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Buprenorphine misuse in Finland Aalto, M., Halme, J., Visapaa, J. P. and Salaspuro, M. Substance Use & Misuse. 2007; 42(6): 1027-1028. Letter. IF 1.376 Combined effects of thrombosis pathway gene variants predict cardiovascular events Auro, K., Alanne, M., Kristiansson, K., Silander, K., Kuulasmaa, K., Salomaa, V., Peltonen, L. and Perola, M. PLoS Genet. 2007; 3(7): e120. Journal Article. IF 7.671 The genetic background of complex diseases is proposed to consist of several low-penetrance risk loci. Addressing this complexity likely requires both large sample size and simultaneous analysis of different predisposing variants. We investigated the role of four thrombosis genes: coagulation factor V (F5), intercellular adhesion molecule 1 (ICAM1), protein C (PROC), and thrombomodulin (THBD) in cardiovascular diseases. Single allelic gene variants and their pair-wise combinations were analyzed in two independently sampled population cohorts from Finland. From among 14,140 FINRISK participants (FINRISK-92, n = 5,999 and FINRISK-97, n = 8,141), we selected for genotyping a sample of 2,222, including 528 incident cardiovascular disease (CVD) cases and random subcohorts totaling 786. To cover all known common haplotypes (>10%), 54 single nucleotide polymorphisms (SNPs) were genotyped. Classification-tree analysis identified 11 SNPs that were further analyzed in Cox's proportional hazard model as single variants and pair-wise combinations. Multiple testing was controlled by use of two independent cohorts and with false-discovery rate. Several CVD risk variants were identified: In women, the combination of F5 rs7542281 x THBD rs1042580, together with three single F5 SNPs, was associated with CVD events. Among men, PROC rs1041296, when combined with either ICAM1 rs5030341 or F5 rs2269648, was associated with total mortality. As a single variant, PROC rs1401296, together with the F5 Leiden mutation, was associated with ischemic stroke events. Our strategy to combine the classification-tree analysis with more traditional genetic models was successful in identifying SNPs-acting either in combination or as single variants--predisposing to CVD, and produced consistent results in two independent cohorts. These results suggest that variants in these four thrombosis genes contribute to arterial cardiovascular events at population level. Bykov, I., Jauhiainen, M., Olkkonen, V. M., Saarikoski, S. T., Ehnholm, C., Junnikkala, S., Vakeva, A., Lindros, K. O. and Meri, S. J Hepatol. 2007; 46(5): 907-14. Journal Article. IF 6.073 BACKGROUND/AIMS: Fatty infiltration initiates alcohol-induced liver changes and complement component C3 affects lipid metabolism. We recently observed that ethanol-induced steatosis seen in normal (C3(+/+)) mice was absent in livers of C3-deficient (C3(-/-)) mice. To understand the underlying molecular mechanisms we analyzed lipid parameters and liver gene expression profiles in these mice. METHODS: A Western-type high-fat diet with ethanol or carbohydrates (control) was fed for 6 weeks to C3(+/+) and C3(-/-) mice. Serum and liver lipid parameters were analyzed and liver mRNA expression patterns studied by micro-array analysis and RT-PCR. RESULTS: In both genotypes ethanol markedly reduced serum cholesterol, apolipoprotein A-I, phospholipid transfer protein activity and hepatic mRNA levels of fatty acid-binding proteins and fatty acid beta-oxidation enzymes. In contrast, exclusively in C3(-/-) mice, ethanol treatment increased serum and liver adiponectin levels but down-regulated transcripts of lipogenic enzymes, adiponectin receptor 2 and adipose differentiation-related protein and up-regulated phospholipase D1. CONCLUSIONS: We propose that these ethanol-induced alterations observed exclusively in C3(-/-) mice contribute to protection against fatty infiltration and subsequent inflammatory processes in the liver of these mice. The results suggest important cross-talk between complement factor C3 and lipid regulators in ethanol-induced steatosis. Ellman, L. M., Huttunen, M., Lonnqvist, J. and Cannon, T. D. Schizophrenia Research. 2007; 93(1-3): 229-236. Journal Article. IF 4.264 The purpose of this study was to determine whether a genetic vulnerability for schizophrenia and/or health-risk behaviors among schizophrenic pregnant women were associated with an increased incidence of obstetric complications (OCs). Method: A high-risk birth cohort was formed by searching the Finnish Perinatal Register for all births from 1991-2000 with arterial cord pH values below 7.20, an indication of fetal asphyxia. This database was merged with national hospital discharge registries to determine psychiatric morbidity of the mothers and the mothers' first-degree relatives. Mothers were divided into 3 groups: women diagnosed with schizophrenia/schizoaffective disorder (n=53), mothers with a first-degree relative with schizophrenia/schizoaffective disorder (n = 590) and healthy controls (n = 36,895). Result: Schizophrenic women had significantly more OCs than mothers with a first-degree schizophrenic relative and controls. These women had significantly increased rates of eclampsia, premature delivery, prenatal hospitalizations, and marginally significant increases in high blood pressure. Offspring of schizophrenic mothers had significantly decreased APGAR scores and birth weight and increased medical complications after birth. In contrast, women with a schizophrenic first-degree relative had no significant increases in OCs compared to controls. Schizophrenic mothers also smoked more than the other groups and smoking was found to mediate the relationship between maternal schizophrenic status and decreased birth weight among offspring. Conclusions: Maternal schizophrenia during pregnancy leads to an increased risk of OCs, possibly due to engagement in health-risk behaviors during pregnancy, such as smoking, whereas genetic susceptibility to schizophrenia, by itself, does not appear to be related to incidence of OCs. (c) 2007 Elsevier B.V. All rights reserved. Correlation of intestinal disaccharidase activities with the C/T-13910 variant and age World J Gastroenterol. 