Significant disparities in allergy prevalence and microbiota between the young people in Finnish and Russian Karelia.

BACKGROUND: Atopic allergy has been more common among schoolchildren in Finland, as compared to Russian Karelia. These adjacent regions show one of the most contrasting socio-economical differences in the world. OBJECTIVE: We explored changes in allergy from school age to young adulthood from 2003 to 2010/2012 in these two areas. The skin and nasal microbiota were also compared. METHODS: Randomly selected children from Finnish (n = 98) and Russian Karelia (n = 82) were examined in 2003, when the children were 7-11 years of age, and again in 2010 (Finnish Karelia) and 2012 (Russian Karelia). We analysed self-reported allergy symptoms and sensitization to common allergens by serum sIgE values. The skin (volar forearm) and nasal mucosa microbiota, collected in 2012 (aged 15-20 years), identified from DNA samples, were compared with multivariate methods. RESULTS: Asthma, hay fever, atopic eczema, self-reported rhinitis, as well as atopic sensitization, were threefold to 10-fold more common in Finland, as compared to Russian Karelia. Hay fever and peanut sensitization were almost non-existent in Russia. These patterns remained throughout the 10-year follow-up. Skin microbiota, as well as bacterial and fungal communities in nasal mucosa, was contrastingly different between the populations, best characterized by the diversity and abundance of genus Acinetobacter; more abundant and diverse in Russia. Overall, diversity was significantly higher among Russian subjects (Pskin < 0.0001, Pnasal-bacteria < 0.0001 and Pnasal-fungi < 0.01). Allergic diseases were not associated with microbial diversity in Finnish subjects. CONCLUSIONS AND CLINICAL RELEVANCE: Differences in allergic phenotype, developed in early life, remain between populations. A parallel difference in the composition of skin and nasal microbiota suggests a potential underlying mechanism. Our results also suggest that high abundance and diversity of Acinetobacter might contribute to the low allergy prevalence in Russia. Implications of early-life exposure to Acinetobacter should be further investigated.

Time trends in physical activity from 1982 to 2012 in Finland.

The aim of this study was to examine population trends from 1982 to 2012 in Finland for leisure time physical activity (LTPA), commuting physical activity (CPA), occupational physical activity (OPA), and total physical activity. Furthermore, time trends in physical activity by educational levels and body mass index (BMI) categories were explored. Data were collected in independent cross-sectional population surveys, implemented every 5 years from 1982 to 2012. The data comprised 21,903 men and 24,311 women. Participants underwent a health examination and filled in questionnaires. Information on LTPA, CPA, and OPA was used both separately and combined to create an index of total physical activity. Between 1982 and 2012, high LTPA has increased in men (from 21% to 33%) and women (from 12% to 27%). High CPA and high OPA have decreased in men (from 17% to 12% and from 48% to 36%, respectively) and women (from 30% to 20% and from 26% to 21%, respectively). Total physical activity has remained fairly stable. Differences by education and BMI have increased, particularly for LTPA. Marked changes in physical activity have taken place over time. Differences in LTPA and OPA have grown wider across educational groups and BMI categories.

Hunt for the origin of allergy - comparing the Finnish and Russian Karelia.

The Finnish and Russian Karelia are adjacent areas in northern Europe, socio-economically distinct but geoclimatically similar. The Karelia Allergy Study was commenced in 1998 to characterize the allergy profiles in the two areas. Allergy prevalence had increased in Finland since the early 1960s, but the situation in Russia was unknown. The key finding was that allergic symptoms and diseases were systematically more common in Finnish children and adults than in their Russian counterparts. For example, in the early 2000s, hay fever in school children was almost non-existent in Russian Karelia, and only 2% were sensitized to birch pollen compared with 27% in Finnish Karelia. Adult birth cohorts showed that among those born in the 1940s, the sensitization to pollens and pets was at the same low level in both countries, but among younger generation born in the late 1970s, the difference was already manifold. Seropositivity to some pathogens, microbial content in house dust and drinking water seemed to confer allergy protection in Russia. In subsequent studies, it became apparent that on the Finnish side, healthy children had a more biodiverse living environment as well as greater diversity of certain bacterial classes on their skin than atopic children. Abundance of skin commensals, especially Acinetobacter (gammaproteobacteria), associated with anti-inflammatory gene expression in blood leucocytes. In vivo experiments with the mouse model demonstrated that intradermally applied Acinetobacter protected against atopic sensitization and lung inflammation. These observations support the notion that the epidemic of allergy and asthma results from reduced exposure to natural environments with rich microbiota, changed diet and sedentary lifestyle. Genetic studies have confirmed strong influence of lifestyle and environment. With our results from the Karelia study, a 10-year National Allergy Programme was started in 2008 to combat the epidemic in Finland.

DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene.

Lipoprotein lipase plays a central role in lipid metabolism and the gene that encodes this enzyme (LPL) is a candidate susceptibility gene for cardiovascular disease. Here we report the complete sequence of a fraction of the LPL gene for 71 individuals (142 chromosomes) from three populations that may have different histories affecting the organization of the sequence variation. Eighty-eight sites in this 9.7 kb vary among individuals from these three populations. Of these, 79 were single nucleotide substitutions and 9 sites involved insertion-deletion variations. The average nucleotide diversity across the region was 0.2% (or on average 1 variable site every 500 bp). At 34 of these sites, the variation was found in only one of the populations, reflecting the differing population and mutational histories. If LPL is a typical human gene, the pattern of sequence variation that exists in introns as well as exons, even for the small number of samples considered here, will present challenges for the identification of sites, or combinations of sites, that influence variation in risk of disease in the population at large.

The role of family factors and school achievement in the progression of adolescents to regular smoking.

This study examines whether parental smoking and single parenting were related to adolescents' school achievement and anti-smoking parental practices as well as how these factors predicted later smoking. The sample comprised 1163 Finnish students in Grades 7 through 9. Results show that at the beginning of the seventh grade, parental smoking and single parenting were related to adolescents' lower levels of school achievement. Moreover, parental smoking had moderate association with lack of house smoking rules. At the beginning of the ninth grade, these associations were strengthened and lack of house smoking rules as well as loosened perceived parental punishment for smoking was related to both parental smoking and single parenting. The likelihood of ninth grade regular smoking was greater among adolescents whose parents smoked, who had no smoking rules in their homes and had substandard school achievement. These results suggest that smoking parents and single parents had similar anti-smoking regulations for their children at the baseline but once children became older smoking parents were not able to maintain these rules as successfully as non-smoking parents and families with two parents. Motivating parents to uphold these anti-smoking regulations offers a prospective intervention opportunity.

Allergy gap between Finnish and Russian Karelia on increase.

BACKGROUND: Multinational time-trend analyses of atopic disease have shown that the East-West gradients in prevalence are shrinking. We set out to clarify whether the disparities in the occurrence of atopy and atopic diseases in Finnish and Russian Karelia during the past 10 years have diminished and how the prevalence of atopy has evolved with successive years of birth. METHODS: Two surveys with identical methodology were performed in 1997/1998 and 2007. The study population comprised randomly selected adults, aged 25-54 years, from Finnish and Russian Karelia. Serum samples were collected for total and specific IgE measurements. Clinical data were obtained by questionnaires. RESULTS: Sensitization rates to birch pollen increased from 7.8% to 14.8% (P < 0.001) and to cat from 6.1% to 10.8% (P < 0.001) in Finland. In Russia, no significant increase was found. Contrary to this, total IgE remained stable in Finland but decreased significantly (P < 0.001) in Russia. Analyses based on years of birth revealed that the prevalence of sensitization to allergens increased with successive birth years in Finland, but remained stable in Russia. Over the 10 years, self-reported physician-diagnosed asthma increased from 5.5% to 8.1% (P = 0.05) and hay fever from 8.1% to 13.2% (P < 0.001) in Finland. CONCLUSIONS: Disparities in the prevalence of atopy and atopic disease between Finnish and Russian Karelia have further grown. The 'allergy epidemic' continues in Finland and is mainly attributable to the years of birth effect shown in atopy prevalence. In Russia, no signs of the epidemic are discernible, although the decrease in total IgE may indicate a change in environmental exposure.

