4.9.2006

Arajärvi, R., Varilo, T., Haukka, J., Suvisaari, J., Suokas, J., Juvonen, H., Muhonen, M., Suominen, K., Hintikka, J., Schreck, M., Tuulio-Henriksson, A., Partonen, T. and Lönnqvist, J.

Psychiatry Res. 2006; 141(2): 161-72. IF 1.957

Family history of schizophrenia has been associated with negative symptoms in the clinical picture. Our aim was to examine the signs and symptoms of schizophrenia in a genetically homogeneous isolate and a nationwide multiplex family sample, and to investigate the symptom dimensions and their association with the degree of familial loading for psychotic disorders and with consanguinity.

For factor analysis of the Scales for the Assessment of Negative and Positive Symptoms, we included 290 patients with a DSM-IV diagnosis of schizophrenia: 63 multiplex family and 133 singleton patients from the isolate, and 94 nationwide multiplex family patients. The factor analysis yielded four factors. There was a significant difference between the multiplex and singleton patients, the former having more severe affective flattening and alogia. Further, the patients in isolate groups had fewer delusions and hallucinations compared with the whole country multiplex patients regardless of their familial loading for schizophrenia. This may be related to genetic homogeneity in the isolate.

We conclude that patients with first-degree relatives with psychotic disorder have more severe negative symptoms.

Twenty-five-year trends in lifestyle and socioeconomic characteristics in Eastern Finland

Barengo, N. C., Nissinen, A., Pekkarinen, H., Halonen, P. and Tuomilehto, J.

Scandinavian Journal of Public Health. 2006; 34(4): 437-444. Article. IF 0.727

Aims: Little is known about changes in lifestyle and socioeconomic characteristics among physical activity subgroups over time. This study aimed at assessing whether the lifestyle and the socioeconomic profile of people with either low total physical activity (TPA) or high TPA changed during 1972-97.

Methods: Six independent cross-sectional surveys were carried out among a middle-aged population at five-year intervals in Eastern Finland, 1972-97. The participation rates varied from 71% to 95% (n=33,712). Physical activity during leisure time (LTPA) and occupational physical activity (OPA) were determined by a self-administered questionnaire. TPA was calculated by combining LTPA and OPA.

Results: Men with low TPA were older, smoked more, and had a higher BMI than men with high TPA. The increase in BMI was almost fourfold in sedentary men (trend 0.4%/5 years, p=0.023 for trend) than in highly active men (trend 0.1%/5 years, p=0.044 for trend). Education no longer accounted for the socioeconomic difference after 1977. Sedentary women had a higher BMI and smoking prevalence than those with high TPA. The difference in age, education, and marital status disappeared between those two groups after 1977.

Conclusions: The lifestyle and the socioeconomic profiles of people with both low TPA and high TPA have changed during 1972-97.

Macrolide and Azithromycin Use Are Linked to Increased Macrolide Resistance in Streptococcus pneumoniae

Bergman, M., Huikko, S., Huovinen, P., Paakkari, P. and Seppälä, H.

Antimicrob Agents Chemother. 2006. IF 4.379

The connection between regional antimicrobial resistance rates in S. pneumoniae and regional antimicrobial use in Finland was investigated.

During the 6-year study period of 1997 - 2002, a total of 31,609 S. pneumoniae isolates were tested for penicillin resistance and a total of 23,769 isolates for macrolide resistance in 18 central hospital districts in Finland. The regional macrolide resistance rates were compared with the local use of (1) all macrolides pooled and (2) azithromycin. The penicillin resistance levels were compared with the consumption data of (1) penicillins, (2) cephalosporins, (3) all betalactames pooled, and (4) all macrolides pooled.

A statistically significant association was found between macrolide resistance and total use of macrolides and the use of azithromycin. Moreover, total use of betalactames and total use of cephalosporins were significantly connected to low-level penicillin resistance. A statistically significant association was not found between penicillin-nonsusceptible isolates and penicillin or total macrolide consumption.

In conclusion, total macrolide use and azithromycin use are associated with increased macrolide resistance, and beta-lactame use and cephalosporin use are connected to increased low-level penicillin resistance in S. pneumoniae. Unnecessary prescribing of macrolides and cephalosporins should be avoided.