2007; 13(25): 3508-12. Journal Article. AIM: To correlate the C/T(-13910) variant, associated with lactase persistence/non-persistence (adult-type hypolactasia) trait, with intestinal disaccharidase activities in different age groups of the adult population. METHODS: Intestinal biopsies were obtained from 222 adults aged 18 to 83 years undergoing upper gastrointestinal endoscopy because of unspecified abdominal complaints. The biopsies were assayed for lactase, sucrase and maltase activities and genotyped for the C/T(-13910) variant using PCR-minisequencing. RESULTS: There was a significant correlation between lactase activity and the C/T(-13910) variant (P < 0.00001). The mean level of lactase activity among subjects with C/C(-13910) genotype was 6.86 +/- 0.35 U/g, with C/T(-13910) genotype 37.8 +/- 1.4 U/g, and with T/T(-13910) genotype 57.6 +/- 2.4 U/g protein, showing a trimodal distribution of this enzyme activity. Significant differences were also observed in maltase activities among individuals with different C/T(-13910) genotypes (P = 0.005). In contrast, in sucrase activity, no significant differences emerged between the C/T(-13910) genotypes (P = 0.14). There were no statistical differences in lactase (P = 0.84), sucrase (P = 0.18), or maltase activity (P = 0.24) among different age groups. In the majority (> 84%) of the patients with the C/C(-13910) genotype associated with lactase non-persistence, the lactase activity was less than 10 U/g protein. CONCLUSION: Our study demonstrates a statistically significant correlation between the C/T(-13910) genotype and lactase activity and this correlation is not affected by age in adults but the cut-off value of 20 U/g protein used for the diagnosis of lactase non-persistence might be too high. Gunnar, T., Engblom, C. and Ariniemi, K. J Chromatogr A. 2007. Journal Article. IF 3.554 Innovative features and technical improvements in modern bench-top quadrupole gas chromatograph-mass spectrometer (GC-MS) have prepared the way for faster and more cost-effective applications while still maintaining sufficient chromatographic resolution, speed of MS data acquisition and reliability of analytical methodology. In this paper, a short wide-bore capillary column with low film thickness (5mx0.32mm i.d., 0.1mum) was used a pre-fractionating column and only chosen heart-cuts were transferred to the second chromatographic dimension (15mx0.25mm i.d., 0.25mum) by means of a pressure-adjusted continual flow type switching device for quantification of five common amphetamine-type stimulant drugs. The instrumental setting used, in combination with carefully optimized operational fast GC and MS parameters, markedly decreased the retention times of the targeted analytes, e.g., amphetamine 0.891min and methamphetamine 1.037min, and the total chromatographic runtime (1.700min), as well as reducing the need for continuous cleaning of the MS ion source and increasing column life compared with conventional GC-MS approaches. The performance of the instrumental configuration and analytical method was evaluated in validation experiments and the method was also applied to authentic samples. The method demonstrates the potential of fast GC-MS in combination with a gas-phase microfluidic Deans switch device for analysing of (semi)volatile compounds, such as amphetamine-type stimulant (ATS) drugs. This should be particularly useful in modern laboratories aiming at cost-efficient analysis as well as the optimum use of available laboratory capacity and instrumentation. Tracing Shigatoxigenic Escherichia coli O103, O145 and O174 Infections from Farm Residents to Cattle Heinikainen, S., Pohjanvirta, T., Eklund, M., Siitonen, A. and Pelkonen, S. J Clin Microbiol. 2007. Journal Article. IF 3.445 Severe diarrheal infections caused by shigatoxigenic Escherichia coli O103:H2:stx1:eae-epsilon:ehx, O145:H28:stx1:eae-gamma:ehx (two cases in a family), and O174:H21:stx2c in farm residents were traced to cattle. Molecular methods were applied in the isolation and characterization of the strains. The causative strains were also isolated from cattle samples one or four months later. Glucose regulation in young adults with very low birth weight - Reply Hovi, P., Andersson, S. and Kajantie, E. New England Journal of Medicine. 2007; 357(6): 617-617. Letter. IF 51.296 Epidemiological studies of exercise in diabetes prevention Hu, G., Lakka, T. A., Kilpelainen, T. O. and Tuomilehto, J. Appl Physiol Nutr Metab. 2007; 32(3): 583-95. Journal Article. Type 2 diabetes is one of the fastest growing public health problems in both developed and developing countries. It is estimated that the number of people with diabetes in the world will double in coming years, from 171 million in 2000 to 366 million in 2030. Cardiovascular disease accounts for more than 70% of total mortality among patients with type 2 diabetes. The associations of physical activity, physical fitness, and changes in the lifestyle with the risk of type 2 diabetes have been assessed by a number of prospective studies and clinical trials in the past decade. Several studies have also evaluated the joint associations of physical activity, body mass index, and glucose levels with the risk of type 2 diabetes. Prospective studies and clinical trials have shown that moderate or high levels of physical activity or physical fitness and changes in the lifestyle (dietary modification and increase in physical activity) can prevent type 2 diabetes. Our review of the scientific evidence confirms that 30 min/d of moderate- or high-level physical activity is an effective and safe way to prevent type 2 diabetes in all populations. Hu, G., Tuomilehto, J., Silventoinen, K., Sarti, C., Mannisto, S. and Jousilahti, P. Archives of Internal Medicine. 