Scientific rationale for the Finnish Allergy Programme 2008-2018: emphasis on prevention and endorsing tolerance.

In similarity to many other western countries, the burden of allergic diseases in Finland is high. Studies worldwide have shown that an environment rich in microbes in early life reduces the subsequent risk of developing allergic diseases. Along with urbanization, such exposure has dramatically reduced, both in terms of diversity and quantity. Continuous stimulation of the immune system by environmental saprophytes via the skin, respiratory tract and gut appears to be necessary for activation of the regulatory network including regulatory T-cells and dendritic cells. Substantial evidence now shows that the balance between allergy and tolerance is dependent on regulatory T-cells. Tolerance induced by allergen-specific regulatory T-cells appears to be the normal immunological response to allergens in non atopic healthy individuals. Healthy subjects have an intact functional allergen-specific regulatory T-cell response, which in allergic subjects is impaired. Evidence on this exists with respect to atopic dermatitis, contact dermatitis, allergic rhinitis and asthma. Restoration of impaired allergen-specific regulatory T-cell response and tolerance induction has furthermore been demonstrated during allergen-specific subcutaneous and sublingual immunotherapy and is crucial for good therapeutic outcome. However, tolerance can also be strengthened unspecifically by simple means, e.g. by consuming farm milk and spending time in nature. Results so far obtained from animal models indicate that it is possible to restore tolerance by administering the allergen in certain circumstances both locally and systemically. It has become increasingly clear that continuous exposure to microbial antigens as well as allergens in foodstuffs and the environment is decisive, and excessive antigen avoidance can be harmful and weaken or even prevent the development of regulatory mechanisms. Success in the Finnish Asthma Programme was an encouraging example of how it is possible to reduce both the costs and morbidity of asthma. The time, in the wake of the Asthma Programme, is now opportune for a national allergy programme, particularly as in the past few years, fundamentally more essential data on tolerance and its mechanisms have been published. In this review, the scientific rationale for the Finnish Allergy Programme 2008-2018 is outlined. The focus is on tolerance and how to endorse tolerance at the population level.

Opposite gene by environment interactions in Karelia for CD14 and CC16 single nucleotide polymorphisms and allergy.

BACKGROUND: Finnish Karelians have a higher prevalence of allergic disease than Russian Karelians. As both populations are generally from the same ethnic group, the Karelian population offers a unique opportunity to analyse genetic and allergic disease interactions between 'Western' and 'Eastern' environments. OBJECTIVES: We investigated associations between allergic diseases and CD14 and CC16 polymorphisms in Finnish vs Russian Karelian women. METHODS: Adult female Karelians (330 Finnish and 274 Russian) were recruited, examined for a range of symptoms and conditions including rhinitis, itchy rash, asthma and atopy and genotyped for CD14 C-159T and CC16 A38G. RESULTS: For both CD14 C-159T and CC16 A38G, the risk allele for atopic phenotypes in Finnish Karelia was the protective allele in Russian Karelia. For CD14 C-159T, an interactive effect on ever itchy rash (P(interaction) = 0.004), itchy rash <12 mo (P(interaction) = 0.001) and dry cough at night in the past 12 months (<12 months) (P(interaction) = 0.011) was found; the risk allele was C in Russians and T in Finns. For CC16 A38G, an interaction was significant for ever rhinitis (P(interaction) = 0.006), rhinitis <12 mo (P(interaction) = 0.004), and marginally significant for ever hayfever (P(interaction) = 0.07), allergic eye symptoms <12 mo (P(interaction) = 0.09); their risk allele was G in Russians and A in Finns. CONCLUSION: An Eastern vs Western environment appears to exert an effect via opposite alleles on risk of allergic diseases in adult women.

Occupational radiation doses in interventional radiology: simulations.

