21.4.2008

Gimeno, D., Ferrie, J. E., Elovainio, M., Pulkki-Raback, L., Keltikangas-Jarvinen, L., Eklund, C., Hurme, M., Lehtimaki, T., Marniemi, J., Viikari, J. S. A., Raitakari, O. T. and Kivimaki, M.

International Journal of Epidemiology. 2008; 37(2): 290-298. Article. IF 4.517

Background It is unclear when in the life course do social inequalities in inflammation emerge.

We examined whether the association between socioeconomic position (SEP) and C-reactive protein (CRP) is determined at conception, in childhood, adolescence or adulthood in 1484 participants from the population-based Cardiovascular Risk in Young Finns Study. Methods Five variants of the CRP gene were used to investigate whether SEP differences in CRP levels are determined at conception. SEP and serum CRP were assessed in childhood (age 39), adolescence (age 1218) and in adulthood (age 2439). SEP was measured using parental education and occupational status in childhood and adolescence, and participants own education and occupational status in adulthood. Participants with CRP 10 mg/l were excluded.

Results All CRP gene variants were associated with circulating CRP concentrations in childhood, but there were no differences in the distribution of these variants by SEP. No strong evidence was found of associations between parental SEP and CRP. A graded association between higher SEP and lower CRP was observed in adulthood for education (P = 0.0005) but not for occupational status. Trajectories that led to high educational achievement both in the participants and their parents were associated with lower (P <= 0.047) CRP levels in adulthood. Excluding participants with infectious diseases, pregnant or lactating women and women using oral contraceptives did not change the findings.

Conclusion In this cohort, SEP differences in CRP concentrations seen in adulthood appear not to be determined at conception or evident in childhood or adolescence.

Genetic influences on growth traits of BMI: A longitudinal study of adult twins

Hjelmborg, J. V. B., Fagnani, C., Silventoinen, K., McGue, M., Korkeila, M., Christensen, K., Rissanen, A. and Kaprio, J.

Obesity. 2008; 16(4): 847-852. Article.

Objective: To investigate the interplay between genetic factors influencing baseline level and changes in BMI in adulthood.

Methods and Procedures: A longitudinal twin study of the cohort of Finnish twins ( N = 10,556 twin individuals) aged 20-46 years at baseline was conducted and followed up 15 years. Data on weight and height were obtained from mailed surveys in 1975, 1981, and 1990.

Results: Latent growth models revealed a substantial genetic influence on BMI level at baseline in males and females ( heritability (h(2)) 80% ( 95% confidence interval 0.79-0.80) for males and h2 = 82% ( 0.81, 0.84) for females) and a moderate-to-high influence on rate of change in BMI ( h(2) = 58% ( 0.50, 0.69) for males and h(2) = 64% ( 0.58, 0.69) for females). Only very weak evidence for genetic pleiotropy was observed; the genetic correlation between baseline and rate of change in BMI was very modest (- 0.070 ( - 0.13, - 0.068) for males and 0.04 ( 0.00, 0.08) for females.

Discussion: Our population-based results provide a basis for identifying genetic variants for change in BMI, in particular weight gain. Furthermore, they demonstrate for the first time that such genetic variants for change in BMI are likely to be different from those affecting level of BMI.

The increasing prevalence of metabolic syndrome among Finnish men and women over a decade

Hu, G., Lindstrom, J., Jousilahti, P., Peltonen, M., Sjoberg, L., Kaaja, R., Sundvall, J. and Tuomilehto, J.

J Clin Endocrinol Metab. 2008; 93(3): 832-6. IF 5.799

OBJECTIVE: Our objective was to assess a 10-yr change in the prevalence of the metabolic syndrome defined by the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) among Finnish men and women.

DESIGN AND SUBJECTS: Two cross-sectional population surveys were performed in Finland in 1992 and 2002. A total of 3495 participants aged 45-64 yr were included in the analysis.