Association of leisure time physical activity and abdominal obesity with fasting serum insulin and 2-h postchallenge plasma glucose levels

Borodulin, K., Tuomilehto, J., Peltonen, M., Lakka, T. A., Sundvall, J. and Jousilahti, P.

Diabetic Medicine. 2006; 23(9): 1025-1028. Article. IF 2.725

Aims We investigated the joint associations of leisure time physical activity and abdominal obesity with fasting insulin and 2-h glucose levels and with the risk of impaired glucose tolerance (IGT) and Type 2 diabetes (Type 2 DM).

Methods A cross-sectional population-based random sample of 1812 Finnish adults 45-74 years of age without a history of cardiovascular disease or diabetes. Relative energy expenditure during the previous 12 months (METh/week), assessed by a questionnaire, was used as a measure of leisure time physical activity. Waist-hip ratio (WHR) was used as a measure of abdominal obesity. IGT and Type 2 DM were assessed by a 2-h oral glucose tolerance test and were defined according to the World Health Organization guidelines.

Results While 2-h glucose and fasting insulin levels increased with increasing WHR (P < 0.001 and P < 0.001, respectively), both of them decreased with increasing physical activity (P = 0.015 and P < 0.001, respectively). The highest 2-h glucose and fasting insulin levels were found among individuals who had most abdominal obesity and were least physically active. Physically inactive individuals had a higher prevalence of IGT and Type 2 DM in all WHR tertiles than physically active persons.

Conclusions Higher levels of leisure time physical activity are associated with lower 2-h glucose and fasting insulin levels and a reduced risk of having IGT and Type 2 DM, independent of the level of abdominal obesity.

Associations of leisure time physical activity, self-rated physical fitness, and estimated aerobic fitness with serum C-reactive protein among 3,803 adults

Borodulin, K., Laatikainen, T., Salomaa, V. and Jousilahti, P.

Atherosclerosis. 2006; 185(2): 381-7. IF 3.777

OBJECTIVE: Serum C-reactive protein (CRP), a marker of systemic inflammation, is a risk factor for cardiovascular disease. Obesity and physical activity are associated with CRP, though population studies are sparse.

METHODS AND RESULTS: We assessed the cross-sectional relationship of physical activity, self-rated fitness and estimated aerobic fitness with serum CRP among a population-based random sample of 3,803 Finnish adults aged 25-74 years. Conditioning, commuting and non-conditioning physical activity was measured by a recall and self-rated physical fitness by a questionnaire. A non-exercise test was used to estimate aerobic fitness. The combined association of aerobic fitness and waist-to-hip ratio (WHR) on CRP was also assessed. Self-rated fitness and aerobic fitness had inverse associations with CRP (adjusted for age, WHR, smoking, anti-hypertensive drugs, aspirin, diabetes, hypercholesterolemia, hormone replacement therapy and menopausal status) in both sexes (p < 0.001). An inverse age-adjusted association of conditioning and non-conditioning physical activity with CRP was found in both sexes. After further adjustments, associations remained significant in women for conditioning and non-conditioning activity (p < 0.001 and p = 0.010, respectively) and borderline significant in men (p = 0.074 and p = 0.070, respectively). Commuting physical activity was inversely associated with CRP among women only (p = 0.012).

CONCLUSIONS: Physical activity and fitness may have an anti-inflammatory effect, which is independent of obesity.

Early growth and adult health outcomes--lessons learned from the Helsinki Birth Cohort Study

Eriksson, J. G.

Matern Child Nutr. 2005; 1(3): 149-54.

Slow growth during fetal life and infancy is often followed by accelerated weight gain in childhood. These patterns of growth seem to precede the development of coronary heart disease (CHD) and type 2 diabetes in adult life. Patterns of growth associated with CHD and type 2 diabetes in adult life are described based upon findings from the Helsinki Birth Cohort Study.

We are beginning to understand that adult degenerative diseases are associated with different patterns of early growth. Yet it is not clear what optimal growth is and how it can be achieved. Most data suggest that the development of many non-communicable diseases involve a number of interactions including genetic ones. Therefore these diseases can best be focused upon from a life cycle perspective.

Children's homes--determinants of moisture damage and asthma in Finnish residences

Haverinen-Shaughnessy, U., Pekkanen, J., Hyvärinen, A., Nevalainen, A., Putus, T., Korppi, M. and Moschandreas, D.

