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Interventions in relation to occupational burnout: The population-based health 2000 study Ahola, K., Honkonen, T., Virtanen, M., Kivimaki, M., Isometsa, E., Aromaa, A. and Lonnqvist, J. Journal of Occupational and Environmental Medicine. 2007; 49(9): 943-952. Journal Article. IF 1.942 Objective: To study participation in occupational and individual-focused interventions in relation to burnout. Methods: We used datafrom a questionnaire, structured interview, national register of psychopharmacological prescriptions, and the Composite International Diagnostic Interview in a nationally representative Finnish sample of 3276 employees (30 to 64 years)' Results: When compared with employees free of burnout, the odds ratio of severe burnout for participation in occupational interventions was 0.41 (95% confidence interval [CI] = 0.26 to 0.65) and in individual-focused interventions 5.36 (95% CI = 3.14 to 9.17). Antidepressant prescriptions were 2.53 (95% CI = 1.04 to 6.15) times more common among those with severe without burnout after adjustment for depressive and anxiety disorders. Conclusions: Employees with burnout were less often targets of occupational interventions but participated more in individual-focused interventions when compared with other employees. The use of antidepressants among employees with severe burnout was not fully explained by ressive or anxiety disorders. Castro, F. A., Haimila, K., Pasanen, K., Kaasila, M., Patama, T., Partanen, J., Surcel, H. M., Pukkala, E. and Lehtinen, M. Int J STD AIDS. 2007; 18(10): 672-9. Journal Article. IF 1.274 Cervical cancer (CxCa) is a long-term sequelae caused by persistent human papillomavirus (HPV) infection. Genetic susceptibility to the persistent infection and CxCa is associated with certain human leucocyte antigen (HLA) types. The same susceptibility genes may also determine whether a woman will be protected against the persistent infection and against CxCa by HPV vaccination or not. A systematic review of literature identified following HLAs to be associated with CxCa: A11 (odds ratio [OR] = 1.4, 95% confidence interval [CI] 1.1-2.0); B7 (1.5, 1.1-2.0); B15 (0.6, 0.4-0.8); DR2 (1.2, 1.1-1.4) and DR6 (0.6, 0.5-0.8). In the Caucasian population, HLA-B7 and DR6, and DR2 and B15 antigens showed at least borderline associations. In view of a bone marrow donor registry at the Finnish Red Cross and the Finnish Cancer Registry, we created geographic distribution maps of index HLA frequencies and CxCa incidence in the fertile-aged Finnish population. Increased incidence of CxCa was found in a region of western coastal Finland, where frequency of two CxCa susceptibility genes (HLA-DR2 and B7) was increased, and frequency of one CxCa resistance gene (HLA-B15) was decreased. Whether or not HLA type determines also regional susceptibility to persistent HPV infection, and the success of HPV vaccination in preventing both the persistent infection and CxCa warrants further investigation. Cooke, R. M., Wilson, A. M., Tuomisto, J. T., Morales, O., Tainio, M. and Evans, J. S. Environmental Science & Technology. 2007; 41(18): 6598-6605. Journal Article. IF 4.040 In support of an assessment of the mortality impacts of the Kuwait Oil Fires we interviewed six European experts in epidemiology and toxicology using formal procedures for elicitation of expert judgment. While the primary focus of the elicitations was to characterize the public health impacts of the fires, the experts provided quantitative estimates of the mortality impacts of hypothetical changes in the levels of ambient fine particulate matter (PM2.5) in both the United States and Europe. Uncertainty was assessed by asking each expert to provide the 5th, 25th, 50th, 75th, and 90th percentiles of their subjective cumulative probability density function for each quantity of interest. The results suggest that many regulatory risk assessments underestimate the impacts Of PM2.5 mortality; confirm that only a small fraction of the mortality impact occurs within the first few months after exposure; and indicate that it may be important to better address the differential toxicities of particles from various source classes. By providing quantitative estimates of the uncertainty in current estimates Of PM2.5 mortality risks, the study facilitates structured analysis of the value of further research on PM2.5 and its impacts. Das, S., Bennett, A. J., Sovio, U., Ruokonen, A., Martikainen, H., Pouta, A., Hartikainen, A. L., Franks, S., Elliott, P., Poulton, J., Jarvelin, M. R. and McCarthy, M. I. Journal of Clinical Endocrinology and Metabolism. 