In interventional radiology, occupational radiation doses can be high. Therefore, many authors have established conversion coefficients from the dose-area product data or from the personal dosemeter reading to the effective dose of the radiologist. These conversion coefficients are studied also in this work, with an emphasis on sensitivity of the results to changes in exposure conditions. Comparison to earlier works indicates that, for the exposure conditions examined in this work, all previous models discussed in this work overestimate the effective dose of the radiologist when a lead apron and a thyroid shield are used. Without the thyroid shield, underestimation may occur with some models.

Contribution of sociodemographic and lifestyle-related factors to the differences in metabolic syndrome among Russian, Somali and Kurdish migrants compared with Finns.

BACKGROUND: Metabolic syndrome (MetS) is associated with a substantially increased risk for cardiovascular disease and diabetes. We examined the contribution of length of residence, socioeconomic position and lifestyle-related factors to the differences in the prevalence of MetS among migrants compared with Finns. METHODS: Cross-sectional data from randomly sampled 30-64year-old health examination participants (318 Russian, 212 Somali, and 321 Kurdish origin migrants) of the Migrant Health and Wellbeing Survey (2010-2012) were used. Health 2011 Survey participants (n=786) were the reference group. RESULTS: Compared with Finns, prevalence of MetS was significantly higher among all migrants except for Somali men. Among men, age-adjusted prevalence ratio (PR) of MetS compared with Finns was 1.71, 95% confidence interval (CI) 1.19-2.46 for Russians, PR 0.95 (95% CI 0.54-1.67) for Somali, and PR 2.10 (95% CI 1.51-2.93) for Kurds. Among women, respective PRs were 1.45 (95% CI 1.08-1.97) for Russians, PR 2.34 (95% CI 1.75-3.14) for Somali and PR 2.22 (95% CI 1.67-2.97) for Kurds. Adjustment for sociodemographic and lifestyle-related factors attenuated the differences in MetS among women but not men. CONCLUSIONS: Further studies should aim at identifying factors related to elevated risk for MetS among Russian and Kurdish men. Interventions aiming at improving lifestyle-related factors are needed for reducing inequalities in the prevalence of MetS among migrant women. Effectiveness of interventions focusing on reducing overweight and obesity among Somali and Kurdish women should be evaluated.

Exhaled nitric oxide in healthy nonatopic school-age children: determinants and height-adjusted reference values.

Exhaled nitric oxide (FENO) was proposed as a marker of airway inflammation, but data about FENO in healthy children measured with standardized methods are so far limited. In order to assess the determinants of FENO in healthy children, we investigated a population-based sample of school-age children (n = 276) with a questionnaire, skin-prick tests, spirometry, and the measurement of FENO. The FENO of 114 nonatopic and nonsmoking children considered healthy were analyzed with stepwise multiple regression analysis, which showed significant associations with age, standing height, weight, and body surface area, but not with gender. Height was found to be the best independent variable for the regression equation for FENO, which on average showed an increase in the height range of 120-180 cm from 7 to 14 ppb. In the random sample of children, increased FENO was associated with atopy (odds ratio, 9.0; 95% confidence interval, 3.9-21.1; P < 0.0001), and significantly with allergic rhinitis and atopic dermatitis, but not with asthma. Respiratory symptom-free children with skin-prick test positivity had significantly higher FENO than healthy nonatopic subjects. We conclude that height is the best determinant of FENO in healthy children. Due to the strong effect of atopy, FENO data should not be interpreted without knowing the atopic status of the child. The present reference values of FENO may serve in clinical assessments for measuring airway inflammation in children.

Aspects of harmonisation of individual monitoring for external radiation in Europe: conclusions of a EURADOS action.

Following the publication of the EU Council Directive 96/29, EURADOS coordinated two working groups (WGs) for promoting the process of harmonisation on individual monitoring of occupationally exposed persons in Europe. An overview of the major findings of the second WG is presented. Information on the technical and quality standards and on the accreditation and approval procedures has been compiled. The catalogue of dosimetric services has been updated and extended. An overview of national regulations and standards for protection from radon and other natural sources in workplaces has been made, attempting to combine the results from individual monitoring for external, internal and workplace monitoring. A first status description of the active personal dosemeters, including legislative and technical information, and their implementation has been made. The importance of practical factors on the uncertainty in the dose measurement has been estimated. Even if a big progress has been made towards harmonisation, there is still work to be done.

