. These results have implications for the financing of long-term care and for targeting of interventions aimed at delaying it. Mikkelsen, S. S., Jensen, S. B., Chiliveru, S., Melchjorsen, J., Julkunen, I., Gaestel, M., Arthur, J. S. C., Flavell, R. A., Ghosh, S. and Paludan, S. R. Journal of Biological Chemistry. 2009; 284(16): 10774-10782. Article. IF 5.581 The innate immune system provides an initial defense system against microbial infections and contributes to the development of adaptive immune response. Type I interferons play a pivotal role for the first line of defense against virus infections, and dendritic cells (DCs) are important sensors of pathogens responsible for priming of adaptive immune responses in lymphoid organs. Here we have investigated the role and mechanisms of activation of the MAPK pathway in innate immune responses induced by Sendai virus, a negative sense single-stranded RNA virus. Both p38 and JNK were activated in fibroblasts and DCs after infection with Sendai virus in a manner dependent on virus replication and RIG-I. Virus replication was also required for stimulation of interferon production in both cell types and interleukin-12 production in DCs. Blocking of p38 MAPK activation by the specific inhibitor SB202190 abolished the expression of these cytokines. p38 MAPK exerted its function independent of the MAPK-activated protein kinases MK2, MNK, and MSK1/2. We also observed that TRAF2 and TAK1 were essential for RIG-I-mediated activation of p38 MAPK. Interestingly, the kinase activity of p38 MAPK was required for its own phosphorylation, which was kinetically associated with TAB1 interaction. By contrast, the canonical p38 upstream kinase MKK3 was not involved in the p38-dependent response. Thus, activation of p38 MAPK by RIG-I proceeds via a TRAF2-TAK1-dependent pathway, where the enzymatic activity of the kinase plays an essential role. The p38 MAPK in turn stimulates important processes in the innate antiviral response. Efficacy of pneumococcal conjugate vaccine against PCR-positive acute otitis media Palmu, A. A., Saukkoriipi, A., Jokinen, J., Leinonen, M. and Kilpi, T. M. Vaccine. 2009; 27(10): 1490-1. IF 3.377 We aimed to assess the efficacy of a pneumococcal conjugate vaccine against acute otitis media (AOM) positive by pneumolysin-PCR (Ply-PCR). 1662 infants vaccinated with PncCRM or control vaccine using random allocation were followed for AOM up to 24 months of age. When AOM was diagnosed a middle ear fluid sample was obtained for etiological assays. During the per protocol follow-up period the PncCRM vaccine efficacy was 19% against Ply-PCR-positive AOM but only 3% when culture-positive cases were excluded. The data do not support effect of PncCRM on AOM in which only Ply-PCR suggests pneumococcal etiology. Breastfeeding stimulates total and cow's milk-specific salivary IgA in infants Piirainen, L., Pesola, J., Pesola, I., Komulainen, J. and Vaarala, O. Pediatric Allergy and Immunology. 2009; 20(3): 295-298. Article. IF 2.454 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. Magnesium treatment in alcoholics: A randomized clinical trial Poikolainen, K. and Alho, H. Substance Abuse Treatment Prevention and Policy. 2008; 3. Article. Background: Magnesium (Mg) deficiency is common among alcoholics. Earlier research suggests that Mg treatment may help to normalize elevated enzyme activities and some other clinically relevant parameters among alcoholics but the evidence is weak. Methods: The effect of Mg was studied in a randomized, parallel group, double-blind trial. The patients were first treated for alcohol withdrawal symptoms and then received for 8 weeks either 500 mg of Mg divided into two tablets or matching placebo. Measurements were made at the beginning and in the end of the Mg treatment period. The primary outcome was serum gammaglutamyltransferase (S-GGT) activity; secondary outcomes included aspartate-aminotransferase (SAST) and alanine-aminotransferase (S-ALT) activity. Results: The number of randomized patients (completers) was 64 (27) in the treatment and 54 (31) in the control group. In intention-to-treat-analyses and in most analyses of study completers, there were no significant differences between the Mg-treated and placebo groups in the outcome variables. When baseline serum Mg level, coffee intake, and the number of unused Mg tablets were controlled for in a multivariate regression model, after-treatment serum Mg levels were found to be higher among the Mg-treated group than in the placebo group (t-test 3.334, df = 53, p = 0.002). After controlling for age, body weight, baseline alcohol intake, subsequent change in alcohol intake and baseline S-AST, the after-treatment S-AST levels were found to be lower among the Mg-treated group than in the placebo group (t-test 2.061, df = 49, p = 0.045). Conclusion: Mg treatment may speed up the S-AST decrease in compliant patients. This might decrease the risk of death from alcoholic liver disease. Trial Registration: ClinicalTrials.gov ID NCT00325299 Personal Invitations for Population-based Breast Cancer Screening Saalasti-Koskinen, U., Makela, M., Saarenmaa, I. and Autti-Ramo, I. Academic Radiology. 