Indoor Air. 2006; 16(3): 248-55. IF 0.978

Certain housing characteristics increase the risk for moisture damage, which has been associated with increased risk for asthma in children. Modeling moisture damage as a function of these characteristics could therefore provide a simple tool to estimate building-related risk for asthma. This study aimed to find out specific associations between asthma case-control status of children and moisture damage and housing characteristics. The data consisted of information on 121 asthmatic children and predominately two age-, gender- and place of residence-matched control children for every case, and information on moisture damage and housing characteristics in the homes of the children. In a previous study, we found a statistically significant association between moisture damage observations in main living areas and asthma in children. Using logistic regression, five models were formulated to predict moisture damage status of the homes and moisture damage status of living areas. The models were able to classify the damage status correctly in 65.0-87.7% of the homes (kappa values 0.10-0.47) as functions of housing characteristics. None of the models qualified as a significant determinant of the case-control status of the children.

PRACTICAL IMPLICATIONS: It can be hypothesized that building-related risk for asthma could be roughly estimated using models predicting moisture damage status of buildings as a function of easily obtainable housing characteristics. The results of this study indicated that, with a moderate certainty, it is possible to model moisture damage status of buildings using housing characteristics. However, the models developed did not associate with asthma in children.

In conclusion, it was not possible to estimate the risk for asthma by studying housing characteristics only, but detailed information on moisture damage (e.g. location of damage) was crucial for such estimation.

Determinants of daily smoking in Estonia, Latvia, Lithuania, and Finland in 1994-2002

Helasoja, V. V., Lahelma, E., Prättälä, R. S., Patja, K. M., Klumbiene, J., Pudule, I. and Kasmel, A.

Scandinavian Journal of Public Health. 2006; 34(4): 353-362. Article. IF 0.727

Aims: To investigate time trends in the smoking prevalence and the sociodemographic and psychosocial background of smoking in the Baltic countries in comparison with Finland during 1994-2002.

Methods: Differences in daily smoking according to age, education, urbanization, and psychological distress in the Baltic countries and Finland were studied using postal surveys in 1994, 1996, 1998, 2000, and 2002 among adults (20-64 years old) in Estonia (n=6,271), Latvia (n=6,106), Lithuania (n=9,824), and Finland (n=15,764).

Results: In 1994, 1996, 1998, 2000, and 2002 the prevalence of smoking in Estonia, Latvia, Lithuania, and Finland was 47%, 54%, 46%, and 29% among men, and 21%, 19%, 11%, and 19% among women, respectively. Smoking increased among Lithuanian women from 6% in 1994 to 13% in 2002, but decreased among Estonian men and women. Smoking was generally more common among younger individuals, the less educated, and people with distress in all four countries. The odds ratios for smoking for those with low education compared with those with high education were 2.18 (1.69-2.81), 3.32 (2.55-4.31), 2.20 (1.79-2.70) and 2.80 (2.40-3.27) in men, and 1.90 (1.42-2.52). 3.09 (2.28-4.18), 0.86 (0.59-1.26), and 3.00 (2.53-3.55) in women, in Estonia, Latvia, Lithuania, and Finland, respectively. There were indications of increasing educational differences in Latvian men. Smoking was less common among rural women in all countries except Estonia.

Conclusions: Estonia, Latvia, and Finland show characteristics of the "mature" phase of a smoking epidemic, and smoking may not increase in these countries. In Lithuanian women smoking may increase. Smoking may be increasingly unequally distributed in the future in all the studied countries.

In vitro and in vivo testing of bioabsorbable antibiotic containing bone filler for osteomyelitis treatment

Koort, J. K., Suokas, E., Veiranto, M., Mäkinen, T. J., Jalava, J., Törmälä, P. and Aro, H. T.

Journal of Biomedical Materials Research Part A. 2006; 78A(3): 532-540. Article. IF 2.743

The use of local antibiotics from a biodegradable implant is appealing concept for treatment of chronic osteomyelitis.

Our aim was to develop a new drug delivery system based on controlled ciprofloxacin release from poly(n/L-lactide). Cylindrical composite pellets (1.0 x 0.9 mm) were manufactured from bioabsorbable poly(D/L-lactide) matrix and ciprofloxacin (7.4 wt %).

