30.7.2007

Ahtiainen, L., Kolikova, J., Mutka, A. L., Luiro, K., Gentile, M., Ikonen, E., Khiroug, L., Jalanko, A. and Kopra, O.

Neurobiol Dis. 2007. Journal Article. IF 4.128

Infantile neuronal ceroid lipofuscinosis (INCL) is a severe neurodegenerative disorder of children, characterized by selective death of neocortical neurons. To understand early disease mechanisms in INCL, we have studied Ppt1(Deltaex4) knock-out mouse neurons in culture and acute brain slices. Global transcript profiling showed deregulation of key neuronal functions in knock-out mice including cholesterol metabolism, neuronal maturation, and calcium homeostasis. Cholesterol metabolism showed major changes; sterol biosynthesis was enhanced and steady-state amounts of sterols were altered at the cellular level. Changes were also present in early maturation of Ppt1(Deltaex4) neurons indicated by increased proliferative capacity of neuronal stem cells. Knock-out neurons presented unaltered electrophysiological properties suggesting uncompromised synaptic function in young animals. However, knock-out neurons exhibited more efficient recovery from glutamate-induced calcium transients, possibly indicating neuroprotective activation. This study established that the neuronal deregulation in INCL is linked to neuronal maturation, lipid metabolism and calcium homeostasis.

Coffee consumption and risk of total and cardiovascular mortality among patients with type 2 diabetes

Bidel, S., Hu, G., Qiao, Q., Jousilahti, P., Antikainen, R. and Tuomilehto, J.

Diabetologia. 2006; 49(11): 2618-26. Journal Article. IF 5.247

AIMS/HYPOTHESIS: Higher habitual coffee drinking has been associated with a lower risk of developing type 2 diabetes. The relation between coffee consumption and risk of cardiovascular disease (CVD) has been examined in many studies, but the issue remains controversial. This study was designed to assess the association between coffee consumption and CVD mortality among patients with type 2 diabetes.

METHODS: We prospectively followed 3,837 randomly ascertained Finnish patients with type 2 diabetes aged 25 to 74 years. Coffee consumption and other study parameters were determined at baseline. The International Classification of Diseases was used to identify CHD, CVD and stroke cases using computerised record linkage to the national Death Registry. The associations between coffee consumption at baseline and risk of total, CVD, CHD, and stroke mortality were analysed by using Cox proportional hazards models.

RESULTS: During the average follow-up of 20.8 years, 1,471 deaths were recorded, of which 909 were coded as CVD, 598 as CHD and 210 as stroke. The respective multivariate-adjusted hazard ratios in participants who drank 0-2, 3-4, 5-6, and > or =7 cups of coffee daily were 1.00, 0.77, 0.68 and 0.70 for total mortality (P<0.001 for trend), 1.00, 0.79, 0.70 and 0.71 for CVD mortality (P=0.006 for trend), 1.00, 0.78, 0.70 and 0.63 for CHD mortality (p=0.01 for trend), and 1.00, 0.77, 0.64 and 0.90 for stroke mortality (p=0.12 for trend).

CONCLUSIONS/INTERPRETATION: In this large prospective study we found that in type 2 diabetic patients coffee drinking is associated with reduced total, CVD and CHD mortality.

Driving under the influence of drugs - amphetamine concentrations in oral fluid and whole blood samples

Engblom, C., Gunnar, T., Rantanen, A. and Lillsunde, P.

J Anal Toxicol. 2007; 31(5): 276-80. Journal Article. IF 1.242

This study investigated amphetamine concentrations in both oral fluid and whole blood samples of persons suspected of driving under the influence of drugs. The data for the study were obtained from 153 cases. The mean volume of oral fluid collected with the Intercept oral fluid collection device was 224 microL. Because of the small sample volume of oral fluid, the results of the amphetamine concentrations in oral fluid were not used in the calculations for 39 cases. The total number of cases positive for amphetamine in oral fluid was 100 out of 114. In seven cases the oral fluid sample was positive (cutoff 25 microg/L), even though the whole blood sample was negative (cutoff 20 microg/L). All of the cases found positive in whole blood (n = 93) were also positive in oral fluid. Oral fluid would therefore be well suited as a testing matrix for amphetamine when driving under the influence is suspected. The results nevertheless indicated that the cutoff used for amphetamine in oral fluid (i.e., 25 microg/L) could be higher to correspond to the window of detection given by the level of 20 microg/L in whole blood.