RESULTS: In both years the metabolic syndrome was more common among men than women. In men the prevalence of the metabolic syndrome tended to increase slightly between 1992 and 2002, from 48.8-52.6% (P=0.139) based on the NCEP definition, and from 51.4-55.6% based on the IDF definition (P=0.102). In women the prevalence of the metabolic syndrome increased significantly from 32.2-39.1% based on the NCEP definition (P=0.003), and from 38.0-45.3% based on the IDF definition (P=0.002). In both sexes the prevalence of high blood pressure decreased, but the abnormalities in glucose metabolism increased between 1992 and 2002. The prevalence of central obesity increased in women between 1992 and 2002.

CONCLUSIONS: In Finland the prevalence of the metabolic syndrome, based both on the NCEP and IDF definitions, is higher in men than women. However, the increase in the prevalence of the metabolic syndrome, from 1992-2002, was significant only among women.

Effect of lifestyle intervention on the occurrence of metabolic syndrome and its components in the Finnish Diabetes Prevention Study

Ilanne-Parikka, P., Eriksson, J. G., Lindstrom, J., Peltonen, M., Aunola, S., Hamalainen, H., Keinanen-Kiukaanniemi, S., Laakso, M., Valle, T. T., Lahtela, J., Uusitupa, M. and Tuomilehto, J.

Diabetes Care. 2008; 31(4): 805-807. Article. IF 7.912

OBJECTIVE - The aim of this secondary analysis of the Finnish Diabetes Prevention Study was to assess the effects of lifestyle intervention on metabolic syndrome and its components.

RESEARCH DESIGN AND METHODS - A total of 522 middle-aged overweight men and women with impaired glucose tolerance were randomized into an individualized lifestyle intervention group or a standard care control group. National Cholesterol Education Program criteria were used for the definition of metabolic syndrome.

RESULTS - At the end of the study, with a mean follow-up of 3.9 years, we found a significant reduction in the prevalence of metabolic syndrome in the intervention group compared with the control group (odds ratio [OR] 0.62 [95% CI 0.40-0.95]) and in the prevalence of abdominal obesity (0.48 [0.28-0.81]).

CONCLUSIONS - The results suggest that lifestyle intervention may also reduce risk of cardiovascular disease in the long run.

Phosphatase-mediated crosstalk between MAPK signalling pathways in the regulation of cell survival

Junttila, M. R., Li, S. P. and Westermarck, J.

Faseb Journal. 2008; 22(4): 954-965. Review. IF 6.721

Mitogen-activated protein kinase (MAPK) pathways constitute a large modular network that regulates a variety of physiological processes, such as cell growth, differentiation, and apoptotic cell death. The function of the ERK pathway has been depicted as survival-promoting, in essence by opposing the proapoptotic activity of the stress-activated c-Jun NH2 terminal kinase (JNK)/p38 MAPK pathways. However, recently published work suggests that extracellular regulated kinase (ERK) pathway activity is suppressed by JNK/p38 kinases during apoptosis induction. In this review, we will summarize the current knowledge about JNK/p38-mediated mechanisms that negatively regulate the ERK pathway. In particular, we will focus on phosphatases (PP2A, MKPs) as inhibitors of ERK pathway activity in regulating apoptosis. A model proposed in this review places the negative regulation of the ERK pathway in a central position for the cellular decision-making process that determines whether cells will five or die in response to apoptosis-promoting signals. In addition, we will discuss the potential functional relevance of negative regulation of ERK pathway activity, for physiological and pathological conditions (e.g:, cellular transformation).

Growth before 2 years of age and serum lipids 60 years later: The Helsinki Birth Cohort Study

Kajantie, E., Barker, D. J. P., Osmond, C., Forsen, T. and Eriksson, J. G.

International Journal of Epidemiology. 2008; 37(2): 280-289. Article. IF 4.517

Background Small body size at birth and slow growth during the first 2 years after birth, leading to low body mass index (BMI) at 2 years, are associated with coronary heart disease and stroke in adult life. We tested the hypothesis that this path of growth is associated with an atherogenic lipid profile in later life.

Methods We measured serum lipid concentrations at age 5770 years in 1999 members of the Helsinki Birth Cohort. They were randomly selected from an original cohort of 8760 people and had on average 11 measurements of height and weight between birth and 2 years of age.