2007; 92(8): 3219-3223. Journal Article. IF 5.799 Context: Mitochondrial dysfunction is increasingly implicated in pathogenesis of adult metabolic disease. Rare mitochondrial (mt) DNA mutations impair glucose homeostasis, but the contribution of common variants is unclear. In small studies, variation within the OriB origin of replication (at mt16189 in particular) has been associated with both early growth and adult metabolic phenotypes and may contribute to life-course relationships between the two. Objective: The aim was to study a large well-characterized cohort to determine whether previously reported small-scale associations between OriB sequence variation and early growth and adult metabolic phenotypes are robust. Design/Setting/Participants: This was a genetic association study of 5470 individuals from the population-based Northern Finland Birth Cohort of 1966, followed prospectively from pregnancy to age 31 yr. Main Outcome Measures: We measured indices of early growth (including birth weight, placental weight, and ponderal index) and adult metabolic homeostasis (including body mass index, fasting glucose and insulin, indices of insulin action and secretion) and their relationship to variation in the OriB region. Results: Previously reported associations could not be confirmed. There were no significant (P < 0.01, uncorrected) associations between OriB sequence variation and measures of early growth including birth weight (P = 0.52, comparing individuals with mt16189T to those with a homopolymeric C-tract) and placental weight (P = 0.49). There were no significant associations with adult metabolic phenotypes including fasting glucose (P = 0.07), fasting insulin (P = 0.42), and homeostatic model assessment-derived measures of insulin sensitivity or secretion (P = 0.45 and P = 0.56, respectively). Conclusion: Despite substantial power to detect previously reported effects, mtDNA variations around OriB are not major contributors to variation in early growth and metabolic phenotypes during early adulthood. Microarray image segmentation using additional dye - An experimental study Gupta, R., Ruosaari, S., Kulathinal, S., Hollmen, J. and Auvinen, P. Molecular and Cellular Probes. 2007; 21(5-6): 321-328. Journal Article. IF 2.016 The DNA microarray technique allows monitoring the expression levels of thousands of genes simultaneously. A single DNA microarray experiment involves a number of error-prone manual and automated processes, which influence the results and have an impact on the subsequent stages of analysis. Typical problems of arrays are pinning errors while probe printing and the corruption of spots by noise patches. These errors should be detected at the time of image analysis in order to prevent the erroneous intensities from ending up in the analysis and inference stages. Results: In this paper we introduce the concept (referred to as SybrSpot) of utilizing information provided by an additional dye, SYBR green RNA II, for segmentation of gene expression microarrays. Owing to the effective binding of the SYBR green RNA II to the array probes, an image with high signal-to-noise ratio is obtained. This image is used to learn about the spot quality and to flag spots which are not reliably hybridized and corrupted by noise. Further, we compare SybrSpot with GenePix and demonstrate that SybrSpot performs better than GenePix when flagging spots with no probes or weak probes. Availability: The code is available upon request to authors. (c) 2007 Elsevier Ltd. All rights reserved. Population risk and exposure-response from exposures to long-range transported wildfire smoke Hanninen, O., Salonen, R. O., Lanki, T., Koistinen, K., Jantunen, M. and Anttila, P. Epidemiology. 2007; 18(5): S191-S191. Meeting Abstract. IF 4.339 Hyvarinen, A., Sebastian, A., Pekkanen, J., Larsson, L., Korppi, M., Putus, T. and Nevalainen, A. Archives of Environmental & Occupational Health. 