2009; 16(5): 546-550. Article. IF 2.094 Rationale and Objectives. Women who are invited for breast cancer screening should get enough information about the benefits and harms of screening to make an informed decision on participation. Personal invitations are an important source of information, because all invited women receive them. The objective of this Study was to evaluate the information breast cancer screening units send to women invited for screening in Finland. Materials and Methods. A questionnaire was sent to all breast cancer screening units in Finland in 2005 and 2008, and the information (eg, invitations, results letters, leaflets) the units sent to women was collected. Results from 2005 were sent as feedback to the units. Data were analyzed descriptively, and results from the 2 years were compared. Results. Screening units sent personal invitation letters usually providing fixed appointment times. Most units informed about participation free of charge and the benefits of detecting breast cancer early. Harm associated with screening was seldom mentioned; no unit mentioned the possibility of false-negative results or overtreatment. Conclusion. The screening units provided very variable information, which often was biased toward optimizing participation. The high participation rate (approximately 88%) in Finland may be due partly to the prescriptive nature of the invitation letters. National templates for information letters would be useful. Schuhmacher, M., Kiviranta, H., Ruokojarvi, P., Nadal, M. and Domingo, J. L. Environment International. 2009; 35(3): 607-613. Article. IF 2.797 The concentrations of polychlorinated dibenzo-p-dioxins and dibenzolfurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) were determined in breast milk from women living in the vicinity of a new hazardous waste incinerator (HWI) in Catalonia, Spain. The results were compared with the levels obtained in two previous surveys carried out in 1998 (baseline study) and 2002. The current concentrations of PCDD/Fs in breast milk ranged from 45 to 143 pg/g fat (2.8 to 11.2 pg WHO-TEQ/g fat), while total PCBs ranged from 114 to 617 pg/g fat (2.8 to 17.6 pg WHO-TEQ/g fat). PBDE concentrations (sum 15 congeners) ranged from 0.57 ng/g fat to 5.9 ng/g fat, with a mean value of 2.5 ng/g fat. A general decrease of the concentrations for PCDD/Fs and both planar and total PCBs was observed. Regarding to PBDE concentrations in breast milk, similar levels between the 2002 and the present study were noted. The levels of PCDD/Fs and PCBs in milk of women living in urban areas were higher than those corresponding to the industrial zones (38% and 40%. respectively). However, the current PBDE levels were slightly lower (13%) in the urban than in the industrial zone. For PCDD/Fs and PCBs, the current decreases are in accordance with the reduction in the dietary intake of these pollutants found in recent studies carried out in the same area of study. (C) 2008 Elsevier Ltd. All rights reserved. Simojoki, K., Vorma, H. and Alho, H. Substance Abuse Treatment Prevention and Policy. 2008; 3. Article. Background: In Finland, buprenorphine (Subutex) is the most abused opioid. In order to curb this problem, many treatment centres transferred ("forced transfer") their buprenorphine patients to the buprenorphine plus naloxone (Suboxone) combination product in late 2003. Methods: Data from a retrospective study involving five different treatment centers, examining the effects of switching patients to Suboxone, were gathered from 64 opioid-dependent patients who had undergone the medication transfer. Results: Most patients (90.6%) switched to Suboxone at the same dose of buprenorphine that they had been receiving as Subutex (average 22 mg). The majority of these patients (71.9%) were maintained at the same dose of Suboxone throughout the 4-week study period. During the first 4 weeks, 50% of the patients reported adverse events and at the four month time point, 26.6% reported adverse events. However, due to adverse events one patient only discontinued treatment with Suboxone during the 4-week study period, and five during the four month follow-up period. Of the 26 patients in the follow-up period, Suboxone was misused intravenously once each by 4 patients and twice by 1 patient. These 5 patients all reported that injecting Suboxone was like injecting "nothing" with any euphoria, or that it was a bad experience. Conclusion: We conclude that when patients are transferred from high doses (> 22 mg) of buprenorphine to the combination product, dose adjustments may be necessary especially in the later phase of the treatment. We recommend that a transfer from Subutex to Suboxone should be carefully discussed and planned in advance with the patients and after the transfer adverse events should be regularly monitored. With regard of buprenorphine IV abuse, the combination product seems to have a less abuse potential than buprenorphine alone. Leaking gut in type 1 diabetes Vaarala, O. Curr Opin Gastroenterol. 