Results The 18 of subjects who used lipid-lowering medication had a lower BMI at birth and at 2 years. These subjects were excluded from the analyses of lipid profiles. A 1 kg/m(2) lower BMI at birth was associated with 0.051 mmol/l (95 CI -0.001 to 0.103; P = 0.05) higher non-HDL cholesterol and 0.018 g/l higher (0.005-0.031; P = 0.006) apolipoprotein B concentrations. A slower increase in BMI during the first 6 months after birth was associated with lower HDL and higher non-HDL cholesterol concentrations. A 1 kg/m(2) lower BMI at 2 years was associated with 0.020 mmol/l lower (0.004-0.036; P = 0.02) HDL cholesterol and 0.059 mmol/l (0.020-0.099; P = 0.003) higher non-HDL cholesterol and 0.018 mmol/l higher (0.008-0.028; P < 0.001) apolipoprotein B concentrations. The age at weaning off breast milk was not associated with lipid profile in later life.

Conclusions Small body size at birth and slow weight gain during infancy are associated with an atherogenic lipid profile in adult life.

Transcript profiles of dendritic cells of PLOSL patients link demyelinating CNS disorders with abnormalities in pathways of actin bundling and immune response

Kiialainen, A., Veckman, V., Saharinen, J., Paloneva, J., Gentile, M., Hakola, P., Hemelsoet, D., Ridha, B., Kopra, O., Julkunen, I. and Peltonen, L.

J Mol Med. 2007; 85(9): 971-83. IF 5.157

Rare monogenic dementias have repeatedly exposed novel pathways guiding to details of the molecular pathogenesis behind this complex clinical phenotype.

In this paper, we have studied polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), an early onset dementia with bone fractures caused by mutations in TYROBP (DAP12) and TREM2 genes, which encode important signaling molecules in human dendritic cells (DCs). To identify the pathways and biological processes associated with DAP12/TREM2-mediated signaling, we performed genome wide transcript analysis of in vitro differentiated DCs of PLOSL patients representing functional knockouts of either DAP12 or TREM2. Both DAP12- and TREM2-deficient cells differentiated into DCs and responded to pathogenic stimuli. However, the DCs showed morphological differences compared to control cells due to defects in the actin filaments. Not unexpectedly, transcript profiles of the patient DCs showed differential expression of genes involved in immune response. Importantly, significantly diverging transcript levels were also evident for genes earlier associated with other disorders of the central nervous system (CNS) and genes involved in the remodeling of bone, linking these two immunological genes with critical tissue phenotypes of patients.

The data underline the functional diversity of the molecules of the innate immune system and implies their significant contribution also in demyelinating CNS disorders, including those resulting in dementia.

Effectiveness of short-term and long-term psychotherapy on work ability and functional capacity - A randomized clinical trial on depressive and anxiety disorders

Knekt, P., Lindfors, O., Laaksonen, M. A., Raitasalo, R., Haaramo, P. and Jarvikoski, A.

Journal of Affective Disorders. 2008; 107(1-3): 95-106. Article. IF 3.138

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. (C) 2007 Elsevier B.V. All rights reserved.

Mortality differences according to living arrangements

Koskinen, S., Joutsenniemi, K., Martelin, T. and Martikainen, P.

Int J Epidemiol. 2007; 36(6): 1255-64. IF 4.517

BACKGROUND: Research has revealed mortality differences between marital status groups in different societies and different periods of time. Due to the increase in consensual unions, living alone and other changes in living arrangements, it is necessary to apply a more detailed classification of living arrangements that incorporates partnership situation and household composition.

METHODS: We analyse mortality by cause-of-death in the total Finnish population aged 30 or over in 1996-2000. The linked register dataset includes 15.7 million person-years and 210,139 deaths.

RESULTS: In the working aged population, cohabiters had nearly 70% excess mortality when compared with married people. Among working aged men living with someone other than a partner and among men living alone, mortality was three times higher than among married men. Among women, mortality in these groups was close to that of cohabiters. In the older population, mortality in the other groups was 15-40% higher than among married persons. Adjusting for education, social class and employment status attenuated the mortality differences by 7-31%. Having no children was associated with excess mortality in working aged women and men in each living arrangement group. The relative differences were greatest in deaths from alcohol-related causes, followed by deaths from accidents among men and working aged women and lung cancer in women.