Individual-level measures of social capital as predictors of all-cause and cardiovascular mortality: a population-based prospective study of men and women in Finland

Hyyppa, M. T., Maki, J., Impivaara, O. and Aromaa, A.

Eur J Epidemiol. 2007. Journal Article. IF 1.605

Individual-level social capital was assessed for prediction of mortality in a nationally representative study population aged 30-99 years at the baseline. A total of 90% of the original sample had participated in a comprehensive health examination (Mini-Finland Health Survey) in 1978-1980. After the first 5 years of the 24-year follow-up period, 1,196 of 3,014 men and 1,280 of 3,689 women died. Individual-level social capital was determined by factor analysis that revealed three factors: residential stability, leisure participation and interpersonal trust. Factor analysis showed a gender difference in leisure social participation. All-cause mortality and cardiovascular mortality were analyzed using Cox proportional hazard models. Adjusted for demographic, life style and biological risk factors, and for health and socio-economic status, leisure participation was associated with reduced all-cause mortality in men (hazard ratio, HR: 0.94; 95% confidence interval, CI: 0.89-1.00). This association seems to be related to economic status in men. Age modifies the effect of interpersonal trust on all-cause mortality in men. In women, leisure participation (HR: 0.96; 95% CI: 0.91-1.00) and interpersonal trust (HR: 0.69; 95% CI: 0.51-0.93) predicted all-cause mortality, and the latter also cardiovascular mortality (HR: 0.93; 95% CI: 0.86-1.00). The associations between individual-level social capital and mortality are gender- and age-related. Understanding the gender and age perspectives appears to be essential for better insight into the interrelations between social capital and health.

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.

Journal of Hospital Infection. 2007; 66(1): 22-28. Journal Article. IF 2.422

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 anatysed. 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 is an element of 386 062 (70% for screening and 25% for contact isolation). Costs due to meticillin resistance in treatment of MRSA infections were is an element of 16 000. The income loss for this hospital due to closed beds was is an element of 1 183 808. 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.

(C) 2007 The Hospital Infection Society. Published by Elsevier Ltd. AR rights reserved.

Panton-Valentine leukocidin genes and staphylococcal chromosomal cassette mec types amongst Finnish community-acquired methicillin-resistant Staphylococcus aureus strains, 1997-1999

Karden-Lilja, M., Ibrahem, S., Vuopio-Varkila, J., Salmenlinna, S., Lyytikainen, O., Siira, L. and Virolainen, A.

Eur J Clin Microbiol Infect Dis. 2007. Journal Article. IF 2.330

Methicillin-resistant Staphylococcus aureus (MRSA) strains from Finland covering years 1997-1999 were studied for the presence of Panton-Valentine leukocidin (PVL) gene loci, and the clinically well-defined community-acquired MRSA (CA-MRSA) strains (n = 108) also for staphylococcal chromosomal cassette mec (SCCmec) and multilocus sequence types (MLST). Only a minority (12%) of the CA-MRSA strains contained the PVL gene loci and possessed genotypes formerly described as typical to CA-MRSA strains. The majority of these strains were heterogenous by MLST and pulsed-field gel electrophoresis (PFGE) analysis but, however, harboured the SCCmec cassette type IV. In conclusion, it seems doubtful to consider only molecular characteristics such as the presence of PVL genes as definite markers for CA-MRSA strains.

Two insulin gene single nucleotide polymorphisms associated with type 1 diabetes risk in the Finnish and Swedish populations

Laine, A. P., Holmberg, H., Nilsson, A., Ortqvist, E., Kiviniemi, M., Vaarala, O., Akerblom, H. K., Simell, O., Knip, M., Ludvigsson, J., Ivarsson, S. A., Larsson, K., Lernmark, A. and Ilonen, J.