2008; 24(6): 701-6. Review IF 3.271 PURPOSE OF REVIEW: Several studies have indicated that children with type 1 diabetes show altered intestinal immune system and, in particular, increased small intestinal permeability. This review discusses the recent research linking the gut and type 1 diabetes, which may reveal novel pathogenic pathways and new possibilities for disease prevention. RECENT FINDINGS: Recent studies indicate that not only patients with manifest type 1 diabetes show increased small intestinal permeability and high serum levels of zonulin, that is protein controlling epithelial tight junctions, but prediabetic, normoglycemic individuals with beta-cell autoimmunity show signs of leaking gut. Also studies in BioBreeding-rat model of autoimmune diabetes suggest that high permeability of the intestine precedes autoimmune diabetes. The enteropathy characterized by increased intestinal permeability and inflammation seems to be the basis for the development of beta-cell destruction, as for example zonulin agonist, which decreases the gut permeability, prevents the development of diabetes. SUMMARY: The leaking gut syndrome with subclinical inflammation is associated with beta-cell autoimmunity and type 1 diabetes. Furthermore, treatment of the leakiness has been reported to modulate development of autoimmune diabetes in animal models suggesting that intestinal environment plays a key role in the destruction of insulin-producing beta-cells in the pancreas. NURSING ADVOCACY IN PROCEDURAL PAIN CARE Vaartio, H., Leino-Kilpi, H., Suominen, T. and Puukka, P. Nursing Ethics. 2009; 16(3): 340-362. Article. IF 0.817 In nursing, the concept of advocacy is often understood in terms of reactive or proactive action aimed at protecting patients' legal or moral rights. However, advocacy activities have not often been researched in the context of everyday clinical nursing practice, at least from patients' point of view. This study investigated the implementation of nursing advocacy in the context of procedural pain care from the perspectives of both patients and nurses. The cross-sectional study was conducted on a cluster sample of surgical otolaryngology patients (n = 405) and nurses (n = 118) from 12 hospital units in Finland. The data were obtained using an instrument specially designed for this purpose, and analysed statistically by descriptive and non-parametric methods. According to the results, patients and nurses have slightly different views about which dimensions of advocacy are implemented in procedural pain care. It seems that advocacy acts are chosen and implemented rather haphazardly, depending partly on how active patients are in expressing their wishes and interests and partly on nurses' empowerment. Hopelessness across phases of bipolar I or II disorder: A prospective study Valtonen, H. M., Suominen, K., Haukka, J., Mantere, O., Arvilommi, P., Leppamaki, S. and Isometsa, E. T. Journal of Affective Disorders. 2009; 115(1-2): 11-17. Article. IF 3.144 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 BID. 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. (C) 2008 Elsevier B.V. All rights reserved. Mobility limitations in persons with psychotic disorder: findings from a population-based survey Viertio, S., Sainio, P., Koskinen, S., Perälä, J., Saarni, S. I., Sihvonen, M., Lönnqvist, J. and Suvisaari, J. Social Psychiatry and Psychiatric Epidemiology. 2009; 44(4): 325-332. Article. IF 1.944 Background There are few reports on mobility limitations in persons with psychotic disorder although restrictions in mobility may aggravate the general functional limitations of these patients. Our aim was to investigate mobility limitations among subjects with psychotic disorder in a general population-based sample. Methods A nationally representative sample of 6,927 persons aged 30 and older self-reported mobility limitations in an interview and was examined in performance tests. Diagnostic assessment of DSM-IV psychotic disorders combined SCID interview and case note data. Lifetime-ever diagnoses of psychotic disorder were classified into schizophrenia, other nonaffective psychotic disorders and affective psychoses. Results Self-reported mobility limitations were highly prevalent in persons with schizophrenia and other nonaffective psychosis, but not in the affective psychosis group. After adjusting for age and sex, persons with schizophrenia and other nonaffective psychoses but not affective psychoses had significantly increased odds of having both self-reported and test-based mobility limitations as well as weak muscle strength. Schizophrenia remained an independent predictor of mobility limitations even after controlling for lifestyle-related factors and chronic medical conditions. Among persons with nonaffective psychoses, higher levels of negative symptoms predicted mobility limitations. Conclusion Self-reported mobility limitations are prevalent already at a young age in persons with schizophrenia and other nonaffective psychotic disorders, and among older persons with these disorders both self-reported limitations and measured performance tests show lower capacity in mobility. Difficulties in mobility are associated with negative symptoms. Mental health care professionals should pay attention to mobility limitations in persons with psychotic disorder. |