CONCLUSIONS: We observed wide mortality differences according to living arrangements, particularly among the working aged. These differences were partly explained by socioeconomic factors. Excessive alcohol use seems to be one major cause of mortality differences.

Trends in self-reported sleep duration and insomnia-related symptoms in Finland from 1972 to 2005: a comparative review and re-analysis of Finnish population samples

Kronholm, E., Partonen, T., Laatikainen, T., Peltonen, M., Harma, M., Hublin, C., Kaprio, J., Aro, A. R., Partinen, M., Fogelholm, M., Valve, R., Vahtera, J., Oksanen, T., Kivimaki, M., Koskenvuo, M. and Sutela, H.

J Sleep Res. 2008; 17(1): 54-62. IF 3.458

A hypothesis concerning habitual sleep reduction and its adverse consequences among general population in modern societies has received wide publicity in the mass media, although scientific evidence supporting the hypothesis is scarce. Similarly, there is an extensively distributed belief, at least in Finland, that the prevalence of insomnia-related symptoms is increasing, but evidence for this is even sparser.

These issues are important because of the known increased risk of mortality and health risks associated with sleep duration deviating from 7 to 8 h. To reveal possible trends in self-reported sleep duration and insomnia-related symptoms, we reanalyzed all available data from surveys carried out in Finland from 1972 to 2005.

The main results were that a minor decrease of self-reported sleep duration has taken place in Finland, especially among working aged men. However, the size of the reduction (about 4%) was relatively small, approximately 5.5 min per each 10 years during the 33 years' time interval under study. The proportion of 7 h sleepers has increased and, correspondingly, the proportion of 8 h sleepers has decreased, but the extreme ends of the sleep duration distribution remained unchanged. Tentative evidence suggesting an increase in insomnia-related symptoms among working aged population during the last 10 years was found.

In conclusion, the Finnish data during the past 33 years indicate a general decrease in self-reported sleep duration of about 18 min and an increase of sleep complaints, especially among the employed middle-aged population.

Serum lipids in relation to sciatica among Finns

Leino-Arjas, P., Kauppila, L., Kaila-Kangas, L., Shiri, R., Heistaro, S. and Heliövaara, M.

Atherosclerosis. 2008; 197(1): 43-49. Article. IF 3.811

Objectives: Atherosclerosis of arteries supplying the lumbar region has been suggested as a mechanism leading to inter-vertebral disc degeneration and sciatica. The study described here examined whether serum lipid levels or pharmacologically treated hyperlipidemia were associated with sciatica.

Methods: A nationally representative sample (n = 8028) of Finns aged 30 years or over was interviewed and examined. Sciatica was assessed by a physician according to preset criteria. Information for the present purpose was available for 74.8% of the sample.

Results: The prevalence of sciatica was 3.3% for men and 2.2% for women. In men without hyperlipidemia treatment, sciatica was associated with total cholesterol (high vs. low tertile: OR 2.28, 95% Cl 1.14-4.55), LDL cholesterol (2.12; 1.11-4.05), and triglycerides (1.92 1.04-3.55), adjusted for age, BMI, exercise, smoking, heavy physical work, and education. HDL was not associated with sciatica. For men in the highest tertile of both total cholesterol and triglycerides, the OR of sciatica was 3.89 (1.68-8.99) in comparison to men with cholesterol in the lowest tertile and triglycerides in the lowest or the middle tertile. In similar analyses among women no associations were seen. Pharmacologically treated hyperlipidemia was associated with sciatica in women (2.02; 1.01-4.04), but not in men (1.71; 0.83-3.55).

Conclusions: Independent of BMI and other possible confounders, clinically assessed sciatica in men was associated with levels of atherogenic serum lipids. Pharmacologically treated hyperlipidemia was associated with sciatica in women. The findings are in accordance with the atherosclerosis-sciatica hypothesis. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

Assessment of the genotoxicity of the rat carcinogen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in rat liver epithelial cells in vitro

Maki-Paakkanen, J. and Hakulinen, P.