2006; 61(4): 149-157. Journal Article. IF 0.279 The authors assessed determinants of ergosterol, 3-OH fatty acids (FAs), and viable microbes in vacuum cleaner dust, and investioated the association between these microbial markets and childhood asthma. The authors studied the homes of 36 children who were new cases of childhood asthma and the homes of 36 controls. Home characteristics explained 34% to 44% of the variation in levels of different microbial groups. Determinants of 3-OH FAs were a lower level of cleanliness, having a fireplace, having livestock, and moisture damage; determinants of viable bacteria were the level of home repair needed and the material used in the building frame of the home. Ergosterol was associated with the presence of livestock and the practice of cleaning rugs outside; viable fungi was associated with the material used in the building frame, visible mold, and the practice of cleaning rugs Outside. Exposure to mesophilic actinonnycetes was nonsignificantly associated with risk of asthma. The authors Concluded that the variation of microbial levels in dust could be explained relatively well by home characteristics, and suggested that exposure to mesophilic actinomycetes may increase the risk of new asthma. Jallinoja, P., Absetz, P., Kuronen, R., Nissinen, A., Talja, M., Uutela, A. and Patja, K. Scand J Prim Health Care. 2007: 1-6. Journal Article. IF 1.541 Objective. To explore physicians' and nurses' views on patient and professional roles in the management of lifestyle-related diseases and their risk factors. Design. A questionnaire study with a focus on adult obesity, dyslipidemia, high blood pressure, type 2 diabetes, and smoking. Setting. Healthcare centres in Paijat-Hame hospital district, Finland. Subjects. Physicians and nurses working in primary healthcare (n=220). Main outcome measures. Perceptions of barriers to treatment of lifestyle-related conditions, perceptions of patients' responsibilities in self-care, experiences of awkwardness in intervening in obesity and smoking, perceptions of rushed schedules, and perceptions of health professionals' roles and own competence in lifestyle counselling. Results. A majority agreed that a major barrier to the treatment of lifestyle-related conditions is patients' unwillingness to change their habits. Patients' insufficient knowledge was considered as such a barrier less often. Self-care was actively encouraged. Although a majority of both physicians and nurses agreed that providing information, and motivating and supporting patients in lifestyle change are part of their tasks, only slightly more than one half estimated that they have sufficient skills in lifestyle counselling. Among nurses, those with less professional experience more often reported having sufficient skills than those with more experience. Two-thirds of the respondents reported that they had been able to help many patients to change their lifestyles into healthier ones. Conclusions. The primary care professionals experienced a dilemma in patients' role in the treatment of lifestyle-related diseases: the patient was recognized as central in disease management but also, if reluctant to change, a major potential barrier to treatment. Juonala, M., Viikari, J. S. A., Alfthan, G., Marniemi, J., Kahonen, M., Taittonen, L., Laitinen, T. and Raitakari, O. T. Circulation. 2007; 116(12): 1367-1373. Journal Article. IF 10.940 Background - Elevated asymmetrical dimethylarginine ( ADMA) is a novel risk factor for atherosclerosis that may impair endothelial function by interfering with endothelial nitric oxide synthesis. To gain insight into the effects of ADMA on systemic endothelial function, we examined the association between ADMA and brachial artery flow-mediated dilation (FMD) in a large population of young adults. Methods and Results - Plasma ADMA and brachial FMD, as well as conventional cardiovascular risk factors, were measured in 2096 white adults aged 24 to 39 years. In univariate analysis, ADMA was inversely correlated with FMD (r=-0.07, P=0.003). The inverse association between ADMA and FMD remained significant in a multivariable regression model adjusted for age, sex, conventional cardiovascular risk factors, estimated glomerular filtration rate, and brachial artery baseline diameter (beta +/- SE -1.56 +/- 0.62%, P=0.01). Conclusions - We conclude that elevated plasma ADMA concentrations are associated with decreased brachial FMD responses in healthy adults. These data provide evidence at the population level that ADMA levels are associated with endothelial function. Kankaanpaa, A., Liukkonen, R. and Ariniemi, K. Forensic Sci Int. 2007; 170(2-3): 133-8.Journal Article. IF 1.397 Gamma-hydroxybutyrate (GHB) is an increasingly popular drug of abuse that causes stimulation, euphoria, anxiolysis or hypnosis, depending on the dose used. Low doses of the drug are used recreationally, and also implicated in drug-facilitated sexual assaults. Because of the unusually steep dose-response curves, accidental GHB overdosing, leading to coma, seizures or death can occur. Being a controlled substance, GHB is often substituted with its non-scheduled precursors gamma-butyrolactone (GBL) and 1,4-butanediol (BD), which are rapidly metabolized into GHB in the body. Here we describe an assay for GHB, GBL and BD in blood and/or urine samples. GHB and BD were extracted from diluted 200 microL aliquots of samples with t-butylmethylether (plus internal standard benzyl alcohol) in test tubes preloaded with NaCl. After acidification and centrifugation the solvent phase was transferred to a test tube preloaded with Na(2)SO(4), incubated for 30 min, centrifuged again, and evaporated in vacuum. The residue was mixed with N-methyl-N-trimethylsilyl-trifluoroacetamide (MSTFA) in acetonitrile, and injected into a GC-MS. When analyzing GBL, the salting-out step was omitted, and analysis was performed with a GC-FID apparatus. As revealed by the validation data this procedure is suitable for quantitative determination of GHB and its precursors in blood and/or urine samples. Kerttula, A. M., Lyytikainen, O., Karden-Lilja, M., Ibrahem, S., Salmenlinna, S., Virolainen, A. and Vuopio-Varkila, J. BMC Infect Dis. 2007; 7: 94. Journal Article. IF 1.898 BACKGROUND: In Finland, the annual number of MRSA notifications to the National Infectious Disease Register (NIDR) has constantly increased since 1995, and molecular typing has revealed numerous outbreak isolates of MRSA. We analyzed the data on MRSA notifications of the NIDR, and MRSA isolates were identified mainly by pulsed-field gel electrophoresis (PFGE) at the National Reference Laboratory (NRL) in Finland during 1997-2004. One isolate representative of each major PFGE type was further characterized by multilocus sequence (MLST)-, staphylococcal cassette chromosome mec (SCCmec)-, and Panton-Valentine leukocidin (PVL)-typing. RESULTS: The annual number of MRSA notifications to the NIDR rose over ten-fold, from 120 in 1997 to 1458 in 2004, and the proportion of MRSA among S. aureus blood isolates tripled, from <1% during 1997-2003 to 2.8% in 2004. During the same period of time, 253 different strains among 4091 MRSA isolates were identified by PFGE: 215 were sporadic and 38 outbreak/epidemic strains, including 24 new strains. Two epidemic strains resembling internationally recognized MRSA clones accounted for most of the increase: FIN-16 (ST125:IA) from <1% in 1997 to 25% in 2004, and FIN-21 (ST228:I) from 6% in 2002 to 28% in 2004. Half of the ten most common strains carried SCCmec IV or V. CONCLUSION: The predominant MRSA strains seem to change over time, which encourages us to continue implementing active control measures with each new MRSA case. Kettunen, J., Lanki, T., Yli-Tuomi, T. and Pekkanen, J. Epidemiology. 2007; 18(5): S35-S36. Meeting Abstract. IF 4.339 The effect of birth order and parental age on the risk of type 1 and 2 diabetes among young adults Lammi, N., Moltchanova, E., Blomstedt, P., Eriksson, J. G., Taskinen, O., Sarti, C., Tuomilehto, J. and Karvonen, M. Diabetologia. 2007. Journal Article. IF 5.247 AIMS/HYPOTHESIS: The aim of this study was to examine the effects of birth order and parental age on the risk of type 1 and type 2 diabetes among Finnish individuals aged 15-39 years. METHODS: Data on all cases of type 1 diabetes (n = 1,345) and type 2 diabetes (n = 1,072), diagnosed between 1992 and 1996, were collected from four sources: standardised national reports from diabetes nurses, the National Hospital Discharge Register, the Drug Prescription Register and the Drug Reimbursement Register. Information on matched controls and the family members of all study subjects were obtained from the National Population Registry. The odds ratios (ORs) for both types of diabetes were estimated using a conditional logistic regression model. RESULTS: There was a U-shaped relationship between maternal age and the risk of type 2 diabetes in the offspring: the risk was higher in children born to young and old mothers compared with children born to mothers aged around 30 years. The children born second (OR 0.76, 95% CI 0.62-0.94), third (OR 0.73, 95% CI 0.55-0.95), or fourth (OR 0.66, 95% CI 0.47-0.94) had a lower risk of type 2 diabetes than the first-born children. Maternal age, paternal age, and birth order did not have an effect on the risk of type 1 diabetes in the individuals aged 15-39 years at the time of diagnosis. CONCLUSIONS/INTERPRETATION: Maternal age and birth order are both associated with the risk of early-onset type 2 diabetes. However, part of these associations may be due to low birthweight. In this study neither parental age nor birth order showed a significant association with the risk of type 1 diabetes diagnosed after 15 years of