2007; 167(13): 1420-1427. Journal Article. IF 7.920 Background: Adiposity is an established risk factor for cardiovascular disease, but the relationship of adiposity with the risk of cerebrovascular disease is still to some extent unclear. Methods: We prospectively investigated the association of different indicators of adiposity (body mass index [BMI] [ calculated as weight in kilograms divided by height in meters squared], waist circumference, and waist-hip ratio) with total and type-specific stroke incidence among 49 996 Finnish participants who were aged 25 to 74 years and free of coronary heart disease and stroke at baseline. Results: During a 19.5-year follow- up, 3228 people developed an incident stroke event ( 674 hemorrhagic and 2554 ischemic). Compared with normal-weight men (BMI, 18.5-24.9), the multivariate-adjusted (age, study year, smoking, physical activity, educational level, family history of stroke, and alcohol drinking) hazard ratios among lean ( BMI, < 18.5), overweight (BMI, 25.0-29.9), and obese (BMI, >= 30.0) men were 0.74 (95% confidence interval [CI], 0.18-2.96), 1.23 (95% CI, 1.10-1.37), and 1.59 (95% CI, 1.37-1.83) for total stroke, and 0.49 (95% CI, 0.07-3.50), 1.27 (95% CI, 1.12-1.44), and 1.70 ( 95% CI, 1.45-2.00) for ischemic stroke, respectively. Among women, the corresponding hazard ratios were 1.87 (95% CI, 1.12-3.14), 1.08 ( 95% CI, 0.95-1.22), and 1.30 (95% CI, 1.14-1.50) for total stroke, and 1.81 ( 95% CI, 0.97-3.41), 1.11 (95% CI, 0.96-1.28), and 1.41 (95% CI, 1.21-1.64) for ischemic stroke. Abdominal adiposity, defined as the highest quartile of waist circumference or waist-hip ratio, was associated with a greater risk of total and ischemic stroke in men but not in women. Conclusions: Body mass index was a risk factor for total and ischemic stroke in men and women. Abdominal adiposity was a risk factor for total and ischemic stroke only in men. Huurre, T., Eerola, M., Rahkonen, O. and Aro, H. Journal of Affective Disorders. 2007; 100(1-3): 55-64. Journal Article. IF 3.138 Background: The aim of this prospective longitudinal study of adolescents was to investigate socioeconomic differences in adult depression and in the domain of social support from adolescence to adulthood. We also studied the modifying effect of social support on the relationship between socioeconomic status (SES) and depression. Methods: All 16-year-old ninth-grade school pupils of one Finnish city completed questionnaires at school (n=2194). Subjects were followed up using postal questionnaires when aged 22 and 32 years. Results: At 32 years of age there was a social gradient in depression, with a substantially higher prevalence among subjects with lower SES. Low parental SES during adolescence did not affect the risk of depression at 32 years of age, but the person's lower level of education at 22 years did. Lower level of support among subjects with lower SES was found particularly in females. Some evidence indicated that low level of social support had a greater impact on depression among lower SES group subjects. However, this relationship varied depending on the domain of social support, life stage and gender. On the other hand, the results did not support the hypothesis that social support would substantially account for the variation in depression across SES groups. Limitations: The assessments and classifications of social support were rather brief and crude, particularly in adolescence and early adulthood. Conclusions: It is important to pay attention to social support resources in preventive programs and also in the treatment settings, with a special focus on lower SES group persons. (C) 2006 Elsevier B.V. All rights reserved. Juonala, M., Viikari, J. S., Alfthan, G., Marniemi, J., Kahonen, M., Taittonen, L., Laitinen, T. and Raitakari, O. T. Circulation. 2007. 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. Incidence of schizophrenia in a nationwide cohort of patients with type 1 diabetes mellitus Juvonen, H., Reunanen, A., Haukka, J., Muhonen, M., Suvisaari, J., Arajarvi, R., Partonen, T. and Lonnqvist, J. Arch Gen Psychiatry. 2007; 64(8): 894-9. Journal Article. IF 13.936 CONTEXT: Patients with schizophrenia have an increased risk of type 2 diabetes mellitus. However, very few studies have dealt with the association of type 1 diabetes and schizophrenia. Preliminary evidence points to a possible inverse association. OBJECTIVE: To investigate the incidence of schizophrenia in a nationwide cohort of patients with type 1 diabetes born in 1950 through 1959 in Finland. DESIGN: A cohort study of individuals born in 1950 through 1959 with a follow-up of 1969 through 1991. SETTING: Finland. PATIENTS: All individuals born in 1950 through 1959 with type 1 diabetes were identified through nationwide registers. The incidence of schizophrenia until 1992 among the total 1950-1959 cohort and in individuals with type 1 diabetes was calculated using information from 3 health care registers. MAIN OUTCOME MEASURE: Incidence of schizophrenia. RESULTS: The incidence of schizophrenia was 0.21 per 10 000 person-years in the group with type 1 diabetes and 0.56 per 10 000 person-years in the group without type 1 diabetes (P < .001). CONCLUSION: The incidence of schizophrenia is decreased in patients with type 1 diabetes. Kahkonen, S., Yamashita, H., Rytsala, H., Suominen, K., Ahveninen, J. and Isometsa, E. J Psychiatry Neurosci. 