Toxicology in Vitro. 2008; 22(2): 535-540. Article. IF 2.045

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a disinfection by-product in chlorinated drinking water, is a multisite carcinogen in rats. One main target organ is the liver. The mechanism of the tumorigenicity was evaluated by testing the genotoxicity of MX in rat liver epithelial cell line cells. In the studies, the single cell gel/Comet assay and the hypoxanthine phosphoribosyl transferase locus assay to 6-thioguanine resistance were used. MX induced a dose-related genotoxic response in the comet assay. The lowest effective concentration was 120 mu M when the exposure was in medium plus supplements and 3.75 mu M when the exposure was in phosphate-buffered salt solution. MX also increased the frequency of TG(r) mutants, when the cells were treated in phosphate-buffered salt solution, at a concentration range of 2.3-9.2 mu M. The present results show for the first time that MX causes DNA damage and gene mutations in rat liver epithelial cells, the target cells of MX's tumorigenicity in rats. We have earlier shown that MX also inhibits gap junctional intercellular communication in the same cells.

The genotoxic effects were induced starting at about 60 times higher concentration, in identical exposure conditions, compared with the lowest concentration of MX causing the tumor promoter effect. (C) 2007 Elsevier Ltd. All rights reserved.

Double-blind, randomized comparison of memantine and escitalopram for the treatment of major depressive disorder comorbid with alcohol dependence

Muhonen, L. H., Loennqvist, J., Juva, K. and Alho, H.

Journal of Clinical Psychiatry. 2008; 69(3): 392-399. Article. IF 5.533

Objective: The aim of the study was to evaluate possible new treatments for major depressive disorder in patients with comorbid alcohol dependence in a municipal alcohol treatment unit. The efficacy of memantine, a noncompetitive glutamate N-methyl-D-aspartate (NMDA)-receptor blocker used for the treatment of moderate to severe Alzheimer's disease, was compared with that of escitalopram, a selective serotonin reuptake inhibitor antidepressant.

Method: Eighty alcohol-dependent outpatients with major depressive disorder (DSM-IV criteria) seeking treatment from municipal alcohol treatment clinics in Helsinki, Finland, were randomly assigned 1: 1 to receive memantine 20 mg/day or escitalopram 20 mg/day. During the study period, patients continued their routine treatment at the clinics. Abstinence was not required. Concomitant interventions or imposed treatment goals were not offered by the study physician. The patients returned to the treatment clinics at weeks 1, 2, 4, 12, and 26 for data collection and for medication checking and dispensing. Outcome measures were the Montgomery-Asberg Depression Rating Scale (MADRS) and Beck Depression Inventory-II for depression, Hamilton Rating Scale for Anxiety (HAM-A) and Beck Anxiety Inventory for anxiety, Consortium to Establish a Registry for Alzheimer's Disease test battery for cognitive functions, and Social and Occupational Functioning Assessment Scale for social and occupational functions and quality-of-life measures. Twenty-nine patients in each group completed the study. All primary and secondary outcome statistical analyses were performed by an independent source for intent-to-treat populations, which included all patients randomly assigned to treatment. The study was conducted from December 2004 to May 2006.

Results: Both treatments significantly reduced the baseline level of depression and anxiety according to MADRS and HAM-A, which were the primary measures (p < .0001). There was no significant difference between the memantine and escitalopram groups. Assessed cognitive functioning scores were primarily within the normative range and were unchanged in both groups. Quality-of-life outcomes equally improved in both treatment groups.

Conclusions: These data provide new evidence for the safety and potential efficacy of memantine and escitaloprarn for major depressive disorder in patients with comorbid alcohol dependence. Clinical Trials Registration: ClinicalTrials.gov identifier NCT00368862.

Impact of different case definitions for acute otitis media on the efficacy estimates of a pneumococcal conjugate vaccine

Palmu, A., Jokinen, J. and Kilpi, T.