age. Liukkonen, T., Rasanen, P., Ruokonen, A., Laitinen, J., Jokelainen, J., Leinonen, M., Meyer-Rochow, V. B. and Timonen, M. Psychosom Med. 2007. Journal Article. IF 3.857 Objective: To investigate whether sleep disturbances are associated with C-reactive protein (CRP) levels at the population level. Elevated CRP levels have been found to accompany sleep disturbances, but evidence so far comes only from limited clinical and experimental studies; epidemiological studies are lacking. Methods: We utilized the Northern Finland 1966 Birth Cohort, whose participants have been followed up to the age of 31 years. The hs-enzyme immunoassay method was used to measure highly sensitive-CRP (hs-CRP) concentrations (4011 participants). Self-reported sleep disturbances were ranked from 1 (no problem) to 5 (severe disturbances). Results: Multivariate analyses, after adjusting for confounders, revealed that hs-CRP levels in men in the sleep disturbance category "moderate, considerable and severe" (i.e., self-reported sleep disturbances rated 3, 4, or 5), were >18% (18.2%, 95% Confidence Interval 3.0% to 36.3%) higher than those in men with "no" sleep disturbance. In women, hs-CRP levels did not significantly differ between different sleep disturbance categories. Conclusions: Our results support the hypothesis that moderate-to-severe sleep disturbances in men are associated with slightly increased CRP levels at the epidemiological level. Further investigations are called for to see whether our results can be replicated in other databases. Manor, Y., Blomqvist, S., Sofer, D., Alfandari, J., Halmut, T., Abramovitz, B., Mendelson, E. and Shulman, L. M. Applied and Environmental Microbiology. 2007; 73(18): 5954-5958. Journal Article. IF 3.532 An improved sewage surveillance algorithm (sample acquisition, processing, and molecular analysis) for wild and vaccine-derived polioviruses was developed and validated. It was based on plaque isolation with sensitive and high-throughput methods. The molecular analysis included sequencing; a comparison of the type, rate, and distribution of nucleotide substitutions with a profile for outbreaks evolving from a single progenitor; and phylogenetic analysis for relative similarity. The analyses revealed that two environmental wild type 1 isolates from the Gaza district in 2002 were imported separately, most likely, from Egyptian southern governorates, and were not linked by endemic circulation. These findings illustrate the continuous spreading potential of wild-type poliovirus and underscore the value of extensive environmental surveillance employing advanced molecular analysis to monitor wild poliovirus in poliomyelitis-free regions. Marttila, K., Piepponen, T. P., Kiianmaa, K. and Ahtee, L. Brain Research. 2007; 1160: 82-90. Journal Article. IF 2.341 Transcription factor Delta FosB has been implicated in the psychomotor responses and rewarding effects of drugs of abuse. In the present study, we compared the effects of cocaine on the expression of Delta FosB-like proteins by immunohistochemistry in striatal brain areas of alcohol-preferring (AA) and alcohol-avoiding (ANA) rats. Cocaine was administered using a previously verified treatment paradigm that sensitized the locomotor response to cocaine in AA. but not in ANA rats. We also studied the rewarding effects of cocaine with a conditioned place preference (CPP) paradigm in both lines of rats. Cocaine treatment increased the FosB/Delta FosB immunoreactivity (IR) in the nucleus accumbens of AA rats but not in ANA rats. In addition, after repeated saline injections the accumbal FosB/Delta FosB IR was significantly greater in saline-injected AA rats than in ANA rats. In the caudate-putamen cocaine significantly increased FosB/Delta FosB IR, but no differences were found between the rats of two lines. In the CPP experiment, AA rats treated with cocaine 2.5 mg/kg preferred the cocaine-associated compartment, in contrast to ANA rats, which did not show such a preference. In conclusion, our findings show that AA rats are more sensitive to cocaine than ANA rats, and suggest that one possible mediator for this increased sensitivity could be the increased expression of fosB-derived proteins in the nucleus accumbens of AA rats. (C) 20107 Elsevier B.V. All rights reserved. Diagnosis and prevention of pneumococcal disease Nohynek, H. Adv Exp Med Biol. 2006; 582: 137-50. Journal Article. IF 0.646 Nyberg, S. D., Meurman, O., Jalava, J. and Rantakokko-Jalava, K. Scand J Infect Dis. 2007: 1-8. Journal Article. IF 1.560 A total of 123 clinical Escherichia coli and Klebsiella spp. isolates