Disease Markers. 2007; 23(3): 139-145. Journal Article. IF 2.438

We have developed high-throughput tests for the detection of the insulin gene region SNPs -23HphI and -2221MspI. The potential of these markers to enhance the efficiency of type I diabetes risk screening was then evaluated by analyzing them in Finnish and Swedish populations. Blood spots on filter paper were analyzed using PCR followed by sequence- specific hybridization and time-resolved fluorometry reading. Distribution of the genotypes at both positions differed significantly among the affected children compared to the controls. The risk genotypes (CC, AA) were significantly more common in Finland than in Sweden, both among patients and controls. The VNTR genotype homozygous for the protective class III alleles showed a significantly stronger protective effect than the heterozygote (p = 0.02). Analyzing both SNPs enabled the detection of VNTR class III subclasses IIIA and IIIB. The observed significance between effects of the protective genotypes was due to the strong protective effect of the IIIA/IIIA genotype. IIIA/IlIA was the only genotype with significant discrepancy between protective effects compared to the other class III genotypes. These observations suggest that heterogeneity between the protective IDDM2 lineages could exist, and analyzing both -23HphI and -2221MspI would thus potentially enhance the sensitivity and specificity of type I diabetes risk estimation.

Nuclear and nucleolar targeting of influenza A virus NS1 protein: Striking differences between different virus subtypes

Melen, K., Kinnunen, L., Fagerlund, R., Ikonen, N., Twu, K. Y., Krug, R. M. and Julkunen, I.

Journal of Virology. 2007; 81(11): 5995-6006. Journal Article. IF 5.341

Influenza A virus nonstructural protein 1 (NSIA protein) is a virulence factor which is targeted into the nucleus. It is a multifunctional protein that inhibits host cell pre-mRNA processing and counteracts host cell antiviral responses. We show that the NSIA protein can interact with all six human importin ct isoforms, indicating that the nuclear translocation of NSIA protein is mediated by the classical importin alpha/beta pathway. The NS1A protein of the H1N1 (WSN/33) virus has only one N-terminal arginine- or lysine-rich nuclear localization signal (NLS1), whereas the NS1A protein of the H3N2 subtype (Udorn/72) virus also has a second C-terminall NLS (NLS2). NLS1 is mapped to residues 35 to 41, which also function in the double-stranded RNA-binding activity of the NS1A protein. NLS2 was created by a 7-amino-acid C-terminal extension (residues 231 to 237) that became prevalent among human influenza A virus types isolated between the years 1950 to 1987. NLS2 includes basic amino acids at positions 219, 220, 224, 229, 231, and 232. Surprisingly, NLS2 also forms a functional nucleolar localization signal NoLS, a function that was retained in H3N2 type virus NSIA proteins even without the C-terminal extension. It is likely that the evolutionarily well-conserved nucleolar targeting function of NS1A protein plays a role in the pathogenesis of influenza A virus.

Consumption of sweetened beverages and intakes of fructose and glucose predict type 2 diabetes occurrence

Montonen, J., Jarvinen, R., Knekt, P., Heliovaara, M. and Reunanen, A.

Journal of Nutrition. 2007; 137(6): 1447-1454. Journal Article. IF 4.009

The role of intakes of different sugars in the development of type 2 diabetes was studied in a cohort of 4,304 men and women aged 40-60 y and initially free of diabetes at baseline in 1967-1972. Food consumption data were collected using a dietary history interview covering the habitual diet during the previous year. The intakes of different sugars were calculated and divided in quartiles. During a 12-y follow-up, 177 incidents of type 2 diabetes cases were identified from a nationwide register. Combined intake of fructose and glucose was associated with the risk of type 2 diabetes but no significant association was observed for intakes of sucrose, lactose, or maltose. The relative risk between the highest and lowest quartiles of combined fructose and glucose intake was 1.87 (95% [Cl] = 1.19, 2.93; P= 0.003). The corresponding relative risks between the extreme quartiles of consumption of food items contributing to sugar intakes were 1.69 (95% [Cl] = 1.17, 2.43; P < 0.001) for sweetened berry juice and 1.67 (95% [Cl] = 0.98, 2.87; P = 0.01) for soft drinks. Our findings support the view that higher intake of fructose and glucose and sweetened beverages may increase type 2 diabetes risk.

Changes in cardiovascular risk factors among adolescents from 1995 to 2004 in the Republic of Karelia, Russia

Rogacheva, A., Laatikainen, T., Tossavainen, K., Vlasoff, T., Panteleev, V. and Vartiainen, E.