Vaccine. 2008. IF 3.159

Considerably higher vaccine efficacy estimate for clinical acute otitis media (AOM) has been obtained for the 11-valent pneumococcal conjugate vaccine with protein D of Haemophilus influenzae as a carrier (PncPD11) in the POET study than for the 7-valent pneumococcal conjugate vaccine (PncCRM7) in the Finnish Otitis Media (FinOM) Vaccine Trial.

We recalculated PncCRM7 efficacy from the FinOM data using a case definition for AOM very close to the POET definition and a definition giving an incidence for AOM in the control group comparable to that obtained in the POET study. The different case definitions had only a slight impact on the vaccine efficacy estimates compared to the original case definitions.

We were not able to show that the differences between the study results would be due to the case definitions used.

Markers of endothelial dysfunction and low-grade inflammation are associated in the offspring of type 2 diabetic subjects

Ruotsalainen, E., Vauhkonen, I., Salmenniemi, U., Pihlajamaki, J., Punnonen, K., Kainulainen, S., Jalkanen, S., Salmi, M. and Laakso, M.

Atherosclerosis. 2008; 197(1): 271-277. Article. IF 3.811

The offspring of type 2 diabetic patients are at elevated risk for type 2 diabetes and cardiovascular disease. The aim of our study was to characterize the role of various biomarkers of endothelial activation in a cohort of offspring of type 2 diabetic subjects and to assess the association of adhesion molecules with inflammatory markers and metabolic parameters. Cytokine and adhesion molecule levels were measured in 19 healthy subjects and in 129 offspring of patients with type 2 diabetes (109 with normal glucose tolerance and 20 with impaired glucose tolerance). Insulin sensitivity was determined with the hyperinsulinemic-euglycemic clamp, insulin secretion with the intravenous glucose tolerance test, and abdominal fat distribution with computed tomography. The levels of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-Selectin and vascular adhesion protein-1 were not increased in offspring of type 2 diabetic subjects, but they correlated with inflammatory markers (C-reactive protein, tumor necrosis-alpha, interleukin-6, interleukin-1beta, interleukin-1 receptor antagonist, interleukin-8, interleukin-10 and interleukin-18).

In conclusion, the levels of adhesion molecules were not elevated in the prediabetic state. Inflammatory markers and adhesion molecules were correlated suggesting that low-grade inflammation may precede the elevation of levels of adhesion molecules. (C) 2007 Published by Elsevier Ireland Ltd.

Air Temperature and Inflammatory Responses in Myocardial Infarction Survivors

Schneider, A., Panagiotakos, D., Picciotto, S., Katsouyanni, K., Lowel, H., Jacquemin, B., Lanki, T., Stafoggia, M., Bellander, T., Koenig, W. and Peters, A.

Epidemiology. 2008; 19(3): 391-400. IF 4.339

BACKGROUND:: Temperature changes have been associated with increased cardiovascular risk, but the role of inflammatory markers in this relationship is not well understood. The objective of this study was to analyze the association between air temperature and C-reactive protein, interleukin-6 and fibrinogen in postmyocardial infarction patients. METHODS:: In a multicenter panel study, the 3 inflammatory blood markers were measured repeatedly. In total, 5813 blood samples in 1003 subjects were collected in 6 European cities representing different climates. Data on patient characteristics and disease history were gathered at the baseline visit. Meteorologic data were obtained from the city-specific network stations. The association was analyzed using a semiparametric model with random patient effects.

RESULTS:: A 10 degrees C decrease in the 5-day-average of air temperature before the blood withdrawal was associated with a 4% increase in C-reactive protein (4.3% [95% confidence interval = 0.2% to 8.1%]). Correspondingly, an increase of interleukin-6 was observed for the same time window (3.3% [0.1% to 6.3%]) whereas fibrinogen showed an increase of 1.3% (0.2% to 2.4%) with a lag of 3 days.

CONCLUSION:: A decrease in air temperature, particularly the average temperature of the last 5 days, was associated with an increase in both C-reactive protein and interleukin-6, whereas fibrinogen seemed to react to temperature changes after 3 days. In susceptible patients this might lead to an additional risk for cardiovascular events and suggests a biologic mechanism for the observed seasonal variation in death from ischemic heart disease and stroke in the elderly.