were included in the study in order to evaluate VITEK 2 AST-NO29 (Nordic) card for detection of extended-spectrum beta-lactamases (ESBL) and to compare the results with genotypic ESBL verification. The results were also compared to alternative phenotypic methods, i.e. agar dilution and disk diffusion. The strains that were ESBL-positive according to AST-N029 were further analysed with the ESBL test card, VITEK 2 AST-N041. Using genotype as reference, Vitek 2 AES had the highest accuracy of the tested methods in classifying the strains as ESBL-positive or -negative (91.1%). When VITEK 2 gave ESBL as the only option for E. coli or K. pneumoniae, 44 of 45 (97.8%) strains had an ESBL gene. VITEK 2 achieved an accuracy of 94.9% and disk diffusion 95.9% compared to the agar dilution method as the phenotypic reference method for the E. coli and K. pneumoniae strains. For the K. oxytoca strains VITEK 2 achieved the highest accuracy (84.0%) of the methods used in this work. Peters, A., Schneider, A., Greven, S., Bellander, T., Forastiere, F., Ibald-Mulli, A., Illig, T., Jacquemin, B., Katsouyanni, K., Koenig, W., Lanki, T., Pekkanen, J., Pershagen, G. and Picciotto, S. Inhalation Toxicology. 2007; 19: 161-175. Journal Article. IF 2.167 Ambient air pollution has been associated with an increased risk of hospital admission and mortality in potentially susceptible sub-populations, including myocardial infarction (MI) survivors. The multicenter epidemiological study described in this report was set up to study the role of air pollution in eliciting inflammation in MI survivors in six European cities, Helsinki, Stockholm, Augsburg, Rome, Barcelona, and Athens. Outcomes of interest are plasma concentrations of the proinflammatory cytokine interleukin 6 (IL-6) and the acute-phase proteins C-reactive protein (CRP) and fibrinogen. In addition, the study was designed to assess the role of candidate gene polymorphisms hypothesized to lead to a modification of the short-term effects of ambient air pollution. In total, 1003 MI survivors were recruited and assessed with at least 2 repeated clinic visits without any signs of infections. In total, 5813 blood samples were collected, equivalent to an average of 5.8 repeated clinic visits per subject (97% of the scheduled 6 repeated visits). Subjects across the six cities varied with respect to risk factor profiles. Most of the subjects were nonsmokers, but light smokers were included in Rome, Barcelona, and Athens. Substantial inter- and intraindividual variability was observed for IL-6 and CRP The study will permit assessing the role of cardiovascular disease risk factors, including ambient air pollution and genetic polymorphisms in candidate genes, in determining the inter- and the intraindividual variability in plasma IL-6, CRP, and fibrinogen concentrations in MI survivors. Rantamaki, T., Hendolin, P., Kankaanpaa, A., Mijatovic, J., Piepponen, P., Domenici, E., Chao, M. V., Mannisto, P. T. and Castren, E. Neuropsychopharmacology. 2007; 32(10): 2152-2162. Journal Article. IF 5.889 Previous studies suggest that brain-derived neurotrophic factor and its receptor TrkB are critically involved in the therapeutic actions of antidepressant drugs. We have previously shown that the antidepressants imipramine and fluoxetine produce a rapid autophosphorylation of TrkB in the rodent brain. In the present study, we have further examined the biochemical and functional characteristics of antidepressant-induced TrkB activation in vivo. We show that all the antidepressants examined, including inhibitors of monoamine transporters and metabolism, activate TrkB rapidly in the rodent anterior cingulate cortex and hippocampus. Furthermore, the results indicate that acute and long-term antidepressant treatments induce TrkB-mediated activation of phospholipase-C gamma 1 (PLC gamma 1) and increase the phosphorylation of cAMP-related element binding protein, a major transcription factor mediating neuronal plasticity. In contrast, we have not observed any modulation of the phosphorylation of TrkB Shc binding site, phosphorylation of mitogen-activated protein kinase or AKT by antidepressants. We also show that in the forced swim test, the behavioral effects of specific serotonergic antidepressant citalopram, but not those of the specific noradrenergic antidepressant reboxetine, are crucially dependent on TrkB signaling. Finally, brain monoamines seem to be critical mediators of antidepressant-induced TrkB activation, as antidepressants reboxetine and citalopram do not produce TrkB activation in the brains of serotonin-or norepinephrine-depleted mice. In conclusion, our data suggest that rapid activation of the TrkB neurotrophin receptor and PLC gamma 1 signaling is a common mechanism for all antidepressant drugs. Work-related physical activity and the risk of dementia and Alzheimer's disease Rovio, S., Kareholt, I., Viitanen, M., Winblad, B., Tuomilehto, J., Soininen, H., Nissinen, A. and Kivipelto, M. International Journal of Geriatric Psychiatry. 