Coffee consumption and the risk of coronary heart disease and death.

OBJECTIVES: To study prospectively the relation of coffee drinking with fatal and nonfatal coronary heart disease (CHD) and all-cause mortality and to perform a cross-sectional analysis at baseline on the association between coffee drinking and CHD risk factors, diagnosed diseases, self-reported symptoms, and use of medicines. METHODS: The study cohort consisted of 20 179 randomly selected eastern Finnish men and women aged 30 to 59 years who participated in a cross-sectional risk factor survey in 1972, 1977, or 1982. Habitual coffee drinking, health behavior, major known CHD risk factors, and medical history were assessed at the baseline examination. Each subject was followed up for 10 years after the survey using the national hospital discharge and death registers. Multivariate analyses were performed by using the Cox proportional hazards model. RESULTS: In men, the risk of nonfatal myocardial infarction was not associated with coffee drinking. The age-adjusted association of coffee drinking was J shaped with CHD mortality and U shaped with all-cause mortality. The highest CHD mortality was found among those who did not drink coffee at all (multivariate adjusted). Also, in women, all-cause mortality decreased by increasing coffee drinking. The prevalence of smoking and the mean level of serum cholesterol increased with increasing coffee drinking. Non-coffee drinkers more often reported a history of various diseases and symptoms, and they also more frequently used several drugs compared with coffee drinkers. CONCLUSIONS: Coffee drinking does not increase the risk of CHD or death. In men, slightly increased mortality from CHD and all causes in heavy coffee drinkers is largely explained by the effects of smoking and a high serum cholesterol level. Arch Intern Med. 2000;160:3393-3400.

Serum levels of human chorionic gonadotropin in nonpregnant women and men are modulated by gonadotropin-releasing hormone and sex steroids.

Serum hCG levels were measured in apparently healthy nonpregnant women and men using a highly sensitive and specific time-resolved immunofluorometric assay. The sensitivity of the assay was 0.03 IU/L. The levels were low in women of fertile age (median, 0.05 IU/L) and in men less than 60 yr of age (median, 0.04 IU/L). In women the median level increased to 1.1 IU/L after the menopause (range, 0.17-4.8 IU/L), and a similar but smaller increase occurred in men after 60 yr of age (median, 0.20 IU/L; range, less than 0.03-2.3). Stimulation with GnRH caused a 2- to 3-fold increase in the hCG level in both men and women. Chronic treatment of postmenopausal women with a combination of estrogen and progestagen lowered their serum hCG levels to about 50% of the pretreatment values. The hCG in serum could be separated from LH by gel chromatography, and the hCG immunoreactivity measured by direct assay of serum corresponded to the immunoreactivity eluted in the hCG fractions after gel chromatography. Thus, the results were not due to cross-reaction with LH. We conclude that serum of nonpregnant women and men contains hCG-like material, whose production is modulated by GnRH and sex steroids.

Evidence for involvement of the type 1 angiotensin II receptor locus in essential hypertension.

Components of the renin-angiotensin system play an important role in the normal regulation of blood pressure. We carried out a comprehensive genetic linkage study of the genes involved in the renin-angiotensin cascade in Finnish hypertensive twins and their affected siblings. We found no evidence for linkage between essential hypertension and the genes coding for renin, angiotensinogen, angiotensin-converting enzyme, or kallikrein 1 in the 329 hypertensive individuals of 142 families studied. In contrast, two intragenic markers for the type 1 angiotensin II receptor (AT1) showed some evidence for linkage in the total sample. A closer examination of this gene locus was carried out using subgroups of nonobese sibpairs with early onset of hypertension and uniform geographical origin. These stratifications yielded suggestive evidence for linkage of hypertension to the genetic area containing the AT1 gene, with a maximal multipoint logarithm of the odds (LOD) score of 2.9. A genetic association study carried out in an independent series of 50 hypertensive cases and 122 normotensive controls showed an increase in the frequency of the A1166-->C allele of the AT1 gene in the hypertensive individuals. In a novel variant of model-free multipoint linkage analysis allowing linkage disequilibrium in the calculations, an LOD score of 5.13 was obtained. Sequence analyses of the entire coding region and 848 bp of promoter region in the DNA sample on 8 index samples did not reveal previously unpublished sequence variations. The data provide evidence that a common genetic variant of the AT1 gene locus influences the risk of essential hypertension in the Finnish population.