Genetics of pubertal timing and its associations with relative weight in childhood and adult height: The Swedish young male twins study

Silventoinen, K., Haukka, J., Dunkel, L., Tynelius, P. and Rasmussen, F.

Pediatrics. 2008; 121(4): E885-E891. Article. IF 5.012

OBJECTIVE. Previous studies have suggested that the timing of puberty is associated with BMI in childhood and adult stature. Because the genetic background of these associations is not thoroughly investigated, we aimed to analyze it in a longitudinal twin cohort.

METHODS. We studied a Swedish cohort of 99 monozygotic and 76 dizygotic twin pairs born between 1973 and 1979 with weight and length or height measured annually from birth to age 18 years. Age at onset of pubertal growth spurt, age at peak height velocity, and final height were estimated by a parametric JPA2 growth model. The genetic architecture and mutual associations of these traits and childhood BMI were analyzed by linear structural equation modeling.

RESULTS. The heritability estimate was 0.91 for age at onset of pubertal growth spurt, 0.93 for age at peak height velocity, and 0.97 for adult height. Age at onset of pubertal growth spurt was negatively associated with BMI from 1 to 10 years of age and stature in early adulthood. For age at peak height velocity, we found similar associations with childhood BMI and stature in early adulthood. These associations were explained by common genetic factors.

CONCLUSION. Growth during puberty is strictly genetically regulated. These genetic factors also explain why boys who matured early had higher BMI through childhood and taller stature in early adulthood.

Adequacy of, attitudes toward, and adherence to treatments by suicidal and nonsuicidal depressed patients

Sokero, P., Melartin, T., Rytsala, H., Leskela, U., Lestela-Mielonen, P. and Isometsa, E.

J Nerv Ment Dis. 2008; 196(3): 223-9. IF 1.957

We examined differences in treatments received, and attitudes and adherence to them between suicidal and nonsuicidal patients with major depressive disorder (MDD).

Psychiatric MDD patients with no suicidal behavior (N = 92), suicidal ideation (N = 92), or attempts (N = 34) were compared during 6 months of follow-up in the Vantaa Depression Study (VDS). Patients with suicidal behavior received antidepressants or adequate antidepressant treatment significantly more often, had more frequent appointments with psychiatrists, more psychotherapeutic support, and more favorable attitudes toward antidepressant treatment than nonsuicidal patients. However, after adjusting for the confounding severity of depression, the significance of these differences was lost. Adherence to treatment was similar in the patient groups.

Overall, among psychiatric patients with MDD, those known to be suicidal have higher suicide risk and should receive more intensive treatment. However, suicidal behavior per se does not seem to markedly influence treatments provided nor should it be associated with negative attitudes or poor adherence to treatments.

Sleep quality in young adults with very low birth weight - the Helsinki study of very low birth weight adults

Strang-Karlsson, S., Raikkonen, K., Kajantie, E., Andersson, S., Hovi, P., Heinonen, K., Pesonen, A. K., Jarvenpaa, A. L., Eriksson, J. G. and Paavonen, E. J.

Journal of Pediatric Psychology. 2008; 33(4): 387-395. Article. IF 3.157

Objective To assess the relationship between very low birth weight (VLBW; 1,500 g) and quality and amount of sleep in young adults.

Methods We compared 89 VLBW and 78 term-born 19- to 26-year-old adults, by actigraphy and the Basic Nordic Sleep Questionnaire.

Results There were no group differences in sleep quality or amount (ps .15), although VLBW adults went to bed on average 36 min earlier (95 confidence interval 666 min). Shorter gestational age was related to longer sleep latency both within VLBW (standardized regression coefficient beta=-.36, p=.040) and term-born adults (beta=-.25, p=.029).

Conclusion Adults with VLBW had similar quality and amount of sleep as those born at term, although VLBW adults went to bed earlier, suggesting an advanced sleep phase. Within each group, a lower gestational age was related to a longer sleep onset.

Uncertainty in mortality response to airborne fine particulate matter: Combining European air pollution experts

Tuomisto, J. T., Wilson, A., Evans, J. S. and Tainio, M.