2007; 22(9): 874-882. Journal Article. IF 1.930 Background Leisure-time physical activity has been related with a reduced risk of dementia and Alzheimer's disease (AD). The effects of occupational and commuting physical activity (physical activity at work and on the way to work) on cognitive health are still unclear. This study aimed to clarify the association between work-related physical activity and dementia/AD. Methods Participants of the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study were derived from random, population-based samples previously studied in a survey carried out in 1972, 1977, 1982, or 1987. After an average follow-up of 21 years, 1449 individuals (73%) aged 65 to 79 years participated in the re-examination in 1998. Results Neither occupational [Odds Ratio (OR) 1.45; 95% Confidence Intervals (CI) 0.66-3.171 nor commuting physical activity (OR 0.46; 95% CI 0.10-2.17) were associated with the risk of dementia or AD after adjustments for age, sex, education, follow-up time, locomotor symptoms, main occupation during life, income at midlife, leisure-time physical activity, other subtype of work-related physical activity, ApoE genotype, vascular disorders and the smoking status. There were also no interactions between work-related physical activity and the ApoE epsilon 4 genotype, leisure-time physical activity or sex. Conclusions In this study, work-related physical activity was not found to be sufficient to protect against dementia and AD later in life. The lack of effect might be partly due to a residual confounding. Nevertheless, physical activity during leisure-time may be beneficial even for people who are physically active at work or when commuting. Copyright (c) 2007 John Wiley & Sons, Ltd. Sahlberg, A. S., Penttinen, M. A., Heiskanen, K. M., Colbert, R. A., Sistonen, L. and Granfors, K. Arthritis and Rheumatism. 2007; 56(8): 2652-2662. Journal Article. IF 7.751 Objective. To investigate the cause of the enhanced intracellular replication of Salmonella enteritidis in HLA-B27-transfected U937 human monocytic cells and the contribution of HLA-B27 heavy chain (HC) misfolding. Methods. U937 monocytic cell transfectants stably expressing pSV2neo resistant vector (mock), wildtype HLA-B27, or mutated HLA-B27 HCs with amino acid substitutions in the B pocket were differentiated, infected with S enteritidis, and treated with signaling pathway inhibitors or specific p38 small interfering RNA (siRNA). The numbers of living intracellular bacteria were determined with the colony-forming unit method. To visualize S enteritidis, the bacteria were transformed with green fluorescent protein, and studied by microscopy. Results. Treatment with the p38 MAPK inhibitors or with p38 siRNA enhanced the replication of S enteritidis in U937 transfectants, whereas the other inhibitors had no effect. In mock-transfected cells and in cells expressing the mutated B27 HCs in which the misfolding had been corrected, p38 inhibitors impaired their ability to resist the replication of bacteria (mock, B27.A2B, B27.E45M, and B27.C67A). In contrast, the number of intracellular bacteria was not significantly increased in p38 inhibitor-treated cells expressing misfolded B27 HCs (B27g, B27cDNA, and B27.H9F). Conclusion. Our results show that p38 activity plays a crucial role in controlling intracellular S enteritidis in U937 cells. Enhanced replication of bacteria in B27-expressing cells requires that the HCs contain glutamic acid at position 45 and cysteine at position 67. Furthermore, in transfectants expressing misfolded B27 HCs, p38 inhibition had no significant effect on bacterial replication, suggesting that in these cells, the p38 pathway may not function properly. Stenholm, S., Sainio, P., Rantanen, T., Alanen, E. and Koskinen, S. Aging Clinical and Experimental Research. 