2007; 32(5): 316-322. Journal Article. IF 4.100 BACKGROUND: Patients with major depressive disorder (MDD) show impairments in cognitive functions. However, neural mechanisms underlying these disturbances are poorly understood. We investigated whether MDD affects neural mechanisms of involuntary attention studied by auditory evoked potentials (AEPs) and auditory evoked magnetic fields (AEFs). METHODS: AEPs and AEFs were studied in a passive odd-ball paradigm in 13 drug-free patients with unipolar MDD during an acute episode and 12 age-and sex-matched healthy subjects. Auditory responses to monaurally presented frequent "standard" tones, infrequent "deviant" tones (10% and 20% frequency change) and occasional "novel" sounds (complex sounds) were simultaneously recorded with whole-head magnetoencephalography (MEG) and electroencephalography (EEG). RESULTS: P1 and P1m latencies were decreased in patients with MDD, compared with those in healthy subjects. Further, the mismatch negativity amplitude to the 10% frequency deviance in the EEG, but not in the MEG, was increased in MDD. We observed no differences in N1/N1m and P3a responses in the MEG and EEG. The magnitude of decrease in P1/P1m latency correlated negatively with the severity of depression in the patients. CONCLUSIONS: Early auditory processing is impaired in patients with MDD during an acute episode, probably reflecting dysfunctional frontotemporal neural circuits. These dysfunctions may contribute to the cognitive disturbances observed in people with MDD. Costs of an outbreak of meticillin-resistant Staphylococcus aureus Kanerva, M., Blom, M., Tuominen, U., Kolho, E., Anttila, V. J., Vaara, M., Virolainen-Julkunen, A. and Lyytikainen, O. J Hosp Infect. 2007; 66(1): 22-8. Journal Article. IF 2.442 An outbreak of meticillin-resistant Staphylococcus aureus (MRSA) occurred in surgical and internal medicine units of a 1752-bed Finnish tertiary care hospital during 2003-2004. In order to analyse the costs of this 14-month outbreak, patients were categorized as follows: patients with MRSA infections; patients with MRSA colonization; patients exposed to MRSA but whose MRSA status remained inconclusive; and exposed patients who were negative for MRSA. We reviewed a sample of patients' charts to determine the types of clinical infections and interviewed staff about the practical implementation of control measures. The number of patients and patient-days involved in the outbreak were identified from the hospital's databases, with the administrative database supplying unit costs of work and materials. Loss of income due to closed beds was analysed. A total of 266 MRSA-positive patients (114 with infections and 152 colonized) and 797 patients exposed to MRSA were identified (11,744 contact isolation days). There were 1240 patients negative after screening (9880 contact isolation days). Total additional costs of MRSA were 386,062 euro (70% for screening and 25% for contact isolation). Costs due to meticillin resistance in treatment of MRSA infections were 16,000 euro. The income loss for this hospital due to closed beds was 1,183,808 euro. The high cost of MRSA screening underlines the importance of appropriate screening methods. Our model of analysing costs might be useful for other hospitals after adapting variables such as local control measures. Knekt, P., Lindfors, O., Laaksonen, M. A., Raitasalo, R., Haaramo, P. and Jarvikoski, A. J Affect Disord. 2007. Journal Article. IF3.138 BACKGROUND: Insufficient evidence exists about the effect of different therapies on work ability for patients with psychiatric disorders. The present study compares improvements in work ability in two short-term therapies and one long-term therapy. METHODS: In the Helsinki Psychotherapy Study, 326 outpatients with depressive or anxiety disorder were randomly assigned to long-term and short-term psychodynamic psychotherapy, and solution-focused therapy. The patients were followed for 3 years from the start of treatment. Primary outcome measures were the Work Ability Index (WAI), the Work-subscale (SAS-Work) of the Social Adjustment Scale (SAS-SR), Perceived Psychological Functioning Scale, the prevalence of patients employed or studying, and the number of sick-leave days. RESULTS: Work ability was statistically significantly improved according to WAI (15%), SAS-Work (17%), and Perceived Psychological Functioning Scale (21%) during the 3-year follow-up. No differences in the work ability scores were found between two short-term therapies. The short-term therapies showed 4-11% more improved work ability scores than long-term therapy at the 7 month follow-up point. During the second year of follow-up, no significant differences were found between therapies. After 3 years of follow-up, long-term therapy was more effective than the short-term therapies with 5-12% more improved scores. No differences in the prevalence of individuals employed or studying or in the number of sick-leave days were found between therapies during follow-up. CONCLUSIONS: Short-term therapies give benefits more quickly than long-term therapy on work ability but in the long run long-term therapy is more effective than short-term therapies. More research is needed to confirm these findings. Baseline psychosocial predictors of survival in localized melanoma Lehto, U. S., Ojanen, M., Dyba, T., Aromaa, A. and Kellokumpu-Lehtinen, P. Journal of Psychosomatic Research. 