Reliability Engineering & System Safety. 2008; 93(5): 732-744. Article. IF 0.920

The authors have performed a structured expert judgement study of the population mortality effects of fine particulate matter (PM2.5) air pollution. The opinions of six European air pollution experts were elicited.

The ability of each expert to probabilistically characterize uncertainty was evaluated using 12 calibration questions-relevant variables whose true values were unknown at the time of elicitation, but available at the time of analysis. The elicited opinions exhibited both uncertainty and disagreement. It emerged that there were significant differences in expert performance. Two combinations of the experts' judgements were computed and evaluated-one in which each expert's views received equal weight; the other in which the expert's judgements were weighted by their performance on the calibration variables. When the performance of these combinations was evaluated the equal-weight combination exhibited acceptable performance, but was nonetheless inferior to the performance-based combination. In general, the experts agreed with published studies for the best estimate of all-cause mortality from PM2.5; however, as would be expected, they gave confidence intervals that were several times broader than the statistical confidence intervals taken directly from the most frequently cited published studies.

The experts were rather comfortable with applying epidemiological results from one geographic region to another. However, there was more uncertainty and disagreement about issues of timing of the effect and about the relative toxicity of different constituents of PM2.5.

Even so, the experts were in fairly good agreement that an appreciable fraction of the long-term health effects occurs within a few months after the exposure and that combustion-derived particles are more toxic than PM2.5 on average, while secondary sulphates, nitrates and/or crustal materials may be less toxic. These assessments bring very valuable and relevant information to air pollution risk assessment. (c) 2007 Elsevier Ltd. All rights reserved.

Transmission of drug-resistant HIV-1 in Europe remains limited to single classes

Wensing, A. M. J., Vercauteren, J., van de Vijver, D. A., Albert, J., Asjo, B., Balotta, C., Camacho, R., Coughlan, S., Grossman, Z., Horban, A., Kucherer, C., Nielsen, C., Paraskevis, D., Loke, W. C., Poggensee, G., Puchhammer-Stockl, E., Riva, C., Ruiz, L., Schmit, J. C., Schuurman, R., Salminen, M., Sonnerborg, A., Stanojevic, M., Struck, D., Vandamme, A. M. and Boucher, C. A. B.

AIDS. 2008; 22(5): 625-635. Article. IF 5.632

Background: The spread of drug-resistant HIV-1 might compromise the future success of current first-line regimens.

Objective: To analyse the extent and impact of transmission of drug-resistant HIV-1 variants in Europe.

Design and methods: The European prospective programme (SPREAD) collected demographic, clinical and virological data from 1245 HIV-1 -infected individuals in 17 countries diagnosed in 2002-2003. The potential impact of transmitted drug resistance mutations (TDRMs) on therapy response was determined by using genotypic interpretation algorithms.

Results: The overall prevalence of viruses with drug-resistance mutations was 9.1% [96/1050; 95% confidence interval: 7.5-11.1]. The majority (71 %) harboured only a single amino acid substitution with limited effect on predicted drug susceptibility. Mutations associated with resistance to nucleoside reverse transcriptase inhibitors were observed most frequently [57/1050 (5.4%)], followed by mutations related to protease inhibitors [32/1050 (3.0%)] and mutations related to non-nucleoside reverse transcriptase inhibitors (NNRTIs) [27/1050 (2.6%)]. In some cases, however, resistance was quite extensive. Four individuals were infected with viruses with reduced susceptibility to all nucleoside reverse transcriptase inhibitors, 3 to all protease inhibitors and 20 to both NNRTIs. Remarkably, in one individual, the resistance pattern was so extensive that none of the available current antiretroviral drugs was predicted to be fully active.

Conclusion: The prevalence of TDRM-HIV is quite prominent (9.1%) but did not increase in comparison with a large retrospective European study. Particularly the presence of single NNRTI mutations may impact the efficacy of the first-line regimens. Continuous prospective monitoring remains indicated to explore the patterns and factors contributing to the transmission of TDRMs as well as the potential clinical consequences. (C) 2008 Wolters Kluwer Health Lippincott Williams & Wilkins