2007; 19(4): 277-283. Journal Article. IF 1.068 Background and aims: Obesity among older persons is rapidly increasing, thus affecting their mobility negatively. The aim of this study was to examine the association of high body mass index (BMI) with walking limitation, and the effect of obesity-related diseases on this association. Methods: In a representative sample of the Finnish population of 55 years and older (2055 women and 1337 men), maximal walking speed, chronic diseases, and BMI were ascertained in a health examination. Walking limitation was defined as maximal walking speed of less than 1.2 m/s or difficulty in walking 500 meters. To analyze the effects of chronic conditions, smoking, marital status, and education on BMI class differences in walking limitation, covariates were sequentially adjusted in logistic regression analyses. Results: In women, an increasing gradient in the age-adjusted risk of walking limitation was observed with higher BMI: overweight (OR 1,47, 95% CI 1.10-1.96), obese (OR 2.77, 95% CI 2.01-3.82), and severely obese (OR 5.80, 95% CI 3.52-9.54). In men, the risk was significantly increased among the obese (OR 1.63, 95% CI 1.04-2.55) and severely obese (OR 4.33, 95% CI 2.20-8.53). After adjustment of multiple covariates, the association remained significant among-the obese (OR 1.99, 95% CI 1.38-2.86) and severely obese women (OR 3.64, 95% CI 2.12-6.26), as well as severely obese men (OR 2.78, 95% CI 1.30-5.95). Knee osteoarthritis in women and diabetes in men contributed most to the excess risk of walking limitation among obese persons, 18 and 32% respectively. Conclusions: Obesity increases the risk of walking limitation, independent of obesity-related diseases, smoking, marital status, and education, especially in older women. The results of this study emphasize the importance of maintaining normal body weight, in order to prevent obesity-related health risks and loss of functioning in older age. Association of smoking status with obesity and diabetes among elderly people Sulander, T., Rahkonen, O., Nissinen, A. and Uutela, A. Arch Gerontol Geriatr. 2007; 45(2): 159-67. Journal Article. The present study was aimed to examine associations of current and ex-smoking status with obesity and diabetes among elderly people. Nationwide study of Finnish elderly people based on biennial surveys from 1985 to 1995, were used to study 7482 people aged 65-79 years. Smoking status included non-, ex-light, ex-heavy, current light, and current heavy smokers. Obesity was set as body mass index (BMI) > or = 30. Information of smoking, BMI, and diabetes was based on self-reports. Logistic regression was used as the main method of analyses. Compared to non-smokers (reference category), ex-heavy smokers had higher (odds ratio, 1.42; 95% confidence interval: 1.09, 1.85) and current light smokers (OR, 0.46; 95% CI: 0.31, 0.69) lower relative risk of obesity. Current light smokers had also lower and ex-heavy smokers higher rate of diabetes than non-smokers. Ex-heavy smokers had a higher risk of obesity (OR, 1.75; 95% CI: 1.30, 2.36) and diabetes (OR, 1.48; 95% CI: 1.10, 2.01) than ex-light smokers. Same pattern for current smokers was found. Heavy ex- and current elderly smokers are at risk of obesity and diabetes. Thus, heavy smokers should be emphasized in programs promoting smoking cessation. Timonen, M., Salmenkaita, I., Jokelainen, J., Laakso, M., Harkonen, P., Koskela, P., Meyer-Rochow, V. B., Peitso, A. and Keinanen-Kiukaanniemi, S. Psychosom Med. 2007. Journal Article. IF 3.857 Objective: To investigate whether the association between insulin resistance (IR) and depressive symptoms is present already in young adult males. The association between IR and depression has been poorly studied, although the existence of a connection of Type II diabetes with depression is well established. We previously demonstrated at epidemiological level in two groups of men aged 31 years and 61 to 63 years that IR is linked with depressive symptoms. Methods: In a cross-sectional study, involving 1054 healthy Finnish male military conscripts of about 19 years of age, IR was defined through homeostasis model assessment (HOMA-IR). The severity of the depressive symptoms was evaluated through a Finnish modification of the 13-item Beck Depression Inventory (R-BDI). Moderate-to-severe depressive symptoms were said to be present, if the R-BDI score was >/=8, and mild depressive symptoms were present if the R-BDI score was 5 to 7. Results: After adjusting for confounders, moderate-to-severe depressive symptoms increased the risk for IR, as defined by the highest decile of the HOMA-IR, up to 2.8-fold (odds ratio = 2.8; 1.2-6.5). Mild depressive symptoms were not significantly associated with IR. Conclusions: In young adult males, co-occurring strictly defined IR seems to be positively associated with current moderate-to-severe depressive symptoms. |