2007; 63(1): 9-15. Journal Article. IF 2.322 Objective: There is no certainty about the contributing factors or the psychological processes involved in cancer progression. Many studies have suffered from poor theoretical basis, methodological flaws, and only one or few psychosocial factors investigated at a time. We examined the simultaneous contribution of several theory-based psychosocial elements to survival time in melanoma. Methods: A consecutive sample of patients with localized (Clarke II-IV) melanoma (N=59) were evaluated with validated questionnaires on coping with cancer, anger expression, perceived social support, noncancer life stresses, and domains of quality of life (QOL) 3-4 months after diagnosis. Cox regression analyses were used to determine the predictors of survival time from the date of diagnosis to the date of death or the last follow-up. Results: After controlling for age, gender, and Breslow depth for the tumor, the baseline psychological variables related to the cancer-prone Type C response pattern, namely, anger nonexpression (repression), hopelessness, and better single-item self-reported QOL predicted shorter survival. Before hopelessness was added to the model, the amount of depressive symptoms and heavy perceived impact of diagnosis were also predictive. In addition, longer survival was strongly predicted by Cognitive Escape-Avoidance coping, which included items close to the concept of denial/minimizing. Conclusion: Anger nonexpression, hopelessness, and overpositive reporting of QOL-all proposed to include in the Type C response style or reflect emotional nonexpression-seem to comprise a set of factors that reduce survival, whereas denial/minimizing response to the diagnosis as such predicts longer survival. (C) 2007 Published by Elsevier Inc. Lyly, A., von Schantz, C., Salonen, T., Kopra, O., Saarela, J., Jauhiainen, M., Kyttala, A. and Jalanko, A. Bmc Cell Biology. 2007; 8. Journal Article. IF 2.742 Background: Neuronal ceroid lipofuscinoses (NCLs) are collectively the most common type of recessively inherited childhood encephalopathies. The most severe form of NCL, infantile neuronal ceroid lipofuscinosis (INCL), is caused by mutations in the CLN1 gene, resulting in a deficiency of the lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1). The deficiency of PPT1 causes a specific death of neocortical neurons by a mechanism, which is currently unclear. To understand the function of PPT1 in more detail, we have further analyzed the basic properties of the protein, especially focusing on possible differences in non-neuronal and neuronal cells. Results: Our study shows that the N-glycosylation of N197 and N232, but not N212, is essential for PPT1's activity and intracellular transport. Deglycosylation of overexpressed PPT1 produced in neurons and fibroblasts demonstrates differentially modified PPT1 in different cell types. Furthermore, antibody internalization assays showed differences in PPT1 transport when compared with a thoroughly characterized lysosomal enzyme aspartylglucosaminidase (AGA), an important observation potentially influencing therapeutic strategies. PPT1 was also demonstrated to form oligomers by size-exclusion chromatography and co-immunoprecipitation assays. Finally, the consequences of disease mutations were analyzed in the perspective of our new results, suggesting that the mutations increase both the degree of glycosylation of PPT1 and its ability to form complexes. Conclusion: Our current study describes novel properties for PPT1. We observe differences in PPT1 processing and trafficking in neuronal and non-neuronal cells, and describe for the first time the ability of PPT1 to form complexes. Understanding the basic characteristics of PPT1 is fundamental in order to clarify the molecular pathogenesis behind neurodegeneration in INCL. Meklin, T., Reponen, T., McKinstry, C., Cho, S. H., Grinshpun, S. A., Nevalainen, A., Vepsalainen, A., Haugland, R. A., Lemasters, G. and Vesper, S. J. Sci Total Environ. 2007; 382(1): 130-4. Journal Article. IF 2.359 Mold specific quantitative PCR (MSQPCR) was used to measure the concentrations of the 36 mold species in indoor and outdoor air samples that were taken simultaneously for 48 h in and around 17 homes in Cincinnati, Ohio. The total spore concentrations of 353 per m(3) of indoor air and 827 per m(3) of outdoor air samples were significantly different (p<or=0.05). However, only the concentrations of Aspergillus penicillioides, Cladosporium cladosporioides types 1 and 2 and Cladosporium herbarum were correlated in indoor and outdoor air samples (p-value<or=0.05 and sufficient data for estimate and absolute value rho estimate >or=0.5). These results suggest that interpretation of the meaning of short-term (<48 h) mold measurements in indoor and outdoor air samples must be made with caution. Ollonqvist, K., Gronlund, R., Karppi, S. L., Salmelainen, U., Poikkeus, L. and Hinkka, K. Scandinavian Journal of Caring Sciences. 