High serum cholesterol and risk of suicide.

OBJECTIVE: The study was conducted to estimate the association between serum total cholesterol concentration and mortality from suicide. METHOD: The baseline serum total cholesterol concentration of 37,635 adults was determined in five independent population surveys conducted during 1972-1992 in Finland. Mortality from different causes of death was monitored for a mean of 14.6 years after the survey dates. The means for violent suicides (N=130) included hanging, firearms, cutting, jumping, and unspecified means. The means for nonviolent suicides (N=46) included drug overdose, poisoning with gases, and drowning. RESULTS: Serum total cholesterol concentration was positively related to the risk of violent suicide. Among subjects whose serum total cholesterol concentration was in the highest category, the adjusted relative risk was more than twofold compared with the lowest category. The violent/nonviolent suicide ratio increased linearly with increasing cholesterol category. No association between serum total cholesterol concentration and the risk of nonviolent suicide was found. CONCLUSIONS: This is the first study to demonstrate the positive relationship of high serum total cholesterol concentration with increased risk of violent suicide.

Selective decrease in low-Mr HMG proteins HMG I and HMG Y during differentiation of mouse teratocarcinoma cells.

We have studied the presence of high-mobility-group (HMG) chromatin proteins in undifferentiated F9 mouse teratocarcinoma cells and F9 cells, which were induced to differentiate by treatment with retinoic acid and dibutyryl-cAMP for 5 days. Acetic acid/urea-polyacrylamide gel electrophoresis and reversed-phase HPLC revealed that the induced F9 cells contained 77 and 62% less HMG I and HMG Y, respectively, than their untreated counterparts. The relative amounts of two other low-Mr HMG proteins HMG 14 and HMG 17 remained essentially unchanged and only a minor decrease was observed in the content of one of the high-Mr HMG proteins, HMG 2. The identity of the low-Mr HMG proteins was verified by amino acid analysis or partial sequencing. These results suggest that HMG I and HMG Y are HMG proteins specific for undifferentiated cells.

Trends in waist-to-hip ratio and its determinants in adults in Finland from 1987 to 1997.

BACKGROUND: Although abdominal obesity has been shown to be an important risk factor for cardiovascular disease and a variety of other diseases, secular changes in fat distribution in populations have rarely been documented. OBJECTIVE: Our objective was to assess trends in waist-to-hip ratio (WHR) in the Finnish population during a 10-y period. In addition, we investigated the associations of WHR with body mass index (BMI), age, education, and lifestyle factors. DESIGN: Three independent cross-sectional surveys were carried out at 5-y intervals between 1987 and 1997. Altogether, 15096 randomly selected men and women aged 25-64 y participated in these surveys. RESULTS: The WHR increased in both men and women during the 10-y period (P: < 0.0001). In men, the strongest upward trend took place in the first 5-y period and then seemed to plateau; in women, the WHR continued to increase into the 1990s. In both sexes, the most prominent increase was observed in subjects aged >/=45 y. The WHR increased in all education-level groups, the lowest WHR being among those with the highest education. Age (18% in men, 12% in women) and BMI (33% in men, 25% in women) accounted for most of the variation in WHR, whereas only 3% was explained by education and lifestyle factors. CONCLUSIONS: Abdominal obesity is a growing problem in Finland, especially in persons aged >/=45 y. These adverse changes in body shape continued to take place, particularly in women, in the 1990s.