European Journal of Public Health. 2007; 17(3): 257-262. Journal Article. IF 1.481

Background: In Russia, cardiovascular mortality is among the highest in the world. Behaviours; related to the development of cardiovascular disease are usually adopted in childhood and adolescence. Very little information exists on prevalence and trends of risk factors among Russian youth. This study aims to investigate changes in the prevalence of cardiovascular risk factors among adolescents in the Republic of Karelia, Russia, from 1995 to 2004.

Methods: Cross-sectional surveys on chronic disease risk factors were carried out among 15-year-old adolescents in Pitkaranta region, in the Republic of Karelia. The surveys were conducted in all 10 secondary schools in the Pitkaranta region. All ninth-grade students in 1995 (N = 385, response rate 95%) and in 2004 (N = 395, response rate 85%) were included in the survey samples.

Results: Systolic blood pressure decreased statistically significantly among boys (from 119 to 116 mmHg). Diastolic blood pressure decreased statistically significantly among both girls (from 64 to 59 mmHg) and boys (from 62 to 59 mmHg). Total cholesterol increased statistically significantly only among girls (from 3.9 to 4.1 mmol/l). Body mass index did not exhibit any significant changes in both genders. Daily smoking rate doubled statistically significantly among girls from 7% to 15%.

Conclusion: The study results show changes in the prevalence of cardiovascular disease risk factors among adolescents in the Republic of Karelia occurring over the last decade. Active measures need to be taken to prevent the increase in smoking prevalence, especially among girls, and to avert the unfavourable development of other risk factors in the future.

Impact of psychiatric disorders on health-related quality of life: general population survey

Saarni, S. I., Suvisaari, J., Sintonen, H., Pirkola, S., Koskinen, S., Aromaa, A. and Lonnqvist, J.

Br J Psychiatry. 2007; 190: 326-32. Journal Article. IF 5.436

BACKGROUND: Measurement of health-related quality of life (HRQoL) with generic preference-based instruments enables comparisons of severity across different conditions and treatments. This is necessary for rational public health policy.

AIMS: To measure HRQoL decrement and loss of quality-adjusted life-years (QALYs) associated with pure and comorbid forms of depressive and anxiety disorders and alcohol dependence.

METHOD: A general population survey was conducted of Finns aged 30 years and over. Psychiatric disorders were diagnosed with the Composite International Diagnostic Interview and HRQoL was measured with the 15D and EQ-5D questionnaires.

RESULTS: Dysthymia, generalised anxiety disorder and social phobia were associated with the largest loss of HRQoL on the individual level before and after adjusting for somatic and psychiatric comorbidity. On the population level, depressive disorders accounted for 55%, anxiety disorders 30%, and alcohol dependence for 15% of QALY loss identified in this study.

CONCLUSIONS: Chronic anxiety disorders and dysthymia are associated with poorer HRQoL than previously thought.

The effects of a three-year smoking prevention programme in secondary schools in Helsinki

Vartiainen, E., Pennanen, M., Haukkala, A., Dijk, F., Lehtovuori, R. and De Vries, H.

European Journal of Public Health. 2007; 17(3): 249-256. Journal Article. IF 1.481

Background: This study evaluates the effects of a 3-year smoking prevention programme in secondary schools in Helsinki. The study is part of the European Smoking prevention Framework Approach (ESFA), in which Denmark, Finland, the Netherlands, Portugal, Spain and the UK participated.

Methods: A total of 27 secondary schools in Finland participated in the programme (n = 1821). Schools were randomised into experimental (13) and control groups (14). The programme included 14 information lessons about smoking and refusal skills training. The 3-year smoking prevention programme was also integrated into the standard curriculum. The community-element of the programme included parents, parish confirmation camps and dentists. The schools in the experimental group received the prevention programme and the schools in the control group received the standard health education curriculum.

Results: Among baseline never smokers (60.8%), the programme had a significant effect on the onset of weekly smoking in the experimental group [OR = 0.63 (0.45-0.90) P = 0.009] when compared with the control group. Being female, doing poorly at school, having parents and best friends who smoke and more pocket money to spend compared with others were associated with an increased likelihood of daily and weekly smoking onset. These predictors did not have an interaction effect with the experimental condition.

Conclusion: This study shows that a school- and community-based smoking prevention programme can prevent smoking onset among adolescents.