In vitro studies were carried out to delineate the release profile of the antibiotic and to verify its antimicrobial activity by means of MIC testing. A long-term study in rabbits was performed to validate the release of ciprofloxacin from the composite in vivo. Therapeutic level of ciprofloxacin (> 2 mu g/mL) was maintained between 60 and 300 days and the concentration remained below the potentially detrimental level of 20 mu g/mL in vitro. The released ciprofloxacin had retained its antimicrobial properties against common pathogens. In an exploratory long-term in vivo study with three rabbits, cip-rofloxacin could not be detected from the serum after moderate filling (160 mg) of the tibia (follow-up 168 days), whereas after high dosing (a total dose of 1000 mg in both tibias) ciprofloxacin was found temporarily at low serum concentrations (14-34 ng/mL) during the follow-up of 300 days. The bone concentrations of ciprofloxacin could be measured in all samples at 168 and 300 days.

The tested copolylactide matrix seems to be a promising option in selection of resorbable carriers for sustained release of antibiotics, but the composite needs modifications to promote ciprofloxacin release during the first 60 days of implantation. (c) 2006 Wiley Periodicals, Inc.

Self-reported sleep duration in Finnish general population

Kronholm, E., Harma, M., Hublin, C., Aro, A. R. and Partonen, T.

Journal of Sleep Research. 2006; 15(3): 276-290. Article. IF 3.329

Self-reported short or long sleep duration has been repeatedly found to be associated with increased mortality and health risks. However, there is still an insufficient amount of detailed knowledge available to characterize the short and long sleep duration groups in general population. Consequently, the underlying mechanisms potentially explaining the health risks associated with short and long sleep duration are unclear.

In the present study, the self-reported sleep duration in a sample of Finnish general population was studied, and its possible associations with such factors as self-perceived health, sociodemographic characteristics, lifestyle, sleep difficulties and daytime concomitants were analyzed. In particular, an effort was made to define mutually statistically-independent determinants of sleep duration. In the Finnish Health 2000 Survey, a representative sample of 8028 subjects of 30 years of age or older and a sample of 1894 subjects of 18-29 years of age were invited to take part in the health interview and health examination. The participation rate of the study was over 80%.

The most important and statistically-independent determinants of short and long sleep duration were gender, physical tiredness, sleep problems, marital status, main occupation and physical activity. However, in the multivariable model they only accounted for approximately 16% of the variance in sleep duration in short and long sleepers, suggesting multiple sources of variance.

The present study also suggests a dose-response like relationship between the sleep duration and many of its determinants within both short and long sleepers. A more detailed analysis of the clinical status of the short and long sleep duration groups is needed to evaluate the possible importance of these findings for health risks associated with sleep duration.

Batten disease (JNCL) is linked to disturbances in mitochondrial, cytoskeletal, and synaptic compartments

Luiro, K., Kopra, O., Blom, T., Gentile, M., Mitchison, H. M., Hovatta, I., Törnquist, K. and Jalanko, A.

J Neurosci Res. 2006. IF 3.239

Intracellular pathways leading to neuronal degeneration are poorly understood in the juvenile neuronal ceroid lipofuscinosis (JNCL, Batten disease), caused by mutations in the CLN3 gene. To elucidate the early pathology, we carried out comparative global transcript profiling of the embryonic, primary cultures of the Cln3(-/-) mouse neurons.

Statistical and functional analyses delineated three major cellular pathways or compartments affected: mitochondrial glucose metabolism, cytoskeleton, and synaptosome. Further functional studies showed a slight mitochondrial dysfunction and abnormalities in the microtubule cytoskeleton plus-end components. Synaptic dysfunction was also indicated by the pathway analysis, and by the gross upregulation of the G protein beta 1 subunit, known to regulate synaptic transmission via the voltage-gated calcium channels. Intracellular calcium imaging showed a delay in the recovery from depolarization in the Cln3(-/-) neurons, when the N-type Ca(2+) channels had been blocked.

The data suggests a link between the mitochondrial dysfunction and cytoskeleton-mediated presynaptic inhibition, thus providing a foundation for further investigation of the disease mechanism underlying JNCL disease. (c) 2006 Wiley-Liss, Inc.