2007; 21(2): 253-261. Journal Article. IF 0.917 Introduction and purpose: Living independently at home promotes the well-being of people aged 65 and over. In Finland, the municipalities are responsible for providing social and health services, including rehabilitation of the elderly. Rehabilitation is in practice carried out by independent rehabilitation centres. The Social Insurance Institution of Finland is a national agency responsible for financing and developing rehabilitation. Combining the efforts of these three agencies, a new network-based inpatient rehabilitation model was established to support the community living of frail elderly persons at high risk of institutionalization. This article describes the new model and evaluates the cooperation within the rehabilitation network, as well as the contents of the rehabilitation. Material and methods: The new model was evaluated in two phases using diverse methods. First, the networks were assessed as they were being established in 2000, and secondly, when they were operational in 2002. The first phase involved 53 networks operating in 46 municipalities and 12 rehabilitation centres, and the second 44 networks in 41 municipalities and seven rehabilitation centres. The data were collected by questionnaires, interviews and reports. Results: The rehabilitation networks were functional, although constant development and search for better working practices was time consuming. Two different approaches in the networks were found: the 'networks of creators' were able to carry out the new tasks highly successfully, while the 'networks of followers' only managed to do the minimum as instructed. Motivated network members and adequate resources appeared to be essential for a successful rehabilitation process. Conclusions: It is possible to create a functional rehabilitation network involving different agencies. Further development work is necessary to make the network-based rehabilitation model more efficient. Osterlund, P. I., Pietila, T. E., Veckman, V., Kotenko, S. V. and Julkunen, I. J Immunol. 2007; 179(6): 3434-42. Journal Article. IF 6.293 Virus replication induces the expression of antiviral type I (IFN-alphabeta) and type III (IFN-lambda1-3 or IL-28A/B and IL-29) IFN genes via TLR-dependent and -independent pathways. Although type III IFNs differ genetically from type I IFNs, their similar biological antiviral functions suggest that their expression is regulated in a similar fashion. Structural and functional characterization of the IFN-lambda1 and IFN-lambda3 gene promoters revealed them to be similar to IFN-beta and IFN-alpha genes, respectively. Both of these promoters had functional IFN-stimulated response element and NF-kappaB binding sites. The binding of IFN regulatory factors (IRF) to type III IFN promoter IFN-stimulated response element sites was the most important event regulating the expression of these genes. Ectopic expression of the components of TLR7 (MyD88 plus IRF1/IRF7), TLR3 (Toll/IL-1R domain-containing adapter-inducing factor), or retinoic acid-inducible gene I (RIG-I) signal transduction pathways induced the activation of IFN-lambda1 promoter, whereas the IFN-lambda3 promoter was efficiently activated only by overexpression of MyD88 and IRF7. The ectopic expression of Pin1, a recently identified suppressor for IRF3-dependent antiviral response, decreased the IFN promoter activation induced by any of these three signal transduction pathways, including the MyD88-dependent one. To conclude, the data suggest that the IFN-lambda1 gene is regulated by virus-activated IRF3 and IRF7, thus resembling that of the IFN-beta gene, whereas IFN-lambda2/3 gene expression is mainly controlled by IRF7, thus resembling those of IFN-alpha genes. Paile-Hyvarinen, M., Wahlbeck, K. and Eriksson, J. G. BMC Fam Pract. 2007; 8: 34. Journal Article. BACKGROUND: Depression is prevalent in people with type 2 diabetes and affects both glycaemic control and overall quality of life. The aim of this investigator-initiated trial was to evaluate the effect of the antidepressant paroxetine on quality of life, metabolic control, and mental well-being in mildly depressed diabetics aged 50-70 years. METHODS: We randomised 49 mildly depressed primary care outpatients with non-optimally controlled diabetes to a 6-month double-blind treatment with either paroxetine 20 mg per day or matching placebo. Primary efficacy measurements were quality of life and glycaemic control. The primary global outcome of the study was defined as a 10 points improvement in the SF-36 quality of life score. The primary metabolic outcome of the study was defined as a 0.8%-units decrease in glycosylated haemoglobin A1c(GHbA1c). Psychiatric symptoms were assessed with the Hospital Anxiety and Depression Scale. RESULTS: Six patients withdrew their consent before starting medication and six dropped out later in the study. We performed analysis of covariance with the baseline value as a covariate. Quality of life and glycaemic control as well as symptoms of depression and anxiety improved in both groups over the 6-month study period. After three months of treatment we found a statistically significant difference between the two treatment groups in GHbA1c (mean difference = 0.59%-units, p = 0.018) and in SF-36 score (mean difference = 11.0 points, p = 0.039). However, at the end of the study, no statistically significant differences between the treatment groups were observed. No severe adverse events occurred. CONCLUSION: This pragmatic study of primary care patients did not confirm earlier preliminary findings indicating a beneficial effect of paroxetine on glycaemic control. The study indicates that in pragmatic circumstances any possible benefit from administration of paroxetine in diabetic patients with sub-threshold depression is likely to be modest and of short duration. Routine antidepressant prescription for patients with diabetes and sub-threshold depressive symptoms is not indicated. TRIAL REGISTRATION: Current controlled trials ISRCTN55819922. Old suspects found guilty - The first genome profile of multiple sclerosis Peltonen, L. New England Journal of Medicine. 2007; 357(9): 927-929. Editorial Material. IF 51.296 Combined genome scans for body stature in 6,602 European twins: evidence for common Caucasian loci Perola, M., Sammalisto, S., Hiekkalinna, T., Martin, N. G., Visscher, P. M., Montgomery, G. W., Benyamin, B., Harris, J. R., Boomsma, D., Willemsen, G., Hottenga, J. J., Christensen, K., Kyvik, K. O., Sorensen, T. I., Pedersen, N. L., Magnusson, P. K., Spector, T. D., Widen, E., Silventoinen, K., Kaprio, J., Palotie, A. and Peltonen, L. PLoS Genet. 2007; 3(6): e97. Journal Article. IF 7.671 Twin cohorts provide a unique advantage for investigations of the role of genetics and environment in the etiology of variation in common complex traits by reducing the variance due to environment, age, and cohort differences. The GenomEUtwin (http://www.genomeutwin.org) consortium consists of eight twin cohorts (Australian, Danish, Dutch, Finnish, Italian, Norwegian, Swedish, and United Kingdom) with the total resource of hundreds of thousands of twin pairs. We performed quantitative trait locus (QTL) analysis of one of the most heritable human complex traits, adult stature (body height) using genome-wide scans performed for 3,817 families (8,450 individuals) derived from twin cohorts from Australia, Denmark, Finland, Netherlands, Sweden, and United Kingdom with an approximate ten-centimorgan microsatellite marker map. The marker maps for different studies differed and they were combined and related to the sequence positions using software developed by us, which is publicly available ( https://apps.bioinfo.helsinki.fi/software/cartographer.aspx). Variance component linkage analysis was performed with age, sex, and country of origin as covariates. The covariate adjusted heritability was 81% for stature in the pooled dataset. We found evidence for a major QTL for human stature on 8q21.3 (multipoint logarithm of the odds 3.28), and suggestive evidence for loci on Chromosomes X, 7, and 20. Some evidence of sex heterogeneity was found, however, no obvious female-specific QTLs emerged. Several cohorts contributed to the identified loci, suggesting an evolutionarily old genetic variant having effects on stature in European-based populations. To facilitate the genetic studies of stature we have also set up a website that lists all stature genome scans published and their most significant loci (http://www.genomeutwin.org/stature_gene_map.htm). No association between common variants in glyoxalase 1 and autism spectrum disorders Rehnstrom, K., Ylisaukko-Oja, T., Vanhala, R., von Wendt, L., Peltonen, L. and Hovatta, I. Am J Med Genet B Neuropsychiatr Genet. 2007. Journal Article. IF 1.772 The autism spectrum disorders (ASDs) are complex diseases with a strong genetic component. Numerous candidate gene studies have tested association between various functional and positional candidate genes and autism, but no common variation predisposing for autism has been identified to date. It has been previously proposed, that glyoxalase 1 (GLO1) might be involved in the pathogenesis of autism as GLO1 protein polarity was significantly changed in the brains of autism patients compared to controls. GLO1 harbors a functional polymorphism that affects the polarity and the enzymatic activity of the protein. In the same study, this polymorphism showed a suggestive association to autism. To investigate whether common variants in GLO1 predispose to autism in the Finnish population, we have genotyped six polymorphisms in GLO1 in families with more than 230 individuals affected with ASDs and carried out both linkage and association analyses. We did not observe significant linkage or association between any SNP and ASDs. Therefore, we suggest that common variants in GLO1 are not significant susceptibility factors for ASDs in the Finnish population. (c) 2007 Wiley-Liss, Inc. Reinikka-Railo, H., Kautiainen, H., Alenius, H., Kalkkinen, N., Kulomaa, M., Reunala, T. and Turjanmaa, K. Allergy. 2007; 62(7): 781-6. Journal Article. IF 5.334 BACKGROUND: Assessment of allergenic potential of medical devices made of natural rubber latex (NRL) requires the measurement of concentrations of specific allergenic proteins or polypeptides eluting from rubber. METHODS: Four NRL allergens (Hev b 1, 3, 5, and 6.02) were quantified in all medical glove brands marketed in Finland in 1999, 2001, and 2003 (n = 208) by a capture enzyme immunoassay. The results were compared with those obtained from previous nationwide market surveys, using a skin prick test-validated human IgE-based ELISA-inhibition method. RESULTS: A high overall correlation (r = 0.87, 95% CI 0.83-0.90) emerged between the sum values of the four allergens(microg/g glove) and IgE-ELISA inhibition (allergen units, AU/ml, 1:5 diluted glove extract). The sum of four allergens when set at 0.15 microg/g discriminated 'low allergenic' (<10 AU/ml) from 'moderate- to high-allergenic' (>/=10 AU/ml) gloves at a sensitivity of 0.93 (95% CI 0.85-0.98) and specificity of 0.90 (95% CI 0.83-0.94). When the sum was below the detection limit (0.03 microg/g) all gloves belonged to the previously defined low-allergen category. CONCLUSIONS: By comparing the sum concentration of four selected NRL allergens with results obtained in human IgE-ELISA inhibition, it was possible set a cut-off level (0.15 microg/g) below which virtually all gloves contain low or insignificant amounts of allergens, and can be considered as low allergenic. At different cut-off-points, one could calculate the likelihood of a given glove to belong to the previously defined low, moderate or high allergen categories. Ruckerl, R., Greven, S., Ljungman, P., Aalto, P., Antoniades, C., Bellander, T., Berglind, N., Chrysohoou, C., Forastiere, F., Jacquemin, B., von Klot, S., Koenig, W., Kuchenhoff, H., Lanki, T., Pekkanen, J., Perucci, C. A., Schneider, A., Sunyer, J. and Peters, A. Environmental Health Perspectives. 2007; 115(7): 1072-1080. Journal Article. IF 5.861 BACKGROUND: Numerous studies have found that ambient air pollution has been associated with cardiovascular disease exacerbation. OBJECTIVES: Given previous findings, we hypothesized that particulate air pollution might induce systemic inflammation in myocardial infarction (MI) survivors, contributing to an increased vulnerability to elevated concentrations of ambient particles. METHODS: A prospective longitudinal study of 1,003 MI survivors was performed in six European cities between May 2003 and July 2004. We compared repeated measurements of interleukin 6 (IL-6), fibrinogen, and C-reactive protein (CRP) with concurrent levels of air pollution. We collected hourly data on particle number concentrations (PNC), mass concentrations of particulate matter (PM) < 10 mu m (PM10) and < 2.5 mu m (PM2.5), gaseous pollutants, and meteorologic data at central monitoring sites in each city. City-specific confounder models were built for each blood marker separately, adjusting for meteorology and time-varying and time-invariant covariates. Data were analyzed with mixed-effects models. RESULTS: Pooled results show an increase in IL-6 when concentrations of PNC were elevate 12-17 hr before blood withdrawal [percent change of geometric mean, 2.7; 95% confidence interval (CI), 1.0-4.6]. Five day cumulative exposure to PM10 was associated with increased fibrinogen concentrations (percent change of arithmetic mean, 0.6; 95% CI, 0.1-1.1). Results remained stable for smokers, diabetics, and patients with heart failure. No consistent associations were found for CRP. CONCLUSIONS: Results indicate an immediate response to PNC on the IL-6 level, possibly leading to the production of acute-phase proteins, as seen in increased fibrinogen levels. This might provide a link between air pollution and adverse cardiac events. Stenholm, S., Sainio, P., Rantanen, T., Alanen, E. and Koskinen, S. Aging Clin Exp Res. 2007; 19(4): 277-83. 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. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes Todd, J. A., Walker, N. M., Cooper, J. D., Smyth, D. J., Downes, K., Plagnol, V., Bailey, R., Nejentsev, S., Field, S. F., Payne, F., Lowe, C. E., Szeszko, J. S., Hafler, J. P., Zeitels, L., Yang, J. H. M., Vella, A., Nutland, S., Stevens, H. E., Schuilenburg, H., Coleman, G., Maisuria, M., Meadows, W., Smink, L. J., Healy, B., Burren, O. S., Lam, A. A. C., Ovington, N. R., Allen, J., Adlem, E., Leung, H. T., Wallace, C., Howson, J. M. M., Guja, C., Ionescu-Tirgoviste, C., Simmonds, M. J., Heward, J. M., Gough, S. C. L., Dunger, D. B., Wicker, L. S. and Clayton, D. G. Nature Genetics. 2007; 39(7): 857-864. Journal Article. IF 24.176 The Wellcome Trust Case Control Consortium (WTCCC) primary genome- wide association (GWA) scan(1) on seven diseases, including the multifactorial autoimmune disease type 1 diabetes (T1D), shows associations at P < 5 x 10(-7) between T1D and six chromosome regions: 12q24, 12q13, 16p13, 18p11, 12p13 and 4q27. Here, we attempted to validate these and six other top findings in 4,000 individuals with T1D, 5,000 controls and 2,997 family trios independent of the WTCCC study. We confirmed unequivocally the associations of 12q24, 12q13, 16p13 and 18p11 ( Pfollow- up <= 1.35 similar to 10(-9); P-overall <= 1.15 x 10(-14)), leaving eight regions with small effects or false- positive associations. We also obtained evidence for chromosome 18q22 ( P-overall 1.38 x 10(-8)) from a GWA study of nonsynonymous SNPs. Several regions, including 18q22 and 18p11, showed association with autoimmune thyroid disease. This study increases the number of T1D loci with compelling evidence from six to at least ten. Pemphigus vulgaris and pemphigus foliaceus: similar prognosis? Zaraa, I., Mokni, M., Hsairi, M., Boubaker, S., Sellami, M., Zitouni, M., Makni, S. and Dhahri, A. B. Int J Dermatol. 2007; 46(9): 923-926. Journal Article. IF 0.998 Background: Pemphigus is a rare, life-threatening, acquired autoimmune bullous dermatosis. The prognosis of pemphigus foliaceus (PF) is usually regarded as more favourable than that of pemphigus vulgaris (PV). Our study aims to compare the clinical course of PV and PF in 37 patients. Patients and Methods: We conducted a retrospective study over a period of eight years (1994-2001). The patients were referred during this period and were followed until December 2003. PF and PV were included based on clinical, histological and immunopathological criteria. Results: In our study there was no significant difference between PF group and PV group concerning; age, sex, duration of the disease, presence of disseminated lesions, treatment, healing time, remission, relapse, complications, death and follows up duration. The survival graph showed no difference between the two groups for the first two relapses. There was a tendency to significance concerning an additional treatment and relapses frequency in the PF group. Conclusions: Few studies in the literature were interested in the evolution of the two forms of pemphigus. They showed that the two populations share the same clinical course; nevertheless they revealed the frequency of partial remission, failed treatment, relapses, necessity of high dose of corticosteroids, and difficulties of discontinuing treatment in PF. Our study, suggests that PF and PV may share the same clinical course. |