Vascular amine oxidases are needed for leukocyte extravasation into inflamed joints in vivo

Marttila-Ichihara, F., Smith, D. J., Stolen, C., Yegutkin, G. G., Elima, K., Mercier, N., Kiviranta, R., Pihlavisto, M., Alaranta, S., Pentikäinen, U., Pentikäinen, O., Fulop, F., Jalkanen, S. and Salmi, M.

Arthritis Rheum. 2006; 54(9): 2852-2862. IF 7.421

OBJECTIVE: Leukocyte traffic from the blood to the joints is crucial in the pathogenesis of arthritis. A bifunctional endothelial cell-surface glycoprotein, AOC3 (amine oxidase, copper-containing 3; also known as vascular adhesion protein 1), has both adhesive and enzymatic properties. We undertook this study to determine the contribution of AOC3 and its oxidase activity to leukocyte trafficking into inflamed joints in vivo.

METHODS: We used gene-modified animals, molecular modeling, an AOC3 enzyme inhibitor, oxidase assays, and arthritis models (adjuvant-induced arthritis [AIA] in rats and anti-type II collagen antibody-induced arthritis in mice) to dissect the importance of AOC3 in vivo.

RESULTS: The AOC3 inhibitor fitted well with a covalent binding mode into the active site of the AOC3 crystal structure. It selectively blocked the oxidase activity of AOC3 in enzyme assays. Intraperitoneal and oral administration of the AOC3 inhibitor significantly ameliorated rat AIA. In anti-type II collagen antibody-induced arthritis in mice, the AOC3 inhibitor also improved the outcome of the joint inflammation. The acute semicarbazide-sensitive amine oxidase blockade by the inhibitor had even more pronounced effects than genetic deletion of AOC3. Enzymatic analyses showed that the inhibitor also blocked 2 other structurally very closely related AOCs, but not any of more than 100 other enzymes tested.

CONCLUSION: These are the first data to demonstrate that the enzymatic activity of the atypical endothelial adhesion molecule AOC3, and possibly that of other closely related ecto-oxidases, is crucial for leukocyte exit from the vessels in inflamed joints in vivo.

Induction of IRF-3 and IRF-7 phosphorylation following activation of the RIG-I pathway

Paz, S., Sun, Q., Nakhaei, P., Romieu-Mourez, R., Goubau, D., Julkunen, I., Lin, R. and Hiscott, J.

Cellular and Molecular Biology. 2006; 52(1): 17-28. Article. IF 1.018

The induction of type I interferon (IFN) and the development of the innate antiviral response are mediated by the activation of interferon regulatory factor (IRF)-3 and IRF-7 under the control of the non-canonical kinases TBK-1 and IKK epsilon. The initial sensing of infection by RNA viruses is mediated by the cytoplasmic, retinoic acid inducible gene I (RIG-I), via a Toll-like receptor (TLR) independent signaling pathway. In the present study, we identify key residues involved in IRF-3 and IRF-7 phosphorylation using TAO-tag purification of TBK-1 and IKK epsilon proteins. Based on the identification of an extended lsequence motif - SxSxxxS - common to both IRF-3 and IRF-7, an IRF-7 pSer477/479 phosphospecific antibody was generated. Virus infection, TBK-1/IKK epsilon expression or co-expression of different signaling adaptors such as RIG-I MAVS and TRIF, all stimulated pSer477/479 phosphorylation. Furthermore, the newly identified adaptor of the RIG-I pathway (MAVS/IPS-1/VISA/Cardif) was able to induce IRF and NF-kappa B (dependent promoter activity as efficiently as the constitutively active form of RIG-I (Delta RIG-1). Co-expression of the NS3/4A protease activity of hepatitis) virus however blocked MAVS-mediated gene activation in a dose dependent manner.

These studies link RIG-I sensing of viral RNA to downstream kinase signaling and phosphorylation of IRF-3 and IRF-7 via the MAVS/IPS/VISA/Cardif adaptor.

Immunological characterization of an AIRE deficient APS1 disease model

Pöntynen, N., Ulmanen, I., Arstilo, T. P., Miettinen, A., Kampe, O. and Peltonen-Palotie, L.

Clinical Immunology. 2006; 119: S15-S16. Meeting Abstract. IF 3.217

Self-reported and test-based mobility limitations in a representative sample of Finns aged 30+

Sainio, P., Koskinen, S., Heliövaara, M., Martelin, T., Härkänen, T., Hurri, H., Miilunpalo, S. and Aromaa, A.

Scandinavian Journal of Public Health. 2006; 34(4): 378-386. Article. IF 0.727

Aims: The object of the present study was to acquire a comprehensive and accurate picture of mobility limitations in the Finnish adult population.

Methods: A nationally representative sample of 8,028 persons aged 30+ with high participation was interviewed and examined in the Health 2000 Survey conducted in 2000-01. Mobility limitations were measured by self-reports and performance tests.

Results: Perceived running difficulties were already common among persons in middle age, while difficulties in moving about indoors were frequent only among persons aged 75+. A third of women and a fifth of men aged 55+ could not reach a walking speed of 1.2 m/s. Working-aged women were more limited than men only in physically demanding tasks, but in the elderly the gender difference was evident in most mobility tasks. A substantial disagreement was found between the self-reported and test-based indicators in stair climbing. Supplementary data collection, carried out to increase participation in the health examination, as well as inclusion of institutionalized persons, provided a more complete estimate of the prevalence of mobility limitations among the elderly.

Conclusions: Both self-reported and performance-based indicators are needed to achieve a comprehensive view of disability and its variation between population groups. Exclusion of institutionalized persons and low participation lead to underestimation of the occurrence of limitations. The number of persons suffering from mobility problems will increase with ageing of the population, which accentuates the importance of early intervention to maintain functional ability, especially in women.

Isolation and automated ribotyping of Mycobacterium lentiflavum from drinking water distribution system and clinical specimens

Tsitko, I., Rahkila, R., Priha, O., Ali-Vehmas, T., Terefework, Z., Soini, H. and Salkinoja-Salonen, M. S.

FEMS Microbiol Lett. 2006; 256(2): 236-43. IF 2.057

Automated ribotyping as a tool for identifying of nontuberculous mycobacteria was evaluated. We created a database comprising of riboprints of 60 strains, representing 32 species of nontuberculous mycobacteria. It was shown that combined ribopatterns generated after digestion with EcoRI and PvuII were distinguishable between species of both slow-growing and rapid-growing mycobacteria.

The findings were in good agreement with the 16S rRNA gene sequencing results, allowing correct identification of Mycobacterium lentiflavum isolated from clinical specimens and from biofilms growing in public water distribution system. The automated ribotyping was powerful in discriminating between M. lentiflavum and closely related species M. simiae and M. palustre. Mycobacterium lentiflavum strains from drinking water biofilms were resistant to two to four antimycobacterial drugs.

The drinking water distribution system may, thus, be a source of nontuberculous mycobacteria resistant to multiple drugs.

Relative validity of a dietary interview for assessing infant diet and compliance in a dietary intervention trial

Vähätalo, L., Barlund, S., Hannila, M. L., Uusitalo, U., Pigg, H. M., Salonen, M., Nucci, A., Krischer, J. P., Knip, M., Åkerblom, H. K. and Virtanen, S. M.

Matern Child Nutr. 2006; 2(3): 181-7.

The objective of this study was to assess the relative validity of a dietary interview method for use in an infant population.

A dietary interview covering a 1-month period was completed during a study visit at 3 or 6 months of age. It included structured questions and a short food frequency questionnaire (FFQ). The information was compared with data from two 48-h recall interviews conducted during the month previous to the study visit.

The agreement between the FFQ and 48-h recalls was analysed as proportion of subjects classified into the same categories of consumption frequency and by the kappa analysis. A total of 100 subjects, at the age of 2-3 months (n = 50) and 5-6 months (n = 50), were included. The kappa values for breastmilk and study formula ranged from 0.82 to 0.95, indicating very good agreement. The agreement for other foods and vitamin D supplementation ranged from fair to very good. We also found a strong correlation for the reported amount of study formula consumed per feeding at 3 months (r(s) = 0.87, n = 24) and 6 months of age (r(s) = 0.73, n = 35) between the questionnaire and 48-h recall data. However, the average amount of study formula per feeding was significantly higher when estimated for a 1-month period, compared with a mean calculated from the two 48-h recalls.

As a conclusion, the interview was found to be a useful tool for assessing